ATM stabilizes DNA double-strand-break complexes during V(D)J recombination

The ATM (ataxia-telangiectasia mutated) protein kinase mediates early cellular responses to DNA double-strand breaks (DSBs) generated during metabolic processes or by DNA-damaging agents. ATM deficiency leads to ataxia-telangiectasia, a disease marked by lymphopenia, genomic instability and an increased predisposition to lymphoid malignancies with chromosomal translocations involving lymphocyte antigen receptor loci. ATM activates cell-cycle checkpoints and can induce apoptosis in response to DNA DSBs. However, defects in these pathways of the DNA damage response cannot fully account for the phenotypes of ATM deficiency. Here, we show that ATM also functions directly in the repair of chromosomal DNA DSBs by maintaining DNA ends in repair complexes generated during lymphocyte antigen receptor gene assembly. When coupled with the cell-cycle checkpoint and pro-apoptotic activities of ATM, these findings provide a molecular explanation for the increase in lymphoid tumours with translocations involving antigen receptor loci associated with ataxia-telangiectasia.     

Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis

Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens.     

Catastrophic extinctions follow deforestation in Singapore

The looming mass extinction of biodiversity in the humid tropics is a major concern for the future, yet most reports of extinctions in these regions are anecdotal or conjectural, with a scarcity of robust, broad-based empirical data. Here we report on local extinctions among a wide range of terrestrial and freshwater taxa from Singapore (540 km2) in relation to habitat loss exceeding 95% over 183 years. Substantial rates of documented and inferred extinctions were found, especially for forest specialists, with the greatest proportion of extinct taxa (34-87%) in butterflies, fish, birds and mammals. Observed extinctions were generally fewer, but inferred losses often higher, in vascular plants, phasmids, decapods, amphibians and reptiles (5-80%). Forest reserves comprising only 0.25% of Singapore's area now harbour over 50% of the residual native biodiversity. Extrapolations of the observed and inferred local extinction data, using a calibrated species-area model, imply that the current unprecedented rate of habitat destruction in Southeast Asia will result in the loss of 13-42% of regional populations over the next century, at least half of which will represent global species extinctions.     

炭基微生物菌剂促进牛粪好氧堆肥腐熟过程研究

为评估炭基微生物菌剂促进牛粪好氧堆肥的腐熟效果,以牛粪为原料加入自制炭基微生物菌剂进行为期34 d的堆肥试验,并以纯牛粪为空白对照,研究堆肥过程中理化指标和微生物群落的变化。结果表明,添加炭基微生物菌剂后,1 d内可使堆温达到53 ℃,堆体最高温度为71.7 ℃,较对照组最高温度高出4.6 ℃,且高温期延长3 d。至堆肥结束时,处理组和对照组的含水率、E₄/E₆,GI分别为29%和33%,1.5和1.9,145.5%和127.6%。通过相关性分析得出,累计温度、含水率、pH值等理化指标相关性数值增大为67%,与细菌门水平间相关性数值增加了56%。添加0.1%(w/w)的炭基微生物菌剂可加快腐熟过程,提高微生物多样性,加快微生物群落的演替和对物料的分解代谢,促进腐熟进程,为炭基微生物菌剂在好氧堆肥中的应用提供了理论依据。     

热输入对深海X70粗晶区组织和韧性的影响

为解决深海X70管线钢在实际焊接中粗晶区(CGHAZ)的脆化问题,在不同热循环工艺下对X70管线钢进行了热模拟研究。采用Gleeble-3800热模拟机模拟X70管线钢CGHAZ,研究CGHAZ在10～60 kJ/cm不同热输入(HI)条件下组织和韧性的变化规律,并通过光学显微镜(OM)、扫描电镜(SEM)和夏比冲击试验等手段表征CGHAZ的组织和韧性。结果表明,不同热输入下试验钢的组织主要由粒状贝氏体(GB)、贝氏体铁素体(BF)和马-奥组元(M-A组元)组成;当HI不断增大时,BF比例减少,GB比例增加,M-A组元粗化,冲击吸收能先升高再降低;当HI为20 kJ/cm时,BF和GB可获得优异组合,断口为韧性断裂,冲击吸收能达到173.8 J;当HI大于20 kJ/cm时,断口解离断裂,冲击吸收能下降明显,最低为18.8 J。因此,较低的热输入可提高CGHAZ的韧性,使X70管线钢具有高强度、高韧性和良好的焊接性。研究结果可为优化焊接工艺提供理论依据。     

