Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10??). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.     

Room-temperature ferroelectricity in supramolecular networks of charge-transfer complexes

Materials exhibiting a spontaneous electrical polarization that can be switched easily between antiparallel orientations are of potential value for sensors, photonics and energy-efficient memories. In this context, organic ferroelectrics are of particular interest because they promise to be lightweight, inexpensive and easily processed into devices. A recently identified family of organic ferroelectric structures is based on intermolecular charge transfer, where donor and acceptor molecules co-crystallize in an alternating fashion known as a mixed stack: in the crystalline lattice, a collective transfer of electrons from donor to acceptor molecules results in the formation of dipoles that can be realigned by an external field as molecules switch partners in the mixed stack. Although mixed stacks have been investigated extensively, only three systems are known to show ferroelectric switching, all below 71 kelvin. Here we describe supramolecular charge-transfer networks that undergo ferroelectric polarization switching with a ferroelectric Curie temperature above room temperature. These polar and switchable systems utilize a structural synergy between a hydrogen-bonded network and charge-transfer complexation of donor and acceptor molecules in a mixed stack. This supramolecular motif could help guide the development of other functional organic systems that can switch polarization under the influence of electric fields at ambient temperatures.     

A novel highly unsaturated fatty acid moiety of lipo-oligosaccharide signals determines host specificity of Rhizobium

In Rhizobium leguminosarum biovar viciae, the nodABC and nodFEL operons are involved in the production of lipo-oligosaccharide signals which mediate host specificity. The structure of these metabolites and those produced in nod mutants links the nodE and nodL genes to specific chemical features of the signal molecules. A nodE-determined, highly unsaturated fatty acid and a nodL-determined O-acetyl substituent are essential for the ability of the signals to induce nodule meristems on the host plant Vicia sativa.     

Structural basis for iron piracy by pathogenic Neisseria

Neisseria are obligate human pathogens causing bacterial meningitis, septicaemia and gonorrhoea. Neisseria require iron for survival and can extract it directly from human transferrin for transport across the outer membrane. The transport system consists of TbpA, an integral outer membrane protein, and TbpB, a co-receptor attached to the cell surface; both proteins are potentially important vaccine and therapeutic targets. Two key questions driving Neisseria research are how human transferrin is specifically targeted, and how the bacteria liberate iron from transferrin at neutral pH. To address these questions, we solved crystal structures of the TbpA-transferrin complex and of the corresponding co-receptor TbpB. We characterized the TbpB-transferrin complex by small-angle X-ray scattering and the TbpA-TbpB-transferrin complex by electron microscopy. Our studies provide a rational basis for the specificity of TbpA for human transferrin, show how TbpA promotes iron release from transferrin, and elucidate how TbpB facilitates this process.     

Diatom carbon export enhanced by silicate upwelling in the northeast Atlantic

Diatoms are unicellular or chain-forming phytoplankton that use silicon (Si) in cell wall construction. Their survival during periods of apparent nutrient exhaustion enhances carbon sequestration in frontal regions of the northern North Atlantic. These regions may therefore have a more important role in the 'biological pump' than they have previously been attributed, but how this is achieved is unknown. Diatom growth depends on silicate availability, in addition to nitrate and phosphate, but northern Atlantic waters are richer in nitrate than silicate. Following the spring stratification, diatoms are the first phytoplankton to bloom. Once silicate is exhausted, diatom blooms subside in a major export event. Here we show that, with nitrate still available for new production, the diatom bloom is prolonged where there is a periodic supply of new silicate: specifically, diatoms thrive by 'mining' deep-water silicate brought to the surface by an unstable ocean front. The mechanism we present here is not limited to silicate fertilization; similar mechanisms could support nitrate-, phosphate- or iron-limited frontal regions in oceans elsewhere.     

A comparison of riparian condition and aquatic invertebrate community indices in central Nevada

The importance of maintaining healthy riparian communities to sustain natural stream processes and function is well documented. Land management agencies in the West are currently developing methods to assess and monitor riparian community condition to adapt land use practices that would better protect rangeland ecosystems. To determine whether these methods also provide an indication of abiotic and biotic stream condition, we compared the classification system of riparian communities developed by the U.S. Forest Service (USFS) to physical parameters of stream condition and to aquatic invertebrate community assemblages. Thirty-three sites in 19 different streams of the Toiyabe Range in central Nevada were measured for water quality, substrate characteristics, and fish abundance and diversity. We sampled aquatic invertebrates and calculated community indices based on environmental tolerance levels, taxonomic diversity, and abundance of sensitive taxa. USFS personnel classified these sites by dominant riparian plant community type (meadow, willow, or aspen) and ecological status (low, moderate, or high) using plant abundance data, rooting depth, and soil infiltration to determine similarities to potential natural communities. Riparian condition indices as well as community diversity were significantly correlated to proportions of fine and small-diameter substrate in streambeds. Accumulation of silt was significantly related to plant community type, with meadow sites expressing highest proportions. Further examinations indicated that 2 of 6 invertebrate community indices were significantly related to ecological status, with highest diversity levels occurring mainly in willow- and aspen-dominated sites in moderate ecological condition. Nevertheless, we show that several other environmental variables, including substrate characteristics, dissolved oxygen, water temperature, and species richness of fish communities, were more strongly and consistently related to invertebrate assemblage patterns. Our results demonstrate that information on aquatic invertebrates and stream condition could augment the existing riparian classification system and provide useful monitoring tools to more thoroughly examine ecosystem health in rangelands.     

Long-term evolution and transmission dynamics of swine influenza A virus

Swine influenza A viruses (SwIV) cause significant economic losses in animal husbandry as well as instances of human disease and occasionally give rise to human pandemics, including that caused by the H1N1/2009 virus. The lack of systematic and longitudinal influenza surveillance in pigs has hampered attempts to reconstruct the origins of this pandemic. Most existing swine data were derived from opportunistic samples collected from diseased pigs in disparate geographical regions, not from prospective studies in defined locations, hence the evolutionary and transmission dynamics of SwIV are poorly understood. Here we quantify the epidemiological, genetic and antigenic dynamics of SwIV in Hong Kong using a data set of more than 650 SwIV isolates and more than 800 swine sera from 12?years of systematic surveillance in this region, supplemented with data stretching back 34?years. Intercontinental virus movement has led to reassortment and lineage replacement, creating an antigenically and genetically diverse virus population whose dynamics are quantitatively different from those previously observed for human influenza viruses. Our findings indicate that increased antigenic drift is associated with reassortment events and offer insights into the emergence of influenza viruses with epidemic potential in swine and humans.     

The landscape of recombination in African Americans

Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P?value 相似文献   

Characterization of the role of the antioxidant proteins metallothioneins 1 and 2 in an animal model of Alzheimer’s disease

Alzheimer’s disease (AD) is by far the most commonly diagnosed dementia, and despite multiple efforts, there are still no effective drugs available for its treatment. One strategy that deserves to be pursued is to alter the expression and/or physiological action of endogenous proteins instead of administering exogenous factors. In this study, we intend to characterize the roles of the antioxidant, anti-inflammatory, and heavy-metal binding proteins, metallothionein-1?+?2 (MT1?+?2), in a mouse model of Alzheimer’s disease, Tg2576 mice. Contrary to expectations, MT1?+?2-deficiency rescued partially the human amyloid precursor protein-induced changes in mortality and body weight in a gender-dependent manner. On the other hand, amyloid plaque burden was decreased in the cortex and hippocampus in both sexes, while the amyloid cascade, neuroinflammation, and behavior were affected in the absence of MT1?+?2 in a complex manner. These results highlight that the control of the endogenous production and/or action of MT1?+?2 could represent a powerful therapeutic target in AD.