Showing papers by "University of Glasgow published in 2009"
Queen's University Belfast1, Collège de France2, English Heritage3, University of Arizona4, University of Sheffield5, University of Oxford6, University of Minnesota7, University of Hohenheim8, University of Kiel9, Lawrence Livermore National Laboratory10, University of Bergen11, ETH Zurich12, University of Waikato13, Woods Hole Oceanographic Institution14, Swiss Federal Institute for Forest, Snow and Landscape Research15, Cornell University16, University of Bristol17, University of Glasgow18, University of California, Irvine19, University of New South Wales20
TL;DR: In this paper, Heaton, AG Hogg, KA Hughen, KF Kaiser, B Kromer, SW Manning, RW Reimer, DA Richards, JR Southon, S Talamo, CSM Turney, J van der Plicht, CE Weyhenmeyer
Abstract: Additional co-authors: TJ Heaton, AG Hogg, KA Hughen, KF Kaiser, B Kromer, SW Manning, RW Reimer, DA Richards, JR Southon, S Talamo, CSM Turney, J van der Plicht, CE Weyhenmeyer
13,605 citations
Kevork N. Abazajian1, Jennifer K. Adelman-McCarthy2, Marcel A. Agüeros3, S. Allam2 +220 more•Institutions (77)
TL;DR: A series of improvements to the spectroscopic reductions are described, including better flat fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities.
Abstract: This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11,663 deg^2 of imaging data, with most of the ~2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry on a 120° long, 2°.5 wide stripe along the celestial equator in the Southern Galactic Cap, with some regions covered by as many as 90 individual imaging runs. We include a co-addition of the best of these data, going roughly 2 mag fainter than the main survey over 250 deg^2. The survey has completed spectroscopy over 9380 deg^2; the spectroscopy is now complete over a large contiguous area of the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog, reducing the rms statistical errors at the bright end to 45 milliarcseconds per coordinate. We further quantify a systematic error in bright galaxy photometry due to poor sky determination; this problem is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities.
5,665 citations
University of Paris-Sud1, French Institute of Health and Medical Research2, Institut Gustave Roussy3, Icahn School of Medicine at Mount Sinai4, University of Texas Southwestern Medical Center5, Thomas Jefferson University6, McMaster University7, University of Massachusetts Medical School8, LSU Health Sciences Center New Orleans9, Roswell Park Cancer Institute10, Boston Children's Hospital11, University of Gothenburg12, University of Freiburg13, Buck Institute for Research on Aging14, University of California, San Francisco15, Centre national de la recherche scientifique16, National Institutes of Health17, Technion – Israel Institute of Technology18, University of Leicester19, University of Chieti-Pescara20, Istituto Superiore di Sanità21, University of North Carolina at Chapel Hill22, New York University23, University of Pennsylvania24, Yale University25, Howard Hughes Medical Institute26, University of Ulm27, University of Burgundy28, Aix-Marseille University29, Pasteur Institute30, University of Strasbourg31, Johns Hopkins University32, University of Zurich33, University of Tokyo34, Weizmann Institute of Science35, University of Michigan36, University College London37, Duke University38, University of Graz39, Ghent University40, Trinity College, Dublin41, University of Amsterdam42, University of Lyon43, University of Rome Tor Vergata44, Stony Brook University45, University of Göttingen46, Kyoto University47, Merck & Co.48, Austrian Academy of Sciences49, National University of Singapore50, University of Chicago51, Royal College of Surgeons in Ireland52, La Trobe University53, University of Buenos Aires54, University of Padua55, University of Lisbon56, University of Cambridge57, University of Würzburg58, University of Geneva59, University of Bern60, Rockefeller University61, University of Lausanne62, Osaka University63, University of California, San Diego64, University of Glasgow65, Harvard University66, Karolinska Institutet67
TL;DR: A nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls is provided and the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells is emphasized.
Abstract: Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios Thus far, dozens of methods have been proposed to quantify cell death-related parameters However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells
2,218 citations
TL;DR: This review summarizes the chemistry, biosynthesis and occurrence of the compounds involved, namely the C6-C3-C6 flavonoids-anthocyanins, dihydrochalcones, Flavan-3-ols, flavanones, flavones, Flavonols and isoflavones, and the mechanisms underlying these processes are discussed.
1,728 citations
01 Dec 2009
TL;DR: An adaptive particle swarm optimization that features better search efficiency than classical particle Swarm optimization (PSO) is presented and can perform a global search over the entire search space with faster convergence speed.
Abstract: An adaptive particle swarm optimization (APSO) that features better search efficiency than classical particle swarm optimization (PSO) is presented. More importantly, it can perform a global search over the entire search space with faster convergence speed. The APSO consists of two main steps. First, by evaluating the population distribution and particle fitness, a real-time evolutionary state estimation procedure is performed to identify one of the following four defined evolutionary states, including exploration, exploitation, convergence, and jumping out in each generation. It enables the automatic control of inertia weight, acceleration coefficients, and other algorithmic parameters at run time to improve the search efficiency and convergence speed. Then, an elitist learning strategy is performed when the evolutionary state is classified as convergence state. The strategy will act on the globally best particle to jump out of the likely local optima. The APSO has comprehensively been evaluated on 12 unimodal and multimodal benchmark functions. The effects of parameter adaptation and elitist learning will be studied. Results show that APSO substantially enhances the performance of the PSO paradigm in terms of convergence speed, global optimality, solution accuracy, and algorithm reliability. As APSO introduces two new parameters to the PSO paradigm only, it does not introduce an additional design or implementation complexity.
1,713 citations
Cristen J. Willer, Elizabeth K. Speliotes1, Elizabeth K. Speliotes2, Ruth J. F. Loos +163 more•Institutions (36)
TL;DR: Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
Abstract: Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
1,710 citations
Broad Institute1, Sainsbury Laboratory2, Ohio Agricultural Research and Development Center3, Uppsala University4, Wageningen University and Research Centre5, Virginia Bioinformatics Institute6, University of California, Riverside7, University of Aberdeen8, Scottish Crop Research Institute9, University of Warwick10, Agricultural Research Service11, Royal Institute of Technology12, Cornell University13, Oregon State University14, Lafayette College15, University of Glasgow16, Harvard University17, Delaware Biotechnology Institute18, North Carolina State University19, University of Delaware20, University of Tennessee21, University of Maryland, Baltimore22, Vanderbilt University23, College of Wooster24, Bowling Green State University25, Edinburgh Cancer Research Centre26, J. Craig Venter Institute27, Tel Aviv University28, University of Wisconsin-Madison29, University of Hohenheim30, University of Dundee31
TL;DR: The sequence of the P. infestans genome is reported, which at ∼240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates and probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
Abstract: Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
1,341 citations
TL;DR: Overall, intensive compared with standard glycaemic control significantly reduces coronary events without an increased risk of death, however, the optimum mechanism, speed, and extent of HbA(1c) reduction might be different in differing populations.
1,327 citations
Christopher Newton-Cheh1, Christopher Newton-Cheh2, Toby Johnson3, Toby Johnson4 +359 more•Institutions (64)
TL;DR: In this paper, the association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2(P = 1 × 10-23), FGF5 (P=1 × 10 -21), SH2B3(P= 3 × 10−18), MTHFR(MTHFR), c10orf107(P), ZNF652(ZNF652), PLCD3 (P,P = 5 × 10 −9),
Abstract: Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
1,205 citations
TL;DR: The potential role of oxidative stress in mediating life-history trade-offs is critically reviewed, a framework for formulating appropriate hypotheses and guiding experimental design is presented, and potentially fruitful areas for further research are indicated.
