A Genome-Wide Association Study of Psoriasis and Psoriatic Arthritis Identifies New Disease Loci

A genome-wide association study was performed to identify genetic factors involved in susceptibility to psoriasis (PS) and psoriatic arthritis (PSA), inflammatory diseases of the skin and joints in humans. 223 PS cases (including 91 with PSA) were genotyped with 311,398 single nucleotide polymorphisms (SNPs), and results were compared with those from 519 Northern European controls. Replications were performed with an independent cohort of 577 PS cases and 737 controls from the U.S., and 576 PSA patients and 480 controls from the U.K.. Strongest associations were with the class I region of the major histocompatibility complex (MHC). The most highly associated SNP was rs10484554, which lies 34.7 kb upstream from HLA-C (P = 7.8×10⁻¹¹, GWA scan; P = 1.8×10⁻³⁰, replication; P = 1.8×10⁻³⁹, combined; U.K. PSA: P = 6.9×10⁻¹¹). However, rs2395029 encoding the G2V polymorphism within the class I gene HCP5 (combined P = 2.13×10⁻²⁶ in U.S. cases) yielded the highest ORs with both PS and PSA (4.1 and 3.2 respectively). This variant is associated with low viral set point following HIV infection and its effect is independent of rs10484554. We replicated the previously reported association with interleukin 23 receptor and interleukin 12B (IL12B) polymorphisms in PS and PSA cohorts (IL23R: rs11209026, U.S. PS, P = 1.4×10⁻⁴; U.K. PSA: P = 8.0×10⁻⁴; IL12B:rs6887695, U.S. PS, P = 5×10⁻⁵ and U.K. PSA, P = 1.3×10⁻³) and detected an independent association in the IL23R region with a SNP 4 kb upstream from IL12RB2 (P = 0.001). Novel associations replicated in the U.S. PS cohort included the region harboring lipoma HMGIC fusion partner (LHFP) and conserved oligomeric golgi complex component 6 (COG6) genes on chromosome 13q13 (combined P = 2×10⁻⁶ for rs7993214; OR = 0.71), the late cornified envelope gene cluster (LCE) from the Epidermal Differentiation Complex (PSORS4) (combined P = 6.2×10⁻⁵ for rs6701216; OR 1.45) and a region of LD at 15q21 (combined P = 2.9×10⁻⁵ for rs3803369; OR = 1.43). This region is of interest because it harbors ubiquitin-specific protease-8 whose processed pseudogene lies upstream from HLA-C. This region of 15q21 also harbors the gene for SPPL2A (signal peptide peptidase like 2a) which activates tumor necrosis factor alpha by cleavage, triggering the expression of IL12 in human dendritic cells. We also identified a novel PSA (and potentially PS) locus on chromosome 4q27. This region harbors the interleukin 2 (IL2) and interleukin 21 (IL21) genes and was recently shown to be associated with four autoimmune diseases (Celiac disease, Type 1 diabetes, Grave''s disease and Rheumatoid Arthritis).     

The influence of multiple dispersal mechanisms and landscape structure on population clustering and connectivity in fragmented artesian spring snail populations

Many organisms occupy heterogeneous landscapes that contain both barriers to movement as well as corridors that facilitate dispersal. The extent to which such features determine population connectivity will depend on the mechanisms utilized by organisms to disperse. Here we examined the interaction between landscape structure and dispersal in the endemic aquatic snail, Fonscochlea accepta , in the fragmented artesian spring ecosystem of arid central Australia. We used frequentist and Bayesian analyses of microsatellite data to identify population structure and immigration for 1130 snails sampled from 50 springs across an entire spring complex. We introduce a modified isolation-by-distance analysis to test hypotheses about how populations are clustered and to distinguish the most likely dispersal pathways within and between those clusters. Highly significant differences in F _ST values and significant isolation-by-distance patterns were detected among springs across the entire complex, while Bayesian assignment tests revealed the presence of two hierarchical levels of spring clustering. Clusters were defined by the spatial aggregation of springs, dynamic aquatic habitat connections between springs and the ecology of the snails. Bayesian immigrant identification and our modified isolation-by-distance analysis revealed that dispersal occurs at two geographical scales via two very different mechanisms. Short range dispersal (usually ≤ 300 m) occurs via active movement facilitated by aquatic connections among springs while long-range dispersal (≥ 3 km) is likely facilitated by an animal vector (phoresy). These results underline the importance of both dispersal mode and landscape structure in influencing connectivity rates and patterns among populations.     

Temperature-dependent sex-biased embryo mortality in a bird

Sex ratios have important evolutionary consequences and are often biased by environmental factors. The effect of developmental temperature on offspring sex ratios has been widely documented across a diverse range of taxa but has rarely been investigated in birds and mammals. However, recent field observations and artificial incubation experiments have demonstrated that the hatching sex ratio of a megapode, the Australian brush-turkey (Alectura lathami), varied with incubation temperature; more females hatched at high incubation temperatures and more males hatched at low temperatures. Here, we investigated the causes of this temperature-dependent sex-biasing system. Molecular sexing of chicks and embryos confirmed that male embryo mortality was greater at high temperatures while female embryo mortality is greater at low temperatures, with mortality in both sexes similar at intermediate incubation temperatures. Temperature-dependent sex-biased embryo mortality represents a novel mechanism of altering sex ratios in birds. This novel mechanism, coupled with the unique breeding biology of the brush-turkey, offers a potentially unparalleled opportunity in which to investigate sex allocation theory in birds.     

Structure and diversity of the Mesozoic wood genus Xenoxylon in Far East Asia: implications for terrestrial palaeoclimates

Although the faunal elements of Far East Asian Mesozoic terrestrial biota have attracted much attention in recent years, their palaeoecology remains poorly known. In particular, features of the palaeoclimate are highly controversial. To address this point we used the Mesozoic fossil wood Xenoxylon , a genus recognized as an indicator of wet temperate biotopes and which is common in the area during the Carnian–Maastrichtian interval. We re-appraised bibliographic data and gathered new data for Xenoxylon in the Mesozoic of Far East Asia. This demonstrated that previous taxonomic approaches to the genus have been so far idiosyncratic. We examined the anatomical diversity of morphogenus Xenoxylon in Far East Asia and compared it to that of samples from Europe. This indicates that in an area centred on north-eastern China, Xenoxylon reached a level of anatomical diversity unmatched elsewhere in the world. We hypothesize that this diversity witnesses the persistence of palaeoecological conditions particularly suitable for Xenoxylon and that a wet temperate climate prevailed over most of the area throughout the Carnian–Maastrichtian interval. It is in this setting that the famous Jehol Biota probably evolved.     

Characterization of the oligomeric structure of the Ca(2+)-activated Cl- channel Ano1/TMEM16A

Members of the Anoctamin (Ano)/TMEM16A family have recently been identified as essential subunits of the Ca²⁺-activated chloride channel (CaCC). For example, Ano1 is highly expressed in multiple tissues including airway epithelia, where it acts as an apical conduit for transepithelial Cl⁻ secretion and helps regulate lung liquid homeostasis and mucus clearance. However, little is known about the oligomerization of this protein in the plasma membrane. Thus, utilizing mCherry- and eGFP-tagged Ano1 constructs, we conducted biochemical and Förster resonance energy transfer (FRET)-based experiments to determine the quaternary structure of Ano1. FRET and co-immunoprecipitation studies revealed that tagged Ano1 subunits directly associated before they reached the plasma membrane. This association was not altered by changes in cytosolic Ca²⁺, suggesting that this is a fixed interaction. To determine the oligomeric structure of Ano1, we performed chemical cross-linking, non-denaturing PAGE, and electromobility shift assays, which revealed that Ano1 exists as a dimer. These data are the first to probe the quaternary structure of Ano1. Understanding the oligomeric nature of Ano1 is an essential step in the development of therapeutic drugs that could be useful in the treatment of cystic fibrosis.     

Backcasting the decline of a vulnerable Great Plains reproductive ecotype: identifying threats and conservation priorities

Conservation efforts for threatened or endangered species are challenging because the multi‐scale factors that relate to their decline or inhibit their recovery are often unknown. To further exacerbate matters, the perceptions associated with the mechanisms of species decline are often viewed myopically rather than across the entire species range. We used over 80 years of fish presence data collected from the Great Plains and associated ecoregions of the United States, to investigate the relative influence of changing environmental factors on the historic and current truncated distributions of the Arkansas River shiner Notropis girardi. Arkansas River shiner represent a threatened reproductive ecotype considered especially well adapted to the harsh environmental extremes of the Great Plains. Historic (n = 163 records) and current (n = 47 records) species distribution models were constructed using a vector‐based approach in MaxEnt by splitting the available data at a time when Arkansas River shiner dramatically declined. Discharge and stream order were significant predictors in both models; however, the shape of the relationship between the predictors and species presence varied between time periods. Drift distance (river fragment length available for ichthyoplankton downstream drift before meeting a barrier) was a more important predictor in the current model and indicated river segments 375–780 km had the highest probability of species presence. Performance for the historic and current models was high (area under the curve; AUC > 0.95); however, forecasting and backcasting to alternative time periods suggested less predictive power. Our results identify fragments that could be considered refuges for endemic plains fish species and we highlight significant environmental factors (e.g., discharge) that could be manipulated to aid recovery.     

5种沉水植物无性繁殖和定居能力的比较研究

 竹叶眼子菜(Potamogeton malaianus)、微齿眼子菜(Potamogeton maackianus)、苦草(Vallisneria spiralis)、穗花狐尾藻(Myriophyllum spicatum)、黑藻(Hydrilla verticillata)是长江中下游湖泊主要的沉水植物。在栽培条件下,它们的无性繁殖速率(单位时间内新增个体数)大小顺序为黑藻>微齿眼子菜>竹叶眼子菜>苦草>穗花狐尾藻。同时采用抛掷实验的方法观察研究了这5种沉水植物及其无性繁殖体的存活和生根情况;完整植株存活率为黑藻>穗花狐尾藻>微齿眼子菜>竹叶眼子菜>苦草,无性繁殖体部分存活率为黑藻>苦草>穗花狐尾藻>微齿眼子菜>竹叶眼子菜。生根能力和其存活时间长短相关,而且生根能力与存活率大小基本一致。在实验中,只有穗花狐尾藻的断枝存活率和生根能力存在差异,故无性繁殖体生根能力为黑藻>苦草>微齿眼子菜>竹叶眼子菜>穗花狐尾藻。