Force-regulated chaperone activity of BiP/ERdj3 is opposite to their homologs DnaK/DnaJ.

Polypeptide chains experience mechanical tension while translocating through cellular tunnels, which are subsequently folded by molecular chaperones. However, interactions between tunnel-associated chaperones and these emerging polypeptides under force is not completely understood. Our investigation focused on mechanical chaperone activity of two tunnel-associated chaperones, BiP and ERdj3 both with and without mechanical constraints and comparing them with their cytoplasmic homologs: DnaK and DnaJ.

Identifying polymorphic cis-regulatory variants as risk markers for lung carcinogenesis and chemotherapy responses in tobacco smokers from eastern India.

Aberrant expression of xenobiotic metabolism and DNA repair genes is critical to lung cancer pathogenesis. This study aims to identify the cis-regulatory variants of the genes modulating lung cancer risk among tobacco smokers and altering their chemotherapy responses. From a list of 2984 SNVs, prioritization and functional annotation revealed 22 cis-eQTLs of 14 genes within the gene expression-correlated DNase I hypersensitive sites using lung tissue-specific ENCODE, GTEx, Roadmap Epigenomics, and TCGA datasets.

Direct Observation of the Mechanical Role of Bacterial Chaperones in Protein Folding.

Protein folding under force is an integral source of generating mechanical energy in various cellular processes, ranging from protein translation to degradation. Although chaperones are well known to interact with proteins under mechanical force, how they respond to force and control cellular energetics remains unknown. To address this question, we introduce a real-time magnetic tweezer technology herein to mimic the physiological force environment on client proteins, keeping the chaperones unperturbed.

Connecting conformational stiffness of the protein with energy landscape by a single experiment.

The structure-function dynamics of a protein as a flexible polymer is essential to describe its biological functions. Here, using single-molecule magnetic tweezers, we have studied the effect of ionic strength on the folding mechanics of protein L, and probed its folding-associated physical properties by re-measuring the same protein in a range of ammonium sulfate concentrations from 150 mM to 650 mM. We observed an electrolyte-dependent conformational dynamics and folding landscape of the protein in a single experiment.

Direct observation of chaperone-modulated talin mechanics with single-molecule resolution.

Talin as a critical focal adhesion mechanosensor exhibits force-dependent folding dynamics and concurrent interactions. Being a cytoplasmic protein, talin also might interact with several cytosolic chaperones; however, the roles of chaperones in talin mechanics remain elusive. To address this question, we investigated the force response of a mechanically stable talin domain with a set of well-known unfoldase (DnaJ, DnaK) and foldase (DnaKJE, DsbA) chaperones, using single-molecule magnetic tweezers.

Integrin Regulated Autoimmune Disorders: Understanding the Role of Mechanical Force in Autoimmunity.

The pathophysiology of autoimmune disorders is multifactorial, where immune cell migration, adhesion, and lymphocyte activation play crucial roles in its progression. These immune processes are majorly regulated by adhesion molecules at cell-extracellular matrix (ECM) and cell-cell junctions. Integrin, a transmembrane focal adhesion protein, plays an indispensable role in these immune cell mechanisms.

No association of the common Asian mitochondrial DNA haplogroups with lung cancer in East Indian population.

Objectives: Mitochondrial dysfunction has long been associated with the pathogenesis of lung cancer (LC). Mitochondrial DNA (mtDNA) haplogroups have been reported to modify the risk of LC in a few different populations; however, no study has been done among the Indians. Here, we explore the relationship between mtDNA haplogroups and LC in a representative eastern Indian sample set.

A comprehensive meta-analysis and a case-control study give insights into genetic susceptibility of lung cancer and subgroups.

Reports of genetic association of polymorphisms with lung cancer in the Indian subcontinent are often conflicting. To summarise and replicate published evidence for association with lung cancer and its subgroups. We performed a meta-analysis of candidate associations on lung cancer, its histological subtypes and smoking status in the Indian subcontinent following PRISMA guidelines.

Cutting-Edge Single-Molecule Technologies Unveil New Mechanics in Cellular Biochemistry.

Single-molecule technologies have expanded our ability to detect biological events individually, in contrast to ensemble biophysical technologies, where the result provides averaged information. Recent developments in atomic force microscopy have not only enabled us to distinguish the heterogeneous phenomena of individual molecules, but also allowed us to view up to the resolution of a single covalent bond. Similarly, optical tweezers, due to their versatility and precision, have emerged as a potent technique to dissect a diverse range of complex biological processes, from the nanomechanics of ClpXP protease-dependent degradation to force-dependent processivity of motor proteins.

A meta-analysis and analysis of polymorphic variants conferring breast cancer risk in the Indian subcontinent.

Genetic association studies on breast cancer on the Indian subcontinent have yielded conflicting results, and the precise effect of these variants on breast cancer pathogenesis is not known. Genomic variants, as obtained from selected studies from the Indian subcontinent, were subjected to random-effects and fixed-effect meta-analysis. Functional annotation of the relevant variants was done through a tried and tested pipeline.

Force-Directed "Mechanointeractome" of Talin-Integrin.

Mechanotransduction from the extracellular matrix into the cell is primarily supervised by a transmembrane receptor, integrin, and a cytosolic protein, talin. Integrin binds ligands on the extracellular side, whereas talin couples integrin receptors to the actin cytoskeleton and later acts as a "force buffer". Talin and integrin together form a mechanosensitive signaling hub that regulates crucial cellular processes and pathways, including cell signaling and formation of focal adhesion complexes, which help cells to sense their mechano-environment and transduce the signal accordingly.

Meta-analysis and prioritization of human skin pigmentation-associated GWAS-SNPs using ENCODE data-based web-tools.

Skin pigmentation in human is a complex trait, which varies widely, both within and between human populations. The exact players governing the trait of skin pigmentation remain elusive till date. Various Genome Wide Association Studies (GWAS) have shown the association of different genomic variants with normal human skin pigmentation, often indicating genes with no direct implications in melanin biosynthesis or distribution.