<p>Shiv Nadar University is a comprehensive, multidisciplinary, research-focused, and student-centric University offering a full range of academic programs at the undergraduate, postgraduate and doctoral level. With state-of-the-art infrastructure, the University comprises of academic wings, sophisticated labs, international standard sports facilities, amphitheaters, auditorium, conference rooms and smart classrooms. The University&rsquo;s goal is to become internationally recognized for the quality of its research and creative endeavors and their applicability to improving quality of life, generating new insights and expanding the boundaries of human knowledge creativity. Committed to excellence in teaching, research and service, the University aims to serve the higher education needs of India and the world beyond.</p>

Shiv Nadar University

(SoNS) School of Natural Sciences

Change in pH plays a crucial role in the stability and function of the dengue envelope (DENV) protein during conformational transition from dimeric (pre-fusion state) to trimeric form (post-fusion state). In the present study we have performed various molecular dynamics (MD) simulations of the trimeric DENV protein at different pH and ionic concentrations. We have used total binding energy to justify the stability of the complex using the MMPBSA method. We found a remarkable increase in the stability of the complex at neutral pH (pH ∼ 7) due to the increment of sodium ions. However, at very low pH (pH ∼ 4), the total energy of the complex becomes high enough to destabilize the complex. At a specific pH, almost at a range of 6, the stability of the complex is significantly better than the stability of the trimer at neutral pH, which connotes that the trimer is most stable at this pH (pH ∼ 6). © 2012 Elsevier B.V. All rights reserved.

Chemistry

World University root node

Biochimica et Biophysica Acta - Proteins and Proteomics

Stability of trimeric DENV envelope protein at low and neutral pH: An insight from MD study

We explore the Jacobi last multiplier (JLM) as a means for deriving the Lagrangian of a fourth-order differential equation. In particular, we consider the classical Pais-Uhlenbeck problem and write down the accompanying Hamiltonian. We then compare such an expression with our alternative derivation of the Hamiltonian that makes use of the Ostrogradski's method and show how a mapping from the one to the other is achievable by variable transformations. © 2013 World Scientific Publishing Company.

Physics

Modern Physics Letters A

Comments on the structural features of the Pais-Uhlenbeck oscillator

We propose a new mechanism for generating a CP phase via a Higgs vacuum expectation value originating from geometry of an extra dimension. A twisted boundary condition is the key to produce an extra-dimension coordinate-dependent vacuum expectation value, which contains a CP phase degree of freedom and can be a new source of a CP phase in higher-dimensional gauge theories. As an illustrative example, we apply our mechanism to a five-dimensional gauge theory with point interactions and show that our mechanism can dynamically produce a nontrivial CP-violating phase with electroweak symmetry breaking, even though the five-dimensional model does not include any CP-violating phases of Yukawa couplings in the five-dimensional Lagrangian because of a single generation of five-dimensional fermions. We apply our mechanism to a model with point interactions, which has no source of CP-violating phases in the couplings of the higher-dimensional action, and show that a nontrivial CP phase dynamically appears. © 2013 American Physical Society.

Fulltext

Physical Review D - Particles, Fields, Gravitation and Cosmology

CP phase from twisted Higgs vacuum expectation value in extra dimension

We propose a new model which can simultaneously and naturally explain the origins of fermion generation, quark mass hierarchy, and the Cabibbo-Kobayashi-Maskawa matrix from the geometry of an extra dimension.We take the extra dimension to be an interval with point interactions, which are additional boundary points in the bulk space of the interval. Because of the Dirichlet boundary condition for fermions at the positions of point interactions, profiles of chiral fermion zero modes are split and localized, and then we can realize three generations from each five-dimensional Dirac fermion. Our model allows fermion flavor mixing but the form of the non-diagonal elements of fermion mass matrices is found to be severely restricted due to the geometry of the extra dimension. The Robin boundary condition for a scalar leads to an extra coordinate-dependent vacuum expectation value, which can naturally explain the fermion mass hierarchy. © The Author(s) 2013.

Progress of Theoretical and Experimental Physics

Quark mass hierarchy and mixing via geometry of extra dimension with point interactions

Inflammation and vascular injury triggered by ischemia/reperfusion (I/R) represent a leading cause of morbidity and mortality in a number of clinical settings. Wnt and its homolog partners R-spondins, in addition to regulating embryonic development have recently been demonstrated to serve as wound-healing agents in inflammation-associated conditions. Here we ask whether R-spondins could prevent inflammation-associated tissue damage in ischemic disorders and thus investigate the role of R-spondin3 (R-spo3) in a mouse model of mesenteric I/R. We demonstrate that R-spo3 ameliorates mesenteric I/R-induced local intestinal as well as remote lung damage by suppressing local and systemic cytokine response and deposition of IgM and complement in intestinal tissues. We also show that decreased inflammatory response is accompanied by tightening of endothelial cell junctions and reduction in vascular leakage. We conclude that R-spo3 stabilizes endothelial junctions and inhibits vascular leakage during I/R and thereby mitigates the inflammatory events and associated tissue damage. Our findings uniquely demonstrate a protective effect of R-spo3 in I/R-related tissue injury and suggest a mechanism by which it may have these effects.

Life Sciences

Proceedings of the National Academy of Sciences of the United States of America

R-spondin3 prevents mesenteric ischemia/reperfusioninduced tissue damage by tightening endothelium and preventing vascular leakage

Hepatitis C virus (HCV) is endemic in many countries due to its high propensity for establishing persistence. The presence of HCV-specific T cells in subjects repeatedly exposed to HCV who test negative for HCV RNA and antibodies and who do not have any history of HCV infection has been interpreted as T cell-mediated protection2-5. Here, we show in nonhuman primates that repeated exposure to human plasma with trace amounts of HCV induced HCV-specific T cells without seroconversion and systemic viremia but did not protect upon subsequent HCV challenge. Rather, HCV-specific recall and de novo T cell responses, as well as intrahepatic T cell recruitment and interferon-γ (IFN-γ) production, were suppressed upon HCV challenge, concomitant with quantitative and qualitative changes in regulatory T cells (Treg cells) that occurred after subinfectious HCV exposure and increased after HCV challenge. In vitro Treg cell depletion restored HCV-specific T cell responses. Thus, T cells primed by trace amounts of HCV do not generate effective recall responses upon subsequent HCV infection. Subinfectious HCV exposure predisposes to Treg cell expansion, which suppresses effector T cells during subsequent infection. Strategies to reverse this exposure-induced immune suppression should be examined to aid in the development of T cell-based vaccines against HCV and other endemic pathogens. © 2013 Nature America, Inc.

Nature Medicine

Subinfectious hepatitis C virus exposures suppress T cell responses against subsequent acute infection

Validation of marker-QTL association for genes grain size 3 (GS3), grain weight 2 (GW2), seed width 5 (qSW5) and a QTL qgrl7.1 for grain length was undertaken in a set of 242 diverse rice germplasm. Further, the study was extended to an F2 mapping population derived from cross of Sonasal, a short grain aromatic rice landrace with Pusa Basmati 1121, a variety with extra long slender grains. Seven gene specific markers, namely, SF28, SR17, RGS1and RGS2 based on GS3, W004 for GW2, MS40671 for qSW5 and RM505 for qgrl7.1, were used for validation. Single marker analysis revealed significant association of these markers to grain size and shape. The marker SF28 explained highest phenotypic variance (37 %) while the marker W004 explained lowest variance (2.6 %) for grain length in the germplasm set at the significance level P &lt; 0.05. Three markers namely, SF28, MS40671 and RM505 were polymorphic between the parents Sonasal and Pusa Basmati 1121. In the F2 population, the marker SF28 linked to gene GS3 explained highest phenotypic variance (32.5 %), while RM505 linked to qgrl7.1 explained 5.4 % of phenotypic variance for grain length. The marker SF28 was found to be most robust in the validation studies both in germplasm and F2 population. The validated gene specific markers can be utilised in marker assisted selection for improving grain size and shape as these traits have significant contribution towards grain quality and grain yield. This is the first study on validation of gene based markers for grain dimension traits in Indian rice germplasm. © 2012 Society for Plant Biochemistry and Biotechnology.

