Showing papers by "University of Bordeaux published in 2011"
TL;DR: This Review gives answers from a chemical perspective, summarizes the state of the art, and highlights the most significant advances in the field of polyphenol research.
Abstract: Eating five servings of fruits and vegetables per day! This is what is highly recommended and heavily advertised nowadays to the general public to stay fit and healthy! Drinking green tea on a regular basis, eating chocolate from time to time, as well as savoring a couple of glasses of red wine per day have been claimed to increase life expectancy even further! Why? The answer is in fact still under scientific scrutiny, but a particular class of compounds naturally occurring in fruits and vegetables is considered to be crucial for the expression of such human health benefits: the polyphenols! What are these plant products really? What are their physicochemical properties? How do they express their biological activity? Are they really valuable for disease prevention? Can they be used to develop new pharmaceutical drugs? What recent progress has been made toward their preparation by organic synthesis? This Review gives answers from a chemical perspective, summarizes the state of the art, and highlights the most significant advances in the field of polyphenol research.
1,902 citations
TL;DR: Meta-analyses of all data provided compelling evidence that ABCA7 and the MS4A gene cluster are new Alzheimer's disease susceptibility loci and independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance.
Abstract: We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10).
1,771 citations
TL;DR: This Research News article is focused on a survey of the tremendous literature published between 2002 and 2010 that exhibits solar cells based on blends of P3HT and PCBM.
Abstract: In the field of polymer-based photovoltaic cells, poly(3-hexylthiophene) (P3HT) and 1-(3-methoxycarbonyl)propyl-1-phenyl[6,6]C61 (PCBM) are, to date, the most-studied active materials around the world for the bulk-heterojunction structure. Various power-conversion efficiencies are reported up to approximately 5%. This Research News article is focused on a survey of the tremendous literature published between 2002 and 2010 that exhibits solar cells based on blends of P3HT and PCBM.
1,193 citations
TL;DR: Simulation of the early Solar System shows how the inward migration of Jupiter to 1.5 au, and its subsequent outward migration, lead to a planetesimal disk truncated at 1’au; the terrestrial planets then form from this disk over the next 30–50 million years, with an Earth/Mars mass ratio consistent with observations.
Abstract: Jupiter and Saturn formed in a few million years from a gas-dominated protoplanetary disk, and were susceptible to gas-driven migration of their orbits on timescales of only approximately 100,000 years. Hydrodynamic simulations show that these giant planets can undergo a two-stage, inward-then-outward, migration. The terrestrial planets finished accreting much later and their characteristics, including Mars' small mass, are best reproduced by starting from a planetesimal disk with an outer edge at about one astronomical unit from the Sun (1 AU is the Earth-Sun distance). Here we report simulations of the early Solar System that show how the inward migration of Jupiter to 1.5 AU, and its subsequent outward migration, lead to a planetesimal disk truncated at 1 AU; the terrestrial planets then form from this disk over the next 30-50 million years, with an Earth/Mars mass ratio consistent with observations. Scattering by Jupiter initially empties but then repopulates the asteroid belt, with inner-belt bodies originating between 1 and 3 AU and outer-belt bodies originating between and beyond the giant planets. This explains the significant compositional differences across the asteroid belt. The key aspect missing from previous models of terrestrial planet formation is the substantial radial migration of the giant planets, which suggests that their behaviour is more similar to that inferred for extrasolar planets than previously thought.
1,174 citations
01 Feb 2011
TL;DR: StarPU as mentioned in this paper is a runtime system that provides a high-level unified execution model for numerical kernel designers with a convenient way to generate parallel tasks over heterogeneous hardware and easily develop and tune powerful scheduling algorithms.
Abstract: In the field of HPC, the current hardware trend is to design multiprocessor architectures featuring heterogeneous technologies such as specialized coprocessors (e.g. Cell/BE) or data-parallel accelerators (e.g. GPUs). Approaching the theoretical performance of these architectures is a complex issue. Indeed, substantial efforts have already been devoted to efficiently offload parts of the computations. However, designing an execution model that unifies all computing units and associated embedded memory remains a main challenge. We therefore designed StarPU, an original runtime system providing a high-level, unified execution model tightly coupled with an expressive data management library. The main goal of StarPU is to provide numerical kernel designers with a convenient way to generate parallel tasks over heterogeneous hardware on the one hand, and easily develop and tune powerful scheduling algorithms on the other hand. We have developed several strategies that can be selected seamlessly at run-time, and we have analyzed their efficiency on several algorithms running simultaneously over multiple cores and a GPU. In addition to substantial improvements regarding execution times, we have obtained consistent superlinear parallelism by actually exploiting the heterogeneous nature of the machine. We eventually show that our dynamic approach competes with the highly optimized MAGMA library and overcomes the limitations of the corresponding static scheduling in a portable way. Copyright © 2010 John Wiley & Sons, Ltd.
