Effect of bovine beta-casomorphins on rat pancreatic beta cells (RIN-5F) under glucotoxic stress.

Beta-casomorphins (BCMs) are the bio-active peptides having opioid properties which are formed by the proteolytic digestion of β-caseins in milk. BCM-7 forms when A1 milk is digested in the small intestine due to a histidine at the 67th position in β-casein, unlike A2 milk, which has proline at this position and produces BCM-9. BCM-7 has further degraded into BCM-5 by the dipeptidyl peptidase-IV (DPP-IV) enzyme in the intestine.

Evolutionary sequence and structural basis for the distinct conformational landscapes of Tyr and Ser/Thr kinases.

Protein kinases are molecular machines with rich sequence variation that distinguishes the two main evolutionary branches - tyrosine kinases (TKs) from serine/threonine kinases (STKs). Using a sequence co-variation Potts statistical energy model we previously concluded that TK catalytic domains are more likely than STKs to adopt an inactive conformation with the activation loop in an autoinhibitory folded conformation, due to intrinsic sequence effects. Here we investigate the structural basis for this phenomenon by integrating the sequence-based model with structure-based molecular dynamics (MD) to determine the effects of mutations on the free energy difference between active and inactive conformations, using a thermodynamic cycle involving many (n = 108) protein-mutation free energy perturbation (FEP) simulations in the active and inactive conformations.

Exploring the Future of Polyhydroxyalkanoate Composites with Organic Fillers: A Review of Challenges and Opportunities.

Biopolymers from renewable materials are promising alternatives to the traditional petroleum-based plastics used today, although they face limitations in terms of performance and processability. Natural fillers have been identified as a strategic route to create sustainable composites, and natural fillers in the form of waste by-products have received particular attention. Consequently, the primary focus of this article is to offer a broad overview of recent breakthroughs in environmentally friendly Polhydroxyalkanoate (PHA) polymers and their composites.

An UltraMNIST classification benchmark to train CNNs for very large images.

Current convolutional neural networks (CNNs) are not designed for large scientific images with rich multi-scale features, such as in satellite and microscopy domain. A new phase of development of CNNs especially designed for large images is awaited. However, application-independent high-quality and challenging datasets needed for such development are still missing.

Deep Learning Approaches for Medical Image Analysis and Diagnosis.

In addition to enhancing diagnostic accuracy, deep learning techniques offer the potential to streamline workflows, reduce interpretation time, and ultimately improve patient outcomes. The scalability and adaptability of deep learning algorithms enable their deployment across diverse clinical settings, ranging from radiology departments to point-of-care facilities. Furthermore, ongoing research efforts focus on addressing the challenges of data heterogeneity, model interpretability, and regulatory compliance, paving the way for seamless integration of deep learning solutions into routine clinical practice.

Evolutionary sequence and structural basis for the distinct conformational landscapes of Tyr and Ser/Thr kinases.

Protein kinases are molecular machines with rich sequence variation that distinguishes the two main evolutionary branches - tyrosine kinases (TKs) from serine/threonine kinases (STKs). Using a sequence co-variation Potts statistical energy model we previously concluded that TK catalytic domains are more likely than STKs to adopt an inactive conformation with the activation loop in an autoinhibitory "folded" conformation, due to intrinsic sequence effects. Here we investigated the structural basis for this phenomenon by integrating the sequence-based model with structure-based molecular dynamics (MD) to determine the effects of mutations on the free energy difference between active and inactive conformations, using a novel thermodynamic cycle involving many (n=108) protein-mutation free energy perturbation (FEP) simulations in the active and inactive conformations.

Evolutionary sequence and structural basis for the distinct conformational landscapes of Tyr and Ser/Thr kinases.

Protein kinases are molecular machines with rich sequence variation that distinguishes the two main evolutionary branches - tyrosine kinases (TKs) from serine/threonine kinases (STKs). Using a sequence co-variation Potts statistical energy model we previously concluded that TK catalytic domains are more likely than STKs to adopt an inactive conformation with the activation loop in an autoinhibitory "folded" conformation, due to intrinsic sequence effects. Here we investigated the structural basis for this phenomenon by integrating the sequence-based model with structure-based molecular dynamics (MD) to determine the effects of mutations on the free energy difference between active and inactive conformations, using a novel thermodynamic cycle involving many (n=108) protein-mutation free energy perturbation (FEP) simulations in the active and inactive conformations.

Potts Hamiltonian Models and Molecular Dynamics Free Energy Simulations for Predicting the Impact of Mutations on Protein Kinase Stability.

Single-point mutations in kinase proteins can affect their stability and fitness, and computational analysis of these effects can provide insights into the relationships among protein sequence, structure, and function for this enzyme family. To assess the impact of mutations on protein stability, we used a sequence-based Potts Hamiltonian model trained on a kinase family multiple-sequence alignment (MSA) to calculate the statistical energy (fitness) effects of mutations and compared these against relative folding free energies (ΔΔs) calculated from all-atom molecular dynamics free energy perturbation (FEP) simulations in explicit solvent. The fitness effects of mutations in the Potts model (Δs) showed good agreement with experimental thermostability data (Pearson = 0.

Tuning Caco-2 permeability by cocrystallization: Insights from molecular dynamics simulation.

Emerging evidence suggests that intestinal permeability can be potentially enhanced through cocrystallization. However, a mechanism for this effect remains to be established. In this study, we first demonstrate the enhancement in intestinal permeability, evaluated by the Caco-2 cell permeability assay, of acetazolamide (ACZ) in the presence of a conformer, p-aminobenzoic acid (PABA), delivered in the form of a 1:1 cocrystal.

SELEX based aptamers with diagnostic and entry inhibitor therapeutic potential for SARS-CoV-2.

Frequent mutation and variable immunological protection against vaccination is a common feature for COVID-19 pandemic. Early detection and confinement remain key to controlling further spread of infection. In response, we have developed an aptamer-based system that possesses both diagnostic and therapeutic potential towards the virus.

Allogenic adipose derived mesenchymal stem cells are effective than antibiotics in treating endometritis.

Endometritis is a uterine inflammatory disease that causes reduced livestock fertility, milk production and lifespan leading to significant economic losses to the dairy industry. Mesenchymal stem cells (MSC) may act as an alternative for inefficacy of antibiotics and rising antibiotic resistance in endometritis. The present study aimed to cure the chronic endometritic buffaloes using allogenic adipose-derived MSCs (AD-MSC).

Coronary Stent Infections - A Systematic Review and Meta-Analysis.

Background: Coronary stent infection (CSI) represents a rare but potentially fatal complication of percutaneous coronary interventions (PCI). A systematic review and meta-analysis of published reports was performed to profile CSI and its management strategies.

Methods: Online database searches were performed using MeSH and keywords.

Kaplan's Lesion in a Child: A Case Report.

Unlabelled: Kaplan's lesion is a rare complex metacarpophalangeal joint dislocation. A 7-year-old female child presented with pain, swelling and inability to move her right index finger. Her mother gave a history of sustaining a fall injury on the same hand around 3 weeks back.

Septic arthritis by : Case report and literature review.

Nocardiosis is a bacterial infection caused by organisms of the genus. The disease typically involves the skin, central nervous system or pulmonary system. Very rarely nocardiosis can cause disease of other organs including bone and joints.

Evolutionary divergence in the conformational landscapes of tyrosine vs serine/threonine kinases.

Inactive conformations of protein kinase catalytic domains where the DFG motif has a "DFG-out" orientation and the activation loop is folded present a druggable binding pocket that is targeted by FDA-approved 'type-II inhibitors' in the treatment of cancers. Tyrosine kinases (TKs) typically show strong binding affinity with a wide spectrum of type-II inhibitors while serine/threonine kinases (STKs) usually bind more weakly which we suggest here is due to differences in the folded to extended conformational equilibrium of the activation loop between TKs vs. STKs.

Stage specific gene expression of folate mediated one-carbon metabolism enzymes and transporters in buffalo oocytes and pre-implantation embryos.

DNA synthesis and methylations are crucial during pre-implantation embryonic development, and are mediated by one-carbon metabolism of folates. Folates, transported into the cells via folate receptors (FOLR1 and FOLR2) and carriers (SLC19A1), are metabolized by various enzymes involved in folate-methionine cycle. However, the variations in temporal expression of folate transporters and folate-methionine cycle enzymes during pre-implantation embryo development is obscure.

Unravelling the role of hemp straw derived cellulose in CMC/PVA hydrogel for sustained release of fluoroquinolone antibiotic.

Cellulose fibres derived from hemp stalks, a prevalent biowaste in Northern India, were effectively converted into carboxymethyl cellulose (HS-CMC). Novel environmentally benign hydrogels were synthesized from HS-CMC and polyvinyl alcohol (PVA) using citric acid, a green crosslinker employing freeze-drying method. The HS-CMC/PVA hydrogels were successfully used for sustained release of fluoroquinolone antibiotic, norfloxacin.

Hesitancy and reactogenicity to mRNA-based COVID-19 vaccines-Early experience with vaccine rollout in a multi-site healthcare system.

Background: Hesitancy and incomplete vaccination against coronavirus disease 2019 (COVID-19) remains an obstacle to achieving herd immunity. Because of fear of vaccine reactions, patients with medical and allergic co-morbidities express heightened hesitancy. Limited information is available to guide these patients.

Statin and aspirin as adjuvant therapy in hospitalised patients with SARS-CoV-2 infection: a randomised clinical trial (RESIST trial).

Background: Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial.

Primer for Designing Main Protease (M) Inhibitors of SARS-CoV-2.

The COVID-19 outbreak has been devastating, with hundreds of millions of infections and millions of deaths reported worldwide. In response, the application of structure-activity relationships (SAR) upon experimentally validated inhibitors of SARS-CoV-2 main protease (M) may provide an avenue for the identification of new lead compounds active against COVID-19. Upon the basis of information gleaned from a combination of reported crystal structures and the docking of experimentally validated inhibitors, four "rules" for designing potent M inhibitors have been proposed.

Minimally-Invasive Plate Osteosynthesis for Clavicle Fractures.

 To analyze the radiological, clinical, and functional outcomes of clavicle fractures treated with the minimally-invasive plate osteosynthesis (MIPO) technique.  From June 2018 to July 2019, 17 cases of clavicular fractures were managed using the MIPO technique under C-arm fluoroscopy. The functional outcomes were assessed using the Constant-Murley score and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire.

Highly efficient poly(acrylic acid-co-aniline) grafted itaconic acid hydrogel: Application in water retention and adsorption of rhodamine B dye for a sustainable environment.

The present study used a free radical co-polymerization approach to synthesize a smart hydrogel of itaconic acid grafted poly(acrylic acid-co-aniline) (ItA-g-poly(AA-co-ANi)). ItA-g-poly(AA-co-ANi) hydrogel was characterized by Fourier transform infrared spectroscopy (FT-IR), Raman, X-ray diffraction (XRD), thermogravimetric analysis (TGA), field emission scanning electron microscope (FE-SEM), and X-ray photoelectron spectroscopy (XPS) analysis. Rhodamine B (RhB) dye was removed from an aqueous medium using ItA-g-poly(AA-co-ANi) hydrogel.