Abstract: The concept of trade-offs is central to our understanding of life-history evolution. The underlying mechanisms, however, have been little studied. Oxidative stress results from a mismatch between the production of damaging reactive oxygen species (ROS) and the organism's capacity to mitigate their damaging effects. Managing oxidative stress is likely to be a major determinant of life histories, as virtually all activities generate ROS. There is a recent burgeoning of interest in how oxidative stress is related to different components of animal performance. The emphasis to date has been on immediate or short-term effects, but there is an increasing realization that oxidative stress will influence life histories over longer time scales. The concept of oxidative stress is currently used somewhat loosely by many ecologists, and the erroneous assumption often made that dietary antioxidants are necessarily the major line of defence against ROS-induced damage. We summarize current knowledge on how oxidative stress occurs and the different methods for measuring it, and highlight where ecologists can be too simplistic in their approach. We critically review the potential role of oxidative stress in mediating life-history trade-offs, and present a framework for formulating appropriate hypotheses and guiding experimental design. We indicate throughout potentially fruitful areas for further research.
1,173 citations
University of Hertfordshire1, University of Alabama at Birmingham2, University of Helsinki3, University of South Florida4, University of Glasgow5, University of Kentucky6, Leiden University Medical Center7, Institute for Animal Health8, University of Guelph9, Katholieke Universiteit Leuven10, Pasteur Institute11, Agriculture and Agri-Food Canada12, University of Bristol13, University of Edinburgh14, Queen's University15
TL;DR: Changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses in February 2015 are listed.
Abstract: Changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses in February 2015 are listed.
TL;DR: An algorithm is presented, PyroNoise, that clusters the flowgrams of 454 pyrosequencing reads using a distance measure that models sequencing noise and infers the true sequences in a collection of amplicons.
Abstract: We present an algorithm, PyroNoise, that clusters the flowgrams of 454 pyrosequencing reads using a distance measure that models sequencing noise. This infers the true sequences in a collection of amplicons. We pyrosequenced a known mixture of microbial 16S rDNA sequences extracted from a lake and found that without noise reduction the number of operational taxonomic units is overestimated but using PyroNoise it can be accurately calculated.
University of Milano-Bicocca1, University of Paris2, University of Brescia3, University of Bologna4, University of Lausanne5, Queen Mary University of London6, Ghent University7, University of Barcelona8, University of Glasgow9, Istanbul University10, Katholieke Universiteit Leuven11, Hannover Medical School12, University of Manchester13, University of Oslo14, Joseph Fourier University15, Gdańsk Medical University16, University of Copenhagen17, University of Münster18, University of Valencia19, Complutense University of Madrid20, University of Erlangen-Nuremberg21, Maastricht University22, University of Amsterdam23, University of Milan24
TL;DR: The objective of this study was to establish a baseline for the design of a systematic literature review of this type of treatment for high blood pressure using a simple, straightforward, and scalable procedure.
Abstract: Abbreviations ACE: angiotensin-converting enzyme; BP: blood pressure; DBP: diastolic blood pressure; eGFR: estimated glomerular filtration rate; ESC: European Society of Cardiology; ESH: European Society of Hypertension; ET: endothelin; IMT: carotid intima-media thickness; JNC: Joint National Commit
TL;DR: For people choosing to start pharmacological prophylaxis, reduction in both LDL cholesterol and hsCRP are indicators of successful treatment with rosuvastatin, and these reductions were predictive of event rates irrespective of the lipid endpoint used.
TL;DR: The taxonomy of herpesviruses has been updated by the International Committee on Taxonomy of Viruses (ICTV), and the names of some nonhuman primate virus species have been changed.
