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Showing papers by "University of California, Davis published in 2011"


Journal ArticleDOI
TL;DR: A conceptual framework and operational research criteria are proposed, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies and it is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD.
Abstract: The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.

5,671 citations


Journal ArticleDOI
TL;DR: In this paper, the topological semimetal, a three-dimensional phase of a magnetic solid, is described and it may be realized in a class of pyrochlore iridates based on calculations using the LDA+U$ method.
Abstract: We investigate novel phases that emerge from the interplay of electron correlations and strong spin-orbit interactions. We focus on describing the topological semimetal, a three-dimensional phase of a magnetic solid, and argue that it may be realized in a class of pyrochlore iridates (such as ${\mathrm{Y}}_{2}$Ir${}_{2}$O${}_{7}$) based on calculations using the $\text{LDA}+U$ method. This state is a three-dimensional analog of graphene with linearly dispersing excitations and provides a condensed-matter realization of Weyl fermions that obeys a two-component Dirac equation. It also exhibits remarkable topological properties manifested by surface states in the form of Fermi arcs, which are impossible to realize in purely two-dimensional band structures. For intermediate correlation strengths, we find this to be the ground state of the pyrochlore iridates, coexisting with noncollinear magnetic order. A narrow window of magnetic ``axion'' insulator may also be present. An applied magnetic field is found to induce a metallic ground state.

3,865 citations


Journal ArticleDOI
TL;DR: This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results.
Abstract: This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results. Criteria for the 3 variants of PPA—nonfluent/agrammatic, semantic, and logopenic—were developed by an international group of PPA investigators who convened on 3 occasions to operationalize earlier published clinical descriptions for PPA subtypes. Patients are first diagnosed with PPA and are then divided into clinical variants based on specific speech and language features characteristic of each subtype. Classification can then be further specified as “imaging-supported” if the expected pattern of atrophy is found and “with definite pathology” if pathologic or genetic data are available. The working recommendations are presented in lists of features, and suggested assessment tasks are also provided. These recommendations have been widely agreed upon by a large group of experts and should be used to ensure consistency of PPA classification in future studies. Future collaborations will collect prospective data to identify relationships between each of these syndromes and specific biomarkers for a more detailed understanding of clinicopathologic correlations.

3,635 citations


Journal ArticleDOI
15 Jul 2011-Science
TL;DR: This empirical work supports long-standing theory about the role of top-down forcing in ecosystems but also highlights the unanticipated impacts of trophic cascades on processes as diverse as the dynamics of disease, wildfire, carbon sequestration, invasive species, and biogeochemical cycles.
Abstract: Until recently, large apex consumers were ubiquitous across the globe and had been for millions of years. The loss of these animals may be humankind's most pervasive influence on nature. Although such losses are widely viewed as an ethical and aesthetic problem, recent research reveals extensive cascading effects of their disappearance in marine, terrestrial, and freshwater ecosystems worldwide. This empirical work supports long-standing theory about the role of top-down forcing in ecosystems but also highlights the unanticipated impacts of trophic cascades on processes as diverse as the dynamics of disease, wildfire, carbon sequestration, invasive species, and biogeochemical cycles. These findings emphasize the urgent need for interdisciplinary research to forecast the effects of trophic downgrading on process, function, and resilience in global ecosystems.

3,130 citations


Journal ArticleDOI
TL;DR: The authors proposed a variance estimator for the OLS estimator as well as for nonlinear estimators such as logit, probit, and GMM that enables cluster-robust inference when there is two-way or multiway clustering that is nonnested.
Abstract: In this article we propose a variance estimator for the OLS estimator as well as for nonlinear estimators such as logit, probit, and GMM. This variance estimator enables cluster-robust inference when there is two-way or multiway clustering that is nonnested. The variance estimator extends the standard cluster-robust variance estimator or sandwich estimator for one-way clustering (e.g., Liang and Zeger 1986; Arellano 1987) and relies on similar relatively weak distributional assumptions. Our method is easily implemented in statistical packages, such as Stata and SAS, that already offer cluster-robust standard errors when there is one-way clustering. The method is demonstrated by a Monte Carlo analysis for a two-way random effects model; a Monte Carlo analysis of a placebo law that extends the state–year effects example of Bertrand, Duflo, and Mullainathan (2004) to two dimensions; and by application to studies in the empirical literature where two-way clustering is present.

