Role of pH in Modulating RNA-Protein Interactions in TRBP2-dsRBD2: An Interplay between Conformational Dynamics and Electrostatic Interactions.

Understanding RNA-protein interactions is crucial for uncovering the mechanisms of cellular processes and can provide insights into the basis of various diseases, paving the way for the development of targeted therapeutic interventions. Exposure to stress conditions, such as hypoxia, leads to a drop in intracellular pH, which, in turn, alters the ionization states of amino acid residues and RNA bases, affecting the charge distribution and electrostatic interactions between RNA and proteins. In addition, pH also perturbs the structure and dynamics of proteins via the disruption of H-bonds and ionic interactions.

Metabolic perturbations associated with hIAPP-induced insulin resistance in skeletal muscles: Implications to the development of type 2 diabetes.

The human islet amyloid polypeptide (hIAPP) tends to misfold and self-assemble to form amyloid fibrils, which has been associated with the loss of function and viability of pancreatic β-cells in type 2 diabetes mellitus (T2DM). The role of hIAPP in the development of insulin resistance (a hallmark of T2DM) in skeletal muscles - the major sites for glucose utilization - needs further investigation. Even though, insulin-resistant conditions have been known to stimulate hIAPP aggregation, the events that lead to the development of insulin resistance due to hIAPP aggregation in skeletal muscles remain unidentified.

Differential conformational dynamics in two type-A RNA-binding domains drive the double-stranded RNA recognition and binding.

Trans-activation response (TAR) RNA-binding protein (TRBP) has emerged as a key player in the RNA interference pathway, wherein it binds to different pre-microRNAs (miRNAs) and small interfering RNAs (siRNAs), each varying in sequence and/or structure. We hypothesize that TRBP displays dynamic adaptability to accommodate heterogeneity in target RNA structures. Thus, it is crucial to ascertain the role of intrinsic and RNA-induced protein dynamics in RNA recognition and binding.

Identification of potential serum biomarkers associated with HbA1c levels in Indian type 2 diabetic subjects using NMR-based metabolomics.

Background: The prevalence of type 2 diabetes mellitus (T2DM), a progressive metabolic disorder characterized by chronic hyperglycemia and the development of insulin resistance, has increased globally, with worrying statistics coming from children, adolescents, and young adults from developing countries like India. Here, we investigated unique circulating metabolic signatures associated with prediabetes and T2DM in an Indian cohort using NMR-based metabolomics.

Materials And Methods: The study subjects included healthy volunteers (N = 101), prediabetic subjects (N = 75), and T2DM patients (N = 108).

Proteomic Analysis of the Outer Membrane for Potential Implications in Uptake of Small Molecules.

Increased resistance to current antimycobacterial agents and a potential bias toward relatively hydrophobic chemical entities highlight an urgent need to understand how current anti-TB drugs enter the tubercle bacilli. While inner membrane proteins are well-studied, how small molecules cross the impenetrable outer membrane remains unknown. Here, we employed mass spectrometry-based proteomics to show that octyl-β-d-glucopyranoside selectively extracts the outer membrane proteins of .

Mapping metabolic perturbations induced by glutathione activatable synthetic ion channels in human breast cancer cells.

Ion channels and transporters play key roles in various biological processes, including cell proliferation and programmed cell death. Recently, we reported that 2,4-dinitrobenzene-sulfonyl-protected N,N-dihexy-2-hydroxyisophthalamide (1) forms ion channels upon activation by glutathione (GSH) and results in the induction of apoptosis by depleting the intracellular GSH reservoir in cancer cells. However, the detailed molecular events leading to the induction of apoptosis by these synthetic transport systems in cancer cells still need to be uncovered.

Water-Controlled Keto-Enol Tautomerization of a Prebiotic Nucleobase.

Barbituric acid is believed to be a proto-RNA nucleobase that was used for biological information transfer on prebiotic earth before DNA and RNA in their present forms evolved. Nucleobases have various tautomeric forms and the relative stability of these forms is critical to their biological function. It has been shown that barbituric acid has a tri-keto form in the gas phase and an enol form in the solid state.

Inherent conformational plasticity in dsRBDs enables interaction with topologically distinct RNAs.

Many double-stranded RNA-binding domains (dsRBDs) interact with topologically distinct dsRNAs in biological pathways pivotal to viral replication, cancer causation, neurodegeneration, and so on. We hypothesized that the adaptability of dsRBDs is essential to target different dsRNA substrates. A model dsRBD and a few dsRNAs, slightly different in shape from each other, were used to test the systematic shape dependence of RNA on the dsRBD-binding using nuclear magnetic resonance (NMR) spectroscopy and molecular modeling.

A Pyridyl-Linked Benzimidazolyl Tautomer Facilitates Prodigious H/Cl Symport through a Cooperative Protonation and Chloride Ion Recognition.

