A mouse knock-in model exposes sequential proteolytic pathways that regulate p27Kip1 in G1 and S phase

The protein p27Kip1 is an inhibitor of cell division. An increase in p27 causes proliferating cells to exit from the cell cycle, and a decrease in p27 is necessary for quiescent cells to resume division. Abnormally low amounts of p27 are associated with pathological states of excessive cell proliferation, especially cancers. In normal and tumour cells, p27 is regulated primarily at the level of translation and protein turnover. Phosphorylation of p27 on threonine 187 (T187) by cyclin-dependent kinase 2 (Cdk2) is thought to initiate the major pathway for p27 proteolysis. To critically test the importance of this pathway in vivo, we replaced the murine p27 gene with one that encoded alanine instead of threonine at position 187 (p27T187A). Here we show that cells expressing p27T187A were unable to downregulate p27 during the S and G2 phases of the cell cycle, but that this had a surprisingly modest effect on cell proliferation both in vitro and in vivo. Our efforts to explain this unexpected result led to the discovery of a second proteolytic pathway for controlling p27, one that is activated by mitogens and degrades p27 exclusively during G1.     

Bird use of riparian vegetation along the Truckee River, Califonia and Nevada

The Truckee River in California and Nevada is subject to diverse water regimes and a corresponding variety of flow rates. Original riparian vegetation has been altered by these variable flow rates and by a variety of human uses resulting in loss of native riparian vegetation from its historic extent. We conducted bird surveys along the Truckee River during spring 193 to (1) determine relationships between birds and the present vegetation; (2) determine the importance of different vegetation types to sensitive bird species that have declined recently in the western United States due to competition from exotic plant species, cowbird ( Molothrus ater ) parasitism, reduction in nesting habitat, or other unidentified reasons; and (3) establish a monitoring program and collect baseline data for future comparisons. The most frequently detected bird species throughout the study was the Brown-headed Cowbird. The greatest number of bird species (98 of 116) was found in the native mixed willow ( Salix spp.) riparian scrub vegetation type. We recommend protecting the remaining native riparian vegetation types for bird habitat along the Truckee River.     

Second nesting record and northward advance of the Great-tailed Grackle ( Quiscalus mexicanus ) in Nevada

The second nesting record for the Great - tailed Grackle ( Quiscalus mexicanus ) in Nevada is reported from the central part of the state approximately 240 km north of the previous record. Since 1912 this species has undergone a dramatic northward extension of its previous range in the United States, presumably as a result of increased agricultural irrigation in areas that were previously desert or short - grass prairie.         

Home range and seasonal movements of Columbian Sharp-tailed Grouse associated with Conservation Reserve Program and mine reclamation

During 1999 and 2000 we trapped and radio-marked 156 Columbian Sharp-tailed Grouse ( Tympanuchus phasianellus columbianus ) on leks in Conservation Reserve Program (CRP, n = 73) and mine reclamation (MR, n = 83) lands in northwestern Colorado. Median spring--fall home range sizes using the 95% fixed kernal and minimum convex polygon estimators for 54 grouse were 86 ha and 61 ha, respectively. Median fixed kernal home range size did not differ between males (79 ha) and females (87 ha). Home ranges of grouse associated with CRP (112 ha) were larger than those of grouse in MR (75 ha). Directional orientation of movements from leks of capture to wintering areas was nonrandom, and there was a positive elevation gain (median = 102 m) associated with these movements. Movements did not differ between grouse captured in CRP and MR for any season but did differ between genders for the spring--fall period. Males exhibited stronger fidelity and less variation in their movements than females; 96% of males compared with only 77% of females remained within 2.0 km of their lek of capture from spring through fall. Ninety percent of females nested within 2.5 km of their lek of capture. During winter all grouse were found farther (median = 21.5 km) from lek sites than in any other season. Males remained on the breeding range longer in the fall and returned earlier in the spring than females even though they wintered similar distances away (median males = 21.5 km, median females = 21.4 km). Our findings support the 2.0-km radius used in the Habitat Suitability Index model for Columbian Sharptailed Grouse to assess nest and brood-rearing cover around leks, but not the 6.5-km radius used to evaluate winter cover.     

Managing a complex exotic vegetation program in Yellowstone National Park

The number of documented exotic plants in Yellowstone National Park has increased from 85 known in 1986 to over 185 today. Exotic plants are substantially impacting the parks natural and cultural resources and are a high management priority. We have adopted an integrated weed management approach with regard to exotic vegetation, emphasizing prevention, education, early detection and eradication, control, and, to a lesser degree, monitoring. The program involves over 140 staff with program expenditures averaging approximately $190,000 annually. Prevention actions include requiring approved gravel on construction projects; banning hay in the backcountry and allowing transport of only certified weed-seed-free hay through Yellowstone; requiring construction equipment to be pressurecleaned prior to entering the park; and native species revegetation after road, housing, and other construction projects have disturbed ground. Over 4500 acres, primarily along roadsides and in developed areas, are surveyed annually in early detection efforts with emphasis placed on eradicating small, new infestations of highly invasive species such as sulfur cinquefoil ( Potentilla recta L.) and leafy spurge ( Euphorbia esula L.). Control efforts focus on about 30 priority species, such as spotted knapweed ( Centaurea maculosa Lam.), oxeye daisy ( Chrysanthemum leucanthemum L.), and hoary cress ( Cardaria draba [L.] Desv.) using chemical, mechanical, and cultural techniques. A total of 2027 acres were treated during 1998, whereas control efforts for 12 species occurred on 2596 acres during the previous 3-year period, 1995-1997. Strong and expanding partnerships with other federal, state, and local agencies and private companies contribute to management efforts within the park. Future program goals emphasize increases in base funding to ensure continued weed management efforts as well as expanding survey, monitoring, and reclamation efforts. Ultimately, a more rigorous assessment of program effectiveness is desired.     

Understanding beyond grasping propositions: A discussion of chess and fish

In this paper, we argue that, contra Strevens (2013), understanding in the sciences is sometimes partially constituted by the possession of abilities; hence, it is not (in such cases) exhausted by the understander's bearing a particular psychological or epistemic relationship to some set of structured propositions. Specifically, the case will be made that one does not really understand why a modeled phenomenon occurred unless one has the ability to actually work through (meaning run and grasp at each step) a model simulation of the underlying dynamic.     

A conditional knockout resource for the genome-wide study of mouse gene function

Gene targeting in embryonic stem cells has become the principal technology for manipulation of the mouse genome, offering unrivalled accuracy in allele design and access to conditional mutagenesis. To bring these advantages to the wider research community, large-scale mouse knockout programmes are producing a permanent resource of targeted mutations in all protein-coding genes. Here we report the establishment of a high-throughput gene-targeting pipeline for the generation of reporter-tagged, conditional alleles. Computational allele design, 96-well modular vector construction and high-efficiency gene-targeting strategies have been combined to mutate genes on an unprecedented scale. So far, more than 12,000 vectors and 9,000 conditional targeted alleles have been produced in highly germline-competent C57BL/6N embryonic stem cells. High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome.