Pyrazole-based analogs as potential antibacterial agents against methicillin-resistance staphylococcus aureus (MRSA) and its SAR elucidation

Methicillin-resistant Staphylococcus aureus (MRSA) is becoming lethal to humanity due to easy transmission and difficult-to-treat skin and flimsy diseases. The most threatening aspect is the rapid resistance development of MRSA to any approved antibiotics, including vancomycin. The development of new, efficient, and nontoxic drug candidate to fight against MRSA isolates is the need of the hour. The intriguing molecular structure and versatile bioactive pyrazole core attracting to development required novel antibiotics. This review presents the decade developments of pyrazole-containing derivatives with a broad antibacterial movement against diverged bacterial strains. In specific, we correlated the efficacy of structurally diversified pyrazole analogs against MRSA and discussed different angles of structure-activity relationship (SAR). The current survey highlights pyrazole hybrids' present scenario on MRSA studies, covering articles published from 2011 to 2020. This collective information may become an excellent platform to plan and develop new pyrazole-based small MRSA growth inhibitors with minimal side effects. (C) 2020 Elsevier Masson SAS. All rights reserved

MOSAIC: Multi-Object Segmented Arbitrary Stylization Using CLIP

Style transfer driven by text prompts paved a new path for creatively stylizing the images without collecting an actual style image. Despite having promising results, with text-driven stylization, the user has no control over the stylization. If a user wants to create an artistic image, the user requires fine control over the stylization of various entities individually in the content image, which is not addressed by the current state-of-the-art approaches. On the other hand, diffusion style transfer methods also suffer from the same issue because the regional stylization control over the stylized output is ineffective. To address this problem, We propose a new method Multi-Object Segmented Arbitrary Stylization Using CLIP (MOSAIC), that can apply styles to different objects in the image based on the context extracted from the input prompt. Text-based segmentation and stylization modules which are based on vision transformer architecture, were used to segment and stylize the objects. Our method can extend to any arbitrary objects, styles and produce high-quality images compared to the current state of art methods. To our knowledge, this is the first attempt to perform text-guided arbitrary object-wise stylization. We demonstrate the effectiveness of our approach through qualitative and quantitative analysis, showing that it can generate visually appealing stylized images with enhanced control over stylization and the ability to generalize to unseen object classes.Comment: Camera ready, New Ideas in Vision Transformers workshop, ICCV 202

Extensional collapse of the Gondwana orogen: evidence from Cambrian mafic magmatism in the Trivandrum Block, southern India

The assembly of Late Neoproterozoic–Cambrian supercontinent Gondwana involved prolonged subduction and accretion generating arc magmatic and accretionary complexes, culminating in collision and formation of high grade metamorphic orogens. Here we report evidence for mafic magmatism associated with post-collisional extension from a suite of gabbroic rocks in the Trivandrum Block of southern Indian Gondwana fragment. Our petrological and geochemical data on these gabbroic suite show that they are analogous to high Fe tholeiitic basalts with evolution of the parental melts dominantly controlled by fractional crystallization. They display enrichment of LILE and LREE and depletion of HFSE with negative anomalies at Zr–Hf and Ti corresponding to subduction zone magmatic regime. The tectonic affinity of the gabbros coupled with their geochemical features endorse a heterogeneous mantle source with collective melt contributions from sub-slab asthenospheric mantle upwelling through slab break-off and arc-related metasomatized mantle wedge, with magma emplacement in subduction to post-collisional intraplate settings. The high Nb contents and positive Nb–Ta anomalies of the rocks are attributed to inflow of asthenospheric melts containing ancient recycled subducted slab components and/or fusion of subducted slab materials owing to upwelling of hot asthenosphere. Zircon grains from the gabbros show magmatic crystallization texture with low U and Pb content. The LA-ICPMS analyses show 206Pb/238U mean ages in the range of 507–494 Ma suggesting Cambrian mafic magmatism. The post-collisional mafic magmatism identified in our study provides new insights into mantle dynamics during the waning stage of the birth of a supercontinent.Qiong-Yan Yang, Sohini Ganguly, E.Shaji, Yunpeng Dong, V. Nanda-Kuma

Discovery of unusual pulsations in the cool, evolved Am stars HD 98851 and HD 102480

The chemically peculiar (CP) stars HD 98851 and HD 102480 have been discovered to be unusual pulsators during the ``Naini Tal Cape Survey'' programme to search for pulsational variability in CP stars. Time series photometric and spectroscopic observations of these newly discovered stars are reported here. Fourier analyses of the time series photometry reveal that HD 98851 is pulsating mainly with frequencies 0.208 mHz and 0.103 mHz, and HD 102480 is pulsating with frequencies 0.107 mHz, 0.156 mHz and 0.198 mHz. The frequency identifications are all subject to 1 d$^{-1}$ cycle count ambiguities. We have matched the observed low resolution spectra of HD 98851 and HD 102480 in the range 3500-7400 \AA with theoretical synthetic spectra using Kurucz models with solar metallicity and a micro-turbulent velocity 2 km s$^{-1}$. These yield $T_{eff}=7000\pm250$ K, log $g=3.5 \pm 0.5$ for HD 98851 and $T_{eff} = 6750 \pm 250$ K, log $g = 3.0 \pm 0.5$ for HD 102480. We determined the equivalent H-line spectral class of these stars to be F1 IV and F3 III/IV, respectively. A comparison of the location of HD 98851 and HD 102480 in the HR diagram with theoretical stellar evolutionary tracks indicates that both stars are about 1-Gyr-old, 2-$M_{\odot}$ stars that lie towards the red edge of the $\delta$ Sct instability strip. We conclude that HD 98851 and HD 102480 are cool, evolved Am pulsators. The light curves of these pulsating stars have alternating high and low amplitudes, nearly harmonic (or sub-harmonic) period ratios, high pulsational overtones and Am spectral types. This is unusual for both Am and $\delta$ Sct pulsators, making these stars interesting objects.Comment: 9 pages, 6 Figures, Accepted for publication in MNRA

Anomalous anticrossing of neutral exciton states in GaAs/AlGaAs quantum dots

International audienceWe study the effects of heavy hole-light hole (HH-LH) mixing on fine-structure and polarization properties of neutral excitons ( X-0) confined in single GaAs/AlGaAs quantum dots (QDs) under the application of anisotropic biaxial stress. In the large HH-LH mixing regime, these properties are substantially different from the usually observed properties in the case of small or no mixing. By varying the applied stress, the mixing in the initially strain-free QDs changes from similar to 0 to similar to 70% and an anomalous anticrossing of the X-0 bright states is observed. The latter is attributed to stress-induced rotation of the in-plane principal axis of the QD confinement potential. We show that the analysis of free-excitonic emission of bulk GaAs surrounding the QDs not only allows estimation of the stress and mixing in the QDs, but also provides the quantum-confinement-induced HH-LH splitting of the as-grown QDs

Games of Incomplete Information and Myopic Equilibria

A new concept of an equilibrium in games is introduced that solves an open question posed by A. Neyman

Chitohexaose Activates Macrophages by Alternate Pathway through TLR4 and Blocks Endotoxemia

Sepsis is a consequence of systemic bacterial infections leading to hyper activation of immune cells by bacterial products resulting in enhanced release of mediators of inflammation. Endotoxin (LPS) is a major component of the outer membrane of Gram negative bacteria and a critical factor in pathogenesis of sepsis. Development of antagonists that inhibit the storm of inflammatory molecules by blocking Toll like receptors (TLR) has been the main stay of research efforts. We report here that a filarial glycoprotein binds to murine macrophages and human monocytes through TLR4 and activates them through alternate pathway and in the process inhibits LPS mediated classical activation which leads to inflammation associated with endotoxemia. The active component of the nematode glycoprotein mediating alternate activation of macrophages was found to be a carbohydrate residue, Chitohexaose. Murine macrophages and human monocytes up regulated Arginase-1 and released high levels of IL-10 when incubated with chitohexaose. Macrophages of C3H/HeJ mice (non-responsive to LPS) failed to get activated by chitohexaose suggesting that a functional TLR4 is critical for alternate activation of macrophages also. Chitohexaose inhibited LPS induced production of inflammatory molecules TNF-α, IL-1β and IL-6 by macropahges in vitro and in vivo in mice. Intraperitoneal injection of chitohexaose completely protected mice against endotoxemia when challenged with a lethal dose of LPS. Furthermore, Chitohexaose was found to reverse LPS induced endotoxemia in mice even 6/24/48 hrs after its onset. Monocytes of subjects with active filarial infection displayed characteristic alternate activation markers and were refractory to LPS mediated inflammatory activation suggesting an interesting possibility of subjects with filarial infections being less prone to develop of endotoxemia. These observations that innate activation of alternate pathway of macrophages by chtx through TLR4 has offered novel opportunities to cell biologists to study two mutually exclusive activation pathways of macrophages being mediated through a single receptor

