Biology subjects

Gupta, S.

Publications and source records attributed to Gupta, S..

At least 343 records · Page 19Linked to original sources

bioRxiv2019

Gestural Communication of Wild Bonnet Macaques in the Bandipur National Park, Southern India

Nonhuman primate gestures are believed to be crucial evolutionary precursors of human language. Comparative studies on primate gestures in an evolutionary framework have, however, remained largely restricted to the great apes and the potential flexibility and richness of gestural communication in monkeys, especially in the wild, continue to be virtually unknown. In this paper, we followed several criteria, adapted from ape gesture studies, to identify gestures and evaluate their contexts of usage in the repertoire of wild bonnet macaques Macaca radiata in the Bandipur National Park of southern India. This report is the first of its kind to systematically identify gestures in any wild, non-ape species, thus providing a platform for comparative studies across primate taxa, particularly in our efforts to trace out the phylogenetic origins of language-like markers in the primate lineage, earlier than in the great apes.

animal behavior and cognition↗

bioRxiv2019

A single cell atlas of the developing Drosophila ovary identifies follicle stem cell progenitors

Addressing the complexity of organogenesis at a system-wide level requires a complete understanding of adult cell types, their origin and precursor relationships. The Drosophila ovary has been a model to study how coordinated stem cell units, germline and somatic follicle stem cells, maintain and renew an organ. However, lack of cell-type specific tools have limited our ability to study the origin of individual cell types and stem cell units. Here, we use a single cell RNA sequencing approach to uncover all known cell types of the developing ovary, reveal transcriptional signatures, and identify cell type specific markers for lineage tracing. Our study identifies a novel cell type corresponding to the elusive follicle stem cell precursors and predicts sub-types of known cell types. Altogether, we reveal a previously unanticipated complexity of the developing ovary, and provide a comprehensive resource for the systematic analysis of ovary morphogenesis.

developmental biology↗

bioRxiv2019

Parallel Tempering with Lasso for Model Reduction in Systems Biology

Systems Biology models reveal relationships between signaling inputs and observable molecular or cellular behaviors. The complexity of these models, however, often obscures key elements that regulate emergent properties. We use a Bayesian model reduction approach that combines Parallel Tempering with Lasso regularization to identify minimal subsets of reactions in a signaling network that are sufficient to reproduce experimentally observed data. The Bayesian approach finds distinct reduced models that fit data equivalently. A variant of this approach based on Group Lasso is applied to the NF-{kappa}B signaling network to test the necessity of feedback loops for responses to pulsatile and continuous pathway stimulation. Taken together, our results demonstrate that Bayesian parameter estimation combined with regularization can isolate and reveal core motifs sufficient to explain data from complex signaling systems.

systems biology↗

bioRxiv2019

A context-free grammar for Caenorhabditis elegans behavior

Hierarchy is a candidate organizing principle of ethology, where actions grouped into higher order chunks combine in specific ways to generate adaptive behavior. However, demonstrations of hierarchical organization in behavior have been scarce. Moreover, it remains unclear how such underlying organization allows for behavioral flexibility. Here we uncover the hierarchical and flexible nature of Caenorhabditis elegans behavior. By describing worm locomotion as a sequence of discrete postural templates, we identified chunks containing mutually substitutable postures along the dynamics. We then elucidated the rules governing their interactions. We found that stereotypical roaming can be described by a specific sequence of postural chunks, which exhibit flexibility at the lowest postural level. The same chunks get combined differently to produce dwelling, capturing non-stereotypical actions across timescales. We show that worm foraging is organized hierarchically --a feature not explainable via Markovian dynamics--, and derive a context-free grammar governing its behavior --which is different than a regular grammar, or a hidden Markov chain. In sum, in making the analogy with human language concrete (but not literal) our work demonstrates, in line with the foundational insights of classical ethologists, that spontaneous behavior is orderly flexible. Once more, investigating the humble nematode suggests that everything human has its roots in lower animal behavior.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=180 HEIGHT=200 SRC=\"FIGDIR/small/708891v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (25K):\norg.highwire.dtl.DTLVardef@168e648org.highwire.dtl.DTLVardef@1e6b2eeorg.highwire.dtl.DTLVardef@ed3ecdorg.highwire.dtl.DTLVardef@1b60741_HPS_FORMAT_FIGEXP M_FIG Graphical abstract\n\nC_FIG

animal behavior and cognition↗

bioRxiv2019

In-depth and 3-Dimensional Exploration of the Budding Yeast Phosphoproteome

Phosphorylation is one of the most dynamic and widespread post-translational modifications regulating virtually every aspect of eukaryotic cell biology. Here we present a comprehensive phosphoproteomic dataset for budding yeast, comprised of over 30,000 high confidence phosphorylation sites identified by mass spectrometry. This single dataset nearly doubles the size of the known phosphoproteome in budding yeast and defines a set of cell cycle-regulated phosphorylation events. With the goal of enhancing the identification of functional phosphorylation events, we performed computational positioning of phosphorylation sites on available 3D protein structures and systematically identified events predicted to regulate protein complex architecture. Results reveal a large number of phosphorylation sites mapping to or near protein interaction interfaces, many of which result in steric or electrostatic \"clashes\" predicted to disrupt the interaction. Phosphorylation site mutants experimentally validate our predictions and support a role for phosphorylation in negatively regulating protein-protein interactions. With the advancement of Cryo-EM and the increasing number of available structures, our approach should help drive the functional and spatial exploration of the phosphoproteome.

biochemistry↗

bioRxiv2019

Decoding brain functional connectivity implicated in AD and MCI

Deep neural networks have been demonstrated to extract high level features from neuroimaging data when classifying brain states. Identifying salient features characterizing brain states further refines the focus of clinicians and allows design of better diagnostic systems. We demonstrate this while performing classification of resting-state functional magnetic resonance imaging (fMRI) scans of patients suffering from Alzheimers Disease (AD) and Mild Cognitive Impairment (MCI), and Cognitively Normal (CN) subjects from the Alzheimers Disease Neuroimaging Initiative (ADNI). We use a 5-layer feed-forward deep neural network (DNN) to derive relevance scores of input features and show that an empirically selected subset of features improves accuracy scores for patient classification. The common distinctive salient brain regions were in the uncus and medial temporal lobe which closely correspond with previous studies. The proposed methods have cross-modal applications with several neuropsychiatric disorders.

neuroscience↗

bioRxiv2019

Deciphering the transcriptomic insight during organogenesis in castor (Ricinus communis L.), jatropha (Jatropha curcas L.) and sunflower (Helianthus annuus L.)

BackgroundCastor is a non-edible oilseed crop with a multitude of pharmaceutical and industrial uses. Profitable cultivation of the crop is hindered by various factors and one of the approaches for genetic improvement of the crop belonging to a monotypic genus is to exploit biotechnological tools. The major limitation for successful exploitation of biotechnological tools is the in vitro recalcitrance of castor tissues. Response of castor tissues to in vitro culture is poor which necessitated study on understanding the molecular basis of organogenesis in cultured tissues of castor, through de novo transcriptome analysis, by comparing with two other crops (jatropha and sunflower) with good regeneration ability.\n\nResultsRNA-seq analysis was carried out with hypocotyl explants from castor, jatropha and cotyledons from sunflower cultured on MS media supplemented with different concentrations of hormones. Genes that showed strong differential expression analysis during dedifferentiation and organogenic differentiation stages of callus included components of auxin and cytokinin signaling, secondary metabolite synthesis, genes encoding transcription factors, receptor kinases and protein kinases. In castor, many genes involved in auxin biosynthesis and homeostasis like WAT1 (Wall associated thinness), vacuolar transporter genes, transcription factors like short root like protein were down-regulated while genes like DELLA were upregulated accounting for regeneration recalcitrance. Validation of 62 differentially expressed genes through qRT-PCR showed a consensus of 77.4% with the RNA-Seq analysis.\n\nConclusionThis study provides information on the set of genes involved in the process of organogenesis in three oilseed crops which forms a basis for understanding and improving the efficiency of plant regeneration and genetic transformation in castor.