We report two pyridyl-linked benzimidazolyl hydrazones as HCl cotransporters that are 5 and 2 times superior to prodigiosin, a natural product whose transport efficiency has never been routed by synthetic molecules. These hydrazones provide a suitable HCl binding site through a cooperative protonation and chloride ion recognition. HCl transport by the most active compound induces lysosome deacidification.

Construction of Entropically Favored Supramolecular Metal-Ligand Trimeric Assemblies Supported by Flexible Pyridylaminophosphorus(V) Scaffolds.

The self-assembly reactions of tetratopic metal acceptors with the flexible bidentate ligands are known to yield self-assembled molecular squares of the type [ML], triangles of composition [ML], or a mixture of these two. In this work, we demonstrate the preferential formation of a trimeric cage assembly of the formula [Pd()·(BF)] () over the tetrameric cage [Pd()·(BF)] () by employing a flexible dipodal phosphoramide ligand, [PhPO(NH(3-Py))] (; 3-Py = 3-aminopyridine), in a reaction with [Pd(CHCN)·(BF)]. The entropically favored trimeric self-assembly of is the predominant species in the solution [dimethyl sulfoxide (DMSO)-] at room temperature.

Myricetin protects pancreatic β-cells from human islet amyloid polypeptide (hIAPP) induced cytotoxicity and restores islet function.

The aberrant misfolding and self-assembly of human islet amyloid polypeptide (hIAPP)-a hormone that is co-secreted with insulin from pancreatic β-cells-into toxic oligomers, protofibrils and fibrils has been observed in type 2 diabetes mellitus (T2DM). The formation of these insoluble aggregates has been linked with the death and dysfunction of β-cells. Therefore, hIAPP aggregation has been identified as a therapeutic target for T2DM management.

Palladium-Catalyzed Insertion of Ethylene and 1,1-Disubstituted Difunctional Olefins: An Experimental and Computational Study.

Insertion or coordination copolymerization of ethylene with di-substituted olefins is challenging and the choice of di-substituted mono-functional olefin versus di-substituted di-functional olefin (DDO) appears to be decisive. Here we show that DDO-inserted species are amenable to ethylene insertion and polymerization. DDOs such as 2-acetamidoacrylic acid (AAA), methyl 2-acetamidoacrylate (MAAA), and ethyl 2-cyanoacrylate (ECA) were treated with palladium complex [{P∧O}PdMe(L)] (P∧O=κ -P,O-Ar PC H SO O with Ar=2-MeOC H ; L=C H OS) and the existence of respective insertion intermediates in moderate yield (up to 37 %) was established.

NMR analysis of nucleotide π-stacking in prebiotically relevant crowded environment.

The prebiotic soup of a putative 'RNA World' would have been replete with a plethora of molecules resulting from complex chemical syntheses and exogeneous delivery. The presence of background molecules could lead to molecular crowding, potentially affecting the course of the reactions facilitated therein. Using NMR spectroscopy, we have analyzed the effect of crowding on the stacking ability of RNA monomers.

Cold storage reveals distinct metabolic perturbations in processing and non-processing cultivars of potato (Solanum tuberosum L.).

Cold-induced sweetening (CIS) causes considerable losses to the potato processing industry wherein the selection of potato genotypes using biochemical information has found to be advantageous. Here, H NMR spectroscopy was performed to identify metabolic perturbations from tubers of five potato cultivars (Atlantic, Frito Lay-1533, Kufri Jyoti, Kufri Pukhraj, and PU1) differing in their CIS ability and processing characteristics at harvest and after cold storage (4 °C). Thirty-nine water-soluble metabolites were detected wherein significantly affected metabolites after cold storage were categorized into sugars, sugar alcohols, amino acids, and organic acids.

Metabolomics Studies To Decipher Stress Responses in Mycobacterium smegmatis Point to a Putative Pathway of Methylated Amine Biosynthesis.

, the saprophytic soil mycobacterium, is routinely used as a surrogate system to study the human pathogen It has also been reported as an opportunistic pathogen in immunocompromised hosts. In addition, it can exist in several ecological setups, thereby suggesting its capacity to adapt to a variety of environmental cues. In this study, we employed untargeted proton nuclear magnetic resonance (H-NMR)-based metabolomics to identify metabolites and metabolic pathways critical for early adaptive responses to acidic stress, oxidative stress, and nutrient starvation in We identified 31, 20, and 46 metabolites that showed significant changes in levels in response to acidic, oxidative, and nutrient starvation stresses, respectively.

Metabolic signatures suggest o-phosphocholine to UDP-N-acetylglucosamine ratio as a potential biomarker for high-glucose and/or palmitate exposure in pancreatic β-cells.

Introduction: Chronic exposure to high-glucose and free fatty acids (FFA) alone/or in combination; and the resulting gluco-, lipo- and glucolipo-toxic conditions, respectively, have been known to induce dysfunction and apoptosis of β-cells in Diabetes. The molecular mechanisms and the development of biomarkers that can be used to predict similarities and differences behind these conditions would help in easier and earlier diagnosis of Diabetes.

Objectives: This study aims to use metabolomics to gain insight into the mechanisms by which β-cells respond to excess-nutrient stress and identify associated biomarkers.

Correction: Synthesis of barbituric acid containing nucleotides and their implications for the origin of primitive informational polymers.

Correction for 'Synthesis of barbituric acid containing nucleotides and their implications for the origin of primitive informational polymers' by Chaitanya V. Mungi et al., Phys.

H, C and N resonance assignment of domain 1 of trans-activation response element (TAR) RNA binding protein isoform 1 (TRBP2) and its comparison with that of isoform 2 (TRBP1).

TAR RNA binding protein (TRBP) is a double-stranded RNA binding protein involved in various biological processes like cell growth, development, death, etc. The protein exists as two isoforms TRBP2 and TRBP1. TRBP2 contains additional 21 amino acids at its N-terminus, which are proposed to be involved in its membrane localization, when compared to TRBP1.

Imido-P(v) trianion supported enantiopure neutral tetrahedral Pd(ii) cages.

Charge-neutral chiral hosts are attractive due to their ability to recognize a wide range of guest functionalities and support enantioselective processes. However, reports on such charge-neutral cages are very scarce in the literature. Here, we report an enantiomeric pair of tetrahedral Pd(ii) cages built from chiral tris(imido)phosphate trianions and oxalate linkers, which exhibit enantioselective separation capabilities for epichlorohydrin, β-butyrolactone, and 3-methyl- and 3-ethyl cyclopentanone.

miRNAs: Nanomachines That Micromanage the Pathophysiology of Diabetes Mellitus.

Diabetes mellitus (DM) refers to a combination of heterogeneous complex metabolic disorders that are associated with episodes of hyperglycemia and glucose intolerance occurring as a result of defects in insulin secretion, action, or both. The prevalence of DM is increasing at an alarming rate, and there exists a need to develop better therapeutics and prognostic markers for earlier detection and diagnosis. In this review, after giving a brief introduction of diabetes mellitus and microRNA (miRNA) biogenesis pathway, we first describe various in vitro and animal model systems that have been developed to study diabetes.

Origin of the Substitution Mechanism for the Binding of Organic Ligands on the Surface of CsPbBr Perovskite Nanocubes.

Optoelectronic properties of CsPbBr perovskite nanocubes (NCs) depend strongly on the interaction of the organic passivating molecules with the inorganic crystal. To understand this interaction, we employed a combination of synchrotron-based X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance (NMR) spectroscopy, and first-principles density functional theory (DFT)-based calculations. Variable energy XPS elucidated the internal structure of the inorganic part in a layer-by-layer fashion, whereas NMR characterized the organic ligands.

Synthesis of barbituric acid containing nucleotides and their implications for the origin of primitive informational polymers.

Given that all processes in modern biology are encoded and orchestrated by polymers, the origin of informational molecules had to be a crucial and significant step in the origin of life on Earth. An important molecule in this context is RNA that is thought to have allowed the transition from chemistry to biology. However, the RNA molecule is comprised of intramolecular bonds which are prone to hydrolysis, especially so under the harsh conditions of the early Earth.

Engineering a therapeutic lectin by uncoupling mitogenicity from antiviral activity.

A key effector route of the Sugar Code involves lectins that exert crucial regulatory controls by targeting distinct cellular glycans. We demonstrate that a single amino-acid substitution in a banana lectin, replacing histidine 84 with a threonine, significantly reduces its mitogenicity, while preserving its broad-spectrum antiviral potency. X-ray crystallography, NMR spectroscopy, and glycocluster assays reveal that loss of mitogenicity is strongly correlated with loss of pi-pi stacking between aromatic amino acids H84 and Y83, which removes a wall separating two carbohydrate binding sites, thus diminishing multivalent interactions.

miRNAs: early prognostic biomarkers for Type 2 diabetes mellitus?

Type 2 diabetes mellitus (T2DM) has reached epidemic proportions and is associated with peripheral insulin resistance. The currently used therapies aim to delay progression of T2DM. Their efficacy could drastically be improved if implemented at earlier stages.

A neutral cluster cage with a tetrahedral [Pd12(II)L6] framework: crystal structures and host–guest studies.

A charge-neutral tetrahedral [(Pd3X)4L6] cage assembly built from a trinuclear polyhedral building unit (PBU), [Pd3X](3+), cis-blocked with an imido P(V) ligand, [(N(i)Pr)3PO](3-) (X(3-)), and oxalate dianions (L(2-)) is reported. Use of benzoate or ferrocene dicarboxylate anions, which do not offer wide-angle chelation as that of oxalate dianions, leads to smaller prismatic clusters instead of polyhedral cage assemblies. The porosity of the tetrahedral cage assembly was determined by gas adsorption studies, which show a higher uptake capacity for CO2 over N2 and H2.