Biology subjects

Chaudhary, S.

Publications and source records attributed to Chaudhary, S..

51 records · Page 3Linked to original sources

bioRxiv2022

Evaluation of the safety, immunogenicity and efficacy of a new live-attenuated lumpy skin disease vaccine in India

Lumpy skin disease (LSD) was reported for the first time in India in 2019 and since then, it has become endemic. Since a homologous (LSD-virus based) vaccine was not available in the country, goatpox virus (GPV)-based heterologous vaccine was authorized for mass immunization against LSD in cattle. This study describes the evaluation of safety, immunogenicity and efficacy of a new live-attenuated LSD vaccine developed using an Indian field strain (LSDV/India/2019/Ranchi). The virus was attenuated by continuous passage (P=50) in Vero cells. The vaccine (50th LSDV passage in Vero cells, named as Lumpi-ProVacInd) did not induce any local or systemic reaction upon its experimental inoculation in calves (n=10). At day 30 post-vaccination (pv), the vaccinated animals were shown to develop antibody- and cell-mediated immune response and exhibited complete protection upon virulent LSDV challenge. We observed a minimum Neethling response (0.018% animals; 5 out of 26940 animals) of the vaccine in field trials among 26940 animals. There was no significant reduction in the milk yield in lactating animals (n=10108), besides there was no abortion or any other reproductive disorder in the pregnant animals (n=2889). Sero-conversion was observed in 85.18% animals in the field by day 30 pv.

microbiology↗

bioRxiv2022

Career Self-Efficacy Disparities in Underrepresented Biomedical Scientist Trainees

The present study examines racial, ethnic, and gender disparities in career self-efficacy amongst 6077 US citizens and US naturalized graduate and postdoctoral trainees. Respondents from biomedical fields completed surveys administered by the National Institutes of Health Broadening Experiences in Scientific Training (NIH BEST) programs across 17 US institutional sites. Graduate and postdoctoral demographic and survey response data were examined to evaluate the impact of intersectional identities on trainee career self-efficacy. The study hypothesized that race, ethnicity and gender, and the relations between these identities, would impact trainee career self-efficacy. The analysis demonstrated that racial and ethnic group, gender, specific career interests (academic principal investigator vs. other careers), and seniority (junior vs. senior trainee level) were, to various degrees, all associated with trainee career self-efficacy and the effects were consistent across graduate and postdoctoral respondents. Implications for differing levels of self-efficacy are discussed, including factors and events during training that may contribute to (or undermine) career self-efficacy. The importance of mentorship for building research and career self-efficacy of trainees is discussed, especially with respect to those identifying as women and belonging to racial/ethnic populations underrepresented in biomedical sciences. The results underscore the need for change in the biomedical academic research community in order to retain a diverse biomedical workforce.

scientific communication and education↗

bioRxiv2022

Detection and Role of Feline Apolipoprotein B mRNA-editing Enzyme Catalytic Polypeptide Subunit 3G-Like Protein in Feline Cells and Tissues

The innate host defence system is designed to resist pathogenic microorganism infections. Despite the compelling scientific evidence, our understanding of the full potential of the mechanism is still unclear due to the complex interactions between hosts and invaders. We previously reported latency in cat mucosal infected with low-dose cell-associated feline immunodeficiency virus (102 and 103 infected cells). Here we investigated the expression of Apolipoprotein B mRNA-editing enzyme catalytic subunit 3G (APOBEC3G or A3G) in feline cells and tissues and whether its presence antagonizes the viral pre-integration complex resulting in partial or complete FIV latency. Total RNA and protein lysates were collected from cell lines, blood, and tissue samples. Real-time RT-PCR and western blot assays were used to quantify fA3G-like protein in cats exposed to high versus low-dose cell-associated FIV. We consistently detected fA3G-like protein in mock T-cell lines (E-CD4+, MYA-1, Crandell feline kidney cells) and primary bone marrow-derived macrophages with variable expressions in feline peripheral blood mononuclear cells (PBMC). In addition, the fA3G-like protein was found to interact with FIV group-specific antigen (Gag) protein through immunoprecipitation assays. The protein expression was utterly abrogated following FIV infection. However, in lytic FIV infection (in vivo), fA3G-like protein decreased in early post-infection, whereas latently infected cats showed stable expression. These data are the first report of the fA3G-like protein expression in felines and its abrogation in lytic but not in latent FIV-infected individuals. These results might provide new insight into the role of fA3G-like protein in the host defence mechanism against retrovirus infections.

cell biology↗

bioRxiv2022

Shared and distinct neural activity during anticipation and outcome of win and loss: A meta-analysis of the monetary incentive delay task

Reward and punishment motivate decision making and behavioral changes. Numerous studies have examined regional activities during anticipation and outcome of win and loss in the monetary incentive delay task (MIDT). However, the great majority of studies reported findings of anticipation or outcome and of win or loss alone. It remains unclear how the neural correlates share and differentiate amongst these processes. We conducted an Activation Likelihood Estimation meta-analysis of 77 studies of the MIDT (5,779 subjects), including 24 published since the most recent meta-analysis, to identify and, with conjunction and subtraction, contrast regional responses to win anticipation, loss anticipation, win outcome, and loss outcome. Win and loss anticipation engaged a shared network of bilateral anterior insula (AI), striatum, thalamus, supplementary motor area (SMA), and precentral gyrus. Win and loss outcomes did not share regional activities. Win and loss outcome each engaged higher activity in medial orbitofrontal cortex (mOFC) and dorsal anterior cingulate cortex. Bilateral striatum and right occipital cortex responded to both anticipation and outcome of win, and right AI to both phases of loss. Win anticipation vs. outcome engaged higher activity in bilateral AI, striatum, SMA and precentral gyrus and right thalamus, and lower activity in bilateral mOFC and posterior cingulate cortex as well as right inferior frontal and angular gyri. Loss anticipation relative to outcome involved higher activity in bilateral striatum and left AI. These findings collectively suggest shared and distinct regional responses during monetary wins and losses. Delineating the neural correlates of these component processes may facilitate empirical research of motivated behavior and dysfunctional approach and avoidance in psychopathology. HighlightsO_LIWin and loss anticipation both engaged the fronto-striatal-thalamic network. C_LIO_LIWin and loss outcomes shared no regional activities. C_LIO_LIThe mOFC and dACC play distinct roles each in processing win and loss outcome. C_LIO_LIWin and loss anticipation engaged bilateral AI; loss outcome only the right AI. C_LIO_LIWin/loss anticipation vs. outcome engaged predominantly right/left AI. C_LI

neuroscience↗

bioRxiv2022

A pro-oxidant combination of resveratrol and copper down-regulates multiple biological hallmarks of ageing and neurodegeneration

Several hundred billion to a trillion cells die in the body every day, and cell-free chromatin particles (cfChPs) that are released from them enter into the extracellular compartments of the body, including into the circulation. We have earlier reported that cfChPs can readily enter into healthy cells to damage their DNA, activate apoptotic pathways and induce inflammatory cytokines. We hypothesized that repeated lifelong assault on healthy cells by cfChPs is the underlying cause of ageing, and that the ageing process could be retarded by deactivating cfChPs. The latter can be effected by oxygen radicals that are generated upon admixing the nutraceuticals resveratrol (R) and copper (Cu). Using confocal microscopy and antibodies against DNA and histone we detected copious presence of extra-cellular cfChPs in brain of ageing mice, and observed that these were deactivated / eradicated following prolong oral administration of small quantities of R-Cu. Deactivation / eradication of cfChPs was associated with down-regulation of several biological hallmarks of ageing in brain cells which included reduction in: 1) telomere attrition, 2) amyloid deposition, 3) DNA damage, 4) apoptosis, 5) inflammation, 6) senescence, 7) aneuploidy and 8) mitochondrial dysfunction. At a systemic level, R- Cu treatment led to significant reduction in blood levels of glucose, cholesterol and C-reactive protein. These results suggest that cfChPs may be global instigators of ageing and neurodegeneration, and that therapeutic use of R-Cu may help to retard the process of ageing.

neuroscience↗

bioRxiv2022

Fast, Efficient, and Accurate Neuro-Imaging Denoising via Deep Learning

Volumetric functional imaging is widely used for recording neuron activities in vivo, but there exist tradeoffs between the quality of the extracted calcium traces, imaging speed, and laser power. While deep-learning methods have recently been applied to denoise images, their applications to downstream analyses, such as recovering high-SNR calcium traces, have been limited. Further, these methods require temporally-linked pre-registered data with ultrafast rates. Here, we demonstrate supervised deep-denoising methods to circumvent these tradeoffs for several applications, including whole-brain imaging, large field-of-view imaging in freely moving animals, and recovering complex neurite structures in C. elegans. Our framework has 30x smaller memory footprint, and is fast in training and inference (50-70ms); it is highly accurate and generalizable, and further, only small, non-temporally-sequential, independently-acquired training datasets ([~]500 images) are needed. We envision that the framework will enable faster and long-term imaging experiments necessary to study neuronal mechanisms of many behaviors.

neuroscience↗

bioRxiv2021

Proteomic portraits reveal evolutionarily conserved and divergent responses to spinal cord injury

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of CSF and serum samples from 111 acute SCI patients and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at six months with an AUC of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response, and establish the CSF abundance of glial fibrillary acidic protein (GFAP) as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

neuroscience↗

bioRxiv2020

Comprehensive studies of Head Maralla, Punjab, Pakistan vegetation for ethnopharmacological and ethnobotanical uses and their elaboration through quantitative indices

Head Maralla is a non-recognized wetland with diversified flora that becomes focus of current studies. Whole plant or their parts are being used for treating various maladies and they are the integral part of livelihood in the area. Unique species including Osmunda regalis is used for blood and renal diseases purifier. Wild plant resources are key to traditional ethnobotanical knowledge based practices and industrial applications. Current study reports Head Marala inhabitants interaction with these resources and identify priorities at species and habitat level for conservation. Four sites viz., River Tavi, Upstream Chenab, River Manawarwala Tavi and Bhalolpur were designated to record traditional knowledge through questionnaire and interviews during field trips. One hundred nineteen (119) plant species were identified belonging to 54 families, of which 87 species were of dicot, 12monocots, 05ferns, and 4 species of bryophytes. Fifty percent of the plant species were utilized as a whole for therapeutic purposes, followed by leaves which had more than 20% usage of total consumption. Ailments viz., urination (14%) followed by cough (8%), cold (7%), stomach (6%), asthma (6%), constipation (5%), laxative (5%), diarrhea (4%) etc., were associated with vegetation. Bronchial disorders, pneumonia, dyspepsia, anthelmintic and kidney stones, etc., were also among other diseases commonly cured by traditional knowledge. Fifteen percent of vegetation contributes as fodder species consumed by local community for livestock while almost 17% of local plants were utilized for industrial purposes like timber, fuel, furniture, wooden pots and sports goods. In conclusion the ecosystem of Head Maralla is a complex of aquatic, terrestrial and agricultural land that is located on climatic and geographical divides, which further add to botanical interest as included many wetland habitats with unique diversity of plants. It is suggested to devise comprehensive conservation strategies to safe indigenous knowledge in systematic way for comprehending ecological services.

plant biology↗

bioRxiv2020

Multi-omics analysis of aspirin treatment response in mice provide molecular insights and targets linked to liver fibrosis regression.

Background & Aims Aspirin has potent anti-platelet activities and possibly helps regression of fibrosis. We investigated antifibrotic mechanisms of aspirin in the murine CCl4 model and in patients with hepatic fibrosis.Methods Multiomics analysis identified networks and molecular targets regulated by aspirin which were validated in murine model and in patients with liver fibrosis.Results Biochemical/histopathological changes and hepatic fibrosis were greater in CCl4-treated mice compared to CCl4-aspirin (CCl4+ASA) or control mice (p<0.05). In CCl4+ASA mice, integrated proteome-metabolome analysis showed an increase in autophagy, drug metabolism, glutathione and energy metabolism (p<0.05) and decrease in inflammatory pathways, arachidonic acid and butanoate metabolism (p<0.05). Global cross-correlation analysis linked fibrosis markers with protein-metabolite pathways (r2>0.5, p<0.05). Liver proteome enrichment for immune clusters using blood transcription module correlated with histidine and tryptophan metabolism (r2>0.5, p<0.05). Aspirin decreased Ryanodine-receptor-2 (RYR2;oxidative-stress), Arginase-1 (ARG-1;urea cycle), Arachidonate-5-lipoxygenase (ALOX5;leukotriene metabolism), and Kynurenine-3-monooxygenase (KMO;tryptophan metabolism; p<0.05) which correlated with reduction in α-SMA, PDGFR-β and degree of hepatic fibrosis (r2>0.75; p<0.05) in animal and human studies, and, in-vitro analysis. Aspirin modulated intracellular-calcium and oxidative-stress levels by reducing RYR2 expression in activated LX-2 cells. It modulated the liver microbiome and its functions which also correlated with ARG1, ALOX5, RYR2 expression (r2>0.5, p<0.05). Metaproteome analysis showed significant microbiome similarity at phylum level in murine liver tissues and fecal samples. Aspirin increased the abundance of Firmicutes (Ruminococcaceae, Lachnospiraceae, and Clostridiaceae) and their functionality, as assessed by glycerol-3-phosphate dehydrogenase (NAD(P)(+) and dTMP-kinase activity (p<0.05).Conclusions Aspirin demonstrates broad beneficial effects following oxidative injury, inflammation, and hepatic fibrosis. Aspirin induces distinctive hepatic proteome/metabolome and intrahepatic microbiome changes which are indicative of fibrosis regression and could be further explored as therapeutic targets.Competing Interest StatementThe authors have declared no competing interest.View Full Text

molecular biology↗

bioRxiv2020

1q21.3 amplification modulates therapy sensitivity in Triple-Negative Breast Cancer

The contrast in therapy sensitivity and response across triple negative breast cancer (TNBC) patients suggest underlying genotypic heterogeneity. Using publicly available data, we found significant associations between DNA-level copy number alterations of 1q21.3 locus and therapy sensitivity. We show that in spite of their aggressive nature, 1q21.3 amplified tumors are more responsive to commonly used cytotoxic therapies, highlighting the relevance of 1q21.3 copy number status as a genetic marker for risk stratification, therapy selection and response.

cancer biology↗

bioRxiv2020

Automated Annotation of Cell Identities in Dense Cellular Images

Although identifying cell names in dense image stacks is critical in analyzing functional whole-brain data enabling comparison across experiments, unbiased identification is very difficult, and relies heavily on researchers experiences. Here we present a probabilistic-graphical-model framework, CRF_ID, based on Conditional Random Fields, for unbiased and automated cell identification. CRF_ID focuses on maximizing intrinsic similarity between shapes. Compared to existing methods, CRF_ID achieves higher accuracy on simulated and ground-truth experimental datasets, and better robustness against challenging noise conditions common in experimental data. CRF_ID can further boost accuracy by building atlases from annotated data in highly computationally efficient manner, and by easily adding new features (e.g. from new strains). We demonstrate cell annotation in C. elegans images across strains, animal orientations, and tasks including gene-expression localization, multi-cellular and whole-brain functional imaging experiments. Together, these successes demonstrate that unbiased cell annotation can facilitate biological discovery, and this approach may be valuable to annotation tasks for other systems.

neuroscience↗

bioRxiv2018

A novel mutation alters the stability of PapA2 resulting in the complete abrogation of sulfolipids in clinical mycobacterial strains

The analysis of whole genome has revealed specific geographical distribution of Mycobacterium tuberculosis (Mtb) strains across the globe suggestive of unique host dependent adaptive mechanisms in Mtb evolved out of selective pressures. We provide an important correlation of a genome-based mutation to a molecular phenotype across two predominant clinical Mtb lineages of the Indian subcontinent. We have identified a distinct lineage specific mutation-G247C, translating into an alanine to proline conversion in the papA2 gene of Indo oceanic lineage 1 [L1] Mtb strains; restoration of cell wall sulfolipids by simple genetic complementation of papA2 from lineage 3 [L3] or from H37Rv (Lineage 4-L4) attributed the loss of this glycolipid to this specific mutation in Indo oceanic L1 Mtb. Investigation into the structure of Mtb PapA2 revealed a distinct non-ribosomal peptide synthetase (NRPS) C domain conformation with an unconventional presence of Zinc binding motif. Surprisingly, the A83P mutation did not map to either the catalytic centre in the N-terminal subdomain or any of the substrate binding region of the protein. On the contrary, the inherent ability of mutant PapA2 to form insoluble aggregates and molecular simulations with the Wt/ mut PapA2 purports an important role for the surface associated 83rd residue in protein conformation. The present study demonstrates the importance of a critical structural residue in the papA2 protein of Mtb and helps establish a link between observed genomic alteration and its molecular consequence in the successful human pathogen Mtb.

molecular biology↗

bioRxiv2018

Carbonic anhydrase network of genes trigger cytosolic pH enabling differentiation from quiescence

BackgroundCarbonic anhydrase regulates various cellular processes. Intracellular pH flux impacted by carbonic anhydrase alters the enzymes allosteric active site which effects several downstream cellular processes. Earlier, we reported that, the catalytic activity of carbonic anhydrase is independent, but direction of catalysis is affected by cellular pH level. On the other hand carbonic anhydrase alters the cytosolic pH level to facilitate allosteric phosphorylation of proteins which further leads to cellular differentiation through a process being regulated by ncRNAs.\n\nResultsThis study illustrates various ways of cell differentiation/ organ development regulation via carbonic anhydrase interacting network of proteins involved in various cellular processes. It is involved in protein degradation process of other proteins like RPT, 26S proteasome, AT3G15120 and its variant producing ncRNA, etc. Carbonic anhydrase indirectly involved in signaling process along with MAPK in providing innate resistance against biotic and abiotic stresses. It is also indirectly linked to cell membrane transporters like H+-ATPase and V-ATPase B.\n\nConclusionsThough carbonic anhydrase is not directly linked with EMS1 as revealed by network analyses and protein-protein interaction there could be a suitable condition generated by the carbonic anhydrase for EMS1 to be active. Hence, we report that carbonic anhydrase, along with other pH regulating gene complexes plays a major role for making EMS1 functional.

systems biology↗

bioRxiv2018

Fast, versatile, and quantitative annotation of complex images

We report a generic smartphone app for quantitative annotation of complex images. The app is simple enough to be used by children, and annotation tasks are distributed across app users, contributing to efficient annotation. We demonstrate its flexibility and speed by annotating >30,000 images, including features of rice root growth and structure, stem cell aggregate morphology, and complex worm (C. elegans) postures, for which we show that the speed of annotation is >130-fold faster than state-of-the-art techniques with similar accuracy.

bioengineering↗

bioRxiv2018

FabElm_BarcodeDb: matK barcode database of legumes

BackgroundDNA barcoding is an imperative implementation of chloroplast rbcL and matK regions exploited as standard molecular barcodes for species identification. MatK is highly conserved in plants and has been used extensively as a phylogenetic marker for classification of plants. In this study matK sequences of Leguminosae were retrieved for variant analysis and phylogentics. From online resources, maturase sequences were retrieved; redundant sequences and partials along with poor quality reads were filtered to compile 3639 complete non-redundant matK sequences and constructed into a database for ready reference. The database FabElm_BarcodeDb made available at app.bioelm.com was constructed using available sequence resources.\n\nResultsThe chloroplast genome of plants contains matK gene of 1500 bp, positioned between intron of trnK associated in-group II intron splicing. Mitochondrial matR and genomic matN sequences were compared with chloroplast matK. These maturase sequences share regions of homology with chloroplast and mitochondrial regions and are expected to be regulated by miRNA in producing splice variants contributing to speciation.\n\nConclusionBase substitution rates of nuclear maturase were comparable with mitochondrial maturase and are different from matK sequences. Hence, few identified species in this investigation were clustered with other tribes when analysed using matK. MatK is effective in resolving the species level variations as splicing contributes to speciation; but utilization of matK alone as a barcode marker for legumes is dubious, as it could not resolve some species identity.\n\nAbbreviations

plant biology↗