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131.
Gallego Romero I Basu Mallick C Liebert A Crivellaro F Chaubey G Itan Y Metspalu M Eaaswarkhanth M Pitchappan R Villems R Reich D Singh L Thangaraj K Thomas MG Swallow DM Mirazón Lahr M Kivisild T 《Molecular biology and evolution》2012,29(1):249-260
Milk consumption and lactose digestion after weaning are exclusively human traits made possible by the continued production of the enzyme lactase in adulthood. Multiple independent mutations in a 100-bp region--part of an enhancer--approximately 14-kb upstream of the LCT gene are associated with this trait in Europeans and pastoralists from Saudi Arabia and Africa. However, a single mutation of purported western Eurasian origin accounts for much of observed lactase persistence outside Africa. Given the high levels of present-day milk consumption in India, together with archaeological and genetic evidence for the independent domestication of cattle in the Indus valley roughly 7,000 years ago, we sought to determine whether lactase persistence has evolved independently in the subcontinent. Here, we present the results of the first comprehensive survey of the LCT enhancer region in south Asia. Having genotyped 2,284 DNA samples from across the Indian subcontinent, we find that the previously described west Eurasian -13910 C>T mutation accounts for nearly all the genetic variation we observed in the 400- to 700-bp LCT regulatory region that we sequenced. Geography is a significant predictor of -13910*T allele frequency, and consistent with other genomic loci, its distribution in India follows a general northwest to southeast declining pattern, although frequencies among certain neighboring populations vary substantially. We confirm that the mutation is identical by descent to the European allele and is associated with the same>1 Mb extended haplotype in both populations. 相似文献
132.
Cherney DZ Reich HN Scholey JW Lai V Slorach C Zinman B Bradley TJ 《Canadian journal of physiology and pharmacology》2012,90(1):113-121
The protein kinase Cβ (PKCβ) system has been implicated in the deleterious vascular responses to hyperglycemia and angiotensin II (Ang?II) in experimental models of diabetes (DM). Whether these interactions are important in humans is unknown. Flow-mediated vasodilatation (FMD) was measured during clamped euglycemia and hyperglycemia, before and after randomization to PKCβ inhibition (ruboxistaurin; RBX, 32?mg daily, n = 13) or a placebo (n = 7) for 8?weeks in renin-angiotensin system (RAS) blockade-treated subjects with type 1 DM. Blood pressure responses to infused Ang?II were measured before and after randomization to RBX or a placebo. The RBX and placebo groups displayed similar clinical characteristics. Before RBX, FMD declined in response to hyperglycemia (6.8%?± 2.8% to 4.9%?± 1.8%). This effect was reversed after treatment with RBX (5.6%?± 3.1% to 6.0%?± 1.6% (within-group change, p = 0.009 (ANOVA)). No changes were observed in the placebo group. Infused Ang?II was associated with hypertensive responses in the RBX and placebo groups (p?< 0.05 (ANOVA)), and RBX did not influence this effect. In conclusion, RBX blunted the effect of hyperglycemia on FMD, suggesting that PKCβ may modulate endothelial function in type 1 DM. The lack of effect on Ang?II responses suggests that PKCβ inhibition may act through non-RAS pathways in humans with DM. 相似文献
133.
The acquired pellicle is a tenacious organic layer covering the surface of teeth, protecting the underlying dental hard tissues. Lipids account for about one quarter of the pellicle's dry weight and are assumed to be of considerable importance for their protective properties. Nevertheless, only preliminary information is available about the nature of lipids in the pellicle. Gas chromatography coupled with electron impact ionization mass spectrometry was used to establish a convenient analytical protocol in order to obtain a qualitative and quantitative characterization of a wide range of FAs (C(12)-C(22)). In situ biofilm formation was performed on bovine enamel slabs mounted on individual splints carried by 10 subjects. A modified Folch extraction procedure was adopted to extract the lipids from the detached pellicle, followed by transesterification to fatty acid methyl esters using methanol and concentrated hydrochloric acid. Tridecanoic and nonadecanoic acid were used as internal standards suitable and reliable for robust, precise and accurate measurements. The present study demonstrates, for the first time, a procedure based on a combination of innovative specimen generation and convenient sample preparation with sensitive GC-MS analysis for the determination of the fatty acid profile of the initial oral biofilm. 相似文献
134.
AL Williams N Patterson J Glessner H Hakonarson D Reich 《American journal of human genetics》2012,91(2):238-251
Haplotypes are an important resource for a large number of applications in human genetics, but computationally inferred haplotypes are subject to switch errors that decrease their utility. The accuracy of computationally inferred haplotypes increases with sample size, and although ever larger genotypic data sets are being generated, the fact that existing methods require substantial computational resources limits their applicability to data sets containing tens or hundreds of thousands of samples. Here, we present HAPI-UR (haplotype inference for unrelated samples), an algorithm that is designed to handle unrelated and/or trio and duo family data, that has accuracy comparable to or greater than existing methods, and that is computationally efficient and can be applied to 100,000 samples or more. We use HAPI-UR to phase a data set with 58,207 samples and show that it achieves practical runtime and that switch errors decrease with sample size even with the use of samples from multiple ethnicities. Using a data set with 16,353 samples, we compare HAPI-UR to Beagle, MaCH, IMPUTE2, and SHAPEIT and show that HAPI-UR runs 18× faster than all methods and has a lower switch-error rate than do other methods except for Beagle; with the use of consensus phasing, running HAPI-UR three times gives a slightly lower switch-error rate than Beagle does and is more than six times faster. We demonstrate results similar to those from Beagle on another data set with a higher marker density. Lastly, we show that HAPI-UR has better runtime scaling properties than does Beagle so that for larger data sets, HAPI-UR will be practical and will have an even larger runtime advantage. HAPI-UR is available online (see Web Resources). 相似文献
135.
DNA methylation is a key regulator of gene expression and changes in DNA methylation occur early in tumorigenesis. Mutations in the de novo DNA methyltransferase gene, DNMT3A, frequently occur in adult acute myeloid leukemia patients with poor prognoses. Most of the mutations occur within the dimer or tetramer interface, including Arg-882. We have identified that the most prevalent mutation, R882H, and three additional mutants along the tetramer interface disrupt tetramerization. The processive methylation of multiple CpG sites is disrupted when tetramerization is eliminated. Our results provide a possible mechanism that accounts for how DNMT3A mutations may contribute to oncogenesis and its progression. 相似文献
136.
Lee E. Frelich Rolf O. Peterson Martin Dov?iak Peter B. Reich John A. Vucetich Nico Eisenhauer 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2012,367(1605):2955-2961
As the climate warms, boreal tree species are expected to be gradually replaced by temperate species within the southern boreal forest. Warming will be accompanied by changes in above- and below-ground consumers: large moose (Alces alces) replaced by smaller deer (Odocoileus virginianus) above-ground, and small detritivores replaced by larger exotic earthworms below-ground. These shifts may induce a cascade of ecological impacts across trophic levels that could alter the boreal to temperate forest transition. Deer are more likely to browse saplings of temperate tree species, and European earthworms favour seedlings of boreal tree species more than temperate species, potentially hindering the ability of temperate tree species to expand northwards. We hypothesize that warming-induced changes in consumers will lead to novel plant communities by changing the filter on plant species success, and that above- and below-ground cascades of trophic interactions will allow boreal tree species to persist during early phases of warming, leading to an abrupt change at a later time. The synthesis of evidence suggests that consumers can modify the climate change-induced transition of ecosystems. 相似文献
137.
Reich PB 《Proceedings. Biological sciences / The Royal Society》2012,279(1736):2128-2134
Quantifying the mechanistic links between carbon fluxes and forest canopy attributes will advance understanding of leaf-to-ecosystem scaling and its potential application to assessing terrestrial ecosystem metabolism. Important advances have been made, but prior studies that related carbon fluxes to multiple canopy traits are scarce. Herein, presenting data for 128 cold temperate and boreal forests across a regional gradient of 600 km and 5.4°C (from 2.4°C to 7.8°C) in mean annual temperature, I show that stand-scale productivity is a function of the capacity to harvest light (represented by leaf area index, LAI), and to biochemically fix carbon (represented by canopy nitrogen concentration, %N). In combination, LAI and canopy %N explain greater than 75 per cent of variation in above-ground net primary productivity among forests, expressed per year or per day of growing season. After accounting for growing season length and climate effects, less than 10 per cent of the variance remained unexplained. These results mirror similar relations of leaf-scale and canopy-scale (eddy covariance) maximum photosynthetic rates to LAI and %N. Collectively, these findings indicate that canopy structure and chemistry translate from instantaneous physiology to annual carbon fluxes. Given the increasing capacity to remotely sense canopy LAI, %N and phenology, these results support the idea that physiologically based scaling relations can be useful tools for global modelling. 相似文献
138.
Adult stem cells must balance self-renewal and differentiation for tissue homeostasis. The Drosophila ovary has provided a wealth of information about the extrinsic niche signals and intrinsic molecular processes required to ensure appropriate germline stem cell renewal and differentiation. The factors controlling behavior of the more recently identified follicle stem cells of the ovary are less well-understood but equally important for fertility. Here we report that translational regulators play a critical role in controlling these cells. Specifically, the translational regulator Caprin (Capr) is required in the follicle stem cell lineage to ensure maintenance of this stem cell population and proper encapsulation of developing germ cells by follicle stem cell progeny. In addition, reduction of one copy of the gene fmr1, encoding the translational regulator Fragile X Mental Retardation Protein, exacerbates the Capr encapsulation phenotype, suggesting Capr and fmr1 are regulating a common process. Caprin was previously characterized in vertebrates as Cytoplasmic Activation/Proliferation-Associated Protein. Significantly, we find that loss of Caprin alters the dynamics of the cell cycle, and we present evidence that misregulation of CycB contributes to the disruption in behavior of follicle stem cell progeny. Our findings support the idea that translational regulators may provide a conserved mechanism for oversight of developmentally critical cell cycles such as those in stem cell populations. 相似文献
139.
Global change belowground: impacts of elevated CO2, nitrogen,and summer drought on soil food webs and biodiversity 总被引:1,自引:0,他引:1
Nico Eisenhauer Simone Cesarz Robert Koller Kally Worm Peter B. Reich 《Global Change Biology》2012,18(2):435-447
The world's ecosystems are subjected to various anthropogenic global change agents, such as enrichment of atmospheric CO2 concentrations, nitrogen (N) deposition, and changes in precipitation regimes. Despite the increasing appreciation that the consequences of impending global change can be better understood if varying agents are studied in concert, there is a paucity of multi‐factor long‐term studies, particularly on belowground processes. Herein, we address this gap by examining the responses of soil food webs and biodiversity to enrichment of CO2, elevated N, and summer drought in a long‐term grassland study at Cedar Creek, Minnesota, USA (BioCON experiment). We use structural equation modeling (SEM), various abiotic and biotic explanatory variables, and data on soil microorganisms, protozoa, nematodes, and soil microarthropods to identify the impacts of multiple global change effects on drivers belowground. We found that long‐term (13‐year) changes in CO2 and N availability resulted in modest alterations of soil biotic food webs and biodiversity via several mechanisms, encompassing soil water availability, plant productivity, and – most importantly – changes in rhizodeposition. Four years of manipulation of summer drought exerted surprisingly minor effects, only detrimentally affecting belowground herbivores and ciliate protists at elevated N. Elevated CO2 increased microbial biomass and the density of ciliates, microarthropod detritivores, and gamasid mites, most likely by fueling soil food webs with labile C. Moreover, beneficial bottom‐up effects of elevated CO2 compensated for detrimental elevated N effects on soil microarthropod taxa richness. In contrast, nematode taxa richness was lowest at elevated CO2 and elevated N. Thus, enrichment of atmospheric CO2 concentrations and N deposition may result in taxonomically and functionally altered, potentially simplified, soil communities. Detrimental effects of N deposition on soil biodiversity underscore recent reports on plant community simplification. This is of particular concern, as soils house a considerable fraction of global biodiversity and ecosystem functions. 相似文献
140.
Rising temperatures are predicted to cause temperate tree species to expand north into currently boreal dominated forests. Other factors, such as overabundant deer, may hinder temperate expansion. We examined how interactions among temperature, browse pressure, light availability, and initial size impact height and radial growth of naturally regenerated, competing temperate and boreal saplings across their overlapping range limits in central North America. In 9 of 10 growth model comparisons, the inclusion of mean summer temperature and browse damage as explanatory variables strongly improved model performance over the base model with only initial size and light availability as parameters. Potential growth reductions due to browse damage and temperature limitation were similar in magnitude (up to ~50%). Temperate sapling growth increased and boreal growth decreased with temperature across a regional summer temperature gradient (2.3 °C), causing a rank reversal in growth rates, and suggesting that temperature is a key driver of sapling performance and range boundaries. However, under high browse pressure positive temperate responses to temperature were eliminated, essentially pushing the crossover point in growth between temperate and boreal species further south. These results highlight the importance of interactions among global change agents and potential impediments for tree species to track a rapidly changing climate. 相似文献