Astrometry and Photometry for ≈\approx1000 L, T, and Y Dwarfs from the UKIRT Hemisphere Survey

We present positions, proper motions, and near-infrared photometry for 966 known objects with spectral types later than M observed as part of the the UKIRT Hemisphere Survey (UHS). We augment the photometry and astrometry from UHS with information from Gaia DR3, Pan-STARRS DR2, and CatWISE 2020 to produce a database of homogeneous photometry and astrometry for this sample. The multi-epoch survey strategy of UHS allows us to determine proper motions for most sources, with a median proper motion uncertainty of $\sim$3.6 mas yr$^{-1}$. Our UHS proper motion measurements are generally in good agreement with those from Gaia DR3, Pan-STARRS, and CatWISE 2020, with UHS proper motions typically more precise than those from CatWISE 2020 and Pan-STARRS but not Gaia DR3. We critically analyze publicly available spectra for 406 members of this sample and provide updated near-infrared spectral types for $\sim$100 objects. We determine typical colors as a function of spectral type and provide absolute magnitude vs. spectral type relations for UHS $J$- and $K$-band photometry. Using newly determined proper motions, we highlight several objects of interest, such as objects with large tangential velocities, widely separated co-moving companions, and potential members of young nearby associations.Comment: Accepted to A

Pre-main sequence stars in the Cepheus flare region

We present results of optical spectroscopic and BVR_CI_C photometric observations of 77 pre-main sequence (PMS) stars in the Cepheus flare region. A total of 64 of these are newly confirmed PMS stars, originally selected from various published candidate lists. We estimate effective temperatures and luminosities for the PMS stars, and comparing the results with pre-main sequence evolutionary models we estimate stellar masses of 0.2-2.4M_sun and stellar ages of 0.1-15 Myr. Among the PMS stars, we identify 15 visual binaries with separations of 2-10 arcsec. From archival IRAS, 2MASS, and Spitzer data, we construct their spectral energy distributions and classify 5% of the stars as Class I, 10% as Flat SED, 60% as Class II, and 3% as Class III young stellar objects (YSOs). We identify 12 CTTS and 2 WTTS as members of NGC 7023, with mean age of 1.6 Myr. The 13 PMS stars associated with L1228 belong to three small aggregates: RNO 129, L1228A, and L1228S. The age distribution of the 17 PMS stars associated with L1251 suggests that star formation has propagated with the expansion of the Cepheus flare shell. We detect sparse aggregates of 6-7 Myr old PMS stars around the dark clouds L1177 and L1219, at a distance of 400 pc. Three T Tauri stars appear to be associated with the Herbig Ae star SV Cep at a distance of 600 pc. Our results confirm that the molecular complex in the Cepheus flare region contains clouds of various distances and star forming histories.Comment: 61 pages, 27 figures, 8 tables; accepted for publication by ApJ

Preliminary Trigonometric Parallaxes of 184 Late-T and Y Dwarfs and an Analysis of the Field Substellar Mass Function into the "Planetary" Mass Regime

We present preliminary trigonometric parallaxes of 184 late-T and Y dwarfs using observations from Spitzer (143), USNO (18), NTT (14), and UKIRT (9). To complete the 20-pc census of $\ge$T6 dwarfs, we combine these measurements with previously published trigonometric parallaxes for an additional 44 objects and spectrophotometric distance estimates for another 7. For these 235 objects, we estimate temperatures, sift into five 150K-wide $T_{\rm eff}$ bins covering the range 300-1050K, determine the completeness limit for each, and compute space densities. To anchor the high-mass end of the brown dwarf mass spectrum, we compile a list of early- to mid-L dwarfs within 20 pc. We run simulations using various functional forms of the mass function passed through two different sets of evolutionary code to compute predicted distributions in $T_{\rm eff}$. The best fit of these predictions to our L, T, and Y observations is a simple power-law model with $\alpha \approx 0.6$ (where $dN/dM \propto M^{-\alpha}$), meaning that the slope of the field substellar mass function is in rough agreement with that found for brown dwarfs in nearby star forming regions and young clusters. Furthermore, we find that published versions of the log-normal form do not predict the steady rise seen in the space densities from 1050K to 350K. We also find that the low-mass cutoff to formation, if one exists, is lower than $\sim$5 $M_{Jup}$, which corroborates findings in young, nearby moving groups and implies that extremely low-mass objects have been forming over the lifetime of the Milky Way.Comment: 86 pages with 19 figures. Accepted for publication in The Astrophysical Journal Supplement Series on 2018 Dec 0

Large-scale mapping of mutations affecting zebrafish development

BACKGROUND: Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers. RESULTS: We have selected a set of microsatellite markers and developed methods and scoring criteria suitable for efficient, high-throughput genome scanning. We have used these methods to successfully obtain a rough map position for 319 mutant loci from the Tübingen I mutagenesis screen and subsequent screening of the mutant collection. For 277 of these the corresponding gene is not yet identified. Mapping was successful for 80 % of the tested loci. By comparing 21 mutation and gene positions of cloned mutations we have validated the correctness of our linkage group assignments and estimated the standard error of our map positions to be approximately 6 cM. CONCLUSION: By obtaining rough map positions for over 300 zebrafish loci with developmental phenotypes, we have generated a dataset that will be useful not only for cloning of the affected genes, but also to suggest allelism of mutations with similar phenotypes that will be identified in future screens. Furthermore this work validates the usefulness of our methodology for rapid, systematic and inexpensive microsatellite mapping of zebrafish mutations

A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes: The EPIC-InterAct case-cohort study.

BACKGROUND: Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated. METHODS AND FINDINGS: We measured plasma phospholipid fatty acids by gas chromatography in 27,296 adults, including 12,132 incident cases of T2D, over the follow-up period between baseline (1991-1998) and 31 December 2007 in 8 European countries in EPIC-InterAct, a nested case-cohort study. The first principal component derived by principal component analysis of 27 individual fatty acids (mole percentage) was the main exposure (subsequently called the fatty acid pattern score [FA-pattern score]). The FA-pattern score was partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated fatty acids and low concentrations of γ-linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids, and it explained 16.1% of the overall variability of the 27 fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifth of the score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19-0.29) adjusted for potential confounders and 0.37 (95% CI 0.27-0.50) further adjusted for metabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and was positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p < 0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding. CONCLUSIONS: A combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors

Preliminary Trigonometric Parallaxes of 184 Late-T and Y Dwarfs and an Analysis of the Field Substellar Mass Function into the "Planetary" Mass Regime

We present preliminary trigonometric parallaxes of 184 late-T and Y dwarfs using observations from Spitzer (143), the U.S. Naval Observatory (18), the New Technology Telescope (14), and the United Kingdom Infrared Telescope (9). To complete the 20 pc census of ⩾T6 dwarfs, we combine these measurements with previously published trigonometric parallaxes for an additional 44 objects and spectrophotometric distance estimates for another 7. For these 235 objects, we estimate temperatures, sift into five 150 K wide T_(eff) bins covering the range 300–1050 K, determine the completeness limit for each, and compute space densities. To anchor the high-mass end of the brown dwarf mass spectrum, we compile a list of early- to mid-L dwarfs within 20 pc. We run simulations using various functional forms of the mass function passed through two different sets of evolutionary code to compute predicted distributions in T_(eff). The best fit of these predictions to our L, T, and Y observations is a simple power-law model with α ≈ 0.6 (where dN/dM ∝ M^(-α)), meaning that the slope of the field substellar mass function is in rough agreement with that found for brown dwarfs in nearby star-forming regions and young clusters. Furthermore, we find that published versions of the log-normal form do not predict the steady rise seen in the space densities from 1050 to 350 K. We also find that the low-mass cutoff to formation, if one exists, is lower than ~5 M_(Jup), which corroborates findings in young, nearby moving groups and implies that extremely low-mass objects have been forming over the lifetime of the Milky Way

A20 Modulates Lipid Metabolism and Energy Production to Promote Liver Regeneration

Background: Liver Regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-$\kappa$B inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR) in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice. Methodology and Principal Findings: We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.$\beta$galactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-$\kappa$B, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV. Conclusion: This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings support pursuit of A20-based therapies to improve patients' outcomes in the context of extreme liver injury and extensive LR for tumor treatment or donation

Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects