Showing papers by "University of Nice Sophia Antipolis published in 2010"

Sarcopenia: European consensus on definition and diagnosis Report of the European Working Group on Sarcopenia in Older People

Abstract: The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. EWGSOP included representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics-European Region and the International Association of Nutrition and Aging. These organisations endorsed the findings in the final document. The group met and addressed the following questions, using the medical literature to build evidence-based answers: (i) What is sarcopenia? (ii) What parameters define sarcopenia? (iii) What variables reflect these parameters, and what measurement tools and cut-off points can be used? (iv) How does sarcopenia relate to cachexia, frailty and sarcopenic obesity? For the diagnosis of sarcopenia, EWGSOP recommends using the presence of both low muscle mass + low muscle function (strength or performance). EWGSOP variously applies these characteristics to further define conceptual stages as 'presarcopenia', 'sarcopenia' and 'severe sarcopenia'. EWGSOP reviewed a wide range of tools that can be used to measure the specific variables of muscle mass, muscle strength and physical performance. Our paper summarises currently available data defining sarcopenia cut-off points by age and gender; suggests an algorithm for sarcopenia case finding in older individuals based on measurements of gait speed, grip strength and muscle mass; and presents a list of suggested primary and secondary outcome domains for research. Once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to define the natural course of sarcopenia and to develop and define effective treatment.

Revising the definition of Alzheimer's disease: a new lexicon.

Abstract: Alzheimer's disease (AD) is classically defined as a dual clinicopathological entity. The recent advances in use of reliable biomarkers of AD that provide in-vivo evidence of the disease has stimulated the development of new research criteria that reconceptualise the diagnosis around both a specific pattern of cognitive changes and structural/biological evidence of Alzheimer's pathology. This new diagnostic framework has stimulated debate about the definition of AD and related conditions. The potential for drugs to intercede in the pathogenic cascade of the disease adds some urgency to this debate. This paper by the International Working Group for New Research Criteria for the Diagnosis of AD aims to advance the scientific discussion by providing broader diagnostic coverage of the AD clinical spectrum and by proposing a common lexicon as a point of reference for the clinical and research communities. The cornerstone of this lexicon is to consider AD solely as a clinical and symptomatic entity that encompasses both predementia and dementia phases.

The Einstein Telescope: a third-generation gravitational wave observatory

Abstract: Advanced gravitational wave interferometers, currently under realization, will soon permit the detection of gravitational waves from astronomical sources. To open the era of precision gravitational wave astronomy, a further substantial improvement in sensitivity is required. The future space-based Laser Interferometer Space Antenna and the third-generation ground-based observatory Einstein Telescope (ET) promise to achieve the required sensitivity improvements in frequency ranges. The vastly improved sensitivity of the third generation of gravitational wave observatories could permit detailed measurements of the sources' physical parameters and could complement, in a multi-messenger approach, the observation of signals emitted by cosmological sources obtained through other kinds of telescopes. This paper describes the progress of the ET project which is currently in its design study phase.

ERK and cell death: Mechanisms of ERK‐induced cell death – apoptosis, autophagy and senescence

Abstract: The Ras/Raf/extracellular signal-regulated kinase (ERK) signaling pathway plays a crucial role in almost all cell functions and therefore requires exquisite control of its spatiotemporal activity. Depending on the cell type and stimulus, ERK activity will mediate different antiproliferative events, such as apoptosis, autophagy and senescence in vitro and in vivo. ERK activity can promote either intrinsic or extrinsic apoptotic pathways by induction of mitochondrial cytochrome c release or caspase-8 activation, permanent cell cycle arrest or autophagic vacuolization. These unusual effects require sustained ERK activity in specific subcellular compartments and could depend on the presence of reactive oxygen species. We will summarize the mechanisms involved in Ras/Raf/ERK antiproliferative functions.

