RecA acts in trans to allow replication of damaged DNA by DNA polymerase V

The DNA polymerase V (pol V) and RecA proteins are essential components of a mutagenic translesion synthesis pathway in Escherichia coli designed to cope with DNA damage. Previously, it has been assumed that RecA binds to the DNA template strand being copied. Here we show, however, that pol-V-catalysed translesion synthesis, in the presence or absence of the beta-processivity-clamp, occurs only when RecA nucleoprotein filaments assemble or RecA protomers bind on separate single-stranded (ss)DNA molecules in trans. A 3'-proximal RecA filament end on trans DNA is essential for stimulation; however, synthesis is strengthened by further pol V-RecA interactions occurring elsewhere along a trans nucleoprotein filament. We suggest that trans-stimulation of pol V by RecA bound to ssDNA reflects a distinctive regulatory mechanism of mutation that resolves the paradox of RecA filaments assembled in cis on a damaged template strand obstructing translesion DNA synthesis despite the absolute requirement of RecA for SOS mutagenesis.     

Detection of a direct carbon dioxide effect in continental river runoff records

Continental runoff has increased through the twentieth century despite more intensive human water consumption. Possible reasons for the increase include: climate change and variability, deforestation, solar dimming, and direct atmospheric carbon dioxide (CO2) effects on plant transpiration. All of these mechanisms have the potential to affect precipitation and/or evaporation and thereby modify runoff. Here we use a mechanistic land-surface model and optimal fingerprinting statistical techniques to attribute observational runoff changes into contributions due to these factors. The model successfully captures the climate-driven inter-annual runoff variability, but twentieth-century climate alone is insufficient to explain the runoff trends. Instead we find that the trends are consistent with a suppression of plant transpiration due to CO2-induced stomatal closure. This result will affect projections of freshwater availability, and also represents the detection of a direct CO2 effect on the functioning of the terrestrial biosphere.     

Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus

Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.     

Accurate whole human genome sequencing using reversible terminator chemistry

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.     

From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing

Understanding the basic biology of human ageing is a key milestone in attempting to ameliorate the deleterious consequences of old age. This is an urgent research priority given the global demographic shift towards an ageing population. Although some molecular pathways that have been proposed to contribute to ageing have been discovered using classical biochemistry and genetics, the complex, polygenic and stochastic nature of ageing is such that the process as a whole is not immediately amenable to biochemical analysis. Thus, attempts have been made to elucidate the causes of monogenic progeroid disorders that recapitulate some, if not all, features of normal ageing in the hope that this may contribute to our understanding of normal human ageing. Two canonical progeroid disorders are Werner's syndrome and Hutchinson-Gilford progeroid syndrome (also known as progeria). Because such disorders are essentially phenocopies of ageing, rather than ageing itself, advances made in understanding their pathogenesis must always be contextualised within theories proposed to help explain how the normal process operates. One such possible ageing mechanism is described by the cell senescence hypothesis of ageing. Here, we discuss this hypothesis and demonstrate that it provides a plausible explanation for many of the ageing phenotypes seen in Werner's syndrome and Hutchinson-Gilford progeriod syndrome. The recent exciting advances made in potential therapies for these two syndromes are also reviewed.     

模拟光链路 理论和实践

本书介绍模拟光链路的设计基础。首先介绍用在直接和外调制两者中公用的电一光元件小信号模型的发展，并用分析工具，逐一详细分析光链路的四个重要参数：增益、带宽、噪声系数和动态范围，最后探索四个重要链路参数间的一些折衷办法。     

Substrate color matching in the grasshopper, Circotettix rabula (Orthoptera: Acrididae)

Mechanisms important in maintaining substrate color matching in the grasshopper, Circotettix rabula, were studied near Aspen, Colorado, during the summers of 1968 – 70. Studies concentrated on populations on gray shale and red sandstone substrates. In both areas, collections revealed appreciable numbers of mismatched phenotypes among all age groups. The possibility of developmental homochromy was examined by observation of nymphs held in rearing boxes on matching and contrasting soil colors. The behavioral selection of matching substrate colors was tested by preference experiments. While not negating the possibility of these mechanisms, results suggested that they were of minor importance. Predation experiments, using Sceloporus lizards, demonstrated significant levels of selective predation on mismatched nymphs on both red and gray substrates. Experiments with bird and mammal predators, using adult grasshoppers, gave similar results. Release - recapture experiments with marked adults in areas of red and gray substrates showed markedly higher disappearance rates for mismatched animals. These results are interpreted to indicate that selective predation on mismatched animals is a major factor in maintaining substrate color matching in this species.     

Terrestrial vertabrates of Scotts Bluff National Monument, Nebraska

A survey of terrestrial vertebrates was conducted at the Scotts Bluff National Monument (SBNM), Nebraska, to determine species composition, relative abundance, and distribution by habitat of the existing amphibians, reptiles, birds, and mammals. Various sampling methods were used to detect animal species richness and to estimate population densities. The seven major habitat types at SBNM contained 4 species of amphibians, 8 reptiles, 96 birds, and 28 mammals. The only endangered or threatened species observed was a dead bald eagle ( Haliaeetus leucocephalus ). The racer ( Coluber constrictor ) and prairie rattlesnake ( Crotalus viridis ) were the two most abundant snakes. The prairie falcon ( Falco mexicanus ) was a common raptor that nested in Scotts Bluff. Sympatric populations of mule deer ( Odocoileus hemionus ) and white-tailed deer ( Odocoileus virginianus ) appeared to be hybridizing. The riverine woodland contained the greatest number of fauna species with only 4% surface area of SBNM. Sharp-tailed grouse ( Tympanuchus phasianellus ) and pronghorn antelope ( Antilocapra americana ), absent from the Monument, are two potential native species for reintroduction.