Pattern of care and treatment outcomes of metastatic non-clear cell kidney cancer: a single centre experience from India.

Background: Non-clear-cell renal cell carcinoma (nccRCC) refers to a rare diverse heterogeneous group of tumours; usually treated with immune check point inhibitors and or tyrosine kinase inhibitors (TKIs). Prospective large-scale data from Asian countries is limited.

Methods: This is a retrospective study of patients with metastatic nccRCC treated at Tata Medical Centre, Kolkata, India, from 2012 to 2022.

Nick Induced Dynamics in Supercoiled DNA Facilitates the Protein Target Search Process.

A DNA nick, defined as a discontinuity in a double-stranded DNA molecule where the phosphodiester bond between adjacent nucleotides of one strand is absent due to enzyme action, serves as an effective mechanism to alleviate stress in supercoiled DNA. This stress release is essential for the smooth operation of transcriptional machinery. However, the underlying mechanisms and their impact on protein search dynamics, which are crucial for initiating transcription, remain unclear.

Role of Shape Deformation of DNA-Binding Sites in Regulating the Efficiency and Specificity in Their Recognition by DNA-Binding Proteins.

Accurate transcription of genetic information is crucial, involving precise recognition of the binding motifs by DNA-binding proteins. While some proteins rely on short-range hydrophobic and hydrogen bonding interactions at binding sites, others employ a DNA shape readout mechanism for specific recognition. In this mechanism, variations in DNA shape at the binding motif resulted from either inherent flexibility or binding of proteins at adjacent sites are sensed and capitalized by the searching proteins to locate them specifically.

The relationship between telemedicine tools and physician satisfaction, quality of care, and patient visits during the COVID-19 pandemic.

Objective: The objective of our study is to investigate the impacts of telemedicine technology and its specific tools on physicians' overall satisfaction, quality of care, and percentage of patient visits in ambulatory care settings after the COVID-19 lockdowns.

Materials And Methods: Data for our analysis was sourced from the 2021 annual National Electronic Health Records Survey (NEHRS), which included 1,875 complete questionnaire responses from physicians in the 2021 NEHRS. We used regression models to test the effects of telemedicine on physicians' overall satisfaction, quality of care, and percentage of patients' visits.

The role of nucleotide opening dynamics in facilitated target search by DNA-repair proteins.

Preserving the genomic integrity stands a fundamental necessity, primarily achieved by the DNA repair proteins through their continuous patrolling on the DNA in search of lesions. However, comprehending how even a single base-pair lesion can be swiftly and specifically recognized amidst millions of base-pair sites remains a formidable challenge. In this study, we employ extensive molecular dynamics simulations using an appropriately tuned model of both protein and DNA to probe the underlying molecular principles.

Reducing musculoskeletal disorders in iron ore mine operators: A fuzzy-based intervention approach.

Background: This study focuses on evaluating the exposure to whole-body vibration (WBV) and association of musculoskeletal disorders (MSDs) with various risk factors among dumper operators in the mining industry. Despite the issue's significance, prior research has been limited.

Objective: The study introduces a novel fuzzy-based approach for identifying, selecting, and prioritizing safety measures to mitigate MSD risks.

Unusual weak and delayed GTPase activity of FtsZ from human pathogenic bacteria Helicobacter pylori.

Actively treadmilling FtsZ acts as the pivotal scaffold for bacterial cell divisome components providing them with a circumferential ride along the site of future division. FtsZ from slow growing Helicobacter pylori (HpFtsZ), a class I carcinogen which thrives abundantly in the acidic environment is poorly understood. We studied HpFtsZ as a function of pH, cations and time and compared it with well-studied E.

Spatial transcriptomics reveals the distinct organization of mouse prefrontal cortex and neuronal subtypes regulating chronic pain.

The prefrontal cortex (PFC) is a complex brain region that regulates diverse functions ranging from cognition, emotion and executive action to even pain processing. To decode the cellular and circuit organization of such diverse functions, we employed spatially resolved single-cell transcriptome profiling of the adult mouse PFC. Results revealed that PFC has distinct cell-type composition and gene-expression patterns relative to neighboring cortical areas-with neuronal excitability-regulating genes differently expressed.

Associations between School-Behavior-Health Difficulties and Subsequent Injuries among Younger Adolescents: A Population-based Study.

School-behavior-health difficulties (SBHDs) may alter physical/mental capabilities and consequently increase injury risk during daily activities. This study assessed the associations of potential SBHDs and their cumulative number (SBHDcn) with various injury types among younger adolescents. The study population included 1,559 middle-school adolescents in France (10-18 years, 98% under 16,778 boys and 781 girls).

How Do Nucleosome Dynamics Regulate Protein Search on DNA?

Nearly three-fourths of all eukaryotic DNA is occupied by nucleosomes, protein-DNA complexes comprising octameric histone core proteins and ∼150 base pairs of DNA. In addition to acting as a DNA compaction vehicle, the dynamics of nucleosomes regulate the DNA site accessibility for the nonhistone proteins, thereby controlling regulatory processes involved in determining the cell identity and cell fate. Here, we propose an analytical framework to analyze the role of nucleosome dynamics on the target search process of transcription factors through a simple discrete-state stochastic description of the search process.

Interdomain dynamics in human Replication Protein A regulates kinetics and thermodynamics of its binding to ssDNA.

Human Replication Protein A (hRPA) is a multidomain protein that interacts with ssDNA intermediates to provide the latter much-needed stability during DNA metabolism and maintain genomic integrity. Although the ssDNA organization with hRPA was studied recently through experimental means, characterizing the underlying mechanism at the atomic level remains challenging because of the dynamic domain architecture of hRPA and poorly understood heterogeneity of ssDNA-protein interactions. Here, we used a computational framework, precisely tailored to capture protein-ssDNA interactions, and investigated the binding of hRPA with a 60 nt ssDNA.

Understanding the Target Search by Multiple Transcription Factors on Nucleosomal DNA.

The association of multiple Transcription Factors (TFs) in the cis-regulatory region is imperative for developmental changes in eukaryotes. The underlying process is exceedingly complex, and it is not at all clear what orchestrates the overall search process by multiple TFs. In this study, by developing a theoretical model based on a discrete-state stochastic approach, we investigated the target search mechanism of multiple TFs on nucleosomal DNA.

Cytogenomic Characterization of a Novel de novo Balanced Reciprocal Translocation t(1;12) by Genome Sequencing Leading to Fusion Gene Formation of .

Introduction: The accurate detection of breakpoint regions of disease-associated chromosomal rearrangements helps understand the molecular mechanisms and identify the risks involved with disrupted genes.

Methods: In this study, a girl with growth retardation is characterized using positional cloning and genome sequencing. The techniques include fluorescence in situ hybridization (FISH) with paint (WCP) and bacterial-artificial chromosomes (BAC) probes, PCR, real-time PCR, and short and long-read sequencing.

Understanding protein diffusion on force-induced stretched DNA conformation.

DNA morphology is subjected to environmental conditions and is closely coupled with its function. For example, DNA experiences stretching forces during several biological processes, including transcription and genome transactions, that significantly alter its conformation from that of B-DNA. Indeed, a well-defined 1.

Development of an intervention program to reduce whole-body vibration exposure based on occupational and individual determinants among dumper operators.

Studies related to a systematic approach for intervention design to reduce whole-body vibration (WBV) exposure are scarce. This study presents a systematic approach to identifying, selecting and prioritizing safety interventions to fulfill that research gap. A total of 130 vibration readings for dumper operators were taken from two surface iron ore mines to identify significant determinants of WBV exposure.

Nucleosome breathing facilitates cooperative binding of pluripotency factors Sox2 and Oct4 to DNA.

Critical lineage commitment events are staged by multiple transcription factors (TFs) binding to their cognate motifs, often positioned at nucleosome-enriched regions of chromatin. The underlying mechanism remains elusive due to difficulty in disentangling the heterogeneity in chromatin states. Using a novel coarse-grained model and molecular dynamics simulations, here we probe the association of Sox2 and Oct4 proteins that show clustered binding at the entry-exit region of a nucleosome.

A molecularly defined D1 medium spiny neuron subtype negatively regulates cocaine addiction.

The striatum plays a critical role in regulating addiction-related behaviors. The conventional dichotomy model suggests that striatal D1/D2 medium spiny neurons (MSNs) positively/negatively regulate addiction-related behaviors. However, this model does not account for the neuronal heterogeneity and functional diversity of the striatum, and whether MSN subtypes beyond the pan-D1/D2 populations play distinct roles in drug addiction remains unknown.

Mechanism and kinetics of chlorpyrifos co-metabolism by using environment restoring microbes isolated from rhizosphere of horticultural crops under subtropics.

The indiscriminate use of organophosphate insecticide chlorpyrifos in agricultural crops causes significant soil and water pollution and poses a serious threat to the global community. In this study, a microbial consortium ERM C-1 containing bacterial strains T7, M2, M6, and a fungal strain TF1 was developed for the effective degradation of chlorpyrifos. Results revealed that microbial strains were not only utilizing chlorpyrifos (500 mg L) but also coupled with plant growth-promoting characteristics and laccase production.

Spectral response of vibrational polaritons in an optomechanical cavity.

Vibrational strong coupling provides a convenient way to modify the energy of molecular vibrations and to explore the control of chemical reactivity. In this work, we theoretically report the various vibrational anharmonicities that modulate the dynamics of optomechanically coupled W(CO)-cavity. The optomechanical free-space cavity consists of movable photonic crystal membrane, which creates photonic bound states to interact with the molecular vibration.

Superstructure Detection in Nucleosome Distribution Shows Common Pattern within a Chromosome and within the Genome.

Nucleosome positioning plays an important role in crucial biological processes such as replication, transcription, and gene regulation. It has been widely used to predict the genome's function and chromatin organisation. So far, the studies of patterns in nucleosome positioning have been limited to transcription start sites, CTCFs binding sites, and some promoter and loci regions.

Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis.

Schizophrenia (SCZ) is a chronic, serious mental disorder. Although more than 200 SCZ-associated genes have been identified, the underlying molecular and cellular mechanisms remain largely unknown. Here, we generated a Setd1a (SET domain containing 1A) haploinsufficiency mouse model to understand how this SCZ-associated epigenetic factor affects gene expression in brain regions highly relevant to SCZ.

Water-Induced Restructuring of the Surface of a Deep Eutectic Solvent.

We study the molecular-scale structure of the surface of Reline, a DES made from urea and choline chloride, using heterodyne-detected vibrational sum frequency generation (HD-VSFG). Reline absorbs water when exposed to the ambient atmosphere, and following structure-specific changes at the Reline/air interface is crucial and difficult. For Reline (dry, 0 wt %, w/w, water) we observe vibrational signatures of both urea and choline ions at the surface.