plant biology↗

bioRxiv2019

HBV seroepidemiology data for Africa provides insights into transmission and prevention

International goals for elimination of hepatitis B virus (HBV) infection set ambitious targets for 2030. In many African populations, HBV prevalence remains high ([≥]8%) despite the roll-out of infant HBV immunisation from the mid-1990s onwards. Enhanced efforts are now urgently required to improve an understanding of population epidemiology, in order to determine which interventions are most likely to be effective in advancing populations towards elimination goals. In populations with a high prevalence of infection, catch-up HBV vaccination of adults has sometimes been deployed as a preventive strategy. An alternative approach of test and treat could be applied as a tool to interrupt transmission. We used a systematic approach to investigate the relationship between prevalence of HBV infection (HBsAg) and exposure (anti-HBc) in Africa, and then applied a mathematical model to investigate the impact of catch-up vaccination and a test and treat strategy in Uganda, representing a high prevalence setting. We demonstrate a strong relationship between the prevalence of HBsAg and anti-HBc (p<0.0001), but with region-specific differences that may reflect different patterns of transmission. In high prevalence settings, catch-up vaccination may have a transient effect but this intervention does not contribute to a sustained decline in prevalence. In contrast, diagnosing and treating infection has a marked impact on reducing prevalence, equivalent to that of infant immunisation. Conclusion: We have developed a high-resolution picture of HBV epidemiology across Africa. Developing insights into regional differences provides an evidence base for the most effective interventions. In combination with robust neonatal immunisation programmes, testing and treating infection is likely to be of most impact in making advances towards elimination targets.

epidemiology↗

bioRxiv2019

Abrogating ALIX interactions results in stuttering of the ESCRT machinery

ESCRTs are cellular proteins that catalyze the fission of membranes and play an important role in biology of disease including cancer and infectious virus release 1. ESCRT associated protein ALIX plays an essential role in HIV budding 2-4, exosome release 5,6, down regulation of G-protein coupled receptors 7, cytokinesis 8,9 and multi vesicular budding 1. The consensus view is that ALIX plays a role by binding to the viral late domains 2-4/Syntenin late domain 5/Cepp55 8,9 and helps recruit downstream protein CHMP4 2,8,10,11 which along with VPS4 catalyzes the fission of the membrane 12,13. Using live imaging we have visualized the recruitment of ALIX, CHMP4 and VPS4 during budding of HIV with abrogated Gag-ALIX interactions. Based on the canonical view, we were expecting to find reduced recruitment of ALIX under these conditions. Instead we report observing multiple rounds of transient recruitment of ALIX, CHMP4 and VPS4 prior to virion release. We further show that during each, transient recruitment, stoichiometry of all ESCRT components remained the same regardless of mutations abrogating ALIX and Gag interaction. In addition, mutations abrogating interactions between Gag and TSG101 result in recruitment of ESCRTs with a substantial delay while maintaining similar stoichiometry. Our results demonstrate that recruitment of ESCRTs is driven by a robust network of interactions resulting in an \"On/Off\" switch behavior and ALIXs interactions with late domains of HIV Gag play a crucial role during final catalysis of membrane fission after assembly of the full ESCRT machinery.

cell biology↗

bioRxiv2019

Deciphering the unique SNPs among leading Indian Tomato Cultivars using Double Digestion Restriction Associated DNA sequencing

World-wide grown and consumed tomato (Solanum lycopersicum) crop used as model system for new cultivar and fruit development. Genetic and genomic research of Indian tomato cultivars will provide an insight to develop new breeding strategies and crop improvement. The present study aimed to identify the high quality common and unique single nucleotide polymorphisms (SNPs), present in 9 different Indian tomato cultivars using double digestion restriction associated DNA sequencing (ddRAD-seq). Total of 36,847,092 raw reads (3.68 GB) were generated for all samples and 3,329,625 of high-quality reads were aligned uniquely to the reference tomato genome. Using stringent filtering, a total of 1,165 SNPs and 69 INDELs were found in genic regions, along with the unique variants to each cultivar was observed. Similarly, 7 and 33 variants were identified in chloroplast and mitochondrial genome of tomato. In addition, the population structure and genetic relationship among these cultivars suggested 4 well-differentiated sub-populations. Functional annotation of SNP/INDLEs associated with flanking sequences along with gene ontology and pathway analysis was performed. Identified SNPs/INDELs could be useful as markers for variety identification for genetic purity analysis. Findings from this work will be useful to plant breeders and research community to deepen their understanding and enhance tomato breeding programs.

genomics↗

bioRxiv2019

Unveiling the transcriptome complexity of the High- and Low- Zinc & Iron accumulating Indian wheat (Triticum aestivum L.) cultivars

Development of Zinc (Zn), Iron (Fe) and other minerals rich grains along with various stress tolerance and susceptible (STR) wheat genotype, will help to reduce globally spread malnutrition problem. Current study deals with transcriptome profiling of 4 high- and 3 low- Zn & Fe accumulating wheat genotypes (HZFWGs) and (LZFWGs). Functional characterization of expressed and high and low specific genes, accompanied by metabolic pathways analysis reveals, phenylpropanoid biosynthesis, and other associated pathways are mainly participating in plant stress defense mechanism in both genotypes. Chlorophyll synthesis, Zn & Fe binding, metal ion transport, and ATP-Synthase coupled transport mechanism are highly active in HZFWGs while in LZFWGs ribosomal formation, biomolecules binding activities and secondary metabolite biosynthesis. Transcripts accountable for minerals uptake and purine metabolism in HZFWGs are highly enriched. Identified transcripts may be used for marker-assisted selection and breeding to develop minerals rich crops.

bioinformatics↗

bioRxiv2019

Assessing the remarkable morphological diversity and transcriptomic basis of leaf shape in Ipomoea batatas (sweetpotato)

O_LILeaf shape, a spectacularly diverse plant trait, varies across taxonomic levels, geography, and in response to environmental differences. However, comprehensive intraspecific analyses of leaf shape variation across variable environments is surprisingly absent. Here, we perform a multi-level analysis of leaf shape using diverse accessions of sweetpotato (Ipomoea batatas), and uncover the role of genetics, environment, and GxE on this important trait.\nC_LIO_LIWe examine leaf shape using a variety of morphometric analyses, and complement this with a transcriptomic survey to identify gene expression changes associated with shape variation. Additionally, we examine the role of genetics and environment on leaf shape by performing field studies in two geographically separate common gardens.\nC_LIO_LIWe show that extensive leaf shape variation exists within I. batatas, and identify promising candidate genes underlying this variation. Interestingly, when considering traditional measures, we find that genetic factors are largely responsible for most of leaf shape variation, but that the environment is highly influential when using more quantitative measures via leaf outlines.\nC_LIO_LIThis extensive and multi-level examination of leaf shape shows an important role of genetics underlying a potentially important agronomic trait, and highlights that the environment can be a strong influence when using more quantitative measures of leaf shape.\nC_LI

plant biology↗

bioRxiv2019

Cdk1 in germline and the dose of somatic EGFR signaling determine the rate of transit amplification

The division rates of stem cells and their progeny shape the growth and maintenance of tissues. Here, we present a mathematical model that could estimate the stage-wise lifespans of germline stem cells (GSCs) and subsequent transit amplifying (TA) cells from their steady-state distribution in Drosophila testis. Analysis of the wild-type data using this model indicated that the inter-division lifespans of the first two TA cycles remain similar to that of the GSCs, and then reduce by nearly 2-folds for the third and fourth cycles. Also, loss of Cyclin E and Cdk1 functions in the early germline cells, which decreased the rates of GSC divisions, is suggested to extend the lifespans of GSCs and the TA stages without affecting subsequent differentiation. Similar perturbations at the 4 and 8-cell stages, however, arrested the mitoses at the 8-cell stage, and only the Cyclin E-deficient cells continued with premature meiosis. Together, these results suggest that regulation of the G1-S and G2-M transitions in the GSCs and the rapidly dividing TA stages differentially impacts the amplification of the germline pool and subsequent differentiation. The model also helped to quantify distinct influences of these cell cycle regulatory molecules in determining the lifespans at different TA stages.\n\nHighlightsA model for calculating the lifespans of transit amplifying stages from demography. Transit-amplifying divisions accelerate by nearly 2-folds after the second mitosis. Cyclin E and Cdk1 regulate the lifespans of GSCs and transit amplifying cells. The premature arrest of the final transit amplifying division induces meiosis.

