Search

The behaviour of suspended particulate matter (SPM), salinity profile, dissolved nutrients, total (T.Chl- a) and size fractionated chlorophyll- a (F.Chl- a) were studied seasonally at Chilika Lagoon, east coast of India, during 2008-2009. The study showed large spatio-temporal variations among these parameters. The concentration of dissolved inorganic nitrogen and inorganic phosphate were found to be maximum during the monsoon, followed by post- and pre-monsoon, although the mean N:P ratios, which indicate the relative availability of N with respect to P, were 9.13 ± 3.09, 16.57 ± 11.53 and 5.47 ± 3.13, respectively. It was evident from the results that during pre-monsoon and postmonsoon, the lagoon exhibits nitrogen limitation. Mean T.Chl- a biomass in the lagoon showed distinct seasonality with maximum values during the pre-monsoon (23.12 ± 9.75 mg m) followed by monsoon and post-monsoon. Irrespective of seasons, maximum T.Chl- a was found in the northern part of the lagoon. SPM concentrations during the monsoon were relatively higher in the freshwater dominated zones compared to seawater dominated areas, indicating its riverine sources. The correlation between SPM and various dissolved nutrients ( p < 0.05) suggests its influence on the physico-chemical conditions at varying levels. It is summarized that seasonal variation of SPM and nutrients contributed by rivers, wind induced re-suspension events and in situ regeneration processes play a crucial role in the lagoon biogeochemical cycle. [ABSTRACT FROM AUTHOR]

Abstract: Results from a variety of complementary aerosol measurements made as part of the Indian Space Research Organization-Geosphere Biosphere Program (ISRO-GBP) road campaign experiment conducted during Feb 2004 in the central Indian region are reported. An instrumented vehicle fitted with the Micro Pulse Lidar for aerosol vertical profile measurements, nephelometer for scattering and athelometer for absorption coefficients measurements, Microtops II sun-photometer for column aerosol optical depth, Quartz Crystal Microbalance for aerosol mass concentration and Grimm spectrometer for aerosol number concentration was used in the campaign. The synergy of results from these complementary measurements is reflected in the computed aerosol radiative forcing for the region. We show that the large spatial and temporal variations found in the aerosol characteristics over the northwest Indian region are caused mainly by the naturally produced dust particles. The variation in their concentration modulates the overall atmospheric radiative forcing over this region. We also show that apart from the large north to south gradient in aerosol forcing caused due to transport of aerosols from the continent to the Indian Ocean region and reported during INDOEX, there is also a positive gradient in aerosol forcing from west to east, from the Arabian Sea to the Bay of Bengal region. A considerable portion of particles produced from the Indian main land is flushed to the Bay of Bengal region before being transported to the Indian Ocean, causing this west to east gradient. [Copyright &y& Elsevier]

Climate change and air pollution have important societal consequences, especially in emerging economies, wherein transitions from polluting technologies to cleaner alternatives coincide with high population vulnerability to environmental threats. India is home to a fifth of the world's population and a gamut of human activities, employing a far ranging spectrum of technologies and fuels, with consequent emissions. Atmospheric fine particles or aerosols in the region predominate in carbonaceous constituents and dust. Multi-institutional studies in the region have earlier focused on natural and anthropogenic climate forcing by aerosols and feedbacks on regional and global climate. Important gaps remain in understanding human activities influencing emissions, emission aerosol properties, and regional atmospheric processes, specifically those related to carbonaceous aerosol impacts on climate and air quality. With an aim to address these gaps, the COALESCE (Carbonaceous Aerosol Emissions, Source Apportionment and Climate Impacts) project was launched on 7 July 2017. The project adopts integration of scientific methods developed by both the climate and air quality research communities. New fundamental knowledge from the project and strong links to India's policy framework would enable climate and clean-air action in the region. The article describes the scientific rationale, objectives, and planned activities under COALESCE to explore engagement with the international climate and air quality research communities and to enable eventual dissemination of research findings, knowledge products, and decision-support tools. [ABSTRACT FROM AUTHOR]

Abstract: Efforts have been made to investigate the variability in the photosynthetically derived dissolved organic carbon (DOCP) and particulate organic carbon (POCP) at 11 locations during two seasons in a Asia's largest brackish water coastal ecosystem (Chilika Lagoon, India), together with the quantitative importance of DOCP as a substrate to the heterotrophic pelagic bacteria. The rates of DOCP and POCP ranged between 15.8–77.8μgCL−1 d−1 and 82.01–296.41μgCL−1 d−1 during pre-monsoon, 12.9–69.2μgCL−1 d−1 and 62.5–182.3μgCL−1 d−1 during monsoon, respectively. The mean primary production (TPP=POCP+DOCP) in the lagoon during pre-monsoon and monsoon were found to be 267.21 and 160.95μgCL−1 d−1, respectively, and their corresponding mean DOCP rates were about 19% and 23.33%, indicated that even in the semi-enclosed coastal waters the TPP was significantly underestimated, if the dissolved products of photosynthesis are not taken into account. Heterotrophic bacteria assimilated the non-humic components of the DOCP at higher rates (up to 85% of the released non-humic fraction of DOCP) than the humic components. Annually, DOCP satisfied 30% of bacterial carbon requirement for their metabolic activities in the lagoon. In spite of the relatively high percentage of extracellular release (PER) values observed during monsoon, the measured DOCP rates were much lower than the estimated bacterial carbon requirement, suggesting a weak coupling between phytoplankton exudation and bacterial metabolism. In addition to phytoplankton exudes, the heterotrophic bacteria may satisfy with other sources (autochthonous/allochthonous) of dissolved organic carbon to achieve their carbon requirement. [Copyright &y& Elsevier]

A survey along the coast of India (~1100 km stretch) between Benaulim (Goa) in the west coast and Thoothukudi (Tamil Nadu) in the east coast was conducted during summer 2014, to evaluate the mesozooplankton community structure. Zooplankton community was dominated by holoplanktonic forms representing 93.7% of the total zooplankton, while meroplanktonic forms constituted 6.3%. Zooplankton was generally dominated by copepods which contributed about 69%. In total, forty-eight species of copepods belonging to eighteen families dominated the zooplankton abundance, with a significant contribution of small-sized copepod genera, viz. Bestiolina , Parvocalanus , Acrocalanus , Corycaeus , Oncaea and Oithona. Total mesozooplankton and copepod density ranged from 80 ind. m−3 to 804 ind. m−3 and 28 ind. m−3 to 570 ind. m−3, respectively. Considerably higher abundance of cladocerans (Penilia avirostris and Evadne tergestina) with a significant contribution to zooplankton biomass (r2 = 0.984, p < 0.01) compared to copepods was recorded along the east coast. The results of RDA analysis revealed that the sea surface temperature (SST), nutrients (SiO 4 and NO 2), dissolved oxygen (DO) and total suspended matter (TSM) were significant environmental variables (p < 0.05; 999 Monte Carlo permutations) associated with the community structure during pre-monsoon period. Both copepod diversity (H ′) and dominance (λ) index were higher along the west coast, suggesting the influence of high nutrient and organic input from riverine influx coupled with complex environmental features. The inverse relationship between chlorophyll- a and copepod diversity (H′ : r = −0.488, p < 0.01) substantiated the importance of grazing pressure in these coastal waters. In contrast, a positive relationship between chlorophyll- a and copepod dominance (λ : r = 0.434, p < 0.05) indicated that copepods abstained from grazing on phytoplankton. Further characterization of this variability in community structure along the coastal waters requires long-term monitoring at a lower taxonomic level. • Mesozooplankton and hydrographic conditions assessed for long coast in a single stretch. • Small-sized copepods contribute significantly to total zooplankton abundance. • Copepod heterogeneity attributed to the riverine influx and other environmental conditions. • An abundance of cladocerans over copepods coincide with low temperature recorded. [ABSTRACT FROM AUTHOR]

• Microplastics were studied in key environmental matrices, southwest coast of India. • Fragments, primarily made of polyethylene were dominant in water and beach sediments. • Urbanization, river transport, fisheries and tourism regulate its distribution. • White coloured polyethylene fibres/lines were present in 21.4% of the 70 fishes. • Cd and Pb were the most dominant metals in polyethylene of beach sediments. Plastics in the marine environment are introduced through multiple pathways, and pose serious threats to aquatic biota. Recently microplastic pollution and its possible consequences in India have been recognized by the scientific community, however the extent of the crisis has not yet been quantified. The present study attempted to ascertain the abundance, distribution and characteristics of microplastics in coastal waters (14 locations), beach sediments (22 locations) and marine fishes (11 locations) from the state of Kerala, southwest coast of India. The results showed that the mean microplastic abundance was 1.25 ± 0.88 particles/m3 in coastal waters and 40.7 ± 33.2 particles/m2 in beach sediments with higher concentrations in the southern coast of the state. The abundance of microplastics, mostly contributed by fragments, fibre/line and foam, in both coastal waters and beach sediments, were highly influenced by river runoff and proximity to urban agglomeration. Fourier Transform Infrared Spectroscopy-Attenuated Total Reflection (FTIR-ATR) revealed that polyethylene (PE) and polypropylene (PP) were the dominant polymers in the marine environment. The digestive tracts of 15 out of 70 commercially important fishes studied, contained 22 microplastic particles. Polyethylene (PE; 38.46%) followed by cellulose (CE; 23.08%), rayon (RY; 15.38%), polyester (PL; 15.38%) and polypropylene (PP; 7.69%) were the major contributors in the fish ingested microplastic composition. A broad range of heavy metals, metalloids and other elements that are potentially indicative of hazardous chemicals were present in microplastics collected from the beaches of Kerala. These results enhance our understanding on the sources, transport pathways and the associated environmental risks of microplastics to marine ecosystems. [ABSTRACT FROM AUTHOR]

Amyloidosis is a condition marked by misfolded proteins that build up in tissues and eventually destroy organs. It has been connected to a number of fatal illnesses, including non-neuropathic and neurodegenerative conditions, which in turn have a significant influence on the worldwide health sector. The inability to identify the underlying etiology of amyloidosis has hampered efforts to find a treatment for the condition. Despite the identification of a multitude of putative pathogenic variables that may operate independently or in combination, the molecular mechanisms responsible for the development and progression of the disease remain unclear. A thorough investigation into protein aggregation and the impacts of toxic aggregated species will help to clarify the cytotoxicity of aggregation-mediated cellular apoptosis and lay the groundwork for future studies aimed at creating effective treatments and medications. This review article provides a thorough summary of the combination of various experimental and computational approaches to modulate amyloid aggregation. Further, an overview of the latest developments of novel therapeutic agents is given, along with a discussion of the possible obstacles and viewpoints on this developing field. We believe that the information provided by this review will help scientists create innovative treatment strategies that affect the way proteins aggregate.

Excited-state interactions at the interfaces of nanocrystals play a crucial role in determining photocatalytic efficiency. CsPbBr 3 nanocrystals (CPB NCs), celebrated for their exceptional photophysical properties, have been explored for organic photocatalysis. However, their intrinsic limitations, such as charge carrier recombination and stability issues, hinder their full potential. Strategies to enhance exciton dissociation, such as complexing CPB NCs with charge-shuttling molecules, have shown promise but remain underexplored for fully realizing their potential in improving the photocatalytic performance. We coupled ferrocene carboxylic acid (FcA) with CPB to extract the photogenerated holes, leveraging them to oxidize (1,2-dibromoethyl)benzene to phenacyl bromide. Optimization using pristine CPB NCs achieved a production rate of 5 μmol g cat -1 h -1 , which increased to 13.1 μmol g cat -1 h -1 upon FcA incorporation, marking a 2.5-fold enhancement. Mechanistic investigations revealed the simultaneous involvement of electrons and holes, with oxygen acting as a reactant contributing to the oxygenated product. Halide vacancies were identified as critical adsorption sites for the substrate, with post-synthetic treatments enhancing these vacancies, resulting in over a 2-fold increase in the reaction rate. This work not only establishes an effective approach for phenacyl bromide synthesis but also highlights the potential of leveraging dissociated charge carriers to enhance photocatalysis using CPB NCs.

Fragments of α-synuclein, an intrinsically disordered protein, whose misfolding and aggregation are responsible for diseases like Parkinson's disease and others, can co-exist in different polymorphs like 'rod' and 'twister'. Their apparently stable structures have different degrees of tolerance to perturbations like point mutations. The molecular basis of this is investigated using molecular dynamics-based conformational sampling. A charge-swapping mutation, E46K, known to be a reason for the early onset of Parkinson's disease, has differential impact on two polymorphs, and its molecular reason has been probed by investigating the intra-fibril interaction network that is responsible for stabilizing the aggregates. Two different quaternary level arrangement of the peptides in two polymorphs, establishing two different types of interrelations between residues of the peptide monomers, form the basis of their differential stabilities; a Deep Neural Network (DNN)-based analysis has extracted different pairs of residues and their spatial proximities as features to distinguish the states of two polymorphs. It has revealed that difference in these molecular arrangements intrinsically assigns key roles to different sets of residues in two different forms, like a feedback loop from quaternary structure to sequence level; an important insight into the sequence-structure relationship in general. Such atomic level insights were substantiated with the proof of differences in the dynamic correlation between residue pairs, altered mobilities of the sidechains that affects packing and redistribution of the weightage of different principal modes of internal motions in different systems. The identification of key residues with altered significance in different polymorphs is likely to benefit the planned design of fibril breaking molecules.

Background: Little scientific evidence exists on maternal and fetal outcomes in aplastic anemia (AA) during pregnancy., Aim: The review was conducted to assess the maternal and fetal outcomes due to AA during pregnancy., Data Sources: Web of Science, EMBASE, PubMed, Scopus, Cochrane CENTRAL, and registries until May 5, 2024., Study Eligibility Criteria: Studies (prospective, retrospective cohort, cross-sectional, one arm, survey, follow-up studies) evaluating AA during pregnancy were searched as per PROSPERO registered protocol (CRD42024506668). Case reports, case series, expert opinion letters, and studies assessing less than or equal to 10 pregnant women were not considered. The primary outcome was the prevalence of preeclampsia in AA pregnancies. The secondary outcomes included spontaneous abortion, preterm premature rupture of membranes, premature rupture of membranes, fetal growth restriction, type of delivery, intrauterine fetal death, maternal and neonatal mortality, and pre and post-pregnancy remission status comparison., Methods: The quality of research was checked using the New Castle-Ottawa risk-of-bias tool. A meta-analysis model with a random effect distribution, coupled with meta-regression, sensitivity analysis, and publication bias assessment, was used in the statistical software R. Standard Equator network study reporting guidelines were followed., Results: Seven (one prospective and six retrospective cohort) studies included patients with confirmed AA diagnosis in 248 pregnancies. The pooled prevalence of preeclampsia was 13% (95% CI, 8%-20%). Heterogeneity was low in the present meta-analysis (I 2  = 26%). The secondary outcome evaluation showed a pooled prevalence of 5% (95% CI, 3%-11%) for spontaneous abortion, 4% (95% CI, 1%-11%) for preterm premature rupture of membranes, 10% (95% CI, 3%-28%) for premature rupture of membranes, 6% (95% CI, 3%-11%) for fetal growth restriction, 5% (95% CI, 2%-13%) for intrauterine fetal death, 12% (95% CI, 5%-26%) for post-partum hemorrhage, 74% (95% CI, 45%-91%) for intrapartum transfusion requirement, and 55% (95% CI, 27%-80%) for the cesarean delivery opting. The maternal mortality in pregnancies with AA was 4% (95% CI, 0.01-0.14), whereas neonatal mortality was 7% (95% CI, 0.03-0.18). The odds of AA complete remission were better in pre-pregnancy than post-pregnancy (OR = 0.36; 95% CI = 0.08-1.66), although the results remain insignificant. The leave-one-out sensitivity analysis did not change the pooled estimates for the primary outcome., Conclusion: A risk of developing preeclampsia was observed in every eighth pregnant woman with an AA diagnosis. AA remission status might worsen after undergoing pregnancy, considering the significant obstetric morbidity and mortality burden., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The process of T-lymphocyte migration involves a complex interplay of chemical and mechanical signals. Mechanotransduction mechanisms in T lymphocytes enable them to efficiently navigate through diverse architectural and topographical features of the dynamic tissue macro- and micro-niches encountered during immune responses. Piezo1 mechanosensors are crucial for driving optimal T-cell migration by driving actin-cytoskeletal remodeling. Chemokine-stimulated T lymphocytes demonstrate significant asymmetry or polarity of Piezo1 and actin along the cell axis. The establishment and maintenance of polarity in migrating cells are paramount for facilitating coordinated and directional movements along gradients of chemokine signals. Live-cell imaging techniques are widely employed to study the trajectories of migrating cells. Our approach expands upon current methodologies by not only tracking migrating cells but also imaging fluorescently labeled cellular components. Specifically, our method enables measurement of protein enrichment in the front and rear halves of the moving cell by analyzing the temporal direction of cell trajectories, subsequently bisecting the cell into front-back halves, and measuring the intensities of the fluorescent signals in each cell half at each time frame. Our protocol also facilitates the quantification of the angular distribution of fluorescent signals, enabling visualization of the spatial distribution of signals relative to the direction of cell migration. The protocol describes the examination of polarity in chemokine-treated Jurkat cells transfected with Piezo1-mCherry and actin-GFP constructs. This approach can be extended to live-cell imaging and polarity assessment of other fluorescently labeled proteins. Key features • This experimental protocol allows real-time imaging of Jurkat cells expressing two fluorescent proteins (Piezo1 mCherry and actin-GFP). • Measures cell polarity by examining spatial enrichment of Piezo1 and actin proteins within the front and rear halves of a moving Jurkat cell. • The protocol enables analysis of cell polarity in 2D tracks of moving cells. • Polarity analysis includes measuring fluorescent signal intensities in front-rear halves of a moving cell and calculation of signal polarization angles relative to the cell trajectory., Competing Interests: Competing interestsThe authors declare no competing financial interests., (©Copyright : © 2024 The Authors; This is an open access article under the CC BY-NC license.)

Three-dimensional (3D) printing of hydrogel structures using jammed microgel inks offer distinct advantages of improved printing functionalities, as these inks are strain-yielding and self-recovering types. However, interparticle binding in granular hydrogel inks is a challenge to overcome the limited integrity and reduced macroscale modulus prevalent in the 3D printed microgel scaffolds. In this study, we prepared chemically annealable agarose microgels through a process of xerogel rehydration, applying a low-cost and high throughput method of spray drying. The crosslinked jammed microgel matrix is found to have superior mechanical properties with a Young's modulus of 2.23 MPa and extensibility up to 7.2%, surpassing those of traditional biopolymer-based and microgel-based inks. Furthermore, this study addresses the complexities encountered in the existing system of printing thermoresponsive agarose bioink using this jammed microgel printing approach. The jammed agarose microgel ink exhibited to be self-recovering, yield stress fluid and validated the temperature-independent printing. Furthermore, the 3D printed jammed microgel scaffold demonstrated good cell responsiveness as evaluated through the viability and morphological study in-vitro with mesenchymal stem cells cultured in it. This unique fabrication approach offers exciting possibilities to expand on microgel printing for varied requirements in tissue engineering., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

ATPase cation transporting 13A2 (ATP13A2) is an endolysosomal P-type ATPase known to be a polyamine transporter, explored mostly in neurons. As endolysosomal functions are also crucial in innate immune cells, we aimed to explore the potential role of ATP13A2 in the human immunocellular compartment. We found that human plasmacytoid dendritic cells (pDCs), the professional type I IFN-producing immune cells, especially have a prominent enrichment of ATP13A2 expression in endolysosomal compartments. ATP13A2 knockdown in human pDCs interferes with cytokine induction in response to TLR9/7 activation in response to bona fide ligands. ATP13A2 plays this crucial role in TLR9/7 activation in human pDCs by regulating endolysosomal pH and mitochondrial reactive oxygen generation. This (to our knowledge) hitherto unknown regulatory mechanism in pDCs involving ATP13A2 opens up a new avenue of research, given the crucial role of pDC-derived type I IFNs in protective immunity against infections as well as in the immunopathogenesis of myriad contexts of autoreactive inflammation., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Scrub typhus, a prevalent tropical infection, may sometimes manifest with unusual complications. Here, we present the case of a young man who was admitted to our facility with a fever for the past 3 days and passage of dark-coloured urine since that morning. On investigation, we identified intravascular haemolytic anaemia. Through meticulous examination, a black necrotic lesion (eschar) was discovered on his right buttock, a pathognomonic sign of scrub typhus infection. Treatment was initiated with oral doxycycline 100 mg two times a day. Subsequently, diagnosis of scrub typhus was confirmed through positive results from scrub typhus IgM via ELISA and PCR analysis from the eschar tissue. The patient responded well to oral doxycycline and his symptoms resolved within the next few days. This case highlights severe intravascular haemolysis associated with scrub typhus infection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

In recent years, there has been a surge in the publication of clinical trial reports, making it challenging to conduct systematic reviews. Automatically extracting Population, Intervention, Comparator, and Outcome (PICO) from clinical trial studies can alleviate the traditionally time-consuming process of manually scrutinizing systematic reviews. Existing approaches of PICO frame extraction involves supervised approach that relies on the existence of manually annotated data points in the form of BIO label tagging. Recent approaches, such as In-Context Learning (ICL), which has been shown to be effective for a number of downstream NLP tasks, require the use of labeled examples. In this work, we adopt ICL strategy by employing the pretrained knowledge of Large Language Models (LLMs), gathered during the pretraining phase of an LLM, to automatically extract the PICO-related terminologies from clinical trial documents in unsupervised set up to bypass the availability of large number of annotated data instances. Additionally, to showcase the highest effectiveness of LLM in oracle scenario where large number of annotated samples are available, we adopt the instruction tuning strategy by employing Low Rank Adaptation (LORA) to conduct the training of gigantic model in low resource environment for the PICO frame extraction task. More specifically, both of the proposed frameworks utilize AlpaCare as base LLM which employs both few-shot in-context learning and instruction tuning techniques to extract PICO-related terms from the clinical trial reports. We applied these approaches to the widely used coarse-grained datasets such as EBM-NLP, EBM-COMET and fine-grained datasets such as EBM-NLP rev and EBM-NLP h . Our empirical results show that our proposed ICL-based framework produces comparable results on all the version of EBM-NLP datasets and the proposed instruction tuned version of our framework produces state-of-the-art results on all the different EBM-NLP datasets. Our project is available at https://github.com/shrimonmuke0202/AlpaPICO.git., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that they don't have any financial interests/personal relationships that may be considered as potential competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Piezo1, a mechano-activated ion channel, has wide-ranging physiological and therapeutic implications, with the ongoing development of specific agonists unveiling cellular responses to mechanical stimuli. In our study, we systematically analyzed the chemical subunits in Piezo1 protein agonist Yoda1 to comprehend the structure-activity relationship and push forward next-generation agonist development. Preliminary screening assays for Piezo1 agonism were performed using the Piezo1-mCherry-transfected HEK293A cell line, keeping Yoda1 as a positive control. We introduce a novel Piezo1 agonist Yaddle1 ( 34 , 0.40 μM), featuring a trifluoromethyl group, with further exploration through in vitro studies and density functional theory calculations, emphasizing its tetrel interactions, to act as an ambidextrous wedge between the domains of Piezo1. In contrast to the poor solubility of the established agonist Yoda1, our results showed that the kinetic solubility of Yaddle1 (26.72 ± 1.8 μM at pH 7.4) is 10-fold better than that of Yoda1 (1.22 ± 0.11 μM at pH 7.4). Yaddle1 ( 34 ) induces Ca 2+ influx in human CD4 + T cell, suggesting its potential as a vaccine adjuvant for enhanced T cell activation.

The oxidative potential (OP) of particulate matter (PM) is a major driver of PM-associated health effects. In India, the emission sources defining PM-OP, and their local/regional nature, are yet to be established. Here, to address this gap we determine the geographical origin, sources of PM, and its OP at five Indo-Gangetic Plain sites inside and outside Delhi. Our findings reveal that although uniformly high PM concentrations are recorded across the entire region, local emission sources and formation processes dominate PM pollution. Specifically, ammonium chloride, and organic aerosols (OA) from traffic exhaust, residential heating, and oxidation of unsaturated vapors from fossil fuels are the dominant PM sources inside Delhi. Ammonium sulfate and nitrate, and secondary OA from biomass burning vapors, are produced outside Delhi. Nevertheless, PM-OP is overwhelmingly driven by OA from incomplete combustion of biomass and fossil fuels, including traffic. These findings suggest that addressing local inefficient combustion processes can effectively mitigate PM health exposure in northern India., (© 2024. The Author(s).)

Visceral leishmaniasis is a potentially fatal disease caused by infection by the intracellular protist pathogens Leishmania donovani or Leishmania infantum. Present therapies are ineffective because of high costs, variable efficacy against different species, the requirement for hospitalization, toxicity and drug resistance. Detailed analysis of previously published hit molecules suggested a crucial role of 'guanidine' linkage for their efficacy against L. donovani. Here we report the design of 2-aminoquinazoline heterocycle as a basic pharmacophore-bearing guanidine linkage. The introduction of various groups and functionality at different positions of the quinazoline scaffold results in enhanced antiparasitic potency with modest host cell cytotoxicity using a physiologically relevant THP-1 transformed macrophage infection model. In terms of the ADME profile, the C7 position of quinazoline was identified as a guiding tool for designing better molecules. The good ADME profile of the compounds suggests that they merit further consideration as lead compounds for treating visceral leishmaniasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Polymers with furan functionality have been the subject of extensive research on developing sustainable materials applying a limited number of dynamic covalent approaches. Herein, we introduce a facile, dynamic non-covalent approach to make a furan polymer readily accessible for self-healing applications based on its electrophilic substitution (ES) with a commercially available 1,2,4-triazoline-3,5-dione (TAD) derivative, 4-phenyl-TAD (PTAD). A tailor-made furan polymer, poly(furfuryl methacrylate) (PFMA), considering it an initial illustrative example, was rapidly ES modified with PTAD to produce furfuryl-tagged triazolidine that subsequently associated via inter-molecular hydrogen (H-) bonding to produce a thermally reversible supramolecular polymer network under ambient conditions. The H-bonded network was experimentally quantified via ATR-IR analysis and theoretically rationalized via the density functional theory (DFT) study using smaller organic model compounds analogous to the macromolecular system. Thermoreversible feature of the H-bonded triazolidine-derived supramolecular polymer network enabled the solution reprocessing and self-healing of the polymer material., (© 2023 Wiley‐VCH GmbH.)

T cells are crucial for efficient antigen-specific immune responses and thus their migration within the body, to inflamed tissues from circulating blood or to secondary lymphoid organs, plays a very critical role. T cell extravasation in inflamed tissues depends on chemotactic cues and interaction between endothelial adhesion molecules and cellular integrins. A migrating T cell is expected to sense diverse external and membrane-intrinsic mechano-physical cues, but molecular mechanisms of such mechanosensing in cell migration are not established. We explored if the professional mechanosensor Piezo1 plays any role during integrin-dependent chemotaxis of human T cells. We found that deficiency of Piezo1 in human T cells interfered with integrin-dependent cellular motility on ICAM-1-coated surface. Piezo1 recruitment at the leading edge of moving T cells is dependent on and follows focal adhesion formation at the leading edge and local increase in membrane tension upon chemokine receptor activation. Piezo1 recruitment and activation, followed by calcium influx and calpain activation, in turn, are crucial for the integrin LFA1 (CD11a/CD18) recruitment at the leading edge of the chemotactic human T cells. Thus, we find that Piezo1 activation in response to local mechanical cues constitutes a membrane-intrinsic component of the 'outside-in' signaling in human T cells, migrating in response to chemokines, that mediates integrin recruitment to the leading edge., Competing Interests: CL, TM, PB, MH, PB, BS, JS, RD, DS, BS, DG No competing interests declared, (© 2023, Liu et al.)

We investigate gender differences in time-use patterns in 1891 children and assess how time is reallocated in response to challenges faced by households in India. We use adaptations made within a household during adversities to understand how gender inequality in time use is produced and reinforced. Using three waves of the Young Lives Panel Survey (2009, 2013, and 2016), we find that boys spend significantly more time on school and leisure than girls. Girls spend more time on household chores, care work, and studying at home than boys while spending fewer hours on school and leisure. Girls perform paid work during household adversities besides carrying out additional care work and household chores. Boys are more likely to engage in unpaid work than girls but are similarly affected in other domains. However, their time for education and leisure is often protected. Thus, girls labor more than boys daily and respond in equal measure during adversities, demonstrating that gender inequality in time use emerges at an early age., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A standard model that is able to generalize data on myriad involvement of the immune system in organismal physio-pathology and to provide a unified evolutionary teleology for immune functions in multicellular organisms remains elusive. A number of such 'general theories of immunity' have been proposed based on contemporaneously available data, starting with the usual description of self-nonself discrimination, followed by the 'danger model' and the more recent 'discontinuity theory.' More recent data deluge on involvement of immune mechanisms in a wide variety of clinical contexts, a number of which fail to get readily accommodated into the available teleologic standard models, makes deriving a standard model of immunity more challenging. But technological advances enabling multi-omics investigations into an ongoing immune response, covering genome, epigenome, coding and regulatory transcriptome, proteome, metabolome and tissue-resident microbiome, bring newer opportunities for developing a more integrative insight into immunocellular mechanisms within different clinical contexts. The new ability to map the heterogeneity of composition, trajectory and endpoints of immune responses, in both health and disease, also necessitates incorporation into the potential standard model of immune functions, which again can only be achieved through multi-omics probing of immune responses and integrated analyses of the multi-dimensional data., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

India is at a high risk of heat stress-induced health impacts and economic losses owing to its tropical climate, high population density, and inadequate adaptive planning. The health impacts of heat stress across climate zones in India have not been adequately explored. Here, we examine and report the vulnerability to heat stress in India using 42 years (1979-2020) of meteorological data from ERA-5 and developed climate-zone-specific percentile-based human comfort class thresholds. We found that the heat stress is usually 1-4 °C higher on heatwave (HW) days than on nonheatwave (NHW) days. However, the stress on NHW days remains considerable and cannot be neglected. We then showed the association of a newly formulated India heat index (IHI) with daily all-cause mortality in three cities - Delhi (semiarid), Varanasi (humid subtropical), and Chennai (tropical wet and dry), using a semiparametric quasi-Poisson regression model, adjusted for nonlinear confounding effects of time and PM 2.5 . The all-cause mortality risk was enhanced by 8.1% (95% confidence interval, CI: 6.0-10.3), 5.9% (4.6-7.2), and 8.0% (1.7-14.2) during "sweltering" days in Varanasi, Delhi, and Chennai, respectively, relative to "comfortable" days. Across four age groups, the impact was more severe in Varanasi (ranging from a 3.2 to 7.5% increase in mortality risk for a unit rise in IHI) than in Delhi (2.6-4.2% higher risk) and Chennai (0.9-5.7% higher risk). We observed a 3-6 days lag effect of heat stress on mortality in these cities. Our results reveal heterogeneity in heat stress impact across diverse climate zones in India and call for developing an early warning system keeping in mind these regional variations.

The C-terminal of tumor suppressor protein p53 is intrinsically disordered while unbound. This particular segment often shows structural plasticity when bound to other binding partners. The disordered component undergoes a disordered to ordered transition upon recognition. Post-translational modifications (PTMs), namely phosphorylation and acetylation, significantly alter the structural motifs of the segment. Among the various types of PTMs, phosphorylation, and acetylation of p53 at both N- and C- terminals lead to stabilization and activation. It has been noted experimentally that phosphorylation often regulates (enhances or reduces) the acetylation at specific sites. The phosphorylation of Thr377 and Ser378 reduces the acetylation of Lys373 and Lys382. Mutations of Thr377 and Ser378 to neutral Ala enhance and phospho mimic Asp reduce the acetylation of Lys373 and Lys382. Simulations of several single-point and pair-wise mutated systems have been generated to compare how the presence or absence of phosphorylation favors or disfavors the acetylation by thermodynamic and conformational analysis. We are using implicit solvent replica exchange molecular dynamics simulations to get 200 ns well-converged conformational ensembles of each system. Different sets of systems having both single and double PTMs are simulated. The results admit the appreciable change in the secondary structural level upon specific PTM. Also, the residual structure of the unbound p53 with single-point PTM varies significantly with pair-wise modifications. These observations further shed light on the relationship between the interdependencies of the specific PTM sites and the secondary structural levels.Communicated by Ramaswamy H. Sarma.

Ambient PM 2.5 exposure statistics in countries with limited ground monitors are derived from satellite aerosol optical depth (AOD) products that have spatial gaps. Here, we quantified the biases in PM 2.5 exposure and associated health burden in India due to the sampling gaps in AOD retrieved by a Moderate Resolution Imaging Spectroradiometer. We filled the sampling gaps and derived PM 2.5 in recent years (2017-2022) over India, which showed fivefold cross-validation R 2 of 0.92 and root mean square error (RMSE) of 11.8 μg m -3 on an annual scale against ground-based measurements. If the missing AOD values are not accounted for, the exposure would be overestimated by 19.1%, translating to an overestimation in the mortality burden by 93,986 (95% confidence interval: 78,638-110,597) during these years. With the gap-filled data, we found that the rising ambient PM 2.5 trend in India has started showing a sign of stabilization in recent years. However, a reduction in population-weighted exposure balanced out the effect of the increasing population and maintained the mortality burden attributable to ambient PM 2.5 for 2022 (991,058:798,220-1,183,896) comparable to the 2017 level (1,014,766:812,186-1,217,346). Therefore, a decline in exposure alone is not sufficient to significantly reduce the health burden attributable to ambient PM 2.5 in India.

Intraguild interactions among carnivores have long held the fascination of ecologists. Ranging from competition to facilitation and coexistence, these interactions and their complex interplay influence everything from species persistence to ecosystem functioning. Yet, the patterns and pathways of such interactions are far from understood in tropical forest systems, particularly across countries in the Global South. Here, we examined the determinants and consequences of competitive interactions between dholes Cuon alpinus and the two large felids (leopards Panthera pardus and tigers Panthera tigris) with which they most commonly co-occur across Asia. Using a combination of traditional and novel data sources (N = 118), we integrate information from spatial, temporal, and dietary niche dimensions. These three species have faced catastrophic declines in their extent of co-occurrence over the past century; most of their source populations are now confined to Protected Areas. Analysis of dyadic interactions between species pairs showed a clear social hierarchy. Tigers were dominant over dholes, although pack strength in dholes helped ameliorate some of these effects; leopards were subordinate to dholes. Population-level spatio-temporal interactions assessed at 25 locations across Asia did not show a clear pattern of overlap or avoidance between species pairs. Diet-profile assessments indicated that wild ungulate biomass consumption by tigers was highest, while leopards consumed more primate and livestock prey as compared to their co-predators. In terms of prey offtake (ratio of wild prey biomass consumed to biomass available), the three species together harvested 0.4-30.2% of available prey, with the highest offtake recorded from the location where the carnivores reach very high densities. When re-examined in the context of prey availability and offtake, locations with low wild prey availability showed spatial avoidance and temporal overlap among the carnivore pairs, and locations with high wild prey availability showed spatial overlap and temporal segregation. Based on these observations, we make predictions for 40 Protected Areas in India where temporally synchronous estimates of predator and prey densities are available. We expect that low prey availability will lead to higher competition, and in extreme cases, to the complete exclusion of one or more species. In Protected Areas with high prey availability, we expect intraguild coexistence and conspecific competition among carnivores, with spill-over to forest-edge habitats and subsequent prey-switching to livestock. We stress that dhole-leopard-tiger co-occurrence across their range is facilitated through an intricate yet fragile balance between prey availability, and intraguild and conspecific competition. Data gaps and limitations notwithstanding, our study shows how insights from fundamental ecology can be of immense utility for applied aspects like large predator conservation and management of human-carnivore interactions. Our findings also highlight potential avenues for future research on tropical carnivores that can broaden current understanding of intraguild competition in forest systems of Asia and beyond., (© 2023 Cambridge Philosophical Society.)

An electrochemical method was developed to accomplish the reagentless synthesis of 4,5-disubstituted triazole derivatives employing secondary propargyl alcohol as C-3 synthon and sodium azide as cycloaddition counterpart. The reaction was conducted at room temperature in an undivided cell with a constant current using a pencil graphite (C) anode and stainless-steel cathode in a MeCN solvent system. The proposed reaction mechanism was convincingly established by carrying out a series of control experiments and further supported by electrochemical and density functional theory (DFT) studies.

Understanding the dynamic changes in gene expression during Acute Respiratory Distress Syndrome (ARDS) progression in post-acute infection patients is crucial for unraveling the underlying mechanisms. Study investigates the longitudinal changes in gene/transcript expression patterns in hospital-admitted severe COVID-19 patients with ARDS post-acute SARS-CoV-2 infection. Blood samples were collected at three time points and patients were stratified into severe and mild ARDS, based on their oxygenation saturation (SpO 2 /FiO 2 ) kinetics over 7 d. Decline in transcript diversity was observed over time, particularly in patients with higher severity, indicating dysregulated transcriptional landscape. Comparing gene/transcript-level analyses highlighted a rather limited overlap. With disease progression, a transition towards an inflammatory state was evident. Strong association was found between antibody response and disease severity, characterized by decreased antibody response and activated B cell population in severe cases. Bayesian network analysis identified various factors associated with disease progression and severity, viz. humoral response, TLR signaling, inflammatory response, interferon response, and effector T cell abundance. The findings highlight dynamic gene/transcript expression changes during ARDS progression, impact on tissue oxygenation and elucidate disease pathogenesis., (© 2023 Mehta et al.)

Background: Child marriage, defined as marriage under the age of 18 years, remains pervasive in India. Global evidence documents a negative association between child marriage and women's reproductive and sexual health outcomes; however, its relationship with non-communicable diseases (NCDs) remains underexplored., Methods: We utilize biomarkers and self-reported data from the nationally representative National Family and Health Survey 4 (2015-2016) to examine the associations between child marriage and hypertension, diabetes, heart disease, asthma and thyroid disorder among currently married women (N = 421 107). We use regression models adjusted for a range of demographic and socio-economic controls to assess the association between child marriage and NCDs among women in India. We further assess whether and to what extent these relationships are mediated by early motherhood using the Karlson, Holm and Breen method of decomposition., Results: Child marriage was associated with hypertension [adjusted odds ratio 1.20 (95% CI: 1.17-1.24)], diabetes [1.29 (1.22-1.37)], heart disease [1.27 (1.18-1.36)], asthma [1.19 (1.11-1.28)] and thyroid disorder [1.10 (1.02-1.18)]. Early motherhood also increased the risk of NCDs among women. Furthermore, it emerged as a pathway linking child marriage with hypertension, diabetes and heart disease; however, it provided a partial explanation for the disadvantage associated with child marriages., Conclusions: Child marriage emerges as a risk factor for NCDs among women in India. Health systems need to recognize the enduring influence of child marriages on women's health and ensure early detection and effective treatment of NCDs for this vulnerable group., (© The Author(s) 2023; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

India aims for ambitious solar energy goal to fulfill its climate commitment but there are limited studies on solar resource assessment considering both environmental and land availability constraints. The present work attempts to address this issue using satellite-derived air pollution, radiation, and land use data over the Indian region. Surface insolation over India has been decreasing at a rate of -0.29 ± 0.19 Wm -2 y -1 between 2001 and 2018. Solar resources over nearly 98%, 40%, and 39% of the Indian landmass are significantly impacted by aerosols, clouds, and both aerosols and clouds respectively. Only 29.3% of the Indian landmass is presently suitable for effective solar photovoltaic harnessing, but this is further declining by -0.21% annually, causing a presumptive loss of 50 GW solar potential, translating 75 TWh power generation. Lowering two decades of aerosol burden can make 8% additional landmass apt for photovoltaic use. Alleviating aerosol-induced dimming can fast-track India's solar energy expansion., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Objective: Visceral adipose tissue (VAT) inflammation contributes to metabolic dysregulation in obesity. VAT recruitment and activation of plasmacytoid dendritic cells (pDCs) through toll-like receptor 9 (TLR9) recognition of self-DNA, leading to induction of type I interferons, are crucial innate triggers for this VAT inflammation. It was hypothesized that mitochondrial DNA (mtDNA) can contribute to TLR9 activation in VAT-recruited pDCs in obesity, and this study aimed to identify the carrier protein for ligand access to TLR9 and to explore whether this also provides for a source of autoantigens in this context., Methods: VAT samples, used for gene expression studies as well as adipose explant cultures, were collected from patients with obesity (n = 54) and lean patients (n = 10). Supernatants from human pDC cultures, treated with adipose explant culture supernatants, were used for interferon α ELISA. Venous plasma, from patients with (n = 114) and without (n = 45) obesity, was used for an ELISA for autoantibodies., Results: MtDNA from VAT in obesity, in complex with mitochondrial transcription factor A protein (TFAM), acts as interferogenic ligands for pDCs. Humoral autoreactivity against TFAM is also induced in obesity., Conclusions: Interferogenic ligands and an autoantigen can be sourced from dysfunctional mitochondria in VAT of humans with obesity. Further therapeutic and prognostic potential for this immune mechanism in obesity warrants exploration., (© 2023 The Obesity Society.)