Molecular simulation reveals that pathogenic mutations in BTB/ANK domains of Arabidopsis thaliana NPR1 circumscribe the EDS1-mediated immune regulation.

The NPR1 (nonexpressor of pathogenesis-related genes 1) is a key regulator of the salicylic-acid-mediated immune response caused by pathogens in Arabidopsis thaliana. Mutations C150Y and H334Y in the BTB/ANK domains of NPR1 inhibit the defense response, and transcriptional co-activity with enhanced disease susceptibility 1 (EDS1) has been revealed experimentally. This study examined the conformational changes and reduced NPR1-EDS1 interaction upon mutation using a molecular dynamics simulation.

Prevalence of generalized anxiety disorder among patients attending medicine outpatient department in a tertiary care center: A cross-sectional study.

Background: Generalized anxiety disorder is commonly underdiagnosed and undertreated in medical settings.

Aim: The objectives of this study were to determine the prevalence and correlates of generalized anxiety disorder among patients presenting to medicine outpatient department in a tertiary care centre.

Materials And Methods: A cross-sectional observational study was conducted among the patients visiting the outpatient department of General Medicine in a tertiary care teaching hospital.

Structural localization of pathogenic mutations in the central nucleotide-binding domain (NBD) of nucleotide-binding oligomerization domain-2 (NOD2) protein and their inference in inflammatory disorders.

The human NBD domain which is centrally located in the NOD2 protein displays an essential role in oligomerization and initiates the immune response via CARD-RIPK2 interaction. The mutations associated with the NBD domain have been largely implicated in inflammatory disorders such as Blau syndrome and sarcoidosis. This study aims to determine the structural and phenotypic effect of a lethal mutation that occurs in the NBD domain which has an axiomatic impact on protein dysfunction.

Exploring the structural significance of molecular switch mechanism alias motif phosphorylation in Wnt/β-catenin and their crucial role in triple-negative breast cancer.

β-Catenin, a key transcriptional factor involved in the canonical Wnt signaling pathway, is regulated by a cascade of phosphorylations and plays a major role in the progression of triple-negative breast cancer (TNBC). However, the phosphorylation induced conformational changes in a β-Catenin is still poorly understood. Hence, we adopted a conventional molecular dynamics approach to study phosphorylations present in a sequence motif Ser and Tyr of the β-Catenin domain and analyzed in terms of structural transitions, bond formation, and folding-misfolding conformations.

Delineating the folding perturbations and molecular mechanisms of Thr-Ala 642 mutation in Rab-GTPase activating protein Akt substrate of 160kDa and its impact on the aetiology of diabetes.

Diabetes Mellitus is a complex metabolic disorder with one of the highest prevalence rates in the world. The present study probes into the ThrAla 642 mutation of Akt substrate of 160 kDa (AS160) which has been implicated in diabetes by the dysregulation of glucose transported vesicle 4 (GLUT4) translocation. Our study provides a possible evidence on structural basis dysfunction of AS160 and how the association of phosphorylated AS160 with 14-3-3, a downstream binding partner regulating GLUT4 translocation got disrupted due to T642A mutation.

A cross-sectional study of psychiatric morbidity and quality of life among participants utilizing the preventive health-care services of a tertiary hospital.

Background: The burden of mental disorders has been increasingly recognized and 450 million people globally are suffering from mental illness. Mental-physical comorbidity has adverse effects on the overall outcome. Research is scarce with regard to mental health screening in the context of "preventive health care" in India.

Structural debilitation of mutation G322D associated with MSH2 and their role in triple negative breast cancer.

The missense mutation in the underlies in several hereditary cancers. In this study, we have detailed the disruptive mutation of G322D that overtly pathogenic and clinically relevant to the triple negative breast cancer (TNBC) on the basis of structural aspect to untangle the unknown factors. We systematically evaluated the conformational changes that undergo upon mutation from the annotation of intra-residual contacts, secondary structural arrangements and fold recognition through molecular dynamics simulation.

Differentially expressed gene (DEG) based protein-protein interaction (PPI) network identifies a spectrum of gene interactome, transcriptome and correlated miRNA in nondisjunction Down syndrome.

Down syndrome, a genetic disorder of known attribution reveals several types of brain abnormalities resulting in mental retardation, inadequacy in speech and memory. In this study, we have presented a consolidative network approach to comprehend the intricacy of the associated genes of Down syndrome. In this analysis, the differentially expressed genes (DEG's) were identified and the central networks were constructed as upregulated and downregulated.

A molecular simulation analysis of vitamin D targets interleukin 13 (IL13) as an alternative to mometasone in asthma.

Asthma, a chronic lung disease characterized by obstruction of airway passage is characterized by inflammation and hyperresponsiveness with increase in the number of eosinophils. Interleukin-13, plays a significant role in causing inflammation during an asthmatic attack by bronchial constriction. Mometasone, a glucocorticoid has been used as the first line of administration for people affected with asthma for almost a decade.

R516Q mutation in Melanoma differentiation-associated protein 5 (MDA5) and its pathogenic role towards rare Singleton-Merten syndrome; a signature associated molecular dynamics study.

Singleton-Merten syndrome, a critical and rare multifactorial disorder that is closely linked to R516Q mutation in MDA5 protein associated with an enhanced interferon response in the affected individual. In the present study, we provide conclusive key evidence on R516Q mutation and their connectivity towards sequence-structural basis dysfunction of MDA5 protein. Among the various mutations, we found R516Q is the most pathogenic mutation based on mutational signature Q-A-[RE]-G-R-[GA]-R-A-[ED]-[DE]-S-[ST]-Y-[TSAV]-L-V designed from our work.

Systematic prioritization of functional hotspot in RIG-1 domains using pattern based conventional molecular dynamic simulation.

Background: Retinoic acid inducible gene 1 (RIG-1), multi-domain protein has a role-play in detecting viral nucleic acids and stimulates the antiviral response. Dysfunction of this protein due to mutations makes the route vulnerable to viral diseases.

Aim: Identification of functional hotspots that maintains conformational stability in RIG-1 domains.

Casting the critical regions in nucleotide binding oligomerization domain 2 protein: a signature mediated structural dynamics approach.

Nucleotide binding oligomerization domain 2 (NOD2), a protein involved in the first line defence mechanism has a pivotal role in innate immunity. Impaired function of this protein is implicated in disorders such as Blau syndrome and Crohn's disease. Since an altered function is linked to protein's structure, we framed a systematic strategy to interpret the structure-function relationship of the protein.