Biology subjects

Rathore, A.

Publications and source records attributed to Rathore, A..

11 recordsLinked to original sources

bioRxiv2026

Decoding the role of ADAptor2 (ADA2) of HAT complex in autophagy and phospholipid metabolism to maintain ER homeostasis and triterpene regulation

In yeast, transcriptional adaptor 2 (ADA2; SAGA complex subunit ADA2), a member of histone acetyltransferase (HAT) complex, regulates transcription through cell signalling, but its precise role in cellular metabolism remains unclear. In this study, genetic loss of ADA2 (ada2{Delta}) induces squalene (SQ) accumulation, indicating aberrant triterpene metabolism, coupled with endoplasmic reticulum (ER)/nuclear ER (nER) expansion. Lipid analyses of ada2{Delta} revealed elevated phosphatidic acid (PA) and phosphatidylcholine (PC) levels, indicating disrupted phospholipid metabolism. The expanded ER causes basal autophagy elevation, cellular recycling, and nER phagy, suggesting a regulatory role for ADA2 in autophagy. Downregulation of phosphatidate cytidylyltransferase (CDS1) and inositol-3-phosphate synthase (INO1), coupled with elevated PA and PC in ada2{Delta}, points to a significant disruption in cytidine-diphosphate-diacylglycerol and phosphatidylinositol pathway. Overexpression of CDS1 or INO1, or the inositol supplementation, in ada2{Delta} restores SQ, basal autophagy and ER phagy. The observed target of rapamycin Ser/Thr kinase complex (TORC1) activity in ada2{Delta} is due to the high PA content. Rapamycin-mediated inhibition of TORC1 reduced SQ, PA and ER expansion while increasing lipid droplets. In contrast, a rapamycin-treated ada2{Delta}pah1{Delta} strain retained high PA, SQ and ER expansion, underscoring the functional role of TORC1-nuclear envelope morphology protein 1 (Nem1)/sporulation-specific protein SPO7 (Spo7)-Pah1 axis. Notably, SQ levels remained unchanged in a rapamycin-treated ada2{Delta}atg39{Delta} strain, suggesting that loss of nER-phagy receptor, Atg39, impairs the effectiveness of TORC1 inhibition. In conclusion, our data unveiled a critical role for Ada2 in maintaining the intricate relationship between lipid and triterpene/sterol metabolism and connecting autophagy and ER homeostasis.

biochemistry↗

bioRxiv2024

Patterns of leaf, flower and fruit phenology and environmental relationships in a seasonal tropical forest in the Indian Eastern Himalaya

Tree phenology plays an important role in determining the structure and function of tropical forest communities. However, there are few long-term studies on tree phenology from South Asia. We monitored 716 trees of 54 species monthly from 2011 to 2023 for leaf flush, flowering, and fruiting in Pakke Tiger Reserve, Arunachal Pradesh, India. We examined monthly patterns in the percentage of species and trees in leaf flush, flower and fruit and characterized phenological seasonality using circular statistics. Flowering periodicity was classified using Fourier analysis and we examined the relationships between phenological activity and temperature, rainfall, solar radiation and daylength using GAMLSS. Leaf flush and flowering were moderately seasonal, peaking in the warm dry season months of March to May. Fruiting patterns and their seasonality differed among dispersal modes. At the community level and for bird-dispersed species, fruiting was bimodal and relatively aseasonal, peaking in April and October. The highly seasonal fruiting of mammal-dispersed species peaked in October, while that of mechanically-dispersed species was bimodal and concentrated in the dry season months. The majority of species (78.13%) and trees (51.17%) flowered annually. Daylength, solar radiation and minimum temperature had significant nonlinear effects on phenology. This indicated the existence of narrow ranges of optimal climatic conditions for phenology, which could be affected by climate change. Our study emphasizes the need for long-term monitoring to rigorously quantify phenological patterns, particularly in the context of rapid global change.

plant biology↗

bioRxiv2023

Leadership and information transfer in groups escaping a (simulated) threat in the wild

Collective motion in many species is believed to be driven by predation, which is considered a crucial evolutionary force. However, there are limited studies on how information about predators spreads through a group, particularly in natural settings. Here, using high-resolution drone-based recordings, we analyze the collective escape dynamics of a group living species - blackbuck (Antilope cervicara), an Indian antelope - under the conditions of a simulated threat in their natural grassland habitat. Our analysis reveals that, in response to the simulated threat, group cohesion first increases, followed by a simultaneous increase in median speed and polarization. We also observe the emergence of a temporary leader-follower relationship during the collective escape. Interestingly, we found that the distance of individuals from the "predator" affected only their response time, not their influence on the group movement. The individuals furthest from the threat were the least likely to initiate movement and were uncoordinated with the groups speed. Additionally, we discovered that the most influential individuals during the collective escape were the least likely to occupy front positions during group movement. Instead, our results indicate that individuals at the rear "push" individuals at the front during collective escape events. This contrasts with the typical notion of individuals at the front determining group movement and those at the back trying to catch up.

animal behavior and cognition↗

bioRxiv2023

Metabolic alterations unravel the materno fetal immune responses with disease severity in pregnant women infected with SARS-CoV-2

BackgroundPregnancy being immune compromised state, COVID-19 disease poses high risk of premature delivery and threat to fetus. Plasma metabolome regulates immune cellular responses and we aimed to analyze the plasma secretome, metabolome and immune cells in COVID-19 positive pregnant mother and cord blood. MethodsCOVID-19 RT-PCR positive pregnant females (n=112) asymptomatic (n=82), or with mild (n=21) or moderate (n=9) disease and control healthy pregnant (n=10) females were included. Mothers blood and cord blood (n=80) was analysed for untargeted metabolome profiling and plasma cytokines by high-resolution mass spectrometry (MS) and multiplex cytokine bead array. Immune scan in mothers was done using flow cytometry. ResultsIn asymptomatic SARS-CoV-2 infection, --the amino acid metabolic pathways such as glycine, serine, L-lactate and threonine metabolism was upregulated, riboflavin and tyrosine metabolism, downregulated. In mild to moderate disease, the pyruvate and NAD+ metabolism (energy metabolic pathways) were mostly altered. In addition to raised TNF-, IFN-, IFN-{gamma}, IL-6 cytokine storm, IL-9 was increased in both mothers and neonates. Pyruvate and NAD+ metabolic pathways along with IL-9 and IFN-{gamma} had impact on non-classical monocytes, increased CD4 T cells and B cells but depleted CD8+ T cells. Cord blood mimicked the mothers metabolomic profiles by showing altered valine, leucine, isoleucine, glycine, serine, threonine in asymptomatic and NAD+ and riboflavin metabolism in mild and moderate disease subjects. ConclusionsOur results demonstrate a graduated immune-metabolomic interplay in mother and fetus in pregnant females with different degrees of severity of COVID-19 disease. IL-9 and IFN- {gamma} regulated pyruvate, lactate TCA metabolism and riboflavin metabolism with context to disease severity are hall marks of this materno-fetal metabolome. HighlightsO_LISARS-CoV-2 infection alters energy consumption metabolic pathways during pregnancy. C_LIO_LIPregnant women with mild to moderate COVID-19 show increased energy demands, and consume stored glucose by upregulating pyruvate and NAD+ metabolism. C_LIO_LIIncreased TNF- and IL-9 in mild COVID-19 disease involve TCA cycle to produce lactate and consume stored glucose by up regulating pyruvate and nicotinamide and nicotinate metabolism. C_LIO_LIWith mild to moderate disease, raised IL-9 and TNF-, decreased riboflavin pathway, exhaustion of T and B cells cause pathogenesis. C_LIO_LICord blood mimics the metabolic profile of mothers peripheral blood, SARS- CoV-2 infection reshapes immune-metabolic profiles of mother-infant dyad. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=141 HEIGHT=200 SRC="FIGDIR/small/540101v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@657cc3org.highwire.dtl.DTLVardef@e1e76forg.highwire.dtl.DTLVardef@12153f2org.highwire.dtl.DTLVardef@10e5332_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2022

DeepVariant calling provides insights into race diversity and its implication for sorghum breeding

Due to evolutionary divergence, sorghum race populations exhibit vast genetic and morphological variations. A k-mer-based sorghum race sequence comparison identified the conserved k-mers of all sorghum race accessions and the race-specific genetic signatures identified the gene variability in 10,321 genes (PAVs). To understand the sorghum race structure, diversity and domestication, deep learning-based variant calling approach was employed in a set of genotypic data derived from a diverse panel of 272 sorghum accessions. The data resulted in 1.7 million high-quality genome-wide SNPs and identified selective signature (both positive and negative) regions through a genome-wide scan with different (iHS and XP-EHH) statistical methods. We discovered 2,370 genes associated with selection signatures including 179 selective sweep regions distributed over 10 chromosomes. Localization of these regions undergoing selective pressure with previously reported QTLs and genes revealed that the signatures of selection could be related to the domestication of important agronomic traits such as biomass and plant height. The developed k-mer signatures will be useful in the future to identify the sorghum race and SNP markers assist in plant breeding programs.

plant biology↗

bioRxiv2021

Sorghum pan-genome explores the functional utility to accelerate the genetic gain

Sorghum (Sorghum bicolor L.) is one of the most important food crops in the arid and rainfed production ecologies. It is a part of resilient farming and is projected as a smart crop to overcome the food and nutritional challenges in the developing world. The development and characterisation of the sorghum pan-genome will provide insight into genome diversity and functionality, supporting sorghum improvement. We built a sorghum pan-genome using reference genomes as well as 354 genetically diverse sorghum accessions belonging to different races. We explored the structural and functional characteristics of the pan-genome and explain its utility in supporting genetic gain. The newly-developed pan-genome has a total of 35,719 genes, a core genome of 16,821 genes and an average of 32,795 genes in each cultivar. The variable genes are enriched with environment responsive genes and classify the sorghum accessions according to their race. We show that 53% of genes display presence-absence variation, and some of these variable genes are predicted to be functionally associated with drought traits. Using more than two million SNPs from the pan-genome, association analysis identified 398 SNPs significantly associated with important agronomic traits, of which, 92 were in genes. Drought gene expression analysis identified 1,788 genes that are functionally linked to different conditions, of which 79 were absent from the reference genome assembly. This study provides comprehensive genomic diversity resources in sorghum which can be used in genome assisted crop improvement.

bioinformatics↗

bioRxiv2020

Microbial metabolites of flavanols in urine are associated with enhanced anti-proliferative activity in bladder cancer cells in vitro

Dietary flavanols and their metabolites are excreted primarily via the urine, suggesting uroepithelial cells as a site of activity due to lengthy exposure to high concentrations of these compounds. Flavanols are metabolized by the gut microbiota to numerous bioavailable metabolites. The observed effects of flavanols, including cancer chemoprevention, may be due in part to the activities of microbial metabolites. Most in vitro mechanistic work in this area relies on a limited pool of commercially available or synthesized flavanol microbial metabolites, and little work has been done in the area of bladder cancer. The impact of physiologically relevant mixtures of native flavanols and their metabolites generated in vivo remains unknown. Rats were fed various flavanols after which 48 h urine samples, approximating the total bioavailable metabolome, were collected. Urine samples were profiled by UPLC-MS/MS, and their anti-proliferative activities were assayed in vitro in four bladder cancer cell models. Significant interindividual variability was observed for chemical profiles and anti-proliferative activities. Concentrations of microbial metabolites (valerolactones, phenylalkyl acids and hippuric acids) were positively associated with reduced bladder cancer cell proliferation in vitro, while native flavanols were poorly correlated with activity. These results suggest that microbial metabolites may be the primary compounds responsible for chemoprevention in uroepithelial cell following flavanol consumption. Furthermore, this highlights the potential for exploiting knowledge about individual genetics, microbiome profiles, flavonoid metabolism profiles, tumor characteristics, etc. to design personalized dietary interventions for cancer prevention and/or adjuvant therapy to reduce bladder cancer incidence and improve outcomes.

cancer biology↗

bioRxiv2020

Patterns of roost site use by Asian hornbills and implications for seed dispersal

Animals spend a significant amount of time roosting. Therefore, understanding roosting patterns and the processes that influence roosting behaviour and roost site choice is essential. Hornbills exhibit interesting roosting patterns with some species roosting communally in large flocks. They are important seed dispersers and patterns of roost site use can have a significant influence on seed dispersal distributions and thereby on plant recruitment. We documented roost site use by four Great Hornbills (Buceros bicornis) and one Wreathed Hornbill (Rhyticeros undulatus) at a site in north-east India using GPS telemetry. We examined the influence of riverine habitats, nests and foraging range on roost selection. We determined the proportion of seeds that hornbills disperse at roosts and the dispersal distances of seeds dispersed at roosts from the source trees. Through telemetry, we found that roosts of Great Hornbills were generally in forested habitats. Our telemetry data showed that Wreathed Hornbill roosts were close to the river. These results were corroborated by observational data from roost sites where we had regular detections of relatively large flocks of Wreathed Hornbills and occasionally Great Hornbills. The roost sites were not close to the nest sites and were generally within the 95% kernel density diurnal activity ranges. Hornbills dispersed a small proportion of seeds at roost sites. Seeds dispersed at roost sites had almost twice the dispersal distances compared to those dispersed at non-roost sites. This study highlights variation in roost site pattern across individual hornbills and its implications for seed dispersal.

ecology↗

bioRxiv2020

Multi-Object Tracking in Heterogeneous environments (MOTHe) for animal space-use studies

O_LIVideo recordings of animals are used for many areas of research such as collective movement, animal space-use, animal censuses and behavioural neuroscience. They provide us with behavioural data at scales and resolutions not possible with manual observations. Many automated methods are being developed to extract data from these high-resolution videos. However, the task of animal detection and tracking for videos taken in natural settings remains challenging due to heterogeneous environments. C_LIO_LIWe present an open-source end-to-end pipeline called Multi-Object Tracking in Heterogenous environments (MOTHe), a python-based application that uses a basic convolutional neural network for object detection. MOTHe allows researchers with minimal coding experience to track multiple animals in their natural habitats. It identifies animals even when individuals are stationary or partially camouflaged. C_LIO_LIMOTHe has a command-line-based interface with one command for each action, for example, finding animals in an image and tracking each individual. Parameters used by the algorithm are well described in a configuration file along with example values for different types of tracking scenario. MOTHe doesnt require any sophisticated infrastructure and can be run on basic desktop computing units. C_LIO_LIWe demonstrate MOTHe on six video clips from two species in their natural habitat - wasp colonies on their nests (up to 12 individuals per colony) and antelope herds in four different types of habitats (up to 156 individuals in a herd). Using MOTHe, we are able to detect and track all individuals in these animal group videos. MOTHes computing time on a personal computer with 4 GB RAM and i5 processor is 5 minutes for a 30-second long ultra-HD (4K resolution) video recorded at 30 frames per second. C_LIO_LIMOTHe is available as an open-source repository with a detailed user guide and demonstrations at Github (https://github.com/tee-lab/MOTHe). C_LI

ecology↗

bioRxiv2019

A sorghum Practical Haplotype Graph facilitates genome-wide imputation and cost-effective genomic prediction

Successful management and utilization of increasingly large genomic datasets is essential for breeding programs to increase genetic gain and accelerate cultivar development. To help with data management and storage, we developed a sorghum Practical Haplotype Graph (PHG) pangenome database that stores all identified haplotypes and variant information for a given set of individuals. We developed two PHGs in sorghum, one with 24 individuals and another with 398 individuals, that reflect the diversity across genic regions of the sorghum genome. 24 founders of the Chibas sorghum breeding program were sequenced at low coverage (0.01x) and processed through the PHG to identify genome-wide variants. The PHG called SNPs with only 5.9% error at 0.01x coverage - only 3% lower than its accuracy when calling SNPs from 8x coverage sequence. Additionally, 207 progeny from the Chibas genomic selection (GS) training population were sequenced and processed through the PHG. Missing genotypes in the progeny were imputed from the parental haplotypes available in the PHG and used for genomic prediction. Mean prediction accuracies with PHG SNP calls range from 0.57-0.73 for different traits, and are similar to prediction accuracies obtained with genotyping-by-sequencing (GBS) or markers from sequencing targeted amplicons (rhAmpSeq). This study provides a proof of concept for using a sorghum PHG to call and impute SNPs from low-coverage sequence data and also shows that the PHG can unify genotype calls from different sequencing platforms. By reducing the amount of input sequence needed, the PHG has the potential to decrease the cost of genotyping for genomic selection, making GS more feasible and facilitating larger breeding populations that can capture maximum recombination. Our results demonstrate that the PHG is a useful research and breeding tool that can maintain variant information from a diverse group of taxa, store sequence data in a condensed but readily accessible format, unify genotypes from different genotyping methods, and provide a cost-effective option for genomic selection for any species.

genomics↗

bioRxiv2019

The pneumococcal two-component system VisRH is linked to enhanced intracellular survival of Streptococcus pneumoniae in influenza-infected pneumocytes

The virus-bacterial synergism implicated in secondary bacterial infections caused by Streptococcus pneumoniae following infection with epidemic or pandemic influenza A virus (IAV) is well documented. However, the molecular mechanisms behind such synergism remain largely ill-defined. In pneumocytes infected with influenza A virus, subsequent infection with S. pneumoniae leads to enhanced pneumococcal intracellular survival. The pneumococcal two-component system VisRH appears essential for such enhanced survival. Through comparative transcriptomic analysis between the {Delta}visR and wt strains, a list of 179 differentially expressed genes was defined. Among those, the clpL protein chaperone gene and the psaB Mn+2 transporter gene, which are involved in the stress response, are important in enhancing S. pneumoniae survival in influenza-infected cells. The {Delta}visR, {Delta}clpL and {Delta}psaB deletion mutants display increased susceptibility to acidic and oxidative stress and no enhancement of intracellular survival in IAV-infected pneumocyte cells. These results suggest that the VisRH two-component system senses IAV-induced stress conditions and controls adaptive responses that allow survival of S. pneumoniae in IAV-infected pneumocytes.\n\nAuthor summaryS. pneumoniae is an inhabitant of the human nasopharynx that is capable of causing a variety of infections contributing to an estimated 1.6 million deaths each year. Many of these deaths occur as result of secondary S. pneumoniae infections following seasonal or pandemic influenza. Although S. pneumoniae is considered a typical extracellular pathogen, an intracellular survival mechanism has been more recently recognized as significant in bacterial pathogenesis. The synergistic effects between influenza A and S. pneumoniae in secondary bacterial infection are well documented; however, the effects of influenza infections on intracellular survival of S. pneumoniae are ill-defined. Here, we provide evidence that influenza infection increases S. pneumoniae intracellular survival in pneumocytes. We demonstrate that the poorly understood VisRH signal transduction system in pneumococcus controls the expression of genes involved in the stress response that S. pneumoniae needs to increase intracellular survival in influenza A-infected pneumocytes. These findings have important implications for understanding secondary bacterial pathogenesis following influenza and for the treatment of such infections in influenza-stricken patients.

microbiology↗