Biology subjects

Chandra, K.

Publications and source records attributed to Chandra, K..

16 recordsLinked to original sources

bioRxiv2026

Gene duplication and retrotransposition diversify the antiviral repertoire of macaque IFITM proteins

Interferon-induced transmembrane (IFITM) proteins are broad-spectrum antiviral restriction factors that inhibit viral entry of diverse enveloped viruses. Comparative genomic studies have revealed extensive lineage-specific diversification of IFITM genes, yet the functional consequences of this diversification remain poorly understood. We previously identified an expanded IFITM repertoire in macaques consisting of the canonical IFITM proteins, IFITM1 and IFITM3, a duplicated IFITM3 paralog (IFITM3A), and two retrotransposed IFITM3-derived genes (IFITM3-R1 and IFITM3-R2). Here, we thoroughly characterized the antiviral activities, intracellular localization, and mechanisms of regulation of canonical and non-canonical macaque IFITMs against vesicular stomatitis virus (VSV), influenza A virus (IAV), Sendai virus, and HIV-1. IFITM3A exhibited enhanced antiviral activity relative to IFITM3, particularly against VSV and HIV-1. Comparative mutational analyses identified amino acid substitutions in IFITM3 that contribute to the enhanced antiviral phenotype of IFITM3A. In contrast, the retrocopy IFITM3-R1 exhibited markedly reduced expression due to lysosome-dependent protein turnover mediated by a PPxY motif and a unique lysine residue (K51). Alteration of these determinants increased IFITM3-R1 expression and selectively enhanced restriction of VSV and IAV. Although several macaque IFITMs reduced HIV-1 infectivity when expressed in producer cells, none significantly inhibited HIV-1 infection in target cells. Furthermore, differential incorporation of IFITMs into HIV-1 virions did not consistently correlate with antiviral activity, indicating that virion incorporation alone is insufficient to explain HIV-1 restriction. Together, these findings demonstrate that gene duplication and retrotransposition have generated a functionally diverse IFITM repertoire in macaques and provide insight into how evolutionary diversification expands innate antiviral defenses in primates. ImportanceIFITM proteins are broad-spectrum antiviral restriction factors that inhibit infection of numerous enveloped viruses. Although IFITM genes have undergone extensive diversification during mammalian evolution, the functional consequences of this diversification remain poorly understood. Here, we show that expansion of the macaque IFITM locus through gene duplication and retrotransposition generated proteins with distinct antiviral activities, intracellular localization patterns, and regulatory mechanisms. We identify amino acid determinants that contribute to the enhanced antiviral activity of the duplicated paralog IFITM3A and demonstrate that lysosome-dependent turnover mediated by a PPxY motif and a unique lysine residue limits expression and antiviral activity of the retrocopy IFITM3-R1. We further show that macaque IFITMs inhibit HIV-1 predominantly through producer-cell-dependent mechanisms and reveal that IFITM virion incorporation alone does not predict antiviral potency. These findings provide mechanistic insight into how restriction factor diversification expands innate antiviral defenses and shapes host-virus interactions in primates.

microbiology↗

bioRxiv2025

The JAW-TCP-FUL genetic axis triggers an early reorientation of cell anisotropy to initiate and drive fertilization-dependent fruit elongation in Arabidopsis

In angiosperms, the ovary grows and develops into a fruit after fertilization, and the seeds are formed within to ensure reproductive success. Although genetic regulators suppressing fertilization-independent fruit growth or parthenocarpy have been identified in the Brassicaceae model Arabidopsis thaliana, the fertilization-dependent activator of fruit growth has not been elucidated. Here, we show that the miR319-regulated TCP transcription factors (JAW-TCPs) directly activate the transcription of the FRUITFULL (FUL) gene and promote fruit morphogenesis. By activating FUL, JAW-TCPs indirectly repress the four valve-margin specifying genes SHATTERPROOF1, SHATTERPROOF2, INDEHISCENT and ALCATRAZ in the valves. Mutating these genes suppresses defects caused by the combined loss of JAW-TCPs and FUL. Through extensive confocal imaging studies, we deciphered the cellular basis of JAW-TCP function revealing that JAW-TCPs promote fruit elongation by triggering the reorientation of cell anisotropy along the length axis at an early growth stage after fertilization. Our study uncovers a fertilization-dependent genetic module driving fruit elongation and sets the stage to identify other genetic regulators in this pathway.

plant biology↗

bioRxiv2022

Prolactin-induced AMPK stabilizes alveologenesis and lactogenesis through regulation of STAT5 signaling

AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that regulates energy homeostasis at cellular and organismal levels. It has been shown to affect several steps of breast cancer progression in a context-dependent manner. However, its role in normal mammary gland development and physiology remains ill-explored. Here, we show that AMPK expression and activity increased within murine mammary epithelia from puberty to pregnancy with highest levels during lactation, and then declined during involution. In ex vivo cultures of mammary epithelial cells (MECs) in organotypic scaffolds, treatment with lactogenic hormone prolactin (PRL) enhanced AMPK expression and activity. To understand the role of AMPK on mammary morphogenesis in vivo, we generated mice with conditional knockout of AMPK isoforms 1 and 2 (AMPK KO) in MECs. AMPK KO mammary glands showed accelerated alveolar development with increased epithelial content of both luminal and myoepithelial lineages, suggestive of hyperproliferation. AMPK KO mice also showed elevated beta-casein expression during pregnancy and lactation. These observations were phenocopied upon treatment of ex vivo cultivated wild-type MECs with a cognate AMPK inhibitor. AMPK null MECs showed increased phosphorylated STAT5 which is known to drive alveologenesis downstream of prolactin signaling. Our study identifies a novel interplay between AMPK and PRL-STAT5 signaling that determines mammary alveologenesis and differentiation.

developmental biology↗

bioRxiv2021

GH18 family glycoside hydrolase Chitinase A of Salmonella facilitates bacterial invasion and survival by modulating host immune responses

Salmonella is a facultative intracellular pathogen that has co-evolved with its host and has also developed various strategies to evade the host immune responses. Salmonella recruits an array of virulence factors to escape from host defense mechanisms. Previously chitinase A (chiA) was found to be upregulated in intracellular Salmonella. Although studies show that chitinases and chitin binding proteins (CBP) of many human pathogens have a profound role in various aspects of pathogenesis, like adhesion, virulence and immune evasion, the role of chitinase in strict intravacuolar pathogen Salmonella has not yet been elucidated. In this study, we deciphered the role of chitinase of Salmonella in the pathogenesis of the serovars, Typhimurium and Typhi. Our data propose that ChiA mediated modification of the glycosylation on the epithelial cell surface facilitates the invasion of the pathogen into the epithelial cells. Further we found that ChiA aids in reactive nitrogen species (RNS) and reactive oxygen species (ROS) production in phagocytes, leading to MHCII downregulation followed by suppression of antigen presentation and antibacterial responses. In continuation of the study in animal model C. elegans, Salmonella Typhi ChiA was found to facilitate attachment to the intestinal epithelium, gut colonization and persistence by downregulating antimicrobial peptides.

microbiology↗

bioRxiv2021

Understanding distribution and occupancy of Himalayan Monal in Uttarkashi district, Uttarakhand

The Himalayan Monal is a conservation priority species in its entire distribution range. Its population is declining in many areas due to various anthropogenic threats. The information on species distribution and its abundance is lacking in many areas which are vital for conservation and management planning. Hence, through the present study, we have assessed the abundance and occupancy of Himalayan monal in Uttarkashi district (Uttarakhand). We used camera traps and conventional sign surveys for documenting the species during 2018-2019. We installed a total of 69 camera traps (2819 trap nights) and surveyed 54 trails (650 km) which represents entire habitat and topographic variability of the landscape. The occupancy and detection probability was modelled using the habitat variables. The top model showed that occupancy probability of Himalayan monal was positively influenced by the slope ({beta} =27.52 {+/-}16.25) and negatively influenced by Reserve Forest (RF) ({beta}= -8.14 SE {+/-} 4.99). The observed naive occupancy of Himalayan Monal was 0.69 in the study area, which was slightly lower than the estimated occupancy. However, in the null model, the site occupancy estimated was found to be 0.82{+/-}0.08 and with detection probability 0.23{+/-}0.03. The overall abundance of monal was estimated about 171.58 {+/-}10.2 in the study area with an average density of 0.62/ km2. The activity pattern analysis indicates that monal remains very active between 6.00 hrs -12.00 hrs and relatively less active during mid-day when humans are most active 11.30 hrs-16.30 hrs. The present study is a first attempt to estimate occupancy and abundance using camera traps as well as sign survey for the species primarily from non-Protected Area (PA). We found that Himalayan monal is abundant outside the PAs, which is a good indication for its long-term viability and also identified areas for conservation and management prioritization in Uttarkashi.

ecology↗

bioRxiv2020

New insights on species divergence in red panda

With the recent classification of red panda into two phylogenetic species, we propose Siang river as a potential boundary for species divergence between the Himalayan red panda (Ailurus fulgens) and the Chinese red panda (Ailurus styani). Bayesian based phylogeny and MJ network splited all the sequences into two distinct clusters in accordance to the origin of the samples collected from the east and west side of the Siang river. The clade 1, that represented Himalayan red panda, was formed by inclusion of samples originated from the north West Bengal, Sikkim, and central Arunachal Pradesh and South Tibet. While, clade 2 represented Chinese red panda by inclusion of the samples originated from Dibang valley of eastern Arunachal Pradesh, India and Southwest China. We suggest being associated with diverse habitats, threats and transboundary distribution, both species of red panda require regional as well as multilateral cooperation for making species survival plan.

evolutionary biology↗

bioRxiv2020

Fine-scale landscape genetics unveiling contemporary asymmetric movement of red panda (Ailurus fulgens) in Kangchenjunga landscape, India

Wildlife management in rapid changing landscapes requires critical planning through cross cutting networks, and understanding of landscape features, often affected by the anthropogenic activities. The present study demonstrates fine-scale spatial patterns of genetic variation and contemporary gene flow of red panda (Ailurus fulgens) populations with respect to landscape connectivity in Kangchenjunga Landscape (KL), India. The study found about 1309.54 Km2 area suitable for red panda in KL-India, of which 62.21% area fell under the Protected Area network. We identified 24 unique individuals from 234 feces collected at nine microsatellite loci. The spatially explicit and non-explicit Bayesian clustering algorithms evident to exhibit population structuring and supported red panda populations to exist in meta-population frame work. In concurrence to the habitat suitability and landscape connectivity models, gene flow results supported a contemporary asymmetric movement of red panda by connecting KL- India in a crescent arc. We demonstrate the structural-operational connectivity of corridors in KL-India that facilitated red panda movement in the past. We also seek for cooperation in Nepal, Bhutan and China to aid in preparing for a comprehensive monitoring plan for the long-term conservation and management of red panda in trans-boundary landscapes.

genetics↗

bioRxiv2020

New insights of zoogeographical distribution of Himalayan goral (Naemorhedus goral) from Indian Himalayan Region

In the present study, we explored the intraspecific genetic variation and phylogeographic relationship among all the reported species in the genus Naemorhedus distributed in a wide range of habitats. The Bayesian based phylogeny demonstrated that Himalayan goral, is a highly diverged species from the other reported species of gorals. We claim the presence of two valid sub-species of Himalayan goral, i.e. N. g. bedfordi and N. g. goral, distributed in the western and central Himalaya, respectively. The comparative analysis with the inclusion of data available from different ranges, suggests the presence of plausibly six species of gorals across the distribution with a few valid subspecies. Further, we report that N. griseus is a valid species and not the synonyms of N. goral considering the observed discrepancy in the available sequences. We recommend all the sub-species present at distant locations may be considered as Evolutionary Significant Units (ESUs) and, therefore, appeal to provide them special attention for long term conservation and management.

genetics↗

bioRxiv2020

Global transcriptional regulation by cell-free supernatant of Salmonella Typhimurium peptide transporter mutant leads to inhibition of intra-species biofilm initiation

