We report on the redshift measurement and CO line excitation of HERMES J105751.1+573027 (HLSW-01), a strongly lensed submillimeter galaxy discovered in Herschel/SPIRE observations as part of the ...Herschel Multi-tiered Extragalactic Survey (HerMES). HLSW-01 is an ultra-luminous galaxy with an intrinsic far-infrared luminosity of L FIR = 1.4 X 1013 L , and is lensed by a massive group of galaxies into at least four images with a total magnification of Delta *m = 10.9 ? 0.7. With the 100 GHz instantaneous bandwidth of the Z-Spec instrument on the Caltech Submillimeter Observatory, we robustly identify a redshift of z = 2.958 ? 0.007 for this source, using the simultaneous detection of four CO emission lines (J = 7 -> 6, J = 8 -> 7, J = 9 -> 8, and J = 10 -> 9). Combining the measured line fluxes for these high-J transitions with the J = 1 -> 0, J = 3 -> 2, and J = 5 -> 4 line fluxes measured with the Green Bank Telescope, the Combined Array for Research in Millimeter Astronomy, and the Plateau de Bure Interferometer, respectively, we model the physical properties of the molecular gas in this galaxy. We find that the full CO spectral line energy distribution is described well by warm, moderate-density gas with T kin = 86-235 K and cm--3. However, it is possible that the highest-J transitions are tracing a small fraction of very dense gas in molecular cloud cores, and two-component models that include a warm/dense molecular gas phase with T kin ~ 200 K, cm--3 are also consistent with these data. Higher signal-to-noise measurements of the J up >= 7 transitions with high spectral resolution, combined with high spatial resolution CO maps, are needed to improve our understanding of the gas excitation, morphology, and dynamics of this interesting high-redshift galaxy.
Little is known about reproductive health in severely obese women. In this study, we present associations between different levels of severe obesity and a wide range of health outcomes in the mother ...and child.
From the Danish National Birth Cohort, we obtained self-reported information about prepregnant body mass index (BMI) for 2451 severely obese women and 2450 randomly selected women from the remaining cohort who served as a comparison group. Information about maternal and infant outcomes was also self-reported or came from registers. Logistic regression was used to estimate the association between different levels of severe obesity and reproductive outcomes.
Subfecundity was more frequent in severely obese women, and during pregnancy, they had an excess risk of urinary tract infections, gestational diabetes, preeclampsia and other hypertensive disorders which increased with severity of obesity. They tended to have a higher risk of both pre- and post-term birth, and risk of cesarean and instrumental deliveries increased across obesity categories. After birth, severely obese women more often failed to initiate or sustain breastfeeding. Risk of weight retention 1.5 years after birth was similar to that of other women, but after adjustment for gestational weight gain, the risk was increased, especially in women in the lowest obesity category. In infants, increasing maternal obesity was associated with decreased risk of a low birth weight and increased risk of a high birth weight. Estimates for ponderal index showed the same pattern indicating an increasing risk of neonatal fatness with severity of obesity. Infant obesity measured one year after birth was also increased in children of severely obese mothers.
Severe obesity is correlated with a substantial disease burden in reproductive health. Although the causal mechanisms remain elusive, these findings are useful for making predictions and planning health care at the individual level.
Panchromatic observations of the best candidate hyperluminous infrared galaxies from the widest Herschel extragalactic imaging survey have led to the discovery of at least four intrinsically luminous ...z = 2.41 galaxies across an approximately 100 kpc region-a cluster of starbursting protoellipticals. Via subarcsecond interferometric imaging we have measured accurate gas and star formation surface densities. The two brightest galaxies span ~3 kpc FWHM in submillimeter/radio continuum and CO J = 4-3, and double that in CO J = 1-0. The broad CO line is due partly to the multitude of constituent galaxies and partly to large rotational velocities in two counter-rotating gas disks-a scenario predicted to lead to the most intense starbursts, which will therefore come in pairs. The disks have M sub(dyn) of several x 10 super(11) M sub(middot in circle) and gas fractions of ~40%. Velocity dispersions are modest so the disks are unstable, potentially on scales commensurate with their radii: these galaxies are undergoing extreme bursts of star formation, not confined to their nuclei, at close to the Eddington limit. Their specific star formation rates place them gap 5x above the main sequence, which supposedly comprises large gas disks like these. Their high star formation efficiencies are difficult to reconcile with a simple volumetric star formation law. N-body and dark matter simulations suggest that this system is the progenitor of a B(inary)-type gap 10 super(14.6)-M sub(mid dot in circle) cluster.
