Scientifica The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Update on Abdominal Aortic Aneurysm Research: From Clinical to Genetic Studies Thu, 17 Apr 2014 00:00:00 +0000 An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta with a diameter of at least 3.0 cm. AAAs are often asymptomatic and are discovered as incidental findings in imaging studies or when the AAA ruptures leading to a medical emergency. AAAs are more common in males than females, in individuals of European ancestry, and in those over 65 years of age. Smoking is the most important environmental risk factor. In addition, a positive family history of AAA increases the person’s risk for AAA. Interestingly, diabetes has been shown to be a protective factor for AAA in many large studies. Hallmarks of AAA pathogenesis include inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. Autoimmunity may also play a role in AAA development and progression. In this Outlook paper, we summarize our recent studies on AAA including clinical studies related to surgical repair of AAA and genetic risk factor and large-scale gene expression studies. We conclude with a discussion on our research projects using large data sets available through electronic medical records and biobanks. Helena Kuivaniemi, Evan J. Ryer, James R. Elmore, Irene Hinterseher, Diane T. Smelser, and Gerard Tromp Copyright © 2014 Helena Kuivaniemi et al. All rights reserved. Biofilm Localization in the Vertical Wall of Shaking 96-Well Plates Sun, 13 Apr 2014 13:22:51 +0000 Microtiter plates with 96 wells are being increasingly used for biofilm studies due to their high throughput, low cost, easy handling, and easy application of several analytical methods to evaluate different biofilm parameters. These methods provide bulk information about the biofilm formed in each well but lack in detail, namely, regarding the spatial location of the biofilms. This location can be obtained by microscopy observation using optical and electron microscopes, but these techniques have lower throughput and higher cost and are subjected to equipment availability. This work describes a differential crystal violet (CV) staining method that enabled the determination of the spatial location of Escherichia coli biofilms formed in the vertical wall of shaking 96-well plates. It was shown that the biofilms were unevenly distributed on the wall with denser cell accumulation near the air-liquid interface. The results were corroborated by scanning electron microscopy and a correlation was found between biofilm accumulation and the wall shear strain rates determined by computational fluid dynamics. The developed method is quicker and less expensive and has a higher throughput than the existing methods available for spatial location of biofilms in microtiter plates. Luciana C. Gomes, Joana M. R. Moreira, Manuel Simões, Luís F. Melo, and Filipe J. Mergulhão Copyright © 2014 Luciana C. Gomes et al. All rights reserved. Erratum to “Hox Targets and Cellular Functions” Sun, 13 Apr 2014 00:00:00 +0000 Ernesto Sánchez-Herrero Copyright © 2014 Ernesto Sánchez-Herrero. All rights reserved. Distinct Functions of Specialized Dendritic Cell Subsets in Atherosclerosis and the Road Ahead Thu, 10 Apr 2014 17:53:31 +0000 Atherosclerotic vascular disease is modulated by immune mechanisms. Dendritic cells (DCs) and T cells are present within atherosclerotic lesions and function as central players in the initiation and modulation of adaptive immune responses. In previous years, we have studied the functional contribution of distinct DC subsets in disease development, namely, that of CCL17-expressing DCs as well as that of plasmacytoid DCs that play specialized roles in disease development. This review focuses on important findings gathered in these studies and dissects the multifaceted contribution of CCL17-expressing DCs and pDCs to the pathogenesis of atherosclerosis. Furthermore, an outlook on future challenges faced when studying DCs in this detrimental disease are provided, and hurdles that will need to be overcome in order to enable a better understanding of the contribution of DCs to atherogenesis are discussed, a prerequisite for their therapeutic targeting in atherosclerosis. Alma Zernecke Copyright © 2014 Alma Zernecke. All rights reserved. Autophagy in Macrophages: Impacting Inflammation and Bacterial Infection Wed, 09 Apr 2014 12:22:13 +0000 Macrophages are on the front line of host defense. They possess an array of germline-encoded pattern recognition receptors/sensors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and which activate downstream effectors/pathways to help mediate innate immune responses and host defense. Innate immune responses include the rapid induction of transcriptional networks that trigger the production of cytokines, chemokines, and cytotoxic molecules; the mobilization of cells including neutrophils and other leukocytes; the engulfment of pathogens by phagocytosis and their delivery to lysosome for degradation; and the induction of autophagy. Autophagy is a catabolic process that normally maintains cellular homeostasis in a lysosome-dependent manner, but it also functions as a cytoprotective response that intersects with a variety of general stress-response pathways. This review focuses on the intimately linked molecular mechanisms that help govern the autophagic pathway and macrophage innate immune responses. Ali Vural and John H. Kehrl Copyright © 2014 Ali Vural and John H. Kehrl. All rights reserved. Volatile Anaesthetic Depression of the Carotid Body Chemoreflex-Mediated Ventilatory Response to Hypoxia: Directions for Future Research Sun, 06 Apr 2014 13:49:06 +0000 In assessing whether volatile anaesthetics directly depress the carotid body response to hypoxia it is necessary to combine in meta-analysis studies of when it is “functionally isolated” (e.g., recordings are made from its afferent nerve). Key articles were retrieved (full papers in English) and subjected to quantitative analysis to yield an aggregate estimate of effect. Results from articles that did not use such methodology were assessed separately from this quantitative approach, to see what could be learned also from a nonquantitative overview. Just 7 articles met the inclusion criteria for hypoxia and just 6 articles for hypercapnia. Within these articles, the anaesthetic (mean dose 0.75, standard deviation (SD) 0.40 minimum alveolar concentration, MAC) statistically significantly depressed carotid body hypoxic response by 24% (), but a similar dose (mean 0.81 (0.42) MAC) did not affect the hypercapnic response. The articles not included in the quantitative analysis (31 articles), assessed qualitatively, also indicated that anaesthetics depress carotid body function. This conclusion helps direct future research on the anaesthetic effects on putative cellular/molecular processes that underlie the transduction of hypoxia in the carotid body. J. J. Pandit Copyright © 2014 J. J. Pandit. All rights reserved. A Review of the Antiviral Susceptibility of Human and Avian Influenza Viruses over the Last Decade Wed, 02 Apr 2014 00:00:00 +0000 Antivirals play an important role in the prevention and treatment of influenza infections, particularly in high-risk or severely ill patients. Two classes of influenza antivirals have been available in many countries over the last decade (2004–2013), the adamantanes and the neuraminidase inhibitors (NAIs). During this period, widespread adamantane resistance has developed in circulating influenza viruses rendering these drugs useless, resulting in the reliance on the most widely available NAI, oseltamivir. However, the emergence of oseltamivir-resistant seasonal A(H1N1) viruses in 2008 demonstrated that NAI-resistant viruses could also emerge and spread globally in a similar manner to that seen for adamantane-resistant viruses. Previously, it was believed that NAI-resistant viruses had compromised replication and/or transmission. Fortunately, in 2013, the majority of circulating human influenza viruses remain sensitive to all of the NAIs, but significant work by our laboratory and others is now underway to understand what enables NAI-resistant viruses to retain the capacity to replicate and transmit. In this review, we describe how the susceptibility of circulating human and avian influenza viruses has changed over the last ten years and describe some research studies that aim to understand how NAI-resistant human and avian influenza viruses may emerge in the future. Ding Yuan Oh and Aeron C. Hurt Copyright © 2014 Ding Yuan Oh and Aeron C. Hurt. All rights reserved. Efficacy of 1.5% Dish Washing Solution and 95% Lemon Water in Substituting Perilous Xylene as a Deparaffinizing Agent for Routine H and E Staining Procedure: A Short Study Mon, 31 Mar 2014 14:02:09 +0000 Aim. To assess the efficacy of dish washing solution and diluted lemon water in deparaffinizing sections during conventional hematoxylin and eosin staining technique. Objective. The objective is to utilize eco-friendly economical substitute for xylene. Materials and Methods. Using twenty paraffin embedded tissue blocks, three sections each were prepared. One section was stained with conventional H and E method (Group A) and the other two sections with xylene-free (XF) H and E (Groups B and C). Staining characteristics were compared with xylene and scoring was given. Total score of 3–5 was regarded as adequate for diagnosis and less than that inadequate for diagnosis. Statistical Analysis. Chi-square test, Kruskal Wallis ANOVA test, and Mann-Whitney U test were used. Results. Adequacy of nuclear staining, crispness, and staining for diagnosis were greater in both Groups A and C (100%) than Group B (95%). Adequacy of cytoplasmic staining was similar in all the three groups (100%). Group B showed comparatively superior uniform staining and less retention of wax. Conclusion. Dish washing solution or diluted lemon water can be replaced for xylene as deparaffinizing agent in hematoxylin and eosin procedure. Anuradha Ananthaneni, Srilekha Namala, Vijay Srinivas Guduru, V. V. S. Ramprasad, Sabitha Devi Ramisetty, Urmila Udayashankar, and Kiran Kumar Naik Copyright © 2014 Anuradha Ananthaneni et al. All rights reserved. Dichotomous Effect of Caffeine, Curcumin, and Naringenin on Genomic DNA of Normal and Diabetic Subjects Sun, 30 Mar 2014 07:19:23 +0000 Nutraceutical compounds show antioxidant and prooxidant properties under stress conditions like cancer, diabetes, and other diseases. The objective of this study is to find the dichotomic behavior of caffeine, curcumin, and naringenin on DNA of diabetic and normal subjects in the presence and absence of copper, hydrogen peroxide, and complex of copper-hydrogen peroxide. Hydrogen peroxide releases hydroxyl free radicals (•OH) on oxidation of Cu (I) to Cu (II) through Fenton-type reaction to cause DNA damage. In the results, agarose gel electrophoretic pattern speculates the prooxidant effect of caffeine and antioxidant effect of curcumin on DNA in the presence of copper and hydrogen peroxide. UV-Vis spectral analysis shows hyperchromism on addition of DNA to caffeine, hypochromism with curcumin, and subtle changes with naringenin. The chosen nutraceuticals act as inducers and quenchers of oxidative free radicals arising from diabetes. Debarati Chattopadhyay, Ashok Somaiah, Divya Raghunathan, and Kavitha Thirumurugan Copyright © 2014 Debarati Chattopadhyay et al. All rights reserved. The Role of Helicobacter pylori Seropositivity in Insulin Sensitivity, Beta Cell Function, and Abnormal Glucose Tolerance Tue, 25 Mar 2014 13:35:36 +0000 Infection, for example, Helicobacter pylori (H. pylori), has been thought to play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). Our aim was to determine the role of H. pylori infection in glucose metabolism in an American cohort. We examined data from 4,136 non-Hispanic white (NHW), non-Hispanic black (NHB), and Mexican Americans (MA) aged 18 and over from the NHANES 1999-2000 cohort. We calculated the odds ratios for states of glucose tolerance based on the H. pylori status. We calculated and compared homeostatic model assessment insulin resistance (HOMA-IR) and beta cell function (HOMA-B) in subjects without diabetes based on the H. pylori status. The results were adjusted for age, body mass index (BMI), poverty index, education, alcohol consumption, tobacco use, and physical activity. The H. pylori status was not a risk factor for abnormal glucose tolerance. After adjustment for age and BMI and also adjustment for all covariates, no difference was found in either HOMA-IR or HOMA-B in all ethnic and gender groups except for a marginally significant difference in HOMA-IR in NHB females. H. pylori infection was not a risk factor for abnormal glucose tolerance, nor plays a major role in insulin resistance or beta cell dysfunction. Lou Rose Malamug, Rudruidee Karnchanasorn, Raynald Samoa, and Ken C. Chiu Copyright © 2014 Lou Rose Malamug et al. All rights reserved. Potential Association between Breakfast Skipping and Concomitant Late-Night-Dinner Eating with Metabolic Syndrome and Proteinuria in the Japanese Population Tue, 25 Mar 2014 07:00:09 +0000 Skipping breakfast is considered to be an unhealthy eating habit linked to predispositions to obesity and type 2 diabetes. Because eating dinner late at night can elicit subsequent breakfast skipping, we investigated if skipping breakfast concomitant with late-night-dinner eating (LNDE) was associated with metabolic syndrome (MetS) and proteinuria in the general Japanese population. We examined self-reported habitual breakfast skipping and LNDE, MetS (modified ATP-III criteria), and proteinuria in a cross-sectional study of 60,800 Japanese adults aged 20–75 years. A total of 14,068 subjects (23.1%) skipped breakfast, of whom approximately half (52.8%) skipped breakfast alone (without LNDE). The percentages of subjects who skipped breakfast showed a J-shaped relationship with body mass index (BMI). Multivariate logistic regression analysis showed that skipping breakfast concomitant with LNDE ( = 6,645) was significantly associated with MetS and proteinuria, even after adjusting for relevant confounders (odds ratio (95% CI), 1.17 (1.08–1.28), , and 1.37 (1.24–1.52), , resp.). Skipping breakfast alone and LNDE alone were not associated with MetS and proteinuria, respectively. In conclusion, habitual breakfast skipping concomitant with LNDE may represent poorer eating behavior than skipping breakfast alone, associated with MetS, asymptomatic proteinuria, obesity, and low body weight in the general Japanese population. Ayano Kutsuma, Kei Nakajima, and Kaname Suwa Copyright © 2014 Ayano Kutsuma et al. All rights reserved. Knowledge of, Perception of, and Attitude towards Uterine Fibroids among Women with Fibroids in Lagos, Nigeria Thu, 13 Mar 2014 13:45:20 +0000 Objectives. The study was to assess the level of knowledge of, perception of, and attitude towards uterine fibroids among women diagnosed with the condition. Methods. It is a cross-sectional descriptive study carried out among women diagnosed as having uterine fibroids in two gynaecological clinics in Lagos, Nigeria. Eligible women were recruited and a structured interviewer-administered questionnaire was used to collect the required information. Statistical analysis of data was done using EPI Info 2008. Results. Knowledge of fibroids was reported in 98.6% of the respondents and the information on uterine fibroids was obtained from radio, parents/relatives, health workers, and television in 29%, 27.3%, 18.7%, and 18.3%, respectively, by the respondents. Most of the women believed that being black, being nulliparous, or having positive family history predisposes women to having uterine fibroids. Up to 69.0% of the respondents believed that fibroid is a spiritual problem and many thought it requires spiritual healing. Fear of complications of surgery keeps most sufferers away from the hospital until fibroids become advanced or associated with complications. Conclusion. Awareness of uterine fibroids is high, but correct knowledge on aetiology and proper treatment is low. Intensive enlightenment of the populace using the mass media by trained personnel is recommended. M. A. Adegbesan-Omilabu, K. S. Okunade, and A. Gbadegesin Copyright © 2014 M. A. Adegbesan-Omilabu et al. All rights reserved. Human Interferon Alpha-2b: A Therapeutic Protein for Cancer Treatment Mon, 10 Mar 2014 07:30:26 +0000 Human interferon alpha (hIFN) is a wide biological activity cytokine that is used in hepatitis and cancer treatments. It regulates many genes that are involved in antiviral and antiproliferative activities. This mini review focuses on human interferon alpha-2b (hIFN-2b) as therapeutic protein for cancer treatment. The review covers hIFN-2b molecular characteristic and its molecular mechanism by Janus activated kinase/signal transducer activation of transcription (JAK-STAT) pathway. The JAK-STAT pathway regulates not only proteins involved in inhibition of proliferation but also apoptosis. As additional discussion of clinical applications, the use of recombinant hIFN-2b (rhIFN-2b) as therapeutic protein in several types of cancer is also explained. Ratih Asmana Ningrum Copyright © 2014 Ratih Asmana Ningrum. All rights reserved. Assessment of Technetium-99m Labeled Macroaggregated Albumin Rhinoscintigraphy for the Measurement of Nasal Mucociliary Transport Rate: Intratest, Interobserver, and Intraobserver Reproducibility Wed, 05 Mar 2014 13:13:11 +0000 Objectives. The measurement of mucociliary transport velocity by rhinoscintigraphy with Tc-99m-macroaggregated albumin (99mTc-MAA) is reliable measure of mucociliary clearance. The aim of this study is to assess the intratest, interobserver, and intraobserver reproducibility of nasal mucociliary transport rate (NMTR) measurement. Materials and Methods. Twenty-two subjects were evaluated to determine intratest reproducibility and a group of 35 subjects was examined to determine inter- and intraobserver reproducibility. Rhinoscintigraphy with 99mTc-MAA was used to measure NMTR in all study subjects. Paired NMTR measurements were compared using a range of statistical methodologies. Intraclass correlation coefficients (ICC) and repeatability coefficients and Bland-Altman plots were applied to assess the degree of intratest, interobserver, and intraobserver variation. Results. Statistical analysis of test and retest experiments demonstrated the statistical equivalence of intratest NMTR measurements, interobserver NMTR measurements, and intraobserver NMTR measurements. The intratest ICC, interobserver ICC, and intraobserver ICC were 0.96, 0.83, and 0.91, respectively, indicating that intratest and intraobserver reproducibility are excellent and interobserver reproducibility is good. Conclusions. Rhinoscintigraphy using 99mTc-MAA results in highly reproducible measurement of NMTR. The use of radionuclide imaging in measuring NMTR results in excellent intratest and intraobserver reproducibility and good interobserver reliability. Zeki Dostbil, Yusuf Dag, Ozlem Cetinkaya, Mehmet Akdag, and Bekir Tasdemir Copyright © 2014 Zeki Dostbil et al. All rights reserved. Gender Differences in Pulmonary Function, Respiratory Symptoms, and Macrophage Proteomics among HIV-Infected Smokers Tue, 04 Mar 2014 15:36:44 +0000 Background. HIV-infected subjects have an increased incidence of pulmonary emphysema. There are known gender differences in COPD phenotypic expression and diagnosis, but this is not well characterized in lung disease related to HIV. We analyzed a group at risk for the development of COPD (HIV-infected smokers) to determine gender differences in pulmonary symptoms, pulmonary function tests, and HRCT appearances. Methods. This was a cross-sectional, baseline analysis of a prospective study performed between 2006 and 2010. We performed symptomatic, pulmonary function, and computed tomography assessments in 243 HIV-infected smokers. In a subset bronchoalveolar lavage was performed with proteomic analysis of their alveolar macrophages. Results. The majority of the participants were male 213 (87.6%). There was significantly higher percentage of cough and phlegm production in males. There was also a lower FEV1 and a higher RV in males than females. Proteomic analysis revealed 29 proteins with at least a 2-fold higher expression in males and 13 identified proteins that were higher in females. Conclusions. In this group of HIV-infected smokers, airway symptoms and pulmonary function test abnormalities were higher in men than women. These gender differences may be due to differential expression of certain proteins in this group. Shiva D. Rahmanian, Karen L. Wood, Shili Lin, Mark A. King, April Horne, Shangbin Yang, Haifeng M. Wu, and Philip T. Diaz Copyright © 2014 Shiva D. Rahmanian et al. All rights reserved. Mechanism of Human Tooth Eruption: Review Article Including a New Theory for Future Studies on the Eruption Process Wed, 12 Feb 2014 07:28:05 +0000 Human eruption is a unique developmental process in the organism. The aetiology or the mechanism behind eruption has never been fully understood and the scientific literature in the field is extremely sparse. Human and animal tissues provide different possibilities for eruption analyses, briefly discussed in the introduction. Human studies, mainly clinical and radiological, have focused on normal eruption and gender differences. Why a tooth begins eruption and what enables it to move eruptively and later to end these eruptive movements is not known. Pathological eruption courses contribute to insight into the aetiology behind eruption. A new theory on the eruption mechanism is presented. Accordingly, the mechanism of eruption depends on the correlation between space in the eruption course, created by the crown follicle, eruption pressure triggered by innervation in the apical root membrane, and the ability of the periodontal ligament to adapt to eruptive movements. Animal studies and studies on normal and pathological eruption in humans can support and explain different aspects in the new theory. The eruption mechanism still needs elucidation and the paper recommends that future research on eruption keeps this new theory in mind. Understanding the aetiology of the eruption process is necessary for treating deviant eruption courses. Inger Kjær Copyright © 2014 Inger Kjær. All rights reserved. Light and Darkness: Prevalence of Hepatitis E Virus Infection among the General Population Mon, 10 Feb 2014 14:10:38 +0000 Human hepatitis E virus (HHEV) spreads early in life among the population in areas endemic for genotype 1 and infects mainly adults in areas endemic for genotype 3, where it would be responsible for about 10% of cases of suspected acute viral hepatitis of unknown etiology and for a number of subclinical, unrecognized infections. The overall prevalence of antibody to HHEV is high in most of the former areas and low in most of the later ones, but wide regional differences have been recorded in both cases. “Hot spots” of HHEV infection would exist for both types of strains in particular regions or among particular populations of the world. Studies on pork derivatives, shellfish bivalves, and vegetables for HHEV contamination at the sale point need to be extended for evaluating the impact of the agent on food safety, and the meaning of the finding of HHEV genotype 1 genomes in urban sewage from developed countries should be established through active surveillance. Consensus about technical issues in regard to anti-HEV testing would improve the knowledge of the HHEV epidemiology. Studies in particular regions and populations, and introduction of molecular diagnosis in the clinical setting as a routine tool, would also be required. José-Manuel Echevarría Copyright © 2014 José-Manuel Echevarría. All rights reserved. Influenza Viral Manipulation of Sphingolipid Metabolism and Signaling to Modulate Host Defense System Thu, 23 Jan 2014 12:44:24 +0000 Viruses attempt to create a distinctive cellular environment to favor viral replication and spread. Recent studies uncovered new functions of the sphingolipid signaling/metabolism during pathogenic virus infections. While sphingolipids such as sphingomyelin and ceramide were reported to influence the entry step of several viruses, sphingolipid-metabolizing enzymes could directly alter viral replication processes. Influenza virus was shown to increase the level of sphingosine kinase (SK) 1 to promote virus propagation. The mechanism involves regulation of intracellular signaling pathways, leading to the amplification of influenza viral RNA synthesis and nuclear export of viral ribonucleoprotein (RNP) complex. However, bovine viral diarrhea virus inhibits SK1 to enhance the efficacy of virus replication, demonstrating the presence of virus-specific strategies for modulation of the sphingolipid system. Therefore, investigating the sphingolipid metabolism and signaling in the context of virus replication could help us design innovative therapeutic approaches to improve human health. Madhuvanthi Vijayan and Bumsuk Hahm Copyright © 2014 Madhuvanthi Vijayan and Bumsuk Hahm. All rights reserved. Bacterial Ice Crystal Controlling Proteins Mon, 20 Jan 2014 12:17:45 +0000 Across the world, many ice active bacteria utilize ice crystal controlling proteins for aid in freezing tolerance at subzero temperatures. Ice crystal controlling proteins include both antifreeze and ice nucleation proteins. Antifreeze proteins minimize freezing damage by inhibiting growth of large ice crystals, while ice nucleation proteins induce formation of embryonic ice crystals. Although both protein classes