A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis

Mycobacterium tuberculosis, which causes tuberculosis, is the greatest single infectious cause of mortality worldwide, killing roughly two million people annually. Estimates indicate that one-third of the world population is infected with latent M. tuberculosis. The synergy between tuberculosis and the AIDS epidemic, and the surge of multidrug-resistant clinical isolates of M. tuberculosis have reaffirmed tuberculosis as a primary public health threat. However, new antitubercular drugs with new mechanisms of action have not been developed in over thirty years. Here we report a series of compounds containing a nitroimidazopyran nucleus that possess antitubercular activity. After activation by a mechanism dependent on M. tuberculosis F420 cofactor, nitroimidazopyrans inhibited the synthesis of protein and cell wall lipid. In contrast to current antitubercular drugs, nitroimidazopyrans exhibited bactericidal activity against both replicating and static M. tuberculosis. Lead compound PA-824 showed potent bactericidal activity against multidrugresistant M. tuberculosis and promising oral activity in animal infection models. We conclude that nitroimidazopyrans offer the practical qualities of a small molecule with the potential for the treatment of tuberculosis.     

Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes

The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan on seven diseases, including the multifactorial autoimmune disease type 1 diabetes (T1D), shows associations at P < 5 x 10(-7) between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attempted to validate these and six other top findings in 4,000 individuals with T1D, 5,000 controls and 2,997 family trios independent of the WTCCC study. We confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11 (P(follow-up) 相似文献   

Vegetation response to prescribed fire in Dinosaur National Monument

Much of western North America is dominated by dense, monotypic, late seral stands of big sagebrush ( Artemisia tridentata Nutt.). These stands often have depauperate understories with limited species richness, diversity, and herbaceous cover. The National Park Service at Dinosaur National Monument, Colorado, is using both strategic and natural prescribed fire in Wyoming big sagebrush ( Artemisia tridentata ssp. wyomingensis Beetle and Young) communities to foster intra-community (α -scale) and landscape diversity. This study analyzed an accumulated foliar cover data set between paired burn and control areas on 6 different sites during the last 20 years. Across the monitoring period, mean total vegetation cover of all combined sites was 44% control and 42% burn. Total vegetation cover in burn areas was higher than or equal to paired control areas within 2-3 years post-burn. Shrubs were essentially eliminated in burn areas, but perennial grass cover was 10-35% higher. Mean number of species on all sites and years combined was 17 control and 18 burn. Species richness was different on only 1 site-year, Dry Woman 1995 ( P = 0.001, 15 control, 9 burn). Species similarity by site and between treatments ranged from 44% to 75%. Differences in Shannon-Weiner diversity index values between paired sites occurred in 6 of 20 years ( P < 0.05). Index value differences on these 6 sites were due to a large annual grass component in burn areas. Prescribed burning successfully shifted late successional sagebrushdominated communities to earlier herbaceous-dominated successional stages without lowering total vegetation cover, while maintaining -scale diversity and species richness.     

Variation in the bark call of the red squirrel ( Tamiasciurus hudsonicus )

Calls of the red squirrel ( Tamiasciurus hudsonicus; n = 122) were recorded in wild populations from 15 localities in Arizona, New Mexico, Colorado, Utah, Wyoming, Montana, Idaho, and Washington. Computer-generated audiospectrograms of 20- or 30-second samples from a calling bout of each individual were analyzed. Eighteen bark types (distinct forms of the bark call) were identified plus a 19th category that included rarely used, longer bark calls. The frequency of use of each bark type within the sample was recorded for each squirrel. Differences in frequency of use of the various bark types were found among subspecies, within subspecies, and within populations; additionally, the southern subspecies utilized a reduced number of bark types. The large number of different bark types and the variation in bark type usage within populations suggest the potential for communication of such information as individual identification, behavioral states, or gender identification.     

Flower mites of Trinidad II. The genus Proctolaelaps (Acari: Ascidae)

Nine species of mites of the genus Proctolaelaps were collected in flowers or phoretic in the nares of hummingbirds in Trinidad. Previously named species P. kirmsei , P. glaucis , and P. belemensis are redescribed, and six new species are described: P. jurgatus , P. mermillion , P. rabulatus , P. contumex , P. certator , and P. contentiosus . Proctolaelaps belemensis cyanocompsae is raised to specific status. Host plants are given for all species except P. mermillion , which was collected only from a hummingbird host. New World flower-inhabiting Proctolaelaps are grouped into two hypothetically monophyletic lineages, the kirmsei -group and the belemensis -group, on the basis of adult morphology. A key to the nine Trinidadian species is given.