Small Molecule Modulators of β-arrestins.

Unlabelled: β-arrestins (βarrs) are key regulators of G protein-coupled receptors (GPCRs), essential for modulating signaling pathways and physiological processes. While current pharmacological strategies target GPCR orthosteric and allosteric sites, as well as G protein transducers, comparable tools for studying βarrs are lacking. Here, we present the discovery and characterization of novel small-molecule allosteric inhibitors of βarrs through comprehensive biophysical, biochemical, pharmacological, and structural analyses.

Immunoproteasome inhibition reduces donor specific antibody production and cardiac allograft vasculopathy in a mouse heart transplantation model.

Objective: Cardiac Allograft Vasculopathy (CAV), a process of vascular damage accelerated by antibody-mediated rejection (AMR), is one of the leading causes of cardiac transplant failure. Proteasome inhibitors (PIs) are utilized to treat AMR, however PI-associated toxicity limits their therapeutic utility. Novel immunoproteasome inhibitors (IPIs) have higher specificity for immune cells and have not been investigated for AMR in cardiac transplant patients.

Taxonomy, ontogeny, and ecology of Tonnacypris stewarti (Daday 1908) comb. nov. (Ostracoda: Cyprididae) from Nam Co, Tibetan Plateau.

Taxonomic clarification of Tonnacypris stewarti comb. nov. (= Herpetocypris stewarti), a non-marine ostracod first described by Daday in 1908, was required due to the existence of various synonyms without detailed morphological descriptions.

Impact of active case finding for tuberculosis with mass chest X-ray screening in Glasgow, Scotland, 1950-1963: An epidemiological analysis of historical data.

Background: Community active case finding (ACF) for tuberculosis was widely implemented in Europe and North America between 1940 and 1970, when incidence was comparable to many present-day high-burden countries. Using an interrupted time series analysis, we analysed the effect of the 1957 Glasgow mass chest X-ray campaign to inform contemporary approaches to screening.

Methods And Findings: Case notifications for 1950 to 1963 were extracted from public health records and linked to demographic data.