Abstract: The taxonomy of herpesviruses has been updated by the International Committee on Taxonomy of Viruses (ICTV). The former family Herpesviridae has been split into three families, which have been incorporated into the new order Herpesvirales. The revised family Herpesviridae retains the mammal, bird and reptile viruses, the new family Alloherpesviridae incorporates the fish and frog viruses, and the new family Malacoherpesviridae contains a bivalve virus. Three new genera have been created in the family Herpesviridae, namely Proboscivirus in the subfamily Betaherpesvirinae and Macavirus and Percavirus in the subfamily Gammaherpesvirinae. These genera have been formed by the transfer of species from established genera and the erection of new species, and other new species have been added to some of the established genera. In addition, the names of some nonhuman primate virus species have been changed. The family Alloherpesviridae has been populated by transfer of the genus Ictalurivirus and addition of the new species Cyprinid herpesvirus 3. The family Malacoherpesviridae incorporates the new genus Ostreavirus containing the new species Ostreid herpesvirus 1.
TL;DR: Normalization Process Theory explains how new technologies, ways of acting, and ways of working become routinely embedded in everyday practice, and has applications in the study of implementation processes.
Abstract: Theories are important tools in the social and natural sciences. The methods by which they are derived are rarely described and discussed. Normalization Process Theory explains how new technologies, ways of acting, and ways of working become routinely embedded in everyday practice, and has applications in the study of implementation processes. This paper describes the process by which it was built. Between 1998 and 2008, we developed a theory. We derived a set of empirical generalizations from analysis of data collected in qualitative studies of healthcare work and organization. We developed an applied theoretical model through analysis of empirical generalizations. Finally, we built a formal theory through a process of extension and implication analysis of the applied theoretical model. Each phase of theory development showed that the constructs of the theory did not conflict with each other, had explanatory power, and possessed sufficient robustness for formal testing. As the theory developed, its scope expanded from a set of observed regularities in data with procedural explanations, to an applied theoretical model, to a formal middle-range theory. Normalization Process Theory has been developed through procedures that were properly sceptical and critical, and which were opened to review at each stage of development. The theory has been shown to merit formal testing.
TL;DR: The data suggest that aberrant expression of AR splice variants may be a novel mechanism underlying ablation independence during PCA progression, and AR3 may serve as a prognostic marker to predict patient outcome in response to hormonal therapy.
Abstract: The androgen receptor (AR) plays a key role in progression to incurable androgen ablation–resistant prostate cancer (PCA). We have identified three novel AR splice variants lacking the ligand-binding domain (designated as AR3, AR4, and AR5) in hormone-insensitive PCA cells. AR3, one of the major splice variants expressed in human prostate tissues, is constitutively active, and its transcriptional activity is not regulated by androgens or antiandrogens. Immunohistochemistry analysis on tissue microarrays containing 429 human prostate tissue samples shows that AR3 is significantly up-regulated during PCA progression and AR3 expression level is correlated with the risk of tumor recurrence after radical prostatectomy. Overexpression of AR3 confers ablation-independent growth of PCA cells, whereas specific knockdown of AR3 expression (without altering AR level) in hormone-resistant PCA cells attenuates their growth under androgen-depleted conditions in both cell culture and xenograft models, suggesting an indispensable role of AR3 in ablation-independent growth of PCA cells. Furthermore, AR3 may play a distinct, yet essential, role in ablation-independent growth through the regulation of a unique set of genes, including AKT1 , which are not regulated by the prototype AR. Our data suggest that aberrant expression of AR splice variants may be a novel mechanism underlying ablation independence during PCA progression, and AR3 may serve as a prognostic marker to predict patient outcome in response to hormonal therapy. Given that these novel AR splice variants are not inhibited by currently available antiandrogen drugs, development of new drugs targeting these AR isoforms may potentially be effective for treatment of ablation-resistant PCA. [Cancer Res 2009;69(6):2305–13]
TL;DR: This article reviews several methods that have been applied to investigate interactions between brain regions in source space, and will mainly focus on the different measures used to quantify connectivity, and on theDifferent strategies adopted to identify regions of interest.
Abstract: Interactions between functionally specialized brain regions are crucial for normal brain function. Magnetoencephalography (MEG) and electroencephalography (EEG) are techniques suited to capture these interactions, because they provide whole head measurements of brain activity in the millisecond range. More than one sensor picks up the activity of an underlying source. This field spread severely limits the utility of connectivity measures computed directly between sensor recordings. Consequentially, neuronal interactions should be studied on the level of the reconstructed sources. This article reviews several methods that have been applied to investigate interactions between brain regions in source space. We will mainly focus on the different measures used to quantify connectivity, and on the different strategies adopted to identify regions of interest. Despite various successful accounts of MEG and EEG source connectivity, caution with respect to the interpretation of the results is still warranted. This is due to the fact that effects of field spread can never be completely abolished in source space. However, in this very exciting and developing field of research this cautionary note should not discourage researchers from further investigation into the connectivity between neuronal sources.
TL;DR: In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.
Abstract: Objectives To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus. Design Meta-analysis of randomised trials. Data sources Cochrane controlled trials register, Embase, and Medline. Data abstraction Two independent investigators identified studies on the clinical effects of statins compared with a placebo or control group and with follow-up of at least one year, at least 80% or more participants without established cardiovascular disease, and outcome data on mortality and major cardiovascular disease events. Heterogeneity was assessed using the Q and I 2 statistics. Publication bias was assessed by visual examination of funnel plots and the Egger regression test. Results 10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed. There was no significant heterogeneity of the treatment effect in clinical subgroups. Conclusion In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.
TL;DR: The origins of a cell type critical to the process of pulmonary vascular remodeling, the myofibroblast, are discussed, and the evidence supporting a contribution for the involvement of endothelial-mesenchymal transition and recruitment of circulating mesenchymic progenitor cells is reviewed.
TL;DR: A comprehensive and critical review of the phenomenological, empirical, neuroscientific and theoretical literature pertaining to visual processing in ASD is presented, along with a brief justification of a new theory which may help to explain some of the data and link it with other current hypotheses about the genetic and neural aetiologies of this enigmatic condition.
TL;DR: In this article, it was shown that the Poynting vector has features that are not immediately apparent from the intensity alone, nor from global properties of a beam, but can be easily recognized from the analysis of optical vortices and orbital angular momentum.
Abstract: Publisher Summary The widespread availability of spatially and temporally coherent laser sources makes the production of optical vortices inevitable in any experiment involving scattered laser light. The realization of quantized vortices is not specific to optics: these objects occur in all spatial scalar fields. Although optical vortices are often referred to as “points of phase singularity within a cross section of the field,” physical optical fields extend over three dimensions, and the phase singularities are actually lines of perfect destructive interference that are embedded in the volume filled by the light. Optical vortices are examples of the singularity lines within all complicated scalar fields. By comparison, electromagnetic vector fields do not generally have nodes in all components simultaneously. However, vector fields possess singularities associated with the parameterization of elliptical and partial polarization rather than phase. Polarization singularities are present in many situations, ranging from sunlight to the light transmitted by birefringent materials. Their descriptors are more complicated than their scalar counterpart in that they have both handedness and additional categorization. The study of optical vortices and orbital angular momentum has led to a recognition that the energy flow—characterized by the Poynting vector—has features not immediately apparent from the intensity alone, nor from global properties of a beam.
TL;DR: A modest effect of purifying selection on the mtDNA coding region is confirmed and an improved molecular clock for dating human mtDNA is proposed, based on a worldwide phylogeny of > 2000 complete mtDNA genomes and calibrating against recent evidence for the divergence time of humans and chimpanzees.
Abstract: There is currently no calibration available for the whole human mtDNA genome, incorporating both coding and control regions. Furthermore, as several authors have pointed out recently, linear molecular clocks that incorporate selectable characters are in any case problematic. We here confirm a modest effect of purifying selection on the mtDNA coding region and propose an improved molecular clock for dating human mtDNA, based on a worldwide phylogeny of > 2000 complete mtDNA genomes and calibrating against recent evidence for the divergence time of humans and chimpanzees. We focus on a time-dependent mutation rate based on the entire mtDNA genome and supported by a neutral clock based on synonymous mutations alone. We show that the corrected rate is further corroborated by archaeological dating for the settlement of the Canary Islands and Remote Oceania and also, given certain phylogeographic assumptions, by the timing of the first modern human settlement of Europe and resettlement after the Last Glacial Maximum. The corrected rate yields an age of modern human expansion in the Americas at ∼15 kya that—unlike the uncorrected clock—matches the archaeological evidence, but continues to indicate an out-of-Africa dispersal at around 55–70 kya, 5–20 ky before any clear archaeological record, suggesting the need for archaeological research efforts focusing on this time window. We also present improved rates for the mtDNA control region, and the first comprehensive estimates of positional mutation rates for human mtDNA, which are essential for defining mutation models in phylogenetic analyses.
TL;DR: It is demonstrated here that IL-33/ST2 plays a significant role in the amplification of AAM polarization and chemokine production which contribute to innate and Ag-induced airway inflammation.
Abstract: Alternatively activated macrophages (AAM) play a crucial role in type 2 immunity. Mice deficient in ST2, a receptor for the latest member of the IL-1 family, IL-33, have impaired type 2 immune responses. We therefore reasoned that IL-33/ST2 signaling may be involved in the differentiation and activation of AAM during airway inflammation. We report here that IL-33 changed the quiescent phenotype of alveolar macrophages toward an AAM phenotype that expressed mannose receptor, IL-4Rα, and produced high levels of CCL24 and CCL17 in an IL-13-dependent manner during IL-33-induced airway inflammation. Neutralization of AAM-derived CCL24 led to an amelioration of IL-33-induced eosinophilia in the lungs. Moreover, depletion of alveolar macrophages reduced IL-33-induced airway inflammation. Additionally, the attenuated OVA-induced airway inflammation in ST2−/− mice was associated with a decrease in AAM differentiation. In vitro, IL-33 amplified IL-13-induced polarization of alveolar- and bone marrow-derived macrophage toward an AAM phenotype by increasing the expression of arginase I, Ym1, as well as the production of CCL24 and CCL17. IL-13/IL-4Rα signaling was crucial for IL-33-driven AAM amplification by inducing the expression of ST2L. Finally, we showed that IL-33 was more abundantly expressed in the lung epithelial cells of asthma patients than those from healthy controls, suggesting that IL-33 may be involved in lung macrophage activation in clinical asthma. Taken together, we demonstrate here that IL-33/ST2 plays a significant role in the amplification of AAM polarization and chemokine production which contribute to innate and Ag-induced airway inflammation.
Cecilia M. Lindgren1, Iris M. Heid2, Joshua C. Randall1, Claudia Lamina3 +152 more•Institutions (36)
TL;DR: By focusing on anthropometric measures of central obesity and fat distribution, a meta-analysis of 16 genome-wide association studies informative for adult waist circumference and waist–hip ratio identified three loci implicated in the regulation of human adiposity.
Abstract: To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
TL;DR: In a randomized trial of 17,802 apparently healthy men and women with both low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (34 mmol per liter) and high-sensitivity C-reactive protein levels of 20 mg per liter or higher to receive rosuvastatin or placebo.
Abstract: Background Controversy persists regarding the extent of shared pathways between arterial and venous thrombosis and whether treatments of known efficacy for one disease process have consistent benefits for the other Observational studies have yielded variable estimates of the effect of statin therapy on the risk of venous thromboembolism, and evidence from randomized trials is lacking Methods We randomly assigned 17,802 apparently healthy men and women with both low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (34 mmol per liter) and high-sensitivity C-reactive protein levels of 20 mg per liter or higher to receive rosuvastatin, 20 mg per day, or placebo We followed participants for the first occurrence of pulmonary embolism or deep-vein thrombosis and performed analyses of the data on an intention-to-treat basis Results During a median follow-up period of 19 years (maximum, 50), symptomatic venous thromboembolism occurred in 94 participants: 34 in the rosuvastatin group and 60 in the placebo group The rates of venous thromboembolism were 018 and 032 event per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio with rosuvastatin, 057; 95% confidence interval [CI], 037 to 086; P = 0007); the corresponding rates for unprovoked venous thromboembolism (ie, occurring in the absence of a known malignant condition, trauma, hospitalization, or surgery) were 010 and 017 (hazard ratio, 061; 95% CI, 035 to 109; P = 009) and for provoked venous thromboembolism (ie, occurring in patients with cancer or during or shortly after trauma, hospitalization, or surgery), 008 and 016 (hazard ratio, 052; 95% CI, 028 to 096; P = 003) The rates of pulmonary embolism were 009 in the rosuvastatin group and 012 in the placebo group (hazard ratio, 077; 95% CI, 041 to 145; P = 042), whereas the rates of deep-vein thrombosis only were 009 and 020, respectively (hazard ratio, 045; 95% CI, 025 to 079; P = 0004) Consistent effects were observed in all the subgroups examined No significant differences were seen between treatment groups in the rates of bleeding episodes Conclusions In this trial of apparently healthy persons, rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism (ClinicalTrialsgov number, NCT00239681)
19 Jul 2009
TL;DR: This work created a collaborative recommendation system that effectively adapts to the personal information needs of each user, and adopts the generic framework of Random Walk with Restarts in order to provide with a more natural and efficient way to represent social networks.
Abstract: Social network systems, like last.fm, play a significant role in Web 2.0, containing large amounts of multimedia-enriched data that are enhanced both by explicit user-provided annotations and implicit aggregated feedback describing the personal preferences of each user. It is also a common tendency for these systems to encourage the creation of virtual networks among their users by allowing them to establish bonds of friendship and thus provide a novel and direct medium for the exchange of data. We investigate the role of these additional relationships in developing a track recommendation system. Taking into account both the social annotation and friendships inherent in the social graph established among users, items and tags, we created a collaborative recommendation system that effectively adapts to the personal information needs of each user. We adopt the generic framework of Random Walk with Restarts in order to provide with a more natural and efficient way to represent social networks. In this work we collected a representative enough portion of the music social network last.fm, capturing explicitly expressed bonds of friendship of the user as well as social tags. We performed a series of comparison experiments between the Random Walk with Restarts model and a user-based collaborative filtering method using the Pearson Correlation similarity. The results show that the graph model system benefits from the additional information embedded in social knowledge. In addition, the graph model outperforms the standard collaborative filtering method.
Utrecht University1, Stanford University2, University Hospital of Lausanne3, University of Duisburg-Essen4, University of Bern5, University Hospital of Basel6, Sheba Medical Center7, University of Glasgow8, Katholieke Universiteit Leuven9, Charité10, Ludwig Maximilian University of Munich11, Heidelberg University12, Helsinki University Central Hospital13, Federal University of Rio de Janeiro14
TL;DR: The results do not support unequivocal superiority of IAT over IVT, and the efficacy of I AT versus IVT in patients with an acute BAO needs to be assessed in a randomised controlled trial.
Abstract: Summary Background Treatment strategies for acute basilar artery occlusion (BAO) are based on case series and data that have been extrapolated from stroke intervention trials in other cerebrovascular territories, and information on the efficacy of different treatments in unselected patients with BAO is scarce. We therefore assessed outcomes and differences in treatment response after BAO. Methods The Basilar Artery International Cooperation Study (BASICS) is a prospective, observational registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO between November 1, 2002, and October 1, 2007. Stroke severity at time of treatment was dichotomised as severe (coma, locked-in state, or tetraplegia) or mild to moderate (any deficit that was less than severe). Outcome was assessed at 1 month. Poor outcome was defined as a modified Rankin scale score of 4 or 5, or death. Patients were divided into three groups according to the treatment they received: antithrombotic treatment only (AT), which comprised antiplatelet drugs or systemic anticoagulation; primary intravenous thrombolysis (IVT), including subsequent intra-arterial thrombolysis; or intra-arterial therapy (IAT), which comprised thrombolysis, mechanical thrombectomy, stenting, or a combination of these approaches. Risk ratios (RR) for treatment effects were adjusted for age, the severity of neurological deficits at the time of treatment, time to treatment, prodromal minor stroke, location of the occlusion, and diabetes. Findings 619 patients were entered in the registry. 27 patients were excluded from the analyses because they did not receive AT, IVT, or IAT, and all had a poor outcome. Of the 592 patients who were analysed, 183 were treated with only AT, 121 with IVT, and 288 with IAT. Overall, 402 (68%) of the analysed patients had a poor outcome. No statistically significant superiority was found for any treatment strategy. Compared with outcome after AT, patients with a mild-to-moderate deficit (n=245) had about the same risk of poor outcome after IVT (adjusted RR 0·94, 95% CI 0·60–1·45) or after IAT (adjusted RR 1·29, 0·97–1·72) but had a worse outcome after IAT compared with IVT (adjusted RR 1·49, 1·00–2·23). Compared with AT, patients with a severe deficit (n=347) had a lower risk of poor outcome after IVT (adjusted RR 0·88, 0·76–1·01) or IAT (adjusted RR 0·94, 0·86–1·02), whereas outcomes were similar after treatment with IAT or IVT (adjusted RR 1·06, 0·91–1·22). Interpretation Most patients in the BASICS registry received IAT. Our results do not support unequivocal superiority of IAT over IVT, and the efficacy of IAT versus IVT in patients with an acute BAO needs to be assessed in a randomised controlled trial. Funding Department of Neurology, University Medical Center Utrecht.
TL;DR: Photomorphogenic signaling stimulates the expression of genes involved in UV-protection and hence promotes plant survival inUV-B, and is mediated by the UV-B-specific component UV RESISTANCE LOCUS8 (UVR8).
Abstract: UV-B radiation is a key environmental signal that initiates diverse responses in plants that affect metabolism, development, and viability. Many effects of UV-B involve the differential regulation of gene expression. The response to UV-B depends on the nature of the UV-B treatment, the extent of adaptation and acclimation to UV-B, and interaction with other environmental factors. Responses to UV-B are mediated by both nonspecific signaling pathways, involving DNA damage, reactive oxygen species, and wound/defense signaling molecules, and UV-B-specific pathways that mediate photomorphogenic responses to low levels of UV-B. Importantly, photomorphogenic signaling stimulates the expression of genes involved in UV-protection and hence promotes plant survival in UV-B. Photomorphogenic UV-B signaling is mediated by the UV-B-specific component UV RESISTANCE LOCUS8 (UVR8). Both UVR8 and CONSTITUTIVE PHOTOMORPHOGENESIS1 (COP1) are required for UV-B-induced expression of the ELONGATED HYPOCOTYL5 (HY5) transcription...
TL;DR: In this article, a structural model for the left ventricular myocardium is proposed, based on the invariants associated with the three mutually orthogonal directions of the myocardia.
Abstract: In this paper, we first of all review the morphology and structure of the myocardium and discuss the main features of the mechanical response of passive myocardium tissue, which is an orthotropic material. Locally within the architecture of the myocardium three mutually orthogonal directions can be identified, forming planes with distinct material responses. We treat the left ventricular myocardium as a non-homogeneous, thick-walled, nonlinearly elastic and incompressible material and develop a general theoretical framework based on invariants associated with the three directions. Within this framework we review existing constitutive models and then develop a structurally based model that accounts for the muscle fibre direction and the myocyte sheet structure. The model is applied to simple shear and biaxial deformations and a specific form fitted to the existing (and somewhat limited) experimental data, emphasizing the orthotropy and the limitations of biaxial tests. The need for additional data is highlighted. A brief discussion of issues of convexity of the model and related matters concludes the paper.