Molecular Basis of UG-Rich Element Recognition by ESRP2 RRM3.

Epithelial splicing regulatory protein 2 (ESRP2) plays a pivotal role in alternative splicing regulation, particularly in maintaining epithelial cell identity and suppressing epithelial-to-mesenchymal transition (EMT). Despite its biological significance, the structural basis for its RNA-binding specificity remains poorly understood. In this study, we report the solution structure and RNA-binding properties of the RNA Recognition Motif (RRM3) of human ESRP2 using an integrative approach combining nuclear magnetic resonance (NMR) spectroscopy, ITC, molecular docking, and MD simulations.

Differentially regulated saliva proteome and metabolome: a way forward for risk-assessment of oral cancer among tobacco abusers.

Oral cancer (OC) is a malignant tumour with high morbidity and mortality. Significant contributory factors include alcohol and tobacco abuse that dysregulate the proteome and metabolome. We assessed saliva as a noninvasive bio-sample to understand the changes in proteome and metabolome in OC, tobacco abusers (TA), and controls.

Drug-Repurposing Screen Identifies Thiostrepton as a Novel Regulator of the Tumor Suppressor DAB2IP.

The tumor suppressor DAB2IP, a RasGAP and cytoplasmic adaptor protein, modulates signal transduction in response to several extracellular stimuli, negatively regulating multiple oncogenic pathways. Accordingly, the loss of DAB2IP in tumor cells fosters metastasis and enhances chemo- and radioresistance. DAB2IP is rarely mutated in cancer but is frequently downregulated or inactivated by multiple mechanisms.

NLRP6 governs hippocampal microglial phagocytosis to resist stress-induced depressive-like behaviors in mice and the intervention effect of bezafibrate.

Introduction: Microglial phagocytosis is crucial for maintaining central nervous system (CNS) homeostasis and is implicated in the development of depression. NOD-like receptor family pyrin domain containing 6 (NLRP6) represents a potential target for depression treatment, but underlying mechanisms remain unclear. Bezafibrate has been shown to exhibit multiple neuroprotective effects.

Assessment of γ-herpesvirus infection dynamics in non-hospitalised people living with HIV during the COVID-19 pandemic in South Africa.

Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are oncogenic human γ-herpesviruses highly prevalent in Sub-Saharan Africa. Both establish latent early-life infections, with intermittent lytic reactivations, often triggered by viral co-infections, particularly in immunocompromised individuals. In this retrospective observational cross-sectional sub-study, we leveraged a cohort of 407 non-hospitalised people living with HIV (PLWH) attending antiretroviral therapy services in South Africa during the COVID-19 pandemic, with previously reported increased reactivation of KSHV upon SARS-CoV-2 exposure, particularly in COVID-19 unvaccinated individuals (Lambarey et al.

Cracking the code of a coastal oil yeast: the genome of INDKK.

INDKK, an oleaginous red yeast isolated from mangrove forest soil, efficiently metabolizes biomass hydrolysates and accumulates lipids of more than 60% of its dry weight. Hybrid genome assembly (Illumina and Oxford Nanopore) produced 24 scaffolds comprising a 21.05 Mb nuclear and ~26 kb mitochondrial genome.

Refining treatment strategies for non-small cell lung cancer lacking actionable mutations: insights from multi-omics studies.

Non-small cell lung cancer (NSCLC) represents a heterogeneous group of malignancies characterised by diverse histological and molecular features. Some NSCLCs, particularly adenocarcinomas, harbour genomic alterations in receptor tyrosine kinases or downstream RAS/RAF signalling pathways, which are targets of effective therapies. NSCLCs lacking actionable genomic alterations often benefit from immune checkpoint inhibitors, though only a minority of patients achieve long-term survival.

Antifungal therapeutic potential of Candida albicans Fun30: screening and validation of novel inhibitors against Candida albicans.

WHO has listed Candida albicans as a fungal pathogen of priority. With the increasing incidence of C. albicans infection and limited treatment strategies, the identification of new drug targets and inhibitor molecules is of global concern.

Indigenous Plasmodium vivax upsurge in the Eastern Mediterranean, Western Pacific, and South East Asia regions - beyond the constant culpability of climate change, COVID-19, and armed conflicts.

