Chemistry and Kinematics of the Late-Forming Dwarf Irregular Galaxies Leo A, Aquarius, and Sagittarius DIG

We present Keck/DEIMOS spectroscopy of individual stars in the relatively isolated Local Group dwarf galaxies Leo A, Aquarius, and the Sagittarius dwarf irregular galaxy. The three galaxies—but especially Leo A and Aquarius—share in common delayed star formation histories (SFHs) relative to many other isolated dwarf galaxies. The stars in all three galaxies are supported by dispersion. We found no evidence of stellar velocity structure, even for Aquarius, which has rotating H i gas. The velocity dispersions indicate that all three galaxies are dark-matter-dominated, with dark-to-baryonic mass ratios ranging from 4.4_(-0.8)^(+1.0) (SagDIG) to 9.6_(-1.8)^(+2.5) (Aquarius). Leo A and SagDIG have lower stellar metallicities than Aquarius, and they also have higher gas fractions, both of which would be expected if Aquarius were further along in its chemical evolution. The metallicity distribution of Leo A is inconsistent with a closed or leaky box model of chemical evolution, suggesting that the galaxy was pre-enriched or acquired external gas during star formation. The metallicities of stars increased steadily for all three galaxies, but possibly at different rates. The [α/Fe] ratios at a given [Fe/H] are lower than that of the Sculptor dwarf spheroidal galaxy, which indicates more extended SFHs than Sculptor, consistent with photometrically derived SFHs. Overall, the bulk kinematic and chemical properties for the late-forming dwarf galaxies do not diverge significantly from those of less delayed dwarf galaxies, including dwarf spheroidal galaxies

STING-dependent interferon signatures restrict osteoclast differentiation and bone loss in mice

Stimulator of interferon genes (STING) is a key mediator of type-I interferon (IFN-I) signaling in response to a variety of stimuli, but the contribution of STING to homeostatic processes is not fully characterized. Previous studies showed that ligand activation of STING limits osteoclast differentiation in vitro through the induction of IFNβ and IFN-I interferon-stimulated genes (ISGs). In a disease model (SAVI) driven by the V154M gain-of-function mutation in STING, fewer osteoclasts form from SAVI precursors in response to receptor activator of NF-kappaB ligand (RANKL) in an IFN-I-dependent manner. Due to the described role of STING-mediated regulation of osteoclastogenesis in activation settings, we sought to determine whether basal STING signaling contributes to bone homeostasis, an unexplored area. Using whole-body and myeloid-specific deficiency, we show that STING signaling prevents trabecular bone loss in mice over time and that myeloid-restricted STING activity is sufficient for this effect. STING-deficient osteoclast precursors differentiate with greater efficiency than wild types. RNA sequencing of wild-type and STING-deficient osteoclast precursor cells and differentiating osteoclasts reveals unique clusters of ISGs including a previously undescribed ISG set expressed in RANKL naïve precursors (tonic expression) and down-regulated during differentiation. We identify a 50 gene tonic ISG signature that is STING dependent and shapes osteoclast differentiation. From this list, we identify interferon-stimulated gene 15 (ISG15) as a tonic STING-regulated ISG that limits osteoclast formation. Thus, STING is an important upstream regulator of tonic IFN-I signatures shaping the commitment to osteoclast fates, providing evidence for a nuanced and unique role for this pathway in bone homeostasis

Interannual Variability in Methane and Nitrous Oxide Concentrations and Sea-Air Fluxes Across the North American Arctic Ocean (2015–2019)

Between 2015 and 2018, we collected approximately 2,000 water column measurements of methane (CH4) and nitrous oxide (N2O) concentrations in the North American Arctic Ocean during summer and early fall. We also obtained 25 measurements of CH4 and N2O concentrations in rivers along the Northwest Passage and Ellesmere Island in midsummer 2017–2019. Our results show that N2O is generated in the highly productive Bering and Chukchi Seas and transported northeastward, producing a persistent subsurface N2O peak in the Beaufort Sea. The Chukchi and Beaufort Sea sediments are a significant source of CH4 to the water column. These sedimentary sources and associated water column consumption display significant spatial gradients and interannual variability. CH4 isotope data demonstrate the importance of CH4 oxidation across the study region. We find that rivers are not a significant source of CH4 or N2O to the Arctic Ocean at the time of year sampled. The estimated annual sea-air flux across the study region (2.3 million km2) had a median (first quartile, third quartile) of 0.009 (0.002, 0.023) Tg CH4 y−1 and −0.003 (−0.013, 0.010) Tg N y−1. These results suggest that the North American Arctic Ocean currently plays a negligible role in global CH4 and N2O budgets. Our expansive data set, with observations at many repeat stations, provides a synopsis of present-day Arctic CH4 and N2O distributions and their range of variability, as well as a benchmark against which future climatedependent changes can be evaluated

Global variations in H2O/Ce: 1. Slab surface temperatures beneath volcanic arcs

We have calculated slab fluid temperatures for 51 volcanoes in 10 subduction zones using the newly developed H2O/Ce thermometer. The slab fluid compositions were calculated from arc eruptives, using melt inclusion-based H2O contents, and were corrected for background mantle contributions. The temperatures, adjusted to h, the vertical depth to the slab beneath the volcanic arc, range from ~730 to 900°C and agree well (within 30°C on average for each arc) with sub-arc slab surface temperatures predicted by recent thermal models. The coherence between slab model and surface observation implies predominantly vertical transport of fluids within the mantle wedge. Slab surface temperatures are well reconciled with the thermal parameter (the product of slab age and vertical descent rate) and h. Arcs with shallow h (~80 to 100 km) yield a larger range in slab surface temperature (up to ~200°C between volcanoes) and more variable magma compositions than arcs with greater h (~120 to 180 km). This diversity is consistent with coupling of the subducting slab and mantle wedge, and subsequent rapid slab heating, at ~80 km. Slab surface temperatures at or warmer than the H2O-saturated solidus suggest that melting at the slab surface is common beneath volcanic arcs. Our results imply that hydrous melts or solute-rich supercritical fluids, and not H2O-rich aqueous fluids, are thus the agents of mass transport to the mantle wedge

Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1

Aberrant activation of the mammalian target of rapamycin complex 1 (mTORC1) is a common molecular event in a variety of pathological settings, including genetic tumor syndromes, cancer, and obesity. However, the cell-intrinsic consequences of mTORC1 activation remain poorly defined. Through a combination of unbiased genomic, metabolomic, and bioinformatic approaches, we demonstrate that mTORC1 activation is sufficient to stimulate specific metabolic pathways, including glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid biosynthesis. This is achieved through the activation of a transcriptional program affecting metabolic gene targets of hypoxia-inducible factor (HIF1α) and sterol regulatory element-binding protein (SREBP1 and SREBP2). We find that SREBP1 and 2 promote proliferation downstream of mTORC1, and the activation of these transcription factors is mediated by S6K1. Therefore, in addition to promoting protein synthesis, mTORC1 activates specific bioenergetic and anabolic cellular processes that are likely to contribute to human physiology and disease

Combatting global grassland degradation

Grasslands are under severe threat from ongoing degradation, undermining their capacity to support biodiversity, ecosystem services and human well-being. Yet, grasslands are largely ignored in sustainable development agendas. In this Perspective, we examine the current state of global grasslands and explore the extent and dominant drivers of their degradation. Socio-ecological solutions are needed to combat degradation and promote restoration. Important strategies include: increasing recognition of grasslands in global policy; developing standardized indicators of degradation; using scientific innovation for effective restoration at regional and landscape scales; and enhancing knowledge transfer and data sharing on restoration experiences. Stakeholder needs can be balanced through standardized assessment and shared understanding of the potential ecosystem service trade-offs in degraded and restored grasslands. The integration of these actions into sustainability policy will aid in halting degradation and enhancing restoration success, and protect the socio-economic, cultural and ecological benefits that grasslands provide