Salmonella is a genus of widely spread Gram negative, facultative anaerobic bacteria, which is known to cause [1/4]th of diarrheal morbidity and mortality globally. It causes typhoid fever and gastroenteritis by gaining access to the host gut through contaminated food and water. Salmonella utilizes its biofilm lifestyle to strongly resist antibiotics and persist in the host. Although biofilm removal or dispersal has been studied widely, the inhibition of the initiation of Salmonella biofilm remains elusive. This study was conducted to determine the anti-biofilm property of the cell-free supernatant obtained from a carbon-starvation inducible proline peptide transporter mutant ({Delta}yjiY) strain. Our study shows that Salmonella {Delta}yjiY culture supernatant primarily inhibits biofilm initiation by regulating biofilm-associated transcriptional network. This work demonstrates that highly abundant proteases such as HslV and GrpE cleave the protein aggregates, whereas global transcription regulators H-NS, FlgM regulate expression of SPIs and flagellar genes. Relatively low abundances of flavoredoxin, glutaredoxin, thiol peroxidase etc. leads to accumulation of ROS within the biofilm, and subsequent toxicity. This work further suggests that targeting these oxidative stress relieving proteins might be a good druggable choice to reduce Salmonella biofilm. ImportanceThe enteric pathogen Salmonella forms biofilm in the internal organs of asymptomatic carriers, and on abiotic surfaces that leads to contamination of food and water. Biofilms are highly drug-resistant life forms that also helps in host immune evasion. Therefore, recent insurgence of drug tolerant strains necessitates development of biofilm inhibitory strategies, and finding novel druggable targets. In this study we investigated the bioactive molecules present in the cell-free supernatant of a biofilm deficient strain of Salmonella Typhimurium that inhibit biofilm initiation by the wildtype strain. Further we showed that the supernatant treatment leads to virulence defect in vivo. Collectively, our results suggest a comprehensive view of virulence regulation in Salmonella by the cell-free supernatant of the biofilm deficient strain.

microbiology↗

bioRxiv2020

How did SARS-CoV-19 spread in India from Italy, Iran and China? Genetic surveillance of early cases and virus demography

SARS-CoV-19 after emerging from Wuhan, drastically devastated all sectors of human life by crushing down the global economy and increased psychological burden on public, government, and healthcare professionals. We manifested by analyzing 35 early coronavirus cases of India, that virus introduction in India, occurred from Italy, Iran and China and population demography apparently revealed a rapid population expansion after the outbreak with a present steady growth. We depicted nucleotide substitutions in structural genes, drove for the adaptive selection and plead for sequencing more genomes to facilitate identification of new emerged mutants, genetic evolution and disease transmission caused by coronavirus.

genomics↗

bioRxiv2020

Designing a multi-epitope peptide-based vaccine against SARS-CoV-2

COVID-19 pandemic has resulted so far 14,395,16 confirmed cases with 85,711 deaths from the 212 countries, or territories. Due to multifacet issues and challenges in implementation of the safety & preventive measures, inconsistent coordination between societies-governments and most importanly lack of specific vaccine to SARS-CoV-2, the spread of Wuhan originated virus is still uprising after taking a heavy toll on human life. In the present study, we mapped several immunogenic epitopes (B-cell, T-cell, and IFN-gamma) over the entire structural proteins of SARS-CoV-2 and by applying various computational and immunoinformatics approaches, we designed a multi-epitope peptide based vaccine that predicted high immunogenic response in the largest proportion of worlds human population. To ensure high expression of the recombinant vaccine in E. coli, codon optimization and in-silico cloning were also carried out. The designed vaccine with high molecular affinity to TLR3 and TLR4, was found capable to initiate effective innate and adaptive immune response. The immune simulation also suggested uprising high levels of both B-cell and T-cell mediated immunity which on subsequent exposure cleared antigen from the system. The proposed vaccine found promising by yielding desired results and hence, should be tested by practical experimentations for its functioning and efficacy to neutralize SARS-CoV-2.

