Computational Analysis of the Accumulation of Mutations in Therapeutically Important RNA Viral Proteins During Pandemics with Special Emphasis on SARS-CoV-2.

Single stranded RNA viruses are primary causative agents for pandemics, causing extensive morbidity and mortality worldwide. A pivotal question in pandemic preparedness and therapeutic intervention is what are the specific mutations which are more likely to emerge during such global health crises? This study aims to identify markers for mutations with the highest probability of emergence in these pandemics, focusing on the SARS-CoV-2 spike protein, an essential and therapeutically significant viral protein, starting from sequence information from the onset of the pandemic until July 2022. Quite consistently, we observed that emerged mutations tended to demonstrate a high genetic score, which reflects high similarity of the type of codon required for translation between an amino acid and to the mutated one.

Evolutionary dynamics of dengue virus in India.

More than a hundred thousand dengue cases are diagnosed in India annually, and about half of the country's population carries dengue virus-specific antibodies. Dengue propagates and adapts to the selection pressures imposed by a multitude of factors that can lead to the emergence of new variants. Yet, there has been no systematic analysis of the evolution of the dengue virus in the country.

Bioinformatics Analysis of Mutations Sheds Light on the Evolution of Dengue NS1 Protein With Implications in the Identification of Potential Functional and Druggable Sites.

Non-structural protein (NS1) is a 350 amino acid long conserved protein in the dengue virus. Conservation of NS1 is expected due to its importance in dengue pathogenesis. The protein is known to exist in dimeric and hexameric states.

Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin.

Preservation of a small population of cancer stem cells (CSCs) within a heterogeneous carcinoma serves as a paradigm to understand how select cells in a tissue maintain their undifferentiated status. In both embryogenesis and cancer, Snail has been correlated with stemness, but the molecular underpinning of this phenomenon remains largely ill-defined. In models of cutaneous squamous cell carcinoma (cSCC), we discovered a non-epithelial-mesenchymal transition function for the transcription factor Snail in maintaining the stemness of epidermal keratinocytes.

Building Indian Biomedical Leadership to Bridge the Gap Between Science, Primary Health Care and Public Health.

The Indian biomedical landscape has been characterized by the existence of somewhat polarized institutional structures and professional growth. While some scientific and public health challenges have been met with existing structures, there is still a large unmet scientific and public health need. Broadly, the physical separation of science, engineering, medical campuses and industry has led to silos of excellence and accomplishment with huge gaps in innovation and implementation.

Versatile role of miR-24/24-1*/24-2* expression in cancer and other human diseases.

MiRNAs (miRs) have been proven to be well-validated therapeutic targets. Emerging evidence has demonstrated that intricate, intrinsic and paradoxical functions of miRs are context-dependent because of their multiple upstream regulators, broad spectrum of downstream molecular targets and distinct expression in various tissues, organs and disease states. Targeted therapy has become an emerging field of research.

Immune profile and responses of a novel dengue DNA vaccine encoding an EDIII-NS1 consensus design based on Indo-African sequences.

The ongoing COVID-19 pandemic highlights the need to tackle viral variants, expand the number of antigens, and assess diverse delivery systems for vaccines against emerging viruses. In the present study, a DNA vaccine candidate was generated by combining in tandem envelope protein domain III (EDIII) of dengue virus serotypes 1-4 and a dengue virus (DENV)-2 non-structural protein 1 (NS1) protein-coding region. Each domain was designed as a serotype-specific consensus coding sequence derived from different genotypes based on the whole genome sequencing of clinical isolates in India and complemented with data from Africa.

HT-SELEX-based identification of binding pre-miRNA hairpin-motif for small molecules.

Selective targeting of biologically relevant RNAs with small molecules is a long-standing challenge due to the lack of clear understanding of the binding RNA motifs for small molecules. The standard SELEX procedure allows the identification of specific RNA binders (aptamers) for the target of interest. However, more effort is needed to identify and characterize the sequence-structure motifs in the aptamers important for binding to the target.

