Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional growth factor that has profound regulatory effects on many developmental and physiological processes. Disruption of the TGF-beta 1 gene by homologous recombination in murine embryonic stem cells enables mice to be generated that carry the disrupted allele. Animals homozygous for the mutated TGF-beta 1 allele show no gross developmental abnormalities, but about 20 days after birth they succumb to a wasting syndrome accompanied by a multifocal, mixed inflammatory cell response and tissue necrosis, leading to organ failure and death. TGF-beta 1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.     

Chromosomal effects of adeno-associated virus vector integration.

Adeno-associated virus (AAV) vectors are currently being used in several clinical gene-therapy trials (see the NIH OBA Human Gene Transfer Clinical Trials Database); however, little is known about the chromosomal effects of vector integration. Here we report that integrated vector proviruses are associated with chromosomal deletions and other rearrangements and are frequently located on chromosome 19 (although not at the wildtype AAV integration site).     

Ni2MnGa铁磁形状记忆材料

铁磁形状记忆合金 (FSMA)是在一定温度范围马氏体相稳定同时又具铁磁性的一类特殊的形状记忆合金。Ni2MnGa铁磁形状记忆合金近年来成为呈现磁场驱动大应变的新型驱动材料 ,这些应变来自磁场诱发马氏体孪晶的重排 ,而不是磁场对奥氏体至马氏体相变的作用。孪晶变体的重排在宏观上呈现为正或切应变 ,一非化学计量比Ni2 MnGa单晶于室温加 0 .4T磁场能产生6 %的应变 ,Ni Mn Ga单晶在高至 15 0Hz的交变磁场仍可得到 2 .5 %的应变。本文阐述了与这种磁控形状记忆效应相关的孪晶界迁动的磁学和晶体学理论。马氏体相的大磁晶各向异性能使磁化沿c轴方向有利 ,穿过孪晶界c轴刚好转动 90度 ,同时 ,这个孪晶界也构成了约 90度的畴界。在各向异性的情况下 ,孪晶界的迁动仅有相邻孪晶变体的Zeeman能差驱动 ,μ0 ΔMis·Hi。磁场和外应力对应变的影响通过对一简单的自由能表达式取极小值来表示 ,自由能表达式包括Zeeman能、磁晶各向异性能和外应力以及在某些情况下需考虑的内部弹性能 ,模型的所有参数可通过应力 应变曲线和磁化曲线测量得到。铁磁形状记忆合金的磁场诱发应变可类比传统热弹性形状记忆效应 ,与更为人们所熟知的磁致伸缩现象不同。     

Extraction of a weak climatic signal by an ecosystem

The complexity of ecosystems can cause subtle and chaotic responses to changes in external forcing. Although ecosystems may not normally behave chaotically, sensitivity to external influences associated with nonlinearity can lead to amplification of climatic signals. Strong correlations between an El Ni?o index and rainfall and maize yield in Zimbabwe have been demonstrated; the correlation with maize yield was stronger than that with rainfall. A second example is the 100,000-year ice-age cycle, which may arise from a weak cycle in radiation through its influence on the concentration of atmospheric CO2 (ref. 5). Such integration of a weak climatic signal has yet to be demonstrated in a realistic theoretical system. Here we use a particular climatic phenomenon-the observed association between plankton populations around the UK and the position of the Gulf Stream-as a probe to demonstrate how a detailed marine ecosystem model extracts a weak signal that is spread across different meteorological variables. Biological systems may therefore respond to climatic signals other than those that dominate the driving variables.     

Climate-driven trends in contemporary ocean productivity

Contributing roughly half of the biosphere's net primary production (NPP), photosynthesis by oceanic phytoplankton is a vital link in the cycling of carbon between living and inorganic stocks. Each day, more than a hundred million tons of carbon in the form of CO2 are fixed into organic material by these ubiquitous, microscopic plants of the upper ocean, and each day a similar amount of organic carbon is transferred into marine ecosystems by sinking and grazing. The distribution of phytoplankton biomass and NPP is defined by the availability of light and nutrients (nitrogen, phosphate, iron). These growth-limiting factors are in turn regulated by physical processes of ocean circulation, mixed-layer dynamics, upwelling, atmospheric dust deposition, and the solar cycle. Satellite measurements of ocean colour provide a means of quantifying ocean productivity on a global scale and linking its variability to environmental factors. Here we describe global ocean NPP changes detected from space over the past decade. The period is dominated by an initial increase in NPP of 1,930 teragrams of carbon a year (Tg C yr(-1)), followed by a prolonged decrease averaging 190 Tg C yr(-1). These trends are driven by changes occurring in the expansive stratified low-latitude oceans and are tightly coupled to coincident climate variability. This link between the physical environment and ocean biology functions through changes in upper-ocean temperature and stratification, which influence the availability of nutrients for phytoplankton growth. The observed reductions in ocean productivity during the recent post-1999 warming period provide insight on how future climate change can alter marine food webs.     

Genome sequencing in microfabricated high-density picolitre reactors

The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.     

High levels of gene flow in the California vole ( Microtus californicus ) are consistent across spatial scales

Gene flow links the genetic and demographic structures of species. Despite the fact that similar genetic and demographic patterns shape both local population structure and regional phylogeography, the 2 levels of population connectivity are rarely studied simultaneously. Here, we studied gene flow in the California vole ( Microtus californicus ), a small-bodied rodent with limited vagility but high local abundance. Within a 4.86-km 2 preserve in central California, genetic diversity in 6 microsatellites was high, and Bayesian methods indicated a single genetic cluster. However, individual-based genetic analysis detected a clear signal for isolation-by-distance (IBD) and fine-scale population structure. Mitochondrial cytochrome b sequencing revealed 11 unique haplotypes from the one local area where we sequenced 62 individuals. Phylogeographic analysis of these individuals combined with those sampled from the northern geographic range of the species (the range of the species spans western North America from southern Oregon to northern Mexico and is centered geographically within the state of California) again indicated a lack of structure but a signal for IBD. Patterns of gene flow thus are consistent across spatial scales: while dispersal of the California vole is limited across geographic distance, there is nonetheless considerable movement across the landscape. We conclude that in this species, high local population abundances overcome the potential genetic and demographic effects of limited dispersal.     

Foliage age as a factor in food utilization by the western spruce budworm, Choristoneura occidentalis

The influence of current year foliage age on food consumption and utilization by the western spruce budworm, Choristoneura occidentalis (Lepidoptera:Tortricidae), was examined. Larvae were fed immature foliage of Douglas-fir ( Pseudotsuga menziesii var. glauca ), Engelmann spruce ( Picea engelmannii ), and corkbark fir ( Abies lasiocarpa var. arizonica ) in June and August of 1981 and Douglas fir in June and July of 1982. All larvae feeding on early season (June) foliage reached maturity. Larvae feeding on middle (July) and late (August) season foliage died before reaching pupation. Relative growth rate and efficiency of conversion of ingested food decreased with foliage age in both the 1981 and 1982 experiments. Relative consumption rate increased with foliage age in the 1981 and decreased in the 1982 experiment.