97 research outputs found

    Estimation of greenhouse gas emissions from spontaneous combustion/fire of coal in opencast mines – Indian context

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    There are a significant number of uncontrolled coal mine fires (primarily due to spontaneous combustion of coal), which are currently burning all over the world. These spontaneous combustion sources emit greenhouse gases (GHGs). A critical review reveals that there are no standard measurement methods to estimate GHG emissions from mine fire/spontaneous combustion areas. The objective of this research paper was to estimate GHGs emissions from spontaneous combustion of coals in the Indian context. A sampling chamber (SC) method was successfully used to assess emissions at two locations of the Enna Opencast Project (OCP), Jharia Coalfield (JCF), for 3 months. The study reveals that measured cumulative average emission rate for CO2 varies from 75.02 to 286.03 gs−1m−1 and CH4 varies from 41.49 to 40.34 gs−1m−1 for low- and medium-temperature zones. The total GHG emissions predicted from this single fire affecting mines of JCF vary from 16.86 to 20.19 Mtyr−

    Malaria pigment crystals as magnetic micro-rotors: Key for high-sensitivity diagnosis

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    The need to develop new methods for the high-sensitivity diagnosis of malaria has initiated a global activity in medical and interdisciplinary sciences. Most of the diverse variety of emerging techniques are based on research-grade instruments, sophisticated reagent-based assays or rely on expertise. Here, we suggest an alternative optical methodology with an easy-to- use and cost-effective instrumentation based on unique properties of malaria pigment reported previously and determined quantitatively in the present study. Malaria pigment, also called hemozoin, is an insoluble microcrystalline form of heme. These crystallites show remarkable magnetic and optical anisotropy distinctly from any other components of blood. As a consequence, they can simultaneously act as magnetically driven micro-rotors and spinning polarizers in suspensions. These properties can gain importance not only in malaria diagnosis and therapies, where hemozoin is considered as drug target or immune modulator, but also in the magnetic manipulation of cells and tissues on the microscopic scale

    In vitro nuclear interactome of the HIV-1 Tat protein

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    <p>Abstract</p> <p>Background</p> <p>One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86–101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry.</p> <p>Results</p> <p>Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied <it>in silico </it>analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture.</p> <p>Conclusion</p> <p>We have completed the <it>in vitro </it>Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will provide a framework to further advance our understanding of the mechanisms of HIV-1 proviral gene silencing and activation.</p

    Targeting de novo purine biosynthesis for tuberculosis treatment

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    For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.Data availability: All data supporting the findings of this study are available in this published article (and its Supplementary Information). Should any raw data files be needed in another format, they are available from the corresponding authors on reasonable request. The synthesis and chemical verification of all compounds described are provided in the Supplementary Methods. Source data are provided with this paper.Code availability: No custom codes or mathematical algorithms were used in the article. Data from the dose–response curves were measured with Perkin Elmer EnVision and modelled using Genedata. Microscopy data were processed using LAS-X and FIJI software. Mass spectroscopy data were obtained using Thermo Q-Exactive and Waters TargetLynx, then further analysed using either the Skyline software (24.1.1.339) or the Agilent MassHunter software suite. The ACD/Spectrus software (2023 v1.1) and Bruker TOPSPIN programme (v4.1) were used to support medicinal chemistry efforts. Schrödinger software was used for the computational modelling (release 2024-2). Final analysis and figure preparation were performed using Microsoft Excel and GraphPad Prism 10.Extended data figures and tables are available online at: https://www.nature.com/articles/s41586-025-09177-7#Sec44 .Supplementary Information is available online at: .https://www.nature.com/articles/s41586-025-09177-7#Sec45Source data are available online at: https://www.nature.com/articles/s41586-025-09177-7#Sec46 .Tuberculosis remains the leading cause of death from an infectious disease1,2. Here we report the discovery of a first-in-class small-molecule inhibitor targeting PurF, the first enzyme in the mycobacterial de novo purine biosynthesis pathway. The lead candidate, JNJ-6640, exhibited nanomolar bactericidal activity in vitro. Comprehensive genetic and biochemical approaches confirmed that JNJ-6640 was highly selective for mycobacterial PurF. Single-cell-level microscopy demonstrated a downstream effect on DNA replication. We determined the physiologically relevant concentrations of nucleobases in human and mouse lung tissue, showing that these levels were insufficient to salvage PurF inhibition. Indeed, proof-of-concept studies using a long-acting injectable formulation demonstrated the in vivo efficacy of the compound. Finally, we show that inclusion of JNJ-6640 could have a crucial role in improving current treatment regimens for drug-resistant tuberculosis. Together, we demonstrate that JNJ-6640 is a promising chemical lead and that targeting de novo purine biosynthesis represents a novel strategy for tuberculosis drug development.N.D. acknowledges support from the Canadian Institutes of Health Research (185715) and funding from Janssen Pharmaceutica. The Vaccine and Infectious Disease Organization receives operational funding from the Government of Saskatchewan through Innovation Saskatchewan and the Ministry of Agriculture and from the Canada Foundation for Innovation through the Major Science Initiatives Fund. The work at the London School of Hygiene and Tropical Medicine was supported by funding from Janssen Pharmaceutica (to A.K. and R.J.W.). Work at the Center for Discovery and Innovation was funded by Bill and Melinda Gates Foundation grant INV-040485 (to J.P.S.). Work at Tufts University was funded by Bill and Melinda Gates Foundation grant INV-027276 (to B.B.A.). This work was funded in part by NIH R61/R33AI138280 (to A.J.C.S.). We are grateful to the Global Research Resource for Human Tuberculosis supported by NIH R24AI186591 (to A.J.C.S.) for providing human TB tissue specimens. This research was funded in part by the Wellcome Trust (Africa Health Research Institute strategic core award 227167/A/23/Z)

    Microalgae as second generation biofuel. A review

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    International audienc

    Acid mine drainage control in an opencast coal mine

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