Anticancer Activity of Root's Extract toward Human Cervical Cancer and Identification of Potential Bioactive Compounds.

is traditionally used to cure several diseases including cancer, wounds, and hypertension. The present study was designed to investigate the anticancer activity of the methanolic root extract of (IC-MeOH). The water-soluble tetrazolium-1 and colony formation assays were used to check the proliferation ability of the cells.

Antimicrobial Resistance Profiling and Phylogenetic Analysis of Clinical Isolates From Kenya in a Resource-Limited Setting.

Background: Africa has one of the highest incidences of gonorrhea. is gaining resistance to most of the available antibiotics, compromising treatment across the world. Whole-genome sequencing (WGS) is an efficient way of predicting AMR determinants and their spread in the population.

CD24 gene inhibition and TIMP-4 gene upregulation by Imperata cylindrica's root extract prevents metastasis of CaSki cells via inhibiting PI3K/Akt/snail signaling pathway and blocking EMT.

Ethnopharmacological Relevance: Imperata cylindrica (L.) Raeusch (Gramineae) is a medicinal spice traditionally used in the treatment of hypertension and cancer.

Aim Of The Study: To assess the anti-metastatic potential of the methanol extract of I.

DETECTing Merkel Cell Polyomavirus in Merkel Tumors.

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer caused either by Merkel cell polyomavirus (MCV) T antigen expression, post-integration (~80% cases), or by UV-mediated DNA damage. Interestingly, overall survival of MCV-positive Merkel cell carcinoma patients is better, making this differential information of significant diagnostic and prognostic value. Also, MCV provides a direct target for therapy in MCC patients.

Notch signalling in cervical cancer.

The initial discovery of key developmental signalling pathways, largely using classical genetic approaches in model organisms, was followed by an intense burst of characterisation of the molecular components. Studies also began demonstrating a role for these pathways in oncogenesis. Patterns of mutations in Notch pathway components, such as those reported in subsets of hematological malignancies, have been easier to study, and the cumulative information is leading to potentially new therapies.

Merkel cell polyomavirus is implicated in a subset of Merkel cell carcinomas, in the Indian subcontinent.

Merkel cell carcinoma is a rare, lethal cancer histopathologically composed of cells showing similarity with mechanoreceptor Merkel cells. Merkel cell tumors manifest in two distinct forms. While a virus called Merkel cell polyomavirus is involved in the pathogenesis of one form of Merkel tumors, the other is driven by ultraviolet (UV)-linked mutations.

RhoC regulates radioresistance via crosstalk of ROCK2 with the DNA repair machinery in cervical cancer.

Background: Radioresistance remains a challenge to the successful treatment of various tumors. Intrinsic factors like alterations in signaling pathways regulate response to radiation. RhoC, which has been shown to modulate several tumor phenotypes has been investigated in this report for its role in radioresistance.

A SUV39H1-low chromatin state characterises and promotes migratory properties of cervical cancer cells.

Metastatic progression is a major cause of mortality in cervical cancers, but factors regulating migratory and pre-metastatic cell populations remain poorly understood. Here, we sought to assess whether a SUV39H1-low chromatin state promotes migratory cell populations in cervical cancers, using meta-analysis of data from The Cancer Genome Atlas (TCGA), immunohistochemistry, genomics and functional assays. Cervical cancer cells sorted based on migratory ability in vitro have low levels of SUV39H1 protein, and SUV39H1 knockdown in vitro enhanced cervical cancer cell migration.

Complete assembly of a dengue virus type 3 genome from a recent genotype III clade by metagenomic sequencing of serum.

Mosquito-borne flaviviruses, such as dengue and Japanese encephalitis virus (JEV), cause life-threatening diseases, particularly in the tropics. Here we performed unbiased metagenomic sequencing of RNA extracted from the serum of four patients and the plasma of one patient, all hospitalized at a tertiary care centre in South India with severe or prolonged febrile illness, together with the serum from one healthy control, in 2014. We identified and assembled a complete dengue virus type 3 sequence from a case of severe dengue fever.

Isolation and molecular characterization of dengue virus clinical isolates from pediatric patients in New Delhi.

Objective: To characterize the in vitro replication fitness, viral diversity, and phylogeny of dengue viruses (DENV) isolated from Indian patients.

Methods: DENV was isolated from whole blood collected from patients by passaging in cell culture. Passage 3 viruses were used for growth kinetics in C6/36 mosquito cells.

Recovery of Five Complete Influenza A(H1N1)pdm09 Genome Sequences from the 2015 Influenza Outbreak in India by Metagenomic Sequencing.

Five complete (H1N1)pdm09 viral sequences were recovered from hospitalized individuals during the 2015 influenza outbreak by metagenomic sequencing. Four of the genomes are from oropharyngeal swabs, and one is from an isolate. All five sequences belong to an emerging 6B clade.

Oestrogen Receptor-α binds the FOXP3 promoter and modulates regulatory T-cell function in human cervical cancer.

Oestrogen controls Foxp3 expression in regulatory T cells (T cells) via a mechanism thought to involve oestrogen receptor alpha (ERα), but the molecular basis and functional impact of ERα signalling in T cells remain unclear. We report that ERα ligand oestradiol (E2) is significantly increased in human cervical cancer (CxCa) tissues and tumour-infiltrating T cells (CD4CD25CD127), whereas blocking ERα with the antagonist ICI 182,780 abolishes FOXP3 expression and impairs the function of CxCa infiltrating T cells. Using a novel approach of co-immunoprecipitation with antibodies to E2 for capture, we identified binding of E2:ERα complexes to FOXP3 protein in CxCa-derived T cells.

MiRNA182 regulates percentage of myeloid and erythroid cells in chronic myeloid leukemia.

The deregulation of lineage control programs is often associated with the progression of haematological malignancies. The molecular regulators of lineage choices in the context of tyrosine kinase inhibitor (TKI) resistance remain poorly understood in chronic myeloid leukemia (CML). To find a potential molecular regulator contributing to lineage distribution and TKI resistance, we undertook an RNA-sequencing approach for identifying microRNAs (miRNAs).

CD66 and CD49f expressing cells are associated with distinct neoplastic phenotypes and progression in human cervical cancer.

Background: In this study, building on our recent work identifying a subset of CD66+ve cells with distinctive tumourigenic properties in human cervical cancers, we examine patterns of expression and function of these cells; to generate insights into the process of metastasis.

Methods: Our broad approach in this study has been to compare the expression and function of two subsets marked by CD66 and CD49f. We use a combination of histopathology, immunostaining and flow cytometry, functional analysis of an established cervical cancer cell line and a retrospective analysis of a cohort of cervical cancer.

CD66+ cells in cervical precancers are partially differentiated progenitors with neoplastic traits.

Cervical cancers, a malignancy associated with oncogenic papilloma viruses, remain a major disease burden in the absence of effective implementation of preventive strategies. CD66(+) cells have previously been identified as a tumor-propagating subset in cervical cancers. We investigated the existence, differentiation state, and neoplastic potential of CD66(+) cells in a precancer cell line harboring HPV31b episomes.

Toll-like receptors 7, 8, and 9 expression and function in primary human cervical cancer Langerhans cells: evidence of anergy.

Objective: Human papillomavirus oncoproteins E6 and E7 down modulate Toll-like receptor (TLR) 9 expression in infected keratinocytes. We explored the status of expression and function of TLR7, TLR8, and TLR9 in primary human Langerhans cells (LCs) isolated from cervical tumors.

Methodology: Single-cell suspensions were made from fresh tissues of squamous cell carcinoma (International Federation of Gynecology and Obstetrics stage IB2); myeloid dendritic cells were purified using CD1c magnetic activated cell separation kits.