Evolutionary relevance of single nucleotide variants within the forebrain exclusive human accelerated enhancer regions.

Background: Human accelerated regions (HARs) are short conserved genomic sequences that have acquired significantly more nucleotide substitutions than expected in the human lineage after divergence from chimpanzees. The fast evolution of HARs may reflect their roles in the origin of human-specific traits. A recent study has reported positively-selected single nucleotide variants (SNVs) within brain-exclusive human accelerated enhancers (BE-HAEs) hs1210 (forebrain), hs563 (hindbrain) and hs304 (midbrain/forebrain).

Overlap of diabetic ketoacidosis and hyperosmolar hyperglycemic state.

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia state (HHS) are two life-threatening metabolic complications of diabetes that significantly increase mortality and morbidity. Despite major advances, reaching a uniform consensus regarding the diagnostic criteria and treatment of both conditions has been challenging. A significant overlap between these two extremes of the hyperglycemic crisis spectrum poses an additional hurdle.

Visceral Leishmaniasis (Kala-Azar): A Triumph Against a Trickster Disease.

Leishmaniasis, a protozoan parasitic pathology, is caused by infection with a parasite known as , which is transmitted to humans through the bite of a sand fly. The disease has various manifestations, including cutaneous leishmaniasis, visceral leishmaniasis (VL), and disseminated cutaneous leishmaniasis. Visceral leishmaniasis (VL), also known as kala-azar, is mostly seen in the Asian and African regions and can be deadly if left untreated.

Niemann-Pick Disease Type A: A Rare Disease With a Fatal Outcome.

Niemann-Pick disease (NPD) type A is a fatal autosomal recessive lysosomal storage disorder. This rare condition impairs the metabolization of lipids, leading to their accumulation within the cells. Consequently, it causes growth retardation, pancytopenia, and cellular malfunctioning in various organ systems, including ocular, hepatic, pulmonary, brain, and neuronal tissues.

Recurrent Episodes of Paroxysmal Supraventricular Tachycardia Triggered by Dyspepsia: A Rare Case of Gastrocardiac Syndrome.

Supraventricular tachycardia (SVT) refers to the narrow complex tachycardia originating at or above the bundle of His. Several risk factors are associated with the development and recurrence of SVT, but its association with gastric problems, especially dyspepsia, is relatively rare. We report the case of a 54-year-old female who presented to the emergency room (ER) with palpitations, which were diagnosed as an episode of paroxysmal supraventricular tachycardia (PSVT).

Mutational Landscape of Pirin and Elucidation of the Impact of Most Detrimental Missense Variants That Accelerate the Breast Cancer Pathways: A Computational Modelling Study.

Pirin () protein is highly conserved in both prokaryotic and eukaryotic organisms. Recently, it has been identified that positively regulates breast cancer cell proliferation, xenograft tumor formation, and metastasis, through an enforced transition of G1/S phase of the cell cycle by upregulation of E2F1 expression at the transcriptional level. Keeping in view the importance of in many crucial cellular processes in humans, we used a variety of computational tools to identify non-synonymous single-nucleotide polymorphisms (SNPs) in the gene that are highly deleterious for the structure and function of protein.

Immunogenomics guided design of immunomodulatory multi-epitope subunit vaccine against the SARS-CoV-2 new variants, and its validation through in silico cloning and immune simulation.

Reports of the novel and more contagious strains of SARS-CoV-2 originating in different countries have further aggravated the pandemic situation. The recent substitutions in spike protein may be critical for the virus to evade the host's immune system and therapeutics that have already been developed. Thus, this study has employed an immunoinformatics pipeline to target the spike protein of this novel strain to construct an immunogenic epitope (CTL, HTL, and B cell) vaccine against the new variant.

Evolutionary and structural analysis of SARS-CoV-2 specific evasion of host immunity.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading fast worldwide. There is a pressing need to understand how the virus counteracts host innate immune responses. Deleterious clinical manifestations of coronaviruses have been associated with virus-induced direct dysregulation of innate immune responses occurring via viral macrodomains located within nonstructural protein-3 (Nsp3).

Core amino acid substitutions in HCV-3a isolates from Pakistan and opportunities for multi-epitopic vaccines.

Hepatitis C virus (HCV), which infected 71 million worldwide and about 5%-6% are from Pakistan, is an ssRNA virus, responsible for end-stage liver disease. To date, no effective therapy is available to cure this disease. Hence, it is important to study the most prevalent genotypes infecting human population and design novel vaccine or small molecule inhibitors to control the infections associated with HCV.

Subtractive proteomics and immunoinformatics approaches to explore Bartonella bacilliformis proteome (virulence factors) to design B and T cell multi-epitope subunit vaccine.

Bartonella bacilliformis a gram-negative facultative aerobe responsible for the Carrion's disease widely distributed in Ecuador, Peru, and Colombia with a high mortality rate when no specific treatment is received. B bacilliformis is transmitted by Sand fly (Lutzomyia verrucarum) to healthy individuals. Immunoinformatic and subtractive proteomics approaches were employed in this study to prioritize the best candidates for vaccine designing.

Proteome-wide mapping and reverse vaccinology-based B and T cell multi-epitope subunit vaccine designing for immune response reinforcement against .

a prominent pathogen responsible for acute periodontal diseases, is widely studied by the scientific community for its successful evasion of the host immune system. is associated with rheumatoid arthritis, dementia, and Alzheimer's. The pathogen successfully survives itself against the heavy load of conventional antibiotics because of its ability to evade the host immune system.

Structural insights into the mechanism of RNA recognition by the N-terminal RNA-binding domain of the SARS-CoV-2 nucleocapsid phosphoprotein.

The emergence of recent SARS-CoV-2 has become a global health issue. This single-stranded positive-sense RNA virus is continuously spreading with increasing morbidities and mortalities. The proteome of this virus contains four structural and sixteen nonstructural proteins that ensure the replication of the virus in the host cell.

Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products.

Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable.

Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro).

The current coronavirus (SARS-COV-2) pandemic and phenomenal spread to every nook and cranny of the world has raised major apprehensions about the modern public health care system. So far as a result of this epidemic, 4,434,653 confirmed cases and 302,169 deaths are reported. The growing infection rate and death toll demand the use of all possible approaches to design novel drugs and vaccines to curb this disease.

Dynamics Insights Into the Gain of Flexibility by Helix-12 in ESR1 as a Mechanism of Resistance to Drugs in Breast Cancer Cell Lines.

Incidents of breast cancer (BC) are on the rise on a daily basis and have proven to be the most prevelant cause of death for women in both developed and developing countries. Among total BC cases diagnosed after menopause, 70% of cases are Estrogen Receptor (ER) positive (ER-positive or ER+). Mutations in the LBD (ligand-binding domain) of the ER have recently been reported to be the major cause of resistance to potent antagonists.

Immunoinformatic and systems biology approaches to predict and validate peptide vaccines against Epstein-Barr virus (EBV).

Epstein-Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), is a member of the Herpesviridae family and causes infectious mononucleosis, Burkitt's lymphoma, and nasopharyngeal carcinoma. Even in the United States of America, the situation is alarming, as EBV affects 95% of the young population between 35 and 40 years of age. In this study, both linear and conformational B-cell epitopes as well as cytotoxic T-lymphocyte (CTL) epitopes were predicted by using the ElliPro and NetCTL.

Sobolev's embedding on time scales.

For , the embeddings of Sobolev spaces of functions defined on an open subset of an arbitrary time scale , , endowed with the Lebesgue Δ-measure have been developed in (Agarwal et al. in Adv. Differ.

Allosteric ligands for the pharmacologically important Flavivirus target (NS5) from ZINC database based on pharmacophoric points, free energy calculations and dynamics correlation.

Dengue virus belongs to a group of human pathogens, which causes different diseases, dengue hemorrhagic fever and dengue shock syndrome in humans. It possesses RNA as a genetic material and is replicated with the aid of NS5 protein. RNA-dependent RNA polymerase (RdRp) is an important domain of NS5 in the replication of that virus.

In-vitro analysis of selective nutraceuticals binding to human transcription factors through computer aided molecular docking predictions.

The contest of cancer couldn't be completed without novel drug with novel modes of action, improved efficacy and acceptable pharmacokinetic properties. Transcription factors are attractive targets to develop anti-cancerous drugs. 6-Gingerol, Anethol analogues, Capsaicinoids, Curcumin, Dibenzoylmethane, Diosgenin, Eugenol, Gambogic acid, Thymoquinone, Ursolic acid, Xanthohumol, Zerumbone are the promising nutraceuticals that help in the prevention of cancer.