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Biology subjects

Thakur, M.

Publications and source records attributed to Thakur, M..

18 recordsLinked to original sources

Extreme drought disrupts the bottom-up regulation of ground-dwelling invertebrate diversity under climate warming

Extreme climate events are becoming more frequent, yet their consequences for the recovery of plant-invertebrate relationships under warming remain poorly understood. We investigated over two years of how ground-dwelling invertebrate communities recovered from a 40-days drought in outdoor grassland mesocosms exposed to ambient conditions, constant warming or periodic heatwaves, and both combined. We then examined how post-drought community shifts were associated with above-ground plant biomass, measured concurrently with invertebrate sampling. Drought had no detectable effect on total invertebrate abundance at either recovery time (one or four months after drought). By contrast, diversity showed warming-dependent responses one month after drought and a delayed drought legacy four months later, when diversity declined only under constant warming, with or without periodic heatwaves. At the four-month post-drought sampling, plant biomass-invertebrate diversity coupling was evident only in non-drought plots, with negative relationships under ambient and heatwave regimes but a positive relationship under constant warming alone. This pattern was largely associated with responses of herbivores, particularly Stylommatophora. Our results highlight lagged drought effects in invertebrate diversity that emerged months later and, under warming, extended to weakened plant biomass-invertebrate diversity coupling, pointing to disrupted bottom-up control with potential consequences for food-web functioning.

ecology↗

Constant and variable warming differentially shape bacterial coexistence through phage-mediated interactions

Frequency-dependent predation helps maintain bacterial diversity, but its stabilizing role may be compromised under climate warming. Whereas theory suggests that warming can weaken predator-prey interactions and destabilize prey coexistence, it remains unclear whether constant and variable warming regimes differentially disrupt predation and alter coexistence outcomes in bacterial communities. Here, we experimentally tested how constant and variable warming (both +4{degrees}C above ambient, but negligible versus high thermal variance) affect the coexistence of two Pseudomonas species in the presence of their lytic phage. Phage predation increased competitive symmetry between the two bacterial species and promoted bacterial coexistence. Under constant warming (negligible variance), this phage-mediated frequency dependence buffered competitive asymmetries and often promoted persistence of the otherwise inferior P. putida, thereby magnifying coexistence. In contrast, variable warming (high variance) weakened phage control, shifted the advantage to P. protegens, and increased competitive exclusion events. The erosion of top-down control under variable warming was consistent with strong thermal sensitivity of phage infection rates, revealed by thermal performance curves. Our findings demonstrate that phage reduction of competitive asymmetry between bacterial hosts is amplified under constant warming but undermined under variable warming, conditions that are becoming increasingly frequent under climate change.

ecology↗

Searching for a New Home or Rare Dispersal? Habitat Suitability and Landscape Connectivity of the Tibetan Brown Bear across the Indian Cold Deserts and the Tibetan Plateau

Understanding habitat suitability and landscape connectivity is essential for conserving wide-ranging carnivores in climate-sensitive high-altitude mountain ecosystems. The first occurrence record of the Tibetan brown bear (Ursus arctos pruinosus) from the Changthang region of Ladakh, India, has raised questions about whether this individual represents an isolated dispersal event or reflects functional connectivity with source populations on the Tibetan Plateau. To evaluate potential habitat suitability and transboundary connectivity, we compiled species occurrence records and associated environmental predictors and developed an ensemble species distribution model using biomod2. We then assessed landscape connectivity using circuit theory implemented in Circuitscape to identify potential ecological corridors. Our models indicate that approximately 1,011,818 km{superscript 2} (21.34%) of the combined Ladakh (India) and the Tibetan Plateau landscape is currently suitable for the species, of which only [~]207,000 km{superscript 2} represents highly suitable habitat. Annual precipitation, precipitation of the wettest month, and precipitation of the warmest quarter were the most influential predictors of habitat suitability. Connectivity analysis identified potential corridors linking the eastern Changthang region of Ladakh with suitable habitat on the Tibetan Plateau, suggesting plausible transboundary ecological connectivity. These results indicate that the recent record from Changthang is more likely driven by landscape-scale functional connectivity than by an isolated dispersal event. Although the mapped corridors represent probable connectivity pathways rather than confirmed movement routes, this study provides the first spatially explicit assessment of habitat suitability and potential transboundary connectivity for the Tibetan brown bear across the Ladakh and Tibetan Plateau landscape.

ecology↗

Single Cell Transcriptomics Reveal Genomic Indicators of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) affects roughly 25% of people globally. This paper seeks to use single cell RNA sequencing (scRNA-seq) to identify genomic markers for the identification of NAFLD and the evaluation of therapeutic methods in silico. Publicly available scRNA-seq datasets of livers of both control and NAFLD mice were analyzed in R using the Seurat package for scRNA-seq analysis. Datasets were clustered as needed using the Seurat standard preprocessing workflow, and the zonation of hepatocyte clusters was identified based on established marker genes. When examining hepatocyte reprogramming during NAFLD, trends were seen in the zonation of hepatocytes expressing fructose metabolism pathways such as Aldob, Slc2a5 and Khk. In one dataset, healthy livers showed elevated expression of fructose metabolism pathways in central hepatocytes, while NAFLD livers exhibited this expression predominantly in portal hepatocytes. Conversely, in a second dataset, this zonation pattern was reversed, with central hepatocytes in NAFLD livers showing higher fructose metabolism expression compared to portal regions. This consistent observation of a zonation switch across datasets strengthens our understanding of hepatocyte reprogramming during NAFLD and fibrosis. Further, the direction of this switching may provide insights into fibrosis etiology, potentially reflecting differences in diet and metabolic stressors that contribute to fibrosis progression. It could also prove valuable in in silico evaluations of therapies for NAFLD by identifying liver fibrosis.

bioinformatics↗

TFE3 fusions direct an oncogenic transcriptional program that drives OXPHOS and unveils vulnerabilities in translocation renal cell carcinoma

Translocation renal cell carcinoma (tRCC) is an aggressive subtype of kidney cancer driven by TFE3 gene fusions, which act via poorly characterized downstream mechanisms. Here we report that TFE3 fusions transcriptionally rewire tRCCs toward oxidative phosphorylation (OXPHOS), contrasting with the highly glycolytic metabolism of most other renal cancers. This TFE3 fusion-driven OXPHOS program, together with heightened glutathione levels found in renal cancers, renders tRCCs sensitive to reductive stress - a metabolic stress state induced by an imbalance of reducing equivalents. Genome-scale CRISPR screening identifies tRCC-selective vulnerabilities linked to this metabolic state, including EGLN1, which hydroxylates HIF-1 and targets it for proteolysis. Inhibition of EGLN1 compromises tRCC cell growth by stabilizing HIF-1a and promoting metabolic reprogramming away from OXPHOS, thus representing a vulnerability to OXPHOS-dependent tRCC cells. Our study defines a distinctive tRCC-essential metabolic program driven by TFE3 fusions and nominates EGLN1 inhibition as a therapeutic strategy to counteract fusion-induced metabolic rewiring.

cancer biology↗

Testing a Method for Quantifying Microplastic Content in Mytilus californianus

With the proliferation of microplastics within the environment, there has been an increased need to quantify them within organic tissues of aquatic species. Several studies have examined the potential role of mussels in filtering these contaminants, prompting interest in characterizing uptake and retention of microplastics in these species. There are a variety of methods to isolate and quantify microplastics, including density separation, enzymatic digestion, and filtration. The applicability of a combined digestion and ultrasonic bath methodology in isolating microplastics from the California mussel (Mytilus californianus Conrad, 1837) was investigated. Microplastics were added to 20-gallon tanks at 0 g (control) 8 mg. Mussel tissues from each tank were digested using potassium hydroxide solutions. These digestions were subjected to vacuum filtration and a sonication bath, then treated with a mixture of sodium hypochlorite and nitric acid. It was found that this method successfully removed organic tissue from the mussels while leaving dyed microplastics intact. The latter were quantified using fluorescent microscopy. This proof-of-principle experiment indicates that this technique can be applied to further studies on environmental impact and retention of microplastics in mussels and may also have utility for other shellfish.

zoology↗

Saccharomyces cerevisiae Rev7 regulates DSB repair pathway choice through binding and blocking Mre11 nuclease and Rad50 ATPase activities

Recent studies have shown that, in human cancer cells, the tetrameric Shieldin complex (comprising REV7, SHLD1, SHLD2, and SHLD3) facilitates non-homologous end-joining (NHEJ) while blocking homologous recombination (HR). Surprisingly, several eukaryotic species lack SHLD1, SHLD2 and SHLD3 orthologs, suggesting that Rev7 may leverage an alternative mechanism to regulate the double-strand break (DSB) repair pathway choice. Exploring this hypothesis, we discovered that Saccharomyces cerevisiae Rev7 physically interacts with the Mre11-Rad50-Xrs2 (MRX) subunits, impedes G-quadruplex DNA synergised-HU-induced toxicity and facilitates NHEJ, while antagonizing HR. Notably, we reveal that a 42-amino acid C-terminal fragment of Rev7 binds to the subunits of MRX complex, protects rev7{Delta} cells from G-quadruplex DNA-HU-induced toxicity, and promotes NHEJ by blocking HR. By comparison, the N-terminal HORMA domain, a conserved protein-protein interaction module, was dispensable. We further show that the full-length Rev7 impedes Mre11 nuclease and Rad50s ATPase activities without affecting the latters ATP-binding ability. Combined, these results provide unanticipated insights into the functional interaction between the MRX subunits and Rev7 and highlight a mechanism by which Rev7 facilitates DSB repair via NHEJ, and attenuation of HR, by blocking Mre11 nuclease and Rad50s ATPase activities in S. cerevisiae. IMPACT STATEMENTThe mechanisms steering DNA double-strand break repair pathway choice is a topic of intense investigation, but remains incompletely understood. Our findings suggest that yeast Rev7 promotes DSB repair via NHEJ and inhibits homologous recombination by blocking Mre11 nuclease and Rad50s ATPase activities.

molecular biology↗

Beyond Traditional Methods: Innovative Integration of LISS IV and Sentinel 2A Imagery for Unparalleled Insight into Himalayan Ibex Habitat Suitability

Despite advancements in remote sensing, satellite imagery is underutilized in conservation research. Multispectral data from various sensors have great potential for mapping landscapes, but distinct spectral and spatial resolution capabilities are crucial for accurately classifying wildlife habitats. Our study aimed to develop a technique for precisely discerning habitat categories for the Himalayan Ibex (Capra sibirica) using different satellite imagery. To address both spectral and spatial challenges, we utilized LISS IV and Sentinel 2A data and integrated the LISS IV data with Sentinel 2A data along with their corresponding geometric information. Employing multiple supervised classification algorithms, we found the Random Forest (RF) algorithm to outperform others. The integrated (LISS IV-Sentinel 2A) classified image achieved the highest accuracy, with an overall accuracy of 86.17% and a Kappa coefficient of 0.84. To map the suitable habitat of the Ibex, we conducted ensemble modeling using the Land Cover Land Use (LCLU) of all three image types (LISS IV, Sentinel 2A, Integrated) and other predictors such as topographical, soil type, vegetation, and water radiometric indices. The integrated model provided the most accurate prediction of suitable habitat for the Ibex, surpassing the other two LCLU classes derived from individual images. The Soil Adjusted Vegetation Index (SAVI) and elevation were identified as crucial factors in identifying suitable habitats These findings hold valuable implications for the development of effective conservation strategies, as accurate classification schemes enable the identification of vital landscape elements. By precisely classifying LULC satellite images and identifying crucial habitats for the Ibex, this pilot study provides a new and valuable strategy for conservation planning. It enhances our ability to preserve and protect the habitat of wildlife species in the mountain ecosystem of the Himalayas.

ecology↗

Understanding distribution and occupancy of Himalayan Monal in Uttarkashi district, Uttarakhand

The Himalayan Monal is a conservation priority species in its entire distribution range. Its population is declining in many areas due to various anthropogenic threats. The information on species distribution and its abundance is lacking in many areas which are vital for conservation and management planning. Hence, through the present study, we have assessed the abundance and occupancy of Himalayan monal in Uttarkashi district (Uttarakhand). We used camera traps and conventional sign surveys for documenting the species during 2018-2019. We installed a total of 69 camera traps (2819 trap nights) and surveyed 54 trails (650 km) which represents entire habitat and topographic variability of the landscape. The occupancy and detection probability was modelled using the habitat variables. The top model showed that occupancy probability of Himalayan monal was positively influenced by the slope ({beta} =27.52 {+/-}16.25) and negatively influenced by Reserve Forest (RF) ({beta}= -8.14 SE {+/-} 4.99). The observed naive occupancy of Himalayan Monal was 0.69 in the study area, which was slightly lower than the estimated occupancy. However, in the null model, the site occupancy estimated was found to be 0.82{+/-}0.08 and with detection probability 0.23{+/-}0.03. The overall abundance of monal was estimated about 171.58 {+/-}10.2 in the study area with an average density of 0.62/ km2. The activity pattern analysis indicates that monal remains very active between 6.00 hrs -12.00 hrs and relatively less active during mid-day when humans are most active 11.30 hrs-16.30 hrs. The present study is a first attempt to estimate occupancy and abundance using camera traps as well as sign survey for the species primarily from non-Protected Area (PA). We found that Himalayan monal is abundant outside the PAs, which is a good indication for its long-term viability and also identified areas for conservation and management prioritization in Uttarkashi.

ecology↗

Swi6/HP1 binding to RNA-DNA hybrids initiates heterochromatin assembly at the centromeric dg-dh repeats in Fission Yeast

Canonically, heterochromatin formation in fission yeast and metazoans is initiated by di/trimethylation of histone H3 at lysine 9 position by the histone methyltransferase Suv39H1/Clr4, followed by binding of Swi6/HP1 to H3-K9-me2/me3 via its chromodomain. Subsequent self-association of Swi6/HP1 on adjacent nucleosomes or a cooperative interaction between Clr4 and Swi6/HP1 leads to folded heterochromatin structure. HP1 binding to RNA is shown to facilitate its localization at and assembly of heterochromatin in metazoans. Likewise, recruitment of Swi6/HP1 to centromere depends on the RNAi pathway in fission yeast; paradoxically, Swi6/HP1 is also thought to play a role in RNA turnover. Here we provide evidence in support of RNAi-independent recruitment of Swi6. We show that, apart from the low affinity binding to RNAs through its hinge domain, as already reported, Swi6/HP1 displays a hierarchy of increasing binding affinity through its chromodomain to the siRNAs corresponding to specific dg-dh repeats and even stronger binding to the cognate siRNA-DNA hybrids than to the siRNA precursors or general RNAs. Our results support a mechanism of recruitment of Swi6, which is dependent on its specific and high affinity binding to siRNA-DNA hybrid at the dg-dh repeats. This binding, which is independent of, albeit augmented by binding to H3-K9-Me2, leads to heterochromatin formation and silencing. We suggest that the net role of Swi6 in RNA physiology may be regulated by a balance between abundance and affinity of Swi6 towards heterochromatic and euchromatic RNAs and siRNAs.

genetics↗

New insights on species divergence in red panda

With the recent classification of red panda into two phylogenetic species, we propose Siang river as a potential boundary for species divergence between the Himalayan red panda (Ailurus fulgens) and the Chinese red panda (Ailurus styani). Bayesian based phylogeny and MJ network splited all the sequences into two distinct clusters in accordance to the origin of the samples collected from the east and west side of the Siang river. The clade 1, that represented Himalayan red panda, was formed by inclusion of samples originated from the north West Bengal, Sikkim, and central Arunachal Pradesh and South Tibet. While, clade 2 represented Chinese red panda by inclusion of the samples originated from Dibang valley of eastern Arunachal Pradesh, India and Southwest China. We suggest being associated with diverse habitats, threats and transboundary distribution, both species of red panda require regional as well as multilateral cooperation for making species survival plan.

evolutionary biology↗

Fine-scale landscape genetics unveiling contemporary asymmetric movement of red panda (Ailurus fulgens) in Kangchenjunga landscape, India

Wildlife management in rapid changing landscapes requires critical planning through cross cutting networks, and understanding of landscape features, often affected by the anthropogenic activities. The present study demonstrates fine-scale spatial patterns of genetic variation and contemporary gene flow of red panda (Ailurus fulgens) populations with respect to landscape connectivity in Kangchenjunga Landscape (KL), India. The study found about 1309.54 Km2 area suitable for red panda in KL-India, of which 62.21% area fell under the Protected Area network. We identified 24 unique individuals from 234 feces collected at nine microsatellite loci. The spatially explicit and non-explicit Bayesian clustering algorithms evident to exhibit population structuring and supported red panda populations to exist in meta-population frame work. In concurrence to the habitat suitability and landscape connectivity models, gene flow results supported a contemporary asymmetric movement of red panda by connecting KL- India in a crescent arc. We demonstrate the structural-operational connectivity of corridors in KL-India that facilitated red panda movement in the past. We also seek for cooperation in Nepal, Bhutan and China to aid in preparing for a comprehensive monitoring plan for the long-term conservation and management of red panda in trans-boundary landscapes.

genetics↗

New insights of zoogeographical distribution of Himalayan goral (Naemorhedus goral) from Indian Himalayan Region

In the present study, we explored the intraspecific genetic variation and phylogeographic relationship among all the reported species in the genus Naemorhedus distributed in a wide range of habitats. The Bayesian based phylogeny demonstrated that Himalayan goral, is a highly diverged species from the other reported species of gorals. We claim the presence of two valid sub-species of Himalayan goral, i.e. N. g. bedfordi and N. g. goral, distributed in the western and central Himalaya, respectively. The comparative analysis with the inclusion of data available from different ranges, suggests the presence of plausibly six species of gorals across the distribution with a few valid subspecies. Further, we report that N. griseus is a valid species and not the synonyms of N. goral considering the observed discrepancy in the available sequences. We recommend all the sub-species present at distant locations may be considered as Evolutionary Significant Units (ESUs) and, therefore, appeal to provide them special attention for long term conservation and management.

genetics↗

How did SARS-CoV-19 spread in India from Italy, Iran and China? Genetic surveillance of early cases and virus demography

SARS-CoV-19 after emerging from Wuhan, drastically devastated all sectors of human life by crushing down the global economy and increased psychological burden on public, government, and healthcare professionals. We manifested by analyzing 35 early coronavirus cases of India, that virus introduction in India, occurred from Italy, Iran and China and population demography apparently revealed a rapid population expansion after the outbreak with a present steady growth. We depicted nucleotide substitutions in structural genes, drove for the adaptive selection and plead for sequencing more genomes to facilitate identification of new emerged mutants, genetic evolution and disease transmission caused by coronavirus.

genomics↗

Designing a multi-epitope peptide-based vaccine against SARS-CoV-2

COVID-19 pandemic has resulted so far 14,395,16 confirmed cases with 85,711 deaths from the 212 countries, or territories. Due to multifacet issues and challenges in implementation of the safety & preventive measures, inconsistent coordination between societies-governments and most importanly lack of specific vaccine to SARS-CoV-2, the spread of Wuhan originated virus is still uprising after taking a heavy toll on human life. In the present study, we mapped several immunogenic epitopes (B-cell, T-cell, and IFN-gamma) over the entire structural proteins of SARS-CoV-2 and by applying various computational and immunoinformatics approaches, we designed a multi-epitope peptide based vaccine that predicted high immunogenic response in the largest proportion of worlds human population. To ensure high expression of the recombinant vaccine in E. coli, codon optimization and in-silico cloning were also carried out. The designed vaccine with high molecular affinity to TLR3 and TLR4, was found capable to initiate effective innate and adaptive immune response. The immune simulation also suggested uprising high levels of both B-cell and T-cell mediated immunity which on subsequent exposure cleared antigen from the system. The proposed vaccine found promising by yielding desired results and hence, should be tested by practical experimentations for its functioning and efficacy to neutralize SARS-CoV-2.

