Journal of Biophysics The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Trends in the Binding of Cell Penetrating Peptides to siRNA: A Molecular Docking Study Tue, 21 Feb 2017 00:00:00 +0000 The use of gene therapeutics, including short interfering RNA (siRNA), is limited by the lack of efficient delivery systems. An appealing approach to deliver gene therapeutics involves noncovalent complexation with cell penetrating peptides (CPPs) which are able to penetrate the cell membranes of mammals. Although a number of CPPs have been discovered, our understanding of their complexation and translocation of siRNA is as yet insufficient. Here, we report on computational studies comparing the binding affinities of CPPs with siRNA, considering a variety of CPPs. Specifically, seventeen CPPs from three different categories, cationic, amphipathic, and hydrophobic CPPs, were studied. Molecular mechanics were used to minimize structures, while molecular docking calculations were used to predict the orientation and favorability of sequentially binding multiple peptides to siRNA. Binding scores from docking calculations were highest for amphipathic peptides over cationic and hydrophobic peptides. Results indicate that initial complexation of peptides will likely occur along the major groove of the siRNA, driven by electrostatic interactions. Subsequent binding of CPPs is likely to occur in the minor groove and later on bind randomly, to siRNA or previously bound CPPs, through hydrophobic interactions. However, hydrophobic CPPs do not show this binding pattern. Ultimately binding yields a positively charged nanoparticle capable of noninvasive cellular import of therapeutic molecules. P. V. G. M. Rathnayake, B. G. C. M. Gunathunge, P. N. Wimalasiri, D. N. Karunaratne, and R. J. K. U. Ranatunga Copyright © 2017 P. V. G. M. Rathnayake et al. All rights reserved. Corrigendum to “Structural Stability, Transitions, and Interactions within SoxYZCD-Thiosulphate from Sulfurimonas denitrificans: An In Silico Molecular Outlook for Maintaining Environmental Sulphur Cycle” Tue, 20 Dec 2016 08:53:43 +0000 Sujay Ray and Arundhati Banerjee Copyright © 2016 Sujay Ray and Arundhati Banerjee. All rights reserved. Detection of Gait Modes Using an Artificial Neural Network during Walking with a Powered Ankle-Foot Orthosis Tue, 13 Dec 2016 12:08:50 +0000 This paper presents an algorithm, for use with a Portable Powered Ankle-Foot Orthosis (i.e., PPAFO) that can automatically detect changes in gait modes (level ground, ascent and descent of stairs or ramps), thus allowing for appropriate ankle actuation control during swing phase. An artificial neural network (ANN) algorithm used input signals from an inertial measurement unit and foot switches, that is, vertical velocity and segment angle of the foot. Output from the ANN was filtered and adjusted to generate a final data set used to classify different gait modes. Five healthy male subjects walked with the PPAFO on the right leg for two test scenarios (walking over level ground and up and down stairs or a ramp; three trials per scenario). Success rate was quantified by the number of correctly classified steps with respect to the total number of steps. The results indicated that the proposed algorithm’s success rate was high (99.3%, 100%, and 98.3% for level, ascent, and descent modes in the stairs scenario, respectively; 98.9%, 97.8%, and 100% in the ramp scenario). The proposed algorithm continuously detected each step’s gait mode with faster timing and higher accuracy compared to a previous algorithm that used a decision tree based on maximizing the reliability of the mode recognition. Mazharul Islam and Elizabeth T. Hsiao-Wecksler Copyright © 2016 Mazharul Islam and Elizabeth T. Hsiao-Wecksler. All rights reserved. Structural Stability, Transitions, and Interactions within SoxYZCD-Thiosulphate from Sulfurimonas denitrificans: An In Silico Molecular Outlook for Maintaining Environmental Sulphur Cycle Thu, 29 Sep 2016 09:01:57 +0000 Thiosulphate oxidation (an essential mechanism) serves to maintain the global sulphur cycle. Earlier experimental and computational studies dealt with environmental thiosulphate oxidation but none dealt with thiosulphate oxidation from deep ocean belts. Wet-laboratory experimental research shows that epsilon-proteobacteria Sulfurimonas denitrificans possess sox (sulphur-oxidizing) operon and perform thiosulphate oxidation efficiently underneath the oceans. From this specific sox operon, SoxCD complex recycles the thiosulphate-bound SoxY from SoxYZ complex to balance the environmental sulphur cycle. So, four chief proteins were variedly modeled and relevant simulated interactive structures were obtained. The final simulated tetraprotein complex (SoxYZCD) from docked SoxYZ and SoxCD complexes was disclosed to be a highly interactive one with predominant ionic residues. Free energy of folding, solvent accessibility, and conformational shifts (coil-like conformation to helices and sheets) were observed in SoxYZ complex after interacting with SoxCD. The stability of the complex (SoxYZCD) after simulation was also observed through the electrostatic surface potential values. These evaluations were rationalized via biostatistics. This aids SoxCD for recycling SoxY along with thiosulphate, which remains interconnected by four H-bonds with SoxY. Therefore, this novel exploration is endowed with the detailed molecular viewpoint for maintaining the sulphur cycle (globally) including the ocean belts. Sujay Ray and Arundhati Banerjee Copyright © 2016 Sujay Ray and Arundhati Banerjee. All rights reserved. A Coupled Phase-Temperature Model for Dynamics of Transient Neuronal Signal in Mammals Cold Receptor Wed, 28 Sep 2016 14:07:22 +0000 We propose a theoretical model consisting of coupled differential equation of membrane potential phase and temperature for describing the neuronal signal in mammals cold receptor. Based on the results from previous work by Roper et al., we modified a nonstochastic phase model for cold receptor neuronal signaling dynamics in mammals. We introduce a new set of temperature adjusted functional parameters which allow saturation characteristic at high and low steady temperatures. The modified model also accommodates the transient neuronal signaling process from high to low temperature by introducing a nonlinear differential equation for the “effective temperature” changes which is coupled to the phase differential equation. This simple model can be considered as a candidate for describing qualitatively the physical mechanism of the corresponding transient process. Firman Ahmad Kirana, Husin Alatas, and Irzaman Sulaiman Husein Copyright © 2016 Firman Ahmad Kirana et al. All rights reserved. Data Acquisition System for In Situ Monitoring of Chemoelectrical Potential in Living Plant Fuel Cells Tue, 30 Aug 2016 08:30:25 +0000 Photosynthesis process in plants generates numerous sources of bioenergy. However, only a small fraction is readily exploited for electrical energy. The impact of environmental factors is one of the significant physiological influences on the electrical potential of the plants. Hence, we developed a data acquisition (DAQ) system for instantaneous monitoring of electrical potential in plants and Aloe vera was used as a plant sample. The static response characterization, capability index (P/T), and Pearson’s coefficient of correlation procedures were applied to assess the reliability of the obtained data. This developed system offers the capability of in situ monitoring and detecting gradual changes in the electrical potential of plants up to a correlational strength of greater than 0.7. Interpretation of the electrical signal mechanisms in the Aloe vera plant and the optimization of the electricity can be achieved through the application of this monitoring system. This system, therefore, can serve as a tool to measure and analyze the electrical signals in plants at different conditions. Fuei Pien Chee, Cheng Ann Chen, Jackson Hian Wui Chang, Ying Ying Choo, and Jedol Dayou Copyright © 2016 Fuei Pien Chee et al. All rights reserved. Physical Non-Contact Communication between Microscopic Aquatic Species: Novel Experimental Evidences for an Interspecies Information Exchange Wed, 02 Mar 2016 07:53:55 +0000 Previous experiments on physical non-contact communication within same species gave rise to test for this type of communication also across the species border, which was the aim of the present study. It was found that autotrophic unicellular organisms (Euglena viridis), separated by cuvettes, affected the proliferation rate of heterotrophic unicellular organisms (Paramecium caudatum). Further, the heterotrophic unicellular organism affected also the proliferation rate of a multicellular heterotrophic organism (Rotatoria sp.) and vice versa. In the case when populations (of Euglena viridis and Paramecium caudatum) were shielded against electromagnetic fields in the optical spectrum from each other, no effects were measured. The results may support the notion that the organisation of ecosystems relies also on the exchange of electromagnetic fields from their constituting biosystems. Daniel Fels Copyright © 2016 Daniel Fels. All rights reserved. Self-Optimized Biological Channels in Facilitating the Transmembrane Movement of Charged Molecules Sun, 28 Feb 2016 11:26:56 +0000 We consider an anisotropically two-dimensional diffusion of a charged molecule (particle) through a large biological channel under an external voltage. The channel is modeled as a cylinder of three structure parameters: radius, length, and surface density of negative charges located at the channel interior-lining. These charges induce inside the channel a potential that plays a key role in controlling the particle current through the channel. It was shown that to facilitate the transmembrane particle movement the channel should be reasonably self-optimized so that its potential coincides with the resonant one, resulting in a large particle current across the channel. Observed facilitation appears to be an intrinsic property of biological channels, regardless of the external voltage or the particle concentration gradient. This facilitation is very selective in the sense that a channel of definite structure parameters can facilitate the transmembrane movement of only particles of proper valence at corresponding temperatures. Calculations also show that the modeled channel is nonohmic with the ion conductance which exhibits a resonance at the same channel potential as that identified in the current. V. T. N. Huyen, Le Bin Ho, Vu Cong Lap, and V. Lien Nguyen Copyright © 2016 V. T. N. Huyen et al. All rights reserved. The Effect of Extremely Low Frequency Alternating Magnetic Field on the Behavior of Animals in the Presence of the Geomagnetic Field Mon, 28 Dec 2015 13:46:47 +0000 It is known that the geomagnetic field can influence animal migration and homing. The magnetic field detection by animals is known as magnetoreception and it is possible due to two different transduction mechanisms: the first one through magnetic nanoparticles able to respond to the geomagnetic field and the second one through chemical reactions influenced by magnetic fields. Another behavior is the magnetic alignment where animals align their bodies to the geomagnetic field. It has been observed that magnetic alignment of cattle can be disrupted near electric power lines around the world. Experimentally, it is known that alternating magnetic fields can influence living beings, but the exact mechanism is unknown. The parametric resonance model proposes a mechanism to explain that effect on living beings and establishes that, in the presence of a constant magnetic field, molecules associated with biochemical reactions inside cells can absorb resonantly alternating magnetic fields with specific frequencies. In the present paper, a review is made about animal magnetoreception and the effects of alternating magnetic fields in living beings. It is suggested how alternating magnetic fields can interfere in the magnetic alignment of animals and a general conclusion is obtained: alternating magnetic field pollution can affect the magnetic sensibility of animals. Natalia A. Belova and Daniel Acosta-Avalos Copyright © 2015 Natalia A. Belova and Daniel Acosta-Avalos. All rights reserved. Efficiency Enhancement of Cocktail Dye of Ixora coccinea and Tradescantia spathacea in DSSC Thu, 17 Dec 2015 14:24:28 +0000 The use of anthocyanin dyes extracted from epidermal leaves of Tradescantia spathacea (Trant) and petals of Ixora coccinea (IX) was evaluated in the application of dye-sensitized solar cells (DSSCs). Subsequently, cocktail anthocyanin dyes from these dyes were prepared and how they enhanced the cell’s overall performance was assessed using five different volume-to-volume ratios. Cocktail dyes absorbed a wider range of light in the visible region, thus increasing the cell efficiencies of the cocktail dyes when compared to the DSSC sensitized by individual dyes. The surface charge (zeta-potential), average size of aggregated anthocyanin molecules (zetasizer), and anthocyanin stability in different storage temperatures were analyzed and recorded. Lower size of aggregated dye molecules as revealed from the cocktail dyes ensured better adsorption onto the TiO2 film. Tradescantia/Ixora pigments mixed in 1 : 4 ratio showed the highest cell efficiency of %, under the irradiance of 100 mW cm−2, with a short-circuit current density 4.185 mA/cm2, open-circuit voltage of 0.346 V, and fill factor of 0.499. It was found that the desired storage temperature for these cocktail dyes to be stable over time was −20°C, in which the anthocyanin half-life was about approximately 1727 days. Zularif Zolkepli, Andery Lim, Piyasiri Ekanayake, and Kushan Tennakoon Copyright © 2015 Zularif Zolkepli et al. All rights reserved. Flexural Stiffness of Myosin Va Subdomains as Measured from Tethered Particle Motion Mon, 30 Nov 2015 06:58:36 +0000 Myosin Va (MyoVa) is a processive molecular motor involved in intracellular cargo transport on the actin cytoskeleton. The motor’s processivity and ability to navigate actin intersections are believed to be governed by the stiffness of various parts of the motor’s structure. Specifically, changes in calcium may regulate motor processivity by altering the motor’s lever arm stiffness and thus its interhead communication. In order to measure the flexural stiffness of MyoVa subdomains, we use tethered particle microscopy, which relates the Brownian motion of fluorescent quantum dots, which are attached to various single- and double-headed MyoVa constructs bound to actin in rigor, to the motor’s flexural stiffness. Based on these measurements, the MyoVa lever arm and coiled-coil rod domain have comparable flexural stiffness (0.034 pN/nm). Upon addition of calcium, the lever arm stiffness is reduced 40% as a result of calmodulins potentially dissociating from the lever arm. In addition, the flexural stiffness of the full-length MyoVa construct is an order of magnitude less stiff than both a single lever arm and the coiled-coil rod. This suggests that the MyoVa lever arm-rod junction provides a flexible hinge that would allow the motor to maneuver cargo through the complex intracellular actin network. Arthur J. Michalek, Guy G. Kennedy, David M. Warshaw, and M. Yusuf Ali Copyright © 2015 Arthur J. Michalek et al. All rights reserved. The Review of Nuclear Microscopy Techniques: An Approach for Nondestructive Trace Elemental Analysis and Mapping of Biological Materials Wed, 18 Nov 2015 13:39:56 +0000 The properties of many biological materials often depend on the spatial distribution and concentration of the trace elements present in a matrix. Scientists have over the years tried various techniques including classical physical and chemical analyzing techniques each with relative level of accuracy. However, with the development of spatially sensitive submicron beams, the nuclear microprobe techniques using focused proton beams for the elemental analysis of biological materials have yielded significant success. In this paper, the basic principles of the commonly used microprobe techniques of STIM, RBS, and PIXE for trace elemental analysis are discussed. The details for sample preparation, the detection, and data collection and analysis are discussed. Finally, an application of the techniques to analysis of corn roots for elemental distribution and concentration is presented. Stephen Juma Mulware Copyright © 2015 Stephen Juma Mulware. All rights reserved. On the Role of the Blood Vessel Endothelial Microvilli in the Blood Flow in Small Capillaries Wed, 28 Oct 2015 09:57:40 +0000 Endothelial microvilli that protrude into the capillary lumen, although invisible in the optical microscopy, may play an important role in the blood flow control in the capillaries. Because of the plug effects, the width of the gap between the capillary wall and the blood cell is especially critical for the blood flow dynamics in capillaries, while microvilli located on the capillary wall can easily control the velocity of the blood flow. We report that microvilli in the capillaries of different vertebrate species have similar characteristics and density, suggesting similarities between the respective regulation mechanisms. A simplified physical model of the capillary effective diameter control by the microvilli is presented. Vladimir Makarov, Lidia Zueva, Priscila Sanabria, William Dave Wessinger, Tatiana Golubeva, Igor Khmelinskii, and Mikhail Inyushin Copyright © 2015 Vladimir Makarov et al. All rights reserved. Informational Theory of Aging: The Life Extension Method Based on the Bone Marrow Transplantation Wed, 30 Sep 2015 09:05:15 +0000 The method of lifespan extension that is a practical application of the informational theory of aging is proposed. In this theory, the degradation (error accumulation) of the genetic information in cells is considered a main cause of aging. According to it, our method is based on the transplantation of genetically identical (or similar) stem cells with the lower number of genomic errors to the old recipients. For humans and large mammals, this method can be realized by cryopreservation of their own stem cells, taken in a young age, for the later autologous transplantation in old age. To test this method experimentally, we chose laboratory animals of relatively short lifespan (mouse). Because it is difficult to isolate the required amount of the stem cells (e.g., bone marrow) without significant damage for animals, we used the bone marrow transplantation from sacrificed inbred young donors. It is shown that the lifespan extension of recipients depends on level of their genetic similarity (syngeneity) with donors. We have achieved the lifespan increase of the experimental mice by 34% when the transplantation of the bone marrow with high level of genetic similarity was used. Alexey V. Karnaukhov, Elena V. Karnaukhova, Larisa A. Sergievich, Natalia A. Karnaukhova, Elena V. Bogdanenko, Irina A. Manokhina, and Valery N. Karnaukhov Copyright © 2015 Alexey V. Karnaukhov et al. 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.