Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss

Glucagon analogs show promise as components of next-generation, multi-target, anti-obesity therapeutics. The biology of chronic glucagon treatment, in particular, its ability to induce energy expenditure and weight loss, remains poorly understood. Using a long-acting glucagon analog, G108, we demonstrate that glucagon-mediated body weight loss is intrinsically linked to the hypoaminoacidemia associated with its known amino acid catabolic action. Mechanistic studies reveal an energy-consuming response to low plasma amino acids in G108-treated mice, prevented by dietary amino acid supplementation and mimicked by a rationally designed low amino acid diet. Therefore, low plasma amino acids are a pre-requisite for G108-mediated energy expenditure and weight loss. However, preventing hypoaminoacidemia with additional dietary protein does not affect the ability of G108 to improve glycemia or hepatic steatosis in obese mice. These studies provide a mechanism for glucagon-mediated weight loss and confirm the hepatic glucagon receptor as an attractive molecular target for metabolic disease therapeutics

Facial expressions depicting compassionate and critical emotions: the development and validation of a new emotional face stimulus set

Attachment with altruistic others requires the ability to appropriately process affiliative and kind facial cues. Yet there is no stimulus set available to investigate such processes. Here, we developed a stimulus set depicting compassionate and critical facial expressions, and validated its effectiveness using well-established visual-probe methodology. In Study 1, 62 participants rated photographs of actors displaying compassionate/kind and critical faces on strength of emotion type. This produced a new stimulus set based on N = 31 actors, whose facial expressions were reliably distinguished as compassionate, critical and neutral. In Study 2, 70 participants completed a visual-probe task measuring attentional orientation to critical and compassionate/kind faces. This revealed that participants lower in self-criticism demonstrated enhanced attention to compassionate/kind faces whereas those higher in self-criticism showed no bias. To sum, the new stimulus set produced interpretable findings using visual-probe methodology and is the first to include higher order, complex positive affect displays

Disease Detection by Ultrasensitive Quantification of Microdosed Synthetic Urinary Biomarkers

The delivery of exogenous agents can enable noninvasive disease monitoring, but existing low-dose approaches require complex infrastructure. In this paper, we describe a microdose-scale injectable formulation of nanoparticles that interrogate the activity of thrombin, a key regulator of clotting, and produce urinary reporters of disease state. We establish a customized single molecule detection assay that enables urinary discrimination of thromboembolic disease in mice using doses of the nanoparticulate diagnostic agents that fall under regulatory guidelines for “microdosing.”National Science Foundation (U.S.). Graduate Research FellowshipNational Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award F32CA159496-02)Burroughs Wellcome Fund (Career Award at the Scientific Interface)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)David H. Koch Institute for Integrative Cancer Research at MIT (Frontier Research Program

The Physical Nature of Lyman Alpha Emitting Galaxies at z=3.1

We selected 40 candidate Lyman Alpha Emitting galaxies (LAEs) at z ~=3.1 with observed frame equivalent widths >150A and inferred emission line fluxes >2.5x10^-17 ergs/cm^2/s from deep narrow-band and broad-band MUSYC images of the Extended Chandra Deep Field South. Covering 992 sq. arcmin, this is the largest ``blank field'' surveyed for LAEs at z ~3, allowing an improved estimate of the space density of this population of 3+-1x10^-4 h_70^3/Mpc^3. Spectroscopic follow-up of 23 candidates yielded 18 redshifts, all at z ~=3.1. Over 80% of the LAEs are dimmer in continuum magnitude than the typical Lyman break galaxy spectroscopic limit of R= 25.5 (AB), with a median continuum magnitude R ~=27 and very blue continuum colors, (V-z) ~=0. Over 80% of the LAEs have the right UVR colors to be selected as Lyman break galaxies, but only 10% also have R<=25.5. Stacking the UBVRIzJK fluxes reveals that LAEs have stellar masses ~=5x10^8 h_70^-2 M_sun and minimal dust extinction, A_V < ~ 0.1. Inferred star formation rates are ~=6 h_70^-2 M_sun/yr, yielding a cosmic star formation rate density of 2x10^-3 h_70 M_sun/yr/Mpc^3. None of our LAE candidates show evidence for rest-frame emission line equivalent widths EW_rest>240A which might imply a non-standard IMF. One candidate is detected by Chandra, implying an AGN fraction of 2+-2% for LAE candidate samples. In summary, LAEs at z ~ 3 have rapid star formation, low stellar mass, little dust obscuration and no evidence for a substantial AGN component.Comment: ApJ Letters, in press, very minor revisions to match accepted version, 4 pages with 2 color figure

Highly functionalized organic nitrates in the southeast United States : Contribution to secondary organic aerosol and reactive nitrogen budgets

Speciated particle-phase organic nitrates (pONs) were quantified using online chemical ionization MS during June and July of 2013 in rural Alabama as part of the Southern Oxidant and Aerosol Study. A large fraction of pONs is highly functionalized, possessing between six and eight oxygen atoms within each carbon number group, and is not the common first generation alkyl nitrates previously reported. Using calibrations for isoprene hydroxynitrates and the measured molecular compositions, we estimate that pONs account for 3% and 8% of total submicrometer organic aerosol mass, on average, during the day and night, respectively. Each of the isoprene-and monoterpenes-derived groups exhibited a strong diel trend consistent with the emission patterns of likely biogenic hydrocarbon precursors. An observationally constrained diel box model can replicate the observed pON assuming that pONs (i) are produced in the gas phase and rapidly establish gas-particle equilibrium and (ii) have a short particle-phase lifetime (similar to 2-4 h). Such dynamic behavior has significant implications for the production and phase partitioning of pONs, organic aerosol mass, and reactive nitrogen speciation in a forested environment.Peer reviewe

Engineering Corynebacterium glutamicum for isobutanol production

The production of isobutanol in microorganisms has recently been achieved by harnessing the highly active 2-keto acid pathways. Since these 2-keto acids are precursors of amino acids, we aimed to construct an isobutanol production platform in Corynebacterium glutamicum, a well-known amino-acid-producing microorganism. Analysis of this host’s sensitivity to isobutanol toxicity revealed that C. glutamicum shows an increased tolerance to isobutanol relative to Escherichia coli. Overexpression of alsS of Bacillus subtilis, ilvC and ilvD of C. glutamicum, kivd of Lactococcus lactis, and a native alcohol dehydrogenase, adhA, led to the production of 2.6 g/L isobutanol and 0.4 g/L 3-methyl-1-butanol in 48 h. In addition, other higher chain alcohols such as 1-propanol, 2-methyl-1-butanol, 1-butanol, and 2-phenylethanol were also detected as byproducts. Using longer-term batch cultures, isobutanol titers reached 4.0 g/L after 96 h with wild-type C. glutamicum as a host. Upon the inactivation of several genes to direct more carbon through the isobutanol pathway, we increased production by ∼25% to 4.9 g/L isobutanol in a ∆pyc∆ldh background. These results show promise in engineering C. glutamicum for higher chain alcohol production using the 2-keto acid pathways

Reading Speed, Comprehension and Eye Movements While Reading Japanese Novels: Evidence from Untrained Readers and Cases of Speed-Reading Trainees

BACKGROUND: A growing body of evidence suggests that meditative training enhances perception and cognition. In Japan, the Park-Sasaki method of speed-reading involves organized visual training while forming both a relaxed and concentrated state of mind, as in meditation. The present study examined relationships between reading speed, sentence comprehension, and eye movements while reading short Japanese novels. In addition to normal untrained readers, three middle-level trainees and one high-level expert on this method were included for the two case studies. METHODOLOGY/PRINCIPAL FINDINGS: In Study 1, three of 17 participants were middle-level trainees on the speed-reading method. Immediately after reading each story once on a computer monitor, participants answered true or false questions regarding the content of the novel. Eye movements while reading were recorded using an eye-tracking system. Results revealed higher reading speed and lower comprehension scores in the trainees than in the untrained participants. Furthermore, eye-tracking data by untrained participants revealed multiple correlations between reading speed, accuracy and eye-movement measures, with faster readers showing shorter fixation durations and larger saccades in X than slower readers. In Study 2, participants included a high-level expert and 14 untrained students. The expert showed higher reading speed and statistically comparable, although numerically lower, comprehension scores compared with the untrained participants. During test sessions this expert moved her eyes along a nearly straight horizontal line as a first pass, without moving her eyes over the whole sentence display as did the untrained students. CONCLUSIONS/SIGNIFICANCE: In addition to revealing correlations between speed, comprehension and eye movements in reading Japanese contemporary novels by untrained readers, we describe cases of speed-reading trainees regarding relationships between these variables. The trainees overall tended to show poor performance influenced by the speed-accuracy trade-off, although this trade-off may be reduced in the case of at least one high-level expert

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Towards an Embodied Sociology of War

While sociology has historically not been a good interlocutor of war, this paper argues that the body has always known war, and that it is to the corporeal that we can turn in an attempt to develop a language to better speak of its myriad violences and its socially generative force. It argues that war is a crucible of social change that is prosecuted, lived and reproduced via the occupation and transformation of myriad bodies in numerous ways from exhilaration to mutilation. War and militarism need to be traced and analysed in terms of their fundamental, diverse and often brutal modes of embodied experience and apprehension. This paper thus invites sociology to extend its imaginative horizon to rethink the crucial and enduring social institution of war as a broad array of fundamentally embodied experiences, practices and regimes