Rare vascular complications in classical Ehlers-Danlos syndromes.

Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders associated with skin, ligament, blood vessel and organ abnormalities. Skin hyperextensibility, joint hypermobility and widened atrophic scars are characteristic of classical EDS. Vascular complications, though rare in classical EDS, can be life-threatening, and this necessitates one to look for vascular associations in non-vascular, such as classical, forms of EDS due to the heterogeneity of the syndrome.

Mechanism of MCUB-dependent inhibition of mitochondrial calcium uptake.

Mitochondrial Ca levels are regulated to balance stimulating respiration against the harm of Ca overload. Contributing to this balance, the main channel transporting Ca into the matrix, the mitochondrial Ca uniporter, can incorporate a dominant-negative subunit (MCUB). MCUB is homologous to the pore-forming subunit MCU, but when present in the pore-lining tetramer, inhibits Ca transport.

Dynamical crossovers and correlations in a harmonic chain of active particles.

We explore the dynamics of a tracer in an active particle harmonic chain, investigating the influence of interactions. Our analysis involves calculating mean-squared displacements (MSDs) and space-time correlations through Green's function techniques and numerical simulations. Depending on chain characteristics, , different time scales determined by interaction stiffness and persistence of activity, tagged-particle MSDs exhibit ballistic, diffusive, and single-file diffusion (SFD) scaling over time, with crossovers explained by our analytic expressions.

Nosocomial meningitis diagnostic test characteristics: a systematic review.

Background: The incidence of nosocomial meningitis, and utility of lumbar puncture, is unclear in hospitalized patients without preceding neurosurgery or head trauma.

Aim: We planned for a systematic review and meta-analysis to evaluate accuracy of clinical features and diagnostic utility of lumbar puncture in nosocomial meningitis.

Methods: We searched MEDLINE, MEDLINE In-Process/ePubs, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science from inception until June 5, 2024.

Direct mitochondrial import of lactate supports resilient carbohydrate oxidation.

Lactate is the highest turnover circulating metabolite in mammals. While traditionally viewed as a waste product, lactate is an important energy source for many organs, but first must be oxidized to pyruvate for entry into the tricarboxylic acid cycle (TCA cycle). This reaction is thought to occur in the cytosol, with pyruvate subsequently transported into mitochondria via the mitochondrial pyruvate carrier (MPC).

Activity-induced phase transition and coarsening dynamics in dry apolar active nematics.

Using the Lebwohl-Lasher interaction for reciprocal local alignment, we present a comprehensive phase diagram for a dry, apolar, active nematic system using its stochastic off-lattice dynamics. The nematic-isotropic transition in this system is first-order and occurs alongside a fluctuation-dominated phase separation. Our phase diagram identifies three distinct regions based on activity and orientational noise relative to alignment strength: a homogeneous isotropic phase, a nematic phase with giant density fluctuations, and a coexistence region.

In silico fragment-based design and pharmacophore modelling of therapeutics against dengue virus envelope protein.

Unlabelled: Dengue virus, an arbovirus of genus Flavivirus, is an infectious disease causing organisms in the tropical environment leading to numerous deaths every year. No therapeutic is available against the virus till date with only symptomatic relief available. Here, we have tried to design therapeutic compounds from scratch by fragment based method followed by pharmacophore based modelling to find suitable similar structure molecules and validated the same by MD simulation, followed by binding energy calculations and ADMET analysis.

Rare cardiac metastasis of lung cancer mimicking aneurysm and tamponade.

Metastasis of non-small cell lung carcinoma (NSCLC) is a rare cause of cardiac metastatic tumors (CMT). We present a case of NSCLC infiltrating the apical left ventricle mimicking cardiac aneurysm and tamponade. The patient, who had a history of NSCLC, presented with acute shortness of breath and an echocardiogram concerning for ruptured left ventricular aneurysm.

Enhancing mitochondrial pyruvate metabolism ameliorates ischemic reperfusion injury in the heart.

The clinical therapy for treating acute myocardial infarction is primary percutaneous coronary intervention (PPCI). PPCI is effective at reperfusing the heart; however, the rapid reintroduction of blood can cause ischemia-reperfusion (I/R). Reperfusion injury is responsible for up to half of the total myocardial damage, but there are no pharmacological interventions to reduce I/R.

Inertia and activity: spiral transitions in semi-flexible, self-avoiding polymers.

We consider a two-dimensional, tangentially active, semi-flexible, self-avoiding polymer to find a dynamical re-entrant transition between motile open chains and spinning achiral spirals with increasing activity. Utilizing probability distributions of the turning number, we ascertain the comparative stability of the spiral structure and present a detailed phase diagram within the activity inertia plane. The onset of spiral formation at low activity levels is governed by a torque balance and is independent of inertia.

Molecular Dynamics Simulation of a Feather-Boa Model of a Bacterial Chromosome.

The chromosome of a bacterium consists of a mega-base pair-long circular DNA, which self-organizes within the micron-sized bacterial cell volume, compacting itself by three orders of magnitude. Unlike eukaryotic chromosomes, it lacks a nuclear membrane and freely floats in the cytosol confined by the cell membrane. It is believed that strong confinement, cross-linking by associated proteins, and molecular crowding all contribute to determine chromosome size and morphology.

Repurposing of FDA-approved drugs against oligomerization domain of dengue virus NS1 protein: a computational approach.

Dengue fever is a serious health hazard on a global scale and its primary causative agent is the dengue virus (DENV). The non-structural protein 1 (NS1) of DENV plays a pivotal role in pathogenesis. It is associated with several autoimmune events, endothelial cell apoptosis, and vascular leakage, which increase mainly during the critical phase of infection.

Repurposing of therapeutic antibodies against dengue virus envelope protein receptor binding domain.

Dengue virus (DENV) is the leading cause of numerous deaths every year due to its high infectivity. In this study we have tried to target the DENV envelope protein receptor binding domain, the region crucial for binding to host receptors which leads to membrane fusion and entry of the viral genome into the human host cell. We have taken 13 known FDA approved antiviral therapeutic antibodies from therapeutic antibody database and tried to repurpose them against the DENV envelope protein.

A mechanistic study on the tolerance of PAM distal end mismatch by SpCas9.

The therapeutic application of CRISPR-Cas9 is limited due to its off-target activity. To have a better understanding of this off-target effect, we focused on its mismatch-prone PAM distal end. The off-target activity of SpCas9 depends directly on the nature of mismatches, which in turn results in deviation of the active site of SpCas9 due to structural instability in the RNA-DNA duplex strand.

Noncovalent Catalyst-cum-Inhibitor Directed Supramolecular Pathway Selection and Asymmetry Amplification by Aggregate Cross-Nucleation.

The key to any controlled supramolecular polymerization (CSP) process lies in controlling the nucleation step, which is typically achieved by sequestering monomers in a kinetically trapped state. However, kinetic traps that are shallow cannot prevent spontaneous nucleation, thus limiting the applicability of the CSP in such systems. We use a molecular additive to overcome this limitation by modifying the energy landscape of a competitive self-assembly process and increasing the kinetic stability of an otherwise short-lived trap state.

Peptide based vaccine designing against endemic causing mammarenavirus using reverse vaccinology approach.

The rodent-borne Arenavirus in humans has led to the emergence of regional endemic situations and has deeply emerged into pandemic-causing viruses. Arenavirus have a bisegmented ambisense RNA that produces four proteins: glycoprotein, nucleocapsid, RdRp and Z protein. The peptide-based vaccine targets the glycoprotein of the virus encountered by the immune system.

Computational Insights into the Conformational Dynamics of HIV-1 Vpr in a Lipid Bilayer for Ion Channel Modeling.

HIV-1 Vpr is a multifunctional accessory protein consisting of 96 amino acids that play a critical role in viral pathogenesis. Among its diverse range of activities, Vpr can create a cation-selective ion channel within the plasma membrane. However, the oligomeric state of this channel has not yet been elucidated.

Repurposing of drugs targeting heparan sulphate binding site of dengue virus envelope protein: an in silico competitive binding study.

Dengue virus, an arbovirus, leads to millions of infections every year ultimately leading to a high rate of mortality. Highly effective and specific therapeutic option is not available till date to combat viral infection. One of the first stages in the virus lifecycle encompasses the viral entry into the host cell which is mediated by the interaction between heparan sulphate and the Dengue virus envelope protein in turn leading to the interaction between the envelope protein receptor binding domain and host cell receptors.

Adverse Effects Related to Corticosteroid Use in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis.

Objectives: We postulate that corticosteroid-related side effects in critically ill patients are similar across sepsis, acute respiratory distress syndrome (ARDS), and community-acquired pneumonia (CAP). By pooling data across all trials that have examined corticosteroids in these three acute conditions, we aim to examine the side effects of corticosteroid use in critical illness.

Data Sources: We performed a comprehensive search of MEDLINE, Embase, Centers for Disease Control and Prevention library of COVID research, CINAHL, and Cochrane center for trials.