Showing papers by "University College Dublin published in 2009"
Cardiff University1, Medical Research Council2, University of Bristol3, National Institute for Health Research4, King's College5, Trinity College, Dublin6, University of Cambridge7, University of Nottingham8, Queen's University Belfast9, University of Southampton10, University of Manchester11, John Radcliffe Hospital12, UCL Institute of Neurology13, University of Bonn14, University of Hamburg15, Charité16, University of Erlangen-Nuremberg17, University of Duisburg-Essen18, Ludwig Maximilian University of Munich19, Heidelberg University20, University College Dublin21, University of Freiburg22, Washington University in St. Louis23, Brigham Young University24, University of Antwerp25, University College London26, Wellcome Trust Sanger Institute27, King's College London28, Aristotle University of Thessaloniki29, National Institutes of Health30, Mayo Clinic31
TL;DR: A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.
Abstract: We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 10-157) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 10-9) and 5' to the PICALM gene (rs3851179, P = 1.9 10-8). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 10-10, odds ratio = 0.86; rs3851179, P = 1.3 10-9, odds ratio = 0.86).
2,956 citations
TL;DR: The Gamma-Ray Burst Monitor (GBM) as mentioned in this paper uses an array of 12 sodium iodide scintillators and two bismuth germanate scintillation detectors to detect gamma rays from 8 keV to 40 MeV over the full unocculted sky.
Abstract: The Gamma-Ray Burst Monitor (GBM) will significantly augment the science return from the Fermi Observatory in the study of gamma-ray bursts (GRBs). The primary objective of GBM is to extend the energy range over which bursts are observed downward from the energy range of the Large Area Telescope (LAT) on Fermi into the hard X-ray range where extensive previous data sets exist. A secondary objective is to compute burst locations onboard to allow re-orienting the spacecraft so that the LAT can observe delayed emission from bright bursts. GBM uses an array of 12 sodium iodide scintillators and two bismuth germanate scintillators to detect gamma rays from ~8 keV to ~40 MeV over the full unocculted sky. The onboard trigger threshold is ~0.7 photons cm–2 s–1 (50-300 keV, 1 s peak). GBM generates onboard triggers for ~250 GRBs per year.
1,206 citations
University of Porto1, The Catholic University of America2, Sheba Medical Center3, Rambam Health Care Campus4, University of Palermo5, Boston Children's Hospital6, University College Dublin7, University of Barcelona8, Western General Hospital9, Guy's and St Thomas' NHS Foundation Trust10, McMaster University11, Université de Montréal12, Mount Sinai Hospital13
TL;DR: The treatment of inflammatory bowel disease has been revolutionised over the past decade by the increasing use of immunomodulators, mainly azathioprine/6-mercaptopurine and methotrexate, together with the advent of biological therapy.
1,150 citations
TL;DR: The aim of this review is to provide an insight into PDT photosensitizers clinically approved for application in oncology, as well as those which show significant potential in ongoing preclinical studies.
Abstract: Photodynamic therapy (PDT) is now a well-recognized modality for the treatment of cancer. While PDT has developed progressively over the last century, great advances have been observed in the field in recent years. The concept of dual selectivity of PDT agents is now widely accepted due to the relative specificity and selectivity of PDT along with the absence of harmful side effects often encountered with chemotherapy or radiotherapy. Traditionally, porphyrin-based photosensitizers have dominated the PDT field but these first generation photosensitizers have several disadvantages, with poor light absorption and cutaneous photosensitivity being the predominant side effects. As a result, the requirement for new photosensitizers, including second generation porphyrins and porphyrin derivatives as well as third generation photosensitizers has arisen, with the aim of alleviating the problems encountered with first generation porphyrins and improving the efficacy of PDT. The investigation of nonporphyrin photosensitizers for the development of novel PDT agents has been considerably less extensive than porphyrin-based compounds; however, structural modification of nonporphyrin photosensitizers has allowed for manipulation of the photochemotherapeutic properties. The aim of this review is to provide an insight into PDT photosensitizers clinically approved for application in oncology, as well as those which show significant potential in ongoing preclinical studies.
1,011 citations
University College Dublin1, Massachusetts Institute of Technology2, Broad Institute3, University of Aveiro4, University of Aberdeen5, Boston University6, University of Minnesota7, Duke University8, Imperial College London9, Stanford University10, University of Exeter11, Leibniz Association12, University of Amsterdam13, Wellcome Trust Sanger Institute14, University of Illinois at Urbana–Champaign15, Stony Brook University16, Newcastle University17, University of Iowa18, University of Sheffield19, University of Texas Health Science Center at Houston20
TL;DR: There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence in Candida albicans species.
Abstract: Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
956 citations
University of Leeds1, University of Yaoundé I2, Forestry Commission3, University of Agriculture, Faisalabad4, Smithsonian Institution5, Mbarara University of Science and Technology6, Wageningen University and Research Centre7, Salisbury University8, Wildlife Conservation Society9, University of York10, Environmental Change Institute11, University of Dar es Salaam12, University of Aberdeen13, University College Dublin14, University of Toronto15
TL;DR: Taxon-specific analyses of African inventory and other data suggest that widespread changes in resource availability, such as increasing atmospheric carbon dioxide concentrations, may be the cause of the increase in carbon stocks, as some theory and models predict.
Abstract: The response of terrestrial vegetation to a globally changing environment is central to predictions of future levels of atmospheric carbon dioxide. The role of tropical forests is critical because they are carbon-dense and highly productive. Inventory plots across Amazonia show that old-growth forests have increased in carbon storage over recent decades, but the response of one-third of the world's tropical forests in Africa is largely unknown owing to an absence of spatially extensive observation networks. Here we report data from a ten-country network of long-term monitoring plots in African tropical forests. We find that across 79 plots (163 ha) above-ground carbon storage in live trees increased by 0.63 Mg C ha(-1) yr(-1) between 1968 and 2007 (95% confidence interval (CI), 0.22-0.94; mean interval, 1987-96). Extrapolation to unmeasured forest components (live roots, small trees, necromass) and scaling to the continent implies a total increase in carbon storage in African tropical forest trees of 0.34 Pg C yr(-1) (CI, 0.15-0.43). These reported changes in carbon storage are similar to those reported for Amazonian forests per unit area, providing evidence that increasing carbon storage in old-growth forests is a pan-tropical phenomenon. Indeed, combining all standardized inventory data from this study and from tropical America and Asia together yields a comparable figure of 0.49 Mg C ha(-1) yr(-1) (n = 156; 562 ha; CI, 0.29-0.66; mean interval, 1987-97). This indicates a carbon sink of 1.3 Pg C yr(-1) (CI, 0.8-1.6) across all tropical forests during recent decades. Taxon-specific analyses of African inventory and other data suggest that widespread changes in resource availability, such as increasing atmospheric carbon dioxide concentrations, may be the cause of the increase in carbon stocks, as some theory and models predict.
941 citations
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TL;DR: It is argued that many recent objections against lab experiments are misguided and that even more lab experiments should be conducted, by comparing them to research based on nonexperimental data and to field experiments.
Abstract: Laboratory experiments are a widely used methodology for advancing causal knowledge in the physical and life sciences. With the exception of psychology, the adoption of laboratory experiments has been much slower in the social sciences, although during the last two decades, the use of lab experiments has accelerated. Nonetheless, there remains considerable resistance among social scientists who argue that lab experiments lack "realism" and "generalizability". In this article we discuss the advantages and limitations of laboratory social science experiments by comparing them to research based on nonexperimental data and to field experiments. We argue that many recent objections against lab experiments are misguided and that even more lab experiments should be conducted.
878 citations
TL;DR: It is concluded that soluble Abeta oligomers perturb synaptic plasticity by altering glutamate recycling at the synapse and promoting synapse depression.
864 citations
TL;DR: The results indicate that high-throughput yeast two-hybrid interactions for human proteins are more precise than literature-curated interactions supported by a single publication, suggesting that HT-Y2H is suitable to map a significant portion of the human interactome.
Abstract: Several attempts have been made to systematically map protein-protein interaction, or 'interactome', networks. However, it remains difficult to assess the quality and coverage of existing data sets. Here we describe a framework that uses an empirically-based approach to rigorously dissect quality parameters of currently available human interactome maps. Our results indicate that high-throughput yeast two-hybrid (HT-Y2H) interactions for human proteins are more precise than literature-curated interactions supported by a single publication, suggesting that HT-Y2H is suitable to map a significant portion of the human interactome. We estimate that the human interactome contains approximately 130,000 binary interactions, most of which remain to be mapped. Similar to estimates of DNA sequence data quality and genome size early in the Human Genome Project, estimates of protein interaction data quality and interactome size are crucial to establish the magnitude of the task of comprehensive human interactome mapping and to elucidate a path toward this goal.
862 citations
Broad Institute1, University of Pavia2, Uppsala University3, University of Bologna4, University of Kentucky5, University of Adelaide6, University of Tampa7, University of Veterinary Medicine Vienna8, University of Bern9, University of California, Davis10, Wellcome Trust Sanger Institute11, Cornell University12, Royal Veterinary College13, Institut national de la recherche agronomique14, Japan Racing Association15, University College Dublin16, Genetic Information Research Institute17, Swedish University of Agricultural Sciences18, University of Minnesota19, University of Bari20, Texas A&M University21, Animal Health Trust22, Massachusetts Institute of Technology23
TL;DR: The analysis reveals an evolutionarily new centromere on equine chromosome 11 that displays properties of an immature but fully functioning Centromere and is devoid of centromeric satellite sequence, suggesting thatCentromeric function may arise before satellite repeat accumulation.
Abstract: We report a high-quality draft sequence of the genome of the horse (Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.
745 citations
TL;DR: New principles for the formation of glycoside bonds are discussed and developments, mainly in the last ten years, that have led to significant advances in oligosaccharide and glycoconjugate synthesis have been compiled and are evaluated.
Abstract: Increased understanding of the important roles that oligosaccharides and glycoconjugates play in biological processes has led to a demand for significant amounts of these materials for biological, medicinal, and pharmacological studies. Therefore, tremendous effort has been made to develop new procedures for the synthesis of glycosides, whereby the main focus is often the formation of the glycosidic bonds. Accordingly, quite a few review articles have been published over the past few years on glycoside synthesis; however, most are confined to either a specific type of glycoside or a specific strategy for glycoside synthesis. In this Review, new principles for the formation of glycoside bonds are discussed. Developments, mainly in the last ten years, that have led to significant advances in oligosaccharide and glycoconjugate synthesis have been compiled and are evaluated.
TL;DR: In this review, antimicrobials from a range of plant, animal, and microbial sources are reviewed along with their potential applications in food systems and factors influencing the antimicrobial activity of such agents are discussed including extraction methods, molecular weight, and agent origin.
Abstract: In this review, antimicrobials from a range of plant, animal, and microbial sources are reviewed along with their potential applications in food systems. Chemical and biochemical antimicrobial compounds derived from these natural sources and their activity against a range of pathogenic and spoilage microorganisms pertinent to food, together with their effects on food organoleptic properties, are outlined. Factors influencing the antimicrobial activity of such agents are discussed including extraction methods, molecular weight, and agent origin. These issues are considered in conjunction with the latest developments in the quantification of the minimum inhibitory (and noninhibitory) concentration of antimicrobials and/or their components. Natural antimicrobials can be used alone or in combination with other novel preservation technologies to facilitate the replacement of traditional approaches. Research priorities and future trends focusing on the impact of product formulation, intrinsic product parameters, and extrinsic storage parameters on the design of efficient food preservation systems are also presented.
TL;DR: The authors discuss the advantages and limitations of laboratory social science experiments by comparing them to research based on nonexperimental data and to field experiments and argue that many recent objections against lab experiments are misguided and that even more lab experiments should be conducted.
Abstract: Laboratory experiments are a widely used methodology for advancing causal knowledge in the physical and life sciences. With the exception of psychology, the adoption of laboratory experiments has been much slower in the social sciences, although during the last two decades, the use of lab experiments has accelerated. Nonetheless, there remains considerable resistance among social scientists who argue that lab experiments lack “realism” and “generalizability”. In this article we discuss the advantages and limitations of laboratory social science experiments by comparing them to research based on nonexperimental data and to field experiments. We argue that many recent objections against lab experiments are misguided and that even more lab experiments should be conducted.
Posted Content•
01 Jan 2009TL;DR: In this article, the effects of stochastic wind and load on the unit commitment and dispatch of power systems with high levels of wind power are examined, by comparing the costs, planned operation and performance of the schedules produced.
Abstract: The stochastic nature of wind alters the unit commitment and dispatch problem. By accounting for this uncertainty when scheduling the system, more robust schedules are produced, which should, on average, reduce expected costs. In this paper, the effects of stochastic wind and load on the unit commitment and dispatch of power systems with high levels of wind power are examined. By comparing the costs, planned operation and performance of the schedules produced, it is shown that stochastic optimization results in less costly, of the order of 0.25%, and better performing schedules than deterministic optimization. The impact of planning the system more frequently to account for updated wind and load forecasts is then examined. More frequent planning means more up to date forecasts are used, which reduces the need for reserve and increases performance of the schedules. It is shown that mid merit and peaking units and the interconnection are the most affected parts of the system where uncertainty of wind is concerned
TL;DR: Several commonly-used sparsity measures are compared based on whether or not they satisfy these six propositions and only two of these measures satisfy all six: the pq-mean with p les 1, q > 1 and the Gini index.
Abstract: Sparsity of representations of signals has been shown to be a key concept of fundamental importance in fields such as blind source separation, compression, sampling and signal analysis. The aim of this paper is to compare several commonly-used sparsity measures based on intuitive attributes. Intuitively, a sparse representation is one in which a small number of coefficients contain a large proportion of the energy. In this paper, six properties are discussed: (Robin Hood, Scaling, Rising Tide, Cloning, Bill Gates, and Babies), each of which a sparsity measure should have. The main contributions of this paper are the proofs and the associated summary table which classify commonly-used sparsity measures based on whether or not they satisfy these six propositions. Only two of these measures satisfy all six: the pq-mean with p les 1, q > 1 and the Gini index.
TL;DR: The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gammaray energy, with the largest apparent energy release yet measured.
Abstract: Gamma-ray bursts (GRBs) are highly energetic explosions signaling the death of massive stars in distant galaxies. The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gamma-ray energy. In September 2008, Fermi observed the exceptionally luminous GRB 080916C, with the largest apparent energy release yet measured. The high-energy gamma rays are observed to start later and persist longer than the lower energy photons. A simple spectral form fits the entire GRB spectrum, providing strong constraints on emission models. The known distance of the burst enables placing lower limits on the bulk Lorentz factor of the outflow and on the quantum gravity mass.
TL;DR: In this paper, the effects of stochastic wind and load on the unit commitment and dispatch of power systems with high levels of wind power are examined, by comparing the costs, planned operation and performance of the schedules produced.
Abstract: The stochastic nature of wind alters the unit commitment and dispatch problem. By accounting for this uncertainty when scheduling the system, more robust schedules are produced, which should, on average, reduce expected costs. In this paper, the effects of stochastic wind and load on the unit commitment and dispatch of power systems with high levels of wind power are examined. By comparing the costs, planned operation and performance of the schedules produced, it is shown that stochastic optimization results in less costly, of the order of 0.25%, and better performing schedules than deterministic optimization. The impact of planning the system more frequently to account for updated wind and load forecasts is then examined. More frequent planning means more up to date forecasts are used, which reduces the need for reserve and increases performance of the schedules. It is shown that mid-merit and peaking units and the interconnection are the most affected parts of the system where uncertainty of wind is concerned.
TL;DR: Data on the vector tick Ixodes ricinus suggest that an extension of its northern and altitude range has been accompanied by an increased prevalence of tick-borne encephalitis, and climate change may also be partly responsible for the change in distribution of Dermacentor reticulatus.
Abstract: Zoonotic tick-borne diseases are an increasing health burden in Europe and there is speculation that this is partly due to climate change affecting vector biology and disease transmission. Data on the vector tick Ixodes ricinus suggest that an extension of its northern and altitude range has been accompanied by an increased prevalence of tick-borne encephalitis. Climate change may also be partly responsible for the change in distribution of Dermacentor reticulatus. Increased winter activity of I. ricinus is probably due to warmer winters and a retrospective study suggests that hotter summers will change the dynamics and pattern of seasonal activity, resulting in the bulk of the tick population becoming active in the latter part of the year. Climate suitability models predict that eight important tick species are likely to establish more northern permanent populations in a climate-warming scenario. However, the complex ecology and epidemiology of such tick-borne diseases as Lyme borreliosis and tick-borne encephalitis make it difficult to implicate climate change as the main cause of their increasing prevalence. Climate change models are required that take account of the dynamic biological processes involved in vector abundance and pathogen transmission in order to predict future tick-borne disease scenarios.
TL;DR: A linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms in a common set of 1,031 multiplex autism families, implicating SEMA5A as an autism susceptibility gene.
Abstract: Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.
TL;DR: The detection of emission up to ∼31 GeV from the distant and short GRB, and no evidence for the violation of Lorentz invariance is found, which disfavour quantum-gravity theories in which the quantum nature of space–time on a very small scale linearly alters the speed of light.
Abstract: A cornerstone of Einstein's special relativity is Lorentz invariance-the postulate that all observers measure exactly the same speed of light in vacuum, independent of photon-energy. While special relativity assumes that there is no fundamental length-scale associated with such invariance, there is a fundamental scale (the Planck scale, l(Planck) approximate to 1.62 x 10(-33) cm or E(Planck) = M(Planck)c(2) approximate to 1.22 x 10(19) GeV), at which quantum effects are expected to strongly affect the nature of space-time. There is great interest in the (not yet validated) idea that Lorentz invariance might break near the Planck scale. A key test of such violation of Lorentz invariance is a possible variation of photon speed with energy(1-7). Even a tiny variation in photon speed, when accumulated over cosmological light-travel times, may be revealed by observing sharp features in gamma-ray burst (GRB) light-curves(2). Here we report the detection of emission up to similar to 31GeV from the distant and short GRB090510. We find no evidence for the violation of Lorentz invariance, and place a lower limit of 1.2E(Planck) on the scale of a linear energy dependence (or an inverse wavelength dependence), subject to reasonable assumptions about the emission (equivalently we have an upper limit of l(Planck)/1.2 on the length scale of the effect). Our results disfavour quantum-gravity theories(3,6,7) in which the quantum nature of space-time on a very small scale linearly alters the speed of light.
Maastricht University1, VU University Medical Center2, Karolinska University Hospital3, Aristotle University of Thessaloniki4, Lund University5, Ludwig Maximilian University of Munich6, University College Dublin7, Radboud University Nijmegen8, Carol Davila University of Medicine and Pharmacy9, Sahlgrenska University Hospital10
TL;DR: In patients with aMCI, a CSF AD profile was predictive of AD-type dementia (OR 26.8, 95% CI 1.6-456.4), and the profile was associated with cognitive decline in patients with naMCI (memory, MMSE, and daily function) and in Patients with a MCI (MMSE and dailyfunction).
Abstract: Summary Background Alzheimer's disease (AD) pathology is common in patients with amnestic mild cognitive impairment (aMCI) without dementia, but the prevalence of AD pathology in patients with subjective cognitive impairment (SCI) and non-amnestic mild cognitive impairment (naMCI) is unknown. AD is characterised by decreased CSF concentrations of Aβ 42 and increased concentrations of tau. We investigated the prevalence of a CSF AD profile in patients with SCI, naMCI, or aMCI and the association of this profile with cognitive outcome in each group. Methods Patients with SCI, naMCI, aMCI, and neurologically healthy controls were recruited from 20 memory clinics across Europe, between January, 2003, and June, 2005, into this prospective cohort study. A CSF AD profile was defined as an abnormal ratio of Aβ 42 :tau. Patients were assessed annually up to 3 years. Outcome measures were changes in memory, overall cognition, mini-mental state examination (MMSE) score, daily function, and progression to AD-type dementia. Findings The CSF AD profile was more common in patients with SCI (31 of 60 [52%]), naMCI (25 of 37 [68%]), and aMCI (56 of 71 [79%]) than in healthy controls (28 of 89 [31%]). The profile was associated with cognitive decline in patients with naMCI (memory, MMSE, and daily function) and in patients with aMCI (MMSE and daily function). In patients with aMCI, a CSF AD profile was predictive of AD-type dementia (OR 26·8, 95% CI 1·6–456·4). Interpretation AD is a common cause of SCI, naMCI, and aMCI and is associated with cognitive decline in patients with naMCI or aMCI. Patients with SCI might be in the early stages of AD, and cognitive decline might become apparent only after longer follow-up. Funding European Commission; Ana Aslan International Foundation.
University of California, Santa Cruz1, National Institutes of Health2, Broad Institute3, University of Los Andes4, University of Guelph5, University of Nottingham6, University of California, Berkeley7, Pennsylvania State University8, Royal Ontario Museum9, Texas A&M University10, Louisiana State University11, Agency for Science, Technology and Research12, University of Kansas13, University of Montana14, American Museum of Natural History15, Oregon State University16, Villanova University17, University of Porto18, Smithsonian Institution19, Oswaldo Cruz Foundation20, Okinawa Institute of Science and Technology21, University of Sheffield22, Harvard University23, Swedish Museum of Natural History24, University of Copenhagen25, Novosibirsk State University26, Australian National University27, Max Planck Society28, Field Museum of Natural History29, Commonwealth Scientific and Industrial Research Organisation30, Science Applications International Corporation31, Stanford University32, University of Illinois at Urbana–Champaign33, George Washington University34, Global Viral35, University of Bedfordshire36, Federal University of Rio de Janeiro37, University of California, Davis38, University of California, Riverside39, Museum Victoria40, University College Dublin41, Monterey Bay Aquarium Research Institute42, Washington University in St. Louis43, University of California, Los Angeles44, Kunming Institute of Zoology45
TL;DR: A precipitous drop in costs and increase in sequencing efficiency is anticipated, with concomitant development of improved annotation technology, and it is proposed to create a collection of tissue and DNA specimens for 10,000 vertebrate species specifically designated for whole-genome sequencing in the very near future.
Abstract: American Genetic Association, Gordon and Betty Moore Foundation, NHGRI Intramural Sequencing Center, and UCSC Alumni Association to cost of the Genome 10K workshop; Howard Hughes Medical Institute to D. H.; Gordon and Betty Moore Foundation to S. C. S.; A
TL;DR: In this paper, the effect of high pressure treatments and conventional thermal processing on antioxidant activity, levels of key antioxidant groups (polyphenols, ascorbic acid and anthocyanins) and the color of strawberry and blackberry purees was assessed.
Abstract: The present study was undertaken to assess the effect of high pressure treatments and conventional thermal processing on antioxidant activity, levels of key antioxidant groups (polyphenols, ascorbic acid and anthocyanins) and the colour of strawberry and blackberry purees. Bioactive compounds (cyanidin-3-glycoside, pelargonidin-3-glucoside, ascorbic acid) and antioxidant activity were measured in strawberry and blackberry purees subjected to high pressure treatment (400, 500, 600 MPa/15 min/10–30 °C) and thermal treatments (70 °C/2 min). Samples were assessed immediately after processing. Different pressure treatments did not cause any significant change in ascorbic acid (p > 0.05). In contrast, following thermal processing (P70 ≥ 2 min) ascorbic acid degradation was 21% (p 0.05), whereas conventional thermal treatments significantly reduced the levels (p Industrial relevance This research paper provides scientific evidence of the potential benefits of high pressure processing in comparison to thermal treatments in retaining important bioactive compounds. Antioxidant activity (ARP), ascorbic acid, and anthocyanins after exposure to high pressure treatments (400–600 MPa) were well retained. Our results also show that redness and colour intensity of strawberry and blackberry purees were better preserved by high pressure processing than conventional thermal treatment. From a nutritional perspective, high pressure processing is an attractive food preservation technology and offers opportunities for horticultural and food processing industries to meet the growing demand from consumers for healthier food products. Therefore high pressure processed foods could be sold at a premium than their thermally processed counterparts as they will have retained their fresh-like properties.
TL;DR: The need for early intervention is motivated by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life, and a suite of new European interventions that will inform this optimal timing debate are discussed.
Abstract: Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the “antenatal investment hypothesis”. We conclude by discussing a suite of new European interventions that will inform this optimal timing debate.
TL;DR: Fluorescence correlation spectroscopy has been used as a quantitative method to understand the binding and exchange behavior of proteins on the surfaces of nanoparticles as discussed by the authors, and it has been shown that it can be used to detect the presence of proteins in nanoparticles.
Abstract: Fluorescence correlation spectroscopy is used as a quantitative method to understand the binding and exchange behaviour of proteins on the surfaces of nanoparticles.
TL;DR: The main obstacles limiting progress are reviewed and recommendations are made to improve the mode of collection and preparation of biological samples, the coverage and quality of mass spectrometry analyses, the extraction and exploitation of the raw data, the identification of the metabolites and the biological interpretation of the results.
Abstract: Mass spectrometry (MS) techniques, because of their sensitivity and selectivity, have become methods of choice to characterize the human metabolome and MS-based metabolomics is increasingly used to characterize the complex metabolic effects of nutrients or foods. However progress is still hampered by many unsolved problems and most notably the lack of well established and standardized methods or procedures, and the difficulties still met in the identification of the metabolites influenced by a given nutritional intervention. The purpose of this paper is to review the main obstacles limiting progress and to make recommendations to overcome them. Propositions are made to improve the mode of collection and preparation of biological samples, the coverage and quality of mass spectrometry analyses, the extraction and exploitation of the raw data, the identification of the metabolites and the biological interpretation of the results.
TL;DR: Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART, and these results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications.
Abstract: Background: Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined. Methods and Findings: A5164 was a randomized strategy trial of ‘‘early ART’’ - given within 14 days of starting acute OI treatment versus ‘‘deferred ART’’ - given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) $50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL ,50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS. 282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively. The difference in the primary endpoint did not reach statistical significance: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p=0.22). However, the early ART arm had fewer AIDS progression/deaths (OR=0.51; 95% CI=0.27–0.94) and a longer time to AIDS progression/death (stratified HR=0.53; 95% CI=0.30–0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p,0.001) and no increase in adverse events. Conclusions: Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications. Trial Registration: ClinicalTrials.gov NCT00055120
Walter and Eliza Hall Institute of Medical Research1, Millennium Institute2, Griffith University3, University of Queensland4, University of Oxford5, University of Tasmania6, Royal Melbourne Hospital7, University of Melbourne8, John Hunter Hospital9, University of Newcastle10, Nepean Hospital11, University of Otago12, University of Auckland13, Box Hill Hospital14, Sir Charles Gairdner Hospital15, Geelong Hospital16, Royal Brisbane and Women's Hospital17, Flinders University18, University College Dublin19
TL;DR: To identify multiple sclerosis (MS) susceptibility loci, a genome-wide association study in 1,618 cases and used shared data for 3,413 controls and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15.
Abstract: To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 x 10(-11); rs10876994, P = 2.7 x 10(-10); rs12368653, P = 1.0 x 10(-7)) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 x 10(-7); rs1569723, P = 2.9 x 10(-7)). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 x 10(-184); CD58, P = 9.6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).
TL;DR: It is shown that A. fumigatus possesses a fully functional sexual reproductive cycle that leads to the production of cleistothecia and ascospores, and the teleomorph Neosartorya fumgata is described, and increased genotypic variation resulting from recombination between mating type and DNA fingerprint markers in ascospore progeny from an Irish environmental subpopulation is demonstrated
Abstract: The fungus Aspergillus fumigatus is an opportunistic human pathogen in immunocompromised individuals and is associated with severe asthma and sinusitis. Despite accumulating evidence that recombination and gene flow occur in Aspergillus, until now only asexual reproduction has been observed in the species. Now, 145 years after it was first characterized, Aspergillus is shown to reproduce sexually. Isolates of two complementary mating types are reported. Implications of this demonstration include a possibility of classical genetic analyses that in turn will facilitate research into the genetic basis of pathogenicity and fungicide resistance. Aspergillus fumigatus is an opportunistic human pathogen in immunocompromised individuals and is associated with severe asthma and sinusitis, and has only been known to reproduce asexually. This paper now shows that it can reproduce sexually, for which isolates of complementary mating type are required. Aspergillus fumigatus is a saprotrophic fungus whose spores are ubiquitous in the atmosphere1. It is also an opportunistic human pathogen in immunocompromised individuals, causing potentially lethal invasive infections2,3, and is associated with severe asthma and sinusitis4. The species is only known to reproduce by asexual means5, but there has been accumulating evidence for recombination and gene flow from population genetic studies5,6,7,8, genome analysis9,10, the presence of mating-type genes8,10 and expression of sex-related genes8 in the fungus. Here we show that A. fumigatus possesses a fully functional sexual reproductive cycle that leads to the production of cleistothecia and ascospores, and the teleomorph Neosartorya fumigata is described. The species has a heterothallic breeding system; isolates of complementary mating types are required for sex to occur. We demonstrate increased genotypic variation resulting from recombination between mating type and DNA fingerprint markers in ascospore progeny from an Irish environmental subpopulation. The ability of A. fumigatus to engage in sexual reproduction is highly significant in understanding the biology and evolution of the species. The presence of a sexual cycle provides an invaluable tool for classical genetic analyses and will facilitate research into the genetic basis of pathogenicity and fungicide resistance in A. fumigatus, with the aim of improving methods for the control of aspergillosis. These results also yield insights into the potential for sexual reproduction in other supposedly ‘asexual’ fungi.
TL;DR: In this article, the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) instruments on-board the Fermi observatory were used to observe the long gamma-ray burst, GRB 090902B.
Abstract: We report on the observation of the bright, long gamma-ray burst (GRB), GRB 090902B, by the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) instruments on-board the Fermi observatory. ...