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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Brain volumetric deficits in MAPT mutation carriers: a multisite study

Objective: MAPT mutations typically cause behavioral variant frontotemporal dementia with or without parkinsonism. Previous studies have shown that symptomatic MAPT mutation carriers have frontotemporal atrophy, yet studies have shown mixed results as to whether presymptomatic carriers have low gray matter volumes. To elucidate whether presymptomatic carriers have lower structural brain volumes within regions atrophied during the symptomatic phase, we studied a large cohort of MAPT mutation carriers using a voxelwise approach. Methods: We studied 22 symptomatic carriers (age 54.7 ± 9.1, 13 female) and 43 presymptomatic carriers (age 39.2 ± 10.4, 21 female). Symptomatic carriers’ clinical syndromes included: behavioral variant frontotemporal dementia (18), an amnestic dementia syndrome (2), Parkinson’s disease (1), and mild cognitive impairment (1). We performed voxel-based morphometry on T1 images and assessed brain volumetrics by clinical subgroup, age, and mutation subtype. Results: Symptomatic carriers showed gray matter atrophy in bilateral frontotemporal cortex, insula, and striatum, and white matter atrophy in bilateral corpus callosum and uncinate fasciculus. Approximately 20% of presymptomatic carriers had low gray matter volumes in bilateral hippocampus, amygdala, and lateral temporal cortex. Within these regions, low gray matter volume

The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

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Objectives. We used data from the Changing Lives of Older Couples (CLOC), a prospective multiwave study of 1,532 married individuals aged 65 and older, to investigate the extent to which spousal loss and death context characteristics are associated with the stress hormone cortisol at six (W1) and 18 (W2) months postbereavement. Method. We used ordinary least squares (OLS) regression models to estimate the effects of death context characteristics (forewarning, caregiving, and postloss numbness, reported at W1) on cortisol levels (at W1 and W2). We controlled for age and gender, and evaluated a two-way interaction term between gender and death circumstances. Results. Bereaved spouses who reported prolonged forewarning of the death evidenced higher cortisol levels at W1 than those who did not experience prolonged forewarning. Bereaved women had higher cortisol levels than bereaved men at W1. A two-way interaction between gender and emotional numbness was statistically significant, where men (but not women) who experienced postloss numbness had elevated cortisol levels a

How does bereavement get under the skin? The effects of late-life spousal loss on cortisol levels.

Objectives.We used data from the Changing Lives of Older Couples, a prospective multiwave study of 1,532 married individuals aged 65 and older, to investigate the extent to which spousal loss and death-context characteristics are associated with the stress hormone cortisol at 6 (W1) and 18 (W2) months postbereavement.Method.We used ordinary least squares regression models to estimate the effects of death-context characteristics (forewarning, caregiving, and postloss numbness, reported at W1) on cortisol levels (at W1 and W2). We included age and gender and evaluated a two-way interaction term between gender and death circumstances

Sleep quality and cortical amyloid-β deposition in postmenopausal women of the Kronos early estrogen prevention study.

Hormone therapy improves sleep in menopausal women and recent data suggest that transdermal 17β-estradiol may reduce the accumulation of cortical amyloid-β. However, how menopausal hormone therapies modify the associations of amyloid-β accumulation with sleep quality is not known. In this study, associations of sleep quality with cortical amyloid-β deposition and cognitive function were assessed in a subset of women who had participated in the Kronos Early Estrogen Prevention Study (KEEPS). KEEPS was a randomized, placebo-controlled trial in which recently menopausal women (age=42–58; 5–36 months past menopause) were randomized to: 1) oral conjugated equine estrogen (oCEE, n=19); 2) transdermal 17β-estradiol (tE2, n=21); 3) placebo pills and patch (n=32) for 4 years. Global sleep quality score was calculated using Pittsburgh Sleep Quality Index, cortical amyloid-β deposition was measured with Pittsburgh compound-B (PiB) PET standard uptake value ratio (SUVr) and cognitive function was assessed in four cognitive domains three years after completion of trial treatments. Lower global sleep quality score (i.e. better sleep quality) correlated with lower cortical PiB SUVr only in the tE2 group (r=0.45, p=0.047). Better global sleep quality also correlated with higher visual attention and executive function scores in the tE2 group (r=−0.54, p=0.02) and in the oCEE group (r=−0.65, p=0.005). Menopausal hormone therapies may influence the effects of sleep on cognitive function, specifically, visual attention and executive function. There also appears to be a complex relationship between sleep, menopausal hormone therapies, cortical amyloid-β accumulation and cognitive function, and tE2 formulation may modify the relationship between sleep and amyloid-β accumulation