Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE

Phospholipase C gamma 1 (PLC-gamma 1) hydrolyses phosphatidylinositol-4,5-bisphosphate to the second messengers inositol-1,4,5-trisphosphate and diacylglycerol. PLC-gamma 1 also has mitogenic activity upon growth-factor-dependent tyrosine phosphorylation; however, this activity is not dependent on the phospholipase activity of PLC-gamma 1, but requires an SH3 domain. Here, we demonstrate that PLC-gamma 1 acts as a guanine nucleotide exchange factor (GEF) for PIKE (phosphatidylinositol-3-OH kinase (PI(3)K) enhancer). PIKE is a nuclear GTPase that activates nuclear PI(3)K activity, and mediates the physiological activation by nerve growth factor (NGF) of nuclear PI(3)K activity. This enzymatic activity accounts for the mitogenic properties of PLC-gamma 1.     

Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease

Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10(-4)). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P< 2 x 10(-7)) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence-each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.     

New bisexual form of Cavernocypris subterranea (Wolf, 1920) (Crustacea, Ostracoda) from Idaho

Males of Cavernocypris subterranea were found for the first time in an Idaho spring. The bisexual form is described on soft body parts and valves. The genus Cavernocypris now includes 2 bisexual and 1 parthenogenteic species.     

A GIS model to predict the location of fossil packrat ( Neotoma ) middens in central Nevada

Fossil packrat ( Neotoma ) middens provide an important source of paleoecologic data in the arid West. This study describes and tests a predictive GIS model that uses the eights-of-evidence method for determining areas with a high probability of containing fossil middens in central Nevada. Model variables included geology, elevation, and aspect. Geology was found to be the most important variable tested. We produced a map of 4 probability classes validated by field-checking 21 randomly selected 1-km 2 sites throughout the study area. Our high-probability category reduced the search area to only 3.5% of the total study area. Fossil middens were found on 8 of 21 sites (38%). Geologic types that contained middens were granite, limestone, and volcanic tuff. A 2nd run of the model with the new midden localities added to the training set helped narrow the total search area even further. This analysis demonstrates that the weights-of-evidence method provides an effective tool both for guiding research design and for helping locate midden sites within specific localities. With only a limited training dataset and a simple set of mapped criteria, a model can be constructed that is both predictive and testable. We intend to continue development of the model to improve our ability to predict the location of Pleistocene-age middens and to locate middens on low-probability sites. This method, designed for mineral exploration, has wide potential application within the natural sciences.