bioinformatics↗

Integrating Genomic and Transcriptomic Data to Reveal Genetic Mechanisms Underlying Piao Chicken Rumpless Trait

Piao chicken, a rare Chinese native poultry breed, lacks primary tail structures, such as pygostyle, caudal vertebra, uropygial gland and tail feathers. So far, the molecular mechanisms underlying tail absence in this breed have remained unclear. We employed comprehensive comparative transcriptomic and genomic analyses to unravel potential genetic underpinnings of rumplessness in the Piao chicken. Our results reveal many biological factors involved in tail development and several genomic regions under strong positive selection in this breed. These regions contain candidate genes associated with rumplessness, including IRX4, IL-18, HSPB2, and CRYAB. Retrieval of quantitative trait loci (QTL) and gene functions implied that rumplessness might be consciously or unconsciously selected along with the high-yield traits in Piao chicken. We hypothesize that strong selection pressures on regulatory elements might lead to gene activity changes in mesenchymal stem cells of the tail bud and eventually result in tail truncation by impeding differentiation and proliferation of the stem cells. Our study provides fundamental insights into early initiation and genetic bases of the rumpless phenotype in Piao chicken.

genetics↗

The Rising Prevalence of Weapons in Unsafe Arming Configurations Discovered in American Airports: the Increasing Practice of Storage and Carry of Firearms with a Round Chambered

BackgroundRecent studies have shown that Americans appear to be increasingly owning and carrying firearms for personal protection, and are increasingly storing their firearms loaded. However, the prevalence of firearm carry and/or storage with a round chambered has not hitherto been studied; in this arming configuration the weapon is loaded, with a bullet resting against the firing pin, ready to fire if the trigger is pulled. Ostensibly this decreases reaction time in a threat situation, but carries an increased risk of accidental discharge. It is unknown what fraction of firearm owners typically carry or store their firearms in this configuration, and if there have been significant temporal trends in the practice.\n\nObjectiveWe examine firearms detected at Transportation Security Administration (TSA) airport security checkpoints between 2012 to 2017, to examine geospatial and temporal trends in the prevalence of unsafe arming configuration in detected firearms.\n\nResultsThe fraction of detected firearms found to be loaded has risen significantly since 2012 (Beta Binomial logistic regression p = 0.011). States with firearm child access prevention laws have significantly fewer firearms found by the TSA to be loaded (p = 0.039).\n\nThe fraction of loaded firearms found by the TSA to also have a round chambered has also risen significantly since 2012 (Beta Binomial logistic regression p < 0.001). By 2017, 36% of firearms found loaded were also found to have a round chambered, representing an apparent concerning trend in unsafe arming configurations during carry and storage.\n\nConclusionsAmericans appear to be increasingly using and storing firearms in unsafe arming configurations. TSA firearm detection data can potentially provide a key source of data when researching trends in firearm injury.

epidemiology↗

Murine MPDZ-Linked Hydrocephalus is Caused by Hyperpermeability of the Choroid Plexus

Though congenital hydrocephalus is heritable, it has been linked only to eight genes, one of which is MPDZ. Humans and mice that carry a truncated version of MPDZ incur severe hydrocephalus resulting in acute morbidity and lethality. We show by magnetic resonance imaging that contrast-medium penetrates into the brain ventricles of mice carrying a Mpdz loss-of-function mutation, whereas none is detected in the ventricles of normal mice, implying that the permeability of the choroid plexus epithelial cell monolayer is abnormally high. Comparative proteomic analysis of the cerebrospinal fluid of normal and hydrocephalic mice revealed up to a 53-fold increase in protein concentration, suggesting that transcytosis through the choroid plexus epithelial cells of Mpdz KO mice is substantially higher than in normal mice. These conclusions are supported by ultrastructural evidence, and by immunohistochemistry and cytology data. Our results provide a straight-forward and concise explanation for the pathophysiology of Mpdz-linked hydrocephalus.

neuroscience↗