Controlling Plasmodium vivax presents greater challenges compared to Plasmodium falciparum. Here, we analyzed epidemiological data on indigenous P. vivax cases from the Eastern Mediterranean, Southeast Asia, and Western Pacific regions in recent years.

Protein functional domain analysis enhances genotype-phenotype associations in comparative genomic studies of .

Introduction: represents a paradigm for studies on antibiotic resistance. Nevertheless, despite the considerable number of genome sequences that have been released in recent years, there is still a paucity of knowledge regarding the genomic determinants of the typical phenotypic traits associated with pulmonary infection.

Methods: The genomes of 40 strains of were sequenced over an 8-year period (2007-2014), isolated from the sputum of a single patient with cystic fibrosis in Trentino, Italy.

VEGFR1 as a Target for Cardiovascular Gene Therapy.

Vascular endothelial growth factor receptor 1 (VEGFR1) is a key regulator of endothelial function, angiogenesis, inflammation, and cardiomyocyte survival, with both beneficial and deleterious effects in cardiovascular disease. In this review, we provide some key information on the molecular biology governing VEGFR1 function, its role in cardiovascular diseases and describe gene therapy strategies targeting either membrane-bound or its soluble isoform sFLT1 to treat these diseases. Clinical Relevance Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide.

Genome wide investigation and transcriptional profiling of SWEET genes in two contrasting cultivars of foxtail millet under abiotic stresses.

The SWEET (Sugars will eventually be exported transporter) gene family is an important class of sugar transporters that regulates diverse aspects of plant physiology such as apoplastic phloem loading, plant-pathogen interactions and plant responses to abiotic stresses. While majority of the studies on SWEET family in plants have been performed in C3 species, there are limited reports on C4 plants. In this study we conducted genome wide investigation of the SWEET gene family in foxtail millet, a naturally stress tolerant C4 crop.

BCG and beyond: unlocking new frontiers in TB vaccine development.

Please confirm that the below Frontiers AI generated Alt-Text is an accurate visual description of your Figure(s). These Figure Alt-text proposals won't replace your figure captions and will not be visible on your article. If you wish to make any changes, kindly provide the exact revised Alt-Text you would like to use, ensuring that the word-count remains at approximately 100 words for best accessibility results.

Phytochemical Analysis, Antioxidant Activity, and Anticancer Potential of Welw-Bark Extract: A Traditional Remedy Utilized by Indigenous Communities in KwaZulu-Natal and Eastern Cape Provinces of South Africa.

Despite the significant advancements in treatment and prevention, the fight against cancer is ongoing worldwide. This study evaluated the pharmacological properties and anticancer activity of bark, traditionally used by the indigenous communities of KwaZulu Natal and Eastern Cape Provinces of South Africa to treat cancer and related illnesses. Phytochemical screening, high-performance liquid chromatography-diode array detection (HPLC-DAD), and Fourier-transform infrared spectroscopy (FTIR) analyses were carried out using established protocols.

BCAP Is an Interferon-Stimulated Gene That Enhances Type I Interferon Activity in Response to Lipopolysaccharide.

The B-cell adapter for PI3K (BCAP) is a protein that connects membrane receptor signaling to the PI3K pathway. In fibroblasts or dendritic cells, priming the cGAS nucleic-acid-sensing pathway increases BCAP expression and enhances type I interferon (IFN-I) production upon lipopolysaccharide (LPS) stimulation. These findings corroborate the idea that BCAP may bias cytokine production toward IFN during inflammation, indicating its potential involvement in IFN-driven diseases like systemic lupus erythematosus (SLE).

Conservation of dark CPD photolyase function in blind cavefish.

DNA damage is generated by various environmental stressors and so DNA repair systems must inevitably adapt to changing environments. Photolyases represent a highly conserved class of enzymes which repair UV-induced covalent crosslinks between adjacent pyrimidine bases (CPD and 6-4 photoproducts) via photoreactivation. In the blind cavefish Phreatichthys andruzzii which has evolved for millions of years completely isolated from UV radiation and visible light, we have documented multiple polymorphisms and loss of function mutations affecting both the 6-4phr and DASHphr photolyase genes while strangely, the CPDphr gene remains highly conserved.