2,542 citations


Journal ArticleDOI
TL;DR: A roadmap of the most widely used and ecologically relevant approaches for analysis through a series of mission statements is provided, distinguishing two types of β diversity: directional turnover along a gradient vs. non-directional variation.
Abstract: A recent increase in studies of β diversity has yielded a confusing array of concepts, measures and methods. Here, we provide a roadmap of the most widely used and ecologically relevant approaches for analysis through a series of mission statements. We distinguish two types of β diversity: directional turnover along a gradient vs. non-directional variation. Different measures emphasize different properties of ecological data. Such properties include the degree of emphasis on presence/absence vs. relative abundance information and the inclusion vs. exclusion of joint absences. Judicious use of multiple measures in concert can uncover the underlying nature of patterns in β diversity for a given dataset. A case study of Indonesian coral assemblages shows the utility of a multi-faceted approach. We advocate careful consideration of relevant questions, matched by appropriate analyses. The rigorous application of null models will also help to reveal potential processes driving observed patterns in β diversity.

1,995 citations


Journal ArticleDOI
TL;DR: Six general mechanisms by which trait variation changes the outcome of ecological interactions are identified and synthesize recent theory and identify several direct effects of trait variation per se and indirect effects arising from the role of genetic variation in trait evolution.
Abstract: Natural populations consist of phenotypically diverse individuals that exhibit variation in their demographic parameters and intra- and inter-specific interactions. Recent experimental work indicates that such variation can have significant ecological effects. However, ecological models typically disregard this variation and focus instead on trait means and total population density. Under what situations is this simplification appropriate? Why might intraspecific variation alter ecological dynamics? In this review we synthesize recent theory and identify six general mechanisms by which trait variation changes the outcome of ecological interactions. These mechanisms include several direct effects of trait variation per se and indirect effects arising from the role of genetic variation in trait evolution.

1,835 citations


Journal ArticleDOI
Adam C. Naj1, Gyungah Jun2, Gary W. Beecham1, Li-San Wang3  +153 moreInstitutions (38)
TL;DR: The Alzheimer Disease Genetics Consortium performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1), two replication stages (stages 2 and 3), and both joint analysis and meta-analysis approaches were used.
Abstract: The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.

1,743 citations


Journal ArticleDOI
21 Oct 2011-Science
TL;DR: It was found that mitochondrial division occurred at positions where ER tubules contacted mitochondria and mediated constriction before Drp1 recruitment, suggesting that ERtubules may play an active role in defining the position of mitochondrial division sites.
Abstract: Mitochondrial structure and distribution are regulated by division and fusion events. Mitochondrial division is regulated by Dnm1/Drp1, a dynamin-related protein that forms helices around mitochondria to mediate fission. Little is known about what determines sites of mitochondrial fission within the mitochondrial network. The endoplasmic reticulum (ER) and mitochondria exhibit tightly coupled dynamics and have extensive contacts. We tested whether ER plays a role in mitochondrial division. We found that mitochondrial division occurred at positions where ER tubules contacted mitochondria and mediated constriction before Drp1 recruitment. Thus, ER tubules may play an active role in defining the position of mitochondrial division sites.

1,622 citations


Journal ArticleDOI
TL;DR: It is demonstrated that models that are inappropriately complex or inappropriately simple show reduced ability to infer habitat quality, reduced able to infer the relative importance of variables in constraining species' distributions, and reduced transferability to other time periods.
Abstract: Maxent, one of the most commonly used methods for inferring species distributions and environmental tolerances from occurrence data, allows users to fit models of arbitrary complexity. Model complexity is typically constrained via a process known as L1 regularization, but at present little guidance is available for setting the appropriate level of regularization, and the effects of inappropriately complex or simple models are largely unknown. In this study, we demonstrate the use of information criterion approaches to setting regularization in Maxent, and we compare models selected using information criteria to models selected using other criteria that are common in the literature. We evaluate model performance using occurrence data generated from a known "true" initial Maxent model, using several different metrics for model quality and transferability. We demonstrate that models that are inappropriately complex or inappropriately simple show reduced ability to infer habitat quality, reduced ability to infer the relative importance of variables in constraining species' distributions, and reduced transferability to other time periods. We also demonstrate that information criteria may offer significant advantages over the methods commonly used in the literature.

