204 research outputs found

    Zircon U-Pb geochronology, Lu-Hf isotope systematics, and geochemistry of bimodal volcanic rocks and associated granitoids from Kotri Belt, Central India: implications for Neoarchean-Paleoproterozoic crustal growth

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    Abstract not availableC. Manikyamba, M. Santosh, B. Chandan Kumar, S. Rambabu, Li Tang, Abhishek Saha, Arubam C. Khelen, Sohini Ganguly, Th. Dhanakumar Singh D.V. Subba Ra

    First case of macrocyclic lactone-resistant Dirofilaria immitis in Europe - Cause for concern

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    Heartworm disease caused by the nematode Dirofilaria immitis is one of the most important parasitoses of dogs. The treatment of the infection is long, complicated, risky and expensive. Conversely, prevention is easy, safe, and effective and it is achieved by the administration of macrocyclic lactones (MLs). In recent years, D. immitis strains resistant to MLs have been described in Southern USA, raising concerns for possible emergence, or spreading in other areas of the world. The present study describes the first case of ML-resistant D. immitis in a dog in Europe. The dog arrived in Rome, Italy, from USA in 2023. Less than 6 months after its arrival in Italy, the dog tested positive for D. immitis circulating antigen and microfilariae, despite it having received monthly the ML milbemycin oxime (plus an isoxazoline) after arrival. The microfilariae suppression test suggested a resistant strain. Microfilariae DNA was examined by droplet digital PCR-based duplex assays targeting four marker positions at single nucleotide polymorphisms (SNP1, SNP2, SNP3, SNP7) which differentiate resistant from susceptible isolates. The genetic analysis showed that microfilariae had a ML-resistant genotype at SNP1 and SNP7 positions, compatible with a resistant strain. It is unlikely that the dog acquired the infection after its arrival in Europe, while it is biologically and epidemiologically plausible that the dog was already infected when imported from USA to Europe. The present report highlights the realistic risk of ML-resistant D. immitis strains being imported and possibly transmitted in Europe and other areas of the world. Monitoring dogs travelling from one area to another, especially if they originate from regions where ML-resistance is well-documented, is imperative. Scientists, practitioners, and pet owners should be aware of the risk and remain vigilant against ML-resistance, in order to monitor and reduce the spreading of resistant D. immitis

    Protein-small molecule interactions: Structural insights and applications in computational drug discovery

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    Deviation from normal healthy conditions, termed as disease, can often be triggered due to the malfunctioning of proteins. Modulating the functions of proteins by administering therapeutic agents (drugs) may alleviate the disease conditions. The majority of the drugs currently available in the market are small organic molecules due to their pharmacological and commercial advantages. These small molecule drugs interact with the protein targets through specific sites on the surface of the protein structure (binding sites). Thus, the structural data of protein-small molecule complexes forms a crucial starting point for most drug discovery programs. The work reported in this thesis deals with understanding various aspects of protein-small molecule interactions. The thesis begins (Chapter 1) with a general introduction on the implication of proteins structural data in drug discovery programs. Chapter 2 provides a fundamental understanding of the general trend in local quality of protein-small molecule crystal complexes deposited in the Protein Data Bank (PDB). Our results suggest ‘seeing is not always believing’ and aims to sensitize the non-crystallographer user community that high-resolution need not always guarantee confident small molecule binding poses. The study indicates 35% of the inspected ~0.28 million protein-small molecule binding site pairs available from ~66000 PDB entries, need serious attention before using those as input in any important applications. Results reported in Chapter 3 suggest that the stereochemical quality of bound small molecules generally agrees well with their crystallographic quality. The findings from this work could be the stepping-stones for developing structure determination technique-independent ligand pose validation tools. The learning from Chapter 3 is extended to Chapter 4 to investigate the stereochemical quality of the small molecules bound to protein structures determined by cryo-EM. Our data shows that the stereochemical quality of small molecules bound to high-resolution protein structures determined by cryo-EM is comparable to high-quality small molecules bound to protein crystal structures. Chapter 5 presents a computational analysis aimed at providing insights into the molecular basis of the specificity of a novel anti-tubercular compound, NU-6027 (identified in a phenotypic screening by experimental collaborators), towards two out of the eleven known Serine-Threonine Protein Kinases in Mycobacterium tuberculosis (Mtb). Chapter 6 reports the development of a freely available web server that facilitates the identification of new uses of old drugs and aid in drug repurposing. In Chapter 7, the principles of ‘neighborhood behavior’ are exploited to identify potential known drugs that could be repurposed against the main protease of SARS-CoV-2. Chapter 8 discusses a virtual screening strategy to identify potential binders of a novel Mtb target, Rv1636 (or the Universal Stress Protein). Collaborators have experimentally validated some of the compounds shortlisted from the computational studies. Chapter 9 summarizes the findings from work reported in the entire thesis and future applications. Overall, this thesis inspects protein-small molecule complexes from a local perspective, aiding the design of rigorous computational experiments that can contribute to solving global unmet medical needs. Interested readers may contact the author directly for Supplementary data at "[email protected]"DST-INSPIRE fellowshi

