ClinVar: updates to support classifications of both germline and somatic variants.

ClinVar (www.ncbi.nlm.

Swelling and Degrafting of Poly(3-sulfopropyl methacrylate) Brushes.

Upon exposure to a good solvent, polymer brushes prepared via surface-initiated polymerization can undergo degrafting via cleavage of bonds that anchor the polymer tethers to the underlying substrate. As polymer brushes are often used in a solvent swollen state, this has implications for the longevity of these polymer coatings. Improving the fundamental understanding of this process is thus also of practical importance.

Cytotoxic T cells drive doxorubicin-induced cardiac fibrosis and systolic dysfunction.

Doxorubicin, the most prescribed chemotherapeutic drug, causes dose-dependent cardiotoxicity and heart failure. However, our understanding of the immune response elicited by doxorubicin is limited. Here we show that an aberrant CD8 T cell immune response following doxorubicin-induced cardiac injury drives adverse remodeling and cardiomyopathy.

Enhanced Energy Transfer in Cavity QED Based Phototransistors.

We leveraged strong light-matter coupling, a quantum process generating hybridized states, to prepare phototransistors using donor-acceptor pairs that transfer energy via Rabi oscillations. In a prototype experiment, we used a cyanine J-aggregate (TDBC; donor) and MoS monolayer (acceptor) in a field effect transistor cavity to study photoresponsivity. Energy migrates through the newly formed polaritonic ladder, with enhanced device efficiency when the cavity is resonant with donors.

Impaired T cell IRE1α/XBP1 signaling directs inflammation in experimental heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a widespread syndrome with limited therapeutic options and poorly understood immune pathophysiology. Using a 2-hit preclinical model of cardiometabolic HFpEF that induces obesity and hypertension, we found that cardiac T cell infiltration and lymphoid expansion occurred concomitantly with cardiac pathology and that diastolic dysfunction, cardiomyocyte hypertrophy, and cardiac phospholamban phosphorylation were T cell dependent. Heart-infiltrating T cells were not restricted to cardiac antigens and were uniquely characterized by impaired activation of the inositol-requiring enzyme 1α/X-box-binding protein 1 (IRE1α/XBP1) arm of the unfolded protein response.

T-Cell MyD88 Is a Novel Regulator of Cardiac Fibrosis Through Modulation of T-Cell Activation.

Background: Cardiac inflammation in heart failure is characterized by the presence of damage-associated molecular patterns, myeloid cells, and T cells. Cardiac damage-associated molecular patterns provide continuous proinflammatory signals to myeloid cells through TLRs (toll-like receptors) that converge onto the adaptor protein MyD88 (myeloid differentiation response 88). These induce activation into efficient antigen-presenting cells that activate T cells through their TCR (T-cell receptor).

Long-Range Energy Transfer in Strongly Coupled Donor-Acceptor Phototransistors.

Strong light-matter coupling offers a way to tailor the optoelectronic properties of materials. Energy transfer between strongly coupled donor-acceptor pairs shows remarkable efficiency beyond the Förster distance via coupling through a confined photon. This long-range energy transfer is facilitated through the collective nature of polaritonic states.

Swelling-Activated, Soft Mechanochemistry in Polymer Materials.

Swelling in polymer materials is a ubiquitous phenomenon. At a molecular level, swelling is dictated by solvent-polymer interactions, and has been thoroughly studied both theoretically and experimentally. Favorable solvent-polymer interactions result in the solvation of polymer chains.

Antigen presentation by cardiac fibroblasts promotes cardiac dysfunction.

Heart failure (HF) is a leading cause of morbidity and mortality. Studies in animal models and patients with HF revealed a prominent role for CD4+ T cell immune responses in the pathogenesis of HF and highlighted an active crosstalk between cardiac fibroblasts and IFNγ producing CD4+ T cells that results in profibrotic myofibroblast transformation. Whether cardiac fibroblasts concomitantly modulate pathogenic cardiac CD4+ T cell immune responses is unknown.

Spin-Boson Quantum Phase Transition in Multilevel Superconducting Qubits.

Superconducting circuits are currently developed as a versatile platform for the exploration of many-body physics, by building on nonlinear elements that are often idealized as two-level qubits. A classic example is given by a charge qubit that is capacitively coupled to a transmission line, which leads to the celebrated spin-boson description of quantum dissipation. We show that the intrinsic multilevel structure of superconducting qubits drastically restricts the validity of the spin-boson paradigm due to phase localization, which spreads the wave function over many charge states.

Sialomucin CD43 Plays a Deleterious Role in the Development of Experimental Heart Failure Induced by Pressure Overload by Modulating Cardiac Inflammation and Fibrosis.

Sialomucin CD43 is a transmembrane protein differentially expressed in leukocytes that include innate and adaptive immune cells. Among a variety of cellular processes, CD43 participates in T cell adhesion to vascular endothelial cells and contributes to the progression of experimental autoimmunity. Sequential infiltration of myeloid cells and T cells in the heart is a hallmark of cardiac inflammation and heart failure (HF).

Gestational diabetes mellitus (GDM) and adverse pregnancy outcome in South Asia: A systematic review.

Introduction: The prevalence of gestational diabetes mellitus (GDM) is increasing in developing countries including the South Asian Nations. The current study aimed to examine the association of GDM with adverse pregnancy outcomes from foetal and maternal perspectives in South Asia.

Methods: A systematic review was conducted including primary studies published since January 2020 from South Asian countries.

Enhanced Charge Transport in Two-Dimensional Materials through Light-Matter Strong Coupling.

Strong light-matter interaction of functional materials is emerging as a promising area of research. Recent experiments suggest that material properties like charge transport can be controlled by coupling to a vacuum electromagnetic field. Here, we explored the design of a Fabry-Perot cavity in a field-effect transistor configuration and studied the charge transport in two-dimensional materials.

Endothelial STING controls T cell transmigration in an IFNI-dependent manner.

The stimulator of IFN genes (STING) protein senses cyclic dinucleotides released in response to double-stranded DNA and functions as an adaptor molecule for type I IFN (IFNI) signaling by activating IFNI-stimulated genes (ISG). We found impaired T cell infiltration into the peritoneum in response to TNF-α in global and EC-specific STING-/- mice and discovered that T cell transendothelial migration (TEM) across mouse and human endothelial cells (EC) deficient in STING was strikingly reduced compared with control EC, whereas T cell adhesion was not impaired. STING-/- T cells showed no defect in TEM or adhesion to EC, or immobilized endothelial cell-expressed molecules ICAM1 and VCAM1, compared with WT T cells.

Self-assembly of protein-polymer conjugates for drug delivery.

Protein-polymer conjugates are a class of molecules that combine the stability of polymers with the diversity, specificity, and functionality of biomolecules. These bioconjugates can result in hybrid materials that display properties not found in their individual components and can be particularly relevant for drug delivery applications. Engineering amphiphilicity into these bioconjugate materials can lead to phase separation and the assembly of high-order structures.

Amino acid-based HS donors: -thiocarboxyanhydrides that release HS with innocuous byproducts.

A library of N-thiocarboxyanhydrides (NTAs) derived from natural amino acids with benign byproducts and controlled H2S-release kinetics is reported. Minimal acute in vitro toxicity was observed in multiple cell lines, while longer-term toxicity in cancer cells was observed, with slow-releasing donors exhibiting the greatest cytotoxic effects.

Transcriptome and proteome mapping in the sheep atria reveal molecular featurets of atrial fibrillation progression.

Aims: Atrial fibrillation (AF) is a progressive cardiac arrhythmia that increases the risk of hospitalization and adverse cardiovascular events. There is a clear demand for more inclusive and large-scale approaches to understand the molecular drivers responsible for AF, as well as the fundamental mechanisms governing the transition from paroxysmal to persistent and permanent forms. In this study, we aimed to create a molecular map of AF and find the distinct molecular programmes underlying cell type-specific atrial remodelling and AF progression.

Gut dysbiosis induced by cardiac pressure overload enhances adverse cardiac remodeling in a T cell-dependent manner.

Despite the existing association of gut dysbiosis and T cell inflammation in heart failure (HF), whether and how gut microbes contribute to T cell immune responses, cardiac fibrosis and dysfunction in HF remains largely unexplored. Our objective was to investigate whether gut dysbiosis is induced by cardiac pressure overload, and its effect in T cell activation, adverse cardiac remodeling, and cardiac dysfunction. We used 16S rRNA sequencing of fecal samples and discovered that cardiac pressure overload-induced by transverse aortic constriction (TAC) results in gut dysbiosis, characterized by a reduction of tryptophan and short-chain fatty acids producing bacteria in WT mice, but not in T cell-deficient mice ( ) mice.

Linker-Regulated HS Release from Aromatic Peptide Amphiphile Hydrogels.

Controlled release is an essential requirement for delivery of hydrogen sulfide (HS) because of its reactive nature, short half-life in biological fluids, and toxicity at high concentrations. In this context, HS delivery via hydrogels may be beneficial as they can deliver HS locally at the site of interest. Herein, we employed hydrogels based on aromatic peptide amphiphiles (APAs) with tunable mechanical properties to modulate the rates of HS release.

Nanoformulations for Ocular Delivery of Drugs - A Patent Perspective.

Efficient delivery of ocular therapeutics with improved efficacy, enhanced bioavailability, and acceptable patient compliance presents unique challenges. This can be attributed to the presence of protective mechanisms, physicobiological barriers, and structural obstacles in the eye. Nanotherapeutic interventions have been explored extensively over the past few years to overcome these limitations.

ClinVar: improvements to accessing data.

ClinVar is a freely available, public archive of human genetic variants and interpretations of their relationships to diseases and other conditions, maintained at the National Institutes of Health (NIH). Submitted interpretations of variants are aggregated and made available on the ClinVar website (https://www.ncbi.

The Benefits of Macromolecular/Supramolecular Approaches in Hydrogen Sulfide Delivery: A Review of Polymeric and Self-Assembled Hydrogen Sulfide Donors.

Cell homeostasis and redox balance are regulated in part by hydrogen sulfide (HS), a gaseous signaling molecule known as a gasotransmitter. Given its biological roles, HS has promising therapeutic potential, but controlled delivery of this reactive and hazardous gas is challenging due to its promiscuity, rapid diffusivity, and toxicity at high doses. Macromolecular and supramolecular drug delivery systems are vital for the effective delivery of many active pharmaceutical ingredients, and HS stands to benefit greatly from the tunable physical, chemical, and pharmacokinetic properties of polymeric and/or self-assembled drug delivery systems.