1,567 citations


Journal ArticleDOI
TL;DR: An overview of the project and the resources it is generating and the application of ENCODE data to interpret the human genome are provided.
Abstract: The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome.

Journal ArticleDOI
TL;DR: A risk stratification schema can establish the risk of chemotherapy toxicity in older adults and Geriatric assessment variables independently predicted therisk of toxicity.
Abstract: Purpose Older adults are vulnerable to chemotherapy toxicity; however, there are limited data to identify those at risk. The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity. Patients and Methods Patients age 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status). Patients were followed through the chemotherapy course to capture grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events. Results In total, 500 patients with a mean age of 73 years (range, 65 to 91 years) with stage I to IV lung (29%), GI (27%), gynecologic (17%), breast (11%), genitourinary (10%), or other (6%) cancer joined this prospective study. Grade 3 to 5 toxicity occurred in 53% of the patients (39% grade 3, 12% grade 4, 2% grade 5). A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables, laboratory test values, and patient, tumor, and treatment characteristics. A scoring system in which the median risk score was 7 (range, 0 to 19) and risk stratification schema (risk score: percent incidence of grade 3 to 5 toxicity) identified older adults at low (0 to 5 points; 30%), intermediate (6 to 9 points; 52%), or high risk (10 to 19 points; 83%) of chemotherapy toxicity (P .001).

Journal ArticleDOI
TL;DR: The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress as mentioned in this paper.
Abstract: A golden age for heavy-quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the B-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations at BESIII, the LHC, RHIC, FAIR, the Super Flavor and/or Tau-Charm factories, JLab, the ILC, and beyond. The list of newly found conventional states expanded to include h(c)(1P), chi(c2)(2P), B-c(+), and eta(b)(1S). In addition, the unexpected and still-fascinating X(3872) has been joined by more than a dozen other charmonium- and bottomonium-like "XYZ" states that appear to lie outside the quark model. Many of these still need experimental confirmation. The plethora of new states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c (c) over bar, b (b) over bar, and b (c) over bar bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. Lattice QCD has grown from a tool with computational possibilities to an industrial-strength effort now dependent more on insight and innovation than pure computational power. New effective field theories for the description of quarkonium in different regimes have been developed and brought to a high degree of sophistication, thus enabling precise and solid theoretical predictions. Many expected decays and transitions have either been measured with precision or for the first time, but the confusing patterns of decays, both above and below open-flavor thresholds, endure and have deepened. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.

Journal ArticleDOI
Pamela Sklar1, Pamela Sklar2, Stephan Ripke3, Stephan Ripke1  +189 moreInstitutions (51)
TL;DR: An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4, and a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals was identified.
Abstract: We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10−7). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.

Journal ArticleDOI
TL;DR: In this paper, the feasibility of providing worldwide energy for all purposes (electric power, transportation, heating/cooling, etc.) from wind, water, and sunlight (WWS) was analyzed.


Journal ArticleDOI
25 Aug 2011-Nature
TL;DR: This work describes how the wMel Wolbachia infection, introduced into the dengue vector Aedes aegypti from Drosophila melanogaster, successfully invaded two natural A. aagypti populations in Australia, reaching near-fixation in a few months following releases of wMel-infected A.A. ae Egyptian adults.
Abstract: Genetic manipulations of insect populations for pest control have been advocated for some time, but there are few cases where manipulated individuals have been released in the field and no cases where they have successfully invaded target populations. Population transformation using the intracellular bacterium Wolbachia is particularly attractive because this maternally-inherited agent provides a powerful mechanism to invade natural populations through cytoplasmic incompatibility. When Wolbachia are introduced into mosquitoes, they interfere with pathogen transmission and influence key life history traits such as lifespan. Here we describe how the wMel Wolbachia infection, introduced into the dengue vector Aedes aegypti from Drosophila melanogaster, successfully invaded two natural A. aegypti populations in Australia, reaching near-fixation in a few months following releases of wMel-infected A. aegypti adults. Models with plausible parameter values indicate that Wolbachia-infected mosquitoes suffered relatively small fitness costs, leading to an unstable equilibrium frequency <30% that must be exceeded for invasion. These findings demonstrate that Wolbachia-based strategies can be deployed as a practical approach to dengue suppression with potential for area-wide implementation.

Journal ArticleDOI
TL;DR: The sibling recurrence rate of ASD is higher than suggested by previous estimates, and the size of the current sample and prospective nature of data collection minimized many limitations of previous studies ofibling recurrence.
Abstract: The recurrence risk of autism spectrum disorders (ASD) is estimated to be between 3% and 10%, but previous research was limited by small sample sizes and biases related to ascertainment, reporting, and stoppage factors. This study used prospective methods to obtain an updated estimate of sibling recurrence risk for ASD. METHODS: A prospective longitudinal study of infants at risk for ASD was conducted by a multisite international network, the Baby Siblings Research Consortium. Infants (n 664) with an older biological sibling with ASD were followed from early in life to 36 months, when they were classified as having or not having ASD. An ASD classification required surpassing the cutoff of the Autism Diagnostic Observation Schedule and receiving a clinical diagnosis from an expert clinician. RESULTS: A total of 18.7% of the infants developed ASD. Infant gender and the presence of 1 older affected sibling were significant predic- tors of ASD outcome, and there was an almost threefold increase in risk for male subjects and an additional twofold increase in risk if there was 1 older affected sibling. The age of the infant at study enrollment, the gender and functioning level of the infant's older sib- ling, and other demographic factors did not predict ASD outcome. CONCLUSIONS: The sibling recurrence rate of ASD is higher than sug- gested by previous estimates. The size of the current sample and pro- spective nature of data collection minimized many limitations of previ- ous studies of sibling recurrence. Clinical implications, including genetic counseling, are discussed. Pediatrics 2011;128:e000

Journal ArticleDOI
John K. Colbourne1, Michael E. Pfrender2, Michael E. Pfrender3, Donald L. Gilbert1, W. Kelley Thomas4, Abraham E. Tucker4, Abraham E. Tucker1, Todd H. Oakley5, Shin-ichi Tokishita6, Andrea Aerts7, Georg J. Arnold8, Malay Kumar Basu9, Malay Kumar Basu10, Darren J Bauer4, Carla E. Cáceres11, Liran Carmel9, Liran Carmel12, Claudio Casola1, Jeong Hyeon Choi1, John C. Detter7, Qunfeng Dong13, Qunfeng Dong1, Serge Dusheyko7, Brian D. Eads1, Thomas Fröhlich8, Kerry Geiler-Samerotte5, Kerry Geiler-Samerotte14, Daniel Gerlach15, Daniel Gerlach16, Phil Hatcher4, Sanjuro Jogdeo4, Sanjuro Jogdeo17, Jeroen Krijgsveld18, Evgenia V. Kriventseva16, Dietmar Kültz19, Christian Laforsch8, Erika Lindquist7, Jacqueline Lopez1, J. Robert Manak20, J. Robert Manak21, Jean Muller22, Jasmyn Pangilinan7, Rupali P Patwardhan23, Rupali P Patwardhan1, Samuel Pitluck7, Ellen J. Pritham24, Andreas Rechtsteiner1, Andreas Rechtsteiner25, Mina Rho1, Igor B. Rogozin9, Onur Sakarya5, Onur Sakarya26, Asaf Salamov7, Sarah Schaack24, Sarah Schaack1, Harris Shapiro7, Yasuhiro Shiga6, Courtney Skalitzky21, Zachary Smith1, Alexander Souvorov9, Way Sung4, Zuojian Tang27, Zuojian Tang1, Dai Tsuchiya1, Hank Tu7, Hank Tu26, Harmjan R. Vos18, Mei Wang7, Yuri I. Wolf9, Hideo Yamagata6, Takuji Yamada, Yuzhen Ye1, Joseph R. Shaw1, Justen Andrews1, Teresa J. Crease28, Haixu Tang1, Susan Lucas7, Hugh M. Robertson11, Peer Bork, Eugene V. Koonin9, Evgeny M. Zdobnov16, Evgeny M. Zdobnov29, Igor V. Grigoriev7, Michael Lynch1, Jeffrey L. Boore30, Jeffrey L. Boore7 
04 Feb 2011-Science
TL;DR: The Daphnia genome reveals a multitude of genes and shows adaptation through gene family expansions, and the coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random.
Abstract: We describe the draft genome of the microcrustacean Daphnia pulex, which is only 200 megabases and contains at least 30,907 genes. The high gene count is a consequence of an elevated rate of gene duplication resulting in tandem gene clusters. More than a third of Daphnia's genes have no detectable homologs in any other available proteome, and the most amplified gene families are specific to the Daphnia lineage. The coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random, and the analysis of gene expression under different environmental conditions reveals that numerous paralogs acquire divergent expression patterns soon after duplication. Daphnia-specific genes, including many additional loci within sequenced regions that are otherwise devoid of annotations, are the most responsive genes to ecological challenges.