1,116 citations
TL;DR: Electrochemical processes are confirmed to be an accurate route to precisely investigate in a continuous way such a complex system and provide a new way to synthesize materials with a very narrow existence range.
Abstract: Sodium layered oxides NaxCoO2 form one of the most fascinating low-dimensional and strongly correlated systems; in particular P2–NaxCoO2 exhibits various single-phase domains with different Na+/vacancy patterns depending on the sodium concentration. Here we used sodium batteries to clearly depict the P2–NaxCoO2 phase diagram for x≥0.50. By coupling the electrochemical process with an in situ X-ray diffraction experiment, we identified the succession of single-phase or two-phase domains appearing on sodium intercalation with a rather good accuracy compared with previous studies. We reported new single-phase domains and we underlined the thermal instability of some ordered phases from an electrochemical study at various temperatures. As each phase is characterized by the position of its Fermi level versus the Na+/Na couple, we showed that the synthesis of each material, even in large amounts, can be carried out electrochemically. The physical properties of the as-prepared Na1/2CoO2 and Na2/3CoO2 ordered phases were characterized and compared. Electrochemical processes are confirmed to be an accurate route to precisely investigate in a continuous way such a complex system and provide a new way to synthesize materials with a very narrow existence range.
1,053 citations
TL;DR: A better knowledge of the regulatory mechanisms of the flavonoids pathway is likely to favour the development of new biotechnological tools for the generation of value-added plants with optimized flavonoid content.
Abstract: Flavonoids are secondary metabolites involved in several aspects of plant development and defence. They colour fruits and flowers, favouring seed and pollen dispersal, and contribute to plant adaptation to environmental conditions such as cold or UV stresses, and pathogen attacks. Because they affect the quality of flowers (for horticulture), fruits and vegetables, and their derivatives (colour, aroma, stringency, etc.), flavonoids have a high economic value. Furthermore, these compounds possess pharmaceutical properties extremely attractive for human health. Thanks to easily detectable mutant phenotypes, such as modification of petal pigmentation and seeds exhibiting transparent testa, the enzymes involved in the flavonoid biosynthetic pathway have been characterized in several plant species. Conserved features as well as specific differences have been described. Regulation of structural gene expression appears tightly organized in a spatial and temporal way during plant development, and is orchestrated by a ternary complex involving transcription factors from the R2R3-MYB, basic helix-loop-helix (bHLH), and WD40 classes. This MYB-bHLH-WD40 (MBW) complex regulates the genes that encode enzymes specifically involved in the late steps of the pathway leading to the biosynthesis of anthocyanins and condensed tannins. Although several genes encoding transcription factors from these three families have been identified, many gaps remain in our understanding of the regulation of this biosynthetic pathway, especially about the respective roles of bHLH and WD40 proteins. A better knowledge of the regulatory mechanisms of the flavonoid pathway is likely to favour the development of new biotechnological tools for the generation of value-added plants with optimized flavonoid content.
908 citations
University of Western Ontario1, Spanish National Research Council2, Ghent University3, University of Utah4, SupAgro5, Instituto Gulbenkian de Ciência6, University of Lisbon7, University of Arizona8, Johns Hopkins University School of Medicine9, University of Bordeaux10, Valparaiso University11, Autonomous University of Madrid12, Georgia Institute of Technology13, University of Texas at Arlington14, Centre national de la recherche scientifique15, Graduate University for Advanced Studies16, Katholieke Universiteit Leuven17, Max Planck Society18, University of Guelph19, Boyce Thompson Institute for Plant Research20, Agriculture and Agri-Food Canada21, Joint Genome Institute22, University of Nice Sophia Antipolis23
TL;DR: The Tetranychus urticae genome is the smallest known arthropod genome as discussed by the authors, which represents the first complete chelicerate genome for a pest and has been annotated with genes associated with feeding on different hosts.
Abstract: The spider mite Tetranychus urticae is a cosmopolitan agricultural pest with an extensive host plant range and an extreme record of pesticide resistance. Here we present the completely sequenced and annotated spider mite genome, representing the first complete chelicerate genome. At 90 megabases T. urticae has the smallest sequenced arthropod genome. Compared with other arthropods, the spider mite genome shows unique changes in the hormonal environment and organization of the Hox complex, and also reveals evolutionary innovation of silk production. We find strong signatures of polyphagy and detoxification in gene families associated with feeding on different hosts and in new gene families acquired by lateral gene transfer. Deep transcriptome analysis of mites feeding on different plants shows how this pest responds to a changing host environment. The T. urticae genome thus offers new insights into arthropod evolution and plant-herbivore interactions, and provides unique opportunities for developing novel plant protection strategies.
