Biology subjects

Sharma, V. K.

Publications and source records attributed to Sharma, V. K..

30 records · Page 2Linked to original sources

bioRxiv2022

Adaptive Immune Landscape of T-Cell Mediated Rejection of Human Kidney Allografts

The frequently occurring T cell mediated rejection (TCMR) is a risk factor for allograft failure. Immunosuppressive therapy fails to reverse almost 40% of TCMRs occurring in human kidney allografts. A better understanding of the molecular mechanisms of TCMR and precision therapeutics may improve allograft longevity. We investigated adaptive immune landscape of TCMR by genome wide RNA sequencing of 34 prototypic kidney allograft biopsies from 34 adult recipients of human kidney allografts. Sixteen of the 34 biopsies were categorized as Banff TCMR and the remaining 18 as Banff Normal biopsies. Computational analysis identified higher intragraft abundance of the gene sets for key players of adaptive immune system in TCMR. TCMR allografts were characterized by, i) increased antigen processing and presentation and T cell receptor signaling, ii) increased memory T cells, Tregs, Th1, Th2 and Th17 subsets, iii) increased aerobic glycolysis of lymphocytes and reduced metabolic activity of graft parenchymal cells, iv) increased T cell inhibitory receptors and exhaustion markers, v) increased apoptosis and necroptosis, and vi) increased extracellular matrix remodeling, all in comparison to Normal biopsies. Our genome-wide transcriptomics provides an atlas of adaptive immune landscape of TCMR in human kidney allografts, help deduce molecular mechanisms and prioritization of therapeutic targets.

immunology↗

bioRxiv2021

Genome sequencing and comparative analysis of Ficus benghalensis and Ficus religiosa trees reveal evolutionary mechanisms of longevity

Ficus benghalensis (Indian banyan tree) and Ficus religiosa (Peepal) trees are well-known for their long lifespan, traditional significance, and medicinal properties. Therefore, to understand the genomic and evolutionary aspect of these characteristics the whole genomes of these two Ficus species were sequenced using 10x Genomics and Oxford Nanopore sequencing platforms. The draft genome assemblies of F. benghalensis (392.89 Mbp genome containing 25,016 high-confidence coding genes), and F. religiosa (332.97 Mbp genome containing 23,929 high-confidence coding genes) were constructed. We also established the genome-wide phylogenetic position of the two Ficus trees with respect to 46 other Angiosperm plant species and studied the comparative population demographic history of these two species to show a population bottleneck event ~0.8 Mya for both the species. We also identified 7,468 orthogroups across 16 phylogenetically closer Eudicot plant species including F. benghalensis and F. religiosa. Comparative evolutionary analyses using these orthogroups, gene family expansion/contraction analysis, and gene duplication analysis showed adaptive evolution in genes involved in cellular pathways and mechanisms that are central to plant growth and development and provide genomic insights into longevity and ecological significance of these large woody trees.

genomics↗

bioRxiv2021

ATR facilitates the degradation of Api5 through the ubiquitin-proteasome pathway via FBXW2 to regulate apoptosis upon DNA damage

Apoptosis inhibitor 5 (Api5) is an inhibitor of apoptosis, which is found to be upregulated in several cancers and promotes invasion as well as metastasis. Over-expression of Api5 is positively co-related with poor survival of cancers and inhibition of DNA damage induced apoptosis in cancerous cells. Acetylation at lysine 251 (K251) on Api5 facilitates the stability of the protein and thus functionally provides resistance to cancer cells against chemotherapeutic or anti-cancerous agents. However, the regulation of Api5 upon DNA damage is not yet known. In this study, we demonstrate that Api5 undergoes degradation following DNA damage via the ubiquitin-proteasome system. Upon DNA damage, ATR was observed to phosphorylate Api5 at serine 138 which led to the cytoplasmic localisation of Api5. The E3-ubiquitin ligase, SCF-FBXW2 ubiquitinates Api5 leading to its proteasomal degradation.

molecular biology↗

bioRxiv2021

Genome sequencing and assembly of Tinospora cordifolia (Giloy) plant

During the ongoing COVID-19 pandemic Tinospora cordifolia also known as Giloy gained immense popularity and use due to its immunity-boosting function and anti-viral properties. T. cordifolia is among the most important medicinal plants that has numerous therapeutic applications in health due to the production of a diverse array of secondary metabolites. Therefore, to gain genomic insights into the medicinal properties of T. cordifolia, the first genome sequencing was carried out using 10x Genomics linked read technology and the draft genome assembly comprised of 1.01 Gbp. This is also the first genome sequenced from the plant family Menispermaceae. We also performed the first genome size estimation for T. cordifolia and was found to be 1.13 Gbp. The deep sequencing of transcriptome from the leaf tissue was also performed followed by transcriptomic analysis to gain insights into the gene expression and functions. The genome and transcriptome assemblies were used to construct the gene set in T. cordifolia that resulted in 19,474 coding gene sequences. Further, the phylogenetic position of T. cordifolia was also determined through the construction of a genome-wide phylogenetic tree using 35 other dicot species and one monocot species as an outgroup species.

genomics↗

bioRxiv2021

Draft genome assembly data of Anoxybacillus sp. strain MB8 isolated from Tattapani hot springs, India

Discovery of novel thermophiles has shown promising applications in the field of biotechnology. Due to their thermal stability, they can survive the harsh processes in the industries, which make them important to be characterized and studied. Members of Anoxybacillus are alkaline tolerant thermophiles and have been extensively isolated from manure, dairy-processed plants, and geothermal hot springs. This article reports the assembled data of an aerobic bacterium Anoxybacillus sp. strain MB8, isolated from the Tattapani hot springs in Central India, where the 16S rRNA gene shares an identity of 97% (99% coverage) with Anoxybacillus kamchatkensis strain G10. The de novo assembly and annotation performed on the genome of Anoxybacillus sp. strain MB8 comprises of 2,898,780 bp (in 190 contigs) with a GC content of 41.8% and includes 2,976 protein-coding genes,1 rRNA operon, 73 tRNAs, 1 tm-RNA and 10 CRISPR arrays. The predicted protein-coding genes have been classified into 21 eggNOG categories. The KEGG Automated Annotation Server (KAAS) analysis indicated the presence of assimilatory sulfate reduction pathway, nitrate reducing pathway, and genes for glycoside hydrolases (GHs) and glycoside transferase (GTs). GHs and GTs hold widespread applications, in the baking and food industry for bread manufacturing, and in the paper, detergent and cosmetic industry. Hence, Anoxybacillus sp. strain MB8 holds the potential to be screened and characterized for such commercially relevant enzymes. Specifications Table O_TBL View this table: org.highwire.dtl.DTLVardef@46be2org.highwire.dtl.DTLVardef@46fbe2org.highwire.dtl.DTLVardef@42cc37org.highwire.dtl.DTLVardef@16d5912org.highwire.dtl.DTLVardef@1f2bcdc_HPS_FORMAT_FIGEXP M_TBL C_TBL Values of DataO_LIThe Anoxybacillus sp. strain MB8 genome assembly data provides insights into functional potential of thermophilic enzymes of this thermotolerant microbe. C_LIO_LIThe presence of genes for Glycoside Hydrolase (GHs) like alpha-amylase, pullulanase, neopullulanase, alpha-glucosidase, beta-fructofuranosidase etc. and genes for Glycosyl Transferase (GTs) like sucrose synthase, maltodextrin phosphorylase, starch synthase, and glycogen phosphorylase were identified, which hold strong industrial values. C_LIO_LIThe taxonomic annotation of Anoxybacillus sp. strain MB8 using different approaches indicates that the closest relatives were Anoxybacillus gonensis NZ CP012152T (96.86% ANI) and Anoxybacillus kamchatkensis G10 NZ CP025535 (96.83% ANI) obtained from. The strain MB8 most likely belongs to the same subspecies of Anoxybacillus gonensis NZ CP012152T. C_LI

genomics↗

bioRxiv2020

Interplay between p300 and HDAC1 regulate acetylation and stability of Api5 to regulate cell proliferation

Api5, is a known anti-apoptotic and nuclear protein that is responsible for inhibiting cell death in serum-starved conditions. The only known post-translational modification of Api5 is acetylation at lysine 251 (K251). K251 acetylation of Api5 is responsible for maintaining its stability while de-acetylated form of Api5 is unstable. This study aimed to find out the enzymes regulating acetylation and deacetylation of Api5 and the effect of acetylation on its function. Our studies suggest that acetylation of Api5 at lysine 251 is mediated by p300 histone acetyltransferase while de-acetylation is carried out by HDAC1. Inhibition of acetylation by p300 leads to reduction in Api5 levels while inhibition of deacetylation by HDAC1 results in increased levels of Api5. This dynamic switch between acetylation and deacetylation regulate the localization of Api5 in the cell. This study also demonstrates that the regulation of acetylation and deacetylation of Api5 is an essential factor for the progression of the cell cycle.

molecular biology↗

bioRxiv2020

Genome sequencing of turmeric provides evolutionary insights into its medicinal properties

Curcuma longa, or turmeric, is traditionally known for its immense medicinal properties and has diverse therapeutic applications. However, the absence of a reference genome sequence is a limiting factor in understanding the genomic basis of the origin of its medicinal properties. In this study, we present the draft genome sequence of Curcuma longa, the first species sequenced from Zingiberaceae plant family, constructed using 10x Genomics linked reads. For comprehensive gene set prediction and for insights into its gene expression, the transcriptome sequencing of leaf tissue was also performed. The draft genome assembly had a size of 1.24 Gbp with ~74% repetitive sequences, and contained 56,036 coding gene sequences. The phylogenetic position of Curcuma longa was resolved through a comprehensive genome-wide phylogenetic analysis with 16 other plant species. Using 5,294 orthogroups, the comparative evolutionary analysis performed across 17 species including Curcuma longa revealed evolution in genes associated with secondary metabolism, plant phytohormones signaling, and various biotic and abiotic stress tolerance responses. These mechanisms are crucial for perennial and rhizomatous plants such as Curcuma longa for defense and environmental stress tolerance via production of secondary metabolites, which are associated with the wide range of medicinal properties in Curcuma longa.

genomics↗

bioRxiv2020

The genome sequence of Aloe vera reveals adaptive evolution of drought tolerance mechanisms

Aloe vera is a species from Asphodelaceae plant family having unique characteristics such as drought resistance and also possesses numerous medicinal properties. However, the genetic basis of these phenotypes is yet unknown, primarily due to the unavailability of its genome sequence. In this study, we report the first Aloe vera draft genome sequence comprising of 13.83 Gbp and harboring 86,177 coding genes. It is also the first genome from the Asphodelaceae plant family and is the largest angiosperm genome sequenced and assembled till date. Further, we report the first genome-wide phylogeny of monocots with Aloe vera using 1,440 one-to-one orthologs that resolves the genome-wide phylogenetic position of Aloe vera with respect to the other monocots. The comprehensive comparative analysis of Aloe vera genome with the other available high-quality monocot genomes revealed adaptive evolution in several genes of the drought stress response, CAM pathway, and circadian rhythm in Aloe vera. Further, genes involved in DNA damage response, a key pathway in several biotic and abiotic stress response mechanisms, were found to be positively selected. This provides the genetic basis of the evolution of drought stress tolerance capabilities of Aloe vera. This also substantiates the previously suggested notion that the evolution of unique characters in this species is perhaps due to selection and adaptive evolution rather than the phylogenetic divergence or isolation.

genomics↗

bioRxiv2020

LC/MS-QToF Profiling, Anti-Diabetic and Anti-Adipogenic potential of Divya MadhuKalp: A Novel Herbo-mineral Formulation

The incidence rate of diabetes mellitus is increasing worldwide. Herbal formulations have recently gained importance as an alternative therapeutic option in controlling diabetes without causing any side effects. In the present study, we have demonstrated maintenance of glycemic homeostasis and anti-adipogenic potential of a herbo-mineral formulation Divya MadhuKalp (DMK). Initially, we evaluated the presence of bioactive compounds in DMK using LC/MS-QToF analysis. In-vitro analysis of DMK in L6 (skeletal muscle) cells showed a significant increase in cellular glucose uptake. Similarly, a human equivalent dose of DMK significantly reduced blood glucose level in normoglycemic and oral glucose tolerance rat model. DMK extract also inhibited formation of advanced glycation end product and showed anti--glucosidase activity. Further analysis of DMK in 3T3 L1 pre-adipocytes demonstrated anti-adipogenic activity through reduction in intracellular lipid accumulation and triglyceride contents along with downregulation of major adipogenic transcriptional factors (PPAR-{gamma} and C/EBP) and, adipocytes marker genes (LPL, AP2 and adiponectin). In conclusion, DMK exhibited anti-diabetic and anti-adipogenic activities by synergistic effect of its bioactive compounds and can be considered as a potent herbo-mineral formulation for treating metabolic diseases.