Epstein-Barr Virus Nuclear Antigen 3C Facilitates G1-S Transition by Stabilizing and Enhancing the Function of Cyclin D1

EBNA3C, one of the Epstein-Barr virus (EBV)-encoded latent antigens, is essential for primary B-cell transformation. Cyclin D1, a key regulator of G1 to S phase progression, is tightly associated and aberrantly expressed in numerous human cancers. Previously, EBNA3C was shown to bind to Cyclin D1 in vitro along with Cyclin A and Cyclin E. In the present study, we provide evidence which demonstrates that EBNA3C forms a complex with Cyclin D1 in human cells. Detailed mapping experiments show that a small N-terminal region which lies between amino acids 130–160 of EBNA3C binds to two different sites of Cyclin D1- the N-terminal pRb binding domain (residues 1–50), and C-terminal domain (residues 171–240), known to regulate Cyclin D1 stability. Cyclin D1 is short-lived and ubiquitin-mediated proteasomal degradation has been targeted as a means of therapeutic intervention. Here, we show that EBNA3C stabilizes Cyclin D1 through inhibition of its poly-ubiquitination, and also increases its nuclear localization by blocking GSK3β activity. We further show that EBNA3C enhances the kinase activity of Cyclin D1/CDK6 which enables subsequent ubiquitination and degradation of pRb. EBNA3C together with Cyclin D1-CDK6 complex also efficiently nullifies the inhibitory effect of pRb on cell growth. Moreover, an sh-RNA based strategy for knock-down of both cyclin D1 and EBNA3C genes in EBV transformed lymphoblastoid cell lines (LCLs) shows a significant reduction in cell-growth. Based on these results, we propose that EBNA3C can stabilize as well as enhance the functional activity of Cyclin D1 thereby facilitating the G1-S transition in EBV transformed lymphoblastoid cell lines

Phylogenetic analysis, based on EPIYA repeats in the cagA gene of Indian Helicobacter pylori, and the implications of sequence variation in tyrosine phosphorylation motifs on determining the clinical outcome

The population of India harbors one of the world’s most highly diverse gene pools, owing to the influx of successive waves of immigrants over regular periods in time. Several phylogenetic studies involving mitochondrial DNA and Y chromosomal variation have demonstrated Europeans to have been the first settlers in India. Nevertheless, certain controversy exists, due to the support given to the thesis that colonization was by the Austro-Asiatic group, prior to the Europeans. Thus, the aim was to investigate pre-historic colonization of India by anatomically modern humans, using conserved stretches of five amino acid (EPIYA) sequences in the cagA gene of Helicobacter pylori. Simultaneously, the existence of a pathogenic relationship of tyrosine phosphorylation motifs (TPMs), in 32 H. pylori strains isolated from subjects with several forms of gastric diseases, was also explored. High resolution sequence analysis of the above described genes was performed. The nucleotide sequences obtained were translated into amino acids using MEGA (version 4.0) software for EPIYA. An MJ-Network was constructed for obtaining TPM haplotypes by using NETWORK (version 4.5) software. The findings of the study suggest that Indian H. pylori strains share a common ancestry with Europeans. No specific association of haplotypes with the outcome of disease was revealed through additional network analysis of TPMs