NSD3 protein methylation and stabilization transforms human ES cells into variant state.

Cultured human embryonic stem cells (hESCs) can develop genetic anomalies that increase their susceptibility to transformation. In this study, we characterized a variant hESC (vhESC) line and investigated the molecular mechanisms leading to the drift towards a transformed state. Our findings revealed that vhESCs up-regulate EMT-specific markers, accelerate wound healing, exhibit compromised lineage differentiation, and retain pluripotency gene expression in teratomas.

Mitochondrial calcium uptake orchestrates vertebrate pigmentation via transcriptional regulation of keratin filaments.

Mitochondria regulate several physiological functions through mitochondrial Ca2+ dynamics. However, role of mitochondrial Ca2+ signaling in melanosome biology remains unknown. Here, we show that pigmentation requires mitochondrial Ca2+ uptake.

A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication.

Protein lysine methyltransferases (PKMTs) methylate histone and non-histone proteins to regulate biological outcomes such as development and disease including viral infection. While PKMTs have been extensively studied for modulating the antiviral responses via host gene regulation, their role in methylation of proteins encoded by viruses and its impact on host-pathogen interactions remain poorly understood. In this study, we discovered distinct nucleo-cytoplasmic form of euchromatic histone methyltransferase 1 (EHMT1N/C), a PKMT, that phase separates into viral inclusion bodies (IBs) upon cytoplasmic RNA-virus infection (Sendai Virus).

Role of miR-128-3p and miR-195-5p as biomarkers of coronary artery disease in Indians: a pilot study.

Coronary artery disease (CAD) imposes a significant economic burden in developing countries like India. Timely diagnosis and treatment should be prioritized to mitigate the disease. Current diagnostic tools being invasive and less specific raise the need to develop less invasive and more reliable molecular biomarkers.

Uracil as a biomarker for spatial pyrimidine metabolism in the development of gingivobuccal oral squamous cell carcinoma.

No biomarker has yet been identified that allows accurate diagnosis and prognosis of oral cancers. In this study, we investigated the presence of key metabolites in oral cancer using proton nuclear magnetic resonance (NMR) spectroscopy to identify metabolic biomarkers of gingivobuccal oral squamous cell carcinoma (GB-OSCC). NMR spectroscopy revealed that uracil was expressed in 83.

Molecular clues unveiling spinocerebellar ataxia type-12 pathogenesis.

Spinocerebellar Ataxia type-12 (SCA12) is a neurodegenerative disease caused by tandem CAG repeat expansion in the 5'-UTR/non-coding region of . Molecular pathology of SCA12 has not been studied in the context of CAG repeats, and no appropriate models exist. We found in human SCA12-iPSC-derived neuronal lineage that expanded CAG in transcript forms nuclear RNA foci and were found to sequester variety of proteins.

Noncoding RNAs: Emerging regulators of behavioral complexity.

The mammalian genome encodes thousands of non-coding RNAs (ncRNAs), ranging in size from about 20 nucleotides (microRNAs or miRNAs) to kilobases (long non-coding RNAs or lncRNAs). ncRNAs contribute to a layer of gene regulation that could explain the evolution of massive phenotypic complexity even as the number of protein-coding genes remains unaltered. We propose that low conservation, poor expression, and highly restricted spatiotemporal expression patterns-conventionally considered ncRNAs may affect behavior through direct, rapid, and often sustained regulation of gene expression at the transcriptional, post-transcriptional, or translational levels.

Gallic Acid Derived 1, 2-Diarylindole as a Potential Antifungal Agent against Candida Strain.

Background: In recent decades, Candida albicans has become a serious issue for public health. The worldwide rapid rise in drug resistance to conventional therapies is the main contributing reason. Moreover, because of their potent activity at low concentrations and apparent lack of toxicity, compounds originating from plants are used in therapeutic treatments because of their potent activity at low concentrations and apparent lack of toxicity.

Evolution of genome diagnostics in epidermolysis bullosa: Unveiling the power of next-generation sequencing.

Background: Genome diagnostics is considered gold standard diagnostics for epidermolysis bullosa (EB), a phenotypically and genetically heterogeneous group of rare disorders characterized by blistering and wounding of mucocutaneous tissues. EB is caused by pathogenic variants in genes encoding proteins of the dermo-epidermal junction. Accurate genetic diagnosis of EB is crucial for prognostication, counselling and precision-medicine.