developmental biology↗

bioRxiv2018

Serotonin regulates mitochondrial biogenesis and function in rodent cortical neurons via the 5-HT2A receptor and SIRT1-PGC-1α axis

Mitochondria in neurons in addition to their primary role in bioenergetics also contribute to specialized functions including regulation of synaptic transmission, Ca2+ homeostasis, neuronal excitability and stress adaptation. However, the factors that influence mitochondrial biogenesis and function in neurons remain poorly elucidated. Here, we identify an important role for serotonin (5-HT) as a regulator of mitochondrial biogenesis and function in rodent cortical neurons, via a 5-HT2A receptor-mediated recruitment of the SIRT1-PGC-1 axis, which is relevant to the neuroprotective action of 5-HT. 5-HT increased mitochondrial biogenesis, reflected through enhanced mtDNA levels, mitotracker staining, and expression of mitochondrial genes. This was accompanied by increased cellular ATP levels, basal and maximal respiration, as well as spare respiratory capacity. Mechanistically the effects of 5-HT were mediated via the 5-HT2A receptor and master modulators of mitochondrial biogenesis, SIRT1 and PGC-1. SIRT1 was required to mediate the effects of 5-HT on mitochondrial biogenesis and function in cortical neurons. In vivo studies revealed that 5-HT2A receptor stimulation increased cortical mtDNA and ATP levels, in a SIRT1 dependent manner. In cortical neurons, 5-HT enhanced expression of anti-oxidant enzymes, decreased cellular reactive oxygen species, and exhibited neuroprotection against excitotoxic and oxidative stress, an effect that required SIRT1. These findings identify 5-HT as a novel upstream regulator of mitochondrial biogenesis and function in cortical neurons, and implicate the mitochondrial effects of 5-HT in its neuroprotective action.

neuroscience↗

bioRxiv2018

Determinants of high residual post-PCV13 pneumococcal vaccine type carriage in Blantyre, Malawi: a modelling study.

BackgroundIn November 2011, Malawi introduced the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant schedule. Four to seven years after introduction (2015-2018), rolling prospective nasopharyngeal carriage surveys were performed in the city of Blantyre. Carriage of Streptococcus pneumoniae vaccine serotypes (VT) remained higher than reported in developed countries, and VT impact was surprisingly asymmetric across age-groups. A dynamic transmission model was fit to survey data using a Bayesian Markov-chain Monte Carlo approach, to obtain insights into the determinants of post-PCV13 age-specific VT carriage.\n\nResultsAccumulation of naturally acquired immunity with age and age-specific transmission potential were both key to reproducing the observed data. VT carriage reduction peaked sequentially over time, earlier in younger and later in older age-groups. Estimated vaccine efficacy (protection against carriage) was 66.87% (95% CI 50.49-82.26%), similar to previous estimates. Ten-year projected vaccine impact (VT carriage reduction) among 0-9 years old was lower than observed in other settings, at 76.23% (CI 95% 68.02-81.96%), with sensitivity analyses demonstrating this to be mainly driven by a high local force of infection.\n\nConclusionsWe have identified both vaccine-related and host-related determinants of post-PCV13 pneumococcal VT transmission in Blantyre with vaccine impact determined by age-related characteristics of the local force of infection. These findings are likely to be generalisable to other Sub-Saharan African countries in which PCV impact has been lower than desired, and have implications for the interpretation of post-PCV carriage studies and future vaccination programs.

epidemiology↗

bioRxiv2018

High residual prevalence of vaccine serotype Streptococcus pneumoniae carriage 4 to 6 years after introduction of 13-valent pneumococcal conjugate vaccine in Malawi: a prospective serial cross-sectional study

