Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis.

Apoptosis has been shown to be a significant form of cell loss in many diseases. Detachment of photoreceptors from the retinal pigment epithelium, as seen in various retinal disorders, causes photoreceptor loss and subsequent vision decline. Although caspase-dependent apoptotic pathways are activated after retinal detachment, caspase inhibition by the pan-caspase inhibitor Z-VAD fails to prevent photoreceptor death; thus, we investigated other pathways leading to cell loss.

Integrating genomics across drug discovery and development.

The sequencing of the human genome was an exceptional achievement, but it was not an end in itself as it set the foundation for building new knowledge in biology and medicine. The laborious, multifaceted science of drug discovery and development also draws tremendous benefits from mining the human genome and exploiting the large palette of genomic technologies. This article discusses how diverse genomic tools have been used to date and how they will continue to be utilized in the future to impact drug discovery and development.

Proteomic identification and early validation of complement 1 inhibitor and pigment epithelium-derived factor: Two novel biomarkers of Alzheimer's disease in human plasma.

Emerging disease modifying therapeutic strategies for Alzheimer's disease (AD) have generated a critical need for biomarkers of early stage disease. Here, we describe the identification and assessment of a number of candidate biomarkers in patients with mild to moderate probable AD. Plasma from 47 probable Alzheimer's patients and 47 matched controls were analysed by proteomics to define a significant number of proteins whose expression appeared to be associated with AD.

Chromosomal translocations as a mechanism of BRAF activation in two cases of large congenital melanocytic nevi.

Genetic studies of melanocytic tumors have mainly demonstrated activation of oncogenes such as NRAS or BRAF through point mutations. In two cases of large congenital melanocytic nevi, we observed a chromosomal translocation involving the BRAF oncogene on chromosome 7q34, resulting in both cases in removal of the auto-inhibitory N-terminal regulatory domain (hence the Ras-guanosine triphosphate binding domain) of BRAF from its protein kinase domain. This is early evidence of BRAF activation through chromosomal translocation in melanocytic tumors.

Interplay of transcriptomics and proteomics.

Despite the obvious attractions of parallel profiling of transcripts and proteins on a global 'omic' scale, there are practical and biological differences involved in their application. Transcriptomics is now a robust, high-throughput, cost-effective technology capable of simultaneously quantifying tens of thousands of defined mRNA species in a miniaturized, automated format. Conversely, proteomic analysis is currently much more limited in breadth and depth of coverage owing to variations in protein abundance, hydrophobicity, stability, size and charge.