894 citations
TL;DR: A short overview of the copper-catalyzed azide alkyne cycloaddition (CuAAC) is presented in this paper, including the introduction of the "click" concept, the conditions of copper(I) catalysis, the regioselectivity, the nature of the catalysts and ligands, mechanistic features, experimental conditions and applications to organic synthesis and organic materials.
852 citations
Texas A&M University1, Agricultural Research Service2, Hebrew University of Jerusalem3, Seoul Women's University4, University of Rennes5, University of Basel6, Norwich Research Park7, University of Bordeaux8, University of Wisconsin-Madison9, North Carolina State University10, University of Bristol11
TL;DR: A short review on each virus of the Top 10 list and its importance is presented, with the intent of initiating discussion and debate amongst the plant virology community, as well as laying down a benchmark, as it will be interesting to see in future years how perceptions change and which viruses enter and leave the Top10.
Abstract: Many scientists, if not all, feel that their particular plant virus should appear in any list of the most important plant viruses. However, to our knowledge, no such list exists. The aim of this review was to survey all plant virologists with an association with Molecular Plant Pathology and ask them to nominate which plant viruses they would place in a 'Top 10' based on scientific/economic importance. The survey generated more than 250 votes from the international community, and allowed the generation of a Top 10 plant virus list for Molecular Plant Pathology. The Top 10 list includes, in rank order, (1) Tobacco mosaic virus, (2) Tomato spotted wilt virus, (3) Tomato yellow leaf curl virus, (4) Cucumber mosaic virus, (5) Potato virus Y, (6) Cauliflower mosaic virus, (7) African cassava mosaic virus, (8) Plum pox virus, (9) Brome mosaic virus and (10) Potato virus X, with honourable mentions for viruses just missing out on the Top 10, including Citrus tristeza virus, Barley yellow dwarf virus, Potato leafroll virus and Tomato bushy stunt virus. This review article presents a short review on each virus of the Top 10 list and its importance, with the intent of initiating discussion and debate amongst the plant virology community, as well as laying down a benchmark, as it will be interesting to see in future years how perceptions change and which viruses enter and leave the Top 10.
842 citations
TL;DR: The molecular dynamics of clathrin-mediated endocytosis in living cells has been mapped with an approximately ten-fold improvement in temporal accuracy, yielding new insights into the molecular mechanism.
Abstract: Dual colour total internal reflection fluorescence microscopy is a powerful tool for decoding the molecular dynamics of clathrin-mediated endocytosis (CME). Typically, the recruitment of a fluorescent protein–tagged endocytic protein was referenced to the disappearance of spot-like clathrin-coated structure (CCS), but the precision of spot-like CCS disappearance as a marker for canonical CME remained unknown. Here we have used an imaging assay based on total internal reflection fluorescence microscopy to detect scission events with a resolution of ∼2 s. We found that scission events engulfed comparable amounts of transferrin receptor cargo at CCSs of different sizes and CCS did not always disappear following scission. We measured the recruitment dynamics of 34 types of endocytic protein to scission events: Abp1, ACK1, amphiphysin1, APPL1, Arp3, BIN1, CALM, CIP4, clathrin light chain (Clc), cofilin, coronin1B, cortactin, dynamin1/2, endophilin2, Eps15, Eps8, epsin2, FBP17, FCHo1/2, GAK, Hip1R, lifeAct, mu2 subunit of the AP2 complex, myosin1E, myosin6, NECAP, N-WASP, OCRL1, Rab5, SNX9, synaptojanin2β1, and syndapin2. For each protein we aligned ∼1,000 recruitment profiles to their respective scission events and constructed characteristic “recruitment signatures” that were grouped, as for yeast, to reveal the modular organization of mammalian CME. A detailed analysis revealed the unanticipated recruitment dynamics of SNX9, FBP17, and CIP4 and showed that the same set of proteins was recruited, in the same order, to scission events at CCSs of different sizes and lifetimes. Collectively these data reveal the fine-grained temporal structure of CME and suggest a simplified canonical model of mammalian CME in which the same core mechanism of CME, involving actin, operates at CCSs of diverse sizes and lifetimes.
TL;DR: Research on long-lived woody perennials is extending the authors' molecular knowledge of complex life histories and adaptations to the environment — enriching a field that has traditionally drawn biological inference from a few short-lived herbaceous species.
Abstract: Over the past two decades, research in forest tree genomics has lagged behind that of model and agricultural systems. However, genomic research in forest trees is poised to enter into an important and productive phase owing to the advent of next-generation sequencing technologies, the enormous genetic diversity in forest trees and the need to mitigate the effects of climate change. Research on long-lived woody perennials is extending our molecular knowledge of complex life histories and adaptations to the environment - enriching a field that has traditionally drawn biological inference from a few short-lived herbaceous species.
TL;DR: This work presents a search for dark matter consisting of weakly interacting massive particles, applying a joint likelihood analysis to 10 satellite galaxies with 24 months of data of the Fermi Large Area Telescope, and is able to rule out models with the most generic cross section, using gamma rays.
Abstract: Satellite galaxies of the Milky Way are among the most promising targets for dark matter searches in gamma rays. We present a search for dark matter consisting of weakly interacting massive particl ...
TL;DR: In this article, a P-band polarimetric SAR with interferometric capability is used to measure the magnitude and distribution of forest biomass globally to improve resource assessment, carbon accounting and carbon models, and to monitor and quantify changes in terrestrial forest biomass.
TL;DR: In this paper, a thermogravimetric analysis was used to obtain lignin, hemicellulose and α-cellulose contents in biomass. But this method cannot be adopted for the determination of the lignins amount.
Abstract: Biomass energy uses organic matter such as wood or plants - lignocellulosic biomass - for creating heat, generating electricity and producing green oil for cars. Modern biomass energy recycles organic leftovers from forestry and agriculture, like corn stovers, rice husks, wood waste and pressed sugar cane, or uses special, fast-growing “energy crops” like willow and switchgrass, as fuel. Biomass is composed of three major components: cellulose, hemicelluloses, and lignin. Their differences in chemical structures lead to different chemical reactivities, making the relative composition in cellulose, hemicelluloses and lignin in the biomass a crucial factor for process design. In this paper thermogravimetric analysis is investigated as a new method to obtain lignin, hemicellulose and α-cellulose contents in biomass. It is shown that this alternative method lead to comparable results than common methods used for the determination of the α-cellulose content, with an enhancement of the accuracy in the determination of the hemicellulose content. Unfortunately, this method cannot be adopted for the determination of the lignin amount.
TL;DR: In this paper, the authors estimate the conversion factor relating CO emission to H2 mass, αCO, in five Local Group galaxies that span approximately an order of magnitude in metallicity.
Abstract: We estimate the conversion factor relating CO emission to H2 mass, αCO, in five Local Group galaxies that span approximately an order of magnitude in metallicity—M 31, M 33, the Large Magellanic Cloud (LMC), NGC 6822, and the Small Magellanic Cloud (SMC). We model the dust mass along the line of sight from infrared (IR) emission and then solve for the αCO that best allows a single gas-to-dust ratio (δGDR) to describe each system. This approach remains sensitive to CO-dark envelopes H2 surrounding molecular clouds. In M 31, M 33, and the LMC we find αCO 3-9 M ☉ pc–2 (K km s–1)–1, consistent with the Milky Way value within the uncertainties. The two lowest metallicity galaxies in our sample, NGC 6822 and the SMC (12 + log (O/H) 8.2 and 8.0), exhibit a much higher αCO. Our best estimates are αNGC6822 CO 30 M ☉ pc–2 (K km s–1)–1 and αSMC CO 70 M ☉ pc–2 (K km s–1)–1. These results are consistent with the conversion factor becoming a strong function of metallicity around 12 + log (O/H) ~ 8.4-8.2. We favor an interpretation where decreased dust shielding leads to the dominance of CO-free envelopes around molecular clouds below this metallicity.
Centre Hospitalier Universitaire de Nice1, International Agency for Research on Cancer2, University of Nice Sophia Antipolis3, University of Strasbourg4, Institut Gustave Roussy5, French Institute of Health and Medical Research6, University of Paris-Sud7, University of Paris8, University of Burgundy9, Claude Bernard University Lyon 110, Curie Institute11, University of Genoa12, University of Barcelona13, Lund University14, Aix-Marseille University15, Joseph Fourier University16, University of Bordeaux17, Centre Hospitalier Universitaire de Toulouse18, University of Évry Val d'Essonne19
TL;DR: A germline missense substitution in MITF (Mi-E318K) is identified that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls and provides insights into the link between SUMOylation, transcription and cancer.
Abstract: So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (ΨKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.
TL;DR: In this article, a mismatch in visibility of acute ischaemic lesion between diffusion-weighted MRI (DWI) and fluid-attenuated inversion recovery (FLAIR) MRI was used to detect patients within the recommended time window for thrombolysis.
Abstract: Summary Background Many patients with stroke are precluded from thrombolysis treatment because the time from onset of their symptoms is unknown. We aimed to test whether a mismatch in visibility of an acute ischaemic lesion between diffusion-weighted MRI (DWI) and fluid-attenuated inversion recovery (FLAIR) MRI (DWI-FLAIR mismatch) can be used to detect patients within the recommended time window for thrombolysis. Methods In this multicentre observational study, we analysed clinical and MRI data from patients presenting between Jan 1, 2001, and May 31, 2009, with acute stroke for whom DWI and FLAIR were done within 12 h of observed symptom onset. Two neurologists masked to clinical data judged the visibility of acute ischaemic lesions on DWI and FLAIR imaging, and DWI-FLAIR mismatch was diagnosed by consensus. We calculated predictive values of DWI-FLAIR mismatch for the identification of patients with symptom onset within 4·5 h and within 6 h and did multivariate regression analysis to identify potential confounding covariates. This study is registered with ClinicalTrials.gov, number NCT01021319. Findings The final analysis included 543 patients. Mean age was 66·0 years (95% CI 64·7–67·3) and median National Institutes of Health Stroke Scale score was 8 (IQR 4–15). Acute ischaemic lesions were identified on DWI in 516 patients (95%) and on FLAIR in 271 patients (50%). Interobserver agreement for acute ischaemic lesion visibility on FLAIR imaging was moderate (κ=0·569, 95% CI 0·504–0·634). DWI-FLAIR mismatch identified patients within 4·5 h of symptom onset with 62% (95% CI 57–67) sensitivity, 78% (72–84) specificity, 83% (79–88) positive predictive value, and 54% (48–60) negative predictive value. Multivariate regression analysis identified a longer time to MRI (p Interpretation Patients with an acute ischaemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomised trial of thrombolysis in patients with unknown time of symptom onset. Funding Else Kroner-Fresenius-Stiftung, National Institutes of Health.
TL;DR: This paper will review common metabolic properties of the fermenting yeast Saccharomyces cerevisiae and tumor cells as well as the possible origins of the Crabtree and Warburg effects.
TL;DR: Surgery is recommended for masses with suspicious radiological aspects and masses causing overt catecholamine or steroid excess and adrenalectomy may be considered when an adequate medical therapy does not reach the treatment goals of associated diseases potentially linked to hypercortisolism.
Abstract: Objective: To assess currently available evidence on adrenal incidentaloma and provide recommendations for clinical practice. Design: A panel of experts (appointed by the Italian Association of Clinical Endocrinologists (AME)) appraised the methodological quality of the relevant studies, summarized their results, and discussed the evidence reports to find consensus. Radiological assessment: Unenhanced computed tomography (CT) is recommended as the initial test with the use of an attenuation value of %10 Hounsfield units (HU) to differentiate between adenomas and non-adenomas. For tumors with a higher baseline attenuation value, we suggest considering delayed contrast-enhanced CT studies. Positron emission tomography (PET) or PET/CT should be considered when CT is inconclusive, whereas fine needle aspiration biopsy may be used only in selected cases suspicious of metastases (after biochemical exclusion of pheochromocytoma). Hormonal assessment: Pheochromocytoma and excessive overt cortisol should be ruled out in all patients, whereas primary aldosteronism has to be considered in hypertensive and/or hypokalemic patients. The 1 mg overnight dexamethasone suppression test is the test recommended for screening of subclinical Cushing’s syndrome (SCS) with a threshold at 138 nmol/l for considering this condition. A value of 50 nmol/l virtually excludes SCS with an area of uncertainty between 50 and 138 nmol/l. Management: Surgery is recommended for masses with suspicious radiological aspects and masses causing overt catecholamine or steroid excess. Data are insufficient to make firm recommendations for or against surgery in patients with SCS. However, adrenalectomy may be considered when an adequate medical therapy does not reach the treatment goals of associated diseases potentially linked to hypercortisolism.
University of Vienna1, University of Oxford2, University of Tübingen3, Masaryk University4, Academy of Sciences of the Czech Republic5, Hungarian Natural History Museum6, University of Pisa7, University of Bordeaux8, Spanish National Research Council9, Centre national de la recherche scientifique10, University of Siena11
TL;DR: The Cavallo human remains are therefore the oldest known European anatomically modern humans, confirming a rapid dispersal of modern humans across the continent before the Aurignacian and the disappearance of Neanderthals.
Abstract: The appearance of anatomically modern humans in Europe and the nature of the transition from the Middle to Upper Palaeolithic are matters of intense debate. Most researchers accept that before the arrival of anatomically modern humans, Neanderthals had adopted several 'transitional' technocomplexes. Two of these, the Uluzzian of southern Europe and the Châtelperronian of western Europe, are key to current interpretations regarding the timing of arrival of anatomically modern humans in the region and their potential interaction with Neanderthal populations. They are also central to current debates regarding the cognitive abilities of Neanderthals and the reasons behind their extinction. However, the actual fossil evidence associated with these assemblages is scant and fragmentary, and recent work has questioned the attribution of the Châtelperronian to Neanderthals on the basis of taphonomic mixing and lithic analysis. Here we reanalyse the deciduous molars from the Grotta del Cavallo (southern Italy), associated with the Uluzzian and originally classified as Neanderthal. Using two independent morphometric methods based on microtomographic data, we show that the Cavallo specimens can be attributed to anatomically modern humans. The secure context of the teeth provides crucial evidence that the makers of the Uluzzian technocomplex were therefore not Neanderthals. In addition, new chronometric data for the Uluzzian layers of Grotta del Cavallo obtained from associated shell beads and included within a Bayesian age model show that the teeth must date to ~45,000-43,000 calendar years before present. The Cavallo human remains are therefore the oldest known European anatomically modern humans, confirming a rapid dispersal of modern humans across the continent before the Aurignacian and the disappearance of Neanderthals.
TL;DR: Early humans mixed and stored ochre pigments in shells 100,000 years ago, an indication of the emergence of higher planning in the evolution of complex human cognition.
Abstract: The conceptual ability to source, combine, and store substances that enhance technology or social practices represents a benchmark in the evolution of complex human cognition. Excavations in 2008 at Blombos Cave, South Africa, revealed a processing workshop where a liquefied ochre-rich mixture was produced and stored in two Haliotis midae (abalone) shells 100,000 years ago. Ochre, bone, charcoal, grindstones, and hammerstones form a composite part of this production toolkit. The application of the mixture is unknown, but possibilities include decoration and skin protection.
Roskilde University1, University of Wisconsin-Madison2, University of Georgia3, University of Pennsylvania4, University of Leicester5, University of Oklahoma Health Sciences Center6, University of Connecticut7, University of Burgundy8, Universidade Federal do Rio Grande do Sul9, Xi'an Jiaotong University10, National Institutes of Health11, Annamalai University12, University of Hawaii at Hilo13, University of Bordeaux14, Indian Institute of Toxicology Research15, Seoul National University16, Medical University of Vienna17, University of Agriculture, Faisalabad18, Medical University of South Carolina19, New York Medical College20
TL;DR: The published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources, and animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials.
Abstract: Background: Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingor, Denmark. Methodology: Literature search in databases as PubMed and ISI Web of Science in combination with manual search was used to answer the following five questions: 1 Can resveratrol be recommended in the prevention or treatment of human diseases?; 2 Are there observed ‘‘side effects’’ caused by the intake of resveratrol in humans?; 3 What is the relevant dose of resveratrol?; 4 What valid data are available regarding an effect in various species of experimental animals?; 5 Which relevant (overall) mechanisms of action of resveratrol have been documented? Conclusions/Significance: The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Finally, we suggest directions for future research in resveratrol regarding its mechanism of action and its safety and toxicology in human subjects.
University of Bordeaux1, Centre national de la recherche scientifique2, Michael J. Fox Foundation3, German Center for Neurodegenerative Diseases4, Rush University Medical Center5, Toronto Western Hospital6, Imperial College London7, University of Navarra8, French Institute of Health and Medical Research9, University College London10, University of Cambridge11, Merck Serono12
TL;DR: This Review describes the most promising biological targets and therapeutic agents that are currently being assessed to address treatment goals of Parkinson's disease.
Abstract: The loss of dopaminergic neurons in the substantia nigra pars compacta leads to the characteristic motor symptoms of Parkinson's disease: bradykinesia, rigidity and resting tremors. Although these symptoms can be improved using currently available dopamine replacement strategies, there is still a need to improve current strategies of treating these symptoms, together with a need to alleviate non-motor symptoms of the disease. Moreover, treatments that provide neuroprotection and/or disease-modifying effects remain an urgent unmet clinical need. This Review describes the most promising biological targets and therapeutic agents that are currently being assessed to address these treatment goals. Progress will rely on understanding genetic mutations or susceptibility factors that lead to Parkinson's disease, better translation between preclinical animal models and clinical research, and improving the design of future clinical trials.
