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result(s) for
"Mishra, Rakesh"
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Patterns of microsatellite distribution across eukaryotic genomes
by
Mishra, Rakesh K.
,
Avvaru, Akshay Kumar
,
Sowpati, Divya Tej
in
Animal Genetics and Genomics
,
Animals
,
Biomedical and Life Sciences
2019
Background
Microsatellites, or Simple Sequence Repeats (SSRs), are short tandem repeats of 1–6 nt motifs present in all genomes. Emerging evidence points to their role in cellular processes and gene regulation. Despite the huge resource of genomic information currently available, SSRs have been studied in a limited context and compared across relatively few species.
Results
We have identified ~ 685 million eukaryotic microsatellites and analyzed their genomic trends across 15 taxonomic subgroups from protists to mammals. The distribution of SSRs reveals taxon-specific variations in their exonic, intronic and intergenic densities. Our analysis reveals the differences among non-related species and novel patterns uniquely demarcating closely related species. We document several repeats common across subgroups as well as rare SSRs that are excluded almost throughout evolution. We further identify species-specific signatures in pathogens like
Leishmania
as well as in cereal crops,
Drosophila
, birds and primates. We also find that distinct SSRs preferentially exist as long repeating units in different subgroups; most unicellular organisms show no length preference for any SSR class, while many SSR motifs accumulate as long repeats in complex organisms, especially in mammals.
Conclusions
We present a comprehensive analysis of SSRs across taxa at an unprecedented scale. Our analysis indicates that the SSR composition of organisms with heterogeneous cell types is highly constrained, while simpler organisms such as protists, green algae and fungi show greater diversity in motif abundance, density and GC content. The microsatellite dataset generated in this work provides a large number of candidates for functional analysis and for studying their roles across the evolutionary landscape.
Journal Article
SARS-CoV-2 genomics: An Indian perspective on sequencing viral variants
2021
Since its emergence as a pneumonia-like outbreak in the Chinese city of Wuhan in late 2019, the novel coronavirus disease COVID-19 has spread widely to become a global pandemic. The first case of COVID-19 in India was reported on 30 January 2020 and since then it has affected more than ten million people and resulted in around 150,000 deaths in the country. Over time, the viral genome has accumulated mutations as it passes through its human hosts, a common evolutionary mechanism found in all microorganisms. This has implications for disease surveillance and management, vaccines and therapeutics, and the emergence of reinfections. Sequencing the viral genome can help monitor these changes and provides an extraordinary opportunity to understand the genetic epidemiology and evolution of the virus as well as tracking its spread in a population. Here we review the past year in the context of the phylogenetic analysis of variants isolated over the course of the pandemic in India and highlight the importance of continued sequencing-based surveillance in the country.
Journal Article
Mediating role of social disengagement and loneliness in the nexus between functional health and mental well-being in older individuals
2024
Few studies have focused sufficiently on the intricate link between functional health and depression among older people aged 60 and above in India. Therefore, the current study investigates the association between functional health and depression among older Indian adults through the mediating role of social disengagement and loneliness and the moderating role of living arrangements using recent data from the Longitudinal Aging Study in India (LASI: 2017–2018). Composite International Diagnostic Interview-Short Form (CIDI-SF) for depression, the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) for functional health, and the indoor/outdoor activities, visits, and religious events for social disengagement were used. The feelings of loneliness and living arrangements were measured using single-item questions and surveys/interviews of household members. Bivariate analysis, logistic regression, and a Partial Least Squares-Structural Equation Model were adopted. The results show that older persons with functional health had 1.85 times higher odds of depression; similarly, those not engaging in social activities and experiencing loneliness were more likely to feel depressed. Living with someone was negatively linked to depression. A significant moderation by living arrangements in the functional health-depression relationship was also observed. The results also indicate significant mediating roles of social disengagement and loneliness, with 22.0% and 3.08% mediation effects, respectively. Therefore, this study recommends the provision of housing and social interaction among older people.
