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Humans navigate diverse social relationships and concurrently interact across multiple social contexts. An individual's behavior in one context can influence behavior in other contexts. Different payoffs associated with interactions in the different domains have motivated recent studies of the evolution of cooperation through the analysis of multichannel games where each individual is simultaneously engaged in multiple repeated games. However, previous investigations have ignored the potential role of network structure in each domain and the effect of playing against distinct interacting partners in different domains. Multiplex networks provide a useful framework to represent social interactions between the same set of agents across different social contexts. We investigate the role of multiplex network structure and strategy linking in multichannel games on the spread of cooperative behavior in all layers of the multiplex. We find that multiplex structure along with strategy linking enhances the cooperation rate in all layers of the multiplex compared to a well-mixed population in Prisoners' Dilemma games, provided the network structure is identical across layers. The effectiveness of strategy linking in enhancing cooperation depends on the degree of similarity of the network structure across the layers and perception errors due to imperfect memory. Higher cooperation rates are achieved when the degree of structural overlap of the different layers is sufficiently large, and the probability of perception error is relatively low. Our work reveals how the social network structure in different layers of a multiplex can affect the spread of cooperation by limiting the ability of individuals to link strategies across different social domains. Author summary: People hold simultaneous membership in different social networks where they are engaged in interactions with neighbors, some of whom may be common across all networks while others may be unique to a specific social network. The distinct nature of interactions in different social networks can be modeled as games with distinct benefits. How does the nature of the interactions in different social networks as well as the underlying structure of each network affect cooperation levels in the population? Can linking behaviors across different social networks aid in enhancing cooperation levels across all such networks? We use the framework of repeated games on multiplex network-structured populations to address these questions. We find that linking behaviors can be favorable for increasing cooperation levels in all social networks if there is significant structural overlap between the different networks and perception errors in recalling past actions of interacting neighbors, are low. [ABSTRACT FROM AUTHOR]

Immunotherapeutic modulation of antigen‐specific T‐cell responses instead of the whole repertoire helps avoid immune‐related adverse events. We have developed an artificial antigen‐presenting system (aAPS) where multiple copies of a multimeric peptide‐MHC class I complex presenting a murine class I MHC restricted ovalbumin‐derived peptide (signal 1), along with a costimulatory ligand (signal 2) are chemically conjugated to a dextran backbone. Cognate naive CD8+ T cells, when treated with this aAPS underwent significant expansion and showed an activated phenotype. Furthermore, elevated expression of effector cytokines led to the differentiation of these cells to cytotoxic T lymphocytes which resulted in target cell lysis, indicative of the functional efficacy of the aAPS. CD8+ T cells with decreased proliferative potential due to repeated antigenic stimulation could also be re‐expanded by the developed aAPS. Thus, the developed aAPS warrants further engineering for future application as a rapidly customizable personalized immunotherapeutic agent, incorporating patient‐specific MHC‐restricted tumor antigens and different costimulatory signals to modulate both naive and antigen‐experienced but exhausted tumor‐specific T cells in cancer. [ABSTRACT FROM AUTHOR]

Genesis of chirality and its link to the origin of life continue to intrigue scientists. Chirality also plays an important role in medicine with the advent of chiral drugs and the consequent importance of asymmetric synthesis. The configuration of a chiral molecule gets inverted in its mirror image, as is manifested by (i) sign of specific rotation and (ii) normally, through the absolute configurational notation (R/S). While the first parameter is always true, the second one, that is the mirror image relationship of R and S configurations, called the reflection variance, may not always hold good. In this manuscript, we have highlighted examples of molecules with combinations of central and axial or planar chirality where the mirror image relationship between R and S configurations does not hold. This reflection invariance originates from the CIP rule of R precedes S. Similar reflection invariance can be observed in P or M forms of conformations of some particular molecules with chiral ligands. Proposal to avoid such reflection invariances, has been put forward. An ignorance about the possibility of reflection invariance in enantiomeric molecules can lead to common mistakes about stereoisomeric relationship or reactivity profile. [ABSTRACT FROM AUTHOR]

Comprehending the molecular strategies employed by Mycobacterium tuberculosis (Mtb) in FAS‐II regulation is of paramount significance for curbing tuberculosis progression. Mtb employs two sets of dehydratases, namely HadAB and HadBC (β‐hydroxyacyl acyl carrier protein dehydratase), for the regulation of the fatty acid synthase (FAS‐II) pathway. We utilized a sequence similarity network to discern the basis for the presence of two copies of the dehydratase gene in Mtb. This analysis groups HadC and HadA in different clusters, which could be attributed to the variability in their physiological role with respect to the acyl chain uptake. Our study reveals structural details pertaining to the crystal structure of the last remaining enzyme of the FAS‐II pathway. It also provides insights into the highly flexible hot‐dog helix and substrate regulatory loop. Additionally, mutational studies assisted in establishing the role of the C‐terminal end in HadC of HadBC in the regulation of acyl carrier protein from Mtb‐mediated interactions. Complemented with surface plasmon resonance and molecular dynamics simulation studies, the present study provides the first evidence of the molecular mechanisms involved in the differential binding affinity of the acyl carrier protein from Mtb towards both mtbHadAB and mtbHadBC. [ABSTRACT FROM AUTHOR]

Human RNA‐binding motif 3 protein (RBM3) is a cold‐shock protein which functions in various aspects of global protein synthesis, cell proliferation and apoptosis by interacting with the components of basal translational machinery. RBM3 plays important roles in tumour progression and cancer metastasis, and also has been shown to be involved in neuroprotection and endoplasmic reticulum stress response. Here, we have solved the solution NMR structure of the N‐terminal 84 residue RNA recognition motif (RRM) of RBM3. The remaining residues are rich in RGG and YGG motifs and are disordered. The RRM domain adopts a βαββαβ topology, which is found in many RNA‐binding proteins. NMR‐monitored titration experiments and molecular dynamic simulations show that the beta‐sheet and two loops form the RNA‐binding interface. Hydrogen bond, pi–pi and pi–cation are the key interactions between the RNA and the RRM domain. NMR, size exclusion chromatography and chemical cross‐linking experiments show that RBM3 forms oligomers in solution, which is favoured by decrease in temperature, thus, potentially linking it to its function as a cold‐shock protein. Temperature‐dependent NMR studies revealed that oligomerization of the RRM domain occurs via nonspecific interactions. Overall, this study provides the detailed structural analysis of RRM domain of RBM3, its interaction with RNA and the molecular basis of its temperature‐dependent oligomerization. [ABSTRACT FROM AUTHOR]

Post-translational modifications (PTMs) impart structural heterogeneities that can alter plasma proteins' functions in various pathophysiological processes. However, the identification and mapping of PTMs in untargeted plasma proteomics is still a challenge due to the presence of diverse components in blood. Here, we report a label-free method for identifying and mapping hydroxylated proteins using tandem mass spectrometry (MS/MS) in the human plasma sample. Our untargeted proteomics approach led us to identify 676 de novo sequenced peptides in human plasma that correspond to 201 proteins, out of which 11 plasma proteins were found to be hydroxylated. Among these hydroxylated proteins, Immunoglobulin A1 (IgA1) heavy chain was found to be modified at residue 285 (Pro285 to Hyp285), which was further validated by MS/MS study. Molecular dynamics (MD) simulation analysis demonstrated that this proline hydroxylation in IgA1 caused both local and global structural changes. Overall, this study provides a comprehensive understanding of the protein profile containing Hyp PTMs in human plasma and shows the future perspective of identifying and discriminating Hyp PTM in the normal and the diseased proteomes. [ABSTRACT FROM AUTHOR]

Luminescent phenanthrene‐naphthalene sulfone has been synthesized having phenanthrene and naphthalene as antenna center with an aim of fluorogenic in vitro detection of highly mutagenic NACs, which are hitherto less explored. The chemosensor could detect NACs selectively over NALs of which TNP detection is highly selective by a swing in fluorescence spectrum from 405 to ∼475 nm with extremely high quenching constant 1.93×105 M−1 and LOD 100 nM. Fluorometric recognition of TNP was explained through a combined complex PET‐RET‐ACQ‐CT pathway. DFT calculation has been performed to obtain the low energy configuration of the host⋅⋅⋅guest adduct. NMR titration reveals the chemical stability of the host in presence of TNP, suggests that the interaction belongs to supramolecular realm that supports the utilization of the chemosensor forin vitro detection of TNP within pollens of Tecoma Stans, Peperomia roots and Candida Albicans, indeed establishes the scaffold as a biocompatible chemosensor. [ABSTRACT FROM AUTHOR]

This study aimed to identify the intracellular binding partner of a unique class of staphylococcal secreted exotoxins called superantigen‐like proteins (SSL) from human macrophage and keratinocyte cell lysates. Here, we report that SSL1 specifically binds to human extracellular signal‐regulated kinase 2 (hERK2), an important stress‐activated kinase in mitogen‐activated protein kinase signaling pathways. Western blot and in vitro binding studies with recombinant hERK2 confirmed the binding interaction of SSL1, SSL7, and SSL10 with hERK2. Moreover, the SSLs‐hERK2 interaction was validated biochemically by ELISA. Our finding shows that SSLs play a novel role by binding with host cell MAP kinase signaling pathway protein. Understanding the SSL‐hERK2 interaction will also provide a basis for designing SSL‐based peptide inhibitors of hERK2 in cancer therapy. [ABSTRACT FROM AUTHOR]

The present investigation deals with the latex stage functionalization of carboxylated acrylonitrile butadiene rubber (XNBR) by chemically grafting cardanol onto its backbone main chain to impart multifunctional characteristics to it. The grafting of cardanol onto XNBR in the latex stage has been accomplished successfully using benzoyl peroxide (BPO) as a free radical initiator. Cardanol grafted XNBR (C-g-XNBR) exhibited an increase in molecular weight (7.5%) with an increase in PDI (polydispersity index). The optimum grafting parameters were found to be of 1 phr BPO with 15 phr cardanol at a reaction temperature of 80 °C and a reaction time of 10 h using "Taguchi methodology". The maximum percentage grafting (PG) and grafting efficiency (GE) were estimated to be 13.8 and 92.8%, respectively at the optimum combination of the reaction parameters. Differential scanning calorimetry and dynamic mechanical analysis results exhibited a decrease in Tg value for the functionalized elastomer. Thermogravimetric analysis displayed an increase in the thermal stability of C-g-XNBR. MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide] assay and hemolysis studies proved that functionalized rubber as biocompatible. Moreover, functionalized XNBR exhibited a potential bactericidal effect against Staphylococcus aureus and Escherichia coli strains. Fire and flame retardancy study revealed an increased LOI (limiting oxygen index) for C-g-XNBR. [ABSTRACT FROM AUTHOR]

In Mycobacterium tuberculosis, acyl carrier protein (AcpM)‐mediated fatty acid synthase type II is integral for the synthesis of mycolic acids. AcpM, designated as an atypical ACP, comprises of a putative 33 amino acid long C‐terminal extension which is distinctive in nature. Here, we aimed at devising an 'easy‐to‐go' method for the generation of crypto‐AcpM loaded with a solvatochromic probe 7‐Nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl, which is linked to the 4′‐phosphopantetheine (Ppant) prosthetic group of AcpM. The crypto‐AcpM, coupled with fluorescence spectroscopy and molecular dynamics simulation studies, was employed to explore the elusive dynamics of Ppant arm in AcpM. This investigation establishes the role of the flexible C‐terminal extension of AcpM in regulating the prosthetic group sequestration ability by modulating the 'Asp‐Ser‐Leu' motif. [ABSTRACT FROM AUTHOR]

The present investigation deals with the functionalization of acrylonitrile butadiene rubber (NBR) by chemically grafting phosphorylated cardanol prepolymer (PCP) onto its backbone chain. The grafting of PCP onto NBR was accomplished in the latex stage successfully using benzoyl peroxide as the free radical initiator. The functionalized NBR (PCP-g-NBR) is characterized by ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and gel permeation chromatography. PCP-g-NBR exhibited an increase in molecular weight (4.4%) with an increase in the polydispersity. The grafting parameters have been optimized using "Taguchi L9 table" and the optimum conditions were found to be "3 phr of initiator concentration, 15 phr of the PCP concentration, reaction temperature of 70°C and reaction time of 6 h." The percentage grafting and grafting efficiency were calculated to be 7.28 and 80.37%, respectively, under optimum processing conditions. The PCP-g-NBR exhibited a reduction in Wallace plasticity number as well as the Mooney viscosity and an enhanced plasticity retention index (PRI) as compared to neat NBR. The rheological measurements exhibited a higher flow behavior index for PCP-g-NBR than the NBR itself. Differential scanning calorimetry and dynamic mechanical analysis results exhibited a decrease in glass transition temperature on functionalization of NBR confirming enhanced plasticization. Thermogravimetric analysis results displayed an increase in thermal stability of the functionalized NBR than that of virgin NBR. The physico-mechanical properties of the PCP-g-NBR vulcanizates were at par with or even better than the neat NBR vulcanizates. 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay and hemolysis studies indicated NBR and PCP-g-NBR are nontoxic and biocompatible. [ABSTRACT FROM AUTHOR]

The MALDI‐based mass spectrometry, over the last three decades, has become an important analytical tool. It is a gentle ionization technique, usually applicable to detect and characterize analytes with high molecular weights like proteins and other macromolecules. The earlier difficulty of detection of analytes with low molecular weights like small organic molecules and metal ion complexes with this technique arose due to the cluster of peaks in the low molecular weight region generated from the matrix. To detect such molecules and metal ion complexes, a four‐prong strategy has been developed. These include use of alternate matrix materials, employment of new surface materials that require no matrix, use of metabolites that directly absorb the laser light, and the laser‐absorbing label‐assisted LDI‐MS (popularly known as LALDI‐MS). This review will highlight the developments with all these strategies with a special emphasis on LALDI‐MS. [ABSTRACT FROM AUTHOR]

This work describes the synthesis of azidonaphthalimide carboxylic acids which act as fluorescent templates with a built-in photoreactive group and a linker thus simplifying the design of protein labeling agents. These were separately connected to selectivity hands like a sulfonamide and ampicillin for successful labeling/detection of HCAII and PBPs, respectively. [ABSTRACT FROM AUTHOR]

A new strategy for the synthesis of 6 H-benzo[ c]chromen-6-ones through judicious use of Garratt-Braverman (GB) Cyclization and Minisci acyloxylation reactions in moderate to good yield is reported. The uniqueness of the GB reaction is exemplified in providing the required biaryl esters, which could be successfully converted into the target skeleton by means of Minisci reaction on the free carboxylates. Ethidium bromide displacement and UV-based assay on the final molecules established them as DNA intercalators with binding constants in the range of about 104. [ABSTRACT FROM AUTHOR]

A convenient synthesis of 4,5-disubstituted 2 H-thiopyran 1,1-dioxides is reported through a base induced process starting from eneyne sulfones. Except for strongly electron-withdrawing groups, the reaction tolerated a wide variety of substituents in the two aryl rings. This finding represents a major departure from the behaviour of the corresponding ethers. The reaction most probably proceeds through a 6π-electrocyclization from an in-situ-generated 1,3,5-trienyl sulfinate. [ABSTRACT FROM AUTHOR]

Financial inclusion plays a positive role in achieving inclusive growth, which itself is required for ensuring the overall sustainable growth of a country. Financial inclusion is viewed as the delivery of banking services at an affordable cost to the vast sections of disadvantaged and low-income groups. It is a fact that there are still a large number of people in rural and urban areas who are financially excluded. They have the need for availing the various types of banking services, especially the savings and money remittance services. Here comes the role of Urban Cooperative Banks (UCBs) and Non-Agricultural Cooperative Credit Societies (NACCSs). This study assesses the role of UCBs and NACCSs of Howrah district, West Bengal, with regard to financial inclusion and designing strategies for ensuring financial inclusion of the poor and disadvantaged. [ABSTRACT FROM AUTHOR]