TL;DR: Two separate gamma-ray flares from a young and energetic pulsar powers the well-known Crab Nebula are described and it is suggested that the gamma rays were emitted via synchrotron radiation from peta–electron-volt electrons in a region smaller than 1.4 × 10−2 parsecs.
Abstract: A young and energetic pulsar powers the well-known Crab Nebula. Here, we describe two separate gamma-ray (photon energy greater than 100 mega-electron volts) flares from this source detected by the Large Area Telescope on board the Fermi Gamma-ray Space Telescope. The first flare occurred in February 2009 and lasted approximately 16 days. The second flare was detected in September 2010 and lasted approximately 4 days. During these outbursts, the gamma-ray flux from the nebula increased by factors of four and six, respectively. The brevity of the flares implies that the gamma rays were emitted via synchrotron radiation from peta-electron-volt (10(15) electron volts) electrons in a region smaller than 1.4 × 10(-2) parsecs. These are the highest-energy particles that can be associated with a discrete astronomical source, and they pose challenges to particle acceleration theory.
TL;DR: The Random Forests algorithm is chosen as a classifier: it runs efficiently on large datasets, and provides measures of feature importance for each class, and the relevance of full-waveform lidar features is demonstrated for building and vegetation area discrimination.
Abstract: Airborne lidar systems have become a source for the acquisition of elevation data. They provide georeferenced, irregularly distributed 3D point clouds of high altimetric accuracy. Moreover, these systems can provide for a single laser pulse, multiple returns or echoes, which correspond to different illuminated objects. In addition to multi-echo laser scanners, full-waveform systems are able to record 1D signals representing a train of echoes caused by reflections at different targets. These systems provide more information about the structure and the physical characteristics of the targets. Many approaches have been developed, for urban mapping, based on aerial lidar solely or combined with multispectral image data. However, they have not assessed the importance of input features. In this paper, we focus on a multi-source framework using aerial lidar (multi-echo and full waveform) and aerial multispectral image data. We aim to study the feature relevance for dense urban scenes. The Random Forests algorithm is chosen as a classifier: it runs efficiently on large datasets, and provides measures of feature importance for each class. The margin theory is used as a confidence measure of the classifier, and to confirm the relevance of input features for urban classification. The quantitative results confirm the importance of the joint use of optical multispectral and lidar data. Moreover, the relevance of full-waveform lidar features is demonstrated for building and vegetation area discrimination.
University of Milan1, University of Bordeaux2, French Institute of Health and Medical Research3, University of Utah4, University of Rome Tor Vergata5, University of Catania6, Charité7, University of Naples Federico II8, University of Zaragoza9, McGill University10, Obafemi Awolowo University11, Catholic University of Korea12
TL;DR: In this study, CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib, and survival was not statistically significantly different from that of the general population.
Abstract: BACKGROUND Imatinib slows development of chronic myeloid leukemia (CML). However, available information on morbidity and mortality is largely based on sponsored trials, whereas independent long-term field studies are lacking. PATIENTS AND METHODS Consecutive CML patients who started imatinib treatment before 2005 and who were in complete cytogenetic remission (CCyR) after 2 years (± 3 months) were eligible for enrollment in the independent multicenter Imatinib Long-Term (Side) Effects (ILTE) study. Incidence of the first serious and nonserious adverse events and loss of CCyR were estimated according to the Kaplan-Meier method and compared with the standard log-rank test. Attainment of negative Philadelphia chromosome hematopoiesis was assessed with cytogenetics and quantitative polymerase chain reaction. Cumulative incidence of death related or unrelated to CML progression was estimated, accounting for competing risks, according to the Kalbleisch-Prentice method. Standardized incidence ratios were calculated based on population rates specific for sex and age classes. Confidence intervals were calculated by the exact method based on the χ(2) distribution. All statistical tests were two-sided. RESULTS A total of 832 patients who were treated for a median of 5.8 years were enrolled. There were 139 recorded serious adverse events, of which 19.4% were imatinib-related. A total of 830 nonserious adverse events were observed in 53% of patients; 560 (68%) were imatinib-related. The most frequent were muscle cramps, asthenia, edema, skin fragility, diarrhea, tendon, or ligament lesions. Nineteen patients (2.3%) discontinued imatinib because of drug-related toxic effects. Forty-five patients lost CCyR, at a rate of 1.4 per 100 person-years. Durable (>1 year) negative Philadelphia chromosome hematopoiesis was attained by 179 patients. Twenty deaths were observed, with a 4.8% mortality incidence rate (standardized incidence ratio = 0.7; 95% confidence interval = 0.40 to 1.10, P = .08), with only six (30%) associated with CML progression. CONCLUSIONS In this study, CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib, and survival was not statistically significantly different from that of the general population.
TL;DR: In this paper, a superparamagnetic hybrid self-assemblies display enhanced contrast properties that open potential applications for magnetic resonance imaging and can also be guided in a magnetic field gradient.
Abstract: Hydrophobically modified maghemite (γ-Fe2O3) nanoparticles were encapsulated within the membrane of poly(trimethylene carbonate)-b-poly(l-glutamic acid) (PTMC-b-PGA) block copolymer vesicles using a nanoprecipitation process. This formation method gives simple access to highly magnetic nanoparticles (MNPs) (loaded up to 70 wt %) together with good control over the vesicles size (100−400 nm). The simultaneous loading of maghemite nanoparticles and doxorubicin was also achieved by nanoprecipitation. The deformation of the vesicle membrane under an applied magnetic field has been evidenced by small angle neutron scattering. These superparamagnetic hybrid self-assemblies display enhanced contrast properties that open potential applications for magnetic resonance imaging. They can also be guided in a magnetic field gradient. The feasibility of controlled drug release by radio frequency magnetic hyperthermia was demonstrated in the case of encapsulated doxorubicin molecules, showing the viability of the concept...
TL;DR: In this paper, the authors modeled the dust mass along the line of sight from infrared (IR) emission and then solved for the alpha-CO that best allows a single gas-to-dust ratio (delta_GDR) to describe each system.
Abstract: We estimate the conversion factor relating CO emission to H2 mass, alpha_CO, in five Local Group galaxies that span approximately an order of magnitude in metallicity - M31, M 33, the Large Magellanic Cloud (LMC), NGC 6822, and the Small Magellanic Cloud (SMC). We model the dust mass along the line of sight from infrared (IR) emission and then solve for the alpha_CO that best allows a single gas-to-dust ratio (delta_GDR) to describe each system. This approach remains sensitive to CO-dark envelopes of H2 surrounding molecular clouds. In M 31, M 33, and the LMC we find alpha_CO \approx 3-9 M_sun pc^-2 (K km s^-1)^-1, consistent with the Milky Way value within the uncertainties. The two lowest metallicity galaxies in our sample, NGC 6822 and the SMC (12 + log(O/H) \approx 8.2 and 8.0), exhibit a much higher alpha_CO. Our best estimates are \alpha_NGC6822 \approx 30 M_sun/pc^-2 (K km s^-1)^-1 and \alpha_SMC \approx 70 M_sun/pc^-2 (K km s-1)-1. These results are consistent with the conversion factor becoming CO a strong function of metallicity around 12 + log(O/H) \sim 8.4 - 8.2. We favor an interpretation where decreased dust-shielding leads to the dominance of CO-free envelopes around molecular clouds below this metallicity.
TL;DR: It is reported here that miR-210 is overexpressed at late stages of non-small cell lung cancer and can regulate mitochondrial function by targeting key ETC component genes with important consequences on cell metabolism, survival and modulation of HIF-1 activity.
Abstract: Following the identification of a set of hypoxia-regulated microRNAs (miRNAs), recent studies have highlighted the importance of miR-210 and of its transcriptional regulation by the transcription factor hypoxia-inducible factor-1 (HIF-1). We report here that miR-210 is overexpressed at late stages of non-small cell lung cancer. Expression of miR-210 in lung adenocarcinoma A549 cells caused an alteration of cell viability associated with induction of caspase-3/7 activity. miR-210 induced a loss of mitochondrial membrane potential and the apparition of an aberrant mitochondrial phenotype. The expression profiling of cells overexpressing miR-210 revealed a specific signature characterized by enrichment for transcripts related to ‘cell death' and ‘mitochondrial dysfunction', including several subunits of the electron transport chain (ETC) complexes I and II. The transcript coding for one of these ETC components, SDHD, subunit D of succinate dehydrogenase complex (SDH), was validated as a bona fide miR-210 target. Moreover, SDHD knockdown mimicked miR-210-mediated mitochondrial alterations. Finally, miR-210-dependent targeting of SDHD was able to activate HIF-1, in line with previous studies linking loss-of-function SDH mutations to HIF-1 activation. miR-210 can thus regulate mitochondrial function by targeting key ETC component genes with important consequences on cell metabolism, survival and modulation of HIF-1 activity. These observations help explain contradictory data regarding miR-210 expression and its putative function in solid tumors.