ATP drives lamina propria T(H)17 cell differentiation

Interleukin (IL)-17-producing CD4(+) T lymphocytes (T(H)17 cells) constitute a subset of T-helper cells involved in host defence and several immune disorders. An intriguing feature of T(H)17 cells is their selective and constitutive presence in the intestinal lamina propria. Here we show that adenosine 5'-triphosphate (ATP) that can be derived from commensal bacteria activates a unique subset of lamina propria cells, CD70(high)CD11c(low) cells, leading to the differentiation of T(H)17 cells. Germ-free mice exhibit much lower concentrations of luminal ATP, accompanied by fewer lamina propria T(H)17 cells, compared to specific-pathogen-free mice. Systemic or rectal administration of ATP into these germ-free mice results in a marked increase in the number of lamina propria T(H)17 cells. A CD70(high)CD11c(low) subset of the lamina propria cells expresses T(H)17-prone molecules, such as IL-6, IL-23p19 and transforming-growth-factor-beta-activating integrin-alphaV and -beta8, in response to ATP stimulation, and preferentially induces T(H)17 differentiation of co-cultured naive CD4(+) T cells. The critical role of ATP is further underscored by the observation that administration of ATP exacerbates a T-cell-mediated colitis model with enhanced T(H)17 differentiation. These observations highlight the importance of commensal bacteria and ATP for T(H)17 differentiation in health and disease, and offer an explanation of why T(H)17 cells specifically present in the intestinal lamina propria.     

Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33

Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 × 10?1? and rs6687758, OR = 1.09, P = 2.27 × 10??, 3q26.2 (rs10936599, OR = 0.93, P = 3.39 × 10??), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 × 10?1? and rs7136702, OR = 1.06, P = 4.02 × 10??) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 × 10?1?). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered.     

Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.     

Life cycle and incidence of Diplostomum spathaceum Rudolphi (1819) (Trematoda: Diplostomatidae) in Utah

Diplostomum spathaceum (Trematoda: Diplostomatidae) causes a disease known as diplostomatosis (eye fluke disease) and has been found to be widespread throughout the fish of Utah. Totals of 756 snails (5 species), 893 fish (21 species) and 6 species of birds were examined for the presence of larval and adult D. spathaceum from 17 collecting sites throughout Utah. Pathologic effects such as blindness, subacute inflammatory reactions, cornea perforation, and ruptured globe due to diplostomatosis upon the fish host are listed. Fish host and parasite infection data of D. spathaceum for the major lakes of Utah are given.     

Observations on natural enemies of western spruce budworm ( Choristoneura occidentalis Freeman)(Lepidoptera, Tortricidae) in the Rocky Mountain area

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Achieving continuity: a story of stellar magnitude

Scientists tell a story of 2,000 years of stellar magnitude research that traces back to Hipparchus. This story of continuity in practices serves an important role in scientific education and outreach. STS scholars point out many ways that stories of continuity, like many narratives about science, are disconnected from practices. Yet the story of continuity in stellar magnitude is a powerful scientific achievement precisely because of its connection to practice. The historical development of star catalogues shows how specific recording practices connected past and present in a useful way. The narrative of continuity in stellar magnitude, however else it might be subject to STS critique of narrative, maintains its power because of its connection to practice. I suggest that more attention be paid to connections between practice and narrative in STS, and in particular to the ways that historical practices sustain narratives by connecting past and present.     

A genome-wide association meta-analysis identifies new childhood obesity loci

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).     

A close halo of large transparent grains around extreme red giant stars

An intermediate-mass star ends its life by ejecting the bulk of its envelope in a slow, dense wind. Stellar pulsations are thought to elevate gas to an altitude cool enough for the condensation of dust, which is then accelerated by radiation pressure, entraining the gas and driving the wind. Explaining the amount of mass loss, however, has been a problem because of the difficulty of observing tenuous gas and dust only tens of milliarcseconds from the star. For this reason, there is no consensus on the way sufficient momentum is transferred from the light from the star to the outflow. Here we report spatially resolved, multiwavelength observations of circumstellar dust shells of three stars on the asymptotic giant branch of the Hertzsprung-Russell diagram. When imaged in scattered light, dust shells were found at remarkably small radii (less than about two stellar radii) and with unexpectedly large grains (about 300 nanometres in radius). This proximity to the photosphere argues for dust species that are transparent to the light from the star and, therefore, resistant to sublimation by the intense radiation field. Although transparency usually implies insufficient radiative pressure to drive a wind, the radiation field can accelerate these large grains through photon scattering rather than absorption--a plausible mass loss mechanism for lower-amplitude pulsating stars.     

A Cenozoic record of the equatorial Pacific carbonate compensation depth

Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5?kilometres during the early Cenozoic (approximately 55?million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth.