This paper presents new trigonometric parallaxes and proper motions for 214 stars. The measurements were made at the US Naval Observatory Flagstaff Station between 1989 and 2017, and the average ...uncertainty in the parallax values is 0.6 mas. We find good agreement with Gaia Data Release 2 measurements for the stars in common, although there may be a small systematic offset similar to what has been found by other investigators. The sample is matched to catalogs and the literature to create a photometric data set that spans the ultraviolet to the mid-infrared. New mid-infrared photometry is obtained for 19 stars from archived Spitzer mosaics. New optical spectroscopy is presented for seven systems and additional spectra were obtained from the literature. We identify a subsample of 179 white dwarfs (WDs) at distances of 25-200 pc. Their spectral energy distributions (SEDs) are analyzed using model atmospheres. The models reproduce the entire flux-calibrated SED very well and provide the atmospheric chemical composition, temperature, surface gravity, mass, and cooling age of each WD. Twenty-six WDs are newly classified, and 12 systems are presented as candidate unresolved binaries. We confirm one WD+red dwarf system and identify two WDs as candidate dust disk systems. Twelve old and high-velocity systems are identified as candidate thick disk or halo objects. The WDs in the sample generally have Galactic disk-like ages of <8 Gyr and masses close to the canonical 0.6 M .
The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological ...conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
Selenite is an inorganic form of selenium that has a cytotoxic effect against several human cancer cell lines: one or more selenite metabolites are considered to be responsible for its toxicity. ...X-ray absorption spectroscopy was used to monitor Se speciation in A549 human lung cancer cells incubated with selenite over 72 h. As anticipated, selenodiglutathione and elemental Se both comprised a large proportion of Se in the cells between 4 and 72 h after treatment, which is in accordance with the reductive metabolism of selenite in the presence of glutathione and glutathione reductase/NADPH system. Selenocystine was also present in the cells but was only detected as a significant component between 24 and 48 h concomitant with a decrease in the proportion of selenocysteine and the viability of the cells. The change in speciation from the selenol, selenocysteine, to the diselenide, selenocystine, is indicative of a change in the redox status of the cells to a more oxidizing environment, likely brought about by metabolites of selenite. X-ray fluorescence microscopy of single cells treated with selenite for 24 h revealed a punctate distribution of Se in the cytoplasm. The accumulation of Se was associated with a greater than 2-fold increase in Cu, which was colocalized with Se. Selenium K-edge extended X-ray absorption fine structure (EXAFS) spectroscopy revealed Se–Se and Se–S bonding, but not Se–Cu bonding, despite the spatial association of Se and Cu. Microprobe X-ray absorption near-edge structure spectroscopy (μ-XANES) showed that the highly localized Se species was mostly elemental Se.
Abstract
We report the discovery of two TESS sub-Neptunes orbiting the early M dwarf TOI-904 (TIC 261257684). Both exoplanets, TOI-904 b and c, were initially observed in TESS Sector 12 with twin ...sizes of
2.426
−
0.157
+
0.163
and
2.167
−
0.118
+
0.130
R
⊕
, respectively. Through observations in five additional sectors in the TESS primary mission and the first and second extended missions, the orbital periods of the planets were measured to be 10.887 ± 0.001 and 83.999 ± 0.001 days, respectively. Reconnaissance radial velocity measurements (taken with EULER/CORALIE and SMARTS/CHIRON) and high-resolution speckle imaging with adaptive optics (obtained from SOAR/HRCAM and Gemini South/ZORRO) show no evidence of an eclipsing binary or a nearby companion, which, together with the low false-positive probabilities calculated with the statistical validation software TRICERATOPS, establishes the planetary nature of these candidates. The outer planet, TOI-904 c, is the longest-period M dwarf exoplanet found by TESS, with an estimated equilibrium temperature of 217 K. As the three other validated planets with comparable host stars and orbital periods were observed by Kepler around much dimmer stars (
J
mag
> 12), TOI-904 c, orbiting a brighter star (
J
mag
= 9.6), is the coldest M dwarf planet easily accessible for atmospheric follow-up. Future mass measurements and transmission spectroscopy of the similar-sized planets in this system could determine whether they are also similar in density and composition, suggesting a common formation pathway, or whether they have distinct origins.
Evaluating the composition of the human gut microbiota greatly facilitates studies on its role in human pathophysiology, and is heavily reliant on culture-independent molecular methods. A microarray ...designated the Human Gut Chip (HuGChip) was developed to analyze and compare human gut microbiota samples. The PhylArray software was used to design specific and sensitive probes. The DNA chip was composed of 4,441 probes (2,442 specific and 1,919 explorative probes) targeting 66 bacterial families. A mock community composed of 16S rRNA gene sequences from intestinal species was used to define the threshold criteria to be used to analyze complex samples. This was then experimentally verified with three human faecal samples and results were compared (i) with pyrosequencing of the V4 hypervariable region of the 16S rRNA gene, (ii) metagenomic data, and (iii) qPCR analysis of three phyla. When compared at both the phylum and the family level, high Pearson's correlation coefficients were obtained between data from all methods. The HuGChip development and validation showed that it is not only able to assess the known human gut microbiota but could also detect unknown species with the explorative probes to reveal the large number of bacterial sequences not yet described in the human gut microbiota, overcoming the main inconvenience encountered when developing microarrays.
Summary Background Genetic determinants of stroke, the leading neurological cause of death and disability, are poorly understood and have seldom been explored in the general population. Our aim was ...to identify additional loci for stroke by doing a meta-analysis of genome-wide association studies. Methods For the discovery sample, we did a genome-wide analysis of common genetic variants associated with incident stroke risk in 18 population-based cohorts comprising 84 961 participants, of whom 4348 had stroke. Stroke diagnosis was ascertained and validated by the study investigators. Mean age at stroke ranged from 45·8 years to 76·4 years, and data collection in the studies took place between 1948 and 2013. We did validation analyses for variants yielding a significant association (at p<5 × 10−6 ) with all-stroke, ischaemic stroke, cardioembolic ischaemic stroke, or non-cardioembolic ischaemic stroke in the largest available cross-sectional studies (70 804 participants, of whom 19 816 had stroke). Summary-level results of discovery and follow-up stages were combined using inverse-variance weighted fixed-effects meta-analysis, and in-silico lookups were done in stroke subtypes. For genome-wide significant findings (at p<5 × 10−8 ), we explored associations with additional cerebrovascular phenotypes and did functional experiments using conditional (inducible) deletion of the probable causal gene in mice. We also studied the expression of orthologs of this probable causal gene and its effects on cerebral vasculature in zebrafish mutants. Findings We replicated seven of eight known loci associated with risk for ischaemic stroke, and identified a novel locus at chromosome 6p25 (rs12204590, near FOXF2 ) associated with risk of all-stroke (odds ratio OR 1·08, 95% CI 1·05–1·12, p=1·48 × 10−8 ; minor allele frequency 21%). The rs12204590 stroke risk allele was also associated with increased MRI-defined burden of white matter hyperintensity—a marker of cerebral small vessel disease—in stroke-free adults (n=21 079; p=0·0025). Consistently, young patients (aged 2–32 years) with segmental deletions of FOXF2 showed an extensive burden of white matter hyperintensity. Deletion of Foxf2 in adult mice resulted in cerebral infarction, reactive gliosis, and microhaemorrhage. The orthologs of FOXF2 in zebrafish (foxf2b and foxf2a ) are expressed in brain pericytes and mutant foxf2b−/− cerebral vessels show decreased smooth muscle cell and pericyte coverage. Interpretation We identified common variants near FOXF2 that are associated with increased stroke susceptibility. Epidemiological and experimental data suggest that FOXF2 mediates this association, potentially via differentiation defects of cerebral vascular mural cells. Further expression studies in appropriate human tissues, and further functional experiments with long follow-up periods are needed to fully understand the underlying mechanisms. Funding NIH, NINDS, NHMRC, CIHR, European national research institutions, Fondation Leducq.
A family of dinuclear cobalt complexes with bridging bis(dioxolene) ligands derived from 3,3,3′,3′-tetramethyl-1,1′-spirobis(indane-5,5′,6,6′-tetrol) (spiroH4) and ancillary ligands based on ...tris(2-pyridylmethyl)amine (tpa) has been synthesized and characterized. The bis(dioxolene) bridging ligand is redox-active and accessible in the (spirocat–cat)4–, (spiroSQ–cat)3–, and (spiroSQ–SQ)2– forms, (cat = catecholate, SQ = semiquinonate). Variation of the ancillary ligand (Me n tpa; n = 0–3) by successive methylation of the 6-position of the pyridine rings influences the redox state of the complex, governing the distribution of electrons between the cobalt centers and the bridging ligands. Pure samples of salts of the complexes Co2(spiro)(tpa)22+ (1), Co2(spiro)(Metpa)22+ (2), Co2(spiro)(Me2tpa)22+ (3), Co2(spiro)(Me3tpa)22+ (4), Co2(spiro)(tpa)23+ (5), and Co2(spiro)(tpa)24+ (6) have been isolated, and 1, 4, and 6 have been characterized by single crystal X-ray diffraction. Studies in the solid and solution states using multiple techniques reveal temperature invariant redox states for 1, 2, and 4–6 and provide clear evidence for four different charge distributions: 1 and 2 are CoIII-(spirocat–cat)-CoIII, 4 is CoII-(spiroSQ–SQ)-CoII, 5 is CoIII-(spiroSQ–cat)-CoIII, and 6 is CoIII-(spiroSQ–SQ)-CoIII. Of the six complexes, only 3 shows evidence of temperature dependence of the charge distribution, displaying a rare thermally induced two-step valence tautomeric transition from the CoIII-(spirocat–cat)-CoIII form to CoII-(spiroSQ–cat)-CoIII and then to CoII-(spiroSQ–SQ)-CoII in both solid and solution states. This is the first time a two-step valence tautomeric (VT) transition has been observed in solution. Partial photoinduction of the VT transition is also possible in the solid. Magnetic and spectroscopic studies of 5 and 6 reveal that spiroconjugation of the bis(dioxolene) ligand allows electronic interaction across the spiro bridge, suggesting that thermally activated vibronic coupling between the two cobalt-dioxolene moieties plays a key role in the two-step transition evident for 3.
Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the ...genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.
A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated ...gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics ...of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
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