Cups for COVID: rapid implementation of a harm reduction initiative to support populations experiencing homelessness during the COVID-19 pandemic.

Setting: As of June 10, 2020, 37 people experiencing homelessness or unstable housing in Calgary, Alberta, had developed lab-confirmed COVID-19. Spread occurred despite standard outbreak controls at affected shelter and supportive housing sites. Among these 37 cases, drink sharing was frequently identified as a modifiable mode of possible transmission.

[OBSTRUCTION OF THE OUTFLOW TRACT OF THE LEFT VENTRICLE DURING CARDIAC SURGERY].

Obstruction of the outflow tract of the left ventricle is well understood as a complication of hypertrophic cardiomyopathy. But other clinical situations are not described in Russian. The aim of this work was the description of the clinical, echocardiographic criteria and pathogenetically substantiated therapy dynamic subaortic obstruction in operations with extracorporeal circulation.

Small-molecule ligands of methyl-lysine binding proteins: optimization of selectivity for L3MBTL3.

Lysine methylation is a key epigenetic mark, the dysregulation of which is linked to many diseases. Small-molecule antagonism of methyl-lysine (Kme) binding proteins that recognize such epigenetic marks can improve our understanding of these regulatory mechanisms and potentially validate Kme binding proteins as drug-discovery targets. We previously reported the discovery of 1 (UNC1215), the first potent and selective small-molecule chemical probe of a methyl-lysine reader protein, L3MBTL3, which antagonizes the mono- and dimethyl-lysine reading function of L3MBTL3.

Discovery of a chemical probe for the L3MBTL3 methyllysine reader domain.

We describe the discovery of UNC1215, a potent and selective chemical probe for the methyllysine (Kme) reading function of L3MBTL3, a member of the malignant brain tumor (MBT) family of chromatin-interacting transcriptional repressors. UNC1215 binds L3MBTL3 with a K(d) of 120 nM, competitively displacing mono- or dimethyllysine-containing peptides, and is greater than 50-fold more potent toward L3MBTL3 than other members of the MBT family while also demonstrating selectivity against more than 200 other reader domains examined. X-ray crystallography identified a unique 2:2 polyvalent mode of interaction between UNC1215 and L3MBTL3.

Histone recognition by human malignant brain tumor domains.

Histone methylation has emerged as an important covalent modification involved in a variety of biological processes, especially regulation of transcription and chromatin dynamics. Lysine methylation is found in three distinct states (monomethylation, dimethylation and trimethylation), which are recognized by specific protein domains. The malignant brain tumor (MBT) domain is one such module found in several chromatin regulatory complexes including Polycomb repressive complex 1.