Journal of Plant Biochemistry and Biotechnology

Validation of gene based marker-QTL association for grain dimension traits in rice

Traumatic brain injury (TBI) causes significant mortality in most developing countries worldwide. At present, it is imperative to identify a treatment to address the devastating post-TBI consequences. Therefore, the present study has been performed to assess the specific effect of immediate exposure to normabaric hyperoxia (NBO) after fluid percussion injury (FPI) in the striatum of mice. To execute FPI, mice were anesthetised and sorted into (i) a TBI group, (ii) a sham group without injury and (iii) a TBI group treated with immediate exposure to NBO for 3 h. Afterwards, brains were harvested for morphological assessment. The results revealed no changes in morphological and neuronal damage in the sham group as compared to the TBI group. Conversely, the TBI group showed severe morphological changes as well as neuronal damage as compared to the TBI group exposed to NBO for 3 h. Interestingly, our findings also suggested that NBO treatment could diminish the neuronal damage in the striatum of mice after FPI. Neuronal damage was evaluated at different points of injury and the neighbouring areas using morphology, neuronal apoptotic cell death and pan-neuronal markers to determine the complete neuronal structure. In conclusion, immediate exposure to NBO following FPI could be a potential therapeutic approach to reduce neuronal damage in the TBI model. © 2013 Indian Academy of Sciences.

Journal of Biosciences

Effect of normabaric hyperoxia treatment on neuronal damage following fluid percussion injury in the striatum of mice: A morphological approach

Transforming growth factor β2 (TGFβ2) is a versatile cytokine with a prominent role in cell migration, invasion, cellular development, and immunomodulation. TGFβ2 promotes the malignancy of tumors by inducing epithelial-mesenchymal transition, angiogenesis, and immunosuppression. As it is well-documented that nucleic acid secondary structure can regulate gene expression, we assessed whether any secondary motif regulates its expression at the post-transcriptional level. Bioinformatics analysis predicts an existence of a 23-nucleotide putative G-quadruplex sequence (PG4) in the 5′ untranslated region (UTR) of TGFβ2 mRNA. The ability of this stretch of sequence to form a highly stable, intramolecular parallel quadruplex was demonstrated using ultraviolet and circular dichroism spectroscopy. Footprinting studies further validated its existence in the presence of a neighboring nucleotide sequence. Following structural characterization, we evaluated the biological relevance of this secondary motif using a dual luciferase assay. Although PG4 inhibits the expression of the reporter gene, its presence in the context of the entire 5′ UTR sequence interestingly enhances gene expression. Mutation or removal of the G-quadruplex sequence from the 5′ UTR of the gene diminished the level of expression of this gene at the translational level. Thus, here we highlight an activating role of the G-quadruplex in modulating gene expression of TGFβ2 at the translational level and its potential to be used as a target for the development of therapeutics against cancer. © 2013 American Chemical Society.

Biochemistry

The G-quadruplex augments translation in the 5′ untranslated region of transforming growth factor β2

The numerous functions of the important class of molecular chaperones, heat shock proteins 70 (Hsp70), rely on cycles of intricate conformational changes driven by ATP-hydrolysis and regulated by cochaperones and substrates. Here, we used Förster resonance energy transfer to study the conformational dynamics of individual molecules of Ssc1, a mitochondrial Hsp70, in real time. The intrinsic dynamics of the substrate-binding domain of Ssc1 was observed to be uncoupled from the dynamic interactions between substrate- and nucleotide-binding domains. Analysis of the fluctuations in the interdomain separation revealed frequent transitions to a nucleotide-free state. The nucleotide-exchange factor Mge1 did not induce ADP release, as expected, but rather facilitated binding of ATP. These results indicate that the conformational cycle of Ssc1 is more elaborate than previously thought and provide insight into how the Hsp70s can perform a wide variety of functions. © 2013 European Molecular Biology Organization.