A Hindbrain Inhibitory Microcircuit Mediates Vagally-Coordinated Glucose Regulation

Neurons in the brainstem dorsal vagal complex integrate neural and humoral signals to coordinate autonomic output to viscera that regulate a variety of physiological functions, but how this circuitry regulates metabolism is murky. We tested the hypothesis that premotor, GABAergic neurons in the nucleus tractus solitarius (NTS) form a hindbrain micro-circuit with preganglionic parasympathetic motorneurons of the dorsal motor nucleus of the vagus (DMV) that is capable of modulating systemic blood glucose concentration. In vitro, neuronal activation or inhibition using either excitatory or inhibitory designer receptor exclusively activated by designer drugs (DREADDs) constructs expressed in GABAergic NTS neurons increased or decreased, respectively, action potential firing of GABAergic NTS neurons and downstream synaptic inhibition of the DMV. In vivo, DREADD-mediated activation of GABAergic NTS neurons increased systemic blood glucose concentration, whereas DREADD-mediated silencing of these neurons was without effect. The DREADD-induced hyperglycemia was abolished by blocking peripheral muscarinic receptors, consistent with the hypothesis that altered parasympathetic drive mediated the response. This effect was paralleled by elevated serum glucagon and hepatic phosphoenolpyruvate carboxykinase 1 (PEPCK1) expression, without affecting insulin levels or muscle metabolism. Activity in a hindbrain inhibitory microcircuit is sufficient to modulate systemic glucose concentration, independent of insulin secretion or utilization

The Hubble Constant

I review the current state of determinations of the Hubble constant, which gives the length scale of the Universe by relating the expansion velocity of objects to their distance. There are two broad categories of measurements. The first uses individual astrophysical objects which have some property that allows their intrinsic luminosity or size to be determined, or allows the determination of their distance by geometric means. The second category comprises the use of all-sky cosmic microwave background, or correlations between large samples of galaxies, to determine information about the geometry of the Universe and hence the Hubble constant, typically in a combination with other cosmological parameters. Many, but not all, object-based measurements give $H_0$ values of around 72-74km/s/Mpc , with typical errors of 2-3km/s/Mpc. This is in mild discrepancy with CMB-based measurements, in particular those from the Planck satellite, which give values of 67-68km/s/Mpc and typical errors of 1-2km/s/Mpc. The size of the remaining systematics indicate that accuracy rather than precision is the remaining problem in a good determination of the Hubble constant. Whether a discrepancy exists, and whether new physics is needed to resolve it, depends on details of the systematics of the object-based methods, and also on the assumptions about other cosmological parameters and which datasets are combined in the case of the all-sky methods.Comment: Extensively revised and updated since the 2007 version: accepted by Living Reviews in Relativity as a major (2014) update of LRR 10, 4, 200

Two-year changes in quality of life in elderly patients with low-energy hip fractures. A case-control study

<p>Abstract</p> <p>Background</p> <p>The long-term effect of hip fracture on health-related quality of life (HRQOL) and global quality of life (GQOL) has not been thoroughly studied in prospective case-control studies.</p> <p>Aims</p> <p>a) to explore whether patients with low-energy hip fracture regain their pre-fracture levels in HRQOL and GQOL compared with changes in age- and sex-matched controls over a two year period; b) to identify predictors of changes in HRQOL and GQOL after two years.</p> <p>Methods</p> <p>We examined 61 patients (mean age = 74 years, <it>SD </it>= 10) and 61 matched controls (mean age = 73 years, <it>SD </it>= 8). The Short Form 36 assessed HRQOL and the Quality of Life Scale assessed GQOL. Paired samples <it>t </it>tests and multiple linear regression analyses were applied.</p> <p>Results</p> <p>HRQOL decreased significantly between baseline and one-year follow-up in patients with hip fractures, within all the SF-36 domains (<it>p </it>< 0.04), except for social functioning (<it>p </it>= 0.091). There were no significant decreases within the SF-36 domains in the controls. Significantly decreased GQOL scores (<it>p </it>< 0.001) were observed both within patients and within controls between baseline and one-year follow-up. The same pattern persisted between baseline and two-year follow-up, except for the HRQOL domain mental health (<it>p </it>= 0.193). The patients with hip fractures did not regain their HRQOL and GQOL. Worsened physical health after two years was predicted by being a patient with hip fracture (B = -5.8, <it>p </it>< 0.001) and old age (B = -1.0, <it>p </it>= 0.015), while worsened mental health was predicted by co-morbidity (B = -2.2, <it>p </it>= 0.029). No significant predictors of differential changes in GQOL were identified.</p> <p>Conclusion</p> <p>A hip fracture has a long-term impact on HRQOL and is a strong predictor of worsened physical health. Our data emphasize the importance of preventing hip fracture in the elderly to maintain physical health. This knowledge should be included in decision-making and health care plans.</p

X-ray Absorption and Reflection in Active Galactic Nuclei

X-ray spectroscopy offers an opportunity to study the complex mixture of emitting and absorbing components in the circumnuclear regions of active galactic nuclei, and to learn about the accretion process that fuels AGN and the feedback of material to their host galaxies. We describe the spectral signatures that may be studied and review the X-ray spectra and spectral variability of active galaxies, concentrating on progress from recent Chandra, XMM-Newton and Suzaku data for local type 1 AGN. We describe the evidence for absorption covering a wide range of column densities, ionization and dynamics, and discuss the growing evidence for partial-covering absorption from data at energies > 10 keV. Such absorption can also explain the observed X-ray spectral curvature and variability in AGN at lower energies and is likely an important factor in shaping the observed properties of this class of source. Consideration of self-consistent models for local AGN indicates that X-ray spectra likely comprise a combination of absorption and reflection effects from material originating within a few light days of the black hole as well as on larger scales. It is likely that AGN X-ray spectra may be strongly affected by the presence of disk-wind outflows that are expected in systems with high accretion rates, and we describe models that attempt to predict the effects of radiative transfer through such winds, and discuss the prospects for new data to test and address these ideas.Comment: Accepted for publication in the Astronomy and Astrophysics Review. 58 pages, 9 figures. V2 has fixed an error in footnote

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

A Tale of Four “Carp”: Invasion Potential and Ecological Niche Modeling

. We assessed the geographic potential of four Eurasian cyprinid fishes (common carp, tench, grass carp, black carp) as invaders in North America via ecological niche modeling (ENM). These “carp” represent four stages of invasion of the continent (a long-established invader with a wide distribution, a long-established invader with a limited distribution, a spreading invader whose distribution is expanding, and a newly introduced potential invader that is not yet established), and as such illustrate the progressive reduction of distributional disequilibrium over the history of species' invasions.We used ENM to estimate the potential distributional area for each species in North America using models based on native range distribution data. Environmental data layers for native and introduced ranges were imported from state, national, and international climate and environmental databases. Models were evaluated using independent validation data on native and invaded areas. We calculated omission error for the independent validation data for each species: all native range tests were highly successful (all omission values <7%); invaded-range predictions were predictive for common and grass carp (omission values 8.8 and 19.8%, respectively). Model omission was high for introduced tench populations (54.7%), but the model correctly identified some areas where the species has been successful; distributional predictions for black carp show that large portions of eastern North America are at risk.ENMs predicted potential ranges of carp species accurately even in regions where the species have not been present until recently. ENM can forecast species' potential geographic ranges with reasonable precision and within the short screening time required by proposed U.S. invasive species legislation

The development of contour processing : evidence from physiology and psychophysics

Object perception and pattern vision depend fundamentally upon the extraction of contours from the visual environment. In adulthood, contour or edge-level processing is supported by the Gestalt heuristics of proximity, collinearity, and closure. Less is known, however, about the developmental trajectory of contour detection and contour integration. Within the physiology of the visual system, long-range horizontal connections in V1 and V2 are the likely candidates for implementing these heuristics. While post-mortem anatomical studies of human infants suggest that horizontal interconnections reach maturity by the second year of life, psychophysical research with infants and children suggests a considerably more protracted development. In the present review, data from infancy to adulthood will be discussed in order to track the development of contour detection and integration. The goal of this review is thus to integrate the development of contour detection and integration with research regarding the development of underlying neural circuitry.We conclude that the ontogeny of this system is best characterized as a developmentally extended period of associative acquisition whereby horizontal connectivity becomes functional over longer and longer distances, thus becoming able to effectively integrate over greater spans of visual space. Keywords

Effect of Calcium Supplementation on Blood Lead Levels in Pregnancy: A Randomized Placebo-Controlled Trial

Background: Prenatal lead exposure is associated with deficits in fetal growth and neurodevelopment. Calcium supplementation may attenuate fetal exposure by inhibiting mobilization of maternal bone lead and/or intestinal absorption of ingested lead. Objective: Our goal was to evaluate the effect of 1,200 mg dietary calcium supplementation on maternal blood lead levels during pregnancy. Methods: In a double-blind, randomized, placebo-controlled trial conducted from 2001 through 2003 in Mexico City, we randomly assigned 670 women in their first trimester of pregnancy to ingest calcium (n = 334) or placebo (n = 336). We followed subjects through pregnancy and evaluated the effect of supplementation on maternal blood lead, using an intent-to-treat analysis by a mixed-effects regression model with random intercept, in 557 participants (83%) who completed follow-up. We then conducted as-treated analyses using similar models stratified by treatment compliance. Results: Adjusting for baseline lead level, age, trimester of pregnancy, and dietary energy and calcium intake, calcium was associated with an average 11% reduction (0.4 μg/dL) in blood lead level relative to placebo (p = 0.004). This reduction was more evident in the second trimester (−14%, p lesss than 0.001) than in the third (−8%, p = 0.107) and was strongest in women who were most compliant (those who consumed ≥ 75% calcium pills; −24%, p less than 0.001), had baseline blood lead greater than 5 μg/dL (−17%, p less than 0.01), or reported use of lead-glazed ceramics and high bone lead (−31%, p less than 0.01). Conclusion: Calcium supplementation was associated with modest reductions in blood lead when administered during pregnancy and may constitute an important secondary prevention effort to reduce circulating maternal lead and, consequently, fetal exposure

Higher-order multipole amplitudes in charmonium radiative transitions

Using 24 million $\psi' \equiv \psi(2S)$ decays in CLEO-c, we have searched for higher multipole admixtures in electric-dipole-dominated radiative transitions in charmonia. We find good agreement between our data and theoretical predictions for magnetic quadrupole (M2) amplitudes in the transitions $\psi' \to \gamma \chi_{c1,2}$ and $\chi_{c1,2} \to \gamma J/\psi$, in striking contrast to some previous measurements. Let $b_2^J$ and $a_2^J$ denote the normalized M2 amplitudes in the respective aforementioned decays, where the superscript $J$ refers to the angular momentum of the $\chi_{cJ}$. By performing unbinned maximum likelihood fits to full five-parameter angular distributions, we determine the ratios $a_2^{J=1}/a_2^{J=2} = 0.67^{+0.19}_{-0.13}$ and $a_2^{J=1}/b_2^{J=1} = -2.27^{+0.57}_{-0.99}$, where the theoretical predictions are independent of the charmed quark magnetic moment and are $a_2^{J=1}/a_2^{J=2} = 0.676 \pm 0.071$ and $a_2^{J=1}/b_2^{J=1} = -2.27 \pm 0.16$.Comment: 32 pages, 7 figures, acceptance updat