Quantitative Characterization of Chain-Flipping of Acyl Carrier Protein of Using Chemical Exchange NMR.

The acyl carrier protein of , termed AcpP, is a prototypical example of type II fatty acid synthase systems found in many bacteria. It serves as a central hub by accepting diverse acyl moieties (4-18 carbons) and shuttling them between its multiple enzymatic partners to generate fatty acids. Prior structures of acyl-AcpPs established that thioester-linked acyl cargos are sequestered within AcpP's hydrophobic lumen.

Epidemiological predictors of quality of life and the role of early markers in children with cerebral palsy: A multi-centric cross-sectional study.

Background: More than 100 million children in the world have at least one type of disability. Among disabled children, approximately 25% of chronic disabilities are of neurological origin. Cerebral Palsy is the leading cause of chronic disability in children, making them not only physically and mentally handicapped but also socially aloof.

Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial.

Objective: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE).

Design: Double-blind pilot randomised controlled trial.

Setting: Eight neonatal units in South Asia.

Phase Separation and Fibrillization of Human Annexin A7 Are Mediated by Its Proline-Rich Domain.

Human annexin A7, a calcium- and phospholipid-binding protein, governs calcium homeostasis, plasma membrane repair, apoptosis, and tumor progression. A7 contains an N-terminal proline-rich domain (PRD; 180 residues, ∼24% prolines) that determines its functional specificity. Using microscopy and dye-binding assays, we show that recombinant A7 and its isolated PRD spontaneously phase separate into spherical condensates, which subsequently transform into β-sheet-rich fibrils.

Reversible phase separation of ESCRT protein ALIX through tyrosine phosphorylation.

Cytokinetic abscission, the last step of cell division, is regulated by the ESCRT machinery. In response to mitotic errors, ESCRT proteins, namely, ALIX, CHMP4B, and CHMP4C, accumulate in the cytosolic compartments termed "abscission checkpoint bodies" (ACBs) to delay abscission and prevent tumorigenesis. ALIX contributes to the biogenesis and stability of ACBs via an unknown mechanism.

ALS Variants of Annexin A11's Proline-Rich Domain Impair Its S100A6-Mediated Fibril Dissolution.

Mutations in the proline-rich domain (PRD) of annexin A11 are linked to amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, and generate abundant neuronal A11 inclusions by an unknown mechanism. Here, we demonstrate that recombinant A11-PRD and its ALS-associated variants form liquidlike condensates that transform into β-sheet-rich amyloid fibrils. Surprisingly, these fibrils dissolved in the presence of S100A6, an A11 binding partner overexpressed in ALS.

Avidity-Based Method for the Efficient Generation of Monoubiquitinated Recombinant Proteins.

Monoubiquitination of proteins governs diverse physiological processes, and its dysregulation is implicated in multiple pathologies. The difficulty of preparing sufficient material often complicates the biophysical studies of monoubiquitinated recombinant proteins. Here we describe a robust avidity-based method that overcomes this problem.

Ursolic acid: a pentacyclic triterpenoid that exhibits anticancer therapeutic potential by modulating multiple oncogenic targets.

The world is currently facing a global challenge against neoplastic diseases. Chemotherapy, hormonal therapy, surgery, and radiation therapy are some approaches used to treat cancer. However, these treatments are frequently causing side effects in patients, such as multidrug resistance, fever, weakness, and allergy, among others side effects.

Surfactant administration in preterm babies (28-36 weeks) with respiratory distress syndrome: LISA versus InSurE, an open-label randomized controlled trial.

Introduction: INtubate-SURfactant-Extubate (InSurE) approach is traditional method of surfactant delivery in preterm neonates with respiratory distress syndrome (RDS). Newer, less invasive surfactant administration (LISA) techniques lessen the need for mechanical ventilation and its adverse consequences. Evidence on the favorable effects of LISA can't be extrapolated from developed to developing countries.

Biosynthesis and biophysical elucidation of CuO nanoparticle from Nyctanthes arbor-tristis Linn Leaf.

Copper oxide nanoparticles (CuO NPs) synthesis using an environmentally benign approach, as well as their antibacterial properties. Copper sulphate pentahydrate (CuSO.5HO) of different concentrations (2 mM, 5 mM and 10 mM) and aqueous Nyctanthes arbor-tristis leaf extract were used to make the CuO NPs.

Outcomes in neonates born to mothers with COVID-19 during the second wave in India.

Unlabelled: COVID-19 pandemic has affected all age groups globally including pregnant women and their neonates. The aim of the study was to understand outcomes in neonates of mothers with COVID-19 during the first and second waves of COVID-19 pandemic. A retrospective analysis of 2524 neonates born to SARS-CoV-2-infected mothers was conducted during the first wave (n = 1782) and second wave (n = 742) of the COVID-19 pandemic at five study sites of the PregCovid registry in Maharashtra, India.

Levetiracetam or Phenobarbitone as a First-Line Anticonvulsant in Asphyxiated Term Newborns? An Open-Label, Single-Center, Randomized, Controlled, Pragmatic Trial.

Background And Objective: Neonatal seizures are one of the most challenging problems for experts across the globe. Although there is no consensus on the "ideal" treatment of neonatal seizures, phenobarbitone has been the drug of choice for decades. Unfortunately, although extensively studied in adults and children, levetiracetam lacks rigorous evaluation in the neonatal population, despite its frequent use as an off-label drug.

Quality improvement in Kangaroo Mother Care: learning from a teaching hospital.

Background: Kangaroo Mother Care (KMC) is a low-resource, evidence-based, high-impact intervention for low-birth weight (LBW) care. Quality improvement in KMC requires meso-level, macro-level and micro-level interventions. Our institution, a public teaching hospital, hosts a level-II/III neonatal intensive care unit (NICU).

Mechanistic roles of tyrosine phosphorylation in reversible amyloids, autoinhibition, and endosomal membrane association of ALIX.

Human apoptosis-linked gene-2 interacting protein X (ALIX), a versatile adapter protein, regulates essential cellular processes by shuttling between late endosomal membranes and the cytosol, determined by its interactions with Src kinase. Here, we investigate the molecular basis of these transitions and the effects of tyrosine phosphorylation on the interplay between structure, assembly, and intramolecular and intermolecular interactions of ALIX. As evidenced by transmission electron microscopy, fluorescence and circular dichroism spectroscopy, the proline-rich domain of ALIX, which encodes binding epitopes of multiple cellular partners, formed rope-like β-sheet-rich reversible amyloid fibrils that dissolved upon Src-mediated phosphorylation and were restored on protein-tyrosine phosphatase 1B-mediated dephosphorylation of its conserved tyrosine residues.

Quantitative NMR Study of Insulin-Degrading Enzyme Using Amyloid-β and HIV-1 p6 Elucidates Its Chaperone Activity.

Insulin-degrading enzyme (IDE) hydrolyzes monomeric polypeptides, including amyloid-β (Aβ) and HIV-1 p6. It also acts as a nonproteolytic chaperone to prevent Aβ polymerization. Here we compare interactions of Aβ and non-amyloidogenic p6 with IDE.

Proline-rich domain of human ALIX contains multiple TSG101-UEV interaction sites and forms phosphorylation-mediated reversible amyloids.

Proline-rich domains (PRDs) are among the most prevalent signaling modules of eukaryotes but often unexplored by biophysical techniques as their heterologous recombinant expression poses significant difficulties. Using a "divide-and-conquer" approach, we present a detailed investigation of a PRD (166 residues; ∼30% prolines) belonging to a human protein ALIX, a versatile adaptor protein involved in essential cellular processes including ESCRT-mediated membrane remodeling, cell adhesion, and apoptosis. In solution, the N-terminal fragment of ALIX-PRD is dynamically disordered.

A micellar mediated novel method for the determination of selenium in environmental samples using a chromogenic reagent.

A novel, simple, sensitive and rapid spectrophotometric method for the determination of selenium(iv) in an acidic medium using rhodamine B hydrazide (RBH) has been developed. The method is based on the micellar mediated oxidation of RBH by Se(iv) in an acidic medium to produce a pinkish violet color of rhodamine B, which was monitored spectrophotometrically at λmax 585 nm. The sensitivity of the method was found to increase when the reaction was performed in a micellar medium.

Inhibition of HIV Maturation via Selective Unfolding and Cross-Linking of Gag Polyprotein by a Mercaptobenzamide Acetylator.

For HIV to become infectious, any new virion produced from an infected cell must undergo a maturation process that involves the assembly of viral polyproteins Gag and Gag-Pol at the membrane surface. The self-assembly of these viral proteins drives formation of a new viral particle as well as the activation of HIV protease, which is needed to cleave the polyproteins so that the final core structure of the virus will properly form. Molecules that interfere with HIV maturation will prevent any new virions from infecting additional cells.

Targeting a Dark Excited State of HIV-1 Nucleocapsid by Antiretroviral Thioesters Revealed by NMR Spectroscopy.

HIV-1 nucleocapsid (NCp7) is a two Cys HisCys zinc knuckle (N-Zn and C-Zn) protein that plays a key role in viral replication. NCp7 conformational dynamics is characterized by NMR relaxation dispersion and chemical exchange saturation transfer measurements. While the N-Zn knuckle is conformationally stable, the C-Zn knuckle interconverts on the millisecond timescale between the major state, in which the zinc is coordinated by three cysteines and a histidine, and two folded minor species (with populations around 1 %) in which one of the coordination bonds (Cys413-Sγ-Zn or His421-Nϵ2-Zn) is hydrolyzed.

Binding kinetics and substrate selectivity in HIV-1 protease-Gag interactions probed at atomic resolution by chemical exchange NMR.

The conversion of immature noninfectious HIV-1 particles to infectious virions is dependent upon the sequential cleavage of the precursor group-specific antigen (Gag) polyprotein by HIV-1 protease. The precise mechanism whereby protease recognizes distinct Gag cleavage sites, located in the intrinsically disordered linkers connecting the globular domains of Gag, remains unclear. Here, we probe the dynamics of the interaction of large fragments of Gag and various variants of protease (including a drug resistant construct) using Carr-Purcell-Meiboom-Gill relaxation dispersion and chemical exchange saturation transfer NMR experiments.

Allergy genuflection? It's surmount with special focus on ear, nose and throat.

The system that protects body from infectious agents is immune system. On occasions, the system seldom reacts with some foreign particles and causes allergy. Allergies of the ear, nose and throat (ENT) often have serious consequences, including impairment and emotional strain that lowers the quality of life of patients.

Transient HIV-1 Gag-protease interactions revealed by paramagnetic NMR suggest origins of compensatory drug resistance mutations.

Cleavage of the group-specific antigen (Gag) polyprotein by HIV-1 protease represents the critical first step in the conversion of immature noninfectious viral particles to mature infectious virions. Selective pressure exerted by HIV-1 protease inhibitors, a mainstay of current anti-HIV-1 therapies, results in the accumulation of drug resistance mutations in both protease and Gag. Surprisingly, a large number of these mutations (known as secondary or compensatory mutations) occur outside the active site of protease or the cleavage sites of Gag (located within intrinsically disordered linkers connecting the globular domains of Gag to one another), suggesting that transient encounter complexes involving the globular domains of Gag may play a role in guiding and facilitating access of the protease to the Gag cleavage sites.

Quantitative Characterization of Configurational Space Sampled by HIV-1 Nucleocapsid Using Solution NMR, X-ray Scattering and Protein Engineering.

Nucleic-acid-related events in the HIV-1 replication cycle are mediated by nucleocapsid, a small protein comprising two zinc knuckles connected by a short flexible linker and flanked by disordered termini. Combining experimental NMR residual dipolar couplings, solution X-ray scattering and protein engineering with ensemble simulated annealing, we obtain a quantitative description of the configurational space sampled by the two zinc knuckles, the linker and disordered termini in the absence of nucleic acids. We first compute the conformational ensemble (with an optimal size of three members) of an engineered nucleocapsid construct lacking the N- and C-termini that satisfies the experimental restraints, and then validate this ensemble, as well as characterize the disordered termini, using the experimental data from the full-length nucleocapsid construct.

Studies on Structural, Morphological and Optical Properties of Chemically Deposited CdS(1-x)Se(x) Thin Films.

The thin films of CdS(1-x)Se(x) were successfully deposited over glass substrates by chemical bath deposition technique. Cadmium acetate, thiourea and sodium selenosulfate were used as source materials for Cd(2+), S(2-) and Se(2-) ions, while 2-mercaptoethanol was used as capping agent. The various deposition conditions such as precursor concentration, deposition temperature, pH and deposition time were optimized for the deposition of CdS(1-x)Se(x) thin films of good quality and the films were annealed at 200° and 300 °C.