cell biology↗

bioRxiv2019

Mechanosensory stimulation via Nanchung expressing neurons can induce daytime sleep in Drosophila

The neurogenetic bases of sleep, a phenomenon considered crucial for well-being of organisms has recently been under investigation using the model organism Drosophila melanogaster. Although sleep is a state where sensory threshold for arousal is enhanced, it is known that certain kinds of repetitive sensory stimuli such as rocking, can in fact promote sleep in humans. Here we report that orbital motion aided mechanosensory stimulation promotes sleep in Drosophila, independent of the circadian clock, but controlled by the homeostatic system. Mechanosensory receptor nanchung (Nan) expressing neurons in the chordotonal organs mediate this sleep induction - flies where these neurons are either silenced or ablated display significantly reduced sleep induction upon mechanosensory stimulation. Transient activation of the Nan-expressing neurons also enhances sleep levels confirming the role of these neurons in sleep induction. Thus, we show for the first time that mechanosensory stimulation promotes sleep even in flies D. melanogaster and that it is mediated by proprioceptors.

neuroscience↗

bioRxiv2019

Comparative analysis of corrected tiger genome provides clues to their neuronal evolution

The availability of completed and draft genome assemblies of tiger, leopard, and other felids provides an opportunity to gain comparative insights on their unique evolutionary adaptations. However, genome-wide comparative analyses are very sensitive to errors in genome sequences and thus require accurate genomic assemblies for reliable evolutionary insights. In this study, while analyzing the tiger genome, we found almost one million erroneous substitutions in the coding and non-coding region of the genome affecting 4,472 genes, hence, biasing the current understanding of tiger evolution. Moreover, these errors produced several misleading observations in previous studies. Thus, to gain insights into the tiger evolution, we corrected the erroneous bases in the genome assembly and gene set of tiger, which was also validated by resequencing of a Bengal tiger genome and transcriptome. A comprehensive evolutionary analysis was performed using 10,920 orthologs from nine mammalian species including the corrected gene sets of tiger and leopard, and using five different methods at three hierarchical levels i.e. felids, Panthera, and tiger. The unique genetic changes in tiger revealed that the genes showing the signatures of adaptation in tiger were enriched in development and neuronal functioning. Specifically, the genes belonging to Notch signalling pathway, which is among the most conserved pathways involved in embryonic and neuronal development, were found to be significantly diverged in tiger in comparison to the other mammals. Our findings suggest the role of adaptive evolution in neuronal functions and development processes, which correlates well with the presence of exceptional traits such as sensory perception, strong neuro-muscular coordination, and hypercarnivorous behavior in tiger.

genomics↗

bioRxiv2018

Genome Sequence of Indian Peacock Reveals the Peculiar Case of a Glittering Bird

The unique ornamental features and extreme sexual traits of Peacock have always intrigued the scientists. However, the genomic evidence to explain its phenotype are yet unknown. Thus, we report the first genome sequence and comparative analysis of peacock with the available high-quality genomes of chicken, turkey, duck, flycatcher and zebra finch. The candidate genes involved in early developmental pathways including TGF-{beta}, BMP, and Wnt signaling pathway, which are also involved in feather patterning, bone morphogenesis, and skeletal muscle development, showed signs of adaptive evolution and provided useful clues on the phenotype of peacock. The innate and adaptive immune components such as complement system and T-cell response also showed signs of adaptive evolution in peacock suggesting their possible role in building a robust immune system which is consistent with the between species predictions of Hamilton-Zuk hypothesis. This study provides novel genomic and evolutionary insights into the molecular understanding towards the phenotypic evolution of Indian peacock.

genomics↗