Mice heterozygous for mutation in Atm,the gene involved in ataxia-telangiectasia,have heightened susceptibility to cancer

Ataxia-telangiectasia is characterized by radiosensitivity, genome instability and predisposition to cancer. Heterozygous carriers of ATM, the gene defective in ataxia-telangiectasia, have a higher than normal risk of developing breast and other cancers. We demonstrate here that Atm 'knock-in' (Atm-Delta SRI) heterozygous mice harboring an in-frame deletion corresponding to the human 7636del9 mutation show an increased susceptibility to developing tumors. In contrast, no tumors are observed in Atm knockout (Atm(+/-)) heterozygous mice. In parallel, we report the appearance of tumors in 6 humans from 12 families who are heterozygous for the 7636del9 mutation. Expression of ATM cDNA containing the 7636del9 mutation had a dominant-negative effect in control cells, inhibiting radiation-induced ATM kinase activity in vivo and in vitro. This reduces the survival of these cells after radiation exposure and enhances the level of radiation-induced chromosomal aberrations. These results show for the first time that mouse carriers of a mutated Atm that are capable of expressing Atm have a higher risk of cancer. This finding provides further support for cancer predisposition in human ataxia-telangiectasia carriers.     

Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth

The inhibitory activity associated with myelin is a major obstacle for successful axon regeneration in the adult mammalian central nervous system (CNS). In addition to myelin-associated glycoprotein (MAG) and Nogo-A, available evidence suggests the existence of additional inhibitors in CNS myelin. We show here that a glycosylphosphatidylinositol (GPI)-anchored CNS myelin protein, oligodendrocyte-myelin glycoprotein (OMgp), is a potent inhibitor of neurite outgrowth in cultured neurons. Like Nogo-A, OMgp contributes significantly to the inhibitory activity associated with CNS myelin. To further elucidate the mechanisms that mediate this inhibitory activity of OMgp, we screened an expression library and identified the Nogo receptor (NgR) as a high-affinity OMgp-binding protein. Cleavage of NgR and other GPI-linked proteins from the cell surface renders axons of dorsal root ganglia insensitive to OMgp. Introduction of exogenous NgR confers OMgp responsiveness to otherwise insensitive neurons. Thus, OMgp is an important inhibitor of neurite outgrowth that acts through NgR and its associated receptor complex. Interfering with the OMgp/NgR pathway may allow lesioned axons to regenerate after injury in vivo.     

S-nitrosothiols signal the ventilatory response to hypoxia

Increased ventilation in response to hypoxia has been appreciated for over a century, but the biochemistry underlying this response remains poorly understood. Here we define a pathway in which increased minute ventilation (&Vdot;E ) is signalled by deoxyhaemoglobin-derived S-nitrosothiols (SNOs). Specifically, we demonstrate that S-nitrosocysteinyl glycine (CGSNO) and S-nitroso-l-cysteine (l-CSNO)-but not S-nitroso-d-cysteine (d-CSNO)-reproduce the ventilatory effects of hypoxia at the level of the nucleus tractus solitarius (NTS). We show that plasma from deoxygenated, but not from oxygenated, blood produces the ventilatory effect of both SNOs and hypoxia. Further, this activity is mediated by S-nitrosoglutathione (GSNO), and GSNO activation by gamma-glutamyl transpeptidase (gamma-GT) is required. The normal response to hypoxia is impaired in a knockout mouse lacking gamma-GT. These observations suggest that S-nitrosothiol biochemistry is of central importance to the regulation of breathing.     

Occurrence, persistence, and expansion of saltcedar ( Tamarix spp.) populations in the Great Plains of Montana

Saltcedar ( Tamarix spp.), a shrub native to Eurasia, is associated with major alterations to wetland and riparian systems in the southwestern United States. Since the 1960s saltcedar has been naturalized in northern states of the U.S. where its growth potential and impacts are not well known. Here, we describe the occurrence, age, size, and relative cover of saltcedar populations in several river basins in central eastern Montana, USA, to identify potential patterns of spread across the region and changes in individual populations as they age. Stands were aged according to the oldest saltcedar individuals and were sampled for dominant plant cover and soil properties. Multiple introductions appear to have occurred in Montana, with the oldest stands occurring on the Bighorn River in southern Montana. Saltcedar absolute and relative cover and stand area increased significantly with stand age, while native tree and shrub relative cover remained low across all stand ages. These results suggest that saltcedar stands establish where woody natives are not abundant and that they persist and expand over time. Although soil salinity remained constant, soil pH decreased with saltcedar stand age, indicating a possible effect of organic matter inputs. An analysis of annual wood increment of saltcedar and sandbar willow (a native with analogous growth form) stems along a latitudinal gradient showed that stem growth of both species did not differ significantly among regions. Stem growth decreased inversely with elevation for both species while growth responses to elevation did not differ between species. Our results show an increase in number of populations and continued viability of these populations. Mechanisms of saltcedar increases in this region are yet to be determined. Anthropogenic influences, such as saltcedar plantings, watershed alterations (e.g., river flow control), and habitat disturbances (e.g., cattle grazing or habitat clearing) may facilitate its spread in similar climates of the Great Plains.     

Distribution, abundance, and genetic population structure of Wood River sculpin, Cottus leiopomus

The Wood River sculpin Cottus leiopomus is endemic to the Wood River Basin in central Idaho and is a nongame species of concern because of its limited distribution. However, status and genetic population structure, 2 factors often central to the conservation and management of species of concern, have not been assessed for this species. We used backpack electrofishers to survey streams that were small enough (i.e., a priori to contain, possibly contain, or not contain the sculpin, respectively. Native redband trout Oncorhynchus mykiss gairdneri were present at 21 study sites, including 18 of the 20 sites that contained Wood River sculpin. Sixty-one study sites (60%) were dry or had too little water to contain any fish. We estimated that a minimum of 1.36 million Wood River sculpin (≥20 mm total length) currently reside in the basin. The presence of Wood River sculpin was positively associated with stream width:depth ratio and percent cobble/boulder substrate and negatively associated with stream gradient. Mitochondrial DNA haplotype differences were observed between and within the 3 major river subbasins supporting sculpin, with the most striking differences observed between populations in the Camas Creek subbasin and the other 2 subbasins, among which no haplotypes were shared, suggesting relatively long-term isolation. Our results suggest that the Wood River sculpin remains relatively widespread and abundant within its endemic range, despite obvious changes in historical stream connectivity caused by irrigation diversions and other chronic habitat alterations.     

Insights into Operationalizing Communities of Practice from SSM-Based Inquiry Processes

Two systemic inquiries, based on soft systems methodology (SSM), into the potential for using community of practice (CoP) theory by an Australian-government created research and development corporation to change its knowledge management (KM) strategy, are reported. Key staff were engaged in the inquiry into how to build a third-order KM strategy based on CoPs; an exploration of key published work on CoPs yielded four SSM activity models—‘being a community practice system’; ‘doing the work of imagination sub-system’; ‘doing the work of alignment sub-system’ and ‘doing the work of engagement sub-system’. These models can be used as heuristics to aid the purposeful design of CoPs in other settings. SSM, enacted as a systemic inquiry, can be understood as a form of systemic action research, which was well equipped to deal with CoP theory and, when enacted participatively, can generate important systemic insights. The inquiry began the process of fostering an appreciation of third order KM but, on the evidence available, did not lead to on-going commitment to a CoPs-based KM strategy. Future research should acknowledge how the framing of research situations influences the research process, the importance of the design of practice change settings and the limited evidence for purposeful interventions leading to successful CoPs.     

中国物理学家正酝酿设计全球最先进的环形对撞机（英文）

The leaders of China’s high energy physics sector will soon unveil initial designs for the world’s most technologically advanced circular collider,set to stage near-speed-of-light particle collisions aimed at recreating the conditions of the universe in the instant following the Big Bang.By accelerating beams of leptons or hadrons to nearly300,000 km/s before colliding them inside the ringed