Journal ArticleDOI
Nevin D. Young1, Frédéric Debellé2, Frédéric Debellé3, Giles E. D. Oldroyd4, René Geurts5, Steven B. Cannon6, Steven B. Cannon7, Michael K. Udvardi, Vagner A. Benedito8, Klaus F. X. Mayer, Jérôme Gouzy3, Jérôme Gouzy2, Heiko Schoof9, Yves Van de Peer10, Sebastian Proost10, Douglas R. Cook11, Blake C. Meyers12, Manuel Spannagl, Foo Cheung13, Stéphane De Mita5, Vivek Krishnakumar13, Heidrun Gundlach, Shiguo Zhou14, Joann Mudge15, Arvind K. Bharti15, Jeremy D. Murray4, Marina Naoumkina, Benjamin D. Rosen11, Kevin A. T. Silverstein1, Haibao Tang13, Stephane Rombauts10, Patrick X. Zhao, Peng Zhou1, Valérie Barbe, Philippe Bardou3, Philippe Bardou2, Michael Bechner14, Arnaud Bellec2, Anne Berger, Hélène Bergès2, Shelby L. Bidwell13, Ton Bisseling16, Ton Bisseling5, Nathalie Choisne, Arnaud Couloux, Roxanne Denny1, Shweta Deshpande17, Xinbin Dai, Jeff J. Doyle18, Anne Marie Dudez2, Anne Marie Dudez3, Andrew Farmer15, Stéphanie Fouteau, Carolien Franken5, Chrystel Gibelin3, Chrystel Gibelin2, John Gish11, Steven A. Goldstein14, Alvaro J. González12, Pamela J. Green12, Asis Hallab19, Marijke Hartog5, Axin Hua17, Sean Humphray20, Dong-Hoon Jeong12, Yi Jing17, Anika Jöcker19, Steve Kenton17, Dong-Jin Kim21, Dong-Jin Kim11, Kathrin Klee19, Hongshing Lai17, Chunting Lang5, Shaoping Lin17, Simone L. Macmil17, Ghislaine Magdelenat, Lucy Matthews20, Jamison McCorrison13, Erin L. Monaghan13, Jeong Hwan Mun11, Jeong Hwan Mun22, Fares Z. Najar17, Christine Nicholson20, Céline Noirot2, Majesta O'Bleness17, Charles Paule1, Julie Poulain, Florent Prion3, Florent Prion2, Baifang Qin17, Chunmei Qu17, Ernest F. Retzel15, Claire Riddle20, Erika Sallet3, Erika Sallet2, Sylvie Samain, Nicolas Samson3, Nicolas Samson2, Iryna Sanders17, Olivier Saurat2, Olivier Saurat3, Claude Scarpelli, Thomas Schiex2, Béatrice Segurens, Andrew J. Severin6, D. Janine Sherrier12, Ruihua Shi17, Sarah Sims20, Susan R. Singer23, Senjuti Sinharoy, Lieven Sterck10, Agnès Viollet, Bing Bing Wang1, Keqin Wang17, Mingyi Wang, Xiaohong Wang1, Jens Warfsmann19, Jean Weissenbach, Doug White17, James D. White17, Graham B. Wiley17, Patrick Wincker, Yanbo Xing17, Limei Yang17, Ziyun Yao17, Fu Ying17, Jixian Zhai12, Liping Zhou17, Antoine Zuber2, Antoine Zuber3, Jean Dénarié3, Jean Dénarié2, Richard A. Dixon, Gregory D. May15, David C. Schwartz14, Jane Rogers24, Francis Quetier, Christopher D. Town13, Bruce A. Roe17 
22 Dec 2011-Nature
TL;DR: The draft sequence of the M. truncatula genome sequence is described, a close relative of alfalfa (Medicago sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics, which provides significant opportunities to expand al falfa’s genomic toolbox.
Abstract: Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation. Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Myr ago). Papilionoids are the largest clade, dating nearly to the origin of legumes and containing most cultivated species. Medicago truncatula is a long-established model for the study of legume biology. Here we describe the draft sequence of the M. truncatula euchromatin based on a recently completed BAC assembly supplemented with Illumina shotgun sequence, together capturing ∼94% of all M. truncatula genes. A whole-genome duplication (WGD) approximately 58 Myr ago had a major role in shaping the M. truncatula genome and thereby contributed to the evolution of endosymbiotic nitrogen fixation. Subsequent to the WGD, the M. truncatula genome experienced higher levels of rearrangement than two other sequenced legumes, Glycine max and Lotus japonicus. M. truncatula is a close relative of alfalfa (Medicago sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics. As such, the M. truncatula genome sequence provides significant opportunities to expand alfalfa's genomic toolbox.

Journal ArticleDOI
TL;DR: The ecotoxicological literature shows that concentrations of Ag NPs below the current and future PECs, as low as just a few ng L(-1), can affect prokaryotes, invertebrates and fish indicating a significant potential, though poorly characterised, risk to the environment.

Journal ArticleDOI
TL;DR: The characterization of the molecular mechanisms regulating hormone synthesis, signaling, and action are facilitating the modification of hormone biosynthetic pathways for the generation of transgenic crop plants with enhanced abiotic stress tolerance.

Journal ArticleDOI
16 May 2011
TL;DR: In this article, the authors provide an overview of what PLC can deliver today by surveying its history and describing the most recent technological advances in the area and discuss the main conclusions one can draw from the literature on these subjects.
Abstract: Are Power Line Communications (PLC) a good candidate for Smart Grid applications? The objective of this paper is to address this important question. To do so, we provide an overview of what PLC can deliver today by surveying its history and describing the most recent technological advances in the area. We then address Smart Grid applications as instances of sensor networking and network control problems and discuss the main conclusions one can draw from the literature on these subjects. The application scenario of PLC within the Smart Grid is then analyzed in detail. Because a necessary ingredient of network planning is modeling, we also discuss two aspects of engineering modeling that relate to our question. The first aspect is modeling the PLC channel through fading models. The second aspect we review is the Smart Grid control and traffic modeling problem which allows us to achieve a better understanding of the communications requirements. Finally, this paper reports recent studies on the electrical and topological properties of a sample power distribution network. Power grid topological studies are very important for PLC networking as the power grid is not only the information source but also the information delivery system-a unique feature when PLC is used for the Smart Grid.

Journal ArticleDOI
Marcos Daniel Actis1, G. Agnetta2, Felix Aharonian3, A. G. Akhperjanian  +682 moreInstitutions (109)
TL;DR: The ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes as mentioned in this paper, which is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100GeV and above 100 TeV.
Abstract: Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.

Journal ArticleDOI
TL;DR: An overview of the intestinal microbiota is provided and the cell biology of Paneth cells is described, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis.
Abstract: Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.

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TL;DR: P porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles are reported that allow a single protocell loaded with a drug cocktail to kill a drug-resistant HCC cell, representing a 106-fold improvement over comparable liposome.
Abstract: Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes.

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TL;DR: Using a sensory ecology approach, a mechanistic framework for predicting variation in behavioural responses to environmental change is presented, drawing from models of decision‐making processes and an understanding of the selective background against which they evolved.
Abstract: Almost all organisms live in environments that have been altered, to some degree, by human activities. Because behaviour mediates interactions between an individual and its environment, the ability of organisms to behave appropriately under these new conditions is crucial for determining their immediate success or failure in these modified environments. While hundreds of species are suffering dramatically from these environmental changes, others, such as urbanized and pest species, are doing better than ever. Our goal is to provide insights into explaining such variation. We first summarize the responses of some species to novel situations, including novel risks and resources, habitat loss/fragmentation, pollutants and climate change. Using a sensory ecology approach, we present a mechanistic framework for predicting variation in behavioural responses to environmental change, drawing from models of decision-making processes and an understanding of the selective background against which they evolved. Where immediate behavioural responses are inadequate, learning or evolutionary adaptation may prove useful, although these mechanisms are also constrained by evolutionary history. Although predicting the responses of species to environmental change is difficult, we highlight the need for a better understanding of the role of evolutionary history in shaping individuals’ responses to their environment and provide suggestion for future work.

Journal ArticleDOI
28 Jan 2011-Science
TL;DR: Only an extensive research effort involving multiple experimental approaches—particularly long-term field experiments—over a variety of ecological communities will provide the answer to the importance of the evolution-to-ecology pathway across systems.
Abstract: The effect of ecological change on evolution has long been a focus of scientific research. The reverse—how evolutionary dynamics affect ecological traits—has only recently captured our attention, however, with the realization that evolution can occur over ecological time scales. This newly highlighted causal direction and the implied feedback loop—eco-evolutionary dynamics—is invigorating both ecologists and evolutionists and blurring the distinction between them. Despite some recent relevant studies, the importance of the evolution-to-ecology pathway across systems is still unknown. Only an extensive research effort involving multiple experimental approaches—particularly long-term field experiments—over a variety of ecological communities will provide the answer.

Journal ArticleDOI
TL;DR: The left MTG showed a particularly extensive structural and functional connectivity pattern which is consistent with the severity of the impairments associated with MTG lesions and which suggests a central role for this region in language comprehension.
Abstract: While traditional models of language comprehension have focused on the left posterior temporal cortex as the neurological basis for language comprehension, lesion and functional imaging studies indicate the involvement of an extensive network of cortical regions. However, the full extent of this network and the white matter pathways that contribute to it remain to be characterized. In an earlier voxel-based lesion-symptom mapping analysis of data from aphasic patients (Dronkers et al., 2004), several brain regions in the left hemisphere were found to be critical for language comprehension: the left posterior middle temporal gyrus (MTG), the anterior part of Brodmann’s area 22 in the superior temporal gyrus (anterior STG/BA22), the posterior superior temporal sulcus (STS) extending into Brodmann’s area 39 (STS/BA39), the orbital part of the inferior frontal gyrus (BA47) and the middle frontal gyrus (BA46). Here, we investigated the white matter pathways associated with these regions using diffusion tensor imaging from healthy subjects. We also used resting-state functional magnetic resonance imaging data to assess the functional connectivity profiles of these regions. Fiber tractography and functional connectivity analyses indicated that the left MTG, anterior STG/BA22, STS/BA39 and BA47 are part of a richly interconnected network that extends to additional frontal, parietal and temporal regions in the two hemispheres. The inferior occipito-frontal fasciculus, the arcuate fasciculus and the middle and inferior longitudinal fasciculi, as well as transcallosal projections via the tapetum were found to be the most prominent white matter pathways bridging the regions important for language comprehension. The left posterior MTG showed a particularly extensive structural and functional connectivity pattern which is consistent with the severity of the impairments associated with MTG lesions and which suggests a central role for this region in language comprehension.

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TL;DR: The state factor approach is used to highlight the role of important aspects of climate, substrate, organisms, relief, and time in differentiating urban from non-urban areas, and for determining heterogeneity within spatially extensive metropolitan areas.