Association of the HLA locus and TNF with type I autoimmune hepatitis susceptibility in New Zealand Caucasians

PURPOSE: The precise etiology of autoimmune hepatitis (AIH) remains unknown, although a number of genetic loci have been implicated in the susceptibility of type 1 AIH. The purpose of this study was to test for association of these loci with type 1 AIH in New Zealand Caucasians. METHODS: 77 AIH patients and 485 healthy controls were genotyped for the SNPs rs2187668 (HLA-DRB*03:01), rs660895 (HLA-DRB*04:01), rs3749971 (HLA-A1-B8-DR3), rs231775 (CLTLA4), rs1800629 (TNF), and rs1800682 (FAS) using predesigned TaqMan SNP genotyping assays. Chi square analysis was used to test for association of allele and genotype with overall AIH, and with severe fibrosis and ALT levels at 6 months. RESULTS: Significant risk of AIH was conferred by the minor alleles of rs2187668 (OR = 2.45, 95% CI 1.65-3.61, p < 0.0001), rs3749971 (OR = 1.89, 95% CI 1.21-2.94, p = 0.004) and rs1800629 (OR = 2.06, 95% CI 1.41-3.01, p = 0.0001). Multivariate analysis showed that rs2187668 was independently associated with type 1 AIH susceptibility (OR = 2.40, 95% CI 1.46-3.93, p = 0.001). The C allele of FAS SNP rs1800682 was associated with increased risk of severe fibrosis at diagnosis (OR = 2.03, 95% CI 1.05-3.93, p = 0.035) and with incomplete normalization of ALT levels at 6 months post-diagnosis (OR = 3.94, 95% CI 1.62-9.54, p = 0.0015). CONCLUSIONS: This is the first population-based study to investigate genetic risk loci for type 1 AIH in New Zealand Caucasians. We report significant independent association of HLA-DRB1*03:01 with overall susceptibility to type 1 AIH, as well as FAS with a more aggressive disease phenotype

A stochastic neuronal model predicts random search behaviors at multiple spatial scales in C. elegans

Random search is a behavioral strategy used by organisms from bacteria to humans to locate food that is randomly distributed and undetectable at a distance. We investigated this behavior in the nematode Caenorhabditis elegans, an organism with a small, well-described nervous system. Here we formulate a mathematical model of random search abstracted from the C. elegans connectome and fit to a large-scale kinematic analysis of C. elegans behavior at submicron resolution. The model predicts behavioral effects of neuronal ablations and genetic perturbations, as well as unexpected aspects of wild type behavior. The predictive success of the model indicates that random search in C. elegans can be understood in terms of a neuronal flip-flop circuit involving reciprocal inhibition between two populations of stochastic neurons. Our findings establish a unified theoretical framework for understanding C. elegans locomotion and a testable neuronal model of random search that can be applied to other organisms

The impact of over 80 years of land cover changes on bee and wasp pollinator communities in England

Change in land cover is thought to be one of the key drivers of pollinator declines, and yet there is a dearth of studies exploring the relationships between historical changes in land cover and shifts in pollinator communities. Here, we explore, for the first time, land cover changes in England over more than 80 years, and relate them to concurrent shifts in bee and wasp species richness and community composition. Using historical data from 14 sites across four counties, we quantify the key land cover changes within and around these sites and estimate the changes in richness and composition of pollinators. Land cover changes within sites, as well as changes within a 1 km radius outside the sites, have significant effects on richness and composition of bee and wasp species, with changes in edge habitats between major land classes also having a key influence. Our results highlight not just the land cover changes that may be detrimental to pollinator communities, but also provide an insight into how increases in habitat diversity may benefit species diversity, and could thus help inform policy and practice for future land management

Characterization of the Companion to μ\mu Her

$\mu$ Her is a nearby quadruple system with a G-subgiant primary and several low mass companions arranged in a 2+2 architecture. While the BC components have been well characterized, the Ab component has been detected astrometrically and with direct imaging but there has been some confusion over its nature, in particular whether the companion is stellar or substellar. Using near-infrared spectroscopy we are able to estimate the spectral type of the companion as a M4$\pm$1V star. In addition, we have measured the astrometry of the system for over a decade. We combined the astrometry with archival radial velocity measurements to compute an orbit of the system. From the combined orbit, we are able to compute the mass sum of the system. Using the estimated mass of the primary, we estimate the mass of the secondary as 0.32 M_sun, which agrees with the estimated spectral type. Our computed orbit is preliminary due to the incomplete orbital phase coverage, but it should be sufficient to predict ephemerides over the next decade.Comment: 7 pages, 5 figures, Accepted to Astronomical Journa

Direct Imaging in Reflected Light: Characterization of Older, Temperate Exoplanets With 30-m Telescopes

Direct detection, also known as direct imaging, is a method for discovering and characterizing the atmospheres of planets at intermediate and wide separations. It is the only means of obtaining spectra of non-transiting exoplanets. Characterizing the atmospheres of planets in the <5 AU regime, where RV surveys have revealed an abundance of other worlds, requires a 30-m-class aperture in combination with an advanced adaptive optics system, coronagraph, and suite of spectrometers and imagers - this concept underlies planned instruments for both TMT (the Planetary Systems Imager, or PSI) and the GMT (GMagAO-X). These instruments could provide astrometry, photometry, and spectroscopy of an unprecedented sample of rocky planets, ice giants, and gas giants. For the first time habitable zone exoplanets will become accessible to direct imaging, and these instruments have the potential to detect and characterize the innermost regions of nearby M-dwarf planetary systems in reflected light. High-resolution spectroscopy will not only illuminate the physics and chemistry of exo-atmospheres, but may also probe rocky, temperate worlds for signs of life in the form of atmospheric biomarkers (combinations of water, oxygen and other molecular species). By completing the census of non-transiting worlds at a range of separations from their host stars, these instruments will provide the final pieces to the puzzle of planetary demographics. This whitepaper explores the science goals of direct imaging on 30-m telescopes and the technology development needed to achieve them.Comment: (March 2018) Submitted to the Exoplanet Science Strategy committee of the NA

Direct Spectrum of the Benchmark T Dwarf HD 19467 B

HD 19467 B is presently the only directly imaged T dwarf companion known to induce a measurable Doppler acceleration around a solar-type star. We present spectroscopy measurements of this important benchmark object taken with the Project 1640 integral field unit at Palomar Observatory. Our high-contrast R ≈ 30 observations obtained simultaneously across the JH bands confirm the cold nature of the companion as reported from the discovery article and determine its spectral type for the first time. Fitting the measured spectral energy distribution to SpeX/IRTF T dwarf standards and synthetic spectra from BT-Settl atmospheric models, we find that HD 19467 B is a T5.5 ± 1 dwarf with effective temperature T_eff=978^(+20)_(-43) K. Our observations reveal significant methane absorption affirming its substellar nature. HD 19467 B shows promise to become the first T dwarf that simultaneously reveals its mass, age, and metallicity independent from the spectrum of light that it emits