BackgroundThere are concerns that pneumococcal conjugate vaccines (PCV) in sub-Saharan Africa sub-optimally interrupt vaccine-serotype (VT) carriage and transmission, thus limiting vaccine-induced direct and indirect protection. We assessed carriage in vaccinated children and unvaccinated populations targeted for indirect protection, between 4 and 7 years after Malawis November 2011 introduction of PCV13 using a 3+0 schedule.\n\nMethodsWe conducted sequential prospective nasopharyngeal carriage surveys between 2015 and 2018 among healthy PCV-vaccinated and PCV-unvaccinated children, and HIV-infected adults. VT and NVT carriage risk by age was analysed by non-linear regression.\n\nResultsAmong PCV-vaccinated children, there was a 24% relative reduction in carriage, from a mean 21.1% to 16.1%; 45% reduction among older PCV-unvaccinated children, from 27.5% to 15.2%; 41.4% reduction among adults, from 15.2% to 8.9%. Using carriage data from children 3.6 to 10 years of age, VT carriage probability declined with age, with a similar prevalence half-life among PCV-vaccinated (3.34 years) and PCV-unvaccinated (3.26 years) children.\n\nConclusionCompared to high-income settings, the 3+0 schedule in Malawi has led to a sub-optimal reduction in pneumococcal carriage prevalence. This is likely due to recolonisation of vaccinated children with waning vaccine-induced immunity, resulting in insufficient indirect protection of unvaccinated populations. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns is required.

epidemiology↗

bioRxiv2018

Loss Of Kat2a Enhances Transcriptional Noise And Depletes Acute Myeloid Leukemia Stem-Like Cells

Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with abnormal progenitor self-renewal and defective myelo-monocytic differentiation. Its pathogenesis comprises subversion of transcriptional regulation, through mutation and by hijacking normal chromatin regulation. Kat2a is a histone acetyltransferase central to promoter activity that we recently associated with stability of pluripotency networks, and identified as a genetic vulnerability in AML. Through combined chromatin profiling and single-cell transcriptomics, we demonstrate that Kat2a contributes to leukemia propagation through homogeneity of transcriptional programs and preservation of leukemia stem-like cells. Kat2a loss reduces transcriptional bursting frequency in a subset of gene promoters, generating enhanced variability of transcript levels but minimal effects on mean gene expression. Destabilization of target programs shifts cellular equilibrium out of self-renewal towards differentiation. We propose that control of transcriptional variability is central to leukemia stem-like cell propagation, and establish a paradigm exploitable in different tumors and at distinct stages of cancer evolution.

cancer biology↗

bioRxiv2018

DIAlign provides precise retention time alignment across distant runs in DIA and targeted proteomics

SWATH-MS has been widely used for proteomics analysis given its high-throughput and reproducibility but ensuring consistent quantification of analytes across large-scale studies of heterogeneous samples such as human-plasma remains challenging. Heterogeneity in large-scale studies can be caused by large time intervals between data-acquisition, acquisition by different operators or instruments, intermittent repair or replacement of parts, such as the liquid chromatography column, all of which affect retention time (RT) reproducibility and successively performance of SWATH-MS data analysis. Here, we present a novel algorithm for retention time alignment of SWATH-MS data based on direct alignment of raw MS2 chromatograms using a hybrid dynamic programming approach. The algorithm does not impose a chronological order of elution and allows for alignment of elution-order swapped peaks. Furthermore, allowing RT-mapping in a certain window around coarse global fit makes it robust against noise. On a manually validated dataset, this strategy outperforms the current state-of-the-art approaches. In addition, on a real-world clinical data, our approach outperforms global alignment methods by mapping 98% of peaks compared to 67% cumulatively and DIAlignR can reduce alignment error up to 30-fold for extremely distant runs. The robustness of technical parameters used in this pairwise alignment strategy has also been demonstrated. The source code is released under the BSD license at https://github.com/Roestlab/DIAlignR.\n\nAbbreviations\n\nData AvailabilityRaw chromatograms and features extracted by OpenSWATH are available on PeptideAtlas.\n\nServername: ftp.peptideatlas.org\n\nUsername: PASS01280\n\nPassword: KQ2592b

bioinformatics↗