The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis. The study of synovial tissue has advanced considerably throughout the past few decades from ...arthroplasty and blind needle biopsy to the use of arthroscopic and ultrasonographic technologies that enable easier visualization and improve the reliability of synovial biopsies. Rapid progress has been made in using synovial tissue to study disease pathogenesis, to stratify patients, to discover biomarkers and novel targets, and to validate therapies, and this progress has been facilitated by increasingly diverse and sophisticated analytical and technological approaches. In this Review, we describe these approaches, and summarize how their use in synovial tissue research has improved our understanding of rheumatoid arthritis and identified candidate biomarkers that could be used in disease diagnosis and stratification, as well as in predicting disease course and treatment response.
We present multiwavelength studies of the 106.6 ms gamma-ray pulsar PSR J1907+06 near the TeV source MGRO J1908+06. Timing observations with Fermi result in a precise position determination for the ...pulsar of R.A. = 19h07m547(2), decl. = +06:02:16(2) placing the pulsar firmly within the TeV source extent, suggesting the TeV source is the pulsar wind nebula of PSR J1907+0602. Pulsed gamma-ray emission is clearly visible at energies from 100 MeV to above 10 GeV. The phase-averaged power-law index in the energy range E > 0.1 GeV is = 1.76 \pm 0.05 with an exponential cutoff energy E_{c} = 3.6 \pm 0.5 GeV. We present the energy-dependent gamma-ray pulsed light curve as well as limits on off-pulse emission associated with the TeV source. We also report the detection of very faint (flux density of ~3.4 microJy) radio pulsations with the Arecibo telescope at 1.5 GHz having a dispersion measure DM = 82.1 \pm 1.1 cm^{-3}pc. This indicates a distance of 3.2 \pm 0.6 kpc and a pseudo-luminosity of L_{1400} ~ 0.035 mJy kpc^2. A Chandra ACIS observation revealed an absorbed, possibly extended, compact <(4 arcsec) X-ray source with significant non-thermal emission at R.A. = 19h07m54.76, decl. = +06:02:14.6 with a flux of 2.3^{+0.6}_{-1.4} X 10^{-14} erg cm^{-2} s^{-1}. From archival ASCA observations, we place upper limits on any arcminute scale 2--10 keV X-ray emission of ~ 1 X 10^{-13} erg cm^{-2} s^{-1}. The implied distance to the pulsar is compatible with that of the supernova remnant G40.5-0.5, located on the far side of the TeV nebula from PSR J1907+0602, and the S74 molecular cloud on the nearer side which we discuss as potential birth sites.
Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the ...precise neuronal populations and cellular mechanisms involved are unclear. The effects of long-term manipulation of hypothalamic AMPK on energy balance are also unknown. To directly address such issues, we generated POMC alpha 2KO and AgRP alpha 2KO mice lacking AMPK alpha2 in proopiomelanocortin- (POMC-) and agouti-related protein-expressing (AgRP-expressing) neurons, key regulators of energy homeostasis. POMC alpha 2KO mice developed obesity due to reduced energy expenditure and dysregulated food intake but remained sensitive to leptin. In contrast, AgRP alpha 2KO mice developed an age-dependent lean phenotype with increased sensitivity to a melanocortin agonist. Electrophysiological studies in AMPK alpha2-deficient POMC or AgRP neurons revealed normal leptin or insulin action but absent responses to alterations in extracellular glucose levels, showing that glucose-sensing signaling mechanisms in these neurons are distinct from those pathways utilized by leptin or insulin. Taken together with the divergent phenotypes of POMC alpha 2KO and AgRP alpha 2KO mice, our findings suggest that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus.
The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We ...aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes.
We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis.
Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m
, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio RR per interquintile range 0·65, 95% CI 0·60-0·72, p<0·0001; I
=53·9%, p
=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88-1·05; p=0·38; I
=63·0%, p
<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all p
≥0·13).
Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.
Funders are shown in the appendix.
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