Biology subjects

Bagchi, S.

Publications and source records attributed to Bagchi, S..

13 recordsLinked to original sources

bioRxiv2026

Maltose aids in the growth of Salmonella Typhimurium in nitrogen-deficient conditions

Enteric pathogens, such as Salmonella, encounter uncertain nutrients in both the host and the environment. Nutrients such as carbon and nitrogen are essential for growth, and when these nutrients are limited, bacteria have developed various mechanisms to overcome stress and thrive in nutrient-rich environments. In this study, we investigated the role of the disaccharide sugar maltose in the growth and pathogenicity of Salmonella Typhimurium (STM) under nitrogen-deficient culture conditions. Throughout the study, we used Burks medium to mimic nitrogen-deficient conditions. STM growth in Burks medium was minimal, and maltose supplementation enhanced STM growth in both liquid and solid Burks media. The STM grown in Burks medium had a reduced bacterial cell length, which increased upon the addition of maltose and became comparable to that of LB-grown STM WT. Growth was dependent on the NtrBC two-component system and sigma factor RpoE. Deletion of ntrB and rpoE significantly reduced the growth in Burks medium during the log phase. Salmonella grown in Burks medium with maltose had reduced invasion in Caco-2 cells, phagocytosis in RAW 264.7 macrophages, and organ burden in C57BL/6 mice. Our findings revealed the role of maltose in enhancing the growth and length of Salmonella under nitrogen-deficient conditions. However, Salmonella grown in Burks medium with maltose is defective in pathogenesis.

microbiology↗

bioRxiv2025

Maltose facilitates Salmonella growth under nitrogen stress while impairing adhesion to epithelial cells

The composition of nutrients in the intestine defines a niche for colonising gut pathogens. The lack of nutrients suitable for pathogens due to competition from resident intestinal microbiota or dietary preferences leads to colonisation failure by pathogens. In this study, we investigated the impact of the disaccharide sugar maltose on Salmonella Typhimurium (STM) pathogenicity during the early phases of infection in C57BL/6 mice and human colon carcinoma cells (Caco-2). We found that supplementation of maltose at lower concentrations inhibited STM colonisation in the ileum of mice. To understand this, we investigated the role of maltose metabolism in human colon epithelial (Caco-2) cells. Deleting the maltose metabolism gene (malQ) increased adhesion to Caco-2 cells. The increased adhesion was due to increased expression of type 1 fimbriae. Inhibiting the type 1 fimbriae-mediated binding to host epithelial cells by incubating with mannose resulted in similar adhesion of STM WT and STM {Delta}malQ. We further identified that malQ regulates the adhesion of Salmonella through the sigma factor RpoE. Overall, malQ in Salmonella inhibits infection in epithelial cells by reducing its adhesion to host epithelial cells.

microbiology↗

bioRxiv2024

Nutrient addition in grasslands worldwide reveals proportional plant diversity decline across spatial scales but little change in beta diversity

Nutrient enrichment typically causes local plant diversity declines. A common but untested expectation is that nutrient enrichment also reduces variation in nutrient conditions among localities and selects for a smaller pool of species, causing greater diversity declines at larger than local scales and thus biotic homogenization. Here we apply a framework that links changes in species richness across scales to changes in the numbers of spatially restricted and widespread species for a standardized nutrient addition experiment across 72 grasslands on six continents. Overall, we find proportionally similar species loss at local and larger scales, suggesting similar declines of spatially restricted and widespread species, and no biotic homogenization after 4 years and up to 14 years of treatment. These patterns of diversity changes are generally consistent across species groups. Thus, nutrient enrichment poses threats to plant diversity, including for widespread species that are often critical for ecosystem functions.

ecology↗

bioRxiv2024

Post-GWAS functional analyses of CNTNAP5 suggests its role in glaucomatous neurodegeneration

Primary angle closure glaucoma (PACG) affects more than 20 million people worldwide, with an increased prevalence in south-east Asia. In a prior haplotype-based GWAS, we identified a novel CNTNAP5 genic region, significantly associated with PACG. In the current study, we have extended our perception of CNTNAP5 involvement in glaucomatous neurodegeneration in a zebrafish model, through investigating phenotypic consequences pertinent to retinal degeneration upon knockdown of cntnap5 by translation-blocking morpholinos. While cntnap5 knockdown was successfully validated using an antibody, immunofluorescence followed by western blot analyses in cntnap5-morphant (MO) zebrafish revealed increased expression of acetylated tubulin indicative of perturbed cytoarchitecture of retinal layers. Moreover, significant loss of Nissl substance is observed in the neuro-retinal layers of cntnap5-MO zebrafish eye, indicating neurodegeneration. Additionally, in spontaneous movement behavioural analysis, cntnap5-MO zebrafish have a significantly lower average distance traversed in light phase compared to mismatch-controls, whereas no significant difference was observed in the dark phase, corroborating with vision loss in the cntnap5-MO zebrafish. This study provides the first direct functional evidence of a putative role of CNTNAP5 in visual neurodegeneration.

genetics↗

bioRxiv2024

Gut feeling: host and habitat as drivers of the microbiome in blackbuck (Antilope cervicapra)

The gut microbiome can be shaped by both intrinsic host factors and extrinsic environmental factors. However, the relative importance of intrinsic and extrinsic factors in gut microbial composition has rarely been investigated, particularly for a single host across its natural range. Here, we characterise the gut microbiome of an endemic, endangered antelope, the blackbuck or Antilope cervicapra. We evaluated the influence of seven predictor variables, which were classified into intrinsic and extrinsic factors, on the gut microbiome. We determined which of these seven variables explains greater variation in the microbiome within (-diversity) and between ({beta}-diversity) the blackbuck host. We analysed the microbiome of 60 blackbuck hosts from ten different populations across India. We recorded 11800 unique OTUs across 30 known phyla and 2.9 million reads. We find an average of 2056 OTUs per individual, with firmicutes and bacteroidetes being the most dominant phyla. We find that nucleotide diversity (intrinsic), blackbuck population density (intrinsic), distance to human settlement (extrinsic), and anthropogenic land-use (extrinsic) explain within-host variation. In contrast, precipitation (extrinsic), nucleotide diversity, distance to human settlement, and anthropogenic land-use explain between-host variation. Overall, we also show that the genetic diversity of the host is more important than their environment for both within- and between-host variation in the microbiome, in blackbuck. Therefore, conservation efforts should be directed to not only preserve natural habitats but also increase the genetic pool of the blackbuck populations, which will positively impact their survival through diverse gut microbiomes.

ecology↗

bioRxiv2023

Diversity and functions of soil microbial communities in the Trans-Himalayan grazing ecosystem: influence of herbivores and abiotic factors

O_LIDiversity-function relationships are well known for producers, and these are also known to be influenced by consumers at higher trophic levels. However, these are not well known for microbial decomposers and decomposition processes in soil. Further, it also remains unknown whether and how consumers such as large mammalian herbivores, who are a major feature across more than one-third of the worlds terrestrial realm, influence soil microbial decomposer diversity-function relationships. C_LIO_LIWe used a14-year old long-term herbivore-exclusion experiment to answer two questions: (a) whether microbial functions vary with microbial diversity (both species richness and composition), and (b) whether herbivores alter the diversity-function relationships among microbial decomposers. We measured functional richness, and functional dispersion from the utilization profiles of 30 metabolic substrates. Alongside, we also measured species richness and species composition of soil microbes. C_LIO_LIWe analysed soils from n=10 paired grazed-and-fenced plots, and sampled them three times during the growth season of 2019. Data were from 60 16S rDNA gene amplicon sequences with 7.6 million reads covering 1937 operational taxonomic units (OTU) across 47 phyla (of which 924 OTUs were identifiable to genus level), and 1800 catabolic profiles. C_LIO_LIFunctional diversity in soil was positively related to microbial community composition, but not to species richness. This parallels the diversity-function relationships between producers and production; it also challenges the prevailing notion of functional redundancy in hyper-diverse soil microbial communities. Since certain combinations of species can outperform others, global change factors which can alter microbial communities may also impact decomposition processes and services. But this coupling between diversity and functions was unaffected by experimental herbivore-exclusion, indicating resilience and resistance among decomposers. C_LIO_LIStructural equation models suggested that the strength of this relationship is favoured by availability of soil moisture. These also showed microbial functions varied more strongly with temporal variables (e.g., seasonality) than with spatial variables (e.g., edaphic factors such as soil texture and pH). Although interpretations can be constrained by which and how many functions are investigated, the relationship between diversity and functions was generalizable and robust once 16 or more functions were quantified. C_LIO_LIWhile ecosystem functions and services derived from microbial decomposers have intrinsic resilience and resistance, they respond strongly to variability in water availability. Decomposition in grazing ecosystems may be particularly susceptible to how microbial community composition responds to rising precipitation variability under ongoing and projected climate change. C_LI HighlightsO_LIDiversity-function relationships for microbial decomposers remain uncertain. C_LIO_LIMicrobial diversity is positively related to functions C_LIO_LIThis relationship is robust to herbivore-exclusion. C_LIO_LIMicrobial diversity-function relationship can be susceptible to altered precipitation C_LI

ecology↗

bioRxiv2022

Nutrient addition increases grassland resistance during dry and wet climate extremes despite functional diversity loss

O_LINutrient enrichment impacts grassland plant diversity such as species richness, functional trait composition and diversity, but whether and how these changes affect ecosystem stability in the face of increasing climate extremes remains largely unknown. C_LIO_LIWe quantified the direct and diversity-mediated effects of nutrient addition (by nitrogen, phosphorus, and potassium) on the stability of aboveground biomass production in 10 long-term grassland experimental sites. We measured five facets of stability as the temporal invariability, resistance during and recovery after extreme dry and wet growing seasons. C_LIO_LILeaf traits (leaf carbon, nitrogen, phosphorus, potassium, and specific leaf area) were measured under ambient and nutrient addition conditions in the field and were used to construct the leaf economic spectrum (LES). We calculated functional trait composition and diversity of LES and of single leaf traits. We quantified the contribution of intraspecific trait shifts and species replacement to change in functional trait composition as responses to nutrient addition and its implications for ecosystem stability. C_LIO_LINutrient addition decreased functional trait diversity and drove grassland communities to the faster end of the LES primarily through intraspecific trait shifts, suggesting that intraspecific trait shifts should be included for accurately predicting ecosystem stability. Moreover, the change in functional trait diversity of the LES in turn influenced different facets of stability. That said, these diversity-mediated effects were overall weak and/or overwhelmed by the direct effects of nutrient addition on stability. As a result, nutrient addition did not strongly impact any of the stability facets. These results were generally consistent using individual leaf traits but the dominant pathways differed. Importantly, major influencing pathways differed using average trait values extracted from global trait databases (e.g. TRY). C_LIO_LISynthesis. Investigating changes in multiple facets of plant diversity and their impacts on multidimensional stability under global changes such as nutrient enrichment can improve our understanding of the processes and mechanisms maintaining ecosystem stability. C_LI

ecology↗

bioRxiv2022

Topology Adaptive Graph Convolution Network With Heterogeneous Entities For Predicting Adverse Events from Drug-Drug-Interactions

In times like this, it is imperative to be cautious about the effects of drugs or vaccination doses on patients who are already suffering from other serious diseases. Its not only the virus which can affect the body metabolisms, drugs to encounter the virus may also end up having unwanted negative effects. Therapeutic activities of drugs are often influenced by co-administration of drugs that may cause inevitable drug-drug interactions and inadvertent side effects. Therefore, prediction and identification of DDIs are extremely vital for patient safety and treatment modalities. In this context, we intend to develop a computational method based on functional similarity of drugs. Our objective has been enhanced by the usage of knowledge graphs which allows capturing underlying information embeddings in a biological network with heterogenous entities. On providing this knowledge graph as the input to a Topology Adaptive Graph Convolution Network which performs topologically-aware flexible convolutions, we achieve improvements on priorly proposed GCN models that has been shown as comparison.

bioinformatics↗

bioRxiv2022

Functional substitutability of native herbivores by livestock for long-term soil carbon sequestration depends on microbial decomposers.

Grazing by large mammalian herbivores impacts climate as it can favor the size and stability of a large carbon (C) pool in soil. As native herbivores in the worlds grasslands, steppes, and savannas are progressively being displaced by livestock, it is important to ask whether livestock can emulate the functional roles of their native counterparts. While livestock and native herbivores can have remarkable similarity in their traits, they can differ greatly in their impacts on vegetation composition which can affect soil-C. It is uncertain how their similarities and differences impact soil-C via their influence on microbial decomposers. We test competing alternative hypotheses with a replicated, long-term, landscape-level, grazing-exclusion experiment to ask whether livestock in the Trans-Himalayan ecosystem of northern India can match decadal-scale (2005-2016) soil-C stocks under native herbivores. We evaluate multiple lines of evidence from 17 variables that influence soil-C (quantity and quality of C-input from plants, microbial biomass and metabolism, microbial community composition, veterinary antibiotics in soil), and asses their inter-relationships. Livestock and native herbivores differed in their effects on several soil microbial processes. Microbial carbon use efficiency (CUE) was 19% lower in soils under livestock. Compared to native herbivores, areas used by livestock contained 1.5 kg C m-2 less soil-C. Structural equation models showed that alongside effects arising from plants, livestock alter soil microbial communities which is detrimental for CUE, and ultimately also for soil-C. Supporting evidence pointed toward a link between veterinary antibiotics used on livestock, microbial communities, and soil-C. Overcoming the challenges of sequestrating antibiotics to minimize their potential impacts on climate, alongside microbial rewilding under livestock, may reconcile the conflicting demands from food-security and ecosystem services. Conservation of native herbivores and better management of livestock is crucial for soil-C stewardship to envision and achieve natural climate solutions.