Financial inclusion plays a positive role in achieving inclusive growth, which itself is required for ensuring the overall sustainable growth of a country. Financial inclusion is viewed as the delivery of banking services at an affordable cost to the vast sections of disadvantaged and low-income groups. It is a fact that there are still a large number of people in rural and urban areas who are financially excluded. They have the need for availing the various types of banking services, especially the savings and money remittance services. Here comes the role of Urban Cooperative Banks (UCBs) and Non-Agricultural Cooperative Credit Societies (NACCSs). This study assesses the role of UCBs and NACCSs of Howrah district, West Bengal, with regard to financial inclusion and designing strategies for ensuring financial inclusion of the poor and disadvantaged. [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI) is one of the most common infectious diseases at the community level. In order to assess the adequacy of empirical therapy, the susceptibility of antibiotics and resistance pattern of bacteria responsible for UTI inWest Bengal, India, were evaluated throughout the period of 2008-2013. The infection reports belonging to all age groups and both sexes were considered. Escherichia coli was the most abundant uropathogen with a prevalence rate of 67.1%, followed by Klebsiella spp. (22%) and Pseudomonas spp. (6%). Penicillin was least effective against UTI-causing E. coli and maximum susceptibility was recorded for the drugs belonging to fourth generation cephalosporins. Other abundant uropathogens, Klebsiella spp., were maximally resistant to broad-spectrum penicillin, followed by aminoglycosides and third generation cephalosporin.The antibiotic resistance pattern of two principal UTI pathogens, E. coli and Klebsiella spp. inWest Bengal, appears in general to be similar to that found in other parts of the Globe. Higher than 50% resistancewere observed for broad-spectrum penicillin. Fourth generation cephalosporin and macrolides seems to be the choice of drug in treating UTIs in Eastern India. Furthermore, improved maintenance of infection incident logs is needed in Eastern Indian hospitals in order to facilitate regular surveillance of the occurrence of antibiotic resistance patterns, since such levels continue to change. [ABSTRACT FROM AUTHOR]

Peptide rational design was used here to guide the creation of two novel short β-lactamase inhibitors, here named dBLIP-1 and -2, with length of five amino acid residues. Molecular modeling associated with peptide synthesis improved bactericidal efficacy in addition to amoxicillin, ampicillin and cefotaxime. Docked structures were consistent with calorimetric analyses against bacterial β-lactamases. These two compounds were further tested in mice. Whereas commercial antibiotics alone failed to cure mice infected with Staphylococcus aureus and Escherichia coli expressing β-lactamases, infection was cleared when treated with antibiotics in combination with dBLIPs, clearly suggesting that peptides were able to neutralize bacterial resistance. Moreover, immunological assays were also performed showing that dBLIPs were unable to modify mammalian immune response in both models, reducing the risks of collateral effects. In summary, the unusual peptides here described provide leads to overcome β-lactamase-based resistance, a remarkable clinical challenge. [ABSTRACT FROM AUTHOR]

Bacterial infections are raising serious concern across the globe. The effectiveness of conventional antibiotics is decreasing due to global emergence of multi-drug-resistant (MDR) bacterial pathogens. This process seems to be primarily caused by an indiscriminate and inappropriate use of antibiotics in non-infected patients and in the food industry. New classes of antibiotics with different actions against MDR pathogens need to be developed urgently. In this context, this review focuses on several ways and future directions to search for the next generation of safe and effective antibiotics compounds including antimicrobial peptides, phage therapy, phytochemicals, metalloantibiotics, lipopolysaccharide, and efflux pump inhibitors to control the infections caused by MDR pathogens. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus produces a family of exotoxins which are structural homologues of superantigens and thus are called staphylococcal superantigen-like proteins (SSLs). Amongst the 14 SSL genes, ssl1 (SAOUHSC_00383) has been cloned in the pQE30 expression vector, overexpressed in Escherichia coli M15 (pREP4) cells and the protein purified to homogeneity. The protein was crystallized using 6% Tacsimate pH 6.0, 0.1 M MES pH 6.0, 25%( w/ v) polyethylene glycol 3350, 100 m M NDSB 256 at 298 K by the sitting-drop vapour-diffusion method. The crystals belonged to space group P21, with unit-cell parameters a = 77.9, b = 70.5, c = 126.5 Å, β = 106.2°. X-ray diffraction data were collected and processed to a maximum resolution of 2.5 Å. The crystal contains six molecules in the asymmetric unit. [ABSTRACT FROM AUTHOR]

Development of new strategies for C-C bond formation remains in the forefront of organic synthesis. The base-mediated rearrangement of bis-propargyl sulfones via bis-allenes generated in situ, now known as the Garratt-Braverman cyclization (GBC), leads to the formation of two new C-C bonds. The reaction has recently drawn attention from organic chemists due to the wide scope as well as interesting mechanism. This report aims to give an account of the developments in this area with particular emphasis on synthetic applications. [ABSTRACT FROM AUTHOR]

Various indolyl carbazoles have been prepared in good yields utilizing Garratt-Braverman cyclization of bisindolyl propargyl sulfones, ethers, and amines as the key step. [ABSTRACT FROM AUTHOR]

Emulsion gels are now emerging as a new class of biomaterials for controlled-release applications. Novel food-grade emulsion gels consisting of indomethacin-loaded vegetable oil droplets dispersed within genipin-cross-linked gelatin-based hydrogels were characterized for their physical and drug-release properties. Varying the weight ratio of the aqueous and oil phases between 5:1 and 5:5 was used to modulate construct swelling and drug release. The dispersed oil droplets generally became larger, more polydispersed and aggregated with an increase in oil fraction. Cross-linking with genipin increased the puncture strength of the gels vs. their uncross-linked counterparts and was necessary to prevent breakdown. Swelling of the emulsion gels demonstrated Fickian behaviour at all gelatin: oil ratios. Indomethacin release followed Fickian diffusion at higher oil fractions only, demonstrating coupled Fickian and super-Case-II transport at lower oil ratios (5:1, 5:2 and 5:3). Overall, the introduction of a dispersed oil phase within a hydrogel was exploited for the release of hydrophobic bioactive compounds, with tailoring of composition used to significantly alter release kinetics. [ABSTRACT FROM AUTHOR]

Hydrogels are extensively studied as carrier matrices for the controlled release of bioactive molecules. The aim of this study was to design gelatin-based hydrogels crosslinked with genipin and study the impact of crosslinking temperature (5, 15 or 25°C) on gel strength, microstructure, cytocompatibility, swelling and drug release. Gels crosslinked at 25°C exhibited the highest Flory-Rehner crosslink density, lowest swelling ratio and the slowest release of indomethacin (Idn, model anti-inflammatory drug). Diffusional exponents ( n) indicated non-Fickian swelling kinetics while drug transport was anomalous. Hydrogel biocompatibility, in vitro cell viability, cell cycle experiments with AH-927 and HaCaT cell lines indicated normal cell proliferation without any effect on cell cycle. Overall, these results substantiated the use of genipin-crosslinked hydrogels as a viable carrier matrix for drug release applications. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM), a clinical manifestation characterized by chronic hyperglycaemia, is often ascribed to either a defect in insulin secretion, insulin resistance or both. Ayurveda (Indian Traditional Medicinal System) have shown promising results in the treatment of diabetes using various plants and herbs with negligible side effects and cost effective treatment. However, only a limited number of these plants have been explored and scientifically validated for their hypoglycemic effect. This review highlights some of the plants being commonly used in India for their hypoglycaemic effects. [ABSTRACT FROM AUTHOR]