Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease

Genes and mechanisms involved in common complex diseases, such as the autoimmune disorders that affect approximately 5% of the population, remain obscure. Here we identify polymorphisms of the cytotoxic T lymphocyte antigen 4 gene (CTLA4)--which encodes a vital negative regulatory molecule of the immune system--as candidates for primary determinants of risk of the common autoimmune disorders Graves' disease, autoimmune hypothyroidism and type 1 diabetes. In humans, disease susceptibility was mapped to a non-coding 6.1 kb 3' region of CTLA4, the common allelic variation of which was correlated with lower messenger RNA levels of the soluble alternative splice form of CTLA4. In the mouse model of type 1 diabetes, susceptibility was also associated with variation in CTLA-4 gene splicing with reduced production of a splice form encoding a molecule lacking the CD80/CD86 ligand-binding domain. Genetic mapping of variants conferring a small disease risk can identify pathways in complex disorders, as exemplified by our discovery of inherited, quantitative alterations of CTLA4 contributing to autoimmune tissue destruction.     

Extra-embryonic function of Rb is essential for embryonic development and viability

The retinoblastoma (Rb) gene was the first tumour suppressor identified. Inactivation of Rb in mice results in unscheduled cell proliferation, apoptosis and widespread developmental defects, leading to embryonic death by day 14.5 (refs 2-4). However, the actual cause of the embryonic lethality has not been fully investigated. Here we show that loss of Rb leads to excessive proliferation of trophoblast cells and a severe disruption of the normal labyrinth architecture in the placenta. This is accompanied by a decrease in vascularization and a reduction in placental transport function. We used two complementary techniques-tetraploid aggregation and conditional knockout strategies-to demonstrate that Rb-deficient embryos supplied with a wild-type placenta can be carried to term, but die soon after birth. Most of the neurological and erythroid abnormalities thought to be responsible for the embryonic lethality of Rb-null animals were virtually absent in rescued Rb-null pups. These findings identify and define a key function of Rb in extra-embryonic cell lineages that is required for embryonic development and viability, and provide a mechanism for the cell autonomous versus non-cell autonomous roles of Rb in development.     

Outgassing from Amazonian rivers and wetlands as a large tropical source of atmospheric CO2

Terrestrial ecosystems in the humid tropics play a potentially important but presently ambiguous role in the global carbon cycle. Whereas global estimates of atmospheric CO2 exchange indicate that the tropics are near equilibrium or are a source with respect to carbon, ground-based estimates indicate that the amount of carbon that is being absorbed by mature rainforests is similar to or greater than that being released by tropical deforestation (about 1.6 Gt C yr-1). Estimates of the magnitude of carbon sequestration are uncertain, however, depending on whether they are derived from measurements of gas fluxes above forests or of biomass accumulation in vegetation and soils. It is also possible that methodological errors may overestimate rates of carbon uptake or that other loss processes have yet to be identified. Here we demonstrate that outgassing (evasion) of CO2 from rivers and wetlands of the central Amazon basin constitutes an important carbon loss process, equal to 1.2 +/- 0.3 Mg C ha-1 yr-1. This carbon probably originates from organic matter transported from upland and flooded forests, which is then respired and outgassed downstream. Extrapolated across the entire basin, this flux-at 0.5 Gt C yr-1-is an order of magnitude greater than fluvial export of organic carbon to the ocean. From these findings, we suggest that the overall carbon budget of rainforests, summed across terrestrial and aquatic environments, appears closer to being in balance than would be inferred from studies of uplands alone.     

Stream denitrification across biomes and its response to anthropogenic nitrate loading

Anthropogenic addition of bioavailable nitrogen to the biosphere is increasing and terrestrial ecosystems are becoming increasingly nitrogen-saturated, causing more bioavailable nitrogen to enter groundwater and surface waters. Large-scale nitrogen budgets show that an average of about 20-25 per cent of the nitrogen added to the biosphere is exported from rivers to the ocean or inland basins, indicating that substantial sinks for nitrogen must exist in the landscape. Streams and rivers may themselves be important sinks for bioavailable nitrogen owing to their hydrological connections with terrestrial systems, high rates of biological activity, and streambed sediment environments that favour microbial denitrification. Here we present data from nitrogen stable isotope tracer experiments across 72 streams and 8 regions representing several biomes. We show that total biotic uptake and denitrification of nitrate increase with stream nitrate concentration, but that the efficiency of biotic uptake and denitrification declines as concentration increases, reducing the proportion of in-stream nitrate that is removed from transport. Our data suggest that the total uptake of nitrate is related to ecosystem photosynthesis and that denitrification is related to ecosystem respiration. In addition, we use a stream network model to demonstrate that excess nitrate in streams elicits a disproportionate increase in the fraction of nitrate that is exported to receiving waters and reduces the relative role of small versus large streams as nitrate sinks.     

中国甘肃一例前足迹主导的翼龙足迹组合:对行为学的影响（英文）

翼龙是已知的、最早飞上天际的脊椎动物,目前已经发现了成千上万件化石,代表着这一大家族从晚三叠世到晚白垩世在全球范围内的蓬勃发展史.自2004年甘肃盐锅峡地区首次报道翼龙足迹以来,中国陆续发现了一批翼龙足迹化石,绝大多数的足迹点都保存了翼龙的前后足迹.2013年,我们在盐锅峡地区发现了至少20个翼龙前足迹的凸型足迹,而没有发现任何后足迹,这些足迹可归于一个单独翼龙遗迹属——Pteraichnus.这是中国第一次发现由前足迹主导的翼龙足迹组合,这可能反映了翼龙前后足迹在同等保存条件下的不同深度.更重要的是,盐锅峡的这批翼龙足迹与当地发现的大量虫迹相关,一些足迹甚至就保存在虫迹面上,这些虫迹包括Cochlichnus,Spongeliomorpha和Paleophycus,因此推断这批翼龙造迹者很可能以这些无脊椎动物造迹者为食.