Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.     

Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation

During immune responses, antibodies are selected for their ability to bind to foreign antigens with high affinity, in part by their ability to undergo homotypic bivalent binding. However, this type of binding is not always possible. For example, the small number of gp140 glycoprotein spikes displayed on the surface of the human immunodeficiency virus (HIV) disfavours homotypic bivalent antibody binding. Here we show that during the human antibody response to HIV, somatic mutations that increase antibody affinity also increase breadth and neutralizing potency. Surprisingly, the responding naive and memory B cells produce polyreactive antibodies, which are capable of bivalent heteroligation between one high-affinity anti-HIV-gp140 combining site and a second low-affinity site on another molecular structure on HIV. Although cross-reactivity to self-antigens or polyreactivity is strongly selected against during B-cell development, it is a common serologic feature of certain infections in humans, including HIV, Epstein-Barr virus and hepatitis C virus. Seventy-five per cent of the 134 monoclonal anti-HIV-gp140 antibodies cloned from six patients with high titres of neutralizing antibodies are polyreactive. Despite the low affinity of the polyreactive combining site, heteroligation demonstrably increases the apparent affinity of polyreactive antibodies to HIV.     

Algal populations in Bottle Hollow Reservoir, Duchesne County, Utah

Bottle Hollow Reservoir contains a diverse algal flora. A total of 289 taxa was observed, 227 of which were diatoms. Both littoral and planktonic communities had high diatom diversity. During summer months filamentous Chlorophvta were diverse and high in biomass in the littoral zone. Phytoplankton collections in Bottle Hollow Reservoir were dominated by four species: Asterionella formosa, Cyclotella comta, Dinobryon divergens, and Fragilaria crotonensis. Plankton samples contained mostly small diatoms in early spring, with larger algae succeeding these as the summer progressed. No blue - green algae were important in this succession. Two peak production periods were observed, one in the fall and one in the spring. Bottle Hollow Reservoir appears to be a healthy mesotrophic system based on the evidences of moderately high algal diversity, insignificance of blue-green algae, and the presence of a suite of diatom species indicative of mesotrophic conditions.     

Contributions to the biology of the woundfin, Plagopterus argentissimus (Pisces: Cyprinidae), an endangered species

The woundfin is a small, streamlined, omnivorous cyprinid that is now limited to the Virgin River basin where it was collected in the mainstream and one tributary during the present study. The woundfin occurred most frequently in runs and over sand substrates and less frequently in riffles and over rock substrates. It was common over at least half of its original range within the Virgin River. It was uncommon in the lower mainstream due to habitat alterations and, presumably, predation by and competition with exotic species.     

Litter decomposition by arthropods in undisturbed and intensively managed mountain brush habitats

The population dynamics and decomposition activities of litter arthropods in an unmanaged sagehrush/bitterbrush habitat in southeastern Wyoming were assessed in 1986. The effects of sagebrush/bitterbrush management practices on litter arthropod communities and the role of these communities in decomposition were also assessed. Insecticide applications were used to selectively exclude arthropods in order to determine the ecological impact of these detritivores. Application of a herbicide, 2,4-D, was associated with increased arthropod populations for 30 days following treatment. Mowing increased arthropod densities at two different times, 10-30 days and 50 days post treatment, perhaps as a result of functional and numerical responses by litter arthropods. Elimination of arthropods from otherwise undisturbed shrub habitats by the use of broad-spectrum insecticides reduced the rate of litter decomposition during the growing season, indicating that these organisms play an important role in decomposition and nutrient cycling.     

Synthesis of Li_4Ti_5O_(12) nanostructural anode materials with high charge–discharge capability

This study demonstrates a facile and efficient hydrothermal method to prepare spindle titanate(Li4Ti5O12 denoted as LTO)and/or carbon-LTO nanocomposites(CLTO),in which the LTO or C-LTO microspheres have diameters of a few micrometers,composed of numerous nanosheets with thickness of*30 nm and edge length of hundreds of nanometers.The morphology and size control of these nanoparticles could be achieved by varying experimental parameters including concentration of titanium butoxide,lithium hydroxide,and cetyltrimethylammonium bromide,as well as reaction temperature and time.These micro-nanostructures were characterized by several advanced techniques,such as transmission electron microscopy,scanning electron microscopy,X-ray diffraction,energy dispersive spectroscopic analysis,surface area,and electrochemical measurements.The LTO and C-LTO microstructures were examined in the charge–discharge capacity at a rate of 50 C,as well as the stability after 100 cycles at a rate of 10 C.The excellent capability may be attributed to good conductivity,large surface area,and stable assembly structure of such micro-nanostructures,which could be explored as a promising anode material for lithium-ion batteries.     

Distribution and three-dimensional structure of AIDS virus envelope spikes

Envelope glycoprotein (Env) spikes on AIDS retroviruses initiate infection of host cells and are therefore targets for vaccine development. Though crystal structures for partial Env subunits are known, the structure and distribution of native Env spikes on virions is obscure. We applied cryoelectron microscopy tomography to define ultrastructural details of spikes. Virions of wild-type human immunodeficiency virus 1 (HIV-1) and a mutant simian immunodeficiency virus (SIV) had approximately 14 and approximately 73 spikes per particle, respectively, with some clustering of HIV-1 spikes. Three-dimensional averaging showed that the surface glycoprotein (gp120) 'head' of each subunit of the trimeric SIV spike contains a primary mass, with two secondary lobes. The transmembrane glycoprotein 'stalk' of each trimer is composed of three independent legs that project obliquely from the trimer head, tripod-like. Reconciling available atomic structures with the three-dimensional whole spike density map yields insights into the orientation of Env spike structural elements and possible structural bases of their functions.     

Superhydrophobicity: drying transition of confined water

Long-range hydrophobic interactions operating underwater are important in the mediation of many natural and synthetic phenomena, such as protein folding, adhesion and colloid stability. Here we show that rough hydrophobic surfaces can experience attractive forces over distances more than 30 times greater than any reported previously, owing to the spontaneous evaporation of the intervening, confined water. Our finding highlights the importance of surface roughness in the interaction of extended structures in water, which has so far been largely overlooked.