bioinformatics↗

bioRxiv2019

The complete mitochondrial genome of endangered Assam Roofed Turtle, Pangshura sylhetensis (Testudines: Geoemydidae): Genomic features and Phylogeny

Assam Roofed Turtle, Pangshura sylhetensis is an endangered and least studied species endemic to India and Bangladesh. The genomic feature of P. sylhetensis mitogenome is still anonymous to the scientific community. The present study decodes the first complete mitochondrial genome of P. sylhetensis (16,568 bp) by using next-generation sequencing. This de novo assembly encodes 13 Protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs), and one control region (CR). Most of the genes were encoded on the majority strand, except NADH dehydrogenase subunit 6 (nad6) and eight tRNAs. Most of the PCGs were started with an ATG initiation codon, except for Cytochrome oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 5 (nad5) with GTG. The study also found the typical cloverleaf secondary structure in most of the tRNA genes, except for serine (trnS1) with lack of conventional DHU arm and loop. Both, Bayesian and Maximum-likelihood topologies showed distinct clustering of all the Testudines species with their respective taxonomic ranks and congruent with the previous phylogenetic hypotheses (Pangshura and Batagur sister taxa). Nevertheless, the mitogenomic phylogeny with other amniotes corroborated the sister relationship of Testudines with Archosaurians (Birds and Crocodilians). Additionally, the mitochondrial Gene Order (GO) analysis indicated that, most of the Testudines species showed plesiomorphy with typical vertebrate GO.

genomics↗

bioRxiv2019

Deciphering the structural intricacy in virulence effectors for proton-motive force mediated unfolding and type-III protein secretion

Many gram-negative pathogenic bacteria use type III secretion system (T3SS) to inject virulence effectors directly into the cytosol of targeted host cells. Given that the protein unfolding requisite for secretion via nano-size pore of T3SS injectisome is an energetically unfavorable process, "How do pathogenic bacteria unfold and secrete hundreds of toxic proteins in seconds" remain largely unknown. In this study, first, from an in-depth analysis of folding and stability of T3SS effector ExoY, we show that the proton-concentration gradient ([~]pH 5.8-6.0) generated by proton-motive force (PMF) can significantly amortize tertiary structural folding and stability of effectors without significant entropic cost. Strikingly, it was found that the lower energetic cost associated with the global unfolding of ExoY is mainly due to its weakly folded geometry and abundance of geometrical frustrations stemming from buried water molecules and native-like folded intermediates in the folded cores. From in-silico structural analysis of 371 T3SS effectors, it can be curtained that T3SS effectors belong to typical class (disorder globules) of IDPs and have evolved similar conserved intrinsic structural archetypes to mediate early-stage unfolding. The slower folding kinetics in effector proteins requisite for efficient T3SS-mediated secretion mostly stems from reduced hydrophobic density and enhanced polar-polar repulsive interactions in their sequence landscapes. Lastly, the positively evolved histidine-mediated stabilizing interactions and gate-keeper residues in effector proteins shed light on collaborative role of evolved structural chemistry in T3SS effectors and PMF in the spatial-temporal regulation of effector folding and stability essential for maintaining balance in secretion and function trade-off.

biophysics↗

bioRxiv2018

The first complete mitochondrial genome of marigold pest thrips, Neohydatothrips samayunkur (Sericothripinae) and comparative analysis

The complete mitogenomes in order Thysanoptera is limited to subfamily Thripinae heretofore. In the present study, we sequenced the first mitochondrial genome of Neohydatothrips samayunkur (15,295 bp), a member of subfamily Sericothripinae. The genome was characterized by 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs) and three control regions (CRs). This mitogenome had two overlapping regions of 4 bp and twenty four intergenic spacers accounting for 165 bp. All the tRNA had typical cloverleaf secondary structures, except for trnV and trnS which lacked DHU stem and loop. The mitogenomes of N. samayunkur was highly rearranged with many unique features as compared to other thrips mitogenomes, atp6 and nad1 were terminated with TAG and TGA stop codons respectively; location of trnL2, trnA, trnC, and trnV was rearranged; and the first control region (CR1) was upstream of nad6. The phylogenetic analysis of 13 PCGs implementing maximum likelihood and Bayesian inference showed the clustering of N. samayunkur with Scirtothrips dorsalis supporting the Scirtothrips genus-group and Sericothripinae morphology based relationships. Generation of more mitogenomes from different hierarchical level in the order Thysanoptera is required to understand the gene rearrangements, phylogeny and evolutionary relationships.

genomics↗

bioRxiv2018

Sequencing and characterization of the complete mitochondrial genome of Critically Endangered Black Soft-shell Turtle (Nilssonia nigricans)

The complete mitochondrial genome (16796 bp) of an endangered freshwater turtle, Nilssonia nigricans was firstly sequenced and annotated. The mitogenome was encoded by 37 genes and a major non-coding Control Region (CR). The mitogenome was A+T biased (62.16%) and spread with six overlapping and 19 intergenic spacer regions. The initiation codons were exceptionally changed as ATA, ATT, and ATC in three Protein-coding genes (PCGs) and a single base (A, T, and C) incomplete termination codons in nine PCGs. The Relative synonymous codon usage (RSCU) value was consistent among all the studied species; exception with significant reduction of Serine (S) frequency in N. nigricans, N. formosa, and R. swinhoei. The secondary structure of N. nigricans showed a lack of conventional dihydrouridine (DHU) arm in trnS (GCT), as well as formed a small loop structure in the acceptor stem of both trnR (TCG) and trnH (GTG). The mitogenome of N. nigricans also revealed two unique tandem repeats (ATTAT)8, and (TATTA)20 in CR. Further, the average Ka/Ks values of 13 PCGs were indicating a strong natural selection in the studied Trionychidae species. The constructed Maximum Likelihood (ML) phylogeny by PCGs shows cohesive clustering of N. nigricans with N. formosa. The resulted phylogeny illustrated the similar topology by all studied species from different taxonomic ranks and supported the previous taxonomic classification. Moreover, further taxon sampling from different taxonomic hierarchy, and their mitogenomics study is vital to reconcile the Testudines phylogeny and assure their evolutionary relationship.

genomics↗

bioRxiv2018

The complete mitochondrial genome of Melon thrips, Thrips palmi (Thripinae) and comparative analysis: A vector for Tospoviruses

The melon thrips, Thrips palmi is a serious pest and vector for plant viruses on a wide range of economically important crops. DNA barcoding evidenced the presence of cryptic diversity in T. palmi and that warrants exhaustive molecular data. Our present study is on decoding the first complete mitochondrial genome of T. palmi (15,333 bp) through NGS technology. The mitogenome contains 37 genes, including 13 PCGs, two rRNAs, 22 tRNAs, and two control regions. The comparative analyses were conducted for gene arrangements, nucleotide composition, codon usage and phylogenetic relationship with other thrips mitogenomes. The nucleotide composition was 78.29% AT, and 21.72% GC with positive AT skewness (0.09) and negative GC skewness (-0.06). The ATN initiation codons were observed in 12 PCGs except cox1 with unique start codon (TTG). The RSCU analysis revealed Phe, Leu, Ile, Tyr, Asn, Lys and Met were the most frequently used amino acids in all PCGs. The codon CGG (Arg) was absent in T. palmi as compared to other thrips mitogenomes. The Ka/Ks ratio ranges from 0.078 in cox1 to 0.913 in atp8. We observed the typical cloverleaf secondary structure in most of the tRNA genes with a few exceptions; absence of DHU stem and loop in trnV and trnS, absence of DHU loop in trnE, lack of T-arm and loop in trnN. The position of trnS1 (between cox3 and CR2) is unique in T. palmi among all the studied thrips mitogenomes. The mitogenome contained 24 intergenic spacer regions and 12 overlapping regions. The CR2 is 63.77% similar to CR1, indicating a possible duplication and translocation in control region. Both the ML and BI phylogenetic trees revealed the close relationships of Thrips with Scirtothrips as compared to Frankliniella. Thus, more mitogenomes on the diverse thrips species is required to understand the in-depth phylogenetic and evolutionary relationships.

genomics↗