Biofilm formation is integral to the pathogenesis of numerous adherent bacteria and contributes to antimicrobial resistance (AMR). The rising threat of AMR means the need to develop novel nonbactericidal antiadhesion approaches against such bacteria is more urgent than ever. Both adherent-invasive (AIEC, implicated in inflammatory bowel disease) and uropathogenic (UPEC, responsible for ∼80% of urinary tract infections) adhere to terminal mannose sugars on epithelial glycoproteins through the FimH adhesin on their type 1 pilus.
View Article and Find Full Text PDFNew methods are described that expand the scope of the Successive Ring Expansion (SuRE) with respect to synthetically challenging lactams. A protocol has been developed for use with 'unreactive' lactams, enabling SuRE reactions to be performed on subsrates that fail under previously established conditions. Ring expansion is also demonstarted on 'reactive' lactams derived from iminosugars for the first time.
View Article and Find Full Text PDFDue to the variety of roles served by the cell membrane, its composition and structure are complex, making it difficult to study. Bioorthogonal reactions, such as the strain promoted azide-alkyne cycloaddition (SPAAC), are powerful tools for exploring the function of biomolecules in their native environment but have been largely unexplored within the context of lipid bilayers. Here, we developed a new approach to study the SPAAC reaction in liposomal membranes using azide- and strained alkyne-functionalized Förster resonance energy transfer (FRET) dye pairs.
View Article and Find Full Text PDFA series of 1,333 patients with non-insulin dependent diabetes (NIDDM) treated with oral hypoglycaemic agents (OHAs) between 1956 and 1988 is described. In addition there were 137 patients with insulin dependent diabetes (IDDM). When last on OHAs 51% of the patients with NIDDM were free from symptoms and satisfactorily controlled; 262 patients are known to have died, 223 have had to be changed to insulin and in 41 patients it has been possible to stop OHAs as no longer being needed, usually owing to better dietary compliance.
View Article and Find Full Text PDFA personal series of 6780 patients with diabetes mellitus is reported. Of these 1410 were thought to have insulin-dependent (Type 1) diabetes and 4926 non-insulin-dependent (Type 2) diabetes. Among the former, 128 patients were only diagnosed when in severe ketoacidosis or coma.
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