Journal of Biophysics The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Higher Performance of DSSC with Dyes from Cladophora sp. as Mixed Cosensitizer through Synergistic Effect Thu, 22 Jan 2015 06:42:30 +0000 Chlorophyll and xanthophyll dyes extracted from a single source of filamentous freshwater green algae (Cladophora sp.) were used to sensitize dye sensitized solar cells and their performances were investigated. A more positive interaction is expected as the derived dyes come from a single natural source because they work mutually in nature. Cell sensitized with mixed chlorophyll and xanthophyll showed synergistic activity with improved cell performance of 1.5- to 2-fold higher than that sensitized with any individual dye. The effect of temperature and the stability of these dyes were also investigated. Xanthophyll dye was found to be more stable compared to chlorophyll that is attributed in the ability of xanthophyll to dissipate extra energy via reversible structural changes. Mixing the dyes resulted to an increase in effective electron life time and reduced the process of electron recombination during solar cell operation, hence exhibiting a synergistic effect. Andery Lim, Noramaliyana Haji Manaf, Kushan Tennakoon, R. L. N. Chandrakanthi, Linda Biaw Leng Lim, J. M. R. Sarath Bandara, and Piyasiri Ekanayake Copyright © 2015 Andery Lim et al. All rights reserved. Effect of Ultraviolet-A (UV-A) and Ultraviolet-C (UV-C) Light on Mechanical Properties of Oyster Mushrooms during Growth Sun, 14 Dec 2014 00:10:03 +0000 This study investigated the effects of ultraviolet-A (UV-A) and ultraviolet-C (UV-C) light on the mechanical properties in oyster mushrooms during the growth. Experiments were carried out with irradiation of the mushrooms with UV-A (365 nm) and UV-C (254 nm) light during growth. The exposure time ranged from 10 minutes to 60 minutes at intervals of 10 minutes and irradiation was done for three days. The samples for experimental studies were cut into cylindrical shapes of diameter 12.50 mm and thickness 3.00 mm. The storage modulus, loss modulus, and loss factor of the irradiated samples and control samples were determined for both UV bands and there was a significant difference between the storage modulus, loss modulus, and loss factor of the irradiated samples by both UV bands with reference to the control sample, . UV-C light irradiated samples had higher loss modulus and loss factor but low storage modulus as temperature increased from 35 to 100°C with respect to the control sample while UV-A light irradiated samples had lower loss modulus, low loss factor, and higher storage modulus than UV-C irradiated samples. Tindibale L. Edward, M. S. K. Kirui, Josiah O. Omolo, Richard G. Ngumbu, and Peter M. Odhiambo Copyright © 2014 Tindibale L. Edward et al. All rights reserved. Effect of Calcium Ion Removal, Ionic Strength, and Temperature on the Conformation Change in Calmodulin Protein at Physiological pH Tue, 09 Dec 2014 00:10:03 +0000 The response of the calmodulin (CaM) protein as a function of calcium ion removal, ionic strength, and temperature at physiological pH condition was investigated using classical molecular dynamics simulations. Changing the ionic strength and temperature came out to be two of the possible routes for observing a conformation change in the protein. This behavior is similar to the conformation change observed in our previous study where a change in the pH was observed to trigger a conformation change in this protein. In the present study, as the calcium ions are removed from the protein, the protein is observed to acquire more flexibility. This flexibility is observed to be more prominent at a higher ionic strength. At a lower ionic strength of 150 mM with all the four calcium ions intact, the N- and C-lobes are observed to come close to a distance of 30 Å starting from an initial separation distance of 48 Å. This conformation change is observed to take place around 50 ns in a simulation of 100 ns. As a second parameter, temperature is observed to play a key role in the conformation change of the protein. With an increase in the temperature, the protein is observed to acquire a more compact form with the formation of different salt bridges between the residues of the N- and the C-lobes. The salt bridge formation leads to an overall lowering of the energy of the protein thus favoring the bending of the two lobes towards each other. The improper and dihedral terms show a significant shift thus leading to a more compact form on increasing the temperature. Another set of simulations is also performed at an increased temperature of 500 K to verify the reproducibility of the results. Thus a set of three possible alterations in the environmental conditions of the protein CaM are studied, with two of them giving rise to a conformation change and one adding flexibility to the protein. Sunita Negi Copyright © 2014 Sunita Negi. All rights reserved. Interaction between Gallotannin and a Recombinant Form of Arginine Kinase of Trypanosoma brucei: Thermodynamic and Spectrofluorimetric Evaluation Tue, 26 Aug 2014 00:00:00 +0000 Current chemotherapies against trypanosomiasis are beset with diverse challenges, a situation which underscores the numerous research efforts aimed at finding newer and effective treatments. Arginine kinase of trypanosome has been validated as target for drug development against trypanosomiasis. The present study investigated the interaction between a recombinant form of the arginine kinase (rTbAK) of trypanosome and gallotannin. The interaction between gallotannin and recombinant arginine kinase of Trypanosoma brucei caused significant decrease of enzyme activity. Kinetic analysis revealed the interaction to be of noncompetitive inhibition. Further thermodynamic analysis showed that the interaction between gallotannin and the recombinant arginine kinase was nonspontaneous and involved hydrophobic forces. The values and the FRET analysis suggest that static quenching of fluorescence intensity by gallotannin was static. Data revealed inhibitory interactions between gallotannin and rTbAK of trypanosome. Although the mechanism of inhibition is not clear yet, molecular docking studies are ongoing to clearly define the inhibitory interactions between the gallotannin and rTbAK. The knowledge of such binding properties would enrich development of selective inhibitors for the arginine kinase of Trypanosoma brucei. O. S. Adeyemi, A. F. Sulaiman, and O. M. Iniaghe Copyright © 2014 O. S. Adeyemi et al. All rights reserved. Analysis of Flow Characteristics of the Blood Flowing through an Inclined Tapered Porous Artery with Mild Stenosis under the Influence of an Inclined Magnetic Field Tue, 25 Feb 2014 13:33:55 +0000 Analytical investigation of MHD blood flow in a porous inclined stenotic artery under the influence of the inclined magnetic field has been done. Blood is considered as an electrically conducting Newtonian fluid. The physics of the problem is described by the usual MHD equations along with appropriate boundary conditions. The flow governing equations are finally transformed to nonhomogeneous second-order ordinary differential equations. This model is consistent with the principles of magnetohydrodynamics. Analytical expressions for the velocity profile, volumetric flow rate, wall shear stress, and pressure gradient have been derived. Blood flow characteristics are computed for a specific set of values of the different parameters involved in the model analysis and are presented graphically. Some of the obtained results show that the flow patterns in converging region (), diverging region (), and nontapered region () are effectively influenced by the presence of magnetic field and change in inclination of artery as well as magnetic field. There is also a significant effect of permeability on the wall shear stress as well as volumetric flow rate. Neetu Srivastava Copyright © 2014 Neetu Srivastava. All rights reserved. Impacts of Temperature on the Stability of Tropical Plant Pigments as Sensitizers for Dye Sensitized Solar Cells Sun, 23 Feb 2014 13:10:54 +0000 Natural dyes have become a viable alternative to expensive organic sensitizers because of their low cost of production, abundance in supply, and eco-friendliness. We evaluated 35 native plants containing anthocyanin pigments as potential sensitizers for DSSCs. Melastoma malabathricum (fruit pulp), Hibiscus rosa-sinensis (flower), and Codiaeum variegatum (leaves) showed the highest absorption peaks. Hence, these were used to determine anthocyanin content and stability based on the impacts of storage temperature. Melastoma malabathricum fruit pulp exhibited the highest anthocyanin content (8.43 mg/L) followed by H. rosa-sinensis and C. variegatum. Significantly greater stability of extracted anthocyanin pigment was shown when all three were stored at 4∘C. The highest half-life periods for anthocyanin in M. malabathricum, H. rosa-sinensis, and C. variegatum were 541, 571, and 353 days at 4∘C. These were rapidly decreased to 111, 220, and 254 days when stored at 25∘C. The photovoltaic efficiency of M. malabathricum was1.16%, while the values for H. rosa-sinensis and C. variegatum were 0.16% and 1.08%, respectively. Hence, M. malabathricum fruit pulp extracts can be further evaluated as an alternative natural sensitizer for DSSCs. Aiman Yusoff, N. T. R. N. Kumara, Andery Lim, Piyasiri Ekanayake, and Kushan U. Tennakoon Copyright © 2014 Aiman Yusoff et al. All rights reserved. The Diamagnetic Susceptibility of the Tubulin Dimer Tue, 18 Feb 2014 12:59:58 +0000 An approximate value of the diamagnetic anisotropy of the tubulin dimer, , has been determined assuming axial symmetry and that only the α-helices and β-sheets contribute to the anisotropy. Two approaches have been utilized: (a) using the value for the for an α-helical peptide bond given by Pauling (1979) and (b) using the previously determined anisotropy of fibrinogen as a calibration standard. The  JT−2 obtained from these measurements are similar to within 20%. Although Cotton-Mouton measurements alone cannot be used to estimate directly, the value we measured,  T−2cm2mg−1, is consistent with the above estimate for . The method utilized for the determination of the tubulin dimer diamagnetic susceptibility is applicable to other proteins and macromolecular assemblies as well. Wim Bras, James Torbet, Gregory P. Diakun, Geert L. J. A. Rikken, and J. Fernando Diaz Copyright © 2014 Wim Bras et al. All rights reserved. The Principle of Stationary Action in Biophysics: Stability in Protein Folding Sat, 28 Dec 2013 12:02:05 +0000 We conceptualize protein folding as motion in a large dimensional dihedral angle space. We use Lagrangian mechanics and introduce an unspecified Lagrangian to study the motion. The fact that we have reliable folding leads us to conjecture the totality of paths forms caustics that can be recognized by the vanishing of the second variation of the action. There are two types of folding processes: stable against modest perturbations and unstable. We also conjecture that natural selection has picked out stable folds. More importantly, the presence of caustics leads naturally to the application of ideas from catastrophe theory and allows us to consider the question of stability for the folding process from that perspective. Powerful stability theorems from mathematics are then applicable to impose more order on the totality of motions. This leads to an immediate explanation for both the insensitivity of folding to solution perturbations and the fact that folding occurs using very little free energy. The theory of folding, based on the above conjectures, can also be used to explain the behavior of energy landscapes, the speed of folding similar to transition state theory, and the fact that random proteins do not fold. Walter Simmons and Joel L. Weiner Copyright © 2013 Walter Simmons and Joel L. Weiner. All rights reserved. Transport Reversal during Heteroexchange: A Kinetic Study Sat, 26 Oct 2013 11:39:33 +0000 It is known that secondary transporters, which utilize transmembrane ionic gradients to drive their substrates up a concentration gradient, can reverse the uptake and instead release their substrates. Unfortunately, the Michaelis-Menten kinetic scheme, which is popular in transporter studies, does not include transporter reversal, and it completely neglects the possibility of equilibrium between the substrate concentrations on both sides of the membrane. We have developed a complex two-substrate kinetic model that includes transport reversal. This model allows us to construct analytical formulas allowing the calculation of a “heteroexchange” and “transacceleration” using standard Michaelis coefficients for respective substrates. This approach can help to understand how glial and other cells accumulate substrates without synthesis and are able to release such substrates and gliotransmitters. V. Makarov, L. Kucheryavykh, Y. Kucheryavykh, A. Rivera, M. J. Eaton, S. N. Skatchkov, and M. Inyushin Copyright © 2013 V. Makarov et al. All rights reserved. A Tree-Like Model for Brain Growth and Structure Mon, 02 Sep 2013 09:23:35 +0000 The Flory-Stockmayer theory for the polycondensation of branched polymers, modified for finite systems beyond the gel point, is applied to the connection (synapses) of neurons, which can be considered highly branched “monomeric” units. Initially, the process is a linear growth and tree-like branching between dendrites and axons of nonself-neurons. After the gel point and at the maximum “tree” size, the tree-like model prescribes, on average, one pair of twin synapses per neuron. About 13% of neurons, “unconnected” to the maximum tree, migrate to the surface to form cortical layers. The number of synapses in each neuron may reach 10000, indicating a tremendous amount of flexible, redundant, and neuroplastic loop-forming linkages which can be preserved or pruned by experience and learning. Benjamin C. Yan and Johnson F. Yan Copyright © 2013 Benjamin C. Yan and Johnson F. Yan. All rights reserved. Cell Matrix Remodeling Ability Shown by Image Spatial Correlation Sun, 14 Jul 2013 09:27:48 +0000 Extracellular matrix (ECM) remodeling is a critical step of many biological and pathological processes. However, most of the studies to date lack a quantitative method to measure ECM remodeling at a scale comparable to cell size. Here, we applied image spatial correlation to collagen second harmonic generation (SHG) images to quantitatively evaluate the degree of collagen remodeling by cells. We propose a simple statistical method based on spatial correlation functions to determine the size of high collagen density area around cells. We applied our method to measure collagen remodeling by two breast cancer cell lines (MDA-MB-231 and MCF-7), which display different degrees of invasiveness, and a fibroblast cell line (NIH/3T3). We found distinct collagen compaction levels of these three cell lines by applying the spatial correlation method, indicating different collagen remodeling ability. Furthermore, we quantitatively measured the effect of Latrunculin B and Marimastat on MDA-MB-231 cell line collagen remodeling ability and showed that significant collagen compaction level decreases with these treatments. Chi-Li Chiu, Michelle A. Digman, and Enrico Gratton Copyright © 2013 Chi-Li Chiu et al. All rights reserved. Analysis of the REJ Module of Polycystin-1 Using Molecular Modeling and Force-Spectroscopy Techniques Sun, 26 May 2013 16:18:25 +0000 Polycystin-1 is a large transmembrane protein, which, when mutated, causes autosomal dominant polycystic kidney disease, one of the most common life-threatening genetic diseases that is a leading cause of kidney failure. The REJ (receptor for egg lelly) module is a major component of PC1 ectodomain that extends to about 1000 amino acids. Many missense disease-causing mutations map to this module; however, very little is known about the structure or function of this region. We used a combination of homology molecular modeling, protein engineering, steered molecular dynamics (SMD) simulations, and single-molecule force spectroscopy (SMFS) to analyze the conformation and mechanical stability of the first ~420 amino acids of REJ. Homology molecular modeling analysis revealed that this region may contain structural elements that have an FNIII-like structure, which we named REJd1, REJd2, REJd3, and REJd4. We found that REJd1 has a higher mechanical stability than REJd2 (~190 pN and 60 pN, resp.). Our data suggest that the putative domains REJd3 and REJd4 likely do not form mechanically stable folds. Our experimental approach opens a new way to systematically study the effects of disease-causing mutations on the structure and mechanical properties of the REJ module of PC1. Meixiang Xu, Liang Ma, Paul J. Bujalowski, Feng Qian, R. Bryan Sutton, and Andres F. Oberhauser Copyright © 2013 Meixiang Xu et al. All rights reserved. Comparative Trace Elemental Analysis in Cancerous and Noncancerous Human Tissues Using PIXE Thu, 16 May 2013 15:37:24 +0000 The effect of high or low levels of trace metals in human tissues has been studied widely. There have been detectable significant variations in the concentrations of trace metals in normal and cancerous tissues suggesting that these variations could be a causative factor to various cancers. Even though essential trace metals play an important role such as stabilizers, enzyme cofactors, elements of structure, and essential elements for normal hormonal functions, their imbalanced toxic effects contribute to the rate of the reactive oxygen species (ROS) and formation of complexities in the body cells which may lead to DNA damage. The induction of oxidative-induced DNA damage by ROS may lead to isolated base lesions or single-strand breaks, complex lesions like double-strand breaks, and some oxidative generated clustered DNA lesions (OCDLs) which are linked to cell apoptosis and mutagenesis. The difference in published works on the level of variations of trace metals in different cancer tissues can be attributed to the accuracy of the analytical techniques, sample preparation methods, and inability of taking uniform samples from the affected tissues. This paper reviews comparative trace elemental concentrations of cancerous and noncancerous tissues using PIXE that has been reported in the published literature. Stephen Juma Mulware Copyright © 2013 Stephen Juma Mulware. All rights reserved. Reduced Dynamic Models in Epithelial Transport Thu, 28 Feb 2013 09:18:59 +0000 Most models developed to represent transport across epithelia assume that the cell interior constitutes a homogeneous compartment, characterized by a single concentration value of the transported species. This conception differs significantly from the current view, in which the cellular compartment is regarded as a highly crowded media of marked structural heterogeneity. Can the finding of relatively simple dynamic properties of transport processes in epithelia be compatible with this complex structural conception of the cell interior? The purpose of this work is to contribute with one simple theoretical approach to answer this question. For this, the techniques of model reduction are utilized to obtain a two-state reduced model from more complex linear models of transcellular transport with a larger number of intermediate states. In these complex models, each state corresponds to the solute concentration in an intermediate intracellular compartment. In addition, the numerical studies reveal that it is possible to approximate a general two-state model under conditions where strict reduction of the complex models cannot be performed. These results contribute with arguments to reconcile the current conception of the cell interior as a highly complex medium with the finding of relatively simple dynamic properties of transport across epithelial cells. Julio A. Hernández Copyright © 2013 Julio A. Hernández. All rights reserved. Potassium Current Is Not Affected by Long-Term Exposure to Ghrelin or GHRP-6 in Somatotropes GC Cells Sun, 24 Feb 2013 15:30:54 +0000 Ghrelin is a growth hormone (GH) secretagogue (GHS) and GHRP-6 is a synthetic peptide analogue; both act through the GHS receptor. GH secretion depends directly on the intracellular concentration of Ca2+; this is determined from the intracellular reserves and by the entrance of Ca2+ through the voltage-dependent calcium channels, which are activated by the membrane depolarization. Membrane potential is mainly determined by K+ channels. In the present work, we investigated the effect of ghrelin (10 nM) or GHRP-6 (100 nM) for 96 h on functional expression of voltage-dependent K+ channels in rat somatotropes: GC cell line. Physiological patch-clamp whole-cell recording was used to register the K+ currents. With Cd2+ (1 mM) and tetrodotoxin (1 μm) in the bath solution recording, three types of currents were characterized on the basis of their biophysical and pharmacological properties. GC cells showed a K+ current with a transitory component sensitive to 4-aminopyridine, which represents ~40% of the total outgoing current; a sustained component named delayed rectifier , sensitive to tetraethylammonium; and a third type of K+ current was recorded at potentials more negative than −80 mV, permitting the entrance of K+ named inward rectifier (KIR). Chronic treatment with ghrelin or GHRP-6 did not modify the functional expression of K+ channels, without significant changes () in the amplitudes of the three currents observed; in addition, there were no modifications in their biophysical properties and kinetic activation or inactivation. Belisario Domínguez Mancera, Eduardo Monjaraz Guzman, Jorge L. V. Flores-Hernández, Manuel Barrientos Morales, José M. Martínez Hernandez, Antonio Hernández Beltran, and Patricia Cervantes Acosta Copyright © 2013 Belisario Domínguez Mancera et al. All rights reserved. Thermal Aggregation of Recombinant Protective Antigen: Aggregate Morphology and Growth Rate Wed, 13 Feb 2013 15:49:35 +0000 The thermal aggregation of the biopharmaceutical protein recombinant protective antigen (rPA) has been explored, and the associated kinetics and thermodynamic parameters have been extracted using optical and environmental scanning electron microscopies (ESEMs) and ultraviolet light scattering spectroscopy (UV-LSS). Visual observations and turbidity measurements provided an overall picture of the aggregation process, suggesting a two-step mechanism. Microscopy was used to examine the structure of aggregates, revealing an open morphology formed by the clustering of the microscopic aggregate particles. UV-LSS was used and developed to elucidate the growth rate of these particles, which formed in the first stage of the aggregation process. Their growth rate is observed to be high initially, before falling to converge on a final size that correlates with the ESEM data. The results suggest that the particle growth rate is limited by rPA monomer concentration, and by obtaining data over a range of incubation temperatures, an approach was developed to model the aggregation kinetics and extract the rate constants and the temperature dependence of aggregation. In doing so, we quantified the susceptibility of rPA aggregation under different temperature and environmental conditions and moreover demonstrated a novel use of UV spectrometry to monitor the particle aggregation quantitatively, in situ, in a nondestructive and time-resolved manner. Daniel J. Belton and Aline F. Miller Copyright © 2013 Daniel J. Belton and Aline F. Miller. All rights reserved. Cytoskeletal Strains in Modeled Optohydrodynamically Stressed Healthy and Diseased Biological Cells Wed, 05 Dec 2012 08:58:57 +0000 Controlled external chemomechanical stimuli have been shown to influence cellular and tissue regeneration/degeneration, especially with regards to distinct disease sequelae or health maintenance. Recently, a unique three-dimensional stress state was mathematically derived to describe the experimental stresses applied to isolated living cells suspended in an optohydrodynamic trap (optical tweezers combined with microfluidics). These formulae were previously developed in two and three dimensions from the fundamental equations describing creeping flows past a suspended sphere. The objective of the current study is to determine the full-field cellular strain response due to the applied three-dimensional stress environment through a multiphysics computational simulation. In this investigation, the multiscale cytoskeletal structures are modeled as homogeneous, isotropic, and linearly elastic. The resulting computational biophysics can be directly compared with experimental strain measurements, other modeling interpretations of cellular mechanics including the liquid drop theory, and biokinetic models of biomolecule dynamics. The described multiphysics computational framework will facilitate more realistic cytoskeletal model interpretations, whose intracellular structures can be distinctly defined, including the cellular membrane substructures, nucleus, and organelles. Sean S. Kohles, Yu Liang, and Asit K. Saha Copyright © 2012 Sean S. Kohles et al. All rights reserved. Redox Regulation of Calcium Signaling in Cancer Cells by Ascorbic Acid Involving the Mitochondrial Electron Transport Chain Sun, 25 Nov 2012 09:15:08 +0000 Previously, we have reported that ascorbic acid regulates calcium signaling in human larynx carcinoma HEp-2 cells. To evaluate the precise mechanism of Ca2+ release by ascorbic acid, the effects of specific inhibitors of the electron transport chain components on mitochondrial reactive oxygen species (ROS) production and Ca2+ mobilization in HEp-2 cells were investigated. It was revealed that the mitochondrial complex III inhibitor (antimycin A) amplifies ascorbate-induced Ca2+ release from intracellular stores. The mitochondrial complex I inhibitor (rotenone) decreases Ca2+ release from intracellular stores in HEp-2 cells caused by ascorbic acid and antimycin A. In the presence of rotenone, antimycin A stimulates ROS production by mitochondria. Ascorbate-induced Ca2+ release in HEp-2 cells is shown to be unaffected by catalase. The results obtained suggest that Ca2+ release in HEp-2 cells caused by ascorbic acid is associated with induced mitochondrial ROS production. The data obtained are in line with the concept of redox signaling that explains oxidant action by compartmentalization of ROS production and oxidant targets. Grigory G. Martinovich, Elena N. Golubeva, Irina V. Martinovich, and Sergey N. Cherenkevich Copyright © 2012 Grigory G. Martinovich et al. All rights reserved. A Molecular Dynamics Approach to Ligand-Receptor Interaction in the Aspirin-Human Serum Albumin Complex Wed, 21 Nov 2012 11:23:00 +0000 In this work, we present a study of the interaction between human serum albumin (HSA) and acetylsalicylic acid (ASA, C9H8O4) by molecular dynamics simulations (MD). Starting from an experimentally resolved structure of the complex, we performed the extraction of the ligand by means of the application of an external force. After stabilization of the system, we quantified the force used to remove the ASA from its specific site of binding to HSA and calculated the mechanical nonequilibrium external work done during this process. We obtain a reasonable value for the upper boundary of the Gibbs free energy difference (an equilibrium thermodynamic potential) between the complexed and noncomplexed states. To achieve this goal, we used the finite sampling estimator of the average work, calculated from the Jarzynski Equality. To evaluate the effect of the solvent, we calculated the so-called “viscous work,” that is, the work done to move the aspirin in the same trajectory through the solvent in absence of the protein, so as to assess the relevance of its contribution to the total work. The results are in good agreement with the available experimental data for the albumin affinity constant for aspirin, obtained through quenching fluorescence methods. H. Ariel Alvarez, Andrés N. McCarthy, and J. Raúl Grigera Copyright © 2012 H. Ariel Alvarez et al. All rights reserved. The Aggregation of Huntingtin and α-Synuclein Thu, 26 Jul 2012 13:01:58 +0000 Huntington’s and Parkinson’s diseases are neurodegenerative disorders associated with unusual protein interactions. Although the origin and evolution of these diseases are completely different, characteristic deposits of protein aggregates (huntingtin and α-synuclein resp.), are a common feature in both diseases. After these observations, many studies are performed with both proteins. Some of them try to understand the nature and driving forces of the aggregation process; others try to find a correlation between the genetic and failure in protein function. Finally with the combination of both approaches, it was proposed that possible strategies deal with pathologic aggregation. Unfortunately, if protein aggregation is a cause or a consequence of the neurodegeneration observed in these pathologies, it is still debatable. This paper describes the process of aggregation of two proteins: huntingtin and α synuclein. The characteristics of the aggregation reaction of these proteins have been followed with novel methods both in vivo and in vitro; these studies include both the combination with other proteins and the presence of various chemical compounds. The ultimate goal of this study was to summarize recent findings on protein aggregation and its possible role as a therapeutic target in neurodegenerative diseases and their role in biomaterial science. María Elena Chánez-Cárdenas and Edgar Vázquez-Contreras Copyright © 2012 María Elena Chánez-Cárdenas and Edgar Vázquez-Contreras. All rights reserved. pH-Dependent Interaction between C-Peptide and Phospholipid Bicelles Mon, 16 Jul 2012 15:00:32 +0000 C-peptide is the connecting peptide between the A and B chains of insulin in proinsulin. In this paper, we investigate the interaction between C-peptide and phospholipid bicelles, by circular dichroism and nuclear magnetic resonance spectroscopy, and in particular the pH dependence of this interaction. The results demonstrate that C-peptide is largely unstructured independent of pH, but that a weak structural induction towards a short stretch of β-sheet is induced at low pH, corresponding to the isoelectric point of the peptide. Furthermore, it is demonstrated that C-peptide associates with neutral phospholipid bicelles as well as acidic phospholipid bicelles at this low pH. C-peptide does not undergo a large structural rearrangement as a consequence of lipid interaction, which indicates that the folding and binding are uncoupled. In vivo, local variations in environment, including pH, may cause C-peptide to associate with lipids, which may affect the aggregation state of the peptide. Sofia Unnerståle and Lena Mäler Copyright © 2012 Sofia Unnerståle and Lena Mäler. All rights reserved. Inhibitory Effects of Arginine on the Aggregation of Bovine Insulin Mon, 09 Jul 2012 11:35:02 +0000 Static and dynamic light scattering were used to investigate the effects of L-arginine, commonly used to inhibit protein aggregation, on the initial aggregation kinetics of solutions of bovine insulin in 20% acetic acid and 0.1 M NaCl as a model system for amyloidosis. Measurements were made as a function of insulin concentration (0.5–2.0 mM), quench temperature (60–85°C), and arginine concentration (10–500 mM). Aggregation kinetics under all conditions had a lag phase, whose duration decreased with increasing temperature and with increasing insulin concentration but which increased by up to a factor of 8 with increasing added arginine. Further, the initial growth rate after the lag phase also slowed by up to a factor of about 20 in the presence of increasing concentrations of arginine. From the temperature dependence of the lag phase duration, we find that the nucleation activation energy doubles from 17±5 to 36±3 kcal/mol in the presence of 500 mM arginine. Michael M. Varughese and Jay Newman Copyright © 2012 Michael M. Varughese and Jay Newman. All rights reserved. Electronic and Spatial Structures of Water-Soluble Dinitrosyl Iron Complexes with Thiol-Containing Ligands Underlying Their Ability to Act as Nitric Oxide and Nitrosonium Ion Donors Tue, 14 Feb 2012 12:14:42 +0000 The ability of mononuclear dinitrosyl iron commplexes (M-DNICs) with thiolate ligands to act as NO donors and to trigger S-nitrosation of thiols can be explain only in the paradigm of the model of the [Fe+(NO+)2] core ({Fe(NO)2}7 according to the Enemark-Feltham classification). Similarly, the {(RS−)2Fe+(NO+)2}+ structure describing the distribution of unpaired electron density in M-DNIC corresponds to the low-spin () state with a d7 electron configuration of the iron atom and predominant localization of the unpaired electron on MO() and the square planar structure of M-DNIC. On the other side, the formation of molecular orbitals of M-DNIC including orbitals of the iron atom, thiolate and nitrosyl ligands results in a transfer of electron density from sulfur atoms to the iron atom and nitrosyl ligands. Under these conditions, the positive charge on the nitrosyl ligands diminishes appreciably, the interaction of the ligands with hydroxyl ions or with thiols slows down and the hydrolysis of nitrosyl ligands and the S-nitrosating effect of the latter are not manifested. Most probably, the S-nitrosating effect of nitrosyl ligands is a result of weak binding of thiolate ligands to the iron atom under conditions favoring destabilization of M-DNIC. Anatoly F. Vanin and Dosymzhan Sh. Burbaev Copyright © 2011 Anatoly F. Vanin and Dosymzhan Sh. Burbaev. All rights reserved. Quantitative Reappraisal of the Helmholtz-Guyton Resonance Theory of Frequency Tuning in the Cochlea Wed, 19 Oct 2011 11:34:54 +0000 To explore the fundamental biomechanics of sound frequency transduction in the cochlea, a two-dimensional analytical model of the basilar membrane was constructed from first principles. Quantitative analysis showed that axial forces along the membrane are negligible, condensing the problem to a set of ordered one-dimensional models in the radial dimension, for which all parameters can be specified from experimental data. Solutions of the radial models for asymmetrical boundary conditions produce realistic deformation patterns. The resulting second-order differential equations, based on the original concepts of Helmholtz and Guyton, and including viscoelastic restoring forces, predict a frequency map and amplitudes of deflections that are consistent with classical observations. They also predict the effects of an observation hole drilled in the surrounding bone, the effects of curvature of the cochlear spiral, as well as apparent traveling waves under a variety of experimental conditions. A quantitative rendition of the classical Helmholtz-Guyton model captures the essence of cochlear mechanics and unifies the competing resonance and traveling wave theories. Charles F. Babbs Copyright © 2011 Charles F. Babbs. All rights reserved. CsmA Protein is Associated with BChl a in the Baseplate Subantenna of Chlorosomes of the Photosynthetic Green Filamentous Bacterium Oscillochloris trichoides belonging to the Family Oscillochloridaceae Thu, 15 Sep 2011 10:21:01 +0000 The baseplate subantenna in chlorosomes of green anoxygenic photosynthetic bacteria, belonging to the families Chloroflexaceae and Chlorobiaceae, is known to represent a complex of bacteriochlorophyll (BChl) a with the ~6 kDa CsmA proteins. Earlier, we showed the existence of a similar BChl a subantenna in chlorosomes of the photosynthetic green bacterium Oscillochloris trichoides, member of Oscillochloridaceae, the third family of green photosynthetic bacteria. However, this BChl a subantenna was not visually identified in absorption spectra of isolated Osc. trichoides chlorosomes in contrast to those of Chloroflexaceae and Chlorobiaceae. In this work, using room and low-temperature absorbance and fluorescence spectroscopy and sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of alkaline-treated and untreated chlorosomes of Osc. trichoides, we showed that the baseplate BChl a subantenna does exist in Oscillochloridaceae chlorosomes as a complex of BChl a with the 5.7 kDa CsmA protein. The present results support the idea that the baseplate subantenna, representing a complex of BChl a with a ~6 kDa CsmA protein, is a universal interface between the BChl c subantenna of chlorosomes and the nearest light-harvesting BChl a subantenna in all three known families of green anoxygenic photosynthetic bacteria. Anastasiya Zobova, Alexandra Taisova, Eugeny Lukashev, Nataliya Fedorova, Ludmila Baratova, and Zoya Fetisova Copyright © 2011 Anastasiya Zobova et al. All rights reserved. F-Ratio Test and Hypothesis Weighting: A Methodology to Optimize Feature Vector Size Wed, 17 Aug 2011 09:56:38 +0000 Reducing a feature vector to an optimized dimensionality is a common problem in biomedical signal analysis. This analysis retrieves the characteristics of the time series and its associated measures with an adequate methodology followed by an appropriate statistical assessment of these measures (e.g., spectral power or fractal dimension). As a step towards such a statistical assessment, we present a data resampling approach. The techniques allow estimating 𝜎2(𝐹), that is, the variance of an F-value from variance analysis. Three test statistics are derived from the so-called F-ratio 𝜎2(𝐹)/𝐹2. A Bayesian formalism assigns weights to hypotheses and their corresponding measures considered (hypothesis weighting). This leads to complete, partial, or noninclusion of these measures into an optimized feature vector. We thus distinguished the EEG of healthy probands from the EEG of patients diagnosed as schizophrenic. A reliable discriminance performance of 81% based on Taken's χ, 𝛼-, and 𝛿-power was found. R. M. Dünki and M. Dressel Copyright © 2011 R. M. Dünki and M. Dressel. All rights reserved. Mechanisms of Cellular Uptake of Cell-Penetrating Peptides Thu, 07 Apr 2011 15:41:37 +0000 Recently, much attention has been given to the problem of drug delivery through the cell-membrane in order to treat and manage several diseases. The discovery of cell penetrating peptides (CPPs) represents a major breakthrough for the transport of large-cargo molecules that may be useful in clinical applications. CPPs are rich in basic amino acids such as arginine and lysine and are able to translocate over membranes and gain access to the cell interior. They can deliver large-cargo molecules, such as oligonucleotides, into cells. Endocytosis and direct penetration have been suggested as the two major uptake mechanisms, a subject still under debate. Unresolved questions include the detailed molecular uptake mechanism(s), reasons for cell toxicity, and the delivery efficiency of CPPs for different cargoes. Here, we give a review focused on uptake mechanisms used by CPPs for membrane translocation and certain experimental factors that affect the mechanism(s). Fatemeh Madani, Staffan Lindberg, Ülo Langel, Shiroh Futaki, and Astrid Gräslund Copyright © 2011 Fatemeh Madani et al. All rights reserved. Examinations of tRNA Range of Motion Using Simulations of Cryo-EM Microscopy and X-Ray Data Mon, 28 Mar 2011 11:37:27 +0000 We examined tRNA flexibility using a combination of steered and unbiased molecular dynamics simulations. Using Maxwell's demon algorithm, molecular dynamics was used to steer X-ray structure data toward that from an alternative state obtained from cryogenic-electron microscopy density maps. Thus, we were able to fit X-ray structures of tRNA onto cryogenic-electron microscopy density maps for hybrid states of tRNA. Additionally, we employed both Maxwell's demon molecular dynamics simulations and unbiased simulation methods to identify possible ribosome-tRNA contact areas where the ribosome may discriminate tRNAs during translation. Herein, we collected >500 ns of simulation data to assess the global range of motion for tRNAs. Biased simulations can be used to steer between known conformational stop points, while unbiased simulations allow for a general testing of conformational space previously unexplored. The unbiased molecular dynamics data describes the global conformational changes of tRNA on a sub-microsecond time scale for comparison with steered data. Additionally, the unbiased molecular dynamics data was used to identify putative contacts between tRNA and the ribosome during the accommodation step of translation. We found that the primary contact regions were H71 and H92 of the 50S subunit and ribosomal proteins L14 and L16. Thomas R. Caulfield, Batsal Devkota, and Geoffrey C. Rollins Copyright © 2011 Thomas R. Caulfield et al. All rights reserved. EI of the Phosphotransferase System of Escherichia coli: Mathematical Modeling Approach to Analysis of Its Kinetic Properties Sun, 20 Mar 2011 13:49:24 +0000 The mathematical model of the operation of the first enzyme of the Escherichia coli phosphotransferase system, EI, is proposed. Parameters of the kinetic model describing the operation of EI under different conditions are identified on the basis of a large amount of known experimental data. The verified model is employed to predict modes of operation of EI under both in vivo physiological conditions and in vitro nonphysiological conditions. The model predicts that under in vivo physiological conditions, the rate of phosphotransfer from EI to the second protein of the phosphotransferase system HPr by the dimer is much higher than by the monomer. A hypothesis is proposed on the basis of calculations that the transfer by a monomer plays a role in the regulation of chemotaxis. At submicromolar pyruvate concentration, the model predicts nonmonotonic dependence of the phosphotransfer rate on the substrate (PEP) concentration. T. A. Karelina, H. Ma, I. Goryanin, and O. V. Demin Copyright © 2011 T. A. Karelina et al. All rights reserved. Exploring the Membrane Mechanism of the Bioactive Peptaibol Ampullosporin A Using Lipid Monolayers and Supported Biomimetic Membranes Thu, 17 Feb 2011 10:39:31 +0000 Ampullosporin A is an antimicrobial, neuroleptic peptaibol, the behavior of which was investigated in different membrane mimetic environments made of egg yolk L-α-phosphatidylcholine. In monolayers, the peptaibol adopted a mixed α/310-helical structure with an in-plane orientation. The binding step was followed by the peptide insertion into the lipid monolayer core. The relevance of the inner lipid leaflet nature was studied by comparing ampullosporin binding on a hybrid bilayer, in which this leaflet was a rigid alkane layer, and on supported fluid lipid bilayers. The membrane binding was examined by surface plasmon resonance spectroscopy and the effect on lipid dynamics was explored using fluorescence recovery after photobleaching. In the absence of voltage and at low concentration, ampullosporin A substantially adsorbed onto lipid surfaces and its interaction with biomimetic models was strongly modified depending on the inner leaflet structure. At high concentration, ampullosporin A addition led to the lipid bilayers disruption. Marguerita Eid, Sonia Rippa, Sabine Castano, Bernard Desbat, Joël Chopineau, Claire Rossi, and Laure Béven Copyright © 2010 Marguerita Eid et al. All rights reserved.