Hydrocarbon stapled temporin-L analogue as potential antibacterial and antiendotoxin agents with enhanced protease stability.

Antimicrobial resistance (AMR) is a serious global concern and a huge burden on the healthcare system. Antimicrobial peptides (AMPs) are considered as a solution of AMR due to their membrane-lytic and intracellular mode of action and therefore resistance development against AMPs is less frequent. One such AMPs, temporin-L (TL) is a 13-mer peptide reported as a potent and broad-spectrum antibacterial agent with significant immunomodulatory activity.

Mapping the genetic architecture of idiopathic pulmonary fibrosis: Meta-analysis and epidemiological evidence of case-control studies.

Background: Idiopathic pulmonary fibrosis (IPF) is a rare and devastating fibrotic lung disorder with unknown etiology. Although it is believed that genetic component is an important risk factor for IPF, a comprehensive understanding of its genetic landscape is lacking. Hence, we aimed to highlight the susceptibility genes and pathways implicated in IPF pathogenesis through a two-staged systematic literature search of genetic association studies on IPF, followed by meta-analysis and pathway enrichment analysis.

Endocrine disruptors: Unravelling the link between chemical exposure and Women's reproductive health.

An Endocrine Disrupting Chemical (EDC) is any compound that disrupts the function of the endocrine system in humans and is ubiquitous in the environment either as a result of natural events or through anthropogenic activities. Bisphenol A, phthalates, parabens, pesticides, triclosan, polychlorinated biphenyls, and heavy metals, which are frequently found in the pharmaceutical, cosmetic, and packaging sectors, are some of the major sources of EDC pollutants. EDCs have been identified to have a deteriorating effect on the female reproductive system, as evidenced by the increasing number of reproductive disorders such as endometriosis, uterine fibroids, polycystic ovary syndrome, premature ovarian failure, menstrual irregularity, menarche, and infertility.

Assessment of clinically actionable pharmacogenetic markers to stratify anti-seizure medications.

Epilepsy treatment is challenging due to heterogeneous syndromes, different seizure types and higher inter-individual variability. Identification of genetic variants predicting drug efficacy, tolerability and risk of adverse-effects for anti-seizure medications (ASMs) is essential. Here, we assessed the clinical actionability of known genetic variants, based on their functional and clinical significance and estimated their diagnostic predictability.

Cdk5-Mediated Brain Unfolded Protein Response Upregulation Associated with Cognitive Impairments in Type 2 Diabetes and Ameliorative Action of NAC.

The role of cyclin-dependent kinase 5 (Cdk5) in the normal functioning of the central nervous system and synaptic plasticity is well established. However, dysregulated kinase activity can have a significant impact on neurodegeneration and cognitive impairment. Cdk5 hyperactivation is linked to diabetes-associated neurodegeneration, but the underlying mechanism is not fully understood.

Mitochondrial calcium signaling mediated transcriptional regulation of keratin filaments is a critical determinant of melanogenesis.

Mitochondria are versatile organelles that regulate several physiological functions. Many mitochondria-controlled processes are driven by mitochondrial Ca signaling. However, role of mitochondrial Ca signaling in melanosome biology remains unknown.

Lipid mediated brain disorders: A perspective.

The brain, one of the most resilient organs of the body is highly enriched in lipid content, suggesting the essential role of lipids in brain physiological activities. Lipids constitute an important structural part of the brain and act as a rich source of metabolic energy. Besides, lipids in their bioactive form (known as bioactive lipids) play an essential signaling and regulatory role, facilitating neurogenesis, synaptogenesis, and cell-cell communication.

Impact of spatial metabolomics on immune-microenvironment in oral cancer prognosis: a clinical report.

MALDI imaging for metabolites and immunohistochemistry for 38 immune markers was used to characterize the spatial biology of 2 primary oral tumours, one from a patient with an early recurrence (Tumour R), and the other from a patient with no recurrence 2 years after treatment completion (Tumour NR). Tumour R had an increased purine nucleotide metabolism in different regions of tumour and adenosine-mediated suppression of immune cells compared to Tumour NR. The differentially expressed markers in the different spatial locations in tumour R were CD33, CD163, TGF-β, COX2, PD-L1, CD8 and CD20.