Journal Article
Single Amino Acid Repeats in the Proteome World: Structural, Functional, and Evolutionary Insights
by
Mishra, Rakesh K.
,
Kumar, Amitha Sampath
,
Sowpati, Divya Tej
in
Alanine
,
Amino acids
,
Analysis
2016
Microsatellites or simple sequence repeats (SSR) are abundant, highly diverse stretches of short DNA repeats present in all genomes. Tandem mono/tri/hexanucleotide repeats in the coding regions contribute to single amino acids repeats (SAARs) in the proteome. While SSRs in the coding region always result in amino acid repeats, a majority of SAARs arise due to a combination of various codons representing the same amino acid and not as a consequence of SSR events. Certain amino acids are abundant in repeat regions indicating a positive selection pressure behind the accumulation of SAARs. By analysing 22 proteomes including the human proteome, we explored the functional and structural relationship of amino acid repeats in an evolutionary context. Only ~15% of repeats are present in any known functional domain, while ~74% of repeats are present in the disordered regions, suggesting that SAARs add to the functionality of proteins by providing flexibility, stability and act as linker elements between domains. Comparison of SAAR containing proteins across species reveals that while shorter repeats are conserved among orthologs, proteins with longer repeats, >15 amino acids, are unique to the respective organism. Lysine repeats are well conserved among orthologs with respect to their length and number of occurrences in a protein. Other amino acids such as glutamic acid, proline, serine and alanine repeats are generally conserved among the orthologs with varying repeat lengths. These findings suggest that SAARs have accumulated in the proteome under positive selection pressure and that they provide flexibility for optimal folding of functional/structural domains of proteins. The insights gained from our observations can help in effective designing and engineering of proteins with novel features.
Journal Article
Evaluation of complex multi-physics phenomena at gas diffusion electrodes during high-pressure water electrolysis with AEMs
2025
The alkaline water electrolysis is a well-established process for producing green hydrogen from renewable energy sources. With up-to-dateAEM electrolyzers, electrochemical gas compression can be realized with water electrolysis and ion pumping membranes, to avoid costly mechanical compression. In this experimental study, we researched an electrolyzer cell with a strong metal structure, for internal pressure difference of up to 100 bar. Micro-porous gas diffusion electrodes containing non-precious nickel catalysts as well as different separators, alkaline membranes and AEMs have been investigated in the range of 300 to 800 mA cm
− 2
. For one preferred AEM, characteristics are shown for hydrogen pressures between 20 and 80 bars, while the anode remains at ambient 1 bar. Impedance spectroscopy diagrams are used to display the individual cell components: the ohmic resistance of the AEM and the complex impedances of both electrodes. Therewith, we could visualize the complex multi-physics phenomena and show that the oxygen electrode works as a Wartburg-element, especially due to higher diffusion rates and therewith entropy production during bubble formation.
Journal Article
CRISPR/Cas9 and FLP-FRT mediated regulatory dissection of the BX-C of Drosophila melanogaster
by
Hajirnis, Nikhil
,
Mishra, Rakesh K
,
Pandey, Shubhanshu
in
Chromosomes
,
CRISPR
,
Drosophila melanogaster
2023
The homeotic genes or Hox define the anterior–posterior (AP) body axis formation in bilaterians and are often present on the chromosome in an order collinear to their function across the AP axis. However, there are many cases wherein the Hox are not collinear, but their expression pattern is conserved across the AP axis. The expression pattern of Hox is attributed to the cis-regulatory modules (CRMs) consisting of enhancers, initiators, or repressor elements that regulate the genes in a segment-specific manner. In the Drosophila melanogaster Hox complex, the bithorax complex (BX-C) and even the CRMs are organized in an order that is collinear to their function in the thoracic and abdominal segments. In the present study, the regulatorily inert regions were targeted using CRISPR/Cas9 to generate a series of transgenic lines with the insertion of FRT sequences. These FRT lines are repurposed to shuffle the CRMs associated with Abd-B to generate modular deletion, duplication, or inversion of multiple CRMs. The rearrangements yielded entirely novel phenotypes in the fly suggesting the requirement of such complex manipulations to address the significance of higher order arrangement of the CRMs. The functional map and the transgenic flies generated in this study are important resources to decipher the collective ability of multiple regulatory elements in the eukaryotic genome to function as complex modules.
Journal Article
Virtual Reality in Neurosurgery: Beyond Neurosurgical Planning
by
Umana, Giuseppe E.
,
Deora, Harsh
,
Montemurro, Nicola
in
Augmented Reality
,
Brain cancer
,
Humans
2022
Background: While several publications have focused on the intuitive role of augmented reality (AR) and virtual reality (VR) in neurosurgical planning, the aim of this review was to explore other avenues, where these technologies have significant utility and applicability. Methods: This review was conducted by searching PubMed, PubMed Central, Google Scholar, the Scopus database, the Web of Science Core Collection database, and the SciELO citation index, from 1989–2021. An example of a search strategy used in PubMed Central is: “Virtual reality” [All Fields] AND (“neurosurgical procedures” [MeSH Terms] OR (“neurosurgical” [All Fields] AND “procedures” [All Fields]) OR “neurosurgical procedures” [All Fields] OR “neurosurgery” [All Fields] OR “neurosurgery” [MeSH Terms]). Using this search strategy, we identified 487 (PubMed), 1097 (PubMed Central), and 275 citations (Web of Science Core Collection database). Results: Articles were found and reviewed showing numerous applications of VR/AR in neurosurgery. These applications included their utility as a supplement and augment for neuronavigation in the fields of diagnosis for complex vascular interventions, spine deformity correction, resident training, procedural practice, pain management, and rehabilitation of neurosurgical patients. These technologies have also shown promise in other area of neurosurgery, such as consent taking, training of ancillary personnel, and improving patient comfort during procedures, as well as a tool for training neurosurgeons in other advancements in the field, such as robotic neurosurgery. Conclusions: We present the first review of the immense possibilities of VR in neurosurgery, beyond merely planning for surgical procedures. The importance of VR and AR, especially in “social distancing” in neurosurgery training, for economically disadvantaged sections, for prevention of medicolegal claims and in pain management and rehabilitation, is promising and warrants further research.
Journal Article
Homeotic Genes: Clustering, Modularity, and Diversity
by
Mishra, Rakesh K.
,
Hajirnis, Nikhil
in
bithorax complex
,
Cell and Developmental Biology
,
evolution
2021
Hox genes code for transcription factors and are evolutionarily conserved. They regulate a plethora of downstream targets to define the anterior-posterior (AP) body axis of a developing bilaterian embryo. Early work suggested a possible role of clustering and ordering of Hox to regulate their expression in a spatially restricted manner along the AP axis. However, the recent availability of many genome assemblies for different organisms uncovered several examples that defy this constraint. With recent advancements in genomics, the current review discusses the arrangement of Hox in various organisms. Further, we revisit their discovery and regulation in Drosophila melanogaster . We also review their regulation in different arthropods and vertebrates, with a significant focus on Hox expression in the crustacean Parahyale hawaiensis . It is noteworthy that subtle changes in the levels of Hox gene expression can contribute to the development of novel features in an organism. We, therefore, delve into the distinct regulation of these genes during primary axis formation, segment identity, and extra-embryonic roles such as in the formation of hair follicles or misregulation leading to cancer. Toward the end of each section, we emphasize the possibilities of several experiments involving various organisms, owing to the advancements in the field of genomics and CRISPR-based genome engineering. Overall, we present a holistic view of the functioning of Hox in the animal world.
Journal Article
Nuclear architecture and the structural basis of mitotic memory
by
Soujanya, Mamilla
,
Hajirnis, Nikhil
,
Pathak, Rashmi U
in
Cell division
,
Chromatin
,
Chromosomes
2023
Abstract The nucleus is a complex organelle that hosts the genome and is essential for vital processes like DNA replication, DNA repair, transcription, and splicing. The genome is non-randomly organized in the three-dimensional space of the nucleus. This functional sub-compartmentalization was thought to be organized on the framework of nuclear matrix (NuMat), a non-chromatin scaffold that functions as a substratum for various molecular processes of the nucleus. More recently, nuclear bodies or membrane-less subcompartments of the nucleus are thought to arise due to phase separation of chromatin, RNA, and proteins. The nuclear architecture is an amalgamation of the relative organization of chromatin, epigenetic landscape, the nuclear bodies, and the nucleoskeleton in the three-dimensional space of the nucleus. During mitosis, the nucleus undergoes drastic changes in morphology to the degree that it ceases to exist as such; various nuclear components, including the envelope that defines the nucleus, disintegrate, and the chromatin acquires mitosis-specific epigenetic marks and condenses to form chromosome. Upon mitotic exit, chromosomes are decondensed, re-establish hierarchical genome organization, and regain epigenetic and transcriptional status similar to that of the mother cell. How this mitotic memory is inherited during cell division remains a puzzle. NuMat components that are a part of the mitotic chromosome in the form of mitotic chromosome scaffold (MiCS) could potentially be the seeds that guide the relative re-establishment of the epigenome, chromosome territories, and the nuclear bodies. Here, we synthesize the advances towards understanding cellular memory of nuclear architecture across mitosis and propose a hypothesis that a subset of NuMat proteome essential for nucleation of various nuclear bodies are retained in MiCS to serve as seeds of mitotic memory, thus ensuring the daughter cells re-establish the complex status of nuclear architecture similar to that of the mother cells, thereby maintaining the pre-mitotic transcriptional status.
Journal Article
Functional diversification of yeast telomere associated protein, Rif1, in higher eukaryotes
by
Sreesankar, Easwaran
,
Senthilkumar, Ramamoorthy
,
Bharathi, Vellaichamy
in
Animal Genetics and Genomics
,
Animals
,
Bioinformatics
2012
Background
Telomeres are nucleoprotein complexes at the end of linear eukaryotic chromosomes which maintain the genome integrity by regulating telomere length, preventing recombination and end to end fusion events. Multiple proteins associate with telomeres and function in concert to carry out these functions. Rap1 interacting factor 1 (Rif1), was identified as a protein involved in telomere length regulation in yeast. Rif1 is conserved upto mammals but its function has diversified from telomere length regulation to maintenance of genome integrity.
Results
We have carried out detailed bioinformatic analyses and identified Rif1 homologues in 92 organisms from yeast to human. We identified Rif1 homologues in
Drosophila melanogaster
, even though fly telomeres are maintained by a telomerase independent pathway. Our analysis shows that
Drosophila
Rif1 (dRif1) sequence is phylogenetically closer to the one of vertebrates than yeast and has identified a few Rif1 specific motifs conserved through evolution. This includes a Rif1 family specific conserved region within the HEAT repeat domain and a motif involved in protein phosphatase1 docking. We show that dRif1 is nuclear localized with a prominent heterochromatin association and unlike human Rif1, it does not respond to DNA damage by localizing to damaged sites. To test the evolutionary conservation of dRif1 function, we expressed the dRif1 protein in yeast and HeLa cells. In yeast, dRif1 did not perturb yeast Rif1 (yRif1) functions; and in HeLa cells it did not colocalize with DNA damage foci.
Conclusions
Telomeres are maintained by retrotransposons in all
Drosophila
species and consequently, telomerase and many of the telomere associated protein homologues are absent, including Rap1, which is the binding partner of Rif1. We found that a homologue of yRif1 protein is present in fly and dRif1 has evolutionarily conserved motifs. Functional studies show that dRif1 responds differently to DNA damage, implying that dRif1 may have a different function and this may be conserved in other organisms as well.
Journal Article