A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers

Cyclin D1 is a component of the core cell cycle machinery. Abnormally high levels of cyclin D1 are detected in many human cancer types. To elucidate the molecular functions of cyclin D1 in human cancers, we performed a proteomic screen for cyclin D1 protein partners in several types of human tumours. Analyses of cyclin D1 interactors revealed a network of DNA repair proteins, including RAD51, a recombinase that drives the homologous recombination process. We found that cyclin D1 directly binds RAD51, and that cyclin D1-RAD51 interaction is induced by radiation. Like RAD51, cyclin D1 is recruited to DNA damage sites in a BRCA2-dependent fashion. Reduction of cyclin D1 levels in human cancer cells impaired recruitment of RAD51 to damaged DNA, impeded the homologous recombination-mediated DNA repair, and increased sensitivity of cells to radiation in vitro and in vivo. This effect was seen in cancer cells lacking the retinoblastoma protein, which do not require D-cyclins for proliferation. These findings reveal an unexpected function of a core cell cycle protein in DNA repair and suggest that targeting cyclin D1 may be beneficial also in retinoblastoma-negative cancers which are currently thought to be unaffected by cyclin D1 inhibition.     

Simulation modeling of American marten ( Martes americana ) populations: vulnerability to extinction

American marten ( Martes Americana ) are medium-sized mammalian carnivores inhabiting forest communities across northern North America. Martens are susceptible to local extinction from habitat alterations, trapping, and other factors. We (RCL) developed a population model called VORTEX to estimate extinction probabilities for marten populations as a management tool. The model permits managers to simulate various levels of timber harvesting, commercial trapping, and other factors to estimate their effects on marten populations. This paper describes this model and illustrates its benefits by using marten data from the Greater Yellowstone Ecosystem of northwestern Wyoming. Results are preliminary. Populations of 50 and 100 martens were simulated. The most optimistic scenario with populations of 100 individuals, no trapping, no logging, and no migrants showed a probability (66%) of surviving 100 years. Extinction probabilities were sensitive to immigration and emigration rates. Numerous scenarios were simulated and showed a range of results. Results of population viability analysis can be translated into area requirements if densities are known or can be estimated. In turn, various habitat patches and interconnecting corridors can be examined for their ability to support viable marten populations. Population modeling is invaluable to ""adaptive management"" of martens as well as other species.     

On the structure and funtion of white-tailed prairie dog burrows

The architecture of burrows of the white-tailed prairie dog ( Cynomys leucurus ) is poorly known. For this reason and for comparative purposes, one recenlty active burrow of this species was excavated in southern Montana; the detailed methodology is described. Data were compiled on the dimensions of 29.3 m of excavated passages, and interpretations of several features are discussed. A ""turning bay,"" sleeping quarters, two hibernacula, and a maternity area are described, the last feature for the first time in print. In addition, we report Cynomys using their teeth to dig, also for the first time. Further, an inadvertent remodeling of the burrows is ascribed to normal animal traffic and appears to confirm a prediction based on late Pleistocene fossil burrows in Alberta.     

Bald eagle winter survey in the Snake River Canyon, Wyoming

A 5-year winter bald eagle survey was conducted along 22 km of the Snake River Canyon in northwestern Wyoming. Surveys were done on 94 days requiring 1,414 hrs and 1,888 km driving. In all, 220 (85 percent adults) bald eagles were seen. Seventy-seven percent of all eagles were perching, 15 percent were flying, 4 percent were feeding on road-killed mule deer, and 4 percent were flying low over water. Perching sites were identified as 32 percent cottonwoods, 30 percent spruce, 17 percent Douglas-fir, and 22 percent other. Eagles were somewhat clumped in distribution.     

Montia linearis (Portulacaceae): a new record for Utah

Montia linearis Dougl., a plant known from British Columbia to Montana, Nevada, and California, is reported from Utah.     

Short-term effects of logging on red-backed voles and deer mice

Clearcutting and selective logging effects on red-backed voles ( Clethrionomys gapperi ) and deer mice ( Peromyscus maniculatus ) were studied (September–November, 1975; June–October, 1976) in Bridger-Teton National Forest, Wyoming. Five selective cuts (total 137 ha) removed 57 percent (range 34–74 percent) of the trees. One clearcut (9.6 ha) eliminate 84 percent of the trees. Soils remained mesic in selective cuts, but became xeric in the clearcut. Snap-trapping indicated that voles were most abundant on the unlogged and selectively cut mesic sites (76 percent of 408 captures), whereas deer mice were more common on the xeric clearcut (80 percent of 60 captures). Species composition remained unchanged on selective cuts following logging (77 percent voles of 256 captures), but changed from predominantly voles to mostly deer mice (80 percent of 60 captures) in the clearcut. Intraspecific age and sex ratios, litter sizes, and morphological measurements were compared between logged and unlogged areas.     

Human granulocyte-macrophage colony-stimulating factor is a neutrophil activator

The polymorphonuclear leukocyte (PMN), or neutrophil, is the major host defence cell protecting the body against invasion by bacteria and fungi. Products of oxidative metabolism mediate PMN microbicidal and tumoricidal activity but the mechanisms by which these pathways become activated are not well understood. We have previously described a human granulocyte-macrophage colony-stimulating factor (GM-CSF) of relative molecular mass (Mr) 22,000 that also inhibits neutrophil motility (NIF-T activity). Because of its direct action on granulocytes, this lymphokine is a candidate for a neutrophil-activating factor. We have studied the effect of GM-CSF/NIF-T on superoxide anion generation in response to the bacterial chemo-attractant N-formylmethionyl-leucylphenylalanine (f-MLP), and report here that PMNs preincubated with either purified natural GM-CSF or biosynthetic (recombinant) GM-CSF showed increased (as much as fourfold) superoxide anion production in response to f-MLP. These results indicate that human GM-CSF is a neutrophil-activating factor.