The Cell Division Activator Protein StCAP Impacts Pathogenesis by Influencing Critical Molecular Events.

Conserved molecular signatures in multidrug-resistant can serve as novel therapeutic targets for mitigation of infection. In this regard, we present the cell division activator protein (StCAP) as a conserved target across variants. From and fluorimetric assessments, we found that StCAP is a DNA-binding protein.

Cannabis-Induced Gastrointestinal Tract Symptoms in the Adult Population: A Systematic Review.

Objective: Cannabinoid usage is widespread in the self-management of various medical ailments. However, adverse effects have been reported with use, especially pertaining to the gastrointestinal system in adults and aged patients. These range from nausea, vomiting, bloating, or abdominal pain.

Spike Protein Mutation-Induced Changes in the Kinetic and Thermodynamic Behavior of Its Receptor Binding Domains Explain Their Higher Propensity to Attain Open States in SARS-CoV-2 Variants of Concern.

Spike (S) protein opening in SARS-CoV-2 controls the accessibility of its receptor binding domains (RBDs) to host receptors and immune recognition. Along the evolution of SARS-CoV-2 to its variants of concern (VOC)-alpha, beta, gamma, delta, and omicron-their S proteins showed a higher propensity to attain open states. Deciphering how mutations in S protein can shape its conformational dynamics will contribute to the understanding of viral host tropism.

Anticonvulsant Properties of 1-Diethylamino-3-phenylprop-2-en-1-one.

There is a need for novel antiepileptic agents whose modes of action differ from those of current antiepileptic drugs. The objective of this study was to determine whether 1-diethylamino-3-phenylprop-2-en-1-one () could prevent or at least diminish convulsions caused by different mechanisms. This amide afforded protection in the maximal electroshock and subcutaneous pentylenetetrazole screens when given intraperitoneally to both mice and rats.

Evolutionarily conserved heat shock protein, HtpX, as an adjunct target against antibiotic-resistant Neisseria gonorrhoeae.

The emergence of multiple drug resistance and extreme drug resistance pathogens necessitates the continuous evaluation of the pathogenic genome to identify conserved molecular targets and their respective inhibitors. In this study, we mapped the global mutational landscape of Neisseria gonorrhoeae (an intracellular pathogen notoriously known to cause the sexually transmitted disease gonorrhoea). We identified highly variable amino acid positions in the antibiotic target genes like the penA, ponA, 23s rRNA, rpoB, gyrA, parC, mtrR and porB.

Deoxyelephantopin-a novel PPARγ agonist regresses pressure overload-induced cardiac fibrosis via IL-6/STAT-3 pathway in crosstalk with PKCδ.

Pathological cardiac hypertrophy is associated with ventricular fibrosis leading to heart failure. The use of thiazolidinediones as Peroxisome Proliferator-Activated Receptor-gamma (PPARγ)-modulating anti-hypertrophic therapeutics has been restricted due to major side-effects. The present study aims to evaluate the anti-fibrotic potential of a novel PPARγ agonist, deoxyelephantopin (DEP) in cardiac hypertrophy.

Polypharmacological repurposing approach identifies approved drugs as potential inhibitors of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (M. tb), the causative pathogen of tuberculosis (TB) remains the leading cause of death from single infectious agent. Furthermore, its evolution to multi-drug resistant (MDR) and extremely drug-resistant (XDR) strains necessitate de novo identification of drug-targets/candidates or to repurpose existing drugs against known targets through drug repurposing.

The therapygenetics of anxiety disorders.

Treatment of anxiety disorders primarily includes pharmacological treatment and psychotherapy, yet a substantial portion of patients do not experience sufficient clinical response. Given the significant impact of anxiety disorders on well-being and quality of life, it is pertinent to strive to ensure available treatments are of paramount efficacy. This review aimed to identify genetic variants and genes that may moderate the outcome of psychotherapy in patients with anxiety disorders, termed 'therapygenetics.

Energetics of Spike Protein Opening of SARS-CoV-1 and SARS-CoV-2 and Its Variants of Concern: Implications in Host Receptor Scanning and Transmission.

The receptor binding domain(s) (RBD) of spike (S) proteins of SARS-CoV-1 and SARS-CoV-2 (severe acute respiratory syndrome coronavirus) undergoes closed to open transition to engage with host ACE2 receptors. In this study, using multi atomistic (equilibrium) and targeted (non-equilibrium) molecular dynamics simulations, we have compared energetics of RBD opening pathways in full-length (modeled from cryo-EM structures) S proteins of SARS-CoV-1 and SARS-CoV-2. Our data indicate that amino acid variations at the RBD interaction interface can culminate into distinct free energy landscapes of RBD opening in these S proteins.

In-silico design of an immunoinformatics based multi-epitope vaccine against Leishmania donovani.

Background: Visceral Leishmaniasis (VL) is a fatal vector-borne parasitic disorder occurring mainly in tropical and subtropical regions. VL falls under the category of neglected tropical diseases with growing drug resistance and lacking a licensed vaccine. Conventional vaccine synthesis techniques are often very laborious and challenging.

Kinetics and selectivity of methane oxidation on an IrO(110) film.

Undercoordinated, bridging O-atoms (O) are highly active as H-acceptors in alkane dehydrogenation on IrO(110) surfaces but transform to HOgroups that are inactive toward hydrocarbons. The low C-H activity and high stability of the HOgroups cause the kinetics and product selectivity during CHoxidation on IrO(110) to depend sensitively on the availability of Oatoms prior to the onset of product desorption. From temperature programmed reaction spectroscopy (TPRS) and kinetic simulations, we identified two O-coverage regimes that distinguish the kinetics and product formation during CHoxidation on IrO(110).

Neuro-fuzzy network incorporating multiple lexicons for social sentiment analysis.

We have proposed MultiLexANFIS which is an adaptive neuro-fuzzy inference system (ANFIS) that incorporates inputs from multiple lexicons to perform sentiment analysis of social media posts. We classify tweets into two classes: neutral and non-neutral; the latter class includes both positive and negative polarity. This type of classification will be considered for applications that aim to test the neutrality of content posted by the users in social media platforms.

Real-Time Molecular Monitoring in Acute Myeloid Leukemia With Circulating Tumor DNA.

The clonal evolution of acute myeloid leukemia (AML), an oligoclonal hematological malignancy, is driven by a plethora of cytogenetic abnormalities, gene mutations, abnormal epigenetic patterns, and aberrant gene expressions. These alterations in the leukemic blasts promote clinically diverse manifestations with common characteristics of high relapse and drug resistance. Defining and real-time monitoring of a personalized panel of these predictive genetic biomarkers is rapidly being adapted in clinical setting for diagnostic, prognostic, and therapeutic decision-making in AML.

Next generation sequencing guided treatment modulation and prognosis in Acute myeloid leukemia: Case vignettes.

Objective: The genomic mutational landscape of Acute Myeloid Leukemia has contributed to better treatment options, risk stratification and prognostication of this genetically heterogeneous disease. With several approved new drugs targeting specific mutations with better outcomes, we describe here two cases of AML in which, NPM1 was detected at diagnosis. The impact of age, type of treatment, stability of NPM1 mutation, and co-occurring mutations on survival are the essential parameters for investigation.

Leveraging Prior Knowledge to Recover Characteristic Immune Regulatory Motifs in Gulf War Illness.

Potentially linked to the basic physiology of stress response, Gulf War Illness (GWI) is a debilitating condition presenting with complex immune, endocrine and neurological symptoms. Here we interrogate the immune response to physiological stress by measuring 16 blood-borne immune markers at 8 time points before, during and after maximum exercise challenge in = 12 GWI veterans and = 11 healthy veteran controls deployed to the same theater. Immune markers were combined into functional sets and the dynamics of their joint expression described as classical rate equations.

Restoring chaos using deep reinforcement learning.

A catastrophic bifurcation in non-linear dynamical systems, called crisis, often leads to their convergence to an undesirable non-chaotic state after some initial chaotic transients. Preventing such behavior has been quite challenging. We demonstrate that deep Reinforcement Learning (RL) is able to restore chaos in a transiently chaotic regime of the Lorenz system of equations.

Redox-mediated transformation of a TbO(111) thin film from the cubic fluorite to bixbyite structure.

We used temperature programmed desorption (TPD) and low energy electron diffraction (LEED) to investigate the isomeric structural transformation of a Tb2O3 thin film grown on Pt(111). We find that repeated oxidation and thermal reduction to 1000 K transforms an oxygen-deficient, cubic fluorite (CF) Tb2O3(111) thin film to the well-defined bixbyite, or c-Tb2O3(111) structure, whereas annealing the CF-Tb2O3(111) film in UHV is ineffective in causing this structural transformation. We estimate that the final stabilized film consists of about ten layers of c-Tb2O3(111) in the surface region plus about eight layers of CF-Tb2O3(111) located between the c-Tb2O3(111) and the Pt(111) substrate.

Structure and Sequence Based Analysis of Pullulanases: Understanding Dual Catalytic Mechanism.

Background: Starch processing requires a combination of enzymes with other chemical and physical processes, which increases cost and time. Enzymes used in these processes have a characteristic (α/β)8 barrel domain architecture, although, show variable activity. Pullulanase type 1 and isoamylase act on α-1-6 linkage, amylase on α-1-4 linkage whereas pullulanase type 2 acts on both α-1-6, and α-1-4 linkages of starch.

Astrocyte-specific transcriptome analysis using the ALDH1L1 bacTRAP mouse reveals novel biomarkers of astrogliosis in response to neurotoxicity.

Neurotoxicology is hampered by the inability to predict regional and cellular targets of toxicant-induced damage. Evaluating astrogliosis overcomes this problem because reactive astrocytes highlight the location of toxicant-induced damage. While enhanced expression of glial fibrillary acidic protein is a hallmark of astrogliosis, few other biomarkers have been identified.

Ferrites: magnetic materials as an alternate source of green electrical energy.

Ferrites samples MgLiFeO for x = 0.0, 0.1, 0.

A retrospective analysis of complications of laparoscopic left donor nephrectomy using the Kocak's modification of Clavien-Dindo system.

Introduction: Kocak described a modification of Clavien-Dindo classification system (CDCS) for reporting procedure-related complications in laparoscopic donor nephrectomy (LDN). We used the Kocak modification in grading and reporting the severity of complications in patients who underwent LDN and in evaluating various parameters that predict them.

Methods: In all, 1430 patients who underwent left LDN from 2000 to 2016 were included in this study.

Single-centre experience of retroperitoneoscopic approach in urology with tips to overcome the steep learning curve.

Context: The retroperitoneoscopic or retroperitoneal (RP) surgical approach has not become as popular as the transperitoneal (TP) one due to the steeper learning curve.

Aims: Our single-institution experience focuses on the feasibility, advantages and complications of retroperitoneoscopic surgeries (RS) performed over the past 10 years. Tips and tricks have been discussed to overcome the steep learning curve and these are emphasised.

Inferring Broad Regulatory Biology from Time Course Data: Have We Reached an Upper Bound under Constraints Typical of In Vivo Studies?

There is a growing appreciation for the network biology that regulates the coordinated expression of molecular and cellular markers however questions persist regarding the identifiability of these networks. Here we explore some of the issues relevant to recovering directed regulatory networks from time course data collected under experimental constraints typical of in vivo studies. NetSim simulations of sparsely connected biological networks were used to evaluate two simple feature selection techniques used in the construction of linear Ordinary Differential Equation (ODE) models, namely truncation of terms versus latent vector projection.