Multiple marker parallel tag environmental DNA sequencing reveals a highly complex eukaryotic community in marine anoxic water

Abstract: Sequencing of ribosomal DNA clone libraries amplified from environmental DNA has revolutionized our understanding of microbial eukaryote diversity and ecology. The results of these analyses have shown that protist groups are far more genetically heterogeneous than their morphological diversity suggests. However, the clone library approach is labour-intensive, relatively expensive, and methodologically biased. Therefore, even the most intensive rDNA library analyses have recovered only small samples of much larger assemblages, indicating that global environments harbour a vast array of unexplored biodiversity. High-throughput parallel tag 454 sequencing offers an unprecedented scale of sampling for molecular detection of microbial diversity. Here, we report a 454 protocol for sampling and characterizing assemblages of eukaryote microbes. We use this approach to sequence two SSU rDNA diversity markers-the variable V4 and V9 regions-from 10 L of anoxic Norwegian fjord water. We identified 38 116 V4 and 15 156 V9 unique sequences. Both markers detect a wide range of taxonomic groups but in both cases the diversity detected was dominated by dinoflagellates and close relatives. Long-tailed rank abundance curves suggest that the 454 sequencing approach provides improved access to rare genotypes. Most tags detected represent genotypes not currently in GenBank, although many are similar to database sequences. We suggest that current understanding of the ecological complexity of protist communities, genetic diversity, and global species richness are severely limited by the sequence data hitherto available, and we discuss the biological significance of this high amplicon diversity.

Predictions for the rates of compact binary coalescences observable by ground-based gravitational-wave detectors

Abstract: We present an up-to-date, comprehensive summary of the rates for all types of compact binary coalescence sources detectable by the initial and advanced versions of the ground-based gravitational-wave detectors LIGO and Virgo. Astrophysical estimates for compact-binary coalescence rates depend on a number of assumptions and unknown model parameters and are still uncertain. The most confident among these estimates are the rate predictions for coalescing binary neutron stars which are based on extrapolations from observed binary pulsars in our galaxy. These yield a likely coalescence rate of 100 Myr−1 per Milky Way Equivalent Galaxy (MWEG), although the rate could plausibly range from 1 Myr−1 MWEG−1 to 1000 Myr−1 MWEG−1 (Kalogera et al 2004 Astrophys. J. 601 L179; Kalogera et al 2004 Astrophys. J. 614 L137 (erratum)). We convert coalescence rates into detection rates based on data from the LIGO S5 and Virgo VSR2 science runs and projected sensitivities for our advanced detectors. Using the detector sensitivities derived from these data, we find a likely detection rate of 0.02 per year for Initial LIGO–Virgo interferometers, with a plausible range between 2 × 10−4 and 0.2 per year. The likely binary neutron–star detection rate for the Advanced LIGO–Virgo network increases to 40 events per year, with a range between 0.4 and 400 per year.

Properties of stellar generations in globular clusters and relations with global parameters

Abstract: We revise the scenario of the formation of Galactic globular clusters (GCs) by adding the observed detailed chemical composition of their different stellar generations to the set of their global parameters. We exploit the unprecedented set of homogeneous abundances of more than 1200 red giants in 19 clusters, as well as additional data from literature, to give a new definition of bona fide GCs, as the stellar aggregates showing the Na-O anticorrelation. We propose a classification of GCs according to their kinematics and location in the Galaxy in three populations: disk/bulge, inner halo, and outer halo. We find that the luminosity function of GCs is fairly independent of their population, suggesting that it is imprinted by the formation mechanism only marginally affected by the ensuing evolution. We show that a large fraction of the primordial population should have been lost by the proto-GCs. The extremely low Al abundances found for the primordial population of massive GCs indicate a very fast enrichment process before the formation of the primordial population. We suggest a scenario for the formation of GCs that includes at least three main phases: i) the formation of a precursor population (likely due to the interaction of cosmological structures similar to those that led to the formation of dwarf spheroidals, but residing at smaller Galactocentric distances, with the early Galaxy or with other structures); ii) the triggering of a long episode of star formation (the primordial population) from the precursor population; and iii) the formation of the current GC, mainly within a cooling flow formed by the slow winds of a fraction of the primordial population. The precursor population is very effective in raising the metal content in massive and/or metal-poor (mainly halo) clusters, while its role is minor in small and/or metal-rich (mainly disk) ones. Finally, we use principal component analysis and multivariate relations to study the phase of metal enrichment from first to second generation. We conclude that most of the chemical signatures of GCs may be ascribed to a few parameters, the most important being metallicity, mass, and cluster age. Location within the Galaxy (as described by the kinematics) also plays some role, while additional parameters are required to describe their dynamical status.

Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer

Abstract: Maintenance of cellular pH homeostasis is fundamental to life. A number of key intracellular pH (pHi) regulating systems including the Na+/H+ exchangers, the proton pump, the monocarboxylate transporters, the HCO3− transporters and exchangers and the membrane-associated and cytosolic carbonic anhydrases cooperate in maintaining a pHi that is permissive for cell survival. A common feature of tumours is acidosis caused by hypoxia (low oxygen tension). In addition to oncogene activation and transformation, hypoxia is responsible for inducing acidosis through a shift in cellular metabolism that generates a high acid load in the tumour microenvironment. However, hypoxia and oncogene activation also allow cells to adapt to the potentially toxic effects of an excess in acidosis. Hypoxia does so by inducing the activity of a transcription factor the hypoxia-inducible factor (HIF), and particularly HIF-1, that in turn enhances the expression of a number of pHi-regulating systems that cope with acidosis. In this review, we will focus on the characterization and function of some of the hypoxia-inducible pH-regulating systems and their induction by hypoxic stress. It is essential to understand the fundamentals of pH regulation to meet the challenge consisting in targeting tumour metabolism and acidosis as an anti-tumour approach. We will summarize strategies that take advantage of intracellular and extracellular pH regulation to target the primary tumour and metastatic growth, and to turn around resistance to chemotherapy and radiotherapy.

Serious Games, Debriefing, and Simulation/Gaming as a Discipline

Abstract: At the close of the 40th Anniversary Symposium of S&G, this editorial offers some thoughts on a few important themes related to simulation/gaming. These are development of the field, the notion of serious games, the importance of debriefing, the need for research, and the emergence of a discipline. I suggest that the serious gaming community has much to offer the discipline of simulation/gaming and that debriefing is vital both for learning and for establishing simulation/gaming as a discipline.

Reconstructing routes of invasion using genetic data: why, how and so what?

Abstract: Detailed knowledge about the geographical pathways followed by propagules from their source to the invading populations—referred to here as routes of invasion—provides information about the history of the invasion process and the origin and genetic composition of the invading populations. The reconstruction of invasion routes is required for defining and testing different hypotheses concerning the environmental and evolutionary factors responsible for biological invasions. In practical terms, it facilitates the design of strategies for controlling or preventing invasions. Most of our knowledge about the introduction routes of invasive species is derived from historical and observational data, which are often sparse, incomplete and, sometimes, misleading. In this context, population genetics has proved a useful approach for reconstructing routes of introduction, highlighting the complexity and the often counterintuitive nature of the true story. This approach has proved particularly useful since the recent development of new model-based methods, such as approximate Bayesian computation, making it possible to make quantitative inferences in the complex evolutionary scenarios typically encountered in invasive species. In this review, we summarize some of the fundamental aspects of routes of invasion, explain why the reconstruction of these routes is useful for addressing both practical and theoretical questions, and comment on the various reconstruction methods available. Finally, we consider the main insights obtained to date from studies of invasion routes.

Bridgehead effect in the worldwide invasion of the biocontrol harlequin ladybird.

Abstract: Recent studies of the routes of worldwide introductions of alien organisms suggest that many widespread invasions could have stemmed not from the native range, but from a particularly successful invasive population, which serves as the source of colonists for remote new territories. We call here this phenomenon the invasive bridgehead effect. Evaluating the likelihood of such a scenario is heuristically challenging. We solved this problem by using approximate Bayesian computation methods to quantitatively compare complex invasion scenarios based on the analysis of population genetics (microsatellite variation) and historical (first observation dates) data. We applied this approach to the Harlequin ladybird Harmonia axyridis (HA), a coccinellid native to Asia that was repeatedly introduced as a biocontrol agent without becoming established for decades. We show that the recent burst of worldwide invasions of HA followed a bridgehead scenario, in which an invasive population in eastern North America acted as the source of the colonists that invaded the European, South American and African continents, with some admixture with a biocontrol strain in Europe. This demonstration of a mechanism of invasion via a bridgehead has important implications both for invasion theory (i.e., a single evolutionary shift in the bridgehead population versus multiple changes in case of introduced populations becoming invasive independently) and for ongoing efforts to manage invasions by alien organisms (i.e., heightened vigilance against invasive bridgeheads).

