41 research outputs found
Synthesis of Nuclearly-Modified Cephalosporin Antibiotics
Approaches are described towards synthesis of 1-hydroxy-1-carba-cephalosporin (1), a chemically interesting nuclearly modified cephalosporin analogue which may possess potent antibiotic activity. Approaches to a bicyclic tetrahydropyridine (27), potentially convertible into carbacephem (1), are also discussed. Oxygenated 1-carbacephems (95) and (97) have been prepared via a route employing the reaction between imines and a ketene precursor to give beta-lactams. The 1alpha-isomer (95) exhibited weak antibiotic properties
Characterization of the hydrolytic activity of a polyclonal catalytic antibody preparation by pH-dependence and chemical modification studies: evidence for the involvement of Tyr and Arg side chains as hydrogen-bond donors
Convergent genetic and expression data implicate immunity in Alzheimer's disease
Background
Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis.
Methods
The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.
Results
ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05).
Conclusions
The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics