BioMed Research International: Physiology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. A Comparison Study of Portable Foot-to-Foot Bioelectrical Impedance Scale to Measure Body Fat Percentage in Asian Adults and Children Thu, 28 Aug 2014 05:57:53 +0000 Objective. To compare the measurements of body fat percentage (BF%) using the foot-to-foot bioelectrical impedance analysis (FTF-BIA) with the direct segmental multifrequency BIA (DSM-BIA). Methods. There were 36 men and 52 women ( years) with 57% Malays, 30% Chinese, and 13% Indian. For children, there were 45 boys and 26 girls ( years) with 52% Malay, 15% Chinese, and 33% Indian. Results. Mean height for men was 168.4 cm, 11 cm taller than women. Men were 10 kg heavier than women at 70 kg. BF% in women was 32% and 33% whereas BF% in men was 23% and 25% when measured using FTF-BIA and DSM-BIA, respectively. In children, BF% measured with FTF-BIA and DSM-BIA was 49% and 46%, respectively. The correlations were significant for men (, SEE = 2.80), women (, SEE = 3.31), boys (, SEE = 5.44), and girls (, SEE = 5.27). The BF% in underweight/normal (, SEE = 2.47) and that in overweight/obese adults (, SEE = 3.61) were strongly correlated. The correlations were significant in normal/underweight (, SEE = 3.78) and obese/overweight children (, SEE = 6.49). All ethnic groups showed significant correlation with BF%. Malay adults (, SEE = 3.27) and children (, SEE = 0.88) showed significant mean differences in BF%. Conclusion. The FTF-BIA showed higher accuracy for all normal/underweight and Chinese group with acceptable overestimation in children and underestimation in adults. Caution should be taken when interpreting BF% depending on gender, BMI, and ethnicity. Pei Ying Sim, Tin Tin Su, Hazreen Abd Majid, Azmi Mohamed Nahar, and Muhammad Yazid Jalaludin Copyright © 2014 Pei Ying Sim et al. All rights reserved. Spaceflight Affects Postnatal Development of the Aortic Wall in Rats Tue, 19 Aug 2014 00:00:00 +0000 We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam). The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta. Shin-ichiro Katsuda, Masao Yamasaki, Hidefumi Waki, Masao Miyake, Hirotaka O-ishi, Kiyoaki Katahira, Tadanori Nagayama, Yukako Miyamoto, Masamitsu Hasegawa, Haruyuki Wago, Toshiyasu Okouchi, and Tsuyoshi Shimizu Copyright © 2014 Shin-ichiro Katsuda et al. All rights reserved. Evaluation of the Performance of Females as Light Infantry Soldiers Mon, 18 Aug 2014 12:59:44 +0000 A few countries permit women to serve in combat roles, but their long term performance in these positions has not been reported. The incidences of overuse injuries and attrition of 85 male and 235 female recruits in a light infantry brigade was followed in a three-year prospective study. Females were shorter (162 cm, CI 161–163 cm) than males (174 cm, CI 173–176), had more body fat (18.9 kg, CI 18.2–19.6 kg) than males (12.6 kg, 11.3–13.8 kg), had lower O2max (36.8 mL·min−1·kg−1, CI 35.8–37.78 mL·min−1·kg−1) than males (50.48 mL·min−1·kg−1, CI 48.4 to 52.48 mL·min−1·kg−1), had more stress fractures (21.0%, 95% CI 16.2–26.5%) than males (2.3%, CI 0.3–8.2%), and had more anterior knee pain (41.2%, CI 34.9–47.7%) than males (24.7%, CI 16.0–35.2%). Three-year attrition was 28% CI 22–34% for females and 37% CI 26–48% for males. The females in this study successfully served as light infantry soldiers. Their lower fitness and high incidence of overuse injuries might impede service as regular infantry soldiers. Aharon S. Finestone, Charles Milgrom, Ran Yanovich, Rachel Evans, Naama Constantini, and Daniel S. Moran Copyright © 2014 Aharon S. Finestone et al. All rights reserved. Morning/Evening Differences in Somatosensory Inputs for Postural Control Mon, 18 Aug 2014 06:28:37 +0000 The underlying processes responsible for the differences between morning and afternoon measurements of postural control have not yet been clearly identified. This study was conducted to specify the role played by vestibular, visual, and somatosensory inputs in postural balance and their link with the diurnal fluctuations of body temperature and vigilance level. Nineteen healthy male subjects (mean age: 20.5 ± 1.3 years) participated in test sessions at 6:00 a.m. and 6:00 p.m. after a normal night’s sleep. Temperature was measured before the subjects completed a sign cancellation test and a postural control evaluation with eyes both open and closed. Our results confirmed that postural control improved throughout the day according to the circadian rhythm of body temperature and sleepiness/vigilance. The path length as a function of surface ratio increased between 6:00 a.m. and 6:00 p.m. This is due to a decrease in the centre-of-pressure surface area, which is associated with an increase in path length. Romberg’s index did not change throughout the day; however, the spectral analysis (fast Fourier transform) of the centre-of-pressure excursions (in anteroposterior and mediolateral directions) indicated that diurnal fluctuations in postural control may occur via changes in the different processes responsible for readjustment via muscle contractions. Clément Bougard and Damien Davenne Copyright © 2014 Clément Bougard and Damien Davenne. All rights reserved. DNA Damage and Its Cellular Response in Mother and Fetus Exposed to Hyperglycemic Environment Thu, 14 Aug 2014 00:00:00 +0000 The increased production of reactive oxygen species (ROS) plays a key role in pathogenesis of diabetic complications. ROS are generated by exogenous and endogenous factors such as during hyperglycemia. When ROS production exceeds the detoxification and scavenging capacity of the cell, oxidative stress ensues. Oxidative stress induces DNA damage and when DNA damage exceeds the cellular capacity to repair it, the accumulation of errors can overwhelm the cell resulting in cell death or fixation of genome mutations that can be transmitted to future cell generations. These mutations can lead to and/or play a role in cancer development. This review aims at (i) understanding the types and consequences of DNA damage during hyperglycemic pregnancy; (ii) identifying the biological role of DNA repair during pregnancy, and (iii) proposing clinical interventions to maintain genome integrity. While hyperglycemia can damage the maternal genetic material, the impact of hyperglycemia on fetal cells is still unclear. DNA repair mechanisms may be important to prevent the deleterious effects of hyperglycemia both in mother and in fetus DNA and, as such, prevent the development of diseases in adulthood. Hence, in clinical practice, maternal glycemic control may represent an important point of intervention to prevent the deleterious effects of maternal hyperglycemia to DNA. Jusciele Brogin Moreli, Janine Hertzog Santos, Clarissa Ribeiro Rocha, Débora Cristina Damasceno, Glilciane Morceli, Marilza Vieira Rudge, Estela Bevilacqua, and Iracema Mattos Paranhos Calderon Copyright © 2014 Jusciele Brogin Moreli et al. All rights reserved. Changes in Biochemical, Strength, Flexibility, and Aerobic Capacity Parameters after a 1700 km Ultraendurance Cycling Race Sun, 10 Aug 2014 13:05:23 +0000 The purpose of the present research was to study the organic response after ultraendurance cycling race. Selected biochemical, leg strength, flexibility, and aerobic capacity parameters were analyzed in 6 subjects 5 days before and 5 days after completing a 1700 km ultraendurance cycling race. After the race, participants presented a significant decrease in Hb (167.8 ± 9.5 versus 141.6 ± 15.7 mg/dL), strength (29.4 ± 2.7 versus 25.5 ± 3.7 cm in a countermovement jump), and oxygen uptake and heart rate at ventilatory threshold (1957.0 ± 458.4 versus 1755.2 ± 281.5 mL/kg/min and 140.0 ± 9.7 versus 130.8 ± 8.3 bpm, resp.). Testosterone presented a decrease tendency (4.2 ± 2.5 versus 3.9 ± 2.6 ng/L) in opposition to the increase tendency of cortisol and ammonium parameters. Transferrin and iron levels presented high values related to an overstimulation of the liver, a normal renal function, a tendency to decrease flexibility, and an increase in aerobic capacity, finding a tendency to increase the absolute maximal oxygen uptake (37.2 ±2.4 versus 38.7 ± 1.8 mL/min) in contrast to previous studies conducted with subjects with similar age. These results can be used to program training interventions, recovery times between probes, and nutritional and/or ergonomic strategies in ultraendurance events. Vicente Javier Clemente-Suarez Copyright © 2014 Vicente Javier Clemente-Suarez. All rights reserved. Effect of Hypoxia on the Calcium and Magnesium Content, Lipid Peroxidation Level, and Ca2+-ATPase Activity of Syncytiotrophoblast Plasma Membranes from Placental Explants Thu, 07 Aug 2014 07:21:25 +0000 In the current study the possible relationship between the Ca2+/Mg2+ ratio of human syncytiotrophoblast plasma membranes and their lipid peroxidation and Ca2+-ATPase activity was determined. Syncytiotrophoblast plasma membranes of placental explants cultured under hypoxia increased their lipid peroxidation and Ca2+ content, diminished their Ca2+-ATPase activity, and kept their Mg2+ content unchanged. Membranes preincubated with different concentrations of Ca2+ increased their Ca2+ content without changes in their Mg2+ content. There is a direct relationship between Ca2+ content and lipid peroxidation of the membranes, as well as an inverse relationship between their Ca2+ content and Ca2+-ATPase activity. On the contrary, preincubation of membranes with different concentrations of Mg2+ showed a higher Mg2+ content without changing their lipid peroxidation and Ca2+-ATPase activity. Explants cultured under hypoxia in the presence of 4 mM MgSO4 showed similar values of lipid peroxidation and Ca2+-ATPase activity of their membranes compared to those of explants cultured under normoxia. Increased Ca2+ content of the membranes by interacting with negatively charged phospholipids could result in destabilizing effects of the membrane structure, exposing hydrocarbon chains of fatty acids to the action of free radicals. Mg2+ might exert a stabilizing effect of the membranes, avoiding their exposure to free radicals. Delia I. Chiarello, Reinaldo Marín, Fulgencio Proverbio, Zully Benzo, Sandy Piñero, Desirée Botana, and Cilia Abad Copyright © 2014 Delia I. Chiarello et al. All rights reserved. The Characterization of Biological Rhythms in Mild Cognitive Impairment Thu, 17 Jul 2014 00:00:00 +0000 Introduction. Patients with dementia, especially Alzheimer’s disease, present several circadian impairments related to an accelerated perturbation of their biological clock that is caused by the illness itself and not merely age-related. Thus, the objective of this work was to elucidate whether these circadian system alterations were already present in patients with mild cognitive impairment (MCI), as compared to healthy age-matched subjects. Methods. 40 subjects (21 patients diagnosed with MCI, 74.1 ± 1.5 y.o., and 19 healthy subjects, 71.7 ± 1.4 y.o.) were subjected to ambulatory monitoring, recording wrist skin temperature, motor activity, body position, and the integrated variable TAP (including temperature, activity, and position) for one week. Nonparametrical analyses were then applied. Results. MCI patients exhibited a significant phase advance with respect to the healthy group for the following phase markers: temperature M5 (mean ± SEM: 04:20 ± 00:21 versus 02:52 ± 00:21) and L10 (14:35 ± 00:27 versus 13:24 ± 00:16) and TAP L5 (04:18 ± 00:14 versus 02:55 ± 00:30) and M10 (14:30 ± 00:18 versus 13:28 ± 00:23). Conclusions. These results suggest that significant advances in the biological clock begin to occur in MCI patients, evidenced by an accelerated aging of the circadian clock, as compared to a healthy population of the same age. Elisabet Ortiz-Tudela, Antonio Martinez-Nicolas, Carmen Díaz-Mardomingo, Sara García-Herranz, Inmaculada Pereda-Pérez, Azucena Valencia, Herminia Peraita, César Venero, Juan Antonio Madrid, and Maria Angeles Rol Copyright © 2014 Elisabet Ortiz-Tudela et al. All rights reserved. Postactivation Potentiation Biases Maximal Isometric Strength Assessment Tue, 15 Jul 2014 12:15:30 +0000 Postactivation potentiation (PAP) is known to enhance force production. Maximal isometric strength assessment protocols usually consist of two or more maximal voluntary isometric contractions (MVCs). The objective of this study was to determine if PAP would influence isometric strength assessment. Healthy male volunteers () performed two five-second MVCs separated by a 180-seconds interval. Changes in isometric peak torque (IPT), time to achieve it (tPTI), contractile impulse (CI), root mean square of the electromyographic signal during PTI (RMS), and rate of torque development (RTD), in different intervals, were measured. Significant increases in IPT (240.6 ± 55.7 N·m versus 248.9 ± 55.1 N·m), RTD (746 ± 152 N·m·s−1versus 727 ± 158 N·m·s−1), and RMS (59.1 ± 12.2%   versus 54.8 ± 9.4% ) were found on the second MVC. tPTI decreased significantly on the second MVC (2373 ± 1200 ms versus 2784 ± 1226 ms). We conclude that a first MVC leads to PAP that elicits significant enhancements in strength-related variables of a second MVC performed 180 seconds later. If disconsidered, this phenomenon might bias maximal isometric strength assessment, overestimating some of these variables. Leonardo Coelho Rabello Lima, Felipe Bruno Dias Oliveira, Thiago Pires Oliveira, Claudio de Oliveira Assumpção, Camila Coelho Greco, Adalgiso Croscato Cardozo, and Benedito Sérgio Denadai Copyright © 2014 Leonardo Coelho Rabello Lima et al. All rights reserved. Perinatal Nitric Oxide Therapy Prevents Adverse Effects of Perinatal Hypoxia on the Adult Pulmonary Circulation Tue, 08 Jul 2014 12:03:09 +0000 Adverse events in utero are associated with the occurrence of chronic diseases in adulthood. We previously demonstrated in mice that perinatal hypoxia resulted in altered pulmonary circulation in adulthood, with a decreased endothelium-dependent relaxation of pulmonary arteries, associated with long-term alterations in the nitric oxide (NO)/cyclic GMP pathway. The present study investigated whether inhaled NO (iNO) administered simultaneously to perinatal hypoxia could have potential beneficial effects on the adult pulmonary circulation. Indeed, iNO is the therapy of choice in humans presenting neonatal pulmonary hypertension. Long-term effects of neonatal iNO therapy on adult pulmonary circulation have not yet been investigated. Pregnant mice were placed in hypoxia (13% O2) with simultaneous administration of iNO 5 days before delivery until 5 days after birth. Pups were then raised in normoxia until adulthood. Perinatal iNO administration completely restored acetylcholine-induced relaxation, as well as endothelial nitric oxide synthase protein content, in isolated pulmonary arteries of adult mice born in hypoxia. Right ventricular hypertrophy observed in old mice born in hypoxia compared to controls was also prevented by perinatal iNO treatment. Therefore, simultaneous administration of iNO during perinatal hypoxic exposure seems able to prevent adverse effects of perinatal hypoxia on the adult pulmonary circulation. Anne-Christine Peyter, Flavien Delhaes, Giacomo Diaceri, Steeve Menétrey, and Jean-François Tolsa Copyright © 2014 Anne-Christine Peyter et al. All rights reserved. New Insight into Adiponectin Role in Obesity and Obesity-Related Diseases Mon, 07 Jul 2014 07:13:09 +0000 Obesity is a major health problem strongly increasing the risk for various severe related complications such as metabolic syndrome, cardiovascular diseases, respiratory disorders, diabetic retinopathy, and cancer. Adipose tissue is an endocrine organ that produces biologically active molecules defined “adipocytokines,” protein hormones with pleiotropic functions involved in the regulation of energy metabolism as well as in appetite, insulin sensitivity, inflammation, atherosclerosis, cell proliferation, and so forth. In obesity, fat accumulation causes dysregulation of adipokine production that strongly contributes to the onset of obesity-related diseases. Several advances have been made in the treatment and prevention of obesity but current medical therapies are often unsuccessful even in compliant patients. Among the adipokines, adiponectin shows protective activity in various processes such as energy metabolism, inflammation, and cell proliferation. In this review, we will focus on the current knowledge regarding the protective properties of adiponectin and its receptors, AdipoRs (“adiponectin system”), on metabolic complications in obesity and obesity-related diseases. Adiponectin, exhibiting antihyperglycemic, antiatherogenic, and anti-inflammatory properties, could have important clinical benefits in terms of development of therapies for the prevention and/or for the treatment of obesity and obesity-related diseases. Ersilia Nigro, Olga Scudiero, Maria Ludovica Monaco, Alessia Palmieri, Gennaro Mazzarella, Ciro Costagliola, Andrea Bianco, and Aurora Daniele Copyright © 2014 Ersilia Nigro et al. All rights reserved. Role of Lectin-Like Oxidized Low Density Lipoprotein-1 in Fetoplacental Vascular Dysfunction in Preeclampsia Sun, 06 Jul 2014 09:59:24 +0000 The bioavailability of nitric oxide (NO) represents a key marker in vascular health. A decrease in NO induces a pathological condition denominated endothelial dysfunction, syndrome observed in different pathologies, such as obesity, diabetes, kidney disease, cardiovascular disease, and preeclampsia (PE). PE is one of the major risks for maternal death and fetal loss. Recent studies suggest that the placenta of pregnant women with PE express high levels of lectin-like oxidized LDL receptor-1 (LOX-1), which induces endothelial dysfunction by increasing reactive oxygen species (ROS) and decreasing intracellular NO. Besides LOX-1 activation induces changes in migration and apoptosis of syncytiotrophoblast cells. However, the role of this receptor in placental tissue is still unknown. In this review we will describes the physiological roles of LOX-1 in normal placenta development and the potential involvement of this receptor in the pathophysiology of PE. Felipe A. Zuniga, Valeska Ormazabal, Nicolas Gutierrez, Valeria Aguilera, Claudia Radojkovic, Carlos Veas, Carlos Escudero, Liliana Lamperti, and Claudio Aguayo Copyright © 2014 Felipe A. Zuniga et al. All rights reserved. Prolonged Sleep Deprivation and Continuous Exercise: Effects on Melatonin, Tympanic Temperature, and Cognitive Function Sun, 06 Jul 2014 06:30:27 +0000 The purpose of this study was to examine tympanic temperature, melatonin, and cognitive function during a 36-hour endurance event. Nine male and three female participants took part in a 36-hour sustained endurance event without sleep (, mean age = yrs). Participants were stopped for data collection at checkpoints throughout the 36-hour event. Tympanic temperature was assessed, a psychomotor vigilance test (PVT) was administered, and saliva samples were collected. Salivary melatonin was determined via immunoassay. During the 36 hours of competition, melatonin levels were negatively correlated with the day of the race (, ) and positively associated with nighttime (, ). Significant main effects of tympanic temperature (), day of the competition (), and a tympanic temperature day of competition interaction () were used to predict minor lapses in attention. No associations between melatonin levels and cognitive function were observed (). During the event tympanic temperature declined and was associated with an increase in lapses in attention. With sustained endurance events becoming more popular future research is warranted to evaluate the physiological impact of participation. Greggory R. Davis, Corey E. Etheredge, Lena Marcus, and David Bellar Copyright © 2014 Greggory R. Davis et al. All rights reserved. Physiology to the Pleiotropic Role of RNAs: Prospecting Novel Therapies Tue, 01 Jul 2014 12:04:07 +0000 Maria Chiara Maiuri, Daniela De Stefano, and Ammad Ahmad Farooqi Copyright © 2014 Maria Chiara Maiuri et al. All rights reserved. Programming of Fetal Insulin Resistance in Pregnancies with Maternal Obesity by ER Stress and Inflammation Mon, 30 Jun 2014 00:00:00 +0000 The global epidemics of obesity during pregnancy and excessive gestational weight gain (GWG) are major public health problems worldwide. Obesity and excessive GWG are related to several maternal and fetal complications, including diabetes (pregestational and gestational diabetes) and intrauterine programming of insulin resistance (IR). Maternal obesity (MO) and neonatal IR are associated with long-term development of obesity, diabetes mellitus, and increased global cardiovascular risk in the offspring. Multiple mechanisms of insulin signaling pathway impairment have been described in obese individuals, involving complex interactions of chronically elevated inflammatory mediators, adipokines, and the critical role of the endoplasmic reticulum (ER) stress-dependent unfolded protein response (UPR). However, the underlying cellular processes linking MO and IR in the offspring have not been fully elucidated. Here, we summarize the state-of-the-art evidence supporting the possibility that adverse metabolic postnatal outcomes such as IR in the offspring of pregnancies with MO and/or excessive GWG may be related to intrauterine activation of ER stress response. Francisco Westermeier, Pablo J. Sáez, Roberto Villalobos-Labra, Luis Sobrevia, and Marcelo Farías-Jofré Copyright © 2014 Francisco Westermeier et al. All rights reserved. Anthropometric Characteristics and Sex Influence Magnitude of Skin Cooling following Exposure to Whole Body Cryotherapy Sun, 29 Jun 2014 08:26:49 +0000 This study explored whether anthropometric measures influence magnitude of skin cooling following exposure to whole body cryotherapy (WBC). Height, weight, body fat percentage, and lean mass were measured in 18 male and 14 female participants. Body surface area, body surface area to mass ratio, body mass index, fat-free mass index, and fat mass index were calculated. Thermal images were captured before and after WBC (−60°C for 30 seconds, −110°C for 2 minutes). Skin temperature was measured at the chest, arm, thigh, and calf. Mean skin temperature before and after WBC and change in mean skin temperature were calculated. was significantly greater in females (°C) than males (°C; , ). A significant relationship was observed between body fat percentage and in the combined dataset (, ) and between fat-free mass index and in males (, ). No other significant associations were found. Skin response of individuals to WBC appears to depend upon anthropometric variables and sex, with individuals with a higher adiposity cooling more than thinner individuals. Effects of sex and anthompometrics should be considered when designing WBC research or treatment protocols. L. E. Hammond, S. Cuttell, P. Nunley, and J. Meyler Copyright © 2014 L. E. Hammond et al. All rights reserved. Effects of a Meal on the Hemorheologic Responses to Exercise in Young Males Thu, 26 Jun 2014 00:00:00 +0000 Aim. This study investigates the changes in hemorheologic parameters resulting from exercise followed by a standard meal. Methods. In twelve moderately active men a period of exercise on a bicycle ergometer for 30 min at 60% was followed by a test meal or by 30 min rest. Venous blood was sampled for further analysis at baseline, after exercise, and after the meal/rest period. Results. The elongation index (EI) was reduced and a marked rise in plasma viscosity was observed after exercise. A significant decrease in half time of total aggregation (T1/2) and a rise in aggregation index (AI) after exercise were observed; however, after the postexercise period these changes were reversed. Conclusion. The present study demonstrates that physical exercise causes several changes in blood rheology parameters, such as an increase of blood viscosity, a decrease in EI and an increase in AI, and a fall in the T1/2 values. The meal eaten in the postexercise period caused a further reduction in EI values indicating higher red cell rigidity, but not in plasma viscosity or aggregations indices. Such alterations in hemorheologic parameters should not impair the function of the cardiovascular system in fit and healthy people but it could constitute a serious risk under various pathophysiological conditions. Jan Bilski, Aneta Teległów, Janusz Pokorski, Jacek Nitecki, Joanna Pokorska, Ewa Nitecka, Anna Marchewka, Zbigniew Dąbrowski, and Jakub Marchewka Copyright © 2014 Jan Bilski et al. All rights reserved. Angiotensin Converting Enzyme Inhibition Reduces Cardiovascular Responses to Acute Stress in Myocardially Infarcted and Chronically Stressed Rats Thu, 19 Jun 2014 00:00:00 +0000 Previous studies showed that chronically stressed and myocardially infarcted rats respond with exaggerated cardiovascular responses to acute stress. The present experiments were designed to elucidate whether this effect can be abolished by treatment with the angiotensin converting enzyme (ACE) inhibitor captopril. Sprague Dawley rats were subjected either to sham surgery (Groups 1 and 2) or to myocardial infarction (Groups 3 and 4). The rats of Groups 2 and 4 were also exposed to mild chronic stressing. Four weeks after the operation, mean arterial blood pressure (MABP) and heart rate (HR) were measured under resting conditions and after application of acute stress. The cardiovascular responses to the acute stress were determined again 24 h after administration of captopril orally. Captopril significantly reduced resting MABP in each group. Before administration of captopril, the maximum increases in MABP evoked by the acute stressor in all (infarcted and sham-operated) chronically stressed rats and also in the infarcted nonchronically stressed rats were significantly greater than in the sham-operated rats not exposed to chronic stressing. These differences were abolished by captopril. The results suggest that ACE may improve tolerance of acute stress in heart failure and during chronic stressing. A. Cudnoch-Jedrzejewska, K. Czarzasta, L. Puchalska, J. Dobruch, O. Borowik, J. Pachucki, and E. Szczepanska-Sadowska Copyright © 2014 A. Cudnoch-Jedrzejewska et al. All rights reserved. Hemodynamic Indexes Derived from Computed Tomography Angiography to Predict Pulmonary Embolism Related Mortality Wed, 18 Jun 2014 08:28:07 +0000 Pulmonary embolism (PE) induces an acute increase in the right ventricle afterload that can lead to right-ventricular dysfunction (RVD) and eventually to circulatory collapse. Hemodynamic status and presence of RVD are important determinants of adverse outcomes in acute PE. Technologic progress allows computed tomography angiography (CTA) to give more information than accurate diagnosis of PE. It may also provide an insight into hemodynamics and right-ventricular function. Proximal localization of emboli, reflux of contrast medium to the hepatic veins, and right-to-left short-axis ventricular diameter ratio seem to be the most relevant CTA predictors of 30-day mortality. These elements require little postprocessing time, an advantage in the emergency room. We herein review the prognostic value of RVD and other CTA mortality predictors for patients with acute PE. Gregor John, Christophe Marti, Pierre-Alexandre Poletti, and Arnaud Perrier Copyright © 2014 Gregor John et al. All rights reserved. Kinetics and Metabolic Contributions Whilst Swimming at 95, 100, and 105% of the Velocity at Wed, 18 Jun 2014 00:00:00 +0000 A bioenergetical analysis of swimming at intensities near competitive distances is inexistent. It was aimed to compare the transient kinetics responses and metabolic contributions whilst swimming at different velocities around . 12 trained male swimmers performed (i) an incremental protocol to determine the velocity at () and (ii) three square wave exercises from rest to 95, 100, and 105% of . was directly measured using a telemetric portable gas analyser and its kinetics analysed through a double-exponential model. Metabolic contributions were assessed through the sum of three energy components. No differences were observed in the fast component response (—15, 18, and 16 s, —36, 34, and 37 , and Gain—32, 29, and 30  at 95, 100, and 105% of the , resp.) but A2 was higher in 95 and 100% compared to 105% intensity (480.76 ± 247.01, 452.18 ± 217.04, and 147.04 ± 60.40 , resp.). The aerobic energy contribution increased with the time sustained (83 ± 5, 74 ± 6, and 59 ± 7% for 95, 100, and 105%, resp.). The adjustment of the cardiovascular and/or pulmonary systems that determine delivery and diffusion to the exercising muscles did not change with changing intensity, with the exception of slow component kinetics metabolic profiles. Ana C. Sousa, João P. Vilas-Boas, and Ricardo J. Fernandes Copyright © 2014 Ana C. Sousa et al. All rights reserved. Associations of Prenatal Growth with Metabolic Syndrome, Insulin Resistance, and Nutritional Status in Chilean Children Sun, 15 Jun 2014 08:08:27 +0000 Introduction. The association of prenatal growth with nutritional status, metabolic syndrome (MS), and insulin resistance (IR) was studied in school-age children. Methods. A retrospective cohort study was designed linking present data of children with perinatal records. 3325 subjects were enrolled. Anthropometry, blood pressure (BP), and pubertal status were assessed. Blood lipids, glucose, and insulin were measured. Linear associations were assessed using the Cochran-Armitage test. Odds ratios and nonlinear associations were computed. Results. 3290 children (52% females, mean age of 11.4 ± 1 years) were analyzed. Prevalence of obesity, stunting, MS, and IR was 16.0%, 3.6%, 7.3%, and 25.5%, respectively. The strongest positive association was between birth weight (BW) and obesity (OR 2.97 (95% CI 2.01–4.40) at BW ≥ 4,000 g compared to BW 2,500–2,999). The strongest inverse association was between birth length (BL) and stunting (OR 8.70 (95% CI 3.66–20.67) at BL < 48 cm compared to BL 52-53 cm). A U-shaped association between BL and BP ≥ 90th percentile was observed. Significant ORs were also found for MS and IR. Adjustments for present fat mass increased or maintained the most prenatal growth influences. Conclusions. Prenatal growth influences MS, IR, and nutritional status. Prenatal growth was more important than present body composition in determining these outcomes. Francisco Mardones, Pilar Arnaiz, Paz Pacheco, Angelica Dominguez, Luis Villarroel, Johan G. Eriksson, Salesa Barja, Marcelo Farías, and Oscar Castillo Copyright © 2014 Francisco Mardones et al. All rights reserved. Docosahexaenoic Acid Supplementation Early in Pregnancy May Prevent Deep Placentation Disorders Thu, 12 Jun 2014 12:59:11 +0000 Uteroplacental ischemia may cause preterm birth, either due to preterm labor, preterm premature rupture of membranes, or medical indication (in the presence of preeclampsia or fetal growth restriction). Uteroplacental ischemia is the product of defective deep placentation, a failure of invasion, and transformation of the spiral arteries by the trophoblast. The failure of normal placentation generates a series of clinical abnormalities nowadays called “deep placentation disorders”; they include preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, in utero fetal death, and placental abruption. Early reports suggested that a LC-PUFAs (long chain polyunsaturated fatty acids) rich diet reduces the incidence of deep placentation disorders. Recent randomized controlled trials are inconsistent to show the benefit of docosahexaenoic acid (DHA) supplementation during pregnancy to prevent deep placentation disorders, but most of them showed that DHA supplementation was associated with lower risk of early preterm birth. We postulate that DHA supplementation, early in pregnancy, may reduce the incidence of deep placentation disorders. If our hypothesis is correct, DHA supplementation, early in pregnancy, will become a safe and effective strategy for primary prevention of highly relevant pregnancy diseases, such as preterm birth, preeclampsia, and fetal growth restriction. Jorge A. Carvajal Copyright © 2014 Jorge A. Carvajal. All rights reserved. The Influence of Hypoxia during Different Pregnancy Stages on Cardiac Collagen Accumulation in the Adult Offspring Wed, 11 Jun 2014 12:45:46 +0000 We evaluated whether the timing of maternal hypoxia during pregnancy influenced cardiac extracellular matrix accumulation in the adult offspring. Rats in different periods of pregnancy were assigned to maternal hypoxia or control groups. Maternal hypoxia from day 3 to 21 of pregnancy or day 9 to 21 of pregnancy increased collagen I and collagen III expression in the left ventricle of adult offspring (both ). Maternal hypoxia from day 15 to 21 of pregnancy had no effect on adult collagen levels. Our results indicate that maternal hypoxia at critical windows of cardiovascular development can induce pathological cardiac remodeling in the adult rat offspring. Lingxing Wang, Meimei Li, Ziyang Huang, and Zhenhua Wang Copyright © 2014 Lingxing Wang et al. All rights reserved. Evaluation of Cardiac Function Index as Measured by Transpulmonary Thermodilution as an Indicator of Left Ventricular Ejection Fraction in Cardiogenic Shock Wed, 11 Jun 2014 08:21:36 +0000 Introduction. The PiCCO transpulmonary thermodilution technique provides two indices of cardiac systolic function, the cardiac function index (CFI) and the global ejection fraction (GEF). Both appear to be correlated with left ventricular ejection fraction (LVEF) measured by echocardiography in patients with circulatory failure, especially in septic shock. The aim of the present study was to test the reliability of CFI as an indicator of LVEF in patients with cardiogenic shock. Methods. In thirty-five patients with cardiogenic shock, we performed (i) simultaneous measurements of echocardiography LVEF and cardiac function index assessed by transpulmonary thermodilution () and (ii) transpulmonary thermodilution before/after increasing inotropic agents (). Results. Mean LVEF was 31% (+/−11.7), CFI 3/min (+/−1), and GEF 14.2% (+/−6). CFI and GEF were both positively correlated with LVEF (, ). CFI and GEF were significantly increased with inotropic infusion (resp., , ). A cardiac function index <3.47/min predicted a left ventricular ejection fraction ≤35% (sensitivity 81.1% and specificity 63%). In patients with right ventricular dysfunction, CFI was not correlated with LVEF. Conclusion. CFI is correlated with LVEF provided that patient does not present severe right ventricular dysfunction. Thus, the PiCCO transpulmonary thermodilution technique is useful for the monitoring of inotropic therapy during cardiogenic shock. Jessica Perny, Antoine Kimmoun, Pierre Perez, and Bruno Levy Copyright © 2014 Jessica Perny et al. All rights reserved. Analysis of the Response Speed of Musculature of the Knee in Professional Male and Female Volleyball Players Mon, 09 Jun 2014 07:04:14 +0000 The aim of this study was to evaluate the normalized response speed (Vrn) of the knee musculature (flexor and extensor) in high competitive level volleyball players using tensiomyography (TMG) and to analyze the muscular response of the vastus medialis (VM), rectus femoris (RF), vastus lateralis (VL), and biceps femoris (BF) in accordance with the specific position they play in their teams. One hundred and sixty-six players (83 women and 83 men) were evaluated. They belonged to eight teams in the Spanish women’s superleague and eight in the Spanish men’s superleague. The use of Vrn allows avoiding possible sample imbalances due to anatomical and functional differences and demands. We found differences between Vrn in each of the muscles responsible for extension (VM, RF, and VL) and flexion (BF) regardless of the sex. Normalized response speed differences seem to be larger in setters, liberos and outside players compared to middle blockers and larger in males when compared to females. These results of Vrn might respond to the differences in the physical and technical demands of each specific position, showing an improved balance response of the knee extensor and flexor musculature in male professional volleyball players. D. Rodríguez-Ruiz, I. Diez-Vega, D. Rodríguez-Matoso, M. Fernandez-del-Valle, R. Sagastume, and J. J. Molina Copyright © 2014 D. Rodríguez-Ruiz et al. All rights reserved. Inhibition of Hepatitis B Virus Replication by Helper Dependent Adenoviral Vectors Expressing Artificial Anti-HBV Pri-miRs from a Liver-Specific Promoter Thu, 05 Jun 2014 07:31:51 +0000 Research on applying RNA interference (RNAi) to counter HBV replication has led to identification of potential therapeutic sequences. However, before clinical application liver-specific expression and efficient delivery of these sequences remain an important objective. We recently reported short-term inhibition of HBV replication in vivo by using helper dependent adenoviral vectors (HD Ads) expressing anti-HBV sequences from a constitutively active cytomegalovirus (CMV) promoter. To develop the use of liver-specific transcription regulatory elements we investigated the utility of the murine transthyretin (MTTR) promoter for expression of anti-HBV primary microRNAs (pri-miRs). HD Ads containing MTTR promoter effected superior expression of anti-HBV pri-miRs in mice compared to HD Ads containing the CMV promoter. MTTR-containing HD Ads resulted in HBV replication knockdown of up to 94% in mice. HD Ads expressing trimeric anti-HBV pri-miRs silenced HBV replication for 5 weeks. We previously showed that the product of the codelivered lacZ gene induces an immune response, and the duration of HBV silencing in vivo is likely to be attenuated by this effect. Nevertheless, expression of anti-HBV pri-miRs from MTTR promoter is well suited to countering HBV replication and development of HD Ads through attenuation of their immunostimulatory effects should advance their clinical utility. Mohube Betty Mowa, Carol Crowther, Abdullah Ely, and Patrick Arbuthnot Copyright © 2014 Mohube Betty Mowa et al. All rights reserved. Computation and Evaluation of Features of Surface Electromyogram to Identify the Force of Muscle Contraction and Muscle Fatigue Wed, 04 Jun 2014 09:51:55 +0000 The relationship between force of muscle contraction and muscle fatigue with six different features of surface electromyogram (sEMG) was determined by conducting experiments on thirty-five volunteers. The participants performed isometric contractions at 50%, 75%, and 100% of their maximum voluntary contraction (MVC). Six features were considered in this study: normalised spectral index (NSM5), median frequency, root mean square, waveform length, normalised root mean square (NRMS), and increase in synchronization (IIS) index. Analysis of variance (ANOVA) and linear regression analysis were performed to determine the significance of the feature with respect to the three factors: muscle force, muscle fatigue, and subject. The results show that IIS index of sEMG had the highest correlation with muscle fatigue and the relationship was statistically significant (), while NSM5 associated best with level of muscle contraction (%MVC) (). Both of these features were not affected by the intersubject variations (). Sridhar P. Arjunan, Dinesh K. Kumar, and Ganesh Naik Copyright © 2014 Sridhar P. Arjunan et al. All rights reserved. Effect of Dietary Polyunsaturated Fatty Acids on Oxidant/Antioxidant Status in Macrosomic Offspring of Diabetic Rats Mon, 02 Jun 2014 11:04:00 +0000 The aim of this work was to determine the effect of dietary PUFA on oxidant/antioxidant status, in vitro very low and low density lipoprotein (VLDL-LDL), and VLDL-LDL-fatty acid composition in macrosomic pups of diabetic mothers. We hypothesized that PUFA would improve oxidative stress in macrosomia. Diabetes was induced in female Wistar rats fed with the ISIO diet (control) or with the EPAX diet (enriched in PUFAs), by streptozotocin. The macrosomic pups were killed at birth (day 0) and at adulthood (day 90). Lipid parameters and VLDL-LDL-fatty acid composition were investigated. The oxidant/antioxidant status was determined by measuring plasma oxygen radical absorbance capacity (ORAC), hydroperoxides, carbonyl proteins, and VLDL-LDL oxidation. Macrosomic rats of ISIO fed diabetic mothers showed an increase in plasma and VLDL-LDL-triglycerides and VLDL-LDL-cholesterol levels and altered VLDL-LDL-fatty acid composition. Plasma ORAC was low with high hydroperoxide and carbonyl protein levels. The in vitro oxidizability of VLDL-LDL was enhanced in these macrosomic rats. The EPAX diet corrected lipid parameters and improved oxidant/antioxidant status but increased VLDL-LDL susceptibility to oxidation. Macrosomia is associated with lipid abnormalities and oxidative stress. PUFA exerts favorable effects on lipid metabolism and on the oxidant/antioxidant status of macrosomic rats. However, there are no evident effects on VLDL-LDL oxidation. B. Guermouche, N. A. Soulimane-Mokhtari, S. Bouanane, H. Merzouk, S. Merzouk, and M. Narce Copyright © 2014 B. Guermouche et al. All rights reserved. Numerical Simulation and Clinical Implications of Stenosis in Coronary Blood Flow Mon, 02 Jun 2014 00:00:00 +0000 Fractional flow reserve (FFR) is the gold standard to guide coronary interventions. However it can only be obtained via invasive angiography. The objective of this study is to propose a noninvasive method to determine by combining computed tomography angiographic (CTA) images and computational fluid dynamics (CFD) technique. Utilizing the method, this study explored the effects of diameter stenosis (DS), stenosis length, and location on . The baseline left anterior descending (LAD) model was reconstructed from CTA of a healthy porcine heart. A series of models were created by adding an idealized stenosis (with DS from 45% to 75%, stenosis length from 4 mm to 16 mm, and at 4 locations separately). Through numerical simulations, it was found that decreased (from 0.89 to 0.74), when DS increased (from 45% to 75%). Similarly, decreased with the increase of stenosis length and the stenosis located at proximal position had lower than that at distal position. These findings are consistent with clinical observations. Applying the same method on two patients’ CTA images yielded close to the FFR values obtained via invasive angiography. The proposed noninvasive computation of is promising for clinical diagnosis of CAD. Jun-Mei Zhang, Liang Zhong, Tong Luo, Yunlong Huo, Swee Yaw Tan, Aaron Sung Lung Wong, Boyang Su, Min Wan, Xiaodan Zhao, Ghassan S. Kassab, Heow Pueh Lee, Boo Cheong Khoo, Chang-Wei Kang, Te Ba, and Ru San Tan Copyright © 2014 Jun-Mei Zhang et al. All rights reserved. Streptozotocin-Induced Diabetes Models: Pathophysiological Mechanisms and Fetal Outcomes Tue, 27 May 2014 12:31:12 +0000 Glucose homeostasis is controlled by endocrine pancreatic cells, and any pancreatic disturbance can result in diabetes. Because 8% to 12% of diabetic pregnant women present with malformed fetuses, there is great interest in understanding the etiology, pathophysiological mechanisms, and treatment of gestational diabetes. Hyperglycemia enhances the production of reactive oxygen species, leading to oxidative stress, which is involved in diabetic teratogenesis. It has also been suggested that maternal diabetes alters embryonic gene expression, which might cause malformations. Due to ethical issues involving human studies that sometimes have invasive aspects and the multiplicity of uncontrolled variables that can alter the uterine environment during clinical studies, it is necessary to use animal models to better understand diabetic pathophysiology. This review aimed to gather information about pathophysiological mechanisms and fetal outcomes in streptozotocin-induced diabetic rats. To understand the pathophysiological mechanisms and factors involved in diabetes, the use of pancreatic regeneration studies is increasing in an attempt to understand the behavior of pancreatic beta cells. In addition, these studies suggest a new preventive concept as a treatment basis for diabetes, introducing therapeutic efforts to minimize or prevent diabetes-induced oxidative stress, DNA damage, and teratogenesis. D. C. Damasceno, A. O. Netto, I. L. Iessi, F. Q. Gallego, S. B. Corvino, B. Dallaqua, Y. K. Sinzato, A. Bueno, I. M. P. Calderon, and M. V. C. Rudge Copyright © 2014 D. C. Damasceno et al. All rights reserved. Enhanced Amelioration of High-Fat Diet-Induced Fatty Liver by Docosahexaenoic Acid and Lysine Supplementations Sun, 25 May 2014 11:04:52 +0000 Fatty liver disease is the most common pathological condition in the liver. Here, we generated high-fat diet-(HFD-) induced nonalcoholic fatty liver disease (NAFLD) in mice and tested the effects of docosahexaenoic acid (DHA) and lysine during a four-week regular chow (RC)feeding. Our results showed that 1% lysine and the combination of 1% lysine + 1% DHA reduced body weight. Moreover, serum triglyceride levels were reduced by 1% DHA and 1% lysine, whereas serum alanine transaminase activity was reduced by 1% DHA and 1% DHA + 0.5% lysine. Switching to RC reduced hepatic lipid droplet accumulation, which was further reduced by the addition of DHA or lysine. Furthermore, the mRNA expressions of hepatic proinflammatory cytokines were suppressed by DHA and combinations of DHA + lysine, whereas the mRNA for the lipogenic gene, acetyl-CoA carboxylase 1 (ACC1), was suppressed by DHA. In the gonadal adipose tissues, combinations of DHA and lysine inhibited mRNA expression of lipid metabolism-associated genes, including ACC1, fatty acid synthase, lipoprotein lipase, and perilipin. In conclusion, the present study demonstrated that, in conjunction with RC-induced benefits, supplementation with DHA or lysine further ameliorated the high-fat diet-induced NAFLD and provided an alternative strategy to treat, and potentially prevent, NAFLD. Hsin-Yu Lin, Chih-Chien Chen, Yu-Jen Chen, Yuan-Yu Lin, Harry J. Mersmann, and Shih-Torng Ding Copyright © 2014 Hsin-Yu Lin et al. All rights reserved. Relationship between Stroke Volume and Pulse Pressure during Blood Volume Perturbation: A Mathematical Analysis Tue, 20 May 2014 11:50:15 +0000 Arterial pulse pressure has been widely used as surrogate of stroke volume, for example, in the guidance of fluid therapy. However, recent experimental investigations suggest that arterial pulse pressure is not linearly proportional to stroke volume. However, mechanisms underlying the relation between the two have not been clearly understood. The goal of this study was to elucidate how arterial pulse pressure and stroke volume respond to a perturbation in the left ventricular blood volume based on a systematic mathematical analysis. Both our mathematical analysis and experimental data showed that the relative change in arterial pulse pressure due to a left ventricular blood volume perturbation was consistently smaller than the corresponding relative change in stroke volume, due to the nonlinear left ventricular pressure-volume relation during diastole that reduces the sensitivity of arterial pulse pressure to perturbations in the left ventricular blood volume. Therefore, arterial pulse pressure must be used with care when used as surrogate of stroke volume in guiding fluid therapy. Ramin Bighamian and Jin-Oh Hahn Copyright © 2014 Ramin Bighamian and Jin-Oh Hahn. All rights reserved. Maternal Obesity, Inflammation, and Developmental Programming Tue, 20 May 2014 00:00:00 +0000 The prevalence of obesity, especially in women of child-bearing age, is a global health concern. In addition to increasing the immediate risk of gestational complications, there is accumulating evidence that maternal obesity also has long-term consequences for the offspring. The concept of developmental programming describes the process in which an environmental stimulus, including altered nutrition, during critical periods of development can program alterations in organogenesis, tissue development, and metabolism, predisposing offspring to obesity and metabolic and cardiovascular disorders in later life. Although the mechanisms underpinning programming of metabolic disorders remain poorly defined, it has become increasingly clear that low-grade inflammation is associated with obesity and its comorbidities. This review will discuss maternal metainflammation as a mediator of programming in insulin sensitive tissues in offspring. Use of nutritional anti-inflammatories in pregnancy including omega 3 fatty acids, resveratrol, curcumin, and taurine may provide beneficial intervention strategies to ameliorate maternal obesity-induced programming. Stephanie A. Segovia, Mark H. Vickers, Clint Gray, and Clare M. Reynolds Copyright © 2014 Stephanie A. Segovia et al. All rights reserved. Systemic Control of Cell Division and Endoreduplication by NAA and BAP by Modulating CDKs in Root Tip Cells of Allium cepa Sun, 18 May 2014 11:45:48 +0000 Molecular mechanism regulated by auxin and cytokinin during endoreduplication, cell division, and elongation process is studied by using Allium cepa roots as a model system. The activity of CDK genes modulated by auxin and cytokinin during cell division, elongation, and endoreduplication process is explained in this research work. To study the significance of auxin and cytokinin in the management of cell division and endoreduplication process in plant meristematic cells at molecular level endoreduplication was developed in root tips of Allium cepa by giving colchicine treatment. There were inhibition of vegetative growth, formation of c-tumor at root tip, and development of endoreduplicated cells after colchicine treatment. This c-tumor was further treated with NAA and BAP to reinitiate vegetative growth in roots. BAP gave positive response in reinitiation of vegetative growth of roots from center of c-tumor. However, NAA gave negative response in reinitiation of vegetative growth of roots from c-tumor. Further, CDKs gene expression analysis from normal, endoreduplicated, and phytohormone (NAA or BAP) treated root tip was done and remarkable changes in transcription level of CDK genes in normal, endoreduplicated, and phytohormones treated cells were observed. Jigna G. Tank and Vrinda S. Thaker Copyright © 2014 Jigna G. Tank and Vrinda S. Thaker. All rights reserved. Endothelium-Independent Vasorelaxant Effects of Hydroalcoholic Extract from Nigella sativa Seed in Rat Aorta: The Roles of Ca2+ and K+ Channels Mon, 12 May 2014 10:09:51 +0000 Objective. The aim of this study was to elucidate the mechanism(s) responsible for the vasorelaxant effect of Nigella sativa (N. sativa). Methods. The activity of different concentrations of N. sativa extract was evaluated on contractile responses of isolated aorta to KCl and phenylephrine (PE). Results. The extract (2–14 mg/mL) induced a concentration dependent relaxation both in endothelium-intact and endothelium-denuded aortic rings precontracted by PE (10−6 M) and KCl (6 × 10−2 M). Extract reduced PE- and KCl-induced contractions in presence of cumulative concentrations of calcium (10−5–10−2 M) significantly. L-NAME and indomethacin had no effect on vasorelaxation effect of extract in PE-induced contraction. Diltiazem and heparin reduced significantly this vasorelaxation at a concentration of 14 mg/mL of extract; however, N. sativa-induced relaxation was not affected by ruthenium red. Tetraethylammonium chloride reduced the extract-induced relaxation in concentrations of 2–6 mg/mL of extract significantly but glibenclamide reduced this relaxative effect in all concentrations of extract. Conclusions. The inhibitory effect of N. sativa seed extract on the contraction induced by PE and KCl was endothelium-independent. This relaxation was mediated mainly through the inhibition of Ca2+ and channels and also intracellular calcium release. Saeed Niazmand, Elahe Fereidouni, Maryam Mahmoudabady, and Seyed Mojtaba Mousavi Copyright © 2014 Saeed Niazmand et al. All rights reserved. Systemic Approach to Identify Serum microRNAs as Potential Biomarkers for Acute Myocardial Infarction Mon, 12 May 2014 07:43:12 +0000 Background. Recent studies have revealed the role of microRNAs (miRNAs) in a variety of biological and pathological processes, including acute myocardial infarction (AMI). We hypothesized that ST-segment elevation myocardial infarction (STEMI) may be associated with an alteration of miRNAs and that circulating miRNAs may be used as diagnostic markers for STEMI. Methods. Expression levels of 270 serum miRNAs were analyzed in 8 STEMI patients and 8 matched healthy controls to identify miRNAs differentially expressed in the sera of patients with AMI. The differentially expressed miRNAs were evaluated in a separate cohort of 62 subjects, including 31 STEMI patients and 31 normal controls. Results. The initial profiling study identified 12 upregulated and 13 downregulated serum miRNAs in the AMI samples. A subsequent validation study confirmed that serum miR-486-3p and miR-150-3p were upregulated while miR-126-3p, miR-26a-5p, and miR-191-5p were significantly downregulated in the sera of patients with AMI. Ratios between the level of upregulated and downregulated miRNAs were also significantly different in those with AMI. Receiver operator characteristics curve analysis using the expression ratio of miR-486-3p and miR-191-5p showed an area under the curve of 0.863. Conclusion. Our results suggest that serum miRNAs may be used as potential diagnostic biomarkers for STEMI. An Hsu, Shu-Jen Chen, Yu-Sun Chang, Hua-Chien Chen, and Pao-Hsien Chu Copyright © 2014 An Hsu et al. All rights reserved. Glucagon Effects on 3H-Histamine Uptake by the Isolated Guinea-Pig Heart during Anaphylaxis Sun, 11 May 2014 09:19:17 +0000 We estimated the influence of acute glucagon applications on 3H-histamine uptake by the isolated guinea-pig heart, during a single 3H-histamine passage through the coronary circulation, before and during anaphylaxis, and the influence of glucagon on level of histamine, NO, , and H2O2 in the venous effluent during anaphylaxis. Before anaphylaxis, glucagon pretreatment does not change 3H-histamine Umax and the level of endogenous histamine. At the same time, in the presence of glucagon, 3H-histamine Unet is increased and backflux is decreased when compared to the corresponding values in the absence of glucagon. During anaphylaxis, in the presence of glucagon, the values of 3H-histamine Umax and Unet are significantly higher and backflux is significantly lower in the presence of glucagon when compared to the corresponding values in the absence of glucagon. The level of endogenous histamine during anaphylaxis in the presence of glucagon (6.9–7.38 × 10−8 μM) is significantly lower than the histamine level in the absence of glucagon (10.35–10.45 × 10−8 μM). Glucagon pretreatment leads to a significant increase in NO release (5.69 nmol/mL) in comparison with the period before glucagon administration (2.49 nmol/mL). Then, in the presence of glucagon, level fails to increase during anaphylaxis. Also, our results show no significant differences in H2O2 levels before, during, and after anaphylaxis in the presence of glucagon, but these values are significantly lower than the corresponding values in the absence of glucagon. In conclusion, our results show that glucagon increases NO release and prevents the increased release of free radicals during anaphylaxis, and decreases histamine level in the venous effluent during cardiac anaphylaxis, which may be a consequence of decreased histamine release and/or intensified histamine capturing by the heart during anaphylaxis. Mirko Rosic, Oberdan Parodi, Vladimir Jakovljevic, Maja Colic, Vladimir Zivkovic, Vuk Jokovic, and Suzana Pantovic Copyright © 2014 Mirko Rosic et al. All rights reserved. The Effect of Prior Upper Body Exercise on Subsequent Wingate Performance Wed, 07 May 2014 12:06:37 +0000 It has been reported previously that the upper body musculature is continually active during high intensity cycle ergometry. The aim of this study was to examine the effects of prior upper body exercise on subsequent Wingate (WAnT) performance. Eleven recreationally active males (20.8 ± 2.2 yrs; 77.7 ± 12.0 kg; 1.79 ± 0.04 m) completed two trials in a randomised order. In one trial participants completed  s WAnT tests (WAnT1 and WAnT2) with a 6 min recovery period; in the other trial, this protocol was preceded with 4 sets of biceps curls to induce localised arm fatigue. Prior upper body exercise was found to have a statistically significant detrimental effect on peak power output (PPO) during WAnT1 but no effect was observed for mean power output (MPO) . Handgrip (HG) strength was also found to be significantly lower following the upper body exercise. These results demonstrate that the upper body is meaningfully involved in the generation of leg power during intense cycling. Marie Clare Grant, Robert Robergs, Marianne Findlay Baird, and Julien S. Baker Copyright © 2014 Marie Clare Grant et al. All rights reserved. Grain Sterility in relation to Dry Mass Production and Distribution in Rice (Oryza sativa L.) Tue, 06 May 2014 08:31:58 +0000 The experiment was conducted to investigate potential causes of grain sterility in widely cultivated rice variety in Malaysia, MR219 and its two mutant lines (RM311 and RM109) by examining the source-sink relations. RM311 produced increased dry matter yield both at heading and maturity and also showed higher grain yield with greater proportion of grain sterility than the other two genotypes (RM109 and MR219) resulting in the lowest harvest index (49.68%). In contrast, harvest index was greater in RM109 (53.34%) and MR219 (52.76%) with less grain sterility percentage than MR311 indicating that dry matter partitioning to economic yield was better in RM109 and MR219 than in MR311. Results indicated that dry matter allocation per spikelet from heading to maturity was important for reducing grain sterility in rice. The greater above-ground crop dry matter per spikelet was observed in RM109 and MR219 as compared to high dry matter producing genotype; RM311 implies that poor grain filling may not have resulted from dry matter production or source limitation. These findings suggest that grain sterility or poor grain filling in rice is the result of poor translocation and partitioning of assimilates into grains (sink) rather than of limited biomass production or source limitation. Adam B. Puteh, M. Monjurul Alam Mondal, Mohd. Razi Ismail, and Mohammad Abdul Latif Copyright © 2014 Adam B. Puteh et al. All rights reserved. The Importance of the Ionic Product for Water to Understand the Physiology of the Acid-Base Balance in Humans Wed, 30 Apr 2014 14:02:17 +0000 Human plasma is an aqueous solution that has to abide by chemical rules such as the principle of electrical neutrality and the constancy of the ionic product for water. These rules define the acid-base balance in the human body. According to the electroneutrality principle, plasma has to be electrically neutral and the sum of its cations equals the sum of its anions. In addition, the ionic product for water has to be constant. Therefore, the plasma concentration of hydrogen ions depends on the plasma ionic composition. Variations in the concentration of plasma ions that alter the relative proportion of anions and cations predictably lead to a change in the plasma concentration of hydrogen ions by driving adaptive adjustments in water ionization that allow plasma electroneutrality while maintaining constant the ionic product for water. The accumulation of plasma anions out of proportion of cations induces an electrical imbalance compensated by a fall of hydroxide ions that brings about a rise in hydrogen ions (acidosis). By contrast, the deficiency of chloride relative to sodium generates plasma alkalosis by increasing hydroxide ions. The adjustment of plasma bicarbonate concentration to these changes is an important compensatory mechanism that protects plasma pH from severe deviations. María M. Adeva-Andany, Natalia Carneiro-Freire, Cristóbal Donapetry-García, Eva Rañal-Muíño, and Yosua López-Pereiro Copyright © 2014 María M. Adeva-Andany et al. All rights reserved. Potential Role of A2B Adenosine Receptors on Proliferation/Migration of Fetal Endothelium Derived from Preeclamptic Pregnancies Mon, 28 Apr 2014 11:23:06 +0000 To investigate the functionality of adenosine receptor (AR) and the nitric oxide (NO) and vascular endothelial growth factor (VEGF) signaling pathway in the endothelial cell proliferation/migration during preeclampsia, we used human umbilical vein endothelial cells (HUVECs) isolated from normal pregnancies or pregnancies with preeclampsia . Experiments were performed in presence or absence of the nonselective adenosine receptor agonist NECA, the AR selective antagonist MRS-1754, and the nitric oxide synthase (NOS) inhibitor L-NAME. Results indicated that cells from preeclampsia exhibited a significant higher protein level of AR and logEC50 for NECA-mediated proliferation than normotensive pregnancies. The stimulatory effect of NECA (10 μM, 24 h) on cell proliferation was prevented by MRS-1754 (5 nM) coincubation only in cells from normotensive pregnancies. Nevertheless, L-NAME (100 μM, 24 h) reduced the NECA-induced cell proliferation/migration in HUVEC from normal pregnancy; however in preeclampsia only NECA-induced cell proliferation was reduced by L-NAME. Moreover, NECA increased protein nitration and abundance of VEGF in cells from normal pregnancy and effect prevented by MRS-1754 coincubation. Nevertheless, in preeclampsia NECA did not affect the protein level of VEGF. In conclusion HUVECs from preeclampsia exhibit elevated protein level of AR and impairment of AR-mediated NO/VEGF signaling pathway. Jesenia Acurio, Felipe Troncoso, Patricio Bertoglia, Carlos Salomon, Claudio Aguayo, Luis Sobrevia, and Carlos Escudero Copyright © 2014 Jesenia Acurio et al. All rights reserved. Haemodynamic Monitoring in the Intensive Care Unit: Results from a Web-Based Swiss Survey Tue, 22 Apr 2014 08:39:46 +0000 Background. The aim of this survey was to describe, in a situation of growing availability of monitoring devices and parameters, the practices in haemodynamic monitoring at the bedside. Methods. We conducted a Web-based survey in Swiss adult ICUs (2009-2010). The questionnaire explored the kind of monitoring used and how the fluid management was addressed. Results. Our survey included 71% of Swiss ICUs. Echocardiography (95%), pulmonary artery catheter (PAC: 85%), and transpulmonary thermodilution (TPTD) (82%) were the most commonly used. TPTD and PAC were frequently both available, although TPTD was the preferred technique. Echocardiography was widely available (95%) but seems to be rarely performed by intensivists themselves. Guidelines for the management of fluid infusion were available in 45% of ICUs. For the prediction of fluid responsiveness, intensivists rely preferentially on dynamic indices or echocardiographic parameters, but static parameters, such as central venous pressure or pulmonary artery occlusion pressure, were still used. Conclusions. In most Swiss ICUs, multiple haemodynamic monitoring devices are available, although TPTD is most commonly used. Despite the usefulness of echocardiography and its large availability, it is not widely performed by Swiss intensivists themselves. Regarding fluid management, several parameters are used without a clear consensus for the optimal method. Nils Siegenthaler, Raphael Giraud, Till Saxer, Delphine S. Courvoisier, Jacques-André Romand, and Karim Bendjelid Copyright © 2014 Nils Siegenthaler et al. All rights reserved. Exploitation of a Very Small Peptide Nucleic Acid as a New Inhibitor of miR-509-3p Involved in the Regulation of Cystic Fibrosis Disease-Gene Expression Tue, 15 Apr 2014 08:45:15 +0000 Computational techniques, and in particular molecular dynamics (MD) simulations, have been successfully used as a complementary technique to predict and analyse the structural behaviour of nucleic acids, including peptide nucleic acid- (PNA-) RNA hybrids. This study shows that a 7-base long PNA complementary to the seed region of miR-509-3p, one of the miRNAs involved in the posttranscriptional regulation of the CFTR disease-gene of Cystic Fibrosis, and bearing suitable functionalization at its N- and C-ends aimed at improving its resistance to nucleases and cellular uptake, is able to revert the expression of the luciferase gene containing the 3′UTR of the gene in A549 human lung cancer cells, in agreement with the MD results that pointed at the formation of a stable RNA/PNA heteroduplex notwithstanding the short sequence of the latter. The here reported results widen the interest towards the use of small PNAs as effective anti-miRNA agents. Felice Amato, Rossella Tomaiuolo, Fabrizia Nici, Nicola Borbone, Ausilia Elce, Bruno Catalanotti, Stefano D'Errico, Carmine Marco Morgillo, Giuseppe De Rosa, Laura Mayol, Gennaro Piccialli, Giorgia Oliviero, and Giuseppe Castaldo Copyright © 2014 Felice Amato et al. All rights reserved. Exercise Training Could Improve Age-Related Changes in Cerebral Blood Flow and Capillary Vascularity through the Upregulation of VEGF and eNOS Sun, 13 Apr 2014 13:06:06 +0000 This study aimed to investigate the effect of exercise training on age-induced microvascular alterations in the brain. Additionally, the association with the protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) was also assessed. Male Wistar rats were divided into four groups: sedentary-young (SE-Young, ), sedentary aged (SE-Aged, ), immersed-aged (IM-Aged, ), and exercise trained-aged (ET-Aged, 60 minutes/day and 5 days/week for 8 weeks, ) rats. The MAPs of all aged groups, SE-Aged, IM-Aged, and ET-Aged, were significantly higher than that of the SE-Young group. The regional cerebral blood flow (rCBF) in the SE-Aged and IM-Aged was significantly decreased as compared to SE-Young groups. However, rCBF of ET-Aged group was significantly higher than that in the IM-Aged group (). Moreover, the percentage of capillary vascularity (%CV) and the levels of VEGF and eNOS in the ET-Aged group were significantly increased compared to the IM-Aged group (). These results imply that exercise training could improve age-induced microvascular changes and hypoperfusion closely associated with the upregulation of VEGF and eNOS. Sheepsumon Viboolvorakul and Suthiluk Patumraj Copyright © 2014 Sheepsumon Viboolvorakul and Suthiluk Patumraj. All rights reserved. Rapid Degradation of Hfq-Free RyhB in Yersinia pestis by PNPase Independent of Putative Ribonucleolytic Complexes Thu, 10 Apr 2014 13:36:53 +0000 The RNA chaperone Hfq in bacteria stabilizes sRNAs by protecting them from the attack of ribonucleases. Upon release from Hfq, sRNAs are preferably degraded by PNPase. PNPase usually forms multienzyme ribonucleolytic complexes with endoribonuclease E and/or RNA helicase RhlB to facilitate the degradation of the structured RNA. However, whether PNPase activity on Hfq-free sRNAs is associated with the assembly of RNase E or RhlB has yet to be determined. Here we examined the roles of the main endoribonucleases, exoribonucleases, and ancillary RNA-modifying enzymes in the degradation of Y. pestis RyhB in the absence of Hfq. Expectedly, the transcript levels of both RyhB1 and RyhB2 increase only after inactivating PNPase, which confirms the importance of PNPase in sRNA degradation. By contrast, the signal of RyhB becomes barely perceptible after inactivating of RNase III, which may be explained by the increase in PNPase levels resulting from the exemption of pnp mRNA from RNase III processing. No significant changes are observed in RyhB stability after deletion of either the PNPase-binding domain of RNase E or rhlB. Therefore, PNPase acts as a major enzyme of RyhB degradation independent of PNPase-containing RNase E and RhlB assembly in the absence of Hfq. Zhongliang Deng, Zizhong Liu, Yujing Bi, Xiaoyi Wang, Dongsheng Zhou, Ruifu Yang, and Yanping Han Copyright © 2014 Zhongliang Deng et al. All rights reserved. Physical Exercise-Induced Adult Neurogenesis: A Good Strategy to Prevent Cognitive Decline in Neurodegenerative Diseases? Wed, 09 Apr 2014 12:09:17 +0000 Cumulative evidence has indicated that there is an important role for adult hippocampal neurogenesis in cognitive function. With the increasing prevalence of cognitive decline associated with neurodegenerative diseases among the ageing population, physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential preventative strategy/treatment to reduce cognitive decline. Here we review the functional role of adult hippocampal neurogenesis in learning and memory, and how this form of structural plasticity is altered in neurodegenerative diseases known to involve cognitive impairment. We further discuss how physical exercise may contribute to cognitive improvement in the ageing brain by preserving adult neurogenesis, and review the recent approaches for measuring changes in neurogenesis in the live human brain. Suk-yu Yau, Joana Gil-Mohapel, Brian R. Christie, and Kwok-fai So Copyright © 2014 Suk-yu Yau et al. All rights reserved. Oleoylethanolamide: A Novel Potential Pharmacological Alternative to Cannabinoid Antagonists for the Control of Appetite Thu, 03 Apr 2014 13:33:27 +0000 The initial pharmaceutical interest for the endocannabinoid system as a target for antiobesity therapies has been restricted by the severe adverse effects of the CB1 antagonist rimonabant. This study points at oleoylethanolamide (OEA), a monounsaturated analogue, and functional antagonist of anandamide, as a potential and safer antiobesity alternative to CB1 antagonism. Mice treated with equal doses (5 or 10 mg/kg, i.p.) of OEA or rimonabant were analyzed for the progressive expression of spontaneous behaviors (eating, grooming, rearing, locomotion, and resting) occurring during the development of satiety, according to the paradigm called behavioral satiety sequence (BSS). Both drugs reduced food (wet mash) intake to a similar extent. OEA treatment decreased eating activity within the first 30 min and caused a temporary increase of resting time that was not accompanied by any decline of horizontal, vertical and total motor activity. Besides decreasing eating activity, rimonabant caused a marked increase of the time spent grooming and decreased horizontal motor activity, alterations that might be indicative of aversive nonmotivational effects on feeding. These results support the idea that OEA suppresses appetite by stimulating satiety and that its profile of action might be predictive of safer effects in humans as a novel antiobesity treatment. Adele Romano, Roberto Coccurello, Giacomo Giacovazzo, Gaurav Bedse, Anna Moles, and Silvana Gaetani Copyright © 2014 Adele Romano et al. All rights reserved. Abnormal Cardiac Autonomic Regulation in Mice Lacking ASIC3 Thu, 03 Apr 2014 06:42:14 +0000 Integration of sympathetic and parasympathetic outflow is essential in maintaining normal cardiac autonomic function. Recent studies demonstrate that acid-sensing ion channel 3 (ASIC3) is a sensitive acid sensor for cardiac ischemia and prolonged mild acidification can open ASIC3 and evoke a sustained inward current that fires action potentials in cardiac sensory neurons. However, the physiological role of ASIC3 in cardiac autonomic regulation is not known. In this study, we elucidate the role of ASIC3 in cardiac autonomic function using Asic3−/− mice. Asic3−/− mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates. Heart rate variability analyses revealed imbalanced autonomic regulation, with decreased sympathetic function. Furthermore, Asic3−/− mice demonstrated a blunted response to isoproterenol-induced cardiac tachycardia and prolonged duration to recover to baseline heart rate. Moreover, quantitative RT-PCR analysis of gene expression in sensory ganglia and heart revealed that no gene compensation for muscarinic acetylcholines receptors and beta-adrenalin receptors were found in Asic3−/− mice. In summary, we unraveled an important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli, which reveals new implications for therapy in autonomic nervous system-related cardiovascular diseases. Ching-Feng Cheng, Terry B. J. Kuo, Wei-Nan Chen, Chao-Chieh Lin, and Chih-Cheng Chen Copyright © 2014 Ching-Feng Cheng et al. All rights reserved. Synthesis and Gene Silencing Properties of siRNAs Containing Terminal Amide Linkages Wed, 26 Mar 2014 16:45:19 +0000 The active components of the RNAi are 21 nucleotides long dsRNAs containing a 2 nucleotide overhang at the 3′ end, carrying 5′-phosphate and 3′-hydroxyl groups (siRNAs). Structural analysis revealed that the siRNA is functionally bound at both ends to RISC. Terminal modifications are considered with interest as the introduction of chemical moieties interferes with the 3′ overhang recognition by the PAZ domain and the 5′-phosphate recognition by the MID and PIWI domains of RISC. Herein, we report the synthesis of modified siRNAs containing terminal amide linkages by introducing hydroxyethylglycine PNA (hegPNA) moieties at 5′, and at 3′ positions and on both terminals. Results of gene silencing studies highlight that some of these modifications are compatible with the RNAi machinery and markedly increase the resistance to serum-derived nucleases even after 24 h of incubation. Molecular docking simulations were attained to give at atomistic level a clearer picture of the effect of the most performing modifications on the interactions with the human Argonaute 2 PAZ, MID, and PIWI domains. This study adds another piece to the puzzle of the heterogeneous chemical modifications that can be attained to enhance the silencing efficiency of siRNAs. Maria Gaglione, M. Emilia Mercurio, Nicoletta Potenza, Nicola Mosca, Aniello Russo, Ettore Novellino, Sandro Cosconati, and Anna Messere Copyright © 2014 Maria Gaglione et al. All rights reserved. Adult Neurogenesis and Glial Oncogenesis: When the Process Fails Tue, 11 Mar 2014 16:27:49 +0000 Malignant brain tumors, including glioblastoma multiforme (GBM), are known for their high degree of invasiveness, aggressiveness, and lethality. These tumors are made up of heterogeneous cell populations and only a small part of these cells (known as cancer stem cells) is responsible for the initiation and recurrence of the tumor. The biology of cancer stem cells and their role in brain tumor growth and therapeutic resistance has been extensively investigated. Recent work suggests that glial tumors arise from neural stem cells that undergo a defective process of differentiation. The understanding of this process might permit the development of novel treatment strategies targeting cancer stem cells. In the present review, we address the mechanisms underlying glial tumor formation, paying special attention to cancer stem cells and the role of the microenvironment in preserving them and promoting tumor growth. Recent advancements in cancer stem cell biology, especially regarding tumor initiation and resistance to chemo- or radiotherapy, have led to the development of novel treatment strategies that focus on the niche of the stem cells that make up the tumor. Encouraging results from preclinical studies predict that these findings will be translated into the clinical field in the near future. Chary Marquez Batista, Eric Domingos Mariano, Breno José Alencar Pires Barbosa, Matthias Morgalla, Suely Kazue Nagahashi Marie, Manoel Jacobsen Teixeira, and Guilherme Lepski Copyright © 2014 Chary Marquez Batista et al. All rights reserved. Omega-3 Fatty Acid Enriched Chevon (Goat Meat) Lowers Plasma Cholesterol Levels and Alters Gene Expressions in Rats Tue, 25 Feb 2014 08:04:01 +0000 In this study, control chevon (goat meat) and omega-3 fatty acid enriched chevon were obtained from goats fed a 50% oil palm frond diet and commercial goat concentrate for 100 days, respectively. Goats fed the 50% oil palm frond diet contained high amounts of -linolenic acid (ALA) in their meat compared to goats fed the control diet. The chevon was then used to prepare two types of pellets (control or enriched chevon) that were then fed to twenty-male-four-month-old Sprague-Dawley rats ( in each group) for 12 weeks to evaluate their effects on plasma cholesterol levels, tissue fatty acids, and gene expression. There was a significant increase in ALA and docosahexaenoic acid (DHA) in the muscle tissues and liver of the rats fed the enriched chevon compared with the control group. Plasma cholesterol also decreased () in rats fed the enriched chevon compared to the control group. The rat pellets containing enriched chevon significantly upregulated the key transcription factor PPAR- and downregulated SREBP-1c expression relative to the control group. The results showed that the omega-3 fatty acid enriched chevon increased the omega-3 fatty acids in the rat tissues and altered PPAR- and SREBP-1c genes expression. Mahdi Ebrahimi, Mohamed Ali Rajion, Goh Yong Meng, and Abdoreza Soleimani Farjam Copyright © 2014 Mahdi Ebrahimi et al. All rights reserved. Swimming Exercise Changes Hemodynamic Responses Evoked by Blockade of Excitatory Amino Receptors in the Rostral Ventrolateral Medulla in Spontaneously Hypertensive Rats Tue, 18 Feb 2014 12:42:20 +0000 Exercise training reduces sympathetic activity in hypertensive humans and rats. We hypothesized that the swimming exercise would change the neurotransmission in the rostral ventrolateral medulla (RVLM), a key region involved in sympathetic outflow, and hemodynamic control in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Bilateral injections of kynurenic acid (KYN) were carried out in the RVLM in sedentary- (S-) or exercised- (E-) SHR and WKY rats submitted to swimming for 6  weeks. Rats were -chloralose anesthetized and artificially ventilated, with Doppler flow probes around the lower abdominal aorta and superior mesenteric artery. Injections into the RVLM were made before and after i.v. L-NAME (nitric oxide synthase, NOS, inhibitor). Injections of KYN into the RVLM elicited a major vasodilation in the hindlimb more than in the mesenteric artery in E-SHR compared to S-SHR, but similar decrease in arterial pressure was observed in both groups. Injections of KYN into the RVLM after i.v. L-NAME attenuated the hindlimb vasodilation evoked by KYN and increased the mesenteric vasodilation in E-SHR. Swimming exercise can enhance the hindlimb vasodilation mediated by peripheral NO release, reducing the activation of neurons with EAA receptors in the RVLM in SHR. Cristiana A. Ogihara, Gerhardus H. M. Schoorlemmer, Maria de Fátima M. Lazari, Gisele Giannocco, Oswaldo U. Lopes, Eduardo Colombari, and Monica A. Sato Copyright © 2014 Cristiana A. Ogihara et al. All rights reserved. Transferrin-Conjugated SNALPs Encapsulating 2′-O-Methylated miR-34a for the Treatment of Multiple Myeloma Thu, 13 Feb 2014 13:14:30 +0000 Stable nucleic acid lipid vesicles (SNALPs) encapsulating miR-34a to treat multiple myeloma (MM) were developed. Wild type or completely 2′-O-methylated (OMet) MiR-34a was used in this study. Moreover, SNALPs were conjugated with transferrin (Tf) in order to target MM cells overexpressing transferrin receptors (TfRs). The type of miR-34a chemical backbone did not significantly affect the characteristics of SNALPs in terms of mean size, polydispersity index, and zeta potential, while the encapsulation of an OMet miR-34a resulted in a significant increase of miRNA encapsulation into the SNALPs. On the other hand, the chemical conjugation of SNALPs with Tf resulted in a significant decrease of the zeta potential, while size characteristics and miR-34a encapsulation into SNALPs were not significantly affected. In an experimental model of MM, all the animals treated with SNALPs encapsulating miR-34a showed a significant inhibition of the tumor growth. However, the use of SNALPs conjugated with Tf and encapsulating OMet miR-34a resulted in the highest increase of mice survival. These results may represent the proof of concept for the use of SNALPs encapsulating miR-34a for the treatment of MM. Immacolata Scognamiglio, Maria Teresa Di Martino, Virginia Campani, Antonella Virgilio, Aldo Galeone, Annamaria Gullà, Maria Eugenia Gallo Cantafio, Gabriella Misso, Pierosandro Tagliaferri, Pierfrancesco Tassone, Michele Caraglia, and Giuseppe De Rosa Copyright © 2014 Immacolata Scognamiglio et al. All rights reserved. NF-B Mediated Regulation of Adult Hippocampal Neurogenesis: Relevance to Mood Disorders and Antidepressant Activity Wed, 12 Feb 2014 00:00:00 +0000 Adult hippocampal neurogenesis is a peculiar form of process of neuroplasticity that in recent years has gained great attention for its potential implication in cognition and in emotional behavior in physiological conditions. Moreover, a vast array of experimental studies suggested that adult hippocampal neurogenesis may be altered in various neuropsychiatric disorders, including major depression, where its disregulation may contribute to cognitive impairment and/or emotional aspects associated with those diseases. An intriguing area of interest is the potential influence of drugs on adult neurogenesis. In particular, several psychoactive drugs, including antidepressants, were shown to positively modulate adult hippocampal neurogenesis. Among molecules which could regulate adult hippocampal neurogenesis the NF-κB family of transcription factors has been receiving particular attention from our and other laboratories. Herein we review recent data supporting the involvement of NF-κB signaling pathways in the regulation of adult neurogenesis and in the effects of drugs that are endowed with proneurogenic and antidepressant activity. The potential implications of these findings on our current understanding of the process of adult neurogenesis in physiological and pathological conditions and on the search for novel antidepressants are also discussed. Valeria Bortolotto, Bruna Cuccurazzu, Pier Luigi Canonico, and Mariagrazia Grilli Copyright © 2014 Valeria Bortolotto et al. All rights reserved. Stress Hormone and Reproductive System in Response to Honey Supplementation Combined with Different Jumping Exercise Intensities in Female Rats Sun, 09 Feb 2014 15:50:27 +0000 This study was performed to determine the effects of 8-week honey supplementation combined with different jumping exercise intensities on serum cortisol, progesterone, estradiol, and reproductive organs. Eighty-four 9-week-old female rats were divided into 7 groups: baseline controls (), sedentary group (C), 20 and 80 jumps per day (, ), honey (H), and combined honey with 20 and 80 jumps per day (, ) groups. Jumping exercise was performed at 5 days/week and honey was given at a dosage of 1 g/kg body weight/day for 7 days/week. The level of serum cortisol was higher in and compared to C. There was significantly lower value of serum cortisol in compared to . Serum progesterone levels were significantly lower in and compared to C. However, serum progesterone levels were significantly higher in and compared to and . Relative uterine weights were significantly greater in compared to C and , respectively. There was no significant difference in estradiol level and relative ovarian weights among all the groups. Therefore, honey elicited beneficial effects in reducing the increase of cortisol and in increasing the reduce of progesterone levels induced by different intensities jumping exercise in female rats. Maryam Mosavat, Foong Kiew Ooi, and Mahaneem Mohamed Copyright © 2014 Maryam Mosavat et al. All rights reserved. Facial Vibrotactile Stimulation Activates the Parasympathetic Nervous System: Study of Salivary Secretion, Heart Rate, Pupillary Reflex, and Functional Near-Infrared Spectroscopy Activity Wed, 08 Jan 2014 14:32:27 +0000 We previously found that the greatest salivation response in healthy human subjects is produced by facial vibrotactile stimulation of 89 Hz frequency with 1.9 μm amplitude (89 Hz-S), as reported by Hiraba et al. (2012, 20011, and 2008). We assessed relationships between the blood flow to brain via functional near-infrared spectroscopy (fNIRS) in the frontal cortex and autonomic parameters. We used the heart rate (HRV: heart rate variability analysis in RR intervals), pupil reflex, and salivation as parameters, but the interrelation between each parameter and fNIRS measures remains unknown. We were to investigate the relationship in response to established paradigms using simultaneously each parameter-fNIRS recording in healthy human subjects. Analysis of fNIRS was examined by a comparison of various values between before and after various stimuli (89 Hz-S, 114 Hz-S, listen to classic music, and “Ahh” vocalization). We confirmed that vibrotactile stimulation (89 Hz) of the parotid glands led to the greatest salivation, greatest increase in heart rate variability, and the most constricted pupils. Furthermore, there were almost no detectable differences between fNIRS during 89 Hz-S and fNIRS during listening to classical music of fans. Thus, vibrotactile stimulation of 89 Hz seems to evoke parasympathetic activity. Hisao Hiraba, Motoharu Inoue, Kanako Gora, Takako Sato, Satoshi Nishimura, Masaru Yamaoka, Ayano Kumakura, Shinya Ono, Hirotugu Wakasa, Enri Nakayama, Kimiko Abe, and Koichiro Ueda Copyright © 2014 Hisao Hiraba et al. All rights reserved. A Novel Bone Morphogenetic Protein 2 Mutant Mouse, , Displays Impaired Intracellular Handling in Skeletal Muscle Thu, 28 Nov 2013 11:38:32 +0000 We recently reported a novel form of BMP2, designated nBMP2, which is translated from an alternative downstream start codon and is localized to the nucleus rather than secreted from the cell. To examine the function of nBMP2 in the nucleus, we engineered a gene-targeted mutant mouse model () in which nBMP2 cannot be translocated to the nucleus. Immunohistochemistry demonstrated the presence of nBMP2 staining in the myonuclei of wild type but not mutant skeletal muscle. The mouse exhibits altered function of skeletal muscle as demonstrated by a significant increase in the time required for relaxation following a stimulated twitch contraction. Force frequency analysis showed elevated force production in mutant muscles compared to controls from 10 to 60 Hz stimulation frequency, consistent with the mutant muscle’s reduced ability to relax between rapidly stimulated contractions. Muscle relaxation after contraction is mediated by the active transport of Ca2+ from the cytoplasm to the sarcoplasmic reticulum by sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), and enzyme activity assays revealed that SERCA activity in skeletal muscle from mice was reduced to approximately 80% of wild type. These results suggest that nBMP2 plays a role in the establishment or maintenance of intracellular Ca2+ transport pathways in skeletal muscle. Laura C. Bridgewater, Jaime L. Mayo, Bradley G. Evanson, Megan E. Whitt, Spencer A. Dean, Joshua D. Yates, Devin N. Holden, Alina D. Schmidt, Christopher L. Fox, Saroj Dhunghel, Kevin S. Steed, Michael M. Adam, Caitlin A. Nichols, Sampath K. Loganathan, Jeffery R. Barrow, and Chad R. Hancock Copyright © 2013 Laura C. Bridgewater et al. All rights reserved. The Effect of Bedding System Selected by Manual Muscle Testing on Sleep-Related Cardiovascular Functions Mon, 25 Nov 2013 15:32:52 +0000 Background. Different types of mattresses affect sleep quality and waking muscle power. Whether manual muscle testing (MMT) predicts the cardiovascular effects of the bedding system was explored using ten healthy young men. Methods. For each participant, two bedding systems, one inducing the strongest limb muscle force (strong bedding system) and the other inducing the weakest limb force (weak bedding system), were identified using MMT. Each bedding system, in total five mattresses and eight pillows of different firmness, was used for two continuous weeks at the participant’s home in a random and double-blind sequence. A sleep log, a questionnaire, and a polysomnography were used to differentiate the two bedding systems. Results and Conclusion. Heart rate variability and arterial pressure variability analyses showed that the strong bedding system resulted in decreased cardiovascular sympathetic modulation, increased cardiac vagal activity, and increased baroreceptor reflex sensitivity during sleep as compared to the weak bedding system. Different bedding systems have distinct cardiovascular effects during sleep that can be predicted by MMT. Terry B. J. Kuo, Jia-Yi Li, Chun-Ting Lai, Yu-Chun Huang, Ya-Chuan Hsu, and Cheryl C. H. Yang Copyright © 2013 Terry B. J. Kuo et al. All rights reserved. Regulation of PKC Autophosphorylation by Calponin in Contractile Vascular Smooth Muscle Tissue Tue, 19 Nov 2013 12:51:06 +0000 Protein kinase C (PKC) is a key enzyme involved in agonist-induced smooth muscle contraction. In some cases, regulatory phosphorylation of PKC is required for full activation of the enzyme. However, this issue has largely been ignored with respect to PKC-dependent regulation of contractile vascular smooth muscle (VSM) contractility. The first event in PKC regulation is a transphosphorylation by PDK at a conserved threonine in the activation loop of PKC, followed by the subsequent autophosphorylation at the turn motif and hydrophobic motif sites. In the present study, we determined whether phosphorylation of PKC is a regulated process in VSM and also investigated a potential role of calponin in the regulation of PKC. We found that calponin increases the level of in vitro PKC phosphorylation at the PDK and hydrophobic sites, but not the turn motif site. In vascular tissues, phosphorylation of the PKC hydrophobic site, but not turn motif site, as well as phosphorylation of PDK at S241 increased in response to phenylephrine. Calponin knockdown inhibits autophosphorylation of cellular PKC in response to phenylephrine, confirming results with recombinant PKC. Thus these results show that autophosphorylation of PKC is regulated in dVSM and calponin is necessary for autophosphorylation of PKC in VSM. Hak Rim Kim, Cynthia Gallant, and Kathleen G. Morgan Copyright © 2013 Hak Rim Kim et al. All rights reserved. Response of C2C12 Myoblasts to Hypoxia: The Relative Roles of Glucose and Oxygen in Adaptive Cellular Metabolism Tue, 05 Nov 2013 11:54:33 +0000 Background. Oxygen and glucose are two important nutrients for mammalian cell function. In this study, the effect of glucose and oxygen concentrations on C2C12 cellular metabolism was characterized with an emphasis on detecting whether cells show oxygen conformance (OC) in response to hypoxia. Methods. After C2C12 cells being cultured in the levels of glucose at 0.6 mM (LG), 5.6 mM (MG), or 23.3 mM(HG) under normoxic or hypoxic (1% oxygen) condition, cellular oxygen consumption, glucose consumption, lactate production, and metabolic status were determined. Short-term oxygen consumption was measured with a novel oxygen biosensor technique. Longer-term measurements were performed with standard glucose, lactate, and cell metabolism assays. Results. It was found that oxygen depletion in normoxia is dependent on the glucose concentration in the medium. Cellular glucose uptake and lactate production increased significantly in hypoxia than those in normoxia. In hypoxia the cellular response to the level of glucose was different to that in normoxia. The metabolic activities decreased while glucose concentration increased in normoxia, while in hypoxia, metabolic activity was reduced in LG and MG, but unchanged in HG condition. The OC phenomenon was not observed in the present study. Conclusions. Our findings suggested that a combination of low oxygen and low glucose damages the viability of C2C12 cells more seriously than low oxygen alone. In addition, when there is sufficient glucose, C2C12 cells will respond to hypoxia by upregulating anaerobic respiration, as shown by lactate production. Wei Li, Zhen-Fu Hu, Bin Chen, and Guo-Xin Ni Copyright © 2013 Wei Li et al. All rights reserved. Evaluating the Importance of the Carotid Chemoreceptors in Controlling Breathing during Exercise in Man Wed, 23 Oct 2013 11:46:20 +0000 Only the carotid chemoreceptors stimulate breathing during hypoxia in Man. They are also ideally located to warn if the brain’s oxygen supply falls, or if hypercapnia occurs. Since their discovery ~80 years ago stimulation, ablation, and recording experiments still leave 3 substantial difficulties in establishing how important the carotid chemoreceptors are in controlling breathing during exercise in Man: (i) they are in the wrong location to measure metabolic rate (but are ideally located to measure any mismatch), (ii) they receive no known signal during exercise linking them with metabolic rate and no overt mismatch signals occur and (iii) their denervation in Man fails to prevent breathing matching metabolic rate in exercise. New research is needed to enable recording from carotid chemoreceptors in Man to establish whether there is any factor that rises with metabolic rate and greatly increases carotid chemoreceptor activity during exercise. Available evidence so far in Man indicates that carotid chemoreceptors are either one of two mechanisms that explain breathing matching metabolic rate or have no importance. We still lack key experimental evidence to distinguish between these two possibilities. M. J. Parkes Copyright © 2013 M. J. Parkes. All rights reserved. Leptin Increases Blood Pressure and Markers of Endothelial Activation during Pregnancy in Rats Thu, 19 Sep 2013 14:46:27 +0000 Raised leptin levels have been reported in the placentae and serum of women with elevated blood pressure and proteinuria during pregnancy. The role of leptin in this however remains unknown. This study investigates the effect of leptin administration on systolic blood pressure (SBP) and proteinuria and serum markers of endothelial activation during pregnancy in Sprague Dawley rats. From day 1 of pregnancy, 24 rats were randomised into those given either saline (group 1) or leptin at 60 or 120 μg/kg/body weight/day (groups 2 and 3 resp.). SBP was measured every 5 days and 24-h urinary protein was measured at days 0 and 20 of pregnancy. Animals were euthanised on day 20 of pregnancy, and serum was collected for estimation of E-selectin and ICAM-1. Compared to group 1, SBP during the latter part of the pregnancy was significantly higher in the leptin-treated group (). Urinary protein excretion, serum E-selectin, and ICAM-1 were significantly higher in leptin-treated rats (). It seems that leptin administration to normotensive Sprague Dawley rats during pregnancy significantly increases SBP, urinary protein excretion, and markers of endothelial activation. However, further studies are required to examine the underlying mechanism responsible for this and its relevance to preeclampsia in humans. Hisham Saleh Ibrahim, Effat Omar, Gabrielle Ruth Anisah Froemming, and Harbindar Jeet Singh Copyright © 2013 Hisham Saleh Ibrahim et al. All rights reserved. Effects of Estrogen Fluctuation during the Menstrual Cycle on the Response to Stretch-Shortening Exercise in Females Thu, 12 Sep 2013 14:10:37 +0000 The aim of this study was to investigate whether variation in estrogen levels during the menstrual cycle influences susceptibility to exercise-induced muscle damage after stretch-shortening cycle exercise. Physically active women (; age = 20.2 ± 1.7 yr) participated in this research. The subjects performed one session of 100 maximal drop jumps on day 1 or 2 of the follicular phase and another identical session on day 1 or 2 of the ovulatory phase; the order of the sessions was randomized. Quadriceps femoris muscle peak torque evoked by electrical stimulation and maximal voluntary contraction, muscle pain, and CK activity were measured before and at various times up to 72 h after exercise. It was found that the high estrogen level during the ovulatory phase might be related to an earlier return to baseline muscle strength after strenuous stretch-shortening cycle exercise in that phase compared with the follicular phase. The estrogen effect appears to be highly specific to the damaged site because the differences in most EIMD markers (CK, soreness, and low-frequency fatigue) between the two menstrual cycle phases were small. Saulė Sipavičienė, Laura Daniusevičiutė, Irina Klizienė, Sigitas Kamandulis, and Albertas Skurvydas Copyright © 2013 Saulė Sipavičienė et al. All rights reserved. Peak Oxygen Uptake Responses to Training in Obese Adolescents: A Multilevel Allometric Framework to Partition the Influence of Body Size and Maturity Status Mon, 15 Jul 2013 14:46:43 +0000 The influence of body size and maturation on the responses in peak oxygen uptake (VO2) to a 12-week aerobic training and nutritional intervention in obese boys (; 10–16 years) was examined using multilevel allometric regressions. Anthropometry, sexual maturity status, peak VO2, and body composition were measured pre- and postintervention. Significant decrements for body mass, body mass index z-score, and waist circumference and increments for stature, fat-free mass, and peak oxygen uptake were observed after intervention. Partitioning body size on peak VO2, the responses of the individuals to training were positive (11.8% to 12.7% for body mass; 7.6% to 8.1% for fat-free mass). Body mass and fat-free mass were found as significant explanatory variables, with an additional positive effect for chronological. The allometric coefficients () in the initial models were and for body mass and fat-free mass, respectively. The coefficients decreased when age was considered ( for body mass; for fat-free mass). Including maturity indicator in the models was not significant, thus the influence of variability in sexual maturity status in responses to exercise-based intervention in peak VO2 may be mediated by the changes in body dimensions. Humberto M. Carvalho, Gerusa E. Milano, Wendell A. Lopes, António J. Figueiredo, Rosana B. Radominski, and Neiva Leite Copyright © 2013 Humberto M. Carvalho et al. All rights reserved. Noninvasive Monitoring of Training Induced Muscle Adaptation with -MRS: Fibre Type Shifts Correlate with Metabolic Changes Mon, 15 Jul 2013 13:59:46 +0000 Purpose. To evaluate training induced metabolic changes noninvasively with magnetic resonance spectroscopy (-MRS) for measuring muscle fibre type adaptation. Methods. Eleven volunteers underwent a 24-week training, consisting of speed-strength, endurance, and detraining (each 8 weeks). Prior to and following each training period, needle biopsies and -MRS of the resting gastrocnemius muscle were performed. Fibre type distribution was analyzed histologically and tested for correlation with the ratios of high energy phosphates ([PCr]/[], [PCr]/[βATP] and [PCr + ]/[βATP]). The correlation between the changes of the -MRS parameters during training and the resulting changes in fibre composition were also analysed. Results. We observed an increased type-II-fibre proportion after speed-strength and detraining. After endurance training the percentage of fast-twitch fibres was reduced. The progression of the [PCr]/[]-ratio was similar to that of the fast-twitch fibres during the training. We found a correlation between the type-II-fibre proportion and [PCr]/[] (, ) or [PCr]/[βATP] (, ); the correlations between its changes (delta) and the fibre-shift were significant as well (delta[PCr]/[] , delta[PCr]/[βATP] , ). Conclusion. Shifts in fibre type composition and high energy phosphate metabolite content covary in human gastrocnemius muscle. Therefore -MRS might be a feasible method for noninvasive monitoring of exercise-induced fibre type transformation. Eike Hoff, Lars Brechtel, Patrick Strube, Paul Konstanczak, Gisela Stoltenburg-Didinger, Carsten Perka, and Michael Putzier Copyright © 2013 Eike Hoff et al. All rights reserved. The Role of Insula-Associated Brain Network in Touch Wed, 10 Jul 2013 13:36:58 +0000 The insula is believed to be associated with touch-evoked effects. In this work, functional MRI was applied to investigate the network model of insula function when 20 normal subjects received tactile stimulation over segregated areas. Data analysis was performed with SPM8 and Conn toolbox. Activations in the contralateral posterior insula were consistently revealed for all stimulation areas, with the overlap located in area Ig2. The area Ig2 was then used as the seed to estimate the insula-associated network. The right insula, left superior parietal lobule, left superior temporal gyrus, and left inferior parietal cortex showed significant functional connectivity with the seed region for all stimulation conditions. Connectivity maps of most stimulation conditions were mainly distributed in the bilateral insula, inferior parietal cortex, and secondary somatosensory cortex. Post hoc ROI-to-ROI analysis and graph theoretical analysis showed that there were higher correlations between the left insula and the right insula, left inferior parietal cortex and right OP1 for all networks and that the global efficiency was more sensitive than the local efficiency to detect differences between notes in a network. These results suggest that the posterior insula serves as a hub to functionally connect other regions in the detected network and may integrate information from these regions. Pengxu Wei and Ruixue Bao Copyright © 2013 Pengxu Wei and Ruixue Bao. All rights reserved. Effect of Intermittent Low-Frequency Electrical Stimulation on the Rat Gastrocnemius Muscle Tue, 09 Jul 2013 11:32:32 +0000 Low-frequency neuromuscular electrical stimulation (NMES) has been used as an endurance exercise model. This study aimed to test whether low-frequency NMES increases the phosphorylation of anabolic signaling molecules and induces skeletal muscle hypertrophy, as seen with high-frequency NMES. Using Sprague-Dawley rats, 1 bout of exercise (with dissection done immediately (Post0) and 3 h (Post3) after exercise) and another 6 sessions of training were performed. All experimental groups consisted of high- and low-frequency stimulation (HFS: 100 Hz; LFS: 10 Hz). Periodic acid-Schiff (PAS) staining was conducted to investigate type II fiber activation, and western blot analysis (WB) was conducted to examine whether NMES leads to anabolic intracellular signaling. At first, we examined the acute effect of exercise. PAS staining revealed that glycogen depletion occurred in both type I and type II fibers. WB results demonstrated that p70S6K phosphorylation was significantly increased by HFS, but there was no significant difference with LFS. In contrast, ERK 1/2 phosphorylation was increased by LFS at Post0. In the 6-session training, the wet weight and myofibrillar protein were significantly increased by both HFS and LFS. In conclusion, LFS has a similar anabolic effect for skeletal muscle hypertrophy as HFS, but the mediating signaling pathway might differ. Arata Tsutaki, Riki Ogasawara, Koji Kobayashi, Kihyuk Lee, Karina Kouzaki, and Koichi Nakazato Copyright © 2013 Arata Tsutaki et al. All rights reserved. Vasculoprotective Effects of Combined Endothelial Progenitor Cells and Mesenchymal Stem Cells in Diabetic Wound Care: Their Potential Role in Decreasing Wound-Oxidative Stress Mon, 17 Jun 2013 10:59:09 +0000 To investigate whether the combined endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) could enhance angiogenesis and wound healing in diabetic mice. Balb/c nude mice were divided into five groups, including a control group, diabetic group (DM), DM injected with 1 × 106  cells MSCs, DM injected with 1 × 106  cells EPCs, and DM injected with combined 0.5 × 106  cells MSCs and 0.5 × 106  cells EPCs. After seven weeks, the mice were anesthetized, and bilateral full-thickness excision skin wounds were made on the dorsorostral back. The percentage of wound closure in DM group decreased significantly than in control and all other treated groups on day 7 and day 14 (). On day 14, the percentage of capillary vascularity in combine-treated group was significantly higher than in DM (). In the present study, we have demonstrated that the combined EPCs and MSCs can increase vascular endothelial growth factor (VEGF) level and angiogenesis which resulted in reduced neutrophil infiltration, decreased malondialdehyde (MDA) levels, and enhanced wound healing in diabetic mice model. Supakanda Sukpat, Nipan Isarasena, Jutamas Wongphoom, and Suthiluk Patumraj Copyright © 2013 Supakanda Sukpat et al. All rights reserved. Differences in Plasma Cytokine Levels between Elite Kayakers and Nonathletes Mon, 27 May 2013 10:18:25 +0000 Regular moderate exercise has been shown to have anti-inflammatory effects that help prevent several chronic diseases. However, the effects of chronic training an elite athletes have not been the focus of much research. This study aimed to determine whether there were differences in cytokine levels (IL-1β, IL-1ra, IL-6, IL-10, IL-18, IFN-γ, and TNF-α) in circulating peripheral blood (PB) between elite kayakers and nonathletes. Subjects were 13 elite male kayakers, aged years, with average body mass of  kg and  cm height and with a of  mL·kg−1·min−1. The nonathletes were 7 men, aged years, body mass of  kg, and  cm height. Blood samples were collected after six weeks of offtraining and before the start of a new training season. PB leukocyte populations were determined by flow cytometry. Cytokine levels were quantified by ELISA. When nonathletes were compared with the kayakers, the latter exhibited lower plasma concentrations of IL-1β, IL-18, and IFN-γ as well as a lower concentration of IL-1ra. Positive correlations between IL-18 and B cells in the athletes were also found. These results seem to reinforce the anti-inflammatory role of regular training. G. F. Borges, L. Rama, S. Pedreiro, F. Alves, A. Santos, A. Massart, A. Paiva, and A. M. Teixeira Copyright © 2013 G. F. Borges et al. All rights reserved. Attenuated Increase in Maximal Force of Rat Medial Gastrocnemius Muscle after Concurrent Peak Power and Endurance Training Sun, 27 Jan 2013 14:17:52 +0000 Improvement of muscle peak power and oxidative capacity are generally presumed to be mutually exclusive. However, this may not be valid by using fibre type-specific recruitment. Since rat medial gastrocnemius muscle (GM) is composed of high and low oxidative compartments which are recruited task specifically, we hypothesised that the adaptive responses to peak power training were unaffected by additional endurance training. Thirty rats were subjected to either no training (control), peak power training (PT), or both peak power and endurance training (PET), which was performed on a treadmill 5 days per week for 6 weeks. Maximal running velocity increased 13.5% throughout the training and was similar in both training groups. Only after PT, GM maximal force was 10% higher than that of the control group. In the low oxidative compartment, mRNA levels of myostatin and MuRF-1 were higher after PT as compared to those of control and PET groups, respectively. Phospho-S6 ribosomal protein levels remained unchanged, suggesting that the elevated myostatin levels after PT did not inhibit mTOR signalling. In conclusion, even by using task-specific recruitment of the compartmentalized rat GM, additional endurance training interfered with the adaptive response of peak power training and attenuated the increase in maximal force after power training. Regula Furrer, Richard T. Jaspers, Hein L. Baggerman, Nathalie Bravenboer, Paul Lips, and Arnold de Haan Copyright © 2013 Regula Furrer et al. All rights reserved. Is the Second Sodium Pump Electrogenic? Wed, 26 Dec 2012 14:44:44 +0000 Transepithelial sodium transport is a process that involves active Na+ transport at the basolateral membrane of the epithelial cell. This process is mediated by the Na+/K+ pump, which exchanges 3 internal Na+ by 2 external K+ inducing a net charge movement and the second Na+ pump, which transports Na+ accompanied by Cl− and water. It has been suggested that this pump could also be electrogenic. Herein, we evaluated, in MDCK cells, the short-circuit current () generated by these Na+ pumps at the basolateral membrane of the epithelial cells, using amphotericin B as an apical permeabilizing agent. In Cl−-containing media, induced by amphotericin B is totally inhibited by ouabain, indicating that only the electrogenic Na+/K+ pump is detectable in the presence of Cl−. Electrogenicity of the second Na+ pump can be demonstrated in Cl−-free media. The existence of a furosemide-sensitive component of , in addition to an ouabain-sensitive one, was identified in absence of chloride. Passive Cl− movement associated with the function of the second Na+ pump seems to be regulated by the pump itself. These results demonstrate that the second Na+ pump is an electroneutral mechanism result from the stoichiometric movement of Na+ and Cl− across the basolateral plasma membrane of the epithelial cell. L. E. Thomas, M. A. Rocafull, and J. R. del Castillo Copyright © 2013 L. E. Thomas et al. All rights reserved. In Silico Studies of C3 Metabolic Pathway Proteins of Wheat (Triticum aestivum) Wed, 26 Dec 2012 13:11:24 +0000 Photosynthesis is essential for plant productivity and critical for plant growth. More than 90% of plants have a C3 metabolic pathway primarily for carbon assimilation. Improving crop yields for food and fuel is a major challenge for plant biology. To enhance the production of wheat there is need to adopt the strategies that can create the change in plants at the molecular level. During the study we have employed computational bioinformatics and interactomics analysis of C3 metabolic pathway proteins in wheat. The three-dimensional protein modeling provided insight into molecular mechanism and enhanced understanding of physiological processes and biological systems. Therefore in our study, initially we constructed models for nine proteins involving C3 metabolic pathway, as these are not determined through wet lab experiment (NMR, X-ray Crystallography) and not available in RCSB Protein Data Bank and UniProt KB. On the basis of docking interaction analysis, we proposed the schematic diagram of C3 metabolic pathway. Accordingly, there also exist vice versa interactions between 3PGK and Rbcl. Future site and directed mutagenesis experiments in C3 plants could be designed on the basis of our findings to confirm the predicted protein interactions. Muhammad Kashif Naeem, Sobiah Rauf, Hina Iqbal, Muhammad Kausar Nawaz Shah, and Asif Mir Copyright © 2013 Muhammad Kashif Naeem et al. All rights reserved. Waterlogging Tolerance of Crops: Breeding, Mechanism of Tolerance, Molecular Approaches, and Future Prospects Mon, 24 Dec 2012 15:29:01 +0000 Submergence or flood is one of the major harmful abiotic stresses in the low-lying countries and crop losses due to waterlogging are considerably high. Plant breeding techniques, conventional or genetic engineering, might be an effective and economic way of developing crops to grow successfully in waterlogged condition. Marker assisted selection (MAS) is a new and more effective approach which can identify genomic regions of crops under stress, which could not be done previously. The discovery of comprehensive molecular linkage maps enables us to do the pyramiding of desirable traits to improve in submergence tolerance through MAS. However, because of genetic and environmental interaction, too many genes encoding a trait, and using undesirable populations the mapping of QTL was hampered to ensure proper growth and yield under waterlogged conditions Steady advances in the field of genomics and proteomics over the years will be helpful to increase the breeding programs which will help to accomplish a significant progress in the field crop variety development and also improvement in near future. Waterlogging response of soybean and major cereal crops, as rice, wheat, barley, and maize and discovery of QTL related with tolerance of waterlogging, development of resistant variety, and, in addition, future prospects have also been discussed. F. Ahmed, M. Y. Rafii, M. R. Ismail, A. S. Juraimi, H. A. Rahim, R. Asfaliza, and M. A. Latif Copyright © 2013 F. Ahmed et al. All rights reserved. Effect of Nanoparticles and Environmental Particles on a Cocultures Model of the Air-Blood Barrier Sun, 23 Dec 2012 11:02:49 +0000 Exposure to engineered nanoparticles (NPs) and to ambient particles (PM) has increased significantly. During the last decades the application of nano-objects to daily-life goods and the emissions produced in highly urbanized cities have considerably augmented. As a consequence, the understanding of the possible effects of NPs and PM on human respiratory system and particularly on the air-blood barrier (ABB) has become of primary interest. The crosstalk between lung epithelial cells and underlying endothelial cells is indeed essential in determining the effects of inhaled particles. Here we report the effects of metal oxides NPs (CuO and TiO2) and of PM on an in vitro model of the ABB constituted by the type II epithelial cell line (NCI-H441) and the endothelial one (HPMEC-ST1.6R). The results demonstrate that apical exposure of alveolar cells induces significant modulation of proinflammatory proteins also in endothelial cells. Rossella Bengalli, Paride Mantecca, Marina Camatini, and Maurizio Gualtieri Copyright © 2013 Rossella Bengalli et al. All rights reserved. Exercise Training and Work Task Induced Metabolic and Stress-Related mRNA and Protein Responses in Myalgic Muscles Wed, 05 Dec 2012 07:37:00 +0000 The aim was to assess mRNA and/or protein levels of heat shock proteins, cytokines, growth regulating, and metabolic proteins in myalgic muscle at rest and in response to work tasks and prolonged exercise training. A randomized controlled trial included 28 females with trapezius myalgia and 16 healthy controls. Those with myalgia performed ~7 hrs repetitive stressful work and were subsequently randomized to 10 weeks of specific strength training, general fitness training, or reference intervention. Muscles biopsies were taken from the trapezius muscle at baseline, after work and after 10 weeks intervention. The main findings are that the capacity of carbohydrate oxidation was reduced in myalgic compared with healthy muscle. Repetitive stressful work increased mRNA content for heat shock proteins and decreased levels of key regulators for growth and oxidative metabolism. In contrast, prolonged general fitness as well as specific strength training decreased mRNA content of heat shock protein while the capacity of carbohydrate oxidation was increased only after specific strength training. Gisela Sjøgaard, Mette K. Zebis, Kristian Kiilerich, Bengt Saltin, and Henriette Pilegaard Copyright © 2013 Gisela Sjøgaard et al. All rights reserved. Relationship between Occlusal Force Distribution and the Activity of Masseter and Anterior Temporalis Muscles in Asymptomatic Young Adults Wed, 05 Dec 2012 07:35:02 +0000 Healthy subjects have a prevalent side on which they display higher-muscle activity during clenching. The relationship between symmetry of masseter muscle (MM) and anterior temporalis (TA) muscle activities and occlusion has been evaluated on the basis of physiological parameters. The aim of the present study was to investigate whether the symmetry of surface EMG (sEMG) activity in asymptomatic young adults is related to symmetry of occlusal contacts. Material. The study population consisted of seventy-two 18-year-old subjects with no temporomandibular disorder (TMD) symptoms. Method. All the participants underwent an sEMG recording with an 8-channel electromyograph (BioEMG III). A T-Scan III evolution 7.01 device was used to analyze the occlusal contact points. Results. The correlation between the activity of right (R) and left (L) TA and the percentage of occlusal contacts was assessed, but no significant differences were found between the RMM and LMM muscles. The differences in the medium values of sEMG between males and females were not statistically significant. Equilibrated muscular activity between RTA and LTA occurred when occlusal contacts reached the percentage of 65% on the left side. Conclusion. The symmetry of sEMG activity in asymptomatic young adults is not related to symmetry of occlusal contacts. Aneta Wieczorek, Jolanta Loster, and Bartlomiej W. Loster Copyright © 2013 Aneta Wieczorek et al. All rights reserved. Structure and Functional Characteristics of Rat’s Left Ventricle Cardiomyocytes under Antiorthostatic Suspension of Various Duration and Subsequent Reloading Tue, 02 Oct 2012 13:36:40 +0000 The goal of the research was to identify the structural and functional characteristics of the rat's left ventricle under antiorthostatic suspension within 1, 3, 7 and 14 days, and subsequent 3 and 7-day reloading after a 14-day suspension. The transversal stiffness of the cardiomyocyte has been determined by the atomic force microscopy, cell respiration—by polarography and proteins content—by Western blotting. Stiffness of the cortical cytoskeleton increases as soon as one day after the suspension and increases up to the 14th day, and starts decreasing during reloading, reaching the control level after 7 days. The stiffness of the contractile apparatus and the intensity of cell respiration also increases. The content of non-muscle isoforms of actin in the cytoplasmic fraction of proteins does not change during the whole experiment, as does not the beta-actin content in the membrane fraction. The content of gamma-actin in the membrane fraction correlates with the change in the transversal stiffness of the cortical cytoskeleton. Increased content of alpha-actinin-1 and alpha-actinin-4 in the membrane fraction of proteins during the suspension is consistent with increased gamma-actin content there. The opposite direction of change of alpha-actinin-1 and alpha-actinin-4 content suggests their involvement into the signal pathways. I. V. Ogneva, T. M. Mirzoev, N. S. Biryukov, O. M. Veselova, and I. M. Larina Copyright © 2012 I. V. Ogneva et al. All rights reserved. Advances in Muscle Physiology and Pathophysiology 2011 Mon, 09 Apr 2012 11:58:42 +0000 Aikaterini Kontrogianni-Konstantopoulos, Guy Benian, and Henk Granzier Copyright © 2012 Aikaterini Kontrogianni-Konstantopoulos et al. All rights reserved. An Experimental Model for Resistance Exercise in Rodents Thu, 16 Feb 2012 10:43:43 +0000 This study aimed to develop an equipment and system of resistance exercise (RE), based on squat-type exercise for rodents, with control of training variables. We developed an operant conditioning system composed of sound, light and feeding devices that allowed optimized RE performance by the animal. With this system, it is not necessary to impose fasting or electric shock for the animal to perform the task proposed (muscle contraction). Furthermore, it is possible to perform muscle function tests in vivo within the context of the exercise proposed and control variables such as intensity, volume (sets and repetitions), and exercise session length, rest interval between sets and repetitions, and concentric strength. Based on the experiments conducted, we demonstrated that the model proposed is able to perform more specific control of other RE variables, especially rest interval between sets and repetitions, and encourages the animal to exercise through short-term energy restriction and “disturbing” stimulus that do not promote alterations in body weight. Therefore, despite experimental limitations, we believe that this RE apparatus is closer to the physiological context observed in humans. Humberto Nicastro, Nelo Eidy Zanchi, Claudia Ribeiro da Luz, Daniela Fojo Seixas Chaves, and Antonio Herbert Lancha Jr. Copyright © 2012 Humberto Nicastro et al. All rights reserved. Distinct Effects of Contraction-Induced Injury In Vivo on Four Different Murine Models of Dysferlinopathy Mon, 06 Feb 2012 13:06:15 +0000 Mutations in the DYSF gene, encoding dysferlin, cause muscular dystrophies in man. We compared 4 dysferlinopathic mouse strains: SJL/J and B10.SJL-Dysfim/AwaJ (B10.SJL), and A/J and B6.A-Dysfprmd/GeneJ (B6.A/J). The former but not the latter two are overtly myopathic and weaker at 3 months of age. Following repetitive large-strain injury (LSI) caused by lengthening contractions, all except B6.A/J showed ~40% loss in contractile torque. Three days later, torque in SJL/J, B10.SJL and controls, but not A/J, recovered nearly completely. B6.A/J showed ~30% torque loss post-LSI and more variable recovery. Pre-injury, all dysferlinopathic strains had more centrally nucleated fibers (CNFs) and all but A/J showed more inflammation than controls. At D3, all dysferlinopathic strains showed increased necrosis and inflammation, but not more CNFs; controls were unchanged. Dystrophin-null DMDmdx mice showed more necrosis and inflammation than all dysferlin-nulls. Torque loss and inflammation on D3 across all strains were linearly related to necrosis. Our results suggest that (1) dysferlin is not required for functional recovery 3 days after LSI; (2) B6.A/J mice recover from LSI erratically; (3) SJL/J and B10.SJL muscles recover rapidly, perhaps due to ongoing myopathy; (4) although they recover function to different levels, all 4 dysferlinopathic strains show increased inflammation and necrosis 3 days after LSI. Joseph A. Roche, Lisa W. Ru, and Robert J. Bloch Copyright © 2012 Joseph A. Roche et al. All rights reserved. Localization and Regulation of the N Terminal Splice Variant of PGC-1α in Adult Skeletal Muscle Fibers Sun, 29 Jan 2012 15:52:36 +0000 The transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) regulates expression of genes for metabolism and muscle fiber type. Recently, a novel splice variant of PGC-1α (NT-PGC-1α, amino acids 1–270) was cloned and found to be expressed in muscle. Here we use Flag-tagged NT-PGC-1α to examine the subcellular localization and regulation of NT-PGC-1α in skeletal muscle fibers. Flag-NT-PGC-1α is located predominantly in the myoplasm. Nuclear NT-PGC-1α can be increased by activation of protein kinase A. Activation of p38 MAPK by muscle activity or of AMPK had no effect on the subcellular distribution of NT-PGC-1α. Inhibition of CRM1-mediated export only caused relatively slow nuclear accumulation of NT-PGC-1α, indicating that nuclear export of NT-PGC-1α may be mediated by both CRM1-dependent and -independent pathways. Together these results suggest that the regulation of NT-PGC-1α in muscle fibers may be very different from that of the full-length PGC-1α, which is exclusively nuclear. Tiansheng Shen, Yewei Liu, and Martin F. Schneider Copyright © 2012 Tiansheng Shen et al. All rights reserved. Expression and Localization of Ryanodine Receptors in the Frog Semicircular Canal Thu, 19 Jan 2012 14:36:56 +0000 Several experiments suggest an important role for store-released Ca2+ in hair cell organs: drugs targeting IP3 and ryanodine (RyRs) receptors affect release from hair cells, and stores are thought to be involved in vesicle recycling at ribbon synapses. In this work we investigated the semicircular canal distribution of RyRs by immunofluorescence, using slice preparations of the sensory epithelium (to distinguish cell types) and flat mounts of the simpler nonsensory regions. RyRs were present in hair cells, mostly in supranuclear spots, but not in supporting cells; as regards nonsensory regions, they were also localized in dark cells and cells from the ductus. No labeling was found in nerve terminals, although nerve branches could be observed in proximity to hair cell RyR spots. The differential expression of RyR isoforms was studied by RT-PCR and immunoblotting, showing the presence of RyRα in both ampulla and canal arm and RyRβ in the ampulla only. Paola Perin, Laura Botta, Simona Tritto, and Umberto Laforenza Copyright © 2012 Paola Perin et al. All rights reserved. Force Characteristics of the Rat Sternomastoid Muscle Reinnervated with End-to-End Nerve Repair Tue, 13 Dec 2011 17:27:07 +0000 The goal of this study was to establish force data for the rat sternomastoid (SM) muscle after reinnervation with nerve end-to-end anastomosis (EEA), which could be used as a baseline for evaluating the efficacy of new reinnervation techniques. The SM muscle on one side was paralyzed by transecting its nerve and then EEA was performed at different time points: immediate EEA, 1-month and 3-month delay EEA. At the end of 3-month recovery period, the magnitude of functional recovery of the reinnervated SM muscle was evaluated by measuring muscle force and comparing with the force of the contralateral control muscle. Our results demonstrated that the immediately reinnervated SM produced approximately 60% of the maximal tetanic force of the control. The SM with delayed nerve repair yielded approximately 40% of the maximal force. Suboptimal recovery of muscle force after EEA demonstrates the importance of developing alternative surgical techniques to treat muscle paralysis. Stanislaw Sobotka and Liancai Mu Copyright © 2011 Stanislaw Sobotka and Liancai Mu. All rights reserved. The Application of Three-Dimensional Collagen-Scaffolds Seeded with Myoblasts to Repair Skeletal Muscle Defects Mon, 12 Dec 2011 13:53:46 +0000 Three-dimensional (3D) engineered tissue constructs are a novel and promising approach to tissue repair and regeneration. 3D tissue constructs have the ability to restore form and function to damaged soft tissue unlike previous methods, such as plastic surgery, which are able to restore only form, leaving the function of the soft tissue often compromised. In this study, we seeded murine myoblasts (C2C12) into a collagen composite scaffold and cultured the scaffold in a roller bottle cell culture system in order to create a 3D tissue graft in vitro. The 3D graft created in vitro was then utilized to investigate muscle tissue repair in vivo. The 3D muscle grafts were implanted into defect sites created in the skeletal muscles in mice. We detected that the scaffolds degraded slowly over time, and muscle healing was improved which was shown by an increased quantity of innervated and vascularized regenerated muscle fibers. Our results suggest that the collagen composite scaffold seeded with myoblasts can create a 3D muscle graft in vitro that can be employed for defect muscle tissue repair in vivo. Jianqun Ma, Kyle Holden, Jinhong Zhu, Haiying Pan, and Yong Li Copyright © 2011 Jianqun Ma et al. All rights reserved. Localization of Magic-F1 Transgene, Involved in Muscular Hypertrophy, during Early Myogenesis Sat, 10 Dec 2011 16:48:36 +0000 We recently showed that Magic-F1 (Met-activating genetically improved chimeric factor 1), a human recombinant protein derived from hepatocyte growth factor/scatter factor (HGF/SF) induces muscle cell hypertrophy but not progenitor cell proliferation, both in vitro and in vivo. Here, we examined the temporal and spatial expression pattern of Magic-F1 in comparison with Pax3 (paired box gene 3) transcription factor during embryogenesis. Ranging from 9.5 to 17.5 dpc (days post coitum) mouse embryos were analyzed by in situ hybridization using whole mounts during early stages of development (9.5–10.5–11.5 dpc) and cryostat sections for later stages (11.5–13.5–15.5–17.5 dpc). We found that Magic-F1 is expressed in developing organs and tissues of mesenchymal origin, where Pax3 signal appears to be downregulated respect to the wt embryos. These data suggest that Magic-F1 could be responsible of muscular hypertrophy, cooperating with Pax3 signal pathway in skeletal muscle precursor cells. Flavio Ronzoni, Matilde Bongio, Silvio Conte, Luigi Vercesi, Marco Cassano, Carla Tribioli, Daniela Galli, Riccardo Bellazzi, Giovanni Magenes, Maria Gabriella Cusella De Angelis, and Maurilio Sampaolesi Copyright © 2011 Flavio Ronzoni et al. All rights reserved. Facilitated Cross-Bridge Interactions with Thin Filaments by Familial Hypertrophic Cardiomyopathy Mutations in α-Tropomyosin Thu, 01 Dec 2011 14:40:33 +0000 Familial hypertrophic cardiomyopathy (FHC) is a disease of cardiac sarcomeres. To identify molecular mechanisms underlying FHC pathology, functional and structural differences in three FHC-related mutations in recombinant α-Tm (V95A, D175N, and E180G) were characterized using both conventional and modified in vitro motility assays and circular dichroism spectroscopy. Mutant Tm's exhibited reduced α-helical structure and increased unordered structure. When thin filaments were fully occupied by regulatory proteins, little or no motion was detected at pCa 9, and maximum speed (pCa 5) was similar for all tropomyosins. Ca2+-responsiveness of filament sliding speed was increased either by increased pCa50 (V95A), reduced cooperativity n (D175N), or both (E180G). When temperature was increased, thin filaments with E180G exhibited dysregulation at temperatures ~10°C lower, and much closer to body temperature, than WT. When HMM density was reduced, thin filaments with D175N required fewer motors to initiate sliding or achieve maximum sliding speed. Fang Wang, Nicolas M. Brunet, Justin R. Grubich, Ewa A. Bienkiewicz, Thomas M. Asbury, Lisa A. Compton, Goran Mihajlovic, Victor F. Miller, and P. Bryant Chase Copyright © 2011 Fang Wang et al. All rights reserved. Electrophoretic Mobility of Cardiac Myosin Heavy Chain Isoforms Revisited: Application of MALDI TOF/TOF Analysis Wed, 30 Nov 2011 10:57:10 +0000 The expression of two cardiac myosin heavy chain (MyHC) isoforms in response to the thyroid status was studied in left ventricles (LVs) of Lewis rats. Major MyHC isoform in euthyroid and hyperthyroid LVs had a higher mobility on SDS-PAGE, whereas hypothyroid LVs predominantly contained a MyHC isoform with a lower mobility corresponding to that of the control soleus muscle. By comparing the MyHC profiles obtained under altered thyroid states together with the control soleus, we concluded that MyHC𝛼 was represented by the lower band with higher mobility and MyHC𝛽 by the upper band. The identity of these two bands in SDS-PAGE gels was confirmed by western blot and mass spectrometry. Thus, in contrast to the literature data, we found that the MyHC𝛼 possessed a higher mobility rate than the MyHC𝛽 isoform. Our data highlighted the importance of the careful identification of the MyHC𝛼 and MyHC𝛽 isoforms analyzed by the SDS-PAGE. Petra Arnostova, Petr L. Jedelsky, Tomáš Soukup, and Jitka Zurmanova Copyright © 2011 Petra Arnostova et al. All rights reserved. Phasic and Tonic Smooth Muscle Function of the Partially Obstructed Guinea Pig Intestine Mon, 21 Nov 2011 11:13:24 +0000 This study was to generate phasic and tonic stress-strain curves for evaluation of smooth muscle function in the obstructed guinea pig jejunum. Partial and sham obstruction of the jejunum in guinea pigs was created surgically, with guinea pigs not being operated on served as normal controls. The animals survived 2, 4, 7, and 14 days, respectively. The jejunal segment was distended to 10 cm H2O. The pressure and outer diameter changes were recorded. Passive conditions were obtained by using papaverine. Total phasic, tonic, and passive circumferential stress and strain were computed from the diameter and pressure data with reference to the zero-stress-state geometry. The active phasic and tonic stresses were defined as the total phasic and tonic stress minus the passive stress. The thickness of intestinal muscle layers increased in a time-dependent manner after obstruction. The amplitude of passive, total phasic, total tonic, active phasic, and active tonic circumferential stresses increased as function of strain 7 days after obstruction. However, when normalized to muscle layer thickness, the amplitude of active stresses did not differ among the groups. In conclusion, the long-term-obstructed intestine exhibits increased total smooth muscle contraction force. However, the contraction force per smooth muscle unit did not increase. Jingbo Zhao, Donghua Liao, Jian Yang, and Hans Gregersen Copyright © 2011 Jingbo Zhao et al. All rights reserved. Distribution of Myosin Attachment Times Predicted from Viscoelastic Mechanics of Striated Muscle Thu, 17 Nov 2011 18:58:25 +0000 We demonstrate that viscoelastic mechanics of striated muscle, measured as elastic and viscous moduli, emerge directly from the myosin crossbridge attachment time, 𝑡att, also called time-on. The distribution of 𝑡att was modeled using a gamma distribution with shape parameter, 𝑝, and scale parameter, 𝛽. At 5 mM MgATP, 𝛽 was similar between mouse 𝛼-MyHC (16.0±3.7 ms) and 𝛽-MyHC (17.9±2.0 ms), and 𝑝 was higher (𝑃<0.05) for 𝛽-MyHC (5.6±0.4 no units) compared to 𝛼-MyHC (3.2±0.9). At 1 mM MgATP, 𝑝 approached a value of 10 in both isoforms, but 𝛽 rose only in the 𝛽-MyHC (34.8±5.8 ms). The estimated mean 𝑡att (i.e., 𝑝𝛽 product) was longer in the 𝛽-MyHC compared to 𝛼-MyHC, and became prolonged in both isoforms as MgATP was reduced as expected. The application of our viscoelastic model to these isoforms and varying MgATP conditions suggest that 𝑡att is better modeled as a gamma distribution due to its representing multiple temporal events occurring within 𝑡att compared to a single exponential distribution which assumes only one temporal event within 𝑡att. Bradley M. Palmer, Yuan Wang, and Mark S. Miller Copyright © 2011 Bradley M. Palmer et al. All rights reserved. Titin-Actin Interaction: PEVK-Actin-Based Viscosity in a Large Animal Tue, 15 Nov 2011 13:14:43 +0000 Titin exhibits an interaction between its PEVK segment and the actin filament resulting in viscosity, a speed dependent resistive force, which significantly influences diastolic filling in mice. While diastolic disease is clinically pervasive, humans express a more compliant titin (N2BA:N2B ratio ~0.5–1.0) than mice (N2BA:N2B ratio ~0.2). To examine PEVK-actin based viscosity in compliant titin-tissues, we used pig cardiac tissue that expresses titin isoforms similar to that in humans. Stretch-hold experiments were performed at speeds from 0.1 to 10 lengths/s from slack sarcomere lengths (SL) to SL of 2.15 μm. Viscosity was calculated from the slope of stress-relaxation vs stretch speed. Recombinant PEVK was added to compete off native interactions and this found to reduce the slope by 35%, suggesting that PEVK-actin interactions are a strong contributor of viscosity. Frequency sweeps were performed at frequencies of 0.1–400 Hz and recombinant protein reduced viscous moduli by 40% at 2.15 μm and by 50% at 2.25 μm, suggesting a SL-dependent nature of viscosity that might prevent SL ``overshoot’’ at long diastolic SLs. This study is the first to show that viscosity is present at physiologic speeds in the pig and supports the physiologic relevance of PEVK-actin interactions in humans in both health and disease. Charles S. Chung, Julius Bogomolovas, Alexander Gasch, Carlos G. Hidalgo, Siegfried Labeit, and Henk L. Granzier Copyright © 2011 Charles S. Chung et al. All rights reserved. The Beneficial Effect of Direct Peritoneal Resuscitation on Septic Shock in Rats Tue, 15 Nov 2011 11:48:02 +0000 The high mortality associated with conventionally resuscitated septic shock and the subsequent multiple-organ failure remain a very significant and costly clinical problem. Conventional simple intravenous resuscitation (CR) from septic shock often fails to restore the progressive splanchnic vasoconstriction and hypoperfusion, and fails to reverse gut-derived systemic inflammatory response and fluid sequestration. Numerous interventions have been used to protect organ systems and cellular viability from the lethal injury accompanying hypoperfusion and ischemia but none of these efforts have been sufficient to halt or reverse the main course of the pathophysiology noted with conventional resuscitated shock. Recently, some studies have found that in hemorrhagic shock, direct peritoneal resuscitation (DPR) not only produces sustained hyperperfusion in viscera but also has immunomodulatory and anti-fluid sequestration effects. Although the etiology and pathogenesis of septic shock and hemorrhagic shock differ, both kinds of shock result in hypoperfusion of the intestines and other internal organs. In this paper, we seek to determine whether DPR has a similar therapeutic effect on septic shock/resuscitation. Xingjun Luo, Daolin Jian, and Zuojun Lv Copyright © 2011 Xingjun Luo et al. All rights reserved. Muscle Plasticity and 𝜷𝟐-Adrenergic Receptors: Adaptive Responses of 𝜷𝟐-Adrenergic Receptor Expression to Muscle Hypertrophy and Atrophy Tue, 15 Nov 2011 11:45:37 +0000 We discuss the functional roles of 𝛽2-adrenergic receptors in skeletal muscle hypertrophy and atrophy as well as the adaptive responses of 𝛽2-adrenergic receptor expression to anabolic and catabolic conditions. 𝛽2-Adrenergic receptor stimulation using anabolic drugs increases muscle mass by promoting muscle protein synthesis and/or attenuating protein degradation. These effects are prevented by the downregulation of the receptor. Endurance training improves oxidative performance partly by increasing 𝛽2-adrenergic receptor density in exercise-recruited slow-twitch muscles. However, excessive stimulation of 𝛽2-adrenergic receptors negates their beneficial effects. Although the preventive effects of 𝛽2-adrenergic receptor stimulation on atrophy induced by muscle disuse and catabolic hormones or drugs are observed, these catabolic conditions decrease 𝛽2-adrenergic receptor expression in slow-twitch muscles. These findings present evidence against the use of 𝛽2-adrenergic agonists in therapy for muscle wasting and weakness. Thus, 𝛽2-adrenergic receptors in the skeletal muscles play an important physiological role in the regulation of protein and energy balance. Shogo Sato, Ken Shirato, Kaoru Tachiyashiki, and Kazuhiko Imaizumi Copyright © 2011 Shogo Sato et al. All rights reserved. The IQ Motif is Crucial for Cav1.1 Function Sun, 13 Nov 2011 11:00:17 +0000 Ca2+-dependent modulation via calmodulin, with consensus CaM-binding IQ motif playing a key role, has been documented for most high-voltage-activated Ca2+ channels. The skeletal muscle Cav1.1 also exhibits Ca2+-/CaM-dependent modulation. Here, whole-cell Ca2+ current, Ca2+ transient, and maximal, immobilization-resistant charge movement (𝑄max) recordings were obtained from cultured mouse myotubes, to test a role of IQ motif in function of Cav1.1. The effect of introducing mutation (IQ to AA) of IQ motif into Cav1.1 was examined. In dysgenic myotubes expressing YFP-Cav1.1AA, neither Ca2+ currents nor evoked Ca2+ transients were detectable. The loss of Ca2+ current and excitation-contraction coupling did not appear to be a consequence of defective trafficking to the sarcolemma. The 𝑄max in dysgenic myotubes expressing YFP-Cav1.1AA was similar to that of normal myotubes. These findings suggest that the IQ motif of the Cav1.1 may be an unrecognized site of structural and functional coupling between DHPR and RyR. Katarina Stroffekova Copyright © 2011 Katarina Stroffekova. All rights reserved. Exact and Approximate Stochastic Simulation of Intracellular Calcium Dynamics Wed, 09 Nov 2011 11:45:26 +0000 In simulations of chemical systems, the main task is to find an exact or approximate solution of the chemical master equation (CME) that satisfies certain constraints with respect to computation time and accuracy. While Brownian motion simulations of single molecules are often too time consuming to represent the mesoscopic level, the classical Gillespie algorithm is a stochastically exact algorithm that provides satisfying results in the representation of calcium microdomains. Gillespie's algorithm can be approximated via the tau-leap method and the chemical Langevin equation (CLE). Both methods lead to a substantial acceleration in computation time and a relatively small decrease in accuracy. Elimination of the noise terms leads to the classical, deterministic reaction rate equations (RRE). For complex multiscale systems, hybrid simulations are increasingly proposed to combine the advantages of stochastic and deterministic algorithms. An often used exemplary cell type in this context are striated muscle cells (e.g., cardiac and skeletal muscle cells). The properties of these cells are well described and they express many common calcium-dependent signaling pathways. The purpose of the present paper is to provide an overview of the aforementioned simulation approaches and their mutual relationships in the spectrum ranging from stochastic to deterministic algorithms. Nicolas Wieder, Rainer H. A. Fink, and Frederic von Wegner Copyright © 2011 Nicolas Wieder et al. All rights reserved. Thin Filament-Reconstituted Skinned Muscle Fibers for the Study of Muscle Physiology Thu, 03 Nov 2011 17:14:30 +0000 We review the use of thin filament-reconstituted muscle fibers in the study of muscle physiology. Thin filament extraction and reconstitution protocol is a powerful technique to study the role of each component of the thin filament. It is also useful for studying the properties of genetically modified molecules such as actin and tropomyosin. We also review the combination of this protocol with sinusoidal analysis, which will provide a solid technique for determining the effect of regulatory proteins on actomyosin interaction and concomitant cross-bridge kinetics. We suggest that thin filament-reconstituted muscle fibers are an ideal system for studying muscle physiology especially when gene modifications of actin or tropomyosin are involved. Sayaka Higuchi, Yoshikazu Tsukasaki, Norio Fukuda, Satoshi Kurihara, and Hideaki Fujita Copyright © 2011 Sayaka Higuchi et al. All rights reserved. Creep Behavior of Passive Bovine Extraocular Muscle Wed, 02 Nov 2011 13:02:03 +0000 This paper characterized bovine extraocular muscles (EOMs) using creep, which represents long-term stretching induced by a constant force. After preliminary optimization of testing conditions, 20 fresh EOM samples were subjected to four different loading rates of 1.67, 3.33, 8.33, and 16.67%/s, after which creep was observed for 1,500 s. A published quasilinear viscoelastic (QLV) relaxation function was transformed to a creep function that was compared with data. Repeatable creep was observed for each loading rate and was similar among all six anatomical EOMs. The mean creep coefficient after 1,500 seconds for a wide range of initial loading rates was at 1.37±0.03 (standard deviation, SD). The creep function derived from the relaxation-based QLV model agreed with observed creep to within 2.7% following 16.67%/s ramp loading. Measured creep agrees closely with a derived QLV model of EOM relaxation, validating a previous QLV model for characterization of EOM biomechanics. Lawrence Yoo, Hansang Kim, Andrew Shin, Vijay Gupta, and Joseph L. Demer Copyright © 2011 Lawrence Yoo et al. All rights reserved. Survival of Exfoliated Epithelial Cells: A Delicate Balance between Anoikis and Apoptosis Thu, 27 Oct 2011 10:14:47 +0000 The recovery of exfoliated cells from biological fluids is a noninvasive technology which is in high demand in the field of translational research. Exfoliated epithelial cells can be isolated from several body fluids (i.e., breast milk, urines, and digestives fluids) as a cellular mixture (senescent, apoptotic, proliferative, or quiescent cells). The most intriguing are quiescent cells which can be used to derive primary cultures indicating that some phenotypes retain clonogenic potentials. Such exfoliated cells are believed to enter rapidly in anoikis after exfoliation. Anoikis can be considered as an autophagic state promoting epithelial cell survival after a timely loss of contact with extracellular matrix and cell neighbors. This paper presents current understanding of exfoliation along with the influence of methodology on the type of gastrointestinal epithelial cells isolated and, finally, speculates on the balance between anoikis and apoptosis to explain the survival of gastrointestinal epithelial cells in the environment. Bertrand Kaeffer Copyright © 2011 Bertrand Kaeffer. All rights reserved. Ion Transport by Pulmonary Epithelia Thu, 27 Oct 2011 08:43:36 +0000 The lung surface of air-breathing vertebrates is formed by a continuous epithelium that is covered by a fluid layer. In the airways, this epithelium is largely pseudostratified consisting of diverse cell types such as ciliated cells, goblet cells, and undifferentiated basal cells, whereas the alveolar epithelium consists of alveolar type I and alveolar type II cells. Regulation and maintenance of the volume and viscosity of the fluid layer covering the epithelium is one of the most important functions of the epithelial barrier that forms the outer surface area of the lungs. Therefore, the epithelial cells are equipped with a wide variety of ion transport proteins, among which Na+, Cl−, and K+ channels have been identified to play a role in the regulation of the fluid layer. Malfunctions of pulmonary epithelial ion transport processes and, thus, impairment of the liquid balance in our lungs is associated with severe diseases, such as cystic fibrosis and pulmonary oedema. Due to the important role of pulmonary epithelial ion transport processes for proper lung function, the present paper summarizes the recent findings about composition, function, and ion transport properties of the airway epithelium as well as of the alveolar epithelium. Monika I. Hollenhorst, Katrin Richter, and Martin Fronius Copyright © 2011 Monika I. Hollenhorst et al. All rights reserved. Contractile Strength during Variable Heart Duration Is Species and Preload Dependent Wed, 26 Oct 2011 08:06:14 +0000 We investigate the effect of beat-to-beat variability on cardiac contractility. Cardiac trabeculae were isolated from the right ventricle of rabbits and beagle dogs and stimulated to isometrically contract, alternating between fixed steady state versus variable interbeat intervals. Trabeculae were stimulated at physiologically relevant frequencies for each species (dog 1 and 4 Hz; rabbit 2 and 4 Hz) intercalating fixed periods with 40% variability. A subset of the trabeculae (at 90% of optimal length) was stretched prior to stimulation between 5 and 13% and stimulated at the same frequencies with a fixed versus 40% variation. Fixed rate response at the same base frequency was measured before and after each variable period and the average force reported. In canine preparations no change in force was observed as a result of the imposed variability in beat-to-beat duration. In the rabbit, we observed a nonsignificant decrease in force between fixed and variable pacing at both 2 and 4 Hz (n = 8) when 40% variability was introduced. When a 5% and 13% stretch was applied, the correlation coefficient sharply increased, indicating a more prominent impact of the prebeat duration on the following cycle with higher preload. Carlos A. A. Torres and Paul M. L. Janssen Copyright © 2011 Carlos A. A. Torres and Paul M. L. Janssen. All rights reserved. The Sarcomeric Z-Disc and Z-Discopathies Tue, 18 Oct 2011 10:05:01 +0000 The sarcomeric Z-disc defines the lateral borders of the sarcomere and has primarily been seen as a structure important for mechanical stability. This view has changed dramatically within the last one or two decades. A multitude of novel Z-disc proteins and their interacting partners have been identified, which has led to the identification of additional functions and which have now been assigned to this structure. This includes its importance for intracellular signalling, for mechanosensation and mechanotransduction in particular, an emerging importance for protein turnover and autophagy, as well as its molecular links to the t-tubular system and the sarcoplasmic reticulum. Moreover, the discovery of mutations in a wide variety of Z-disc proteins, which lead to perturbations of several of the above-mentioned systems, gives rise to a diverse group of diseases which can be termed Z-discopathies. This paper provides a brief overview of these novel aspects as well as points to future research directions. Ralph Knöll, Byambajav Buyandelger, and Max Lab Copyright © 2011 Ralph Knöll et al. All rights reserved. Tropomodulin Capping of Actin Filaments in Striated Muscle Development and Physiology Mon, 17 Oct 2011 10:13:35 +0000 Efficient striated muscle contraction requires precise assembly and regulation of diverse actin filament systems, most notably the sarcomeric thin filaments of the contractile apparatus. By capping the pointed ends of actin filaments, tropomodulins (Tmods) regulate actin filament assembly, lengths, and stability. Here, we explore the current understanding of the expression patterns, localizations, and functions of Tmods in both cardiac and skeletal muscle. We first describe the mechanisms by which Tmods regulate myofibril assembly and thin filament lengths, as well as the roles of closely related Tmod family variants, the leiomodins (Lmods), in these processes. We also discuss emerging functions for Tmods in the sarcoplasmic reticulum. This paper provides abundant evidence that Tmods are key structural regulators of striated muscle cytoarchitecture and physiology. David S. Gokhin and Velia M. Fowler Copyright © 2011 David S. Gokhin and Velia M. Fowler. All rights reserved. Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel Mon, 17 Oct 2011 08:50:17 +0000 Renal epithelial Na+ transport plays an important role in homeostasis of our body fluid content and blood pressure. Further, the Na+ transport in alveolar epithelial cells essentially controls the amount of alveolar fluid that should be kept at an appropriate level for normal gas exchange. The epithelial Na+ transport is generally mediated through two steps: (1) the entry step of Na+ via epithelial Na+ channel (ENaC) at the apical membrane and (2) the extrusion step of Na+ via the Na+, K+-ATPase at the basolateral membrane. In general, the Na+ entry via ENaC is the rate-limiting step. Therefore, the regulation of ENaC plays an essential role in control of blood pressure and normal gas exchange. In this paper, we discuss two major factors in ENaC regulation: (1) activity of individual ENaC and (2) number of ENaC located at the apical membrane. Yoshinori Marunaka, Naomi Niisato, Akiyuki Taruno, Mariko Ohta, Hiroaki Miyazaki, Shigekuni Hosogi, Ken-ichi Nakajima, Katsuyuki Kusuzaki, Eishi Ashihara, Kyosuke Nishio, Yoshinobu Iwasaki, Takashi Nakahari, and Takahiro Kubota Copyright © 2011 Yoshinori Marunaka et al. All rights reserved. The Evolution of the Mitochondria-to-Calcium Release Units Relationship in Vertebrate Skeletal Muscles Thu, 13 Oct 2011 11:22:41 +0000 The spatial relationship between mitochondria and the membrane systems, more specifically the calcium release units (CRUs) of skeletal muscle, is of profound functional significance. CRUs are the sites at which Ca2+ is released from the sarcoplasmic reticulum during muscle activation. Close mitochondrion-CRU proximity allows the organelles to take up Ca2+ and thus stimulate aerobic metabolism. Skeletal muscles of most mammals display an extensive, developmentally regulated, close mitochondrion-CRU association, fostered by tethering links between the organelles. A comparative look at the vertebrate subphylum however shows that this specific association is only present in the higher vertebrates (mammals). Muscles in all other vertebrates, even if capable of fast activity, rely on a less precise and more limited mitochondrion-CRU proximity, despite some tethering connections. This is most evident in fish muscles. Clustering of free subsarcolemmal mitochondria in proximity of capillaries is also more frequently achieved in mammalian than in other vertebrates. Clara Franzini-Armstrong and Simona Boncompagni Copyright © 2011 Clara Franzini-Armstrong and Simona Boncompagni. All rights reserved. Both Basic and Acidic Amino Acid Residues of Are Involved in Triggering Substate of RyR1 Wed, 05 Oct 2011 12:55:40 +0000 Imperatoxin A () is known to modify the gating of skeletal ryanodine receptor (RyR1). In this paper, the ability of charged aa residues of to induce substate of native RyR1 in HSR was examined. Our results show that the basic residues (e.g., Lys19, Lys20, Lys22, Arg23, and Arg24) are important for producing substate of RyR1. In addition, other basic residues (e.g., Lys30, Arg31, and Arg33) near the C-terminus and some acidic residues (e.g., Glu29, Asp13, and Asp2) are also involved in the generation of substate. Residues such as Lys8 and Thr26 may be involved in the self-regulation of substate of RyR1, since alanine substitution of the aa residues led to a drastic conversion to the substate. The modifications of the channel gating by the wild-type and mutant toxins were similar in purified RyR1. Taken together, the specific charge distributions on the surface of are essential for regulation of the channel gating of RyR1. In Ra Seo, Dae Eun Kang, Dong Woo Song, and Do Han Kim Copyright © 2011 In Ra Seo et al. All rights reserved. The Recent Understanding of the Neurotrophin's Role in Skeletal Muscle Adaptation Sun, 25 Sep 2011 08:26:28 +0000 This paper summarizes the various effects of neurotrophins in skeletal muscle and how these proteins act as potential regulators of the maintenance, function, and regeneration of skeletal muscle fibers. Increasing evidence suggests that this family of neurotrophic factors influence not only the survival and function of innervating motoneurons but also the development and differentiation of myoblasts and muscle fibers. Muscle contractions (e.g., exercise) produce BDNF mRNA and protein in skeletal muscle, and the BDNF seems to play a role in enhancing glucose metabolism and may act for myokine to improve various brain disorders (e.g., Alzheimer's disease and major depression). In adults with neuromuscular disorders, variations in neurotrophin expression are found, and the role of neurotrophins under such conditions is beginning to be elucidated. This paper provides a basis for a better understanding of the role of these factors under such pathological conditions and for treatment of human neuromuscular disease. Kunihiro Sakuma and Akihiko Yamaguchi Copyright © 2011 Kunihiro Sakuma and Akihiko Yamaguchi. All rights reserved. Tocotrienol-Rich Fraction Prevents Cell Cycle Arrest and Elongates Telomere Length in Senescent Human Diploid Fibroblasts Wed, 30 Mar 2011 15:07:57 +0000 This study determined the molecular mechanisms of tocotrienol-rich fraction (TRF) in preventing cellular senescence of human diploid fibroblasts (HDFs). Primary culture of HDFs at various passages were incubated with 0.5 mg/mL TRF for 24 h. Telomere shortening with decreased telomerase activity was observed in senescent HDFs while the levels of damaged DNA and number of cells in G0/G1 phase were increased and S phase cells were decreased. Incubation with TRF reversed the morphology of senescent HDFs to resemble that of young cells with decreased activity of SA-β-gal, damaged DNA, and cells in G0/G1 phase while cells in the S phase were increased. Elongated telomere length and restoration of telomerase activity were observed in TRF-treated senescent HDFs. These findings confirmed the ability of tocotrienol-rich fraction in preventing HDFs cellular ageing by restoring telomere length and telomerase activity, reducing damaged DNA, and reversing cell cycle arrest associated with senescence. Suzana Makpol, Lina Wati Durani, Kien Hui Chua, Yasmin Anum Mohd Yusof, and Wan Zurinah Wan Ngah Copyright © 2011 Suzana Makpol et al. All rights reserved. Advances in Muscle Physiology and Pathophysiology Tue, 27 Jul 2010 08:43:31 +0000 Aikaterini Kontrogianni-Konstantopoulos, Guy Benian, and Henk Granzier Copyright © 2010 Aikaterini Kontrogianni-Konstantopoulos et al. All rights reserved. Modulation of Muscle Atrophy, Fatigue and MLC Phosphorylation by MuRF1 as Indicated by Hindlimb Suspension Studies on MuRF1-KO Mice Thu, 24 Jun 2010 13:54:03 +0000 MuRF1 is a member of the TRIM/RBCC superfamily, a gene family that encompasses a large variety of proteins, all sharing the conserved TRIM (Tripartite Motive) sequential array of RING, B-box, and coiled-coil domains. Within this family, MuRF1(also named TRIM63) is a specialized member that contributes to the development of muscle atrophy and sarcopenia. Here we studied MuRF1's role in muscle atrophy during muscle unloading induced by hindlimb suspension. Consistent with previous studies, we found that MuRF1 inactivation leads to an attenuated muscle atrophy response. The amount of protection was higher as compared to the denervation model, and within the 10 day-suspension period the soleus muscle was spared from atrophy in MuRF1-KO mice. Contractility studies on hindlimb suspended muscle tissues suggested that MuRF1's functions extend beyond muscle trophicity and implicate MuRF1 in muscle fatigue and MLC phosphorylation control: soleus muscle from MuRF1-KO mice fatigued significantly faster and in addition showed a reduced posttetanic twitch potentiation. Thus the present work further established the role of MuRF1 in muscle atrophy and for the first time shows that MuRF1 plays a role in muscle fatigue and twitch potentiation. Siegfried Labeit, Christine H. Kohl, Christian C. Witt, Dittmar Labeit, Jeong Jung, and Henk Granzier Copyright © 2010 Siegfried Labeit et al. All rights reserved. Mechanism of Catch Force: Tethering of Thick and Thin Filaments by Twitchin Wed, 23 Jun 2010 15:11:18 +0000 Catch is a mechanical state occurring in some invertebrate smooth muscles characterized by high force maintenance and resistance to stretch during extremely slow relaxation. During catch, intracellular calcium is near basal concentration and myosin crossbridge cyctng rate is extremely slow. Catch force is relaxed by a protein kinase A-mediated phosphorylation of sites near the N- and C- temini of the minititin twitchin (526 kDa). Some catch force maintenance car also occur together with cycling myosin crossbridges at submaximal calcium concentrations, but not when the muscle is maximally activated. Additionally, the link responsible for catch can adjust during shortening of submaximally activated muscles and maintain catch force at the new shorter length. Twitchin binds to both thick and thin filaments, and the thin filament binding shown by both the N- and Cterminal portions of twitchin is decreased by phosphorylation of the sites that regulate catch. The data suggest that the twitchin molecule itself is the catch force beanng tether between thick and thin filaments. We present a model for the regulation of catch in which the twitchin tether can be displaced from thin filaments by both (a) the phosphorylation of twitchin and (b) the attachment of high force myosin crossbridges. Thomas M. Butler and Marion J. Siegman Copyright © 2010 Thomas M. Butler and Marion J. Siegman. All rights reserved. Roles of Titin in the Structure and Elasticity of the Sarcomere Mon, 21 Jun 2010 13:35:03 +0000 The giant protein titin is thought to play major roles in the assembly and function of muscle sarcomeres. Structural details, such as widths of Z- and M-lines and periodicities in the thick filaments, correlate with the substructure in the respective regions of the titin molecule. Sarcomere rest length, its operating range of lengths, and passive elastic properties are also directly controlled by the properties of titin. Here we review some recent titin data and discuss its implications for sarcomere architecture and elasticity. Larissa Tskhovrebova and John Trinick Copyright © 2010 Larissa Tskhovrebova and John Trinick. All rights reserved. Combining Microdialysis and Near-Infrared Spectroscopy for Studying Effects of Low-Load Repetitive Work on the Intramuscular Chemistry in Trapezius Myalgia Sun, 13 Jun 2010 10:11:58 +0000 Epidemiological research provides strong evidence for a link between repetitive work (RW) and the development of chronic trapezius myalgia (TM). The aims were to further elucidate if an accumulation of sensitising substances or impaired oxygenation is evident in painful muscles during RW. Females with TM () were studied during rest, 30 minutes RW and 60 minutes recovery. Microdialysate samples were obtained to determine changes in intramuscular microdialysate (IMMD) [glutamate], [PG], [lactate], and [pyruvate] (i.e., [concentration]) relative to work. Muscle oxygenation (%St) was assessed using near-infrared spectroscopy. During work, all investigated substances, except PG, increased significantly: [glutamate] (54%, ), [lactate] (26%, ), [pyruvate] (19%, ), while the %St decreased (). During recovery [PG] decreased (), [lactate] remained increased (), [pyruvate] increased progressively (), and %St had returned to baseline. Changes in substance concentrations and oxygenation in response to work indicate normal increase in metabolism but no ongoing inflammation in subjects with TM. Gerd M. Flodgren, Albert G. Crenshaw, Fredrik Hellström, and Martin Fahlström Copyright © 2010 Gerd M. Flodgren et al. All rights reserved. Assembly and Dynamics of Myofibrils Thu, 10 Jun 2010 14:29:39 +0000 We review some of the problems in determining how myofibrils may be assembled and just as importantly how this contractile structure may be renewed by sarcomeric proteins moving between the sarcomere and the cytoplasm. We also address in this personal review the recent evidence that indicates that the assembly and dynamics of myofibrils are conserved whether the cells are analyzed in situ or in tissue culture conditions. We suggest that myofibrillogenesis is a fundamentally conserved process, comparable to protein synthesis, mitosis, or cytokinesis, whether examined in situ or in vitro. Joseph W. Sanger, Jushuo Wang, Yingli Fan, Jennifer White, and Jean M. Sanger Copyright © 2010 Joseph W. Sanger et al. All rights reserved. Cardiac Troponin Mutations and Restrictive Cardiomyopathy Tue, 08 Jun 2010 15:19:37 +0000 Mutations in sarcomeric proteins have recently been established as heritable causes of Restrictive Cardiomyopathy (RCM). RCM is clinically characterized as a defect in cardiac diastolic function, such as, impaired ventricular relaxation, reduced diastolic volume and increased end-diastolic pressure. To date, mutations have been identified in the cardiac genes for desmin, -actin, troponin I and troponin T. Functional studies in skinned muscle fibers reconstituted with troponin mutants have established phenotypes consistent with the clinical findings which include an increase in myofilament sensitivity and basal force. Moreover, when RCM mutants are incorporated into reconstituted myofilaments, the ability to inhibit the ATPase activity is reduced. A majority of the mutations cluster in specific regions of cardiac troponin and appear to be mutational “hot spots.” This paper highlights the functional and clinical characteristics of RCM linked mutations within the troponin complex. Michelle S. Parvatiyar, Jose Renato Pinto, David Dweck, and James D. Potter Copyright © 2010 Michelle S. Parvatiyar et al. All rights reserved. Comparative Biomechanics of Thick Filaments and Thin Filaments with Functional Consequences for Muscle Contraction Sun, 06 Jun 2010 15:59:18 +0000 The scaffold of striated muscle is predominantly comprised of myosin and actin polymers known as thick filaments and thin filaments, respectively. The roles these filaments play in muscle contraction are well known, but the extent to which variations in filament mechanical properties influence muscle function is not fully understood. Here we review information on the material properties of thick filaments, thin filaments, and their primary constituents; we also discuss ways in which mechanical properties of filaments impact muscle performance. Mark S. Miller, Bertrand C. W. Tanner, Lori R. Nyland, and Jim O. Vigoreaux Copyright © 2010 Mark S. Miller et al. All rights reserved. Physiologic Basis and Pathophysiologic Implications of the Diastolic Properties of the Cardiac Muscle Wed, 02 Jun 2010 13:37:09 +0000 Although systole was for long considered the core of cardiac function, hemodynamic performance is evenly dependent on appropriate systolic and diastolic functions. The recognition that isolated diastolic dysfunction is the major culprit for approximately fifty percent of all heart failure cases imposes a deeper understanding of its underlying mechanisms so that better diagnostic and therapeutic strategies can be designed. Risk factors leading to diastolic dysfunction affect myocardial relaxation and/or its material properties by disrupting the homeostasis of cardiomyocytes as well as their relation with surrounding matrix and vascular structures. As a consequence, slower ventricular relaxation and higher myocardial stiffness may result in higher ventricular filling pressures and in the risk of hemodynamic decompensation. Thus, determining the mechanisms of diastolic function and their implications in the pathophysiology of heart failure with normal ejection fraction has become a prominent field in basic and clinical research. João Ferreira-Martins and Adelino F. Leite-Moreira Copyright © 2010 João Ferreira-Martins and Adelino F. Leite-Moreira. All rights reserved. New Insights into the Structural Roles of Nebulin in Skeletal Muscle Tue, 01 Jun 2010 09:14:24 +0000 One important feature of muscle structure and function that has remained relatively obscure is the mechanism that regulates thin filament length. Filament length is an important aspect of muscle function as force production is proportional to the amount of overlap between thick and thin filaments. Recent advances, due in part to the generation of nebulin KO models, reveal that nebulin plays an important role in the regulation of thin filament length. Another structural feature of skeletal muscle that is not well understood is the mechanism involved in maintaining the regular lateral alignment of adjacent sarcomeres, that is, myofibrillar connectivity. Recent studies indicate that nebulin is part of a protein complex that mechanically links adjacent myofibrils. Thus, novel structural roles of nebulin in skeletal muscle involve the regulation of thin filament length and maintaining myofibrillar connectivity. When these functions of nebulin are absent, muscle weakness ensues, as is the case in patients with nemaline myopathy with mutations in nebulin. Here we review these new insights in the role of nebulin in skeletal muscle structure. Coen A. C. Ottenheijm and Henk Granzier Copyright © 2010 Coen A. C. Ottenheijm and Henk Granzier. All rights reserved. Inborn Errors of Energy Metabolism Associated with Myopathies Wed, 26 May 2010 14:29:08 +0000 Inherited neuromuscular disorders affect approximately one in 3,500 children. Structural muscular defects are most common; however functional impairment of skeletal and cardiac muscle in both children and adults may be caused by inborn errors of energy metabolism as well. Patients suffering from metabolic myopathies due to compromised energy metabolism may present with exercise intolerance, muscle pain, reversible or progressive muscle weakness, and myoglobinuria. In this review, the physiology of energy metabolism in muscle is described, followed by the presentation of distinct disorders affecting skeletal and cardiac muscle: glycogen storage diseases types III, V, VII, fatty acid oxidation defects, and respiratory chain defects (i.e., mitochondriopathies). The diagnostic work-up and therapeutic options in these disorders are discussed. Anibh M. Das, Ulrike Steuerwald, and Sabine Illsinger Copyright © 2010 Anibh M. Das et al. All rights reserved. Characteristics of Tetanic Force Produced by the Sternomastoid Muscle of the Rat Tue, 25 May 2010 08:48:09 +0000 The sternomastoid (SM) muscle plays an important role in supporting breathing. It also has unique anatomical advantages that allow its wide use in head and neck tissue reconstruction and muscle reinnervation. However, little is known about its contractile properties. The experiments were run on rats and designed to determine in vivo the relationship between muscle force (active muscle contraction to electrical stimulation) with passive tension (passive force changing muscle length) and two parameters (intensity and frequency) of electrical stimulation. The threshold current for initiating noticeable muscle contraction was 0.03 mA. Maximal muscle force (0.94 N) was produced by using moderate muscle length/tension (28 mm/0.08 N), 0.2 mA stimulation current, and 150 Hz stimulation frequency. These data are important not only to better understand the contractile properties of the rat SM muscle, but also to provide normative values which are critical to reliably assess the extent of functional recovery following muscle reinnervation. Stanislaw Sobotka and Liancai Mu Copyright © 2010 Stanislaw Sobotka and Liancai Mu. All rights reserved. Skeletal Dysplasias Associated with Mild Myopathy—A Clinical and Molecular Review Mon, 24 May 2010 11:18:25 +0000 Musculoskeletal system is a complex assembly of tissues which acts as scaffold for the body and enables locomotion. It is often overlooked that different components of this system may biomechanically interact and affect each other. Skeletal dysplasias are diseases predominantly affecting the development of the osseous skeleton. However, in some cases skeletal dysplasia patients are referred to neuromuscular clinics prior to the correct skeletal diagnosis. The muscular complications seen in these cases are usually mild and may stem directly from the muscle defect and/or from the altered interactions between the individual components of the musculoskeletal system. A correct early diagnosis may enable better management of the patients and a better quality of life. This paper attempts to summarise the different components of the musculoskeletal system which are affected in skeletal dysplasias and lists several interesting examples of such diseases in order to enable better understanding of the complexity of human musculoskeletal system. Katarzyna A. Piróg and Michael D. Briggs Copyright © 2010 Katarzyna A. Piróg and Michael D. Briggs. All rights reserved. Proteomic Profiling of the Dystrophin-Deficient MDX Heart Reveals Drastically Altered Levels of Key Metabolic and Contractile Proteins Sun, 23 May 2010 09:35:55 +0000 Although Duchenne muscular dystrophy is primarily classified as a neuromuscular disease, cardiac complications play an important role in the course of this X-linked inherited disorder. The pathobiochemical steps causing a progressive decline in the dystrophic heart are not well understood. We therefore carried out a fluorescence difference in-gel electrophoretic analysis of 9-month-old dystrophin-deficient versus age-matched normal heart, using the established MDX mouse model of muscular dystrophy-related cardiomyopathy. Out of 2,509 detectable protein spots, 79 2D-spots showed a drastic differential expression pattern, with the concentration of 3 proteins being increased, including nucleoside diphosphate kinase and lamin-A/C, and of 26 protein species being decreased, including ATP synthase, fatty acid binding-protein, isocitrate dehydrogenase, NADH dehydrogenase, porin, peroxiredoxin, adenylate kinase, tropomyosin, actin, and myosin light chains. Hence, the lack of cardiac dystrophin appears to trigger a generally perturbed protein expression pattern in the MDX heart, affecting especially energy metabolism and contractile proteins. Caroline Lewis, Harald Jockusch, and Kay Ohlendieck Copyright © 2010 Caroline Lewis et al. All rights reserved. Pre-mRNA Processing Is Partially Impaired in Satellite Cell Nuclei from Aged Muscles Wed, 19 May 2010 07:55:38 +0000 Satellite cells are responsible for the capacity of mature mammalian skeletal muscles to repair and maintain mass. During aging, skeletal muscle mass as well as the muscle strength and endurance progressively decrease, leading to a condition termed sarcopenia. The causes of sarcopenia are manifold and remain to be completely elucidated. One of them could be the remarkable decline in the efficiency of muscle regeneration; this has been associated with decreasing amounts of satellite cells, but also to alterations in their activation, proliferation, and/or differentiation. In this study, we investigated the satellite cell nuclei of biceps and quadriceps muscles from adult and old rats; morphometry and immunocytochemistry at light and electron microscopy have been combined to assess the organization of the nuclear RNP structural constituents involved in different steps of mRNA formation. We demonstrated that in satellite cells the RNA pathways undergo alterations during aging, possibly hampering their responsiveness to muscle damage. Manuela Malatesta, Federica Perdoni, Sylviane Muller, Carlo Pellicciari, and Carlo Zancanaro Copyright © 2010 Manuela Malatesta et al. All rights reserved. Ordered Assembly of the Adhesive and Electrochemical Connections within Newly Formed Intercalated Disks in Primary Cultures of Adult Rat Cardiomyocytes Wed, 12 May 2010 09:15:49 +0000 The intercalated disk (ID) is a complex structure that electromechanically couples adjoining cardiac myocytes into a functional syncitium. The integrity of the disk is essential for normal cardiac function, but how the diverse elements are assembled into a fully integrated structure is not well understood. In this study, we examined the assembly of new IDs in primary cultures of adult rat cardiac myocytes. From 2 to 5 days after dissociation, the cells flatten and spread, establishing new cell-cell contacts in a manner that recapitulates the in vivo processes that occur during heart development and myocardial remodeling. As cells make contact with their neighbors, transmembrane adhesion proteins localize along the line of apposition, concentrating at the sites of membrane attachment of the terminal sarcomeres. Cx43 gap junctions and ankyrin-G, an essential cytoskeletal component of voltage gated sodium channel complexes, were secondarily recruited to membrane domains involved in cell-cell contacts. The consistent order of the assembly process suggests that there are specific scaffolding requirements for integration of the mechanical and electrochemical elements of the disk. Defining the relationships that are the foundation of disk assembly has important implications for understanding the mechanical dysfunction and cardiac arrhythmias that accompany alterations of ID architecture. Sarah B. Geisler, Kathleen J. Green, Lori L. Isom, Sasha Meshinchi, Jeffrey R. Martens, Mario Delmar, and Mark W. Russell Copyright © 2010 Sarah B. Geisler et al. All rights reserved. Isolation of Nebulin from Rabbit Skeletal Muscle and Its Interaction with Actin Wed, 12 May 2010 08:57:17 +0000 Nebulin is about 800 kDa filamentous protein that binds the entire thin filament of vertebrate skeletal muscle sarcomeres. Nebulin cannot be isolated from muscle except in a completely denatured form by direct solubilization of myofibrils with SDS because nebulin is hardly soluble under salt conditions. In the present study, nebulin was solubilized by a salt solution containing 1 M urea and purified by DEAE-Toyopearl column chromatography via 4 M urea elution. Rotary-shadowed images of nebulin showed entangled knit-like particles, about 20 nm in diameter. The purified nebulin bound to actin filaments to form loose bundles. Nebulin was confirmed to bind actin, -actinin, -actinin, and tropomodulin, but not troponin or tropomyosin. The data shows that full-length nebulin can be also obtained in a functional and presumably native form, verified by data from experiments using recombinant subfragments. Ryo Chitose, Atsushi Watanabe, Masato Asano, Akira Hanashima, Kouhei Sasano, Yulong Bao, Koscak Maruyama, and Sumiko Kimura Copyright © 2010 Ryo Chitose et al. All rights reserved. Sarcomere Control Mechanisms and the Dynamics of the Cardiac Cycle Mon, 10 May 2010 09:55:23 +0000 This review focuses on recent developments in the molecular mechanisms by which Ca activates cardiac sarcomeres and how these mechanisms play out in the cardiac cycle. I emphasize the role of mechanisms intrinsic to the sarcomeres as significant determinants of systolic elastance and ventricular stiffening during ejection. Data are presented supporting the idea that processes intrinsic to the thin filaments may promote cooperative activation of the sarcomeres and be an important factor in maintaining and modifying systolic elastance. Application of these ideas to translational medicine and rationale drug design forms an important rationale for detailed understanding of these processes. R. John Solaro Copyright © 2010 R. John Solaro. All rights reserved. Impaired Skeletal Muscle Repair after Ischemia-Reperfusion Injury in Mice Sun, 09 May 2010 12:08:40 +0000 Ischemia/reperfusion (IR) injury can induce skeletal muscle fibre death and subsequent regeneration. By 14 days, absolute and specific maximal forces and fatigue resistance in ischemic/reperfused soleus muscles were still reduced (−89%, −81%, and −75%, resp.) as compared to control muscles (). The decrease of these parameters in ischemic/reperfused muscle was much greater than that of myotoxic injured muscles (−12%, −11%, and −19%; ). In addition, at 14 days ischemic/reperfused muscle structure was still abnormal, showing small muscle fibres expressing neonatal myosin heavy chain and large necrotic muscle fibres that were not observed in myotoxin treated muscles. By 56 days, in contrast to myotoxin treated muscles, specific maximal force and muscle weight of the ischemic/reperfused muscles did not fully recover (). This differential recovery between ischemic/reperfused and myotoxin treated muscles was not related to the differences in the initial cell death, loss of satellite cells after injury, expression of growth factors (IGF1, IGF2..), or capillary density in regenerating muscles. In conclusion, our results demonstrate that IR injury in mice induces long term detrimental effects in skeletal muscles and that the recovery following IR injury was delayed for yet unknown reasons as compared to myotoxic injury. A. Vignaud, C. Hourde, F. Medja, O. Agbulut, G. Butler-Browne, and A. Ferry Copyright © 2010 A. Vignaud et al. All rights reserved. Temporal Adaptive Changes in Contractility and Fatigability of Diaphragm Muscles from Streptozotocin-Diabetic Rats Thu, 06 May 2010 09:57:25 +0000 Diabetes is characterized by ventilatory depression due to decreased diaphragm (DPH) function. This study investigated the changes in contractile properties of rat DPH muscles over a time interval encompassing from 4 days to 14 weeks after the onset of streptozotocin-induced diabetes, with and without insulin treatment for 2 weeks. Maximum tetanic force in intact DPH muscle strips and recovery from fatiguing stimulation were measured. An early (4-day) depression in contractile function in diabetic DPH was followed by gradual improvement in muscle function and fatigue recovery (8 weeks). DPH contractile function deteriorated again at 14 weeks, a process that was completely reversed by insulin treatment. Maximal contractile force and calcium sensitivity assessed in Triton-skinned DPH fibers showed a similar bimodal pattern and the same beneficial effect of insulin treatment. While an extensive analysis of the isoforms of the contractile and regulatory proteins was not conducted, Western blot analysis of tropomyosin suggests that the changes in diabetic DPH response depended, at least in part, on a switch in fiber type. Marco Brotto, Leticia Brotto, J.-P. Jin, Thomas M. Nosek, and Andrea Romani Copyright © 2010 Marco Brotto et al. All rights reserved. Physiological and Histopathological Investigations on the Effects of 𝛼-Lipoic Acid in Rats Exposed to Malathion Wed, 05 May 2010 14:18:18 +0000 The present study was designed to evaluate the influence of 𝛼-lipoic acid treatment in rats exposed to malathion. Forty adult male rats were used in this study and distributed into four groups. Animals of group 1 were untreated and served as control. Rats of group 2 were orally given malathion at a dose level of 100 mg/kg body weight (BW) for a period of one month. Experimental animals of group 3 were orally given 𝛼-lipoic acid at a dose level of 20 mg/kg BW and after 3 hours exposed to malathion at the same dose given to group 2. Rats of group 4 were supplemented with 𝛼-lipoic acid at the same dose given to group 3. The activities of serum glutamic oxaloacetic acid transaminase (GOT), glutamic pyruvic acid transaminase (GPT), alkaline phosphatase (ALP), and acid phosphatase (ACP), and the values of creatinine, urea, and uric acid were statistically increased, while the values of total protein and total albumin were significantly decreased in rats exposed to malathion. Moreover, administration of malathion for one month resulted in damage of liver and kidney structures. Administration of 𝛼-lipoic acid before malathion exposure to rat can prevent severe alterations of hematobiochemical parameters and disruptions of liver and kidney structures. In conclusion, this study obviously demonstrated that pretreatment with 𝛼-lipoic acid significantly attenuated the physiological and histopathological alterations induced by malathion. Also, the present study identifies new areas of research for development of better therapeutic agents for liver, kidney, and other organs' dysfunctions and diseases. Atef M. Al-Attar Copyright © 2010 Atef M. Al-Attar. All rights reserved. The Masticatory Contractile Load Induced Expression and Activation of Akt1/PKB𝛼 in Muscle Fibers at the Myotendinous Junction within Muscle-Tendon-Bone Unit Tue, 04 May 2010 16:09:28 +0000 The cell specific detection of enzyme activation in response to the physiological contractile load within muscle-tendon-bone unit is essential for understanding of the mechanical forces transmission from muscle cells via tendon to the bone. The hypothesis that the physiological mechanical loading regulates activation of Akt1/PKB𝛼 at Thr308 and at Ser473 in muscle fibers within muscle-tendon-bone unit was tested using quantitative immunohistochemistry, confocal double fluorescence analysis, and immunoblot analysis. In comparison to the staining intensities in peripheral regions of the muscle fibers, Akt1/PKB𝛼 was detected with a higher staining intensity in muscle fibers at the myotendinous junction (MTJ) areas. In muscle fibers at the MTJ areas, Akt1/PKB𝛼 is dually phosphorylated at Thr308 and Ser473. The immunohistochemical results were confirmed by immunoblot analysis. We conclude that contractile load generated by masticatory muscles induces local domain-dependent expression of Akt1/PKB𝛼 as well as activation by dually phosphorylation at Thr308 and Ser473 in muscle fibers at the MTJ areas within muscle-tendon-bone unit. Yüksel Korkmaz, Franz J. Klinz, Mehrnoush Moghbeli, Klaus Addicks, Wolfgang H.-M. Raab, and Wilhelm Bloch Copyright © 2010 Yüksel Korkmaz et al. All rights reserved. Ulvan, a Sulfated Polysaccharide from Green Algae, Activates Plant Immunity through the Jasmonic Acid Signaling Pathway Wed, 28 Apr 2010 09:13:59 +0000 The industrial use of elicitors as alternative tools for disease control needs the identification of abundant sources of them. We report on an elicitor obtained from the green algae Ulva spp. A fraction containing most exclusively the sulfated polysaccharide known as ulvan-induced expression of a GUS gene placed under the control of a lipoxygenase gene promoter. Gene expression profiling was performed upon ulvan treatments on Medicago truncatula and compared to phytohormone effects. Ulvan induced a gene expression signature similar to that observed upon methyl jasmonate treatment (MeJA). Involvement of jasmonic acid (JA) in ulvan response was confirmed by detecting induction of protease inhibitory activity and by hormonal profiling of JA, salicylic acid (SA) and abscisic acid (ABA). Ulvan activity on the hormonal pathway was further consolidated by using Arabidopsis hormonal mutants. Altogether, our results demonstrate that green algae are a potential reservoir of ulvan elicitor which acts through the JA pathway. Valérie Jaulneau, Claude Lafitte, Christophe Jacquet, Sylvie Fournier, Sylvie Salamagne, Xavier Briand, Marie-Thérèse Esquerré-Tugayé, and Bernard Dumas Copyright © 2010 Valérie Jaulneau et al. All rights reserved. Pathogenesis of Insulin Resistance in Skeletal Muscle Mon, 26 Apr 2010 08:36:38 +0000 Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle. Muhammad A. Abdul-Ghani and Ralph A. DeFronzo Copyright © 2010 Muhammad A. Abdul-Ghani and Ralph A. DeFronzo. All rights reserved. What We Know and Do Not Know about Sex and Cardiac Disease Thu, 22 Apr 2010 14:24:36 +0000 Cardiovascular disease (CVD) remains the single leading cause of death in both men and women. A large proportion of the population with CVD will die with a diagnosis of congestive heart failure (CHF). It is becoming increasingly recognized that sex differences exist in the etiology, development, and outcome of CHF. For example, compared to male counterparts, women that present with CHF are typically older and have systolic cardiac function that is not impaired. Despite a growing body of literature addressing the underlying mechanisms of sex dimorphisms in cardiac disease, there remain significant inconsistencies reported in these studies. Given that the development of CHF results from the complex integration of genetic and nongenetic cues, it is not surprising that the elucidation and subsequent identification of molecular mechanisms remains unclear. In this review, key aspects of sex differences in CVD and CHF will be highlighted with an emphasis on some of the unanswered questions regarding these differences. The contention is presented that it becomes critical to reference cellular mechanisms within the context of each sex to better understand these sex dimorphisms. John P. Konhilas Copyright © 2010 John P. Konhilas. All rights reserved. Molecular Structure of Sarcomere-to-Membrane Attachment at M-Lines in C. elegans Muscle Mon, 19 Apr 2010 12:59:14 +0000 C. elegans is an excellent model for studying nonmuscle cell focal adhesions and the analogous muscle cell attachment structures. In the major striated muscle of this nematode, all of the M-lines and the Z-disk analogs (dense bodies) are attached to the muscle cell membrane and underlying extracellular matrix. Accumulating at these sites are many proteins associated with integrin. We have found that nematode M-lines contain a set of protein complexes that link integrin-associated proteins to myosin thick filaments. We have also obtained evidence for intriguing additional functions for these muscle cell attachment proteins. Hiroshi Qadota and Guy M. Benian Copyright © 2010 Hiroshi Qadota and Guy M. Benian. All rights reserved. Dynamic Strength of Titin's Z-Disk End Mon, 19 Apr 2010 11:07:04 +0000 Titin is a giant filamentous protein traversing the half sarcomere of striated muscle with putative functions as diverse as providing structural template, generating elastic response, and sensing and relaying mechanical information. The Z-disk region of titin, which corresponds to the N-terminal end of the molecule, has been thought to be a hot spot for mechanosensing while also serving as anchorage for its sarcomeric attachment. Understanding the mechanics of titin's Z-disk region, particularly under the effect of binding proteins, is of great interest. Here we briefly review recent findings on the structure, molecular associations, and mechanics of titin's Z-disk region. In addition, we report experimental results on the dynamic strength of titin's Z1Z2 domains measured by nanomechanical manipulation of the chemical dimer of a recombinant protein fragment. Veronika Kollár, Dávid Szatmári, László Grama, and Miklós S. Z. Kellermayer Copyright © 2010 Veronika Kollár et al. All rights reserved. Efficient Isolation of Cardiac Stem Cells from Brown Adipose Sun, 18 Apr 2010 14:40:29 +0000 Cardiac stem cells represent a logical cell type to exploit in cardiac regeneration. The efficient harvest of cardiac stem cells from a suitable source would turn promising in cardiac stem cell therapy. Brown adipose was recently found to be a new source of cardiac stem cells, instrumental to myocardial regeneration. Unfortunately, an efficient method for the cell isolation is unavailable so far. In our study we have developed a new method for the efficient isolation of cardiac stem cells from brown adipose by combining different enzymes. Results showed that the total cell yield dramatically increased (more than 10 times, ) compared with that by previous method. The content of CD133-positive cells (reported to differentiate into cardiomyocytes with a high frequency) was much higher than that in the previous report (22.43% versus 3.5%). Moreover, the isolated cells could be the efficiently differentiated into functional cardiomyocytes in optimized conditions. Thus, the new method we established would be of great use in further exploring cardiac stem cell therapy. Zhiqiang Liu, Haibin Wang, Ye Zhang, Jin Zhou, Qiuxia Lin, Yanmeng Wang, Cuimi Duan, Kuiwu Wu, and Changyong Wang Copyright © 2010 Zhiqiang Liu et al. All rights reserved. Epo Is Relevant Neither for Microvascular Formation Nor for the New Formation and Maintenance of Mice Skeletal Muscle Fibres in Both Normoxia and Hypoxia Wed, 14 Apr 2010 15:11:37 +0000 Erythropoietin (Epo) and vascular growth factor (VEGF) are known to be involved in the regulation of cellular activity when oxygen transport is reduced as in anaemia or hypoxic conditions. Because it has been suggested that Epo could play a role in skeletal muscle development, regeneration, and angiogenesis, we aimed to assess Epo deficiency in both normoxia and hypoxia by using an Epo-deficient transgenic mouse model (Epo-TAgh). Histoimmunology, ELISA and real time RT-PCR did not show any muscle fiber atrophy or accumulation of active HIF-1𝛼 but an improvement of microvessel network and an upregulation of VEGFR2 mRNA in Epo-deficient gastrocnemius compared with Wild-Type one. In hypoxia, both models exhibit an upregulation of VEGF120 and VEGFR2 mRNA but no accumulation of Epo protein. EpoR mRNA is not up-regulated in both Epo-deficient and hypoxic gastrocnemius. These results suggest that muscle deconditioning observed in patients suffering from renal failure is not due to Epo deficiency. Luciana Hagström, Onnik Agbulut, Raja El-Hasnaoui-Saadani, Dominique Marchant, Fabrice Favret, Jean-Paul Richalet, Michèle Beaudry, and Thierry Launay Copyright © 2010 Luciana Hagström et al. All rights reserved. Titin-Isoform Dependence of Titin-Actin Interaction and Its Regulation by S100A1/ in Skinned Myocardium Wed, 14 Apr 2010 10:06:22 +0000 Titin, also known as connectin, is a large filamentous protein that greatly contributes to passive myocardial stiffness. In vitro evidence suggests that one of titin's spring elements, the PEVK, interacts with actin and that this adds a viscous component to passive stiffness. Differential splicing of titin gives rise to the stiff N2B and more compliant N2BA isoforms. Here we studied the titin-isoform dependence of titin-actin interaction and studied the bovine left atrium (BLA) that expresses mainly N2BA titin, and the bovine left ventricle (BLV) that expresses a mixture of both N2B and N2BA isforms. For comparison we also studied mouse left ventricular (MLV) myocardium which expresses predominately N2B titin. Using the actin-severing protein gelsolin, we obtained evidence that titin-actin interaction contributes significantly to passive myocardial stiffness in all tissue types, but most in MLV, least in BLA, and an intermediate level in BLV. We also studied whether titin-actin interaction is regulated by S100A1/calcium and found that calcium alone or S100A1 alone did not alter passive stiffness, but that combined they significantly lowered stiffness. We propose that titin-actin interaction is a “viscous break” that is on during diastole and off during systole. Hideto Fukushima, Charles S. Chung, and Henk Granzier Copyright © 2010 Hideto Fukushima et al. All rights reserved. Mitochondrial Translation and Beyond: Processes Implicated in Combined Oxidative Phosphorylation Deficiencies Tue, 13 Apr 2010 15:33:28 +0000 Mitochondrial disorders are a heterogeneous group of often multisystemic and early fatal diseases, which are amongst the most common inherited human diseases. These disorders are caused by defects in the oxidative phosphorylation (OXPHOS) system, which comprises five multisubunit enzyme complexes encoded by both the nuclear and the mitochondrial genomes. Due to the multitude of proteins and intricacy of the processes required for a properly functioning OXPHOS system, identifying the genetic defect that underlies an OXPHOS deficiency is not an easy task, especially in the case of combined OXPHOS defects. In the present communication we give an extensive overview of the proteins and processes (in)directly involved in mitochondrial translation and the biogenesis of the OXPHOS system and their roles in combined OXPHOS deficiencies. This knowledge is important for further research into the genetic causes, with the ultimate goal to effectively prevent and cure these complex and often devastating disorders. Paulien Smits, Jan Smeitink, and Lambert van den Heuvel Copyright © 2010 Paulien Smits et al. All rights reserved. Force Transmission between Synergistic Skeletal Muscles through Connective Tissue Linkages Mon, 12 Apr 2010 13:59:10 +0000 The classic view of skeletal muscle is that force is generated within its muscle fibers and then directly transmitted in-series, usually via tendon, onto the skeleton. In contrast, recent results suggest that muscles are mechanically connected to surrounding structures and cannot be considered as independent actuators. This article will review experiments on mechanical interactions between muscles mediated by such epimuscular myofascial force transmission in physiological and pathological muscle conditions. In a reduced preparation, involving supraphysiological muscle conditions, it is shown that connective tissues surrounding muscles are capable of transmitting substantial force. In more physiologically relevant conditions of intact muscles, however, it appears that the role of this myofascial pathway is small. In addition, it is hypothesized that connective tissues can serve as a safety net for traumatic events in muscle or tendon. Future studies are needed to investigate the importance of intermuscular force transmission during movement in health and disease. Huub Maas and Thomas G. Sandercock Copyright © 2010 Huub Maas and Thomas G. Sandercock. All rights reserved. Mechanical and Electrophysiological Properties of the Sarcolemma of Muscle Fibers in Two Murine Models of Muscle Dystrophy: Col6a1 and Mdx Thu, 08 Apr 2010 14:25:18 +0000 This study aimed to analyse the sarcolemma of Col6a1 fibers in comparison with wild type and mdx fibers, taken as positive control in view of the known structural and functional alterations of their membranes. Structural and mechanical properties were studied in single muscle fibers prepared from FDB muscle using atomic force microscopy (AFM) and conventional electrophysiological techniques to measure ionic conductance and capacitance. While the sarcolemma topography was preserved in both types of dystrophic fibers, membrane elasticity was significantly reduced in Col6a1 and increased in mdx fibers. In the membrane of Col6a1 fibers ionic conductance was increased likely due to an increased leakage, whereas capacitance was reduced, and the action potential (ap) depolarization rate was reduced. The picture emerging from experiments on fibers in culture was consistent with that obtained on intact freshly dissected muscle. Mdx fibers in culture showed a reduction of both membrane conductance and capacitance. In contrast, in mdx intact FDB muscle resting conductance was increased while resting potential and ap depolarization rate were reduced, likely indicating the presence of a consistent population of severely altered fibers which disappear during the culture preparation. M. Canato, M. Dal Maschio, F. Sbrana, R. Raiteri, C. Reggiani, S. Vassanelli, and A. Megighian Copyright © 2010 M. Canato et al. All rights reserved. Myosin Binding Protein-C Slow: An Intricate Subfamily of Proteins Thu, 08 Apr 2010 10:37:23 +0000 Myosin binding protein C (MyBP-C) consists of a family of thick filament associated proteins. Three isoforms of MyBP-C exist in striated muscles: cardiac, slow skeletal, and fast skeletal. To date, most studies have focused on the cardiac form, due to its direct involvement in the development of hypertrophic cardiomyopathy. Here we focus on the slow skeletal form, discuss past and current literature, and present evidence to support that: (i) MyBP-C slow comprises a subfamily of four proteins, resulting from complex alternative shuffling of the single MyBP-C slow gene, (ii) the four MyBP-C slow isoforms are expressed in variable amounts in different skeletal muscles, (iii) at least one MyBP-C slow isoform is preferentially found at the periphery of M-bands and (iv) the MyBP-C slow subfamily may play important roles in the assembly and stabilization of sarcomeric M- and A-bands and regulate the contractile properties of the actomyosin filaments. Maegen A. Ackermann and Aikaterini Kontrogianni-Konstantopoulos Copyright © 2010 Maegen A. Ackermann and Aikaterini Kontrogianni-Konstantopoulos. All rights reserved. There Goes the Neighborhood: Pathological Alterations in T-Tubule Morphology and Consequences for Cardiomyocyte Ca𝟐+ Handling Thu, 08 Apr 2010 10:32:16 +0000 T-tubules are invaginations of the cardiomyocyte membrane into the cell interior which form a tortuous network. T-tubules provide proximity between the electrically excitable cell membrane and the sarcoplasmic reticulum, the main intracellular Ca2+ store. Tight coupling between the rapidly spreading action potential and Ca2+ release units in the SR membrane ensures synchronous Ca2+ release throughout the cardiomyocyte. This is a requirement for rapid and powerful contraction. In recent years, it has become clear that T-tubule structure and composition are altered in several pathological states which may importantly contribute to contractile defects in these conditions. In this review, we describe the “neighborhood” of proteins in the dyadic cleft which locally controls cardiomyocyte Ca2+ homeostasis and how alterations in T-tubule structure and composition may alter this neighborhood during heart failure, atrial fibrillation, and diabetic cardiomyopathy. Based on this evidence, we propose that T-tubules have the potential to serve as novel therapeutic targets. William E. Louch, Ole M. Sejersted, and Fredrik Swift Copyright © 2010 William E. Louch et al. All rights reserved. Functional Differences between the N-Terminal Domains of Mouse and Human Myosin Binding Protein-C Wed, 07 Apr 2010 13:47:28 +0000 The N-terminus of cMyBP-C can activate actomyosin interactions in the absence of Ca2+, but it is unclear which domains are necessary. Prior studies suggested that the Pro-Ala rich region of human cMyBP-C activated force in permeabilized human cardiomyocytes, whereas the C1 and M-domains of mouse cMyBP-C activated force in permeabilized rat cardiac trabeculae. Because the amino acid sequence of the P/A region differs between human and mouse cMyBP-C isoforms (46% identity), we investigated whether species-specific differences in the P/A region could account for differences in activating effects. Using chimeric fusion proteins containing combinations of human and mouse C0, Pro-Ala, and C1 domains, we demonstrate here that the human P/A and C1 domains activate actomyosin interactions, whereas the same regions of mouse cMyBP-C are less effective. These results suggest that species-specific differences between homologous cMyBP-C isoforms confer differential effects that could fine-tune cMyBP-C function in hearts of different species. Justin F. Shaffer, Peony Wong, Kristina L. Bezold, and Samantha P. Harris Copyright © 2010 Justin F. Shaffer et al. All rights reserved. The Functional Role of Calcineurin in Hypertrophy, Regeneration, and Disorders of Skeletal Muscle Thu, 01 Apr 2010 15:32:18 +0000 Skeletal muscle uses calcium as a second messenger to respond and adapt to environmental stimuli. Elevations in intracellular calcium levels activate calcineurin, a serine/threonine phosphatase, resulting in the expression of a set of genes involved in the maintenance, growth, and remodeling of skeletal muscle. In this review, we discuss the effects of calcineurin activity on hypertrophy, regeneration, and disorders of skeletal muscle. Calcineurin is a potent regulator of muscle remodeling, enhancing the differentiation through upregulation of myogenin or MEF2A and downregulation of the Id1 family and myostatin. Foxo may also be a downstream candidate for a calcineurin signaling molecule during muscle regeneration. The strategy of controlling the amount of calcineurin may be effective for the treatment of muscular disorders such as DMD, UCMD, and LGMD. Activation of calcineurin produces muscular hypertrophy of the slow-twitch soleus muscle but not fast-twitch muscles. Kunihiro Sakuma and Akihiko Yamaguchi Copyright © 2010 Kunihiro Sakuma and Akihiko Yamaguchi. All rights reserved. Contractile Properties of Esophageal Striated Muscle: Comparison with Cardiac and Skeletal Muscles in Rats Thu, 01 Apr 2010 15:10:14 +0000 The external muscle layer of the mammalian esophagus consists of striated muscles. We investigated the contractile properties of esophageal striated muscle by comparison with those of skeletal and cardiac muscles. Electrical field stimulation with single pulses evoked twitch-like contractile responses in esophageal muscle, similar to those in skeletal muscle in duration and similar to those in cardiac muscle in amplitude. The contractions of esophageal muscle were not affected by an inhibitor of gap junctions. Contractile responses induced by high potassium or caffeine in esophageal muscle were analogous to those in skeletal muscle. High-frequency stimulation induced a transient summation of contractions followed by sustained contractions with amplitudes similar to those of twitch-like contractions, although a large summation was observed in skeletal muscle. The results demonstrate that esophageal muscle has properties similar but not identical to those of skeletal muscle and that some specific properties may be beneficial for esophageal peristalsis. Takahiko Shiina, Takeshi Shima, Kazuaki Masuda, Haruko Hirayama, Momoe Iwami, Tadashi Takewaki, Hirofumi Kuramoto, and Yasutake Shimizu Copyright © 2010 Takahiko Shiina et al. All rights reserved. S100A1: A Regulator of Striated Muscle Sarcoplasmic Reticulum Ca2+ Handling, Sarcomeric, and Mitochondrial Function Sun, 28 Mar 2010 13:30:50 +0000 Calcium () signaling plays a key role in a wide range of physiological functions including control of cardiac and skeletal muscle performance. To assure a precise coordination of both temporally and spatially transduction of intracellular oscillations to downstream signaling networks and target operations, cycling regulation in muscle tissue is conducted by a plethora of diverse molecules. S100A1 is a member of the -binding S100 protein family and represents the most abundant S100 isoform in cardiac and skeletal muscle. Early studies revealed distinct expression patterns of S100A1 in healthy and diseased cardiac tissue from animal models and humans. Further elaborate investigations uncovered S100A1 protein as a basic requirement for striated muscle handling integrity. S100A1 is a critical regulator of cardiomyocyte cycling and contractile performance. S100A1-mediated inotropy unfolds independent and on top of AR-stimulated contractility with unchanged AR downstream signaling. S100A1 has further been detected at different sites within the cardiac sarcomere indicating potential roles in myofilament function. More recently, a study reported a mitochondrial location of S100A1 in cardiomyocytes. Additionally, normalizing the level of S100A1 protein by means of viral cardiac gene transfer in animal heart failure models resulted in a disrupted progression towards cardiac failure and enhanced survival. This brief review is confined to the physiological and pathophysiological relevance of S100A1 in cardiac and skeletal muscle handling with a particular focus on its potential as a molecular target for future therapeutic interventions. Mirko Völkers, David Rohde, Chelain Goodman, and Patrick Most Copyright © 2010 Mirko Völkers et al. All rights reserved. Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium Wed, 24 Mar 2010 09:07:17 +0000 Molecular predisposition of postnatal ventricular myocardium to chamber-dependent (concentric or eccentric) remodeling remains largely elusive. To this end, we compared gene expression in the left (LV) versus right ventricle (RV) in newborn piglets, using a differential display reverse transcription-PCR (DDRT-PCR) technique. Out of more than 5600 DDRT-PCR bands, a total of 153 bands were identified as being differentially displayed. Of these, 96 bands were enriched in the LV, whereas the remaining 57 bands were predominant in the RV. The transcripts, displaying over twofold LV-RV expression differences, were sequenced and identified by BLAST comparison to known mRNA sequences. Among the genes, whose expression was not previously recognized as being chamber-dependent, we identified a small cohort of key regulators of muscle cell growth/proliferation (MAP3K7IP2, MSTN, PHB2, APOBEC3F) and gene expression (PTPLAD1, JMJD1C, CEP290), which may be relevant to the chamber-dependent predisposition of ventricular myocardium to respond differentially to pressure (LV) and volume (RV) overloads after birth. In addition, our data demonstrate chamber-dependent alterations in expression of as yet uncharacterized novel genes, which may also be suitable candidates for association studies in animal models of LV/RV hypertrophy. Mario Torrado, Raquel Iglesias, Beatriz Nespereira, and Alexander T. Mikhailov Copyright © 2010 Mario Torrado et al. All rights reserved. Titin Diversity—Alternative Splicing Gone Wild Sun, 21 Mar 2010 14:17:00 +0000 Titin is an extremely large protein found in highest concentrations in heart and skeletal muscle. The single mammalian gene is expressed in multiple isoforms as a result of alternative splicing. Although titin isoform expression is controlled developmentally and in a tissue specific manner, the vast number of potential splicing pathways far exceeds those described in any other alternatively spliced gene. Over 1 million human splice pathways for a single individual can be potentially derived from the PEVK region alone. A new splicing pattern for the human cardiac N2BA isoform type has been found in which the PEVK region includes only the N2B type exons. The alterations in splicing and titin isoform expression in human heart disease provide impetus for future detailed study of the splicing mechanisms for this giant protein. Wei Guo, Sheila J. Bharmal, Karla Esbona, and Marion L. Greaser Copyright © 2010 Wei Guo et al. All rights reserved. Aquaporin Expression in Normal and Pathological Skeletal Muscles: A Brief Review with Focus on AQP4 Sun, 21 Mar 2010 14:07:27 +0000 Freeze-fracture electron microscopy enabled us to observe the molecular architecture of the biological membranes. We were studying the myofiber plasma membranes of health and disease by using this technique and were interested in the special assembly called orthogonal arrays (OAs). OAs were present in normal myofiber plasma membranes and were especially numerous in fast twitch type 2 myofibers; while OAs were lost from sarcolemmal plasma membranes of severely affected muscles with dystrophinopathy and dysferlinopathy but not with caveolinopathy. In the mid nineties of the last century, the OAs turned out to be a water channel named aquaporin 4 (AQP4). Since this discovery, several groups of investigators have been studying AQP4 expression in diseased muscles. This review summarizes the papers which describe the expression of OAs, AQP4, and other AQPs at the sarcolemma of healthy and diseased muscle and discusses the possible role of AQPs, especially that of AQP4, in normal and pathological skeletal muscles. Yoshihiro Wakayama Copyright © 2010 Yoshihiro Wakayama. All rights reserved. Skeletal Muscle Insulin Resistance in Endocrine Disease Mon, 15 Mar 2010 16:04:48 +0000 We summarize the existing literature data concerning the involvement of skeletal muscle (SM) in whole body glucose homeostasis and the contribution of SM insulin resistance (IR) to the metabolic derangements observed in several endocrine disorders, including polycystic ovary syndrome (PCOS), adrenal disorders and thyroid function abnormalities. IR in PCOS is associated with a unique postbinding defect in insulin receptor signaling in general and in SM in particular, due to a complex interaction between genetic and environmental factors. Adrenal hormone excess is also associated with disrupted insulin action in peripheral tissues, such as SM. Furthermore, both hyper- and hypothyroidism are thought to be insulin resistant states, due to insulin receptor and postreceptor defects. Further studies are definitely needed in order to unravel the underlying pathogenetic mechanisms. In summary, the principal mechanisms involved in muscle IR in the endocrine diseases reviewed herein include abnormal phosphorylation of insulin signaling proteins, altered muscle fiber composition, reduced transcapillary insulin delivery, decreased glycogen synthesis, and impaired mitochondrial oxidative metabolism. Melpomeni Peppa, Chrysi Koliaki, Panagiotis Nikolopoulos, and Sotirios A. Raptis Copyright © 2010 Melpomeni Peppa et al. All rights reserved. Extracorporeal Immunoglobulin Elimination for the Treatment of Severe Myasthenia Gravis Mon, 15 Mar 2010 15:47:41 +0000 Myasthenia gravis (MG) is a neuromuscular disorder leading to fluctuating muscle weakness and fatigue. Rarely, long-term stabilization is not possible through the use of thymectomy or any known drug therapy. We present our experience with extracorporeal immunoglobulin (Ig) elimination by immunoadsorption (adsorbers with human Ig antibodies). Acetylcholine receptor antibodies (AChRAs) were measured during long-term monitoring (4.72.9 years; range 1.1–8.0). A total of 474 samples (232 pairs) were analyzed, and a drop in AChRA levels was observed (). The clinical status of patients improved and stabilized. Roughly 6.8% of patients experienced clinically irrelevant side effects. The method of Ig elimination by extracorporeal immunoadsorption (IA) is a clinical application of the recent biotechnological advances. It offers an effective and safe therapy for severe MG even when the disease is resistant to standard therapy. M. Blaha, J. Pit'ha, V. Blaha, M. Lanska, J. Maly, S. Filip, and H. Langrova Copyright © 2010 M. Blaha et al. All rights reserved. The Role of Exercise-Induced Myokines in Muscle Homeostasis and the Defense against Chronic Diseases Tue, 09 Mar 2010 11:14:37 +0000 Chronic inflammation is involved in the pathogenesis of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth. Regular exercise offers protection against type 2 diabetes, cardiovascular diseases, colon cancer, breast cancer, and dementia. Evidence suggests that the protective effect of exercise may to some extent be ascribed to the antiinflammatory effect of regular exercise. Here we suggest that exercise may exert its anti-inflammatory effect via a reduction in visceral fat mass and/or by induction of an anti-inflammatory environment with each bout of exercise. According to our theory, such effects may in part be mediated via muscle-derived peptides, so-called “myokines”. Contracting skeletal muscles release myokines with endocrine effects, mediating direct anti-inflammatory effects, and/or specific effects on visceral fat. Other myokines work locally within the muscle and exert their effects on signalling pathways involved in fat oxidation and glucose uptake. By mediating anti-inflammatory effects in the muscle itself, myokines may also counteract TNF-driven insulin resistance. In conclusion, exercise-induced myokines appear to be involved in mediating both systemic as well as local anti-inflammatory effects. Claus Brandt and Bente K. Pedersen Copyright © 2010 Claus Brandt and Bente K. Pedersen. All rights reserved. Attenuation of Acute Lung Inflammation and Injury by Whole Body Cooling in a Rat Heatstroke Model Tue, 15 Dec 2009 14:59:56 +0000 Whole body cooling is the current therapy of choice for heatstroke because the therapeutic agents are not available. In this study, we assessed the effects of whole body cooling on several indices of acute lung inflammation and injury which might occur during heatstroke. Anesthetized rats were randomized into the following groups and given (a) no treatment or (b) whole body cooling immediately after onset of heatstroke. As compared with the normothermic controls, the untreated heatstroke rats had higher levels of pleural exudates volume and polymorphonuclear cell numbers, lung myloperoxidase activity and inducible nitric oxide synthase expression, histologic lung injury score, and bronchoalveolar proinflammatory cytokines and glutamate, and . In contrast, the values of mean arterial pressure, heart rate, , pH, and blood were all significantly lower during heatstroke. The acute lung inflammation and injury and electrolyte imbalance that occurred during heatstroke were significantly reduced by whole body cooling. In conclusion, we identified heat-induced acute lung inflammation and injury and electrolyte imbalance could be ameliorated by whole body cooling. Hsi-Hsing Yang, Ching-Ping Chang, Juei-Tang Cheng, and Mao-Tsun Lin Copyright © 2009 Hsi-Hsing Yang et al. All rights reserved. Effect of Plant Oils upon Lipase and Citric Acid Production in Yarrowia lipolytica Yeast Thu, 08 Oct 2009 11:52:52 +0000 The nonconventional yeast Yarrowia lipolytica degrades very efficiently hydrophobic substrates to produce organic acids, single-cell oil, lipases, and so forth. The aim of this study was to investigate the biochemical behavior and simultaneous production of valuable metabolites such as lipase, citric acid (CA), and single-cell protein (SCP) by Yarrowia lipolytica DSM 3286 grown on various plant oils as sole carbon source. Among tested plant oils, olive oil proved to be the best medium for lipase and CA production. The Y. lipolytica DSM 3286 produced 34.6 ± 0.1 U/mL of lipase and also CA and SCP as by-product on olive oil medium supplemented with yeast extract. Urea, as organic nitrogen, was the best nitrogen source for CA production. The results of this study suggest that the two biotechnologically valuable products, lipase and CA, could be produced simultaneously by this strain using renewable low-cost substrates such as plant oils in one procedure. Farshad Darvishi, Iraj Nahvi, Hamid Zarkesh-Esfahani, and Fariborz Momenbeik Copyright © 2009 Farshad Darvishi et al. All rights reserved. Caenorhabditis elegans F09E10.3 Encodes a Putative 3-Oxoacyl-Thioester Reductase of Mitochondrial Type 2 Fatty Acid Synthase FASII that Is Functional in Yeast Mon, 07 Sep 2009 14:51:28 +0000 Caenorhabditis elegans F09E10.3 (dhs-25) was identified as encoding a 3-oxoacyl-thioester reductase, potentially of the mitochondrial type 2 fatty acid synthase (FASII) system. Mitochondrial FASII is a relatively recent discovery in metazoans, and the relevance of this process to animal physiology has not been elucidated. A good animal model to study the role of FASII is the nematode C. elegans. However, the components of nematode mitochondrial FASII have hitherto evaded positive identification. The nematode F09E10.3 protein was ectopically expressed without an additional mitochondrial targeting sequence in Saccharomyces cerevisiae mutant cells lacking the homologous mitochondrial FASII enzyme 3-oxoacyl-ACP reductase Oar1p. These yeast mutants are unable to respire, grow on nonfermentable carbon sources, or synthesize sufficient levels of lipoic acid. Mutant yeast cells producing a full-length mitochondrial F09E10.3 protein contained -dependent 3-oxoacyl-thioester reductase activity and resembled the corresponding mutant overexpressing native Oar1p for the above-mentioned phenotype characteristics. This is the first identification of a metazoan 3-oxoacyl-thioester reductase (see Note Added in Proof). Aner Gurvitz Copyright © 2009 Aner Gurvitz. All rights reserved. Nitric Oxide as a Unique Bioactive Signaling Messenger in Physiology and Pathophysiology Mon, 01 Jan 1900 00:00:00 +0000 Nitric oxide (NO) is an intra- and extracellular messenger that mediates diverse signaling pathways in target cells and is known to play an important role in many physiological processes including neuronal signaling, immune response, inflammatory response, modulation of ion channels, phagocytic defense mechanism, penile erection, and cardiovascular homeostasis and its decompensation in atherogenesis. Recent studies have also revealed a role for NO as signaling molecule in plant, as it activates various defense genes and acts as developmental regulator. In plants, NO can also be produced by nitrate reductase. NO can operate through posttranslational modification of proteins (nitrosylation). NO is also a causative agent in various pathophysiological abnormalities. One of the very important systems, the cardiovascular system, is affected by NO production, as this bioactive molecule is involved in the regulation of cardiovascular motor tone, modulation of myocardial contractivity, control of cell proliferation, and inhibition of platelet activation, aggregation, and adhesion. The prime source of NO in the cardiovascular system is endothelial NO synthase, which is tightly regulated with respect to activity and localization. The inhibition of chronic NO synthesis leads to neurogenic and arterial hypertensions, which later contribute to development of myocardial fibrosis. Overall, the modulation of NO synthesis is associated with hypertension. This review briefly describes the physiology of NO, its synthesis, catabolism, and targeting, the mechanism of NO action, and the pharmacological role of NO with special reference to its essential role in hypertension. Narendra Tuteja, Mahesh Chandra, Renu Tuteja, and Mithilesh K. Misra Copyright © 2004 Hindawi Publishing Corporation. All rights reserved. Patch Clamp Study of Serotonin-Gated Currents via 5-HT Type 3 Receptors by Using a Novel Approach SHAM for Receptor Channel Scanning Mon, 01 Jan 1900 00:00:00 +0000 We studied 5-hydroxy tryptamine type 3 (5-HT3) receptors transfected in tsA-201 cell line to examine serotonin-induced whole cell currents. Using the site-directed mutagenesis technique, we individually mutated each residue in the membrane-spanning M2 segment to histidine. A high proportion of tsA-201 cells cotransfected with the cDNAs of 5-HT3R and CD8 produced large amplitude responses (0.5–7.0 nA) to serotonin. The dose-response curve of wild-type (WT) receptor ranging from 0.5 to 500 μmole increases its Kd values, and Imax of 5-HT3R falls at low external pH as if protonation of an acid group is enough to block the channel. Lysine at position 281, a basic residue, is more susceptible to acidification-induced blockade of the 5-HT3R channel. Dose-response curves of K281S (replacing lysine at the 281 position with serine) at different pH are not significantly modulated, and histidine substitutions at the three consecutive positions 293, 294, and 296 eliminate the pH block of the channel. Fatima-Shad Kaneez and M. White Copyright © 2004 Hindawi Publishing Corporation. All rights reserved. Somatic Embryogenesis, Rhizogenesis, and Morphinan Alkaloids Production in Two Species of Opium Poppy Mon, 01 Jan 1900 00:00:00 +0000 A study of somatic embryogenesis and rhizogenesis and their influence on production of morphinan alkaloids on two species of opium poppy is presented. We identified the ratios of auxin and cytokinin that caused somatic embryogenesis and rhizogenesis in hypocotyl and cotyledons of Papaver somniferum album and Papaver orientale splendidissimum. The hypocotyls and cotyledons both show somatic embryogenesis in Papaver somniferum album whereas only the cotyledons were embryogenic in Papaver orientale splendidissimum. For rhizogenesis, the most important response is on the cotyledons and leaves in these two species. Histology showed characteristic stages of somatic embryo: Globular, cotyledonous, and heart cotyledonary. High performance liquid chromatography analysis showed that the roots of both species synthesized codeine, thebaine, and papaverine. Morphine was only detected in aerial parts of Papaver somniferum album. Codeine and thebaine were detected in the rhizogenous but no embryonic callus. These results suggest that root organogenesis is causally related to alkaloid biosynthesis. My Abdelmajid Kassem and Annie Jacquin Copyright © 2001 Hindawi Publishing Corporation. All rights reserved.