Immunity and other defenses in pea aphids, Acyrthosiphon pisum

Abstract: Recent genomic analyses of arthropod defense mechanisms suggest conservation of key elements underlying responses to pathogens, parasites and stresses. At the center of pathogen-induced immune responses are signaling pathways triggered by the recognition of fungal, bacterial and viral signatures. These pathways result in the production of response molecules, such as antimicrobial peptides and lysozymes, which degrade or destroy invaders. Using the recently sequenced genome of the pea aphid (Acyrthosiphon pisum), we conducted the first extensive annotation of the immune and stress gene repertoire of a hemipterous insect, which is phylogenetically distantly related to previously characterized insects models. Strikingly, pea aphids appear to be missing genes present in insect genomes characterized to date and thought critical for recognition, signaling and killing of microbes. In line with results of gene annotation, experimental analyses designed to characterize immune response through the isolation of RNA transcripts and proteins from immune-challenged pea aphids uncovered few immune-related products. Gene expression studies, however, indicated some expression of immune and stress-related genes. The absence of genes suspected to be essential for the insect immune response suggests that the traditional view of insect immunity may not be as broadly applicable as once thought. The limitations of the aphid immune system may be representative of a broad range of insects, or may be aphid specific. We suggest that several aspects of the aphid life style, such as their association with microbial symbionts, could facilitate survival without strong immune protection.

Thermal conductivity of graphene in corbino membrane geometry.

Abstract: Local laser excitation and temperature readout from the intensity ratio of Stokes to anti-Stokes Raman scattering signals are employed to study the thermal properties of a large graphene membrane. The concluded value of the heat conductivity coefficient κ ≈ 600 W/(m·K) is smaller than previously reported but still validates the conclusion that graphene is a very good thermal conductor.

Resveratrol Promotes Autophagic Cell Death in Chronic Myelogenous Leukemia Cells via JNK-Mediated p62/SQSTM1 Expression and AMPK Activation

Abstract: Autophagy that is induced by starvation or cellular stress can enable cancer cell survival by sustaining energy homeostasis and eliminating damaged organelles and proteins. In response to stress, cancer cells have been reported to accumulate the protein p62/SQSTM1 (p62), but its role in the regulation of autophagy is controversial. Here, we report that the plant phytoalexin resveratrol (RSV) triggers autophagy in imatinib-sensitive and imatinib-resistant chronic myelogenous leukemia (CML) cells via JNK-dependent accumulation of p62. JNK inhibition or p62 knockdown prevented RSV-mediated autophagy and antileukemic effects. RSV also stimulated AMPK, thereby inhibiting the mTOR pathway. AMPK knockdown or mTOR overexpression impaired RSV-induced autophagy but not JNK activation. Lastly, p62 expression and autophagy in CD34+ progenitors from patients with CML was induced by RSV, and disrupting autophagy protected CD34+ CML cells from RSV-mediated cell death. We concluded that RSV triggered autophagic cell death in CML cells via both JNK-mediated p62 overexpression and AMPK activation. Our findings show that the JNK and AMPK pathways can cooperate to eliminate CML cells via autophagy.

The third generation of gravitational wave observatories and their science reach

Abstract: Large gravitational wave interferometric detectors, like Virgo and LIGO, demonstrated the capability to reach their design sensitivity, but to transform these machines into an effective observational instrument for gravitational wave astronomy a large improvement in sensitivity is required. Advanced detectors in the near future and third-generation observatories in more than one decade will open the possibility to perform gravitational wave astronomical observations from the Earth. An overview of the possible science reaches and the technological progress needed to realize a third-generation observatory are discussed in this paper. The status of the project Einstein Telescope (ET), a design study of a third-generation gravitational wave observatory, will be reported.

Distinct clones of Yersinia pestis caused the black death.

Abstract: From AD 1347 to AD 1353, the Black Death killed tens of millions of people in Europe, leaving misery and devastation in its wake, with successive epidemics ravaging the continent until the 18(th) century. The etiology of this disease has remained highly controversial, ranging from claims based on genetics and the historical descriptions of symptoms that it was caused by Yersinia pestis to conclusions that it must have been caused by other pathogens. It has also been disputed whether plague had the same etiology in northern and southern Europe. Here we identified DNA and protein signatures specific for Y. pestis in human skeletons from mass graves in northern, central and southern Europe that were associated archaeologically with the Black Death and subsequent resurgences. We confirm that Y. pestis caused the Black Death and later epidemics on the entire European continent over the course of four centuries. Furthermore, on the basis of 17 single nucleotide polymorphisms plus the absence of a deletion in glpD gene, our aDNA results identified two previously unknown but related clades of Y. pestis associated with distinct medieval mass graves. These findings suggest that plague was imported to Europe on two or more occasions, each following a distinct route. These two clades are ancestral to modern isolates of Y. pestis biovars Orientalis and Medievalis. Our results clarify the etiology of the Black Death and provide a paradigm for a detailed historical reconstruction of the infection routes followed by this disease.

Slip distribution of the February 27, 2010 Mw = 8.8 Maule Earthquake, central Chile, from static and high‐rate GPS, InSAR, and broadband teleseismic data

Abstract: [1] The shallow depth underthrust earthquake of February 27, 2010 (Mw 8.8) ruptured the subduction plate interface in central Chile between 34°S and 38°S. We retrieve the spatial and temporal distribution of slip during this mega-earthquake through a joint inversion of teleseismic records, InSAR and High Rate GPS (HRGPS) data. Additionally, our model is shown to agree with broadband surface waves. Rupture initiated at about 32 km depth and propagated bilaterally resulting in two main slip zones located SSW and NNE of the hypocenter. Nucleation did not take place within or at the edge of one of these main asperities, but in between. During the first 30s, slip propagated predominantly southwards. Later on, the rupture evolved more slowly and more symmetrically. Eventually, the northern asperity became predominant with maximum slip reaching about 20 m. Most of the seismic moment was released within 110s, a relatively short time, explained by the bilateral propagation. The overall average rupture velocity is 2.6 km/s but propagation occurred initially faster towards the south (3.2 km/s). Large slip did not reach the trench, a result consistent with the moderate size of the tsunami. Down-dip, rupture stopped at about 50 km depth, in agreement with the lower limit of the locked zone inferred by Ruegg et al. (2009) from pre-seismic GPS data.

Reactive Oxygen Species during Plant-microorganism Early Interactions

Abstract: Reactive Oxygen Species (ROS) are continuously produced as a result of aerobic metabolism or in response to biotic and abiotic stresses. ROS are not only toxic by-products of aerobic metabolism, but are also signalling molecules involved in several developmental processes in all organisms. Previous studies have clearly shown that an oxidative burst often takes place at the site of attempted invasion during the early stages of most plant-pathogen interactions. Moreover, a second ROS production can be observed during certain types of plant-pathogen interactions, which triggers hypersensitive cell death (HR). This second ROS wave seems absent during symbiotic interactions. This difference between these two responses is thought to play an important signalling role leading to the establishment of plant defense. In order to cope with the deleterious effects of ROS, plants are fitted with a large panel of enzymatic and non-enzymatic antioxidant mechanisms. Thus, increasing numbers of publications report the characterisation of ROS producing and scavenging systems from plants and from microorganisms during interactions. In this review, we present the current knowledge on the ROS signals and their role during plant-microorganism interactions.

EANM procedure guidelines for brain neurotransmission SPECT using (123)I-labelled dopamine transporter ligands, version 2

Abstract: These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aim of the guidelines is to assist nuclear medicine practitioners when making recommendations, performing, interpreting, and reporting the results of clinical dopamine transporter (DAT) single photon emission computed tomography (SPECT) studies using (123)I-labelled radiopharmaceuticals. The aim is to achieve a high-quality standard of DAT SPECT imaging, which will increase the diagnostic impact of this technique in neurological practice. The present document is an update of the 2002 guidelines [1] and has been guided by the views of various national societies: the Task Group Neuro-Nuclear-Medicine of the German Society of Nuclear Medicine [2], a consensus statement of the imaging centres included in the "Kompetenznetz-Parkinson" sponsored by the German Federal Ministry of Education, and the Task Group of Neuro-Nuclear-Medicine of the French Society of Nuclear Medicine [3]. The guidelines reflect the individual experience of experts in European countries. The guidelines are intended to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.

Mitochondrial control of caspase-dependent and -independent cell death.

Abstract: Mitochondria control whether a cell lives or dies. The role mitochondria play in deciding the fate of a cell was first identified in the mid-1990s, because mitochondria-enriched fractions were found to be necessary for activation of death proteases, the caspases, in a cell-free model of apoptotic cell death. Mitochondrial involvement in apoptosis was subsequently shown to be regulated by Bcl-2, a protein that was known to contribute to cancer in specific circumstances. The important role of mitochondria in promoting caspase activation has therefore been a major focus of apoptosis research; however, it is also clear that mitochondria contribute to cell death by caspase-independent mechanisms. In this review, we will highlight recent findings and discuss the mechanism underlying the mitochondrial control of apoptosis and caspase-independent cell death.

Photometric characterization of exoplanets using angular and spectral differential imaging

Abstract: In recent years, there has been intensive research into the direct detection of exoplanets. Data obtained in the future with high-contrast imaging instruments, optimized for the direct detection of giant planets, may be strongly limited by speckle noise. Specific observing strategies and data analysis methods, such as angular and spectral differential imaging, are required to attenuate the noise level and possibly to detect the flux of faint planets. Even though these methods are very efficient at suppressing the speckles, the photometry of faint planets is dominated by the speckle residuals. The determination of the effective temperature and surface gravity of the detected planets from photometric measurements in different bands is then limited by the photometric error on the planet flux. In this paper, we investigate this photometric error and the consequences on the determination of the physical parameters of the detected planets. We perform detailed end-to-end simulation with the CAOS-based software package for spectro-polarimetric high-contrast exoplanet research (SPHERE) to obtain realistic data representing typical observing sequences in the Y, J, H and K s bands with a high-contrast imager. The simulated data are used to measure the photometric accuracy as a function of contrast for planets detected with angular and spectral+angular differential methods. We apply this empirical accuracy to study the characterization capabilities of a high-contrast differential imager. We show that the expected photometric performances will allow the detection and characterization of exoplanets down to a Jupiter mass at angular separations of 1.0 and 0.2 arcsec, respectively, around high-mass and low-mass stars with two observations in different filter pairs. We also show that the determination of the physical parameters of the planets from photometric measurements in different filter pairs is essentially limited by the error on the determination of the surface gravity.

Robust Independent Component Analysis by Iterative Maximization of the Kurtosis Contrast With Algebraic Optimal Step Size

Abstract: Independent component analysis (ICA) aims at decomposing an observed random vector into statistically independent variables Deflation-based implementations, such as the popular one-unit FastICA algorithm and its variants, extract the independent components one after another A novel method for deflationary ICA, referred to as RobustICA, is put forward in this paper This simple technique consists of performing exact line search optimization of the kurtosis contrast function The step size leading to the global maximum of the contrast along the search direction is found among the roots of a fourth-degree polynomial This polynomial rooting can be performed algebraically, and thus at low cost, at each iteration Among other practical benefits, RobustICA can avoid prewhitening and deals with real- and complex-valued mixtures of possibly noncircular sources alike The absence of prewhitening improves asymptotic performance The algorithm is robust to local extrema and shows a very high convergence speed in terms of the computational cost required to reach a given source extraction quality, particularly for short data records These features are demonstrated by a comparative numerical analysis on synthetic data RobustICA's capabilities in processing real-world data involving noncircular complex strongly super-Gaussian sources are illustrated by the biomedical problem of atrial activity (AA) extraction in atrial fibrillation (AF) electrocardiograms (ECGs), where it outperforms an alternative ICA-based technique