have differing functions, these proteins use the same ice binding mechanisms. Rather than direct binding, it is probable that these protein classes create an ice surface prior to ice crystal surface adsorption. Function is differentiated by molecular size of the protein. This paper reviews the similar and different aspects of bacterial antifreeze and ice nucleation proteins, the role of these proteins in freezing tolerance, prevalence of these proteins in psychrophiles, and current mechanisms of protein-ice interactions. Janet S. H. Lorv, David R. Rose, and Bernard R. Glick Copyright © 2014 Janet S. H. Lorv et al. All rights reserved. Oncolytic Immunotherapy: Where Are We Clinically? Thu, 16 Jan 2014 11:49:27 +0000 Following a century of preclinical and clinical work, oncolytic viruses are now proving themselves in randomized phase 3 trials. Interestingly, human data indicates that these agents have potent immunostimulatory activity, raising the possibility that the key consequence of oncolysis might be induction of antitumor immunity, especially in the context of viruses harboring immunostimulatory transgenes. While safety and efficacy of many types of oncolytic viruses, including adenovirus, herpes, reo, and vaccinia seem promising, few mechanisms of action studies have been performed with human substrates. Thus, the relative contribution of “pure” oncolysis, the immune response resulting from oncolysis, and the added benefit of adding a transgene remain poorly understood. Here, the available clinical data on oncolytic viruses is reviewed, with emphasis on immunological aspects. Akseli Hemminki Copyright © 2014 Akseli Hemminki. All rights reserved. Brain Mechanisms and Reading Remediation: More Questions Than Answers Sun, 12 Jan 2014 13:33:50 +0000 Dyslexia is generally diagnosed in childhood and is characterised by poor literacy skills with associated phonological and perceptual problems. Compensated dyslexic readers are adult readers who have a documented history of childhood dyslexia but as adults can read and comprehend written text well. Uncompensated dyslexic readers are adults who similarly have a documented history of reading impairment but remain functionally reading-impaired all their lives. There is little understanding of the neurophysiological basis for how or why some children become compensated, while others do not, and there is little knowledge about neurophysiological changes that occur with remedial programs for reading disability. This paper will review research looking at reading remediation, particularly in the context of the underlying neurophysiology. Kristen Pammer Copyright © 2014 Kristen Pammer. All rights reserved. How Adolescents with Diabetes Experience Social Support from Friends: Two Qualitative Studies Wed, 08 Jan 2014 09:53:39 +0000 Self-management of diabetes is challenging, especially for adolescents who face multiple changes, including closer peer relationships. Few studies have explored how friends can provide constructive support in this effort. The present research investigated, in two qualitative studies, the perceptions of adolescents with diabetes and their friends with respect to the positive social support that friends can offer. In study 1, 28 adolescents aged 12–15 with type 1 diabetes participated in online focus groups. In study 2, 11 of these adolescents were interviewed in person together with their best friends. The data were analysed by means of content analysis. In study 1, the adolescents with diabetes identified various supportive behaviours of friends, particularly concerning emotional support: treating them normally, showing interest, having fun, providing a distraction, and taking their diabetes into account. They differed in their attitude towards support, and this influenced which behaviours they perceived as supportive. Study 2 showed that the adolescents with diabetes and their friends often had similar opinions on the desired degree of support. Fear of stigmatization and sense of autonomy withheld some adolescents with diabetes from soliciting more support. These insights can be useful in patient education aiming to promote social support. Louk W. H. Peters, Laura Nawijn, and Nicole M. C. van Kesteren Copyright © 2014 Louk W. H. Peters et al. All rights reserved. Themes and Variations: Regulation of RpoN-Dependent Flagellar Genes across Diverse Bacterial Species Thu, 02 Jan 2014 15:06:10 +0000 Flagellar biogenesis in bacteria is a complex process in which the transcription of dozens of structural and regulatory genes is coordinated with the assembly of the flagellum. Although the overall process of flagellar biogenesis is conserved among bacteria, the mechanisms used to regulate flagellar gene expression vary greatly among different bacterial species. Many bacteria use the alternative sigma factor σ54 (also known as RpoN) to transcribe specific sets of flagellar genes. These bacteria include members of the Epsilonproteobacteria (e.g., Helicobacter pylori and Campylobacter jejuni), Gammaproteobacteria (e.g., Vibrio and Pseudomonas species), and Alphaproteobacteria (e.g., Caulobacter crescentus). This review characterizes the flagellar transcriptional hierarchies in these bacteria and examines what is known about how flagellar gene regulation is linked with other processes including growth phase, quorum sensing, and host colonization. Jennifer Tsang and Timothy R. Hoover Copyright © 2014 Jennifer Tsang and Timothy R. Hoover. All rights reserved. Maternal Dietary Patterns during Third Trimester in Association with Birthweight Characteristics and Early Infant Growth Tue, 31 Dec 2013 09:05:46 +0000 Our analysis examined the impact of maternal dietary patterns and lifestyle factors on markers of fetal growth, specifically birthweight and size for gestational age (small- (SGA) or large-for-gestational age (LGA)). The Infant Feeding Practices Study II, a prospective cohort study, surveyed pregnant women during their 3rd trimester, of which a subgroup () completed a food frequency questionnaire. Maternal dietary patterns were evaluated by diet scores (Alternative Healthy Eating Index for Pregnancy and alternate Mediterranean diet) and by carbohydrate quality (glycemic index and glycemic load). Poisson regression with robust standard errors was used to examine the relative risk of SGA and separately LGA, with dietary patterns and other lifestyle factors. Linear regression was used to determine the association of birthweight and early infant growth with better dietary patterns. Relative risk of SGA and LGA was not associated with dietary patterns. Birthweight and infant growth were not associated with maternal diet. Smoking, however, increased the risk of delivering an SGA infant (RR = 2.92, 95% CI: 1.58–5.39), while higher prepregnancy BMI increased the risk of delivering an LGA infant (RR = 1.06, 95% CI: 1.03–1.09). Future studies are needed to evaluate whether deficiencies in more specific maternal dietary nutrients play a role in fetal growth. Anna K. Poon, Edwina Yeung, Nansi Boghossian, Paul S. Albert, and Cuilin Zhang Copyright © 2013 Anna K. Poon et al. All rights reserved. Hox Targets and Cellular Functions Mon, 30 Dec 2013 14:52:23 +0000 Hox genes are a group of genes that specify structures along the anteroposterior axis in bilaterians. Although in many cases they do so by modifying a homologous structure with a different (or no) Hox input, there are also examples of Hox genes constructing new organs with no homology in other regions of the body. Hox genes determine structures though the regulation of targets implementing cellular functions and by coordinating cell behavior. The genetic organization to construct or modify a certain organ involves both a genetic cascade through intermediate transcription factors and a direct regulation of targets carrying out cellular functions. In this review I discuss new data from genome-wide techniques, as well as previous genetic and developmental information, to describe some examples of Hox regulation of different cell functions. I also discuss the organization of genetic cascades leading to the development of new organs, mainly using Drosophila melanogaster as the model to analyze Hox function. Ernesto Sánchez-Herrero Copyright © 2013 Ernesto Sánchez-Herrero. All rights reserved. Genetics of Proteasome Diseases Mon, 30 Dec 2013 14:15:12 +0000 The proteasome is a large, multiple subunit complex that is capable of degrading most intracellular proteins. Polymorphisms in proteasome subunits are associated with cardiovascular diseases, diabetes, neurological diseases, and cancer. One polymorphism in the proteasome gene PSMA6 (−8C/G) is associated with three different diseases: type 2 diabetes, myocardial infarction, and coronary artery disease. One type of proteasome, the immunoproteasome, which contains inducible catalytic subunits, is adapted to generate peptides for antigen presentation. It has recently been shown that mutations and polymorphisms in the immunoproteasome catalytic subunit PSMB8 are associated with several inflammatory and autoinflammatory diseases including Nakajo-Nishimura syndrome, CANDLE syndrome, and intestinal M. tuberculosis infection. This comprehensive review describes the disease-related polymorphisms in proteasome genes associated with human diseases and the physiological modulation of proteasome function by these polymorphisms. Given the large number of subunits and the central importance of the proteasome in human physiology as well as the fast pace of detection of proteasome polymorphisms associated with human diseases, it is likely that other polymorphisms in proteasome genes associated with diseases will be detected in the near future. While disease-associated polymorphisms are now readily discovered, the challenge will be to use this genetic information for clinical benefit. Aldrin V. Gomes Copyright © 2013 Aldrin V. Gomes. All rights reserved. Mammalian Tribbles Homologs at the Crossroads of Endoplasmic Reticulum Stress and Mammalian Target of Rapamycin Pathways Mon, 30 Dec 2013 08:46:34 +0000 In 2000, investigators discovered Tribbles, a Drosophila protein that coordinates morphogenesis by inhibiting mitosis. Further work has delineated Xenopus (Xtrb2), Nematode (Nipi-3), and mammalian homologs of Drosophila tribbles, which include TRB1, TRB2, and TRB3. The sequences of tribbles homologs are highly conserved, and despite their protein kinase structure, to date they have not been shown to have kinase activity. TRB family members play a role in the differentiation of macrophages, lymphocytes, muscle cells, adipocytes, and osteoblasts. TRB isoforms also coordinate a number of critical cellular processes including glucose and lipid metabolism, inflammation, cellular stress, survival, apoptosis, and tumorigenesis. TRB family members modulate multiple complex signaling networks including mitogen activated protein kinase cascades, protein kinase B/AKT signaling, mammalian target of rapamycin, and inflammatory pathways. The following review will discuss metazoan homologs of Drosophila tribbles, their structure, expression patterns, and functions. In particular, we will focus on TRB3 function in the kidney in podocytes. This review will also discuss the key signaling pathways with which tribbles proteins interact and provide a rationale for developing novel therapeutics that exploit these interactions to provide better treatment options for both acute and chronic kidney disease. Robyn Cunard Copyright © 2013 Robyn Cunard. All rights reserved. Imaging of Cardiac Valves by Computed Tomography Sun, 29 Dec 2013 16:38:49 +0000 This paper describes “how to” examine cardiac valves with computed tomography, the normal, diseased valves, and prosthetic valves. A review of current scientific literature is provided. Firstly, technical basics, “how to” perform and optimize a multislice CT scan and “how to” interpret valves on CT images are outlined. Then, diagnostic imaging of the entire spectrum of specific valvular disease by CT, including prosthetic heart valves, is highlighted. The last part gives a guide “how to” use CT for planning of transcatheter aortic valve implantation (TAVI), an emerging effective treatment option for patients with severe aortic stenosis. A special focus is placed on clinical applications of cardiac CT in the context of valvular disease. Gudrun Feuchtner Copyright © 2013 Gudrun Feuchtner. All rights reserved. The Role of the Intraplaque Vitamin D System in Atherogenesis Thu, 26 Dec 2013 14:06:26 +0000 Vitamin D has been shown to play critical activities in several physiological pathways not involving the calcium/phosphorus homeostasis. The ubiquitous distribution of the vitamin D receptor that is expressed in a variety of human and mouse tissues has strongly supported research on these “nonclassical” activities of vitamin D. On the other hand, the recent discovery of the expression also for vitamin D-related enzymes (such as 25-hydroxyvitamin D-1α-hydroxylase and the catabolic enzyme 1,25-dihydroxyvitamin D-24-hydroxylase) in several tissues suggested that the vitamin D system is more complex than previously shown and it may act within tissues through autocrine and paracrine pathways. This updated model of vitamin D axis within peripheral tissues has been particularly investigated in atherosclerotic pathophysiology. This review aims at updating the role of the local vitamin D within atherosclerotic plaques, providing an overview of both intracellular mechanisms and cell-to-cell interactions. In addition, clinical findings about the potential causal relationship between vitamin D deficiency and atherogenesis will be analysed and discussed. Federico Carbone and Fabrizio Montecucco Copyright © 2013 Federico Carbone and Fabrizio Montecucco. All rights reserved. Intracellular Regulation of Matrix Metalloproteinase-2 Activity: New Strategies in Treatment and Protection of Heart Subjected to Oxidative Stress Tue, 24 Dec 2013 08:37:50 +0000 Much is known regarding cardiac energy metabolism in ischemia/reperfusion (I/R) injury. Under aerobic conditions, the heart prefers to metabolize fatty acids, which contribute to 60–80% of the required ATP. During ischemia, anaerobic glycolysis increases and becomes an important source of ATP for preservation of ion gradients. With reperfusion, fatty acid oxidation quickly recovers and again predominates as the major source of mitochondrial oxidative metabolism. Although a number of molecular mechanisms have been implicated in the development of I/R injury, their relative contributions remain to be determined. One such mechanism involves the proteolytic degradation of contractile proteins, such as troponin I (TnI), myosin heavy chain, titin, and the myosin light chains (MLC1 and MLC2) by matrix metalloproteinase-2 (MMP-2). However, very little is known about intracellular regulation of MMP-2 activity under physiological and pathological conditions. Greater understanding of the mechanisms that govern MMP-2 activity may lead to the development of new therapeutic strategies aimed at preservation of the contractile function of the heart subjected to myocardial infarction (MI) or I/R. This review discusses the intracellular mechanisms controlling MMP-2 activity and highlights a new intracellular therapeutic direction for the prevention and treatment of heart injury. Grzegorz Sawicki Copyright © 2013 Grzegorz Sawicki. All rights reserved.