Structure-Based Development of Novel Spiro-Piperidine ASH1L Inhibitors.

The absent, small, or homeotic-like 1 (ASH1L) protein is a histone lysine methyltransferase that plays a crucial role in various cancers, including leukemia. Despite representing an attractive therapeutic target, only one class of ASH1L inhibitors was identified to date. Herein, we report development of advanced ASH1L inhibitors targeting the catalytic SET domain, which were designed to access previously unexplored binding pocket on ASH1L.

The impact of the GLOSSY2 and GLOSSY2-LIKE BAHD-proteins in affecting the product profile of the maize fatty acid elongase.

The maize and genes are homologs, which encode proteins that belong to the BAHD family of acyltransferases. genetic studies have demonstrated that these genes may be involved in the elongation of very long chain fatty acids (VLCFAs) that are precursors of the cuticular wax fraction of the plant cuticle. VLCFAs are synthesized by a fatty acyl-CoA elongase complex (FAE) that consists of four component enzymes.

Exertional calf pain at kilometer five - Finding the cause.

A 23-year-old professional distance runner with several years of exertional calf pain was diagnosed with a unique mixed type III and functional popliteal artery entrapment syndrome (PAES). Surgical reduction of the obstructing tissue allowed her to return to professional running. This case highlights the importance of including PAES in the differential for chronic intermittent lower extremity claudication and outlines the work-up required to diagnose this vascular obstruction in younger athletes.

Third generation cephalosporin resistance in clinical non-typhoidal in Germany and emergence of -harbouring pESI plasmids.

Non-typhoidal is an important gastrointestinal pathogen causing a considerable burden of disease. Resistance to third generation cephalosporins poses a serious threat for treatment of severe infections. In this study occurrence, phylogenetic relationship, and mechanisms of third generation cephalosporin resistance were investigated for clinical non-typhoidal isolates in Germany.

A Listeria monocytogenes ST2 clone lacking chitinase ChiB from an outbreak of non-invasive gastroenteritis.

An outbreak with a remarkable Listeria monocytogenes clone causing 163 cases of non-invasive listeriosis occurred in Germany in 2015. Core genome multi locus sequence typing grouped non-invasive outbreak isolates and isolates obtained from related food samples into a single cluster, but clearly separated genetically close isolates obtained from invasive listeriosis cases. A comparative genomic approach identified a premature stop codon in the chiB gene, encoding one of the two L.