Genotyping of Streptococcus agalactiae (group B streptococci) isolated from vaginal and rectal swabs of women at 35-37 weeks of pregnancy

<p>Abstract</p> <p>Background</p> <p>Group B streptococci (GBS), or <it>Streptococcus agalactiae</it>, are the leading bacterial cause of meningitis and bacterial sepsis in newborns. Here we compared different culture media for GBS detection and we compared the occurrence of different genotypes and serotypes of GBS isolates from the vagina and rectum.</p> <p>Methods</p> <p><it>Streptococcus agalactiae </it>was cultured separately from both rectum and vagina, for a total of 150 pregnant women, i) directly onto Columbia CNA agar, or indirectly onto ii) Granada agar resp. iii) Columbia CNA agar, after overnight incubation in Lim broth.</p> <p>Results</p> <p>Thirty six women (24%) were colonized by GBS. Of these, 19 harbored GBS in both rectum and vagina, 9 only in the vagina and 8 exclusively in the rectum. The combination of Lim broth and subculture on Granada agar was the only culture method that detected all GBS positive women. Using RAPD-analysis, a total of 66 genotypes could be established among the 118 isolates from 32 women for which fingerprinting was carried out. Up to 4 different genotypes in total (rectal + vaginal) were found for 4 women, one woman carried 3 different genotypes vaginally and 14 women carried two 2 different genotypes vaginally. Only two subjects were found to carry strains with the same genotype, although the serotype of both of these strains was different.</p> <p>Eighteen of the 19 subjects with GBS at both sites had at least one vaginal and one rectal isolate with the same genotype.</p> <p>We report the presence of two to four different genotypes in 22 (61%) of the 36 GBS positive women and the presence of identical genotypes in both sites for all women but one.</p> <p>Conclusion</p> <p>The combination of Lim broth and subculture on Granada medium provide high sensitivity for GBS detection from vaginal and rectal swabs from pregnant women. We established a higher genotypic diversity per individual than other studies, with up to four different genotypes among a maximum of 6 isolates per individual picked. Still, 18 of the 19 women with GBS from both rectum and vagina had at least one isolate from each sampling site with the same genotype.</p

Rationale and design of a longitudinal study of cerebral small vessel diseases, clinical and imaging outcomes in patients presenting with mild ischaemic stroke: Mild Stroke Study 3

Background: Cerebral small vessel disease is a major cause of dementia and stroke, visible on brain magnetic resonance imaging. Recent data suggest that small vessel disease lesions may be dynamic, damage extends into normal-appearing brain and microvascular dysfunctions include abnormal blood–brain barrier leakage, vasoreactivity and pulsatility, but much remains unknown regarding underlying pathophysiology, symptoms, clinical features and risk factors of small vessel disease. Patients and Methods: The Mild Stroke Study 3 is a prospective observational cohort study to identify risk factors for and clinical implications of small vessel disease progression and regression among up to 300 adults with non-disabling stroke. We perform detailed serial clinical, cognitive, lifestyle, physiological, retinal and brain magnetic resonance imaging assessments over one year; we assess cerebrovascular reactivity, blood flow, pulsatility and blood–brain barrier leakage on magnetic resonance imaging at baseline; we follow up to four years by post and phone. The study is registered ISRCTN 12113543. Summary: Factors which influence direction and rate of change of small vessel disease lesions are poorly understood. We investigate the role of small vessel dysfunction using advanced serial neuroimaging in a deeply phenotyped cohort to increase understanding of the natural history of small vessel disease, identify those at highest risk of early disease progression or regression and uncover novel targets for small vessel disease prevention and therapy

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF &lt;5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants