Calcium Permeable AMPA Receptor-Dependent Long Lasting Plasticity of Intrinsic Excitability in Fast Spiking Interneurons of the Dentate Gyrus Decreases Inhibition in the Granule Cell Layer

The local fast-spiking interneurons (FSINs) are considered to be crucial for the generation, maintenance, and modulation of neuronal network oscillations especially in the gamma frequency band. Gamma frequency oscillations have been associated with different aspects of behavior. But the prolonged effects of gamma frequency synaptic activity on the FSINs remain elusive. Using whole cell current clamp patch recordings, we observed a sustained decrease of intrinsic excitability in the FSINs of the dentate gyrus (DG) following repetitive stimulations of the mossy fibers at 30 Hz (gamma bursts). Surprisingly, the granule cells (GCs) did not express intrinsic plastic changes upon similar synaptic excitation of their apical dendritic inputs. Interestingly, pairing the gamma bursts with membrane hyperpolarization accentuated the plasticity in FSINs following the induction protocol, while the plasticity attenuated following gamma bursts paired with membrane depolarization. Paired pulse ratio measurement of the synaptic responses did not show significant changes during the experiments. However, the induction protocols were accompanied with postsynaptic calcium rise in FSINs. Interestingly, the maximum and the minimum increase occurred during gamma bursts with membrane hyperpolarization and depolarization respectively. Including a selective blocker of calcium-permeable AMPA receptors (CP-AMPARs) in the bath; significantly attenuated the calcium rise and blocked the membrane potential dependence of the calcium rise in the FSINs, suggesting their involvement in the observed phenomenon. Chelation of intracellular calcium, blocking HCN channel conductance or blocking CP-AMPARs during the experiment forbade the long lasting expression of the plasticity. Simultaneous dual patch recordings from FSINs and synaptically connected putative GCs confirmed the decreased inhibition in the GCs accompanying the decreased intrinsic excitability in the FSINs. Experimentally constrained network simulations using NEURON predicted increased spiking in the GC owing to decreased input resistance in the FSIN. We hypothesize that the selective plasticity in the FSINs induced by local network activity may serve to increase information throughput into the downstream hippocampal subfields besides providing neuroprotection to the FSINs. (c) 2014 Wiley Periodicals, Inc.

Microstructure dependent elastic modulus variation in NiTi shape memory alloy

Modulus variation of NiTi shape memory alloy has been investigated at microstructural level through nano dynamical mechanical analysis and compared with bulk experimental measurements. The differences between the modulus values at the macro and micro level as well as within the micro level are discussed and the corresponding variations have been explained based on the crystal structure, orientation and misorientation. The experimental results confirm a higher modulus value for the martensite phase that is in agreement with the theoretical predictions. (C) 2015 Elsevier B. V. All rights reserved.

Percolation on networks with antagonistic and dependent interactions

Drawing inspiration from real world interacting systems, we study a system consisting of two networks that exhibit antagonistic and dependent interactions. By antagonistic and dependent interactions we mean that a proportion of functional nodes in a network cause failure of nodes in the other, while failure of nodes in the other results in failure of links in the first. In contrast to interdependent networks, which can exhibit first-order phase transitions, we find that the phase transitions in such networks are continuous. Our analysis shows that, compared to an isolated network, the system is more robust against random attacks. Surprisingly, we observe a region in the parameter space where the giant connected components of both networks start oscillating. Furthermore, we find that for Erdos-Renyi and scale-free networks the system oscillates only when the dependence and antagonism between the two networks are very high. We believe that this study can further our understanding of real world interacting systems.