Identification of new dasatinib analogues targeting mutated BCR-ABL1: virtual screening, molecular docking, and dynamics simulations studies.

Drug resistance is a major challenge in cancer chemotherapy and accounts for a majority of cancer-related deaths globally. One of the well-identified and characterised mechanisms of drug resistance in chronic myeloid leukaemia (CML) is the presence of BCR-ABL1 mutations, which is responsible for resistance against first-line tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, and nilotinib. In the present work, we first performed a three-tier virtual screening against the human tyrosine kinase ABL1 protein (PDB ID: 2GQG).

Improved Bicyclic Pyrrolidine Analogues Inhibit Growth In Vitro and Cure Infection In Vivo.

Inhibition of phenylalanine tRNA synthetase (PheRS) by bicyclic pyrrolidines provides a potent and specific inhibition of parasite growth. Herein, we describe novel bicyclic pyrrolidines designed to explore structure-activity relationships with vs human PheRS. Modification of the biaryl alkyne extension, which fits into the phenylalanine-binding site, showed a strong preference for hydroxyl addition over and .

Spatiotemporal epidemiology and clinical manifestations of two decades of scrub typhus in India: a systematic review and meta-analysis.

Background: Scrub typhus, once known as tsutsugamushi fever and attributed to Rickettsia, has transformed into a growing public health concern. Despite its increasing incidence in India, comprehensive spatiotemporal analyses of scrub typhus have been lacking.

Methods: This study examines the prevalence of scrub typhus cases reported from 2003 to 2023, using available literature to provide a breakdown of cases by year and state in India, aiming to elucidate the disease's spatiotemporal dynamics.

Isolation, characterization, and biomedical potential of phycoerythrin phycobiliprotein from Kappaphycus alvarezii (Doty) L. M. Liao: antimicrobial, antioxidant, and anticancer activities.

Kappaphycus alvarezii (Doty) L. M. Liao, a red seaweed widely cultivated for carrageenan polysaccharide, is also a potential source of the valuable pigment phycoerythrin (PE).

Genomic and molecular evidence that the LncRNA DSP-AS1 modulates desmoplakin expression.

Cardiac desmosomes are specialized cell junctions responsible for cardiomyocytes mechanical coupling. Mutation in desmosomal genes cause autosomal dominant and recessive familial arrhythmogenic cardiomyopathy. Motivated by evidence that Mendelian diseases share genetic architecture with common complex traits, we assessed whether common variants in any desmosomal gene were associated with cardiac conduction traits in the general population.

Transfusion-transmitted spp. infections and safety challenges for malaria in the Indian subcontinent: a systematic review.

Blood transfusion is a globally life-saving intervention, but blood-borne pathogens can threaten its effectiveness. While blood bags are systematically screened for viral and bacterial pathogens, parasite infections are generally overlooked. In this review, we analysed the current literature on transfusion-transmitted malaria (TTM) in India over the past five decades.

Proteomic Analysis of CHIKV-nsP3 Host Interactions in Liver Cells Identifies Novel Interacting Partners.

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has re-emerged, causing widespread outbreaks and a significant clinical burden. Despite advances in virology, the molecular mechanisms governing CHIKV's interaction with host cells remain poorly understood. In this study, we aimed to identify novel host protein interactors of the CHIKV nonstructural protein 3 (nsP3), a critical component of the viral replication complex, using mass spectrometry-based proteomic profiling in liver-derived Huh7 cells.

Clinical and molecular epidemiology of chikungunya outbreaks during 2019-2022 in India.

Chikungunya fever (CHIKF) is endemic in India, with multiple outbreaks occurring across the country since its reemergence in 2005. Suspected CHIKF patients were recruited from four clinical sites during 2019-2022, with data collected on sociodemographic, clinical, and epidemiological aspects. Sera samples were screened for IgM, IgG antibodies and viral RNA along with their neutralizing capacity.

Immunomodulatory effects of atorvastatin on peripheral blood mononuclear cells infected with .

Background: Tuberculosis (TB) remains a major global health threat, contributing substantially to high morbidity and mortality rates. This underscores the urgent need for more effective interventions. Recent studies highlight the potential of host-directed therapy approaches to enhance immune defences against TB.