Diet and food-niche breadth of Burrowing Owls ( Athene cunicularia ) in the Imperial Valley, California

Burrowing Owls ( Athene cunicularia ) occupy intensively managed agricultural areas within the Imperial Valley of California, where they occur at high densities relative to other areas in the state, and yet reproductive rates are often low. Understanding diet and food-niche breadth may lead to insights into factors contributing to their poor reproductive performance. We tested the relative contribution of sex, year, and season on diet composition and food-niche breadth from analyses of stomach contents of adult Burrowing Owls ( n = 53). Orthoptera dominated the diet; it accounted for 58.9% of the total number of prey items in all stomachs and was found in 98.2% of all samples. Rodents, a source of potentially limiting dietary calcium, were found in only 2 stomachs. We detected yearly and seasonal effects on estimated food-niche breadth. Mean food niche for the breeding season was broader (antilog of Shannons index: 2.38 ± 0.15) and more even (Pielous index: 0.67 ± 0.06) than for the nonbreeding season (1.83 ± 0.13, 0.49 ± 0.07, respectively) partially because of a greater frequency of Araneida, Isopoda, Lepidoptera, and Solpugida in the diet during the breeding season. Mean food-niche breadth for 1997 (2.25 ± 0.23) was broader than during 1994, 1995, and 1996 (2.07 ± 0.23, 1.98 ± 0.20, and 1.82 ± 0.40, respectively) because of a greater frequency of Araneida, Dermaptera, Isopoda, Lepidoptera, and Solpugida. These results, and auxiliary diet information, suggest rodents were infrequent in the diet of Burrowing Owls in the Imperial Valley and may help explain their lower reproductive success relative to other areas of California.     

Exon capture analysis of G protein-coupled receptors identifies activating mutations in GRM3 in melanoma

G protein-coupled receptors (GPCRs), the largest human gene family, are important regulators of signaling pathways. However, knowledge of their genetic alterations is limited. In this study, we used exon capture and massively parallel sequencing methods to analyze the mutational status of 734 GPCRs in melanoma. This investigation revealed that one family member, GRM3, was frequently mutated and that one of its mutations clustered within one position. Biochemical analysis of GRM3 alterations revealed that mutant GRM3 selectively regulated the phosphorylation of MEK, leading to increased anchorage-independent growth and migration. Melanoma cells expressing mutant GRM3 had reduced cell growth and cellular migration after short hairpin RNA-mediated knockdown of GRM3 or treatment with a selective MEK inhibitor, AZD-6244, which is currently being used in phase 2 clinical trials. Our study yields the most comprehensive map of genetic alterations in the GPCR gene family.     

Spatial and temporal patterns of Krüppel gene expression in early Drosophila embryos

The Krüppel (Kr) locus is a member of the 'gap' class of segmentation genes of Drosophila melanogaster. Mutations at the Kr locus cause the deletion of contiguous segments from the embryonic body pattern. We have elucidated the spatial and temporal characteristics of Kr gene expression during early embryo development, the localization of cytoplasmic Kr+ activity and its spatial requirement for normal segmentation.     

‘Tetrazolium oxidase’ identified with the heme-oxidases of human tissues

Résumé Des bandes blanches jusqu'ici mystérieuse, apparaissent quand on teint des traces électrophorétiques avec des réactions de tétrazolium pour faire apparaÎtre diverses enzymes. Ces bandes se révèlent comme étant de l'hémoglobine et d'autres hémo-protéines se trouvant dans le sérum et dans des parties du tissue qui arrÊtent la réduction du tétrazolium. Ces bandes peuvent donc troubler le dessin électrophorétique.     

Towards a proteome-scale map of the human protein-protein interaction network

Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.     

An inhibitor of Bcl-2 family proteins induces regression of solid tumours

Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and resistance to therapy. Bcl-X(L) expression correlates with chemo-resistance of tumour cell lines, and reductions in Bcl-2 increase sensitivity to anticancer drugs and enhance in vivo survival. The development of inhibitors of these proteins as potential anti-cancer therapeutics has been previously explored, but obtaining potent small-molecule inhibitors has proved difficult owing to the necessity of targeting a protein-protein interaction. Here, using nuclear magnetic resonance (NMR)-based screening, parallel synthesis and structure-based design, we have discovered ABT-737, a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w, with an affinity two to three orders of magnitude more potent than previously reported compounds. Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models, ABT-737 improves survival, causes regression of established tumours, and produces cures in a high percentage of the mice.