Membrane-targeting, ultrashort lipopeptide acts as an antibiotic adjuvant and sensitizes MDR gram-negative pathogens toward narrow-spectrum antibiotics.

Globally, infections due to multi-drug resistant (MDR) Gram-negative bacterial (GNB) pathogens are on the rise, negatively impacting morbidity and mortality, necessitating urgent treatment alternatives. Herein, we report a detailed bio-evaluation of an ultrashort, cationic lipopeptide 'SVAP9I' that demonstrated potent antibiotic activity and acted as an adjuvant to potentiate existing antibiotic classes towards GNBs. Newly synthesized lipopeptides were screened against ESKAPE pathogens and cytotoxicity assays were performed to evaluate the selectivity index (SI).

Beyond HbA1c: Identifying Gaps in Glycemic Control Among Children and Young People with Type 1 Diabetes Using Continuous Glucose Monitoring.

Objectives: To describe continuous glucose monitoring (CGM) derived glycemic variables, and study their association with HbA1c and socio-economic factors in young people with Type 1 diabetes mellitus (T1DM).

Methods: Ninety-two participants [age 15.7 ± 5.

Structural and biophysical characterization of PadR family protein Rv1176c of Mycobacterium tuberculosis H37Rv.

Rv1176c of Mycobacterium tuberculosis H37Rv belongs to the PadR-s1 subfamily of the PadR family of protein. Rv1176c forms a stable dimer in solution. Its stability is characterized by a thermal melting transition temperature (Tm) of 39.

Qualification of a LC-HRMS platform method for biosimilar development using NISTmab as a model.

Biosimilars are a cost-effective alternative to biopharmaceuticals, necessitating rigorous analytical methods for consistency and compliance. Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) is a versatile tool for assessing key attributes, encompassing molecular mass, primary structure, and post-translational modifications (PTMs). Adhering to ICH Q2R1, we validated an LC-HRMS based peptide mapping method using NISTmab as a reference.

Basic carbohydrate counting and glycemia in young people with type 1 diabetes in India: A randomized controlled trial.

Objectives: The aim of this study was to evaluate the effect on glycemic control and acceptability of basic carbohydrate counting (BCC) in children and young adults with type 1 diabetes (T1DM).

Methods: Ninety-two children and young adults (6-25 y of age) with T1DM were randomized to receive either routine nutrition education (RNE), which addressed food groups, glycemic index, and effects of food and exercise on glycemia, or learn BCC with personalized portion size education. A continuous glucose monitoring study and glycosylated hemoglobin (HbA1c) were performed at baseline and after 12 wk.

Post synthetically modified IRMOF-3 for efficient recovery and selective sensing of U(vi) from aqueous medium.

A simple and efficient route to develop various novel functionalized MOF materials for rapid and excellent recovery of U(vi) from aqueous medium, along with selective sensing has been demonstrated in the present study. In this connection, a set of four distinct post synthetically modified (PSM) iso-reticular metal organic frameworks were synthesized from IRMOF-3 namely, IRMOF-PC (2-pyridine carboxaldehyde), IRMOF-GA (glutaric anhydride), IRMOF-SMA (sulfamic acid), and IRMOF-DPC (diphenylphosphonic chloride) for the recovery and sensing of U(vi) from aqueous medium. The MOFs were characterized by Fourier transform infrared spectroscopy (FTIR), powder XRD, BET surface area analysis, thermogravimetric analysis (TGA), NMR (C, H and P), Scanning Electron Microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX).

Highly efficient functionalized MOF-LIC-1 for extraction of U(VI) and Th(IV) from aqueous solution: experimental and theoretical studies.

A set of four new functionalized MOFs, namely MOF-LIC-DPPC, MOF-LIC-GA, MOF-LIC-PCA and MOF-LIC-SA, were synthesized the post-synthetic modification (PSM) strategy using MOF-LIC-1 for efficient extraction of U(VI) and Th(IV) from an aqueous medium. FTIR, powder XRD, TGA and SEM-EDX were employed for characterization of the functionalized MOFs. Sorption studies for U(VI) and Th(IV) were performed by monitoring the pH and contact time.

Ofloxacin as a Disruptor of Actin Aggresome "Hirano Bodies": A Potential Repurposed Drug for the Treatment of Neurodegenerative Diseases.

There is a growing number of aging populations that are more prone to the prevalence of neuropathological disorders. Two major diseases that show a late onset of the symptoms include Alzheimer's disorder (AD) and Parkinson's disorder (PD), which are causing an unexpected social and economic impact on the families. A large number of researches in the last decade have focused upon the role of amyloid precursor protein, Aβ-plaque, and intraneuronal neurofibrillary tangles (tau-proteins).

Structural and functional characterization of peptidyl-tRNA hydrolase from Klebsiella pneumoniae.

Klebsiella pneumoniae is a member of the ESKAPE panel of pathogens that are top priority to tackle AMR. Bacterial peptidyl tRNA hydrolase (Pth), an essential, ubiquitous enzyme, hydrolyzes the peptidyl-tRNAs that accumulate in the cytoplasm because of premature termination of translation. Pth cleaves the ester bond between 2' or 3' hydroxyl of the ribose in the tRNA and C-terminal carboxylate of the peptide, thereby making free tRNA available for repeated cycles of protein synthesis and preventing cell death by alleviating tRNA starvation.

Resonance assignments and secondary structure prediction of secretory protein Rv0603 from Mycobacterium tuberculosis H37Rv.

We report the NMR resonance assignments of N-terminal signal sequence deleted secretory protein Rv0603 (∆-Rv0603) from Mycobacterium tuberculosis H37Rv. ∆-Rv0603 displayed good peak yield and signal dispersion in 2D [N-H] HSQC spectrum, which prompted us to proceed for resonance assignments on this construct. Standard triple-resonance experiments for resonance assignments were recorded on [U-N]-∆Rv0603 and [U-N, C]-∆Rv0603 samples.

Assorted functionality-appended UiO-66-NH for highly efficient uranium(vi) sorption at acidic/neutral/basic pH.

A series of functionalized metal organic frameworks (MOFs) were synthesized by the post-synthetic modification (PSM) of Zr(iv)-containing UiO-66-NH MOFs using covalent grafting with various functional groups utilizing pendant -NH moieties. The tethering of amide (with/without pendant carboxylic acid), iminopyridine, phoshinic amide and sulphur-containing functionalities produced a library of eight different UiO-66-NH derivatives. The functionalized MOFs were characterized by FT-IR spectroscopy, NMR, PXRD, TGA, SEM-EDX and BET surface area analysis.

Effect of tetracycline family of antibiotics on actin aggregation, resulting in the formation of Hirano bodies responsible for neuropathological disorders.

Actin, an ATPase superfamily protein, regulates some vital biological functions like cell locomotion, cytokinesis, synaptic plasticity and cell signaling in higher eukaryotes, and is dependent on the dynamics of actin polymerization process. Impaired regulation of actin polymerization has been implicated in the formation and deposition of rod-like paracrystalline structures called as Hirano bodies in neuronal cells of patients suffering from Alzheimer's disease, Pick's disease, Guam amyotrophic lateral sclerosis and parkinsonism-dementia complex. Aggregation of actin forming amorphous deposition in the brain cells is also associated with chronic alcoholism and aging of the neurons.

Molecular interaction between human SUMO-I and histone like DNA binding protein of Helicobacter pylori (Hup) investigated by NMR and other biophysical tools.

The proteins secreted by bacteria contribute to immune mediated gastric inflammation and epithelial damage; thus aid bacterial invasion in host tissue, and may also interact with host proteins, conspirating a mechanism against host-immune system. The Histone-like DNA binding protein is one of the most abundant nucleoid-associated proteins in Helicobacter pylori (H. pylori).

Rv3272 encodes a novel Family III CoA transferase that alters the cell wall lipid profile and protects mycobacteria from acidic and oxidative stress.

The availability of complete genome sequence of Mycobacterium tuberculosis has provided an important tool to understand the mycobacterial biology with respect to host-pathogen interaction, which is an unmet need of the hour owing to continuous increasing drug resistance. Hypothetical proteins are often an overlooked pool though half the genome encodes for such proteins of unknown function that could potentially play vital roles in mycobacterial biology. In this context, we report the structural and functional characterization of the hypothetical protein Rv3272.

Structural and functional characterization of the transcriptional regulator Rv3488 of H37Rv.

Rv3488 of H37Rv has been assigned to the phenolic acid decarboxylase repressor (PadR) family of transcriptional regulators that play key roles in multidrug resistance and virulence of prokaryotes. The binding of cadmium, zinc, and several other metals to Rv3488 was discovered and characterized by isothermal titration calorimetery to be an exothermic process. Crystal structures of apo-Rv3488 and Rv3488 in complex with cadmium or zinc ions were determined by X-ray crystallography.

Structural and Biophysical Characterization of Rab5a from Leishmania Donovani.

Leishmania donovani possess two isoforms of Rab5 (Rab5a and Rab5b), which are involved in fluid phase and receptor-mediated endocytosis, respectively. We have characterized the solution structure and dynamics of a stabilized truncated LdRab5a mutant. For the purpose of NMR structure determination, protein stability was enhanced by systematically introducing various deletions and mutations.

Multistimuli-Responsive Hydrolytically Stable "Smart" Mercury(II) Coordination Polymer.

A new one-dimensional double chain photoluminescent Hg(II) coordination polymer (CP), {[Hg(L)]·(ClO)} (1), was synthesized using a benzimidazole-appended tripodal tridentate ligand, 1,3,5-tris(benzimidazolylmethyl)benzene (L). The dynamic and flexible framework of 1 allows it to be entitled as first Hg(II)-based CP belonging to the rare category of CPs that exhibit multistimuli-responsive photoluminescence sensing properties and called as "smart" material. The sensitivity of this material via luminescence quenching method showing "turn off" behavior to a range of stimuli, including anions, solvents, and nitroaromatic compounds (NACs), offers more fine-grained control over its properties.

Solution structure and dynamics of glia maturation factor from Caenorhabditis elegans.

Background: The GMF class of the ADF-H domain family proteins regulate actin dynamics by binding to the Arp2/3 complex and F-actin through their Site-1 and Site-2, respectively. CeGMF of C. elegans is analogous to GMFγ of human and mouse and is 138 amino acids in length.

Role of methionine 71 in substrate recognition and structural integrity of bacterial peptidyl-tRNA hydrolase.

Background: Bacterial peptidyl-tRNA hydrolase (Pth) is an essential enzyme that alleviates tRNA starvation by recycling prematurely dissociated peptidyl-tRNAs. The specificity of Pth for N-blocked-aminoacyl-tRNA has been proposed to be contingent upon conserved residue N14 forming a hydrogen bond with the carbonyl of the first peptide bond in the substrate. M71 is involved in forming a conserved hydrogen bond with N14.

Structure, dynamics, and biochemical characterization of ADF/cofilin Twinstar from Drosophilamelanogaster.

Background: Twinstar is an ADF/cofilin family protein, which is expressed by the tsr gene in Drosophila melanogaster. Twinstar is one of the main regulators of actin cytoskeleton remodelling and is essential for vital cellular processes like cytokinesis and endocytosis.

Methods: We have characterized the structure and dynamics of Twinstar by solution NMR spectroscopy, the interaction of Twinstar with rabbit muscle actin by ITC, and biochemical activities of Twinstar through different biochemical assays using fluorescence spectroscopy and ultra-centrifugation.

Biophysical and immunological characterization of the ESX-4 system ESAT-6 family proteins Rv3444c and Rv3445c from Mycobacterium tuberculosis H37Rv.

The ESAT-6 family proteins of Mycobacterium tuberculosis are regarded as the key mediators in mycobacterial virulence and are largely considered as antigens that can improve TB vaccines and diagnostics. We have characterized Rv3444c and Rv3445c proteins of the ESX-4 system of ESAT-6 family of M. tuberculosis H37Rv, and have experimentally established that these two proteins interact to form a heterodimeric complex.

Unraveling the stereochemical and dynamic aspects of the catalytic site of bacterial peptidyl-tRNA hydrolase.

Bacterial peptidyl-tRNA hydrolase (Pth; EC 3.1.1.

Characterization of culture filtrate proteins Rv1197 and Rv1198 of ESAT-6 family from Mycobacterium tuberculosis H37Rv.

Background: We have characterized two immunogenic proteins, Rv1197 and Rv1198, of the Esx-5 system of the ESAT-6 family of Mycobacterium tuberculosis H37Rv.

Methods: The complex formation between Rv1197 and Rv1198 was characterized by biophysical techniques. The reactivity of serum from TB patients towards these proteins was characterized by ELISA.

Structural characterization of peptidyl-tRNA hydrolase from Mycobacterium smegmatis by NMR spectroscopy.

Background: Accumulation of toxic peptidyl-tRNAs in the bacterial cytoplasm is averted by the action of peptidyl-tRNA hydrolase (Pth), which cleaves peptidyl-tRNA into free tRNA and peptide. NMR studies are needed for a protein homolog with a complete crystal structure, for comparison with the NMR structure of Mycobacterium tuberculosis Pth.

Methods: The structure and dynamics of Mycobacterium smegmatis Pth (MsPth) were characterized by NMR spectroscopy and MD simulations.