ecology↗

bioRxiv2020

Response of mycorrhizae to herbivory and soil moisture in a semiarid grazing ecosystem

Arbuscular mycorrhizal fungal (AMF) symbioses with plants can be influenced by top-down forces such as grazing, and also by bottom-up forces such as soil resource availability, both of which are being altered by anthropogenic and global change drivers. While the influence of each of these factors on AMF symbioses has been widely studied, explicit tests of the relative strengths of top-down versus bottom-up influences on these ubiquitous plant root symbioses are few. We studied AMF colonization responses of four species of graminoids (3 grasses Elymus longae-aristatus, Leymus secalinus and Stipa orientalis, and a sedge Carex melanantha) common to semiarid high-altitude rangelands of the Spiti region, Trans-Himalaya, to changes in a top-down driver, grazing intensity (through short-term clipping and long-term grazer exclusion experiments), and a bottom-up driver, water availability (using irrigation treatments, and by evaluating responses to annual precipitation levels across years). Over three years, AMF colonization in all four host species was influenced by precipitation, with the highest and lowest AMF colonization levels corresponding to years with the lowest and highest rainfall, respectively. However, responses to long-term grazer exclusion differed among host species, and across years: while some species showed decreases in AMF colonization levels under grazing, others showed increases from ungrazed control levels, and these responses changed, even reversed, across years. Responses to short-term clipping and irrigation treatments also differed among hosts, with some species responding to irrigation alone, some to clipping and irrigation combined, and others showing no changes in AMF colonization from control levels in any of the treatments. In our study, long-term changes in water availability influenced AMF colonization levels, while short-term responses were host specific. Responses to above-ground tissue loss, however, differed among host species both in the long- and short-term. Overall, this study demonstrates that while AMF colonization levels correspond to annual precipitation levels in this semiarid ecosystem, host species also play a role in influencing plant-AMF interactions in these rangelands, with colonization levels and responses to abiotic factors changing with host species.

ecology↗

bioRxiv2020

Lineage specific transcription factor waves reprogram neuroblastoma from self-renewal to differentiation

Temporal regulation of super-enhancer (SE) driven lineage specific transcription factors (TFs) underlies normal developmental programs. Neuroblastoma (NB) arises from an inability of sympathoadrenal progenitors to exit a self-renewal program and terminally differentiate. To identify critical SEs driving TF regulators of NB, we utilized NB cells in which all-trans retinoic acid (ATRA) induces growth arrest and differentiation. H3K27ac ChIP-seq paired with RNA-seq over a time course of ATRA treatment revealed SEs moving in a coordinated manner with four distinct temporal patterns (clusters). SEs that decreased with ATRA linked to 24 TFs involved in stem cell development/specialization (MYCN, GATA3, SOX11) along with LMO1, a transcriptional coregulator and oncogene identified via a genome-wide association study (GWAS) of NB. H3K27ac levels and GATA3 binding at the NB-associated rs2168101 site of the LMO1 SE were reduced with ATRA treatment, resulting in 1.46 fold decreased LMO1 expression. The SOX11 SE was lost coincident with a 50% decrease in mRNA after 8 days of ATRA treatment. CRISPR-Cas9 screening and siRNA inhibition showed a dependency on SOX11 for cell growth in NB cell lines. Silencing of the SOX11 SE using dCAS9-KRAB targeted guides caused a 40% decrease in SOX11 mRNA and inhibited cell growth. Three other TF SE clusters had sequential waves of activation at 2, 4 and 8 days of ATRA treatment and involved TFs regulating neural development (GATA2 and SOX4). Silencing of the gained SOX4 SE using dCAS9-KRAB targeting, caused a 50% decrease in SOX4 expression and attenuated expression of ATRA-induced differentiation genes. Our study has identified candidate oncogenic lineage drivers of NB self-renewal and TFs critical for implementing a differentiation program.

cancer biology↗

bioRxiv2019

High accuracy DNA sequencing on a small, scalable platform via electrical detection of single base incorporations

High throughput DNA sequencing technologies have undergone tremendous development over the past decade. Although optical detection-based sequencing has constituted the majority of data output, it requires a large capital investment and aggregation of samples to achieve optimal cost per sample. We have developed a novel electronic detection-based platform capable of accurately detecting single base incorporations. The GenapSys technology with its electronic detection modality allows the system to be compact, accessible, and affordable. We demonstrate the performance of the system by sequencing several different microbial genomes with varying GC content. The platform is capable of generating up to 2 Gb of high-quality nucleic acid sequence in a single run. We routinely generate sequence data that exceeds 99% raw accuracy with read lengths of up to 175 bp. Average quality scores remain above Q30 (99.9% raw sequencing accuracy) beyond 150 bp, with more than 85% of total bases at or above Q30. The utility of the platform is highlighted by targeted sequencing of the human genome. We show high concordance of SNP detection on the human NA12878 HapMap cell line with data generated on the Illumina sequencing platform. In addition, we sequenced a targeted panel of cancer-associated genes in a well characterized reference standard. With multiple library preparation approaches on this sample, we were able to identify low frequency mutations at expected allele frequencies.

genomics↗

bioRxiv2019

Postdoc X-ray in Europe 2017: work conditions, productivity, institutional support and career outlooks

1.Executive SummaryThis survey and data analysis were conducted by the European Network of Postdoctoral Associations (ENPA) with the aim of assessing the current research and work conditions, aspirations and support received by postdoctoral researchers working in Europe. The Results section is structured into three main parts. The first one describes the study sample of European postdoctoral researchers, including participants demographics, funding sources and income, research outputs, and teaching opportunities. The second section focuses on their professional aspirations and institutional support provided. The third part describes the level of engagement of postdoctoral researchers and their institutions in working towards better research conditions and career development, and what initiatives are emerging within this community. Our Conclusions section pulls together this comprehensive analysis, highlighting some of the most concerning issues currently affecting postdoctoral researchers in Europe. We also make a number of recommendations that would significantly improve the career expectations and aspirations of postdoctoral researchers. These are listed below. Conclusions and recommendationsO_LILonger postdoctoral periods in Southern Europe despite higher publication metrics Recommendation Institutions in Southern Europe should develop clear criteria to support postdoctoral researchers career progression. C_LIO_LISouthern and Eastern Europe pay the lowest salaries and have the lowest number of foreign postdoctoral researchers Recommendation The salary differences across European countries should be addressed as this could be a barrier to mobility and knowledge exchange from higher to lower pay regions. C_LIO_LILack of access to funding is a significant concern of postdoctoral researchers Recommendation Discrepancies in access to funding should be minimized across the different European areas. C_LIO_LIPostdoctoral researchers in Europe work longer hours than required by contract Recommendation The culture of overwork in the research environment should be addressed in order to protect researchers against the risks associated with long hours at work. C_LIO_LIThe majority of full-time postdoctoral work contracts includes an exclusivity clause Recommendation Inclusion of exclusivity clauses in contracts for postdoctoral researchers should be optional in order to allow them to enhance their employability outside academia. C_LIO_LIPostdoctoral researchers career development is poorly supported by their institutions Recommendation Postdoctoral researchers career prospects and career management should be much more supported by institutions in coordination with postdoctoral associations. C_LIO_LILack of postdoctoral representation in governance is linked to unclear institutional duties and rights Recommendation Institutional governance bodies should include postdoctoral researcher representatives. This would ensure that the views of this vital staff group are heard, as well as making postdoctoral researchers feel more engaged with their own institutions. A flexible and proactive communication strategy at the institution and research group level should be developed, taking into account the sometimes transient nature of postdoctoral researchers posts. C_LIO_LIResearchers show higher engagement with their local postdoctoral associations than with workers unions Recommendation Postdoctoral associations are an essential way to advocate for postdoctoral researchers at the governance level. Institutions should engage with, promote and support the work of postdoctoral associations. C_LI

scientific communication and education↗