    Spatiotemporal evaluation of waning grassland habitats for swamp deer conservation across the human-dominated upper Gangetic Plains, India

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    Grassland habitats currently face severe anthropogenic exploitation, thereby affecting the survival of grassland-dependent biodiversity globally. The biodiversity-rich grasslands of India lack quantitative spatiotemporal information on their status. We evaluated the status of upper Gangetic Plains grasslands in 2015 and compared it with those from 1985, 1995 and 2005. On-ground mapping and visual classifications revealed a 57% decline in these grasslands between 1985 (418 km²) and 2015 (178 km²), mostly driven by habitat conversion (74% contribution by cropland). Limited radiotelemetry data from endemic swamp deer indicated a possible grassland-dominated average home range size of 1.02 km², and these patches were highly preferred (average Ivlev’s index = 0.85) over other land-use classes at both spatial and temporal scales. Camera-trapping within the core habitats suggests the critical use of these patches as fawning/breeding grounds. Habitat suitability analysis indicates only c. 17% of the area along the Ganges is suitable as swamp deer habitat. We recommend the protection of these critical grassland patches to maintain ‘dynamic corridors’, with restoration and other management approaches involving multiple stakeholders to ensure the survival of this critical ecosystem.Shrutarshi Paul, Sohini Saha, Parag Nigam, Sk Zeeshan Ali, Navendu Page, Aamer Sohel Khan, Mukesh Kumar, Bilal Habib, Dhananjai Mohan, Bivash Pandav, and Samrat Mondo

    Carrier dynamics in cspbbr3 nanocrystals in presence of electron and hole acceptors: A time resolved terahertz spectroscopy study

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    Study of lead halide perovskites is a burgeoning field of research owing to their applications in solar cells and myriads of other light harvesting and emitting devices. In this work we have employed Terahertz time domain spectroscopy (THz-TDS) and time-resolved THz spectroscopy (TRTS) to study dielectric properties and carrier dynamics occurring within \chem{CsPbBr_3} perovskite nanocrystals (NCs) in presence of electron and hole acceptor molecules. The THz-TDS spectrum of \chem{CsPbBr_3} NCs features a strong and broad band with a peak around 3.4 THz which originates from multiple IR-active optical phonon modes of the nature of Pb-Br stretching and Br-Pb-Br bending vibrations. We observed very efficient electron and/or hole transfer in presence of either an electron or a hole acceptor, or both. Also, in presence of either an electron or hole acceptor the diffusion length reduces to half (4.1 μ\mum) in comparison to parent NCs (9.2 μ\mum). In presence of both, electron and hole acceptor molecules the diffusion length reduces to 0.6 μ\mum. Considerable decrease in mobility values is also observed for the NCs in presence of electron and hole acceptor molecules. Details of the study will be discussed in the talk.Made available in DSpace on 2017-01-26T21:38:44Z (GMT). No. of bitstreams: 3 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 1860.pdf: 17780 bytes, checksum: c5083d26952cb96292689f69f359e98a (MD5) 682620.pptx: 38752525 bytes, checksum: cbfd004a3ac64f7e09458db6c4355a1c (MD5) Previous issue date: 2016-06-2

    Twin Pregnancy in a Woman with Uterus Didelphys

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    Uterus didelphys is one of the congenital uterine anomalies due to defective medial fusion of mullerian ducts. This anomaly is known to have poor reproductive outcome and women with this condition often have to be treated for infertility. Multiple gestation is rare with this condition. An 18 years old primigravida presenting with threatened abortion at eight weeks, was found to have uterus didelphys. She was managed conservatively, aborted one of the fetuses at 16weeks of gestation, and went till term to deliver a healthy baby by cesarean section

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

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    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

    Calcutta Riots of August 1946: Muslim Experiences from the Troubled Times

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    This article is reproduced here with permission from the author and may be found online at http://www.mcrg.ac.in/rw%20files/RW61_62/RW61_62.pdf.This paper revisits the Calcutta Riots of August 1946 to bring to the fore the diversity and complexity of Muslim experiences, which is often neglected in the grand narratives of communalism and communal violence. Along with examining stories of displacements, trauma, and violence, the paper investigates instances of help, protection, and kindness that showed familiar bonds of neighbourliness and remained resilient despite communal polarity. In the final section, the paper reads a few letters written by Muslim residents both to the Congress and to the Muslim League that underscore an erosion of faith in their respective political parties, especially at a time when both parties claimed to represent and protect Muslim interests in the region, albeit in their own specific ways
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