Pms2 suppresses large expansions of the (GAA·TTC)n sequence in neuronal tissues

Copyright @ 2012 Bourn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Expanded trinucleotide repeat sequences are the cause of several inherited neurodegenerative diseases. Disease pathogenesis is correlated with several features of somatic instability of these sequences, including further large expansions in postmitotic tissues. The presence of somatic expansions in postmitotic tissues is consistent with DNA repair being a major determinant of somatic instability. Indeed, proteins in the mismatch repair (MMR) pathway are required for instability of the expanded (CAG·CTG)(n) sequence, likely via recognition of intrastrand hairpins by MutSβ. It is not clear if or how MMR would affect instability of disease-causing expanded trinucleotide repeat sequences that adopt secondary structures other than hairpins, such as the triplex/R-loop forming (GAA·TTC)(n) sequence that causes Friedreich ataxia. We analyzed somatic instability in transgenic mice that carry an expanded (GAA·TTC)(n) sequence in the context of the human FXN locus and lack the individual MMR proteins Msh2, Msh6 or Pms2. The absence of Msh2 or Msh6 resulted in a dramatic reduction in somatic mutations, indicating that mammalian MMR promotes instability of the (GAA·TTC)(n) sequence via MutSα. The absence of Pms2 resulted in increased accumulation of large expansions in the nervous system (cerebellum, cerebrum, and dorsal root ganglia) but not in non-neuronal tissues (heart and kidney), without affecting the prevalence of contractions. Pms2 suppressed large expansions specifically in tissues showing MutSα-dependent somatic instability, suggesting that they may act on the same lesion or structure associated with the expanded (GAA·TTC)(n) sequence. We conclude that Pms2 specifically suppresses large expansions of a pathogenic trinucleotide repeat sequence in neuronal tissues, possibly acting independently of the canonical MMR pathway.IDB was supported by a postdoctoral fellowship from the National Ataxia Foundation. RMP was supported by Ataxia UK. SA was supported by The Wellcome Trust. This research was made possible by grants from the National Institutes of Health (NIH/NINDS) and the Muscular Dystrophy Association to S.I.B

Substellar Companions to Main Sequence Stars: No Brown Dwarf Desert at Wide Separations

We use three field L and T dwarfs which were discovered to be wide companions to known stars by the Two Micron All-Sky Survey (2MASS) to derive a preliminary brown dwarf companion frequency. Observed L and T dwarfs indicate that brown dwarfs are not unusually rare as wide (Delta >1000 A.U.) systems to F-M0 main-sequence stars (M>0.5M_sun, M_V<9.5), even though they are rare at close separation (Delta <3 A.U.), the ``brown dwarf desert.'' Stellar companions in these separation ranges are equally frequent, but brown dwarfs are >~ 10 times as frequent for wide than close separations. A brown dwarf wide-companion frequency as low as the 0.5% seen in the brown dwarf desert is ruled out by currently-available observations.Comment: ApJL, in pres

Nonalcoholic and Alcoholic Beverage Intakes by Adults across 5 Upper-Middle- and High-Income Countries.

BACKGROUND: Despite considerable public health interest in sugary drink consumption, there has been little comparison of intake across countries. OBJECTIVES: This study aimed to compare the consumption frequency and amounts of commonly consumed beverages among adults in 5 upper-middle- and high-income countries, and examine differences in consumption between population subgroups. METHODS: Adults aged 18-65 y completed online surveys in December 2017 in Australia (n = 3264), Canada (n = 2745), Mexico (n = 3152), the United Kingdom (n = 3221), and the USA (n = 4015) as part of the International Food Policy Study. The frequency of consuming beverages from 22 categories in the past 7 d was estimated using the Beverage Frequency Questionnaire. Regression models were used to examine differences in the likelihood of any consumption and in the amounts consumed of sugar-sweetened beverages (SSBs), sugary drinks (SSBs and 100% juice), diet, and alcoholic beverages between countries and across sociodemographic subgroups. RESULTS: The prevalence of reported SSB consumption in the past 7 d ranged from 47% (United Kingdom) to 81% (Mexico), and that of sugary drinks ranged from 62% (United Kingdom) to 87% (Mexico). Rates of consumption of diet drinks ranged from 26% (Mexico) to 37% (United Kingdom), whereas alcoholic drink consumption rates ranged from 45% (USA) to 52% (Canada). Respondents in Mexico were more likely to consume SSBs and sugary drinks, and in greater amounts, than those in other countries. Respondents in the United Kingdom were more likely to consume diet drinks than those in Australia, Canada, and Mexico, and greater amounts of diet drinks were consumed in the United Kingdom and the USA. Across countries, younger respondents and males were more likely to consume greater amounts of SSBs and sugary drinks. CONCLUSIONS: Most adult respondents across all countries consumed SSBs and sugary drinks, with greater consumption in Mexico and the USA. Consumption varied greatly across countries, but patterns of association among subpopulations were relatively similar.The first two waves of the International Food Policy Study were funded by a population health intervention research operating grant from the Canadian Institutes of Health Research (CIHR). Additional support was provided by a CIHR – Public Health Agency of Canada (PHAC) Applied Public Health Chair held by David Hammond. JA receives funding from the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. GS is supported by a Heart Foundation Future Leader Fellowship (102035) from the National Heart Foundation of Australia. He is also a researcher within National Health and Medical Research Council (NHMRC) Centres for Research Excellence entitled Reducing Salt Intake Using Food Policy Interventions (APP1117300) and a Centre of Research Excellence in Food Retail Environments for Health (RE-FRESH) (APP1152968) (Australia). He has also received other funding from the NHMRC, Australian Research Council (ARC) and the World Health Organization (WHO). Data described in the manuscript, code book, and analytic code will be made available upon request pending application and approval by DH

Ultracool Field Brown Dwarf Candidates Selected at 4.5 microns

We have identified a sample of cool field brown dwarf candidates using IRAC data from the Spitzer Deep, Wide-Field Survey (SDWFS). The candidates were selected from 400,000 SDWFS sources with [4.5] <= 18.5 mag and required to have [3.6]-[4.5] >= 1.5 and [4.5] - [8.0] <= 2.0 on the Vega system. The first color requirement selects objects redder than all but a handful of presently known brown dwarfs with spectral classes later than T7, while the second eliminates 14 probable reddened AGN. Optical detection of 4 of the remaining 18 sources implies they are likely also AGN, leaving 14 brown dwarf candidates. For two of the brightest candidates (SDWFS J143524.44+335334.6 and SDWFS J143222.82+323746.5), the spectral energy distributions including near-infrared detections suggest a spectral class of ~ T8. The proper motion is < 0.25 "/yr, consistent with expectations for a luminosity inferred distance of >70 pc. The reddest brown dwarf candidate (SDWFS J143356.62+351849.2) has [3.6] - [4.5]=2.24 and H - [4.5] > 5.7, redder than any published brown dwarf in these colors, and may be the first example of the elusive Y-dwarf spectral class. Models from Burrows et al. (2003) predict larger numbers of cool brown dwarfs should be found for a Chabrier (2003) mass function. Suppressing the model [4.5] flux by a factor of two, as indicated by previous work, brings the Burrows models and observations into reasonable agreement. The recently launched Wide-field Infrared Survey Explorer (WISE) will probe a volume ~40x larger and should find hundreds of brown dwarfs cooler than T7.Comment: 13 pages, 6 figures, accepted for publication in the June 2010 issue of The Astronomical Journa

Laser-controlled fluorescence in two-level systems

The ability to modify the character of fluorescent emission by a laser-controlled, optically nonlinear process has recently been shown theoretically feasible, and several possible applications have already been identified. In operation, a pulse of off-resonant probe laser beam, of sufficient intensity, is applied to a system exhibiting fluorescence, during the interval of excited- state decay following the initial excitation. The result is a rate of decay that can be controllably modified, the associated changes in fluorescence behavior affording new, chemically specific information. In this paper, a two-level emission model is employed in the further analysis of this all-optical process; the results should prove especially relevant to the analysis and imaging of physical systems employing fluorescent markers, these ranging from quantum dots to green fluorescence protein. Expressions are presented for the laser-controlled fluorescence anisotropy exhibited by samples in which the fluorophores are randomly oriented. It is also shown that, in systems with suitably configured electronic levels and symmetry properties, fluorescence emission can be produced from energy levels that would normally decay nonradiatively. © 2010 American Chemical Society

Correction: Faught et al. “Socioeconomic Disadvantage across the Life Course is associated with Diet Quality in Young Adulthood” Nutrients, 2019, 11(2), 242

We noticed an error in the text that requires correcting as it may contribute to an incorrect understanding of our study’s scientific conclusions. In the text accompanying Table 4 (Section 3.3: Mediation Analysis (Pathways Hypothesis), page 11), the third sentence in the paragraph reads: “Adult SEP at the level of university education mediated associations between childhood SEP and mean adult HEI-2015 score (p < 0.001).” This should in fact read: “Adult SEP at the level of high school or less mediated associations between childhood SEP and mean adult HEI-2015 score (p < 0.001).” This correction is consistent with the results presented in Table 4, and in line with the scientific conclusions discussed in the article that a low socioeconomic position (SEP) in adulthood mediates associations between childhood SEP and adult diet quality. SEP at the level of university education was the reference group in this analysis

The Spectra of T Dwarfs I: Near-Infrared Data and Spectral Classification

We present near-infrared spectra for a sample of T dwarfs, including eleven new discoveries made using the Two Micron All Sky Survey. These objects are distinguished from warmer (L-type) brown dwarfs by the presence of methane absorption bands in the 1--2.5 \micron spectral region. A first attempt at a near-infrared classification scheme for T dwarfs is made, based on the strengths of CH$_4$ and H$_2$O bands and the shapes of the 1.25, 1.6, and 2.1 \micron flux peaks. Subtypes T1 V through T8 V are defined, and spectral indices useful for classification are presented. The subclasses appear to follow a decreasing T$_{eff}$ scale, based on the evolution of CH$_4$ and H$_2$O bands and the properties of L and T dwarfs with known distances. However, we speculate that this scale is not linear with spectral type for cool dwarfs, due to the settling of dust layers below the photosphere and subsequent rapid evolution of spectral morphology around T$_{eff}$ $\sim$ 1300--1500 K. Similarities in near-infrared colors and continuity of spectral features suggest that the gap between the latest L dwarfs and earliest T dwarfs has been nearly bridged. This argument is strengthened by the possible role of CH$_4$ as a minor absorber shaping the K-band spectra of the latest L dwarfs. Finally, we discuss one peculiar T dwarf, 2MASS 0937+2931, which has very blue near-infrared colors (J-K$_s$ = $-0.89\pm$0.24) due to suppression of the 2.1 \micron peak. The feature is likely caused by enhanced collision-induced H$_2$ absorption in a high pressure or low metallicity photosphere.Comment: 74 pages including 26 figures, accepted by ApJ v563 December 2001; full paper including all of Table 3 may be downloaded from http://www.gps.caltech.edu/~pa/adam/classification ;also see submission 010844

The Science Case for an Extended Spitzer Mission

Although the final observations of the Spitzer Warm Mission are currently scheduled for March 2019, it can continue operations through the end of the decade with no loss of photometric precision. As we will show, there is a strong science case for extending the current Warm Mission to December 2020. Spitzer has already made major impacts in the fields of exoplanets (including microlensing events), characterizing near Earth objects, enhancing our knowledge of nearby stars and brown dwarfs, understanding the properties and structure of our Milky Way galaxy, and deep wide-field extragalactic surveys to study galaxy birth and evolution. By extending Spitzer through 2020, it can continue to make ground-breaking discoveries in those fields, and provide crucial support to the NASA flagship missions JWST and WFIRST, as well as the upcoming TESS mission, and it will complement ground-based observations by LSST and the new large telescopes of the next decade. This scientific program addresses NASA's Science Mission Directive's objectives in astrophysics, which include discovering how the universe works, exploring how it began and evolved, and searching for life on planets around other stars.Comment: 75 pages. See page 3 for Table of Contents and page 4 for Executive Summar

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

The CatWISE Preliminary Catalog: Motions from WISE{\it WISE} and NEOWISE{\it NEOWISE} Data

CatWISE is a program to catalog sources selected from combined ${\it WISE}$ and ${\it NEOWISE}$ all-sky survey data at 3.4 and 4.6 $\mu$m (W1 and W2). The CatWISE Preliminary Catalog consists of 900,849,014 sources measured in data collected from 2010 to 2016. This dataset represents four times as many exposures and spans over ten times as large a time baseline as that used for the AllWISE Catalog. CatWISE adapts AllWISE software to measure the sources in coadded images created from six-month subsets of these data, each representing one coverage of the inertial sky, or epoch. The catalog includes the measured motion of sources in 8 epochs over the 6.5 year span of the data. From comparison to ${\it Spitzer}$, the SNR=5 limits in magnitudes in the Vega system are W1=17.67 and W2=16.47, compared to W1=16.96 and W2=16.02 for AllWISE. From comparison to ${\it Gaia}$, CatWISE positions have typical accuracies of 50 mas for stars at W1=10 mag and 275 mas for stars at W1=15.5 mag. Proper motions have typical accuracies of 10 mas yr$^{-1}$ and 30 mas yr$^{-1}$ for stars with these brightnesses, an order of magnitude better than from AllWISE. The catalog is available in the WISE/NEOWISE Enhanced and Contributed Products area of the NASA/IPAC Infrared Science Archive.Comment: 53 pages, 20 figures, 5 tables. Accepted by ApJ