Composition dependent non-ideality in aqueous binary mixtures as a signature of avoided spinodal decomposition

We explore the potential energy landscape of structure breaking binary mixtures (SBBM) where two constituents dislike each other, yet remain macroscopically homogeneous at intermediate to high temperatures. Interestingly, we find that the origin of strong composition dependent non-ideal behaviour lies in its phase separated inherent structure. The inherent structure (IS) of SBBM exhibits bi-continuous phase as is usually formed during spinodal decomposition. We draw analogy of this correlation between non-ideality and phase separation in IS to explain observation of non-ideality in real aqueous mixtures of small amphiphilic solutes, containing both hydrophilic and hydrophobic groups. Although we have not been able to obtain IS of these liquids, we find that even at room temperature these liquids sustain formation of fluctuating, transient bi-continuous phase, with limited lifetime (tau less than or similar to 20 ps). While in the model (A, B) binary mixture, the non-ideal composition dependence can be considered as a fluctuation from a phase separated state, a similar scenario is expected to be responsible for the unusually strong non-ideality in these aqueous binary mixtures.

Orotic acid as a useful supramolecular synthon for the fabrication of an OPV based hydrogel: stoichiometry dependent injectable behavior

A facile hydrogelation of a p-pyridylenevinylene derivative (PV) bearing oxyethylene chains in the presence of orotic acid (OA) occurs via various non-covalent interactions. Depending on the PV: OA molar ratio, the hydrogel shows vesicle to either cluster-type aggregate or fiber transformation. Visual color tuning, stimuli-responsiveness and injectable properties of the hydrogel are also observed.

Mode coupling theory analysis of electrolyte solutions: Time dependent diffusion, intermediate scattering function, and ion solvation dynamics

A self-consistent mode coupling theory (MCT) with microscopic inputs of equilibrium pair correlation functions is developed to analyze electrolyte dynamics. We apply the theory to calculate concentration dependence of (i) time dependent ion diffusion, (ii) intermediate scattering function of the constituent ions, and (iii) ion solvation dynamics in electrolyte solution. Brownian dynamics with implicit water molecules and molecular dynamics method with explicit water are used to check the theoretical predictions. The time dependence of ionic self-diffusion coefficient and the corresponding intermediate scattering function evaluated from our MCT approach show quantitative agreement with early experimental and present Brownian dynamic simulation results. With increasing concentration, the dispersion of electrolyte friction is found to occur at increasingly higher frequency, due to the faster relaxation of the ion atmosphere. The wave number dependence of intermediate scattering function, F(k, t), exhibits markedly different relaxation dynamics at different length scales. At small wave numbers, we find the emergence of a step-like relaxation, indicating the presence of both fast and slow time scales in the system. Such behavior allows an intriguing analogy with temperature dependent relaxation dynamics of supercooled liquids. We find that solvation dynamics of a tagged ion exhibits a power law decay at long times-the decay can also be fitted to a stretched exponential form. The emergence of the power law in solvation dynamics has been tested by carrying out long Brownian dynamics simulations with varying ionic concentrations. The solvation time correlation and ion-ion intermediate scattering function indeed exhibit highly interesting, non-trivial dynamical behavior at intermediate to longer times that require further experimental and theoretical studies. (c) 2015 AIP Publishing LLC.

Size Dependent Magnetic Properties of Nd0.7Ca0.3MnO3 Nanomanganite

Nanoscale materials show different properties compared to bulk materials. Due to the size dependent properties the nanoscale materials have potential applications in industry. In this paper the size dependent magnetic properties of Nd0.7Ca0.3MnO3 nanomanganite have been investigated. Nd0.7Ca0.3MnO3 nanoparticles were prepared by low temperature sol-gel method. X-ray diffraction (XRD), Transmission Electron Microscopy (TEM) and EDAX techniques were used to understand the structure, grain size and composition. Nanoparticles prepared were of the sizes 15 nm, 19 nm and 25 nm respectively. SQUID magnetometer was used to study the magnetic behavior of the nanoparticles. Field cooled (FC) and zero field cooled (ZFC) magnetization of all the nanosamples with respect to temperature was studied and compared. We have observed drastic changes in magnetic properties of 15 nm particles compared to the other nanoparticles. The `charge order peak' was seen to have disappeared in 15 nm particles while it was present in the other nanoparticles. All the nano particles exhibit superparamagnetism whose blocking temperature decreases as a function of decreasing particle size. The possible reasons for the influence of the particle size on the magnetic properties are discussed.

Observation of photobleaching and intensity dependent kinetics in Ge22As22Se56 thin films under sub-bandgap light illumination

We experimentally demonstrate photobleaching (PB) in Ge22As22Se56 thin films, when illuminated with a diode pumped solid state laser (DPSSL) of wavelength 671 nm, which is far below the optical bandgap of the sample. Interestingly, we found that PB is a slow process and occurs even at moderate pump beam intensity of 0.2 W/cm(2), however the kinetics remain rather different.

Structural basis for the catalytic mechanism of homoserine dehydrogenase

Homoserine dehydrogenase (HSD) is an oxidoreductase in the aspartic acid pathway. This enzyme coordinates a critical branch point of the metabolic pathway that leads to the synthesis of bacterial cell-wall components such as L-lysine and m-DAP in addition to other amino acids such as L-threonine, L-methionine and L-isoleucine. Here, a structural rationale for the hydride-transfer step in the reaction mechanism of HSD is reported. The structure of Staphylococcus aureus HSD was determined at different pH conditions to understand the basis for the enhanced enzymatic activity at basic pH. An analysis of the crystal structure revealed that Lys105, which is located at the interface of the catalytic and cofactor-binding sites, could mediate the hydride-transfer step of the reaction mechanism. The role of Lys105 was subsequently confirmed by mutational analysis. Put together, these studies reveal the role of conserved water molecules and a lysine residue in hydride transfer between the substrate and the cofactor.

Calcium binding properties of calcium dependent protein kinase 1 (CaCDPK1) from Cicer arietinum

Calcium plays a crucial role as a secondary messenger in all aspects of plant growth, development and survival. Calcium dependent protein kinases (CDPKs) are the major calcium decoders, which couple the changes in calcium level to an appropriate physiological response. The mechanism by which calcium regulates CDPK protein is not well understood. In this study, we investigated the interactions of Ca2+ ions with the CDPK1 isoform of Cicer arietinum (CaCDPK1) using a combination of biophysical tools. CaCDPK1 has four different EF hands as predicted by protein sequence analysis. The fluorescence emission spectrum of CaCDPK1 showed quenching with a 5 nm red shift upon addition of calcium, indicating conformational changes in the tertiary structure. The plot of changes in intensity against calcium concentrations showed a biphasic curve with binding constants of 1.29 mu M and 120 mu M indicating two kinds of binding sites. Isothermal calorimetric (ITC) titration with CaCl2 also showed a biphasic curve with two binding constants of 0.027 mu M and 1.7 mu M. Circular dichroism (CD) spectra showed two prominent peaks at 208 and 222 nm indicating that CaCDPK1 is a alpha-helical rich protein. Calcium binding further increased the alpha-helical content of CaCDPK1 from 75 to 81%. Addition of calcium to CaCDPK1 also increased fluorescence of 8-anilinonaphthalene-1-sulfonic acid (ANS) indicating exposure of hydrophobic surfaces. Thus, on the whole this study provides evidence for calcium induced conformational changes, exposure of hydrophobic surfaces and heterogeneity of EF hands in CaCDPK1. (C) 2015 Elsevier GmbH. All rights reserved.

Homology and enzymatic requirements of microhomology-dependent alternative end joining

Nonhomologous DNA end joining (NHEJ) is one of the major double-strand break (DSB) repair pathways in higher eukaryotes. Recently, it has been shown that alternative NHEJ (A-NHEJ) occurs in the absence of classical NHEJ and is implicated in chromosomal translocations leading to cancer. In the present study, we have developed a novel biochemical assay system utilizing DSBs flanked by varying lengths of microhomology to study microhomology-mediated alternative end joining (MMEJ). We show that MMEJ can operate in normal cells, when microhomology is present, irrespective of occurrence of robust classical NHEJ. Length of the microhomology determines the efficiency of MMEJ, 5 nt being obligatory. Using this biochemical approach, we show that products obtained are due to MMEJ, which is dependent on MRE11, NBS1, LIGASE III, XRCC1, FEN1 and PARP1. Thus, we define the enzymatic machinery and microhomology requirements of alternative NHEJ using a well-defined biochemical system.

DNA intercalative 4-butylaminopyrimido4',5':4,5]thieno(2,3-b)quinoline induces cell cycle arrest and apoptosis in leukemia cells

DNA intercalators are one of the interesting groups in cancer chemotherapy. The development of novel anticancer small molecule has gained remarkable interest over the last decade. In this study, we synthesized and investigated the ability of a tetracyclic-condensed quinoline compound, 4-butylaminopyrimido4',5':4,5]thieno(2,3-b)quinoline (BPTQ), to interact with double-stranded DNA and inhibit cancer cell proliferation. Circular dichroism, topological studies, molecular docking, absorbance, and fluorescence spectral titrations were employed to study the interaction of BPTQ with DNA. Cytotoxicity was studied by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assay. Further, cell cycle analysis by flow cytometry, annexin V staining, mitochondrial membrane potential assay, DNA fragmentation, and western blot analysis were used to elucidate the mechanism of action of BPTQ at the cellular level. Spectral, topological, and docking studies confirmed that BPTQ is a typical intercalator of DNA. BPTQ induces dose-dependent inhibitory effect on the proliferation of cancer cells by arresting cells at S and G2/M phase. Further, BPTQ activates the mitochondria-mediated apoptosis pathway, as explicated by a decrease in mitochondrial membrane potential, increase in the Bax:Bcl-2 ratio, and activation of caspases. These results confirmed that BPTQ is a DNA intercalative anticancer molecule, which could aid in the development of future cancer therapeutic agents.

Sensory cues employed for the acquisition of familiarity-dependent recognition of a shoal of conspecifics by climbing perch (Anabas testudineus Bloch)

In this study we showed that a freshwater fish, the climbing perch (Anabas testudineus) is incapable of using chemical communication but employs visual cues to acquire familiarity and distinguish a familiar group of conspecifics from an unfamiliar one. Moreover, the isolation of olfactory signals from visual cues did not affect the recognition and preference for a familiar shoal in this species.

A common stochastic accumulator with effector-dependent noise can explain eye-hand coordination

The computational architecture that enables the flexible coupling between otherwise independent eye and hand effector systems is not understood. By using a drift diffusion framework, in which variability of the reaction time (RT) distribution scales with mean RT, we tested the ability of a common stochastic accumulator to explain eye-hand coordination. Using a combination of behavior, computational modeling and electromyography, we show how a single stochastic accumulator to threshold, followed by noisy effector-dependent delays, explains eye-hand RT distributions and their correlation, while an alternate independent, interactive eye and hand accumulator model does not. Interestingly, the common accumulator model did not explain the RT distributions of the same subjects when they made eye and hand movements in isolation. Taken together, these data suggest that a dedicated circuit underlies coordinated eye-hand planning.

Phase space path integral approach to harmonic oscillator with a time-dependent force constant

The quantum statistical mechanical propagator for a harmonic oscillator with a time-dependent force constant, m omega(2)(t), has been investigated in the past and was found to have only a formal solution in terms of the solutions of certain ordinary differential equations. Such path integrals are frequently encountered in semiclassical path integral evaluations and having exact analytical expressions for such path integrals is of great interest. In a previous work, we had obtained the exact propagator for motion in an arbitrary time-dependent harmonic potential in the overdamped limit of friction using phase space path integrals in the context of Levy flights - a result that can be easily extended to Brownian motion. In this paper, we make a connection between the overdamped Brownian motion and the imaginary time propagator of quantum mechanics and thereby get yet another way to evaluate the latter exactly. We find that explicit analytic solution for the quantum statistical mechanical propagator can be written when the time-dependent force constant has the form omega(2)(t) = lambda(2)(t) - d lambda(t)/dt where lambda(t) is any arbitrary function of t and use it to evaluate path integrals which have not been evaluated previously. We also employ this method to arrive at a formal solution of the propagator for both Levy flights and Brownian subjected to a time-dependent harmonic potential in the underdamped limit of friction. (C) 2015 Elsevier B.V. All rights reserved.