Backbone assignments of the biotin carboxyl carrier protein domain of Propionyl CoA carboxylase of Leishmania major and its interaction with its cognate Biotin protein ligase.

Propionyl CoA carboxylase (PCC) is a multimeric enzyme composed of two types of subunits, α and β arranged in αβ stoichiometry. The α-subunit consists of an N-terminal carboxylase domain, a carboxyl transferase domains, and a C-terminal biotin carboxyl carrier protein domain (BCCP). The β-subunit is made up of an N- and a C- carboxyl transferase domain.

Structural effect of the H992D/H418D mutation of angiotensin-converting enzyme in the Indian population: implications for health and disease.

The Non synonymous SNPs (nsSNPs) of the renin-angiotensin-system (RAS) pathway, unique to the Indian population were investigated in view of its importance as an endocrine system. nsSNPs of the RAS pathway genes were mined from the IndiGenome database. Damaging nsSNPs were predicted using SIFT, PredictSNP, SNP and GO, Snap2 and Protein Variation Effect Analyzer.

Analysis of SARS-CoV-2 genome evolutionary patterns.

The spread of SARS-CoV-2 virus accompanied by public availability of abundant sequence data provides a window for the determination of viral evolutionary patterns. In this study, SARS-CoV-2 genome sequences were collected from seven countries in the period January 2020-December 2022. The sequences were classified into three phases, namely, pre-vaccination, post-vaccination, and recent period.

3D-QSAR and ADMET studies of morpholino-pyrimidine inhibitors of DprE1 from .

DprE1 is involved in the synthesis of cell wall and is a potent drug target for Tuberculosis (TB) treatment. The structure and dynamics of the loops L-I and L-II flanking the inhibitor binding site was studied using molecular dynamics (MD) simulation and MMPBSA in Amber v18. Docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) of 55 Morpholino-pyrimidine (MP) inhibitors was carried out using Autodock v1.

Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite.

Signalling pathways in malaria parasite remain poorly defined and major reason for this is the lack of understanding of the function of majority of parasite protein kinases and phosphatases in parasite signalling and its biology. In the present study, we have elucidated the function of Protein Kinase 2 (PfPK2), which is known to be indispensable for the survival of human malaria parasite Plasmodium falciparum. We demonstrate that it is involved in the invasion of host erythrocytes, which is critical for establishing infection.

A Novel Framework to Address the Complexities of Housing Insecurity and Its Associated Health Outcomes and Inequities: "Give, Partner, Invest".

The association between housing insecurity and reduced access to healthcare, diminished mental and physical health, and increased mortality is well-known. This association, along with structural racism, social inequities, and lack of economic opportunities, continues to widen the gap in health outcomes and other disparities between those in higher and lower socio-economic strata in the United States and throughout the advanced economies of the world. System-wide infrastructure failures at municipal, state, and federal government levels have inadequately addressed the difficulty with housing affordability and stability and its associated impact on health outcomes and inequities.

Identifying Children Likely to Benefit From Antibiotics for Acute Sinusitis: A Randomized Clinical Trial.

Importance: The large overlap between symptoms of acute sinusitis and viral upper respiratory tract infection suggests that certain subgroups of children being diagnosed with acute sinusitis, and subsequently treated with antibiotics, derive little benefit from antibiotic use.

Objective: To assess if antibiotic therapy could be appropriately withheld in prespecified subgroups.

Design, Setting, And Participants: Randomized clinical trial including 515 children aged 2 to 11 years diagnosed with acute sinusitis based on clinical criteria.

Role of molecular mimicry in the SARS-CoV-2-human interactome for pathogenesis of cardiovascular diseases: An update to ImitateDB.

Mimicry of host proteins is a strategy employed by pathogens to hijack host functions. Domain and motif mimicry was explored in the experimental and predicted SARS-CoV-2-human interactome. The host first interactor proteins were also added to capture the continuum of the interactions.

Short-Course Therapy for Urinary Tract Infections in Children: The SCOUT Randomized Clinical Trial.

Importance: There is a paucity of pediatric-specific comparative data to guide duration of therapy recommendations in children with urinary tract infection (UTI).

Objective: To compare the efficacy of standard-course and short-course therapy for children with UTI.

Design, Setting, Participants: The Short Course Therapy for Urinary Tract Infections (SCOUT) randomized clinical noninferiority trial took place at outpatient clinics and emergency departments at 2 children's hospitals from May 2012, through, August 2019.

Structure-activity relationships of dihydropyrimidone inhibitors against native and auto-processed human neutrophil elastase.

Background: Human neutrophil elastase (HNE) is a key driver of systemic and cardiopulmonary inflammation. Recent studies have established the existence of a pathologically active auto-processed form of HNE with reduced binding affinity against small molecule inhibitors.

Method: AutoDock Vina v1.

Efficacy of a digital mental health intervention embedded in routine care compared with treatment as usual in adolescents and young adults with moderate depressive symptoms: protocol for randomised controlled trial.

Introduction: There are unmet mental health needs of depressed adolescents and young adults (AYAs) across the USA. Behavioural technology adequately integrated into clinical care delivery has potential to improve care access and efficiency. This multisite randomised controlled trial evaluates how a coach-enhanced digital cognitive behavioural intervention (dCBI) enhances usual care for depressed AYAs in paediatric practices with minority enriched samples.

ImitateDB: A database for domain and motif mimicry incorporating host and pathogen protein interactions.

Molecular mimicry of host proteins by pathogens constitutes a strategy to hijack the host pathways. At present, there is no dedicated resource for mimicked domains and motifs in the host-pathogen interactome. In this work, the experimental host-pathogen (HP) and host-host (HH) protein-protein interactions (PPIs) were collated.

Intranasal Surfactant for Acute Otitis Media: A Randomized Trial.

Background: Acute otitis media (AOM) is the most frequent reason for children to be prescribed antimicrobial treatment. Surfactants are naturally occurring substances that may restore the eustachian tube's function and potentially enhance resolution of AOM.

Methods: This was a phase 2a, single-center, double-blind, randomized, placebo-controlled, parallel group clinical trial to assess safety, tolerability, and efficacy of 20 mg per day intranasal OP0201 as an adjunct therapy to oral antimicrobial agents for treating AOM in young children.

Machine Learning for Prediction of Drug Targets in Microbe Associated Cardiovascular Diseases by Incorporating Host-pathogen Interaction Network Parameters.

Host-pathogen interactions play a crucial role in invasion, infection, and induction of immune response in humans. In this work, four machine learning algorithms, namely Logistic regression, K-nearest neighbor, Support Vector Machine, and Random Forest were implemented for the classification of drug targets. The algorithms were trained using 3400 hosts and 3800 pathogen drug and non-drug target proteins as learning instances.

A Survey of Healthcare Providers About Reproductive Healthcare for Adolescent Women With Epilepsy.

Study Objective: To evaluate knowledge, attitudes, and practices about sexual and reproductive health (SRH) for adolescent and young adult (AYA) women with epilepsy among general pediatricians, adolescent medicine specialists, and pediatric gynecologists.

Design: Survey comprising previously validated and novel items that underwent content validity testing and was distributed through specialty listservs. Categorical variables analyzed with χ or Fisher exact tests, and continuous variables with Kruskal-Wallis tests.

Drug repurposing for hyperlipidemia associated disorders: An integrative network biology and machine learning approach.

Hyperlipidemia causes diseases like cardiovascular disease, cancer, Type II Diabetes and Alzheimer's disease. Drugs that specifically target HL associated diseases are required for treatment. 34 KEGG pathways targeted by lipid lowering drugs were used to construct a directed protein-protein interaction network and driver nodes were determined using CytoCtrlAnalyser plugin of Cytoscape 3.

Tympanostomy Tubes or Medical Management for Recurrent Acute Otitis Media.

Background: Official recommendations differ regarding tympanostomy-tube placement for children with recurrent acute otitis media.

Methods: We randomly assigned children 6 to 35 months of age who had had at least three episodes of acute otitis media within 6 months, or at least four episodes within 12 months with at least one episode within the preceding 6 months, to either undergo tympanostomy-tube placement or receive medical management involving episodic antimicrobial treatment. The primary outcome was the mean number of episodes of acute otitis media per child-year (rate) during a 2-year period.

Leishmania major biotin protein ligase forms a unique cross-handshake dimer.

Biotin protein ligase catalyses the post-translational modification of biotin carboxyl carrier protein (BCCP) domains, a modification that is crucial for the function of several carboxylases. It is a two-step process that results in the covalent attachment of biotin to the ϵ-amino group of a conserved lysine of the BCCP domain of a carboxylase in an ATP-dependent manner. In Leishmania, three mitochondrial enzymes, acetyl-CoA carboxylase, methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase, depend on biotinylation for activity.

Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite.

Merozoites formed after asexual division of the malaria parasite invade the host red blood cells (RBCs), which is critical for initiating malaria infection. The process of invasion involves specialized organelles like micronemes and rhoptries that discharge key proteins involved in interaction with host RBC receptors. RhopH complex comprises at least three proteins, which include RhopH3.

Corticosteroids to prevent kidney scarring in children with a febrile urinary tract infection: a randomized trial.

Background: To evaluate the efficacy of adjuvant systemic corticosteroids in reducing kidney scarring. A previous study suggested that use of adjuvant systemic corticosteroids reduces kidney scarring in children radiologically confirmed to have extensive pyelonephritis. Efficacy of corticosteroids for children with febrile urinary tract infection (UTI) has not been studied.

Network analysis of host-pathogen protein interactions in microbe induced cardiovascular diseases.

Large-scale visualization and analysis of HPIs involved in microbial CVDs can provide crucial insights into the mechanisms of pathogenicity. The comparison of CVD associated HPIs with the entire set of HPIs can identify the pathways specific to CVDs. Therefore, topological properties of HPI networks in CVDs and all pathogens was studied using Cytoscape3.

In Silico Screening to Identify Inhibitors of Growth Factor Receptor 2-Focal Adhesion Kinase Interaction for Therapeutic Treatment of Pathological Cardiac Hypertrophy.

The focal adhesion kinase-growth factor receptor 2 (FAK-Grb2) protein-protein interaction is implicated in pathogenesis of stress-induced cardiac hypertrophy. The focal adhesion targeting (FAT) domain of FAK unfolds to form a structural intermediate that interacts with a multibinding hot spot in the SH2 domain of Grb2. Disruption of the Grb2-FAT interaction is a therapeutic strategy for prevention of pathological cardiac hypertrophy.

MorCVD: A Unified Database for Host-Pathogen Protein-Protein Interactions of Cardiovascular Diseases Related to Microbes.

Microbe induced cardiovascular diseases (CVDs) are less studied at present. Host-pathogen interactions (HPIs) between human proteins and microbial proteins associated with CVD can be found dispersed in existing molecular interaction databases. MorCVD database is a curated resource that combines 23,377 protein interactions between human host and 432 unique pathogens involved in CVDs in a single intuitive web application.

Identification, Functional Characterization, and Regulon Prediction of the Zinc Uptake Regulator () of - An Insight Into the Zinc Homeostasis of the Pathogen.

Zinc has an abounding occurrence in the prokaryotes and plays paramount roles including catalytic, structural, and regulatory. Zinc uptake regulator (Zur), a Fur family transcriptional regulator, is connoted in maintaining zinc homeostasis in the pathogenic bacteria by binding to zinc and regulating the genes involved in zinc uptake and mobilization. Zinc homeostasis has been marginally scrutinized in , the top-rated bio-terror agent, with no decipherment of the role of Zur.