Denis C. Shields

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BACKGROUND Short linear motifs (SLiMs) in proteins are functional microdomains of fundamental importance in many biological systems. SLiMs typically consist of a 3 to 10 amino acid stretch of the primary protein sequence, of which as few as two sites may be important for activity, making identification of novel SLiMs extremely difficult. In particular, it(More)
The inaugural Pepducin Science Symposium convened in Cambridge, Massachusetts on March 8-9, 2009 provided the opportunity for an international group of distinguished scientists to present and discuss research regarding G protein-coupled receptor-related research. G protein-coupled receptors (GPCRs) are, arguably, one of the most important molecular targets(More)
To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis(More)
Calpain, a calcium-activated neutral proteinase, has been implicated in myelin and cytoskeletal protein degradation following spinal cord injury. In the present study, we examined the activity and transcriptional expression of calpain in spinal cord injury lesions via Western blotting analysis and RT-PCR, respectively. No increases in transcriptional(More)
Blood lipids are important cardiovascular disease (CVD) risk factors with both genetic and environmental determinants. The Whitehall II study (n=5592) was genotyped with the gene-centric HumanCVD BeadChip (Illumina). We identified 195 SNPs in 16 genes/regions associated with 3 major lipid fractions and 2 apolipoprotein components at p<10(-5), with the(More)
BACKGROUND Aspirin (acetylsalicylic acid) irreversibly inhibits platelet cyclooxygenase (COX)-1, the enzyme that converts arachidonic acid (AA) to the potent platelet agonist thromboxane (TX) A2. Despite clear benefit from aspirin in patients with cardiovascular disease (CAD), evidence of heterogeneity in the way individuals respond has given rise to the(More)
It has been proposed that proteins which are involved in host defence and susceptibility undergo accelerated evolution. Chemokine receptors have roles as pro-inflammatory agents acting in response to infection, and in addition are receptors for entry of viruses and other pathogens into cells. Consistent with this, their rate of evolution is higher than that(More)
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of(More)
Tandem repeat variation in protein-coding regions will alter protein length and may introduce frameshifts. Tandem repeat variants are associated with variation in pathogenicity in bacteria and with human disease. We characterized tandem repeat polymorphism in human proteins, using the UniGene database, and tested whether these were associated with host(More)
The prediction of ancestral protein sequences from multiple sequence alignments is useful for many bioinformatics analyses. Predicting ancestral sequences is not a simple procedure and relies on accurate alignments and phylogenies. Several algorithms exist based on Maximum Parsimony or Maximum Likelihood methods but many current implementations are unable(More)