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"Grant, F."
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Superstars of history : the good, the bad, and the brainy
History doesn't just happen: it's made by real-life superstars. Read about the good deeds of Abraham Lincoln, Gandhi, and Nelson Mandela, the evildoings of Genghis Khan, Hitler, and Stalin, and the superbrainy thinking of Archimedes, Marie Curie, and Einstein.
Book
Genome-scale Capture C promoter interactions implicate effector genes at GWAS loci for bone mineral density
Osteoporosis is a devastating disease with an essential genetic component. GWAS have discovered genetic signals robustly associated with bone mineral density (BMD), but not the precise localization of effector genes. Here, we carry out physical and direct variant to gene mapping in human mesenchymal progenitor cell-derived osteoblasts employing a massively parallel, high resolution Capture C based method in order to simultaneously characterize the genome-wide interactions of all human promoters. By intersecting our Capture C and ATAC-seq data, we observe consistent contacts between candidate causal variants and putative target gene promoters in open chromatin for ~ 17% of the 273 BMD loci investigated. Knockdown of two novel implicated genes,
ING3
at ‘
CPED1-WNT16
’ and
EPDR1
at ‘
STARD3NL
’, inhibits osteoblastogenesis, while promoting adipogenesis. This approach therefore aids target discovery in osteoporosis, here on the example of two relevant genes involved in the fate determination of mesenchymal progenitors, and can be applied to other common genetic diseases.
GWAS have identified numerous genetic loci for bone mineral density (BMD) and fracture risk. Here, the authors map these variants to putative target genes using ATAC-seq and Capture C of human osteoblasts and confirm ING3 and EPDR1 as BMD genes in in vitro osteoblast differentiation experiments.
Journal Article
The personal memoirs of Ulysses S. Grant : the complete annotated edition
President Ulysses S. Grant (1822-1885) was one of the most esteemed individuals of the nineteenth century. His two-volume memoirs, sold door-to-door by former Union soldiers, have never gone out of print and were once as ubiquitous in American households as the Bible. Mark Twain, Gertrude Stein, Matthew Arnold, Henry James, and Edmund Wilson hailed these works as great literature, and presidents Bill Clinton and George W. Bush both credit Grant with influencing their own writing. Yet a judiciously annotated clarifying edition of these memoirs has never been produced until now. The Personal Memoirs of Ulysses S. Grant is the first comprehensively annotated edition of Grant's memoirs, fully representing the great military leader's thoughts on his life and times through the end of the Civil War and his invaluable perspective on battlefield decision making. An introduction contextualizes Grant's life and significance, and lucid editorial commentary allows the president's voice and narrative to shine through. Compiled by the editors in the Ulysses S. Grant Association's Presidential Library, these selections enrich our understanding of the antebellum era, the Mexican War, and the Civil War. Grant provides insight into how rigorously these events tested America's democratic institutions and the cohesion of its social order. The Personal Memoirs of Ulysses S. Grant preserves and extends a work of profound political, historical, and literary significance and serves as the gateway for modern readers of all backgrounds to an American classic.-- Provided by publisher
Book
Changes in precipitation and air temperature contribute comparably to permafrost degradation in a warmer climate
Surface energy budgets of high-latitude permafrost systems are poorly represented in Earth system models (ESMs), yet permafrost is rapidly degrading and these dynamics are critical to future carbon-climate feedback predictions. A potentially important factor in permafrost degradation neglected so far by ESMs is heat transfer from precipitation, although increases in soil temperature and thaw depth have been observed following increases in precipitation. Using observations and a mechanistic ecosystem model, we show here that increases in precipitation hasten active layer development beyond that caused by surface air warming across the North Slope of Alaska (NSA) under recent and 21st century climate (RCP8.5). Modeled active layer depth (ALD) in simulations that allow precipitation heat transfer agreed very well with observations from 28 Circumpolar Active Layer Monitoring sites (R 2 = 0.63; RMSE = 10 cm). Simulations that ignored precipitation heat transfer resulted in lower spatially-averaged soil temperatures and a 39 cm shallower ALD by 2100 across the NSA. The results from our sensitivity analysis show that projected increases in 21st century precipitation deepen the active layer by enhancing precipitation heat transfer and ground thermal conductivity, suggesting that precipitation is as important an environmental control on permafrost degradation as surface air temperature. We conclude that ESMs that do not account for precipitation heat transfer likely underestimate ALD rates of change, and thus likely predict biased ecosystem responses.
Journal Article
The epidemiology of DSM-5 posttraumatic stress disorder in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III
Objectives
To present current, nationally representative US findings on the past-year and lifetime prevalences, sociodemographic correlates, psychiatric comorbidity, associated disability, and treatment of DSM-5 posttraumatic stress disorder (PTSD).
Methods
Face-to-face interviews with 36,309 adults in the 2012–2013 National Epidemiologic Survey on Alcohol and Related Conditions-III. PTSD, alcohol and drug use disorders, and selected mood, anxiety, and personality disorders were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-5.
Results
Past-year and lifetime prevalences were 4.7 and 6.1 %, higher for female, white, Native American, younger, and previously married respondents, those with
Journal Article
Sustainable irrigation based on co-regulation of soil water supply and atmospheric evaporative demand
Irrigation is an important adaptation to reduce crop yield loss due to water stress from both soil water deficit (low soil moisture) and atmospheric aridity (high vapor pressure deficit, VPD). Traditionally, irrigation has primarily focused on soil water deficit. Observational evidence demonstrates that stomatal conductance is co-regulated by soil moisture and VPD from water supply and demand aspects. Here we use a validated hydraulically-driven ecosystem model to reproduce the co-regulation pattern. Specifically, we propose a plant-centric irrigation scheme considering water supply-demand dynamics (SDD), and compare it with soil-moisture-based irrigation scheme (management allowable depletion, MAD) for continuous maize cropping systems in Nebraska, United States. We find that, under current climate conditions, the plant-centric SDD irrigation scheme combining soil moisture and VPD, could significantly reduce irrigation water use (−24.0%) while maintaining crop yields, and increase economic profits (+11.2%) and irrigation water productivity (+25.2%) compared with MAD, thus SDD could significantly improve water sustainability.
Irrigation is the most important use of water. A newly developed irrigation management scheme leads to a significant reduction in water use and increase in economic gains while maintaining crop yields, presenting opportunities for real-world impacts under current and future climate conditions.
Journal Article
Arctic tundra shrubification: a review of mechanisms and impacts on ecosystem carbon balance
Vegetation composition shifts, and in particular, shrub expansion across the Arctic tundra are some of the most important and widely observed responses of high-latitude ecosystems to rapid climate warming. These changes in vegetation potentially alter ecosystem carbon balances by affecting a complex set of soil–plant–atmosphere interactions. In this review, we synthesize the literature on (a) observed shrub expansion, (b) key climatic and environmental controls and mechanisms that affect shrub expansion, (c) impacts of shrub expansion on ecosystem carbon balance, and (d) research gaps and future directions to improve process representations in land models. A broad range of evidence, including in-situ observations, warming experiments, and remotely sensed vegetation indices have shown increases in growth and abundance of woody plants, particularly tall deciduous shrubs, and advancing shrublines across the circumpolar Arctic. This recent shrub expansion is affected by several interacting factors including climate warming, accelerated nutrient cycling, changing disturbance regimes, and local variation in topography and hydrology. Under warmer conditions, tall deciduous shrubs can be more competitive than other plant functional types in tundra ecosystems because of their taller maximum canopy heights and often dense canopy structure. Competitive abilities of tall deciduous shrubs vs herbaceous plants are also controlled by variation in traits that affect carbon and nutrient investments and retention strategies in leaves, stems, and roots. Overall, shrub expansion may affect tundra carbon balances by enhancing ecosystem carbon uptake and altering ecosystem respiration, and through complex feedback mechanisms that affect snowpack dynamics, permafrost degradation, surface energy balance, and litter inputs. Observed and projected tall deciduous shrub expansion and the subsequent effects on surface energy and carbon balances may alter feedbacks to the climate system. Land models, including those integrated in Earth System Models, need to account for differences in plant traits that control competitive interactions to accurately predict decadal- to centennial-scale tundra vegetation and carbon dynamics.
Journal Article
Modelling epilepsy in the mouse: challenges and solutions
In most mouse models of disease, the outward manifestation of a disorder can be measured easily, can be assessed with a trivial test such as hind limb clasping, or can even be observed simply by comparing the gross morphological characteristics of mutant and wild-type littermates. But what if we are trying to model a disorder with a phenotype that appears only sporadically and briefly, like epileptic seizures? The purpose of this Review is to highlight the challenges of modelling epilepsy, in which the most obvious manifestation of the disorder, seizures, occurs only intermittently, possibly very rarely and often at times when the mice are not under direct observation. Over time, researchers have developed a number of ways in which to overcome these challenges, each with their own advantages and disadvantages. In this Review, we describe the genetics of epilepsy and the ways in which genetically altered mouse models have been used. We also discuss the use of induced models in which seizures are brought about by artificial stimulation to the brain of wild-type animals, and conclude with the ways these different approaches could be used to develop a wider range of anti-seizure medications that could benefit larger patient populations.
Journal Article