Éditeur(s) : HAL CCSD Landes Bioscience
Résumé : International audience
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Autophagy

hal-00735751
https://hal.archives-ouvertes.fr/hal-00735751
PUBMED : 22966490

Éditeur(s) : HAL CCSD Royal Society, The
Résumé : International audience
Many studies have focused on the impacts of climate change on biological assemblages, yet little is known about how climate interacts with other major anthropogenic influences on biodiversity, such as habitat disturbance. Using a unique global database of 1128 local ant assemblages , we examined whether climate mediates the effects of habitat disturbance on assemblage structure at a global scale. Species richness and evenness were associated positively with temperature, and negatively with disturbance. However, the interaction among temperature, precipitation and disturbance shaped species richness and evenness. The effect was manifested through a failure of species richness to increase substantially with temperature in transformed habitats at low precipitation. At low precipitation levels, evenness increased with temperature in undisturbed sites, peaked at medium temperatures in disturbed sites and remained low in transformed sites. In warmer climates with lower rainfall, the effects of increasing disturbance on species richness and evenness were akin to decreases in temperature of up to 98C. Anthropogenic disturbance and ongoing climate change may interact in complicated ways to shape the structure of assemblages, with hot, arid environments likely to be at greatest risk.
ISSN: 0962-8452

hal-01323255
https://hal.archives-ouvertes.fr/hal-01323255
DOI : 10.1098/rspb.2015.0418

Éditeur(s) : HAL CCSD Geological Society of America
Résumé : International audience
We present the results of dynamic modeling of the western Mediterranean that accounts for observed global positioning system (GPS) surface deformation of the Alboran Sea and surrounding Rif and Betic Mountains as the result of the combined effects of relative motion of the Eurasian and Nubian plates, low strength in the Alboran Sea region and sub-lithospheric processes occurring beneath the External Rif domain. Assuming that the lithosphere behaves elastically over the short time period of the GPS observations, an elastic plate model is considered in our study, including an area of weak lithosphere (factor of 10) centered on the Alboran Sea and in which lateral boundary conditions consist of the Nubia-Eurasia oblique convergence. Sub-crustal processes are modeled by application of a horizontal traction on a small area (patch) at the base of the elastic plate. Our modeling studies demonstrate the need for sub-crustal or sub-lithospheric, southwestward-directed forcing to account for observed southwestward motion of the Rif and Betic domains. Based on the location, orientation, and small area of the traction patch, we hypothesize that forcing is associated with delamination and rollback of the subducted African continental lithospheric mantle beneath the External Rif zone, due to the pull of the oceanic part of the Western Mediterranean slab, a dynamic process that may be similar to that where the over-riding plate is driven toward the subduction zone during slab rollback.
ISSN: 0091-7613

hal-00524546
https://hal.archives-ouvertes.fr/hal-00524546
DOI : 10.1130/G30963.1

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND & AIMS: Nutrients influence non-alcoholic fatty liver disease. Essential fatty acids deficiency promotes various syndromes, including hepatic steatosis, through increased de novo lipogenesis. The mechanisms underlying such increased lipogenic response remain unidentified. METHODS: We used wild type mice and mice lacking Liver X Receptors to perform a nutrigenomic study that aimed at examining the role of these transcription factors. RESULTS: We showed that, in the absence of Liver X Receptors, essential fatty acids deficiency does not promote steatosis. Consistent with this, Liver X Receptors are required for the elevated expression of genes involved in lipogenesis in response to essential fatty acids deficiency. CONCLUSIONS: This work identifies, for the first time, the central role of Liver X Receptors in steatosis induced by essential fatty acids deficiency.
ISSN: 0168-8278

inserm-00872314
http://www.hal.inserm.fr/inserm-00872314
DOI : 10.1016/j.jhep.2013.01.006
PUBMED : 23333450

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : The area of forest plantations is increasing worldwide helping to meet timber demand and protect natural forests. However, with global change, monospecific plantations are increasingly vulnerable to abiotic and biotic disturbances. As an adaption measure we need to move to plantations that are more diverse in genotypes, species, and structure, with a design underpinned by science. TreeDivNet, a global network of tree diversity experiments, responds to this need by assessing the advantages and disadvantages of mixed species plantations. The network currently consists of 18 experiments, distributed over 36 sites and five ecoregions. With plantations 1-15 years old, TreeDivNet can already provide relevant data for forest policy and management. In this paper, we highlight some early results on the carbon sequestration and pest resistance potential of more diverse plantations. Finally, suggestions are made for new, innovative experiments in understudied regions to complement the existing network.
ISSN: 0044-7447

hal-01204232
https://hal.archives-ouvertes.fr/hal-01204232
DOI : 10.1007/s13280-015-0685-1
PRODINRA : 324368
PUBMED : 26264716

Éditeur(s) : Elsevier
Résumé : Evidence has accumulated that climate variability influences the state and functioning of marine ecosystems. At the same time increasing pressure from exploitation and other human activities has been shown to impact exploited and non-exploited species and potentially modify ecosystem structure. There has been a tendency among marine scientists to pose the question as a dichotomy, i.e., whether (1) "natural" climate variability or (2) fishery exploitation bears the primary responsibility for population declines in fish populations and the associated ecosystem changes. However, effects of both climate and exploitation are probably substantially involved in most cases. More importantly, climate and exploitation interact in their effects, such that climate may cause failure in a fishery management scheme but that fishery exploitation may also disrupt the ability of a resource population to withstand, or adjust to, climate changes. Here, we review how exploitation, by altering the structure of populations and ecosystems, can modify their ability to respond to climate. The demographic effects of fishing (removal of large-old individuals) can have substantial consequences on the capacity of populations to buffer climate variability through various pathways (direct demographic effects, effects on migration, parental effects). In a similar way, selection of population sub-units within metapopulations may also lead to a reduction in the capacity of populations to withstand climate variability and change. At the ecosystem level, reduced complexity by elimination of species, such as might occur by fishing, may be destabilizing and could lead to reduced resilience to perturbations. Differential exploitation of marine resources could also promote increased turnover rates in marine ecosystems, which would exacerbate the effects of environmental changes. Overall (and despite the specificities of local situations) reduction in marine diversity at the individual, population and ecosystem levels will likely lead to a reduction in the resilience and an increase in the response of populations and ecosystems to future climate variability and change. Future management schemes will have to consider the structure and functioning of populations and ecosystems in a wider sense in order to maximise the ability of marine fauna to adapt to future climates. (C) 2009 Elsevier B.V. All rights reserved.
Journal of Marine Systems (0924-7963) (Elsevier), 2010-02 , Vol. 79 , N. 3-4 , P. 403-417

Droits : 2009 Elsevier B.V. All rights reserved.
http://archimer.ifremer.fr/doc/2010/publication-7384.pdf
DOI:10.1016/j.jmarsys.2008.12.018
http://archimer.ifremer.fr/doc/00000/7384/

Droits : 2010 Ifremer/Observatoire du Patrimoine Naturel de Bretagne
http://archimer.ifremer.fr/doc/00026/13737/10865.pdf
http://archimer.ifremer.fr/doc/00026/13737/

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: The RH blood group system has many RHCE variant alleles that have arisen through gene conversion or nucleotide changes. Two probands, with red blood cells (RBCs) that were D+C+E-c+(w) e+ were sent to our laboratories to resolve the weak c expression. STUDY DESIGN AND METHODS: Hemagglutination tests were performed by automated and manual procedures. Genomic DNA analysis was performed by sequencing of Exons 1 to 10 of RHCE and RHD. RESULTS: The probands' RBCs did not react with standard monoclonal anti-E reagents from Bio-Rad, Diagast, DiaMed, Immucor, Ortho, and Quotient. The RBCs reacted variably with anti-c reagents from Diagast, DiaMed, Immucor, or Ortho and did not react with the Quotient anti-c reagent. Surprisingly, sequencing results of RHCE showed the presence of C/G at Position 676 (E/e polymorphism) and the association of the E polymorphism with a 734T>C transition in Exon 5 of the RHCE, encoding a Leu245Pro amino acid substitution in the mature RhcE polypeptide. Replacement of leucine 245 by proline in the eighth transmembrane domain of the RhcE protein may have a steric effect on the protein such that most anti-E reagents do not bind and the interaction between anti-c and c antigen is also affected. CONCLUSION: We report a novel RHCE*cE allele, RHCE*cE734C, which was assigned the provisional ISBT allele name RHCE*cE.14 or RHCE*03.14. It was found in two probands whose RBCs had weakened c expression and typed E- with conventional anti-E reagents. These data, once again, highlight the fact that the genotype does not always reflect the phenotype.
ISSN: 0041-1132

hal-00839022
https://hal.archives-ouvertes.fr/hal-00839022
DOI : 10.1111/j.1537-2995.2012.03860.x
PUBMED : 22958092

Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations.
ISSN: 0305-1048

hal-01146849
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146849
DOI : 10.1093/nar/gkv350
PUBMED : 25897122

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
We present evidence that GPS velocity estimates of plate motions and fault slip rates agree to within uncertainties with geologic estimates during the most recent phase of the geologic evolution of the E Mediterranean region (post-Late Miocene). On this basis, we use the GPS differential velocities to estimate the timing of initiation of the principal structures in NW Turkey, the N Aegean Sea, and central Greece, including, the Marmara Sea, the Gulfs of Evia (GoE) and Corinth (GoC). and the Kephalonia Transform fault (KTF). We interpret these ages to indicate that the North Anatolian fault propagated across the N Aegean, opening the GoE and GoC and initiating the KTF, during the past 1-4 Ma. We further suggest that Aegean extension that was earlier more distributed across the Aegean Basin became focused on this new fault system allowing the southern Aegean and Peloponnisos to translate SW with little internal deformation, as observed today with GPS. This change in tectonic configuration may account for the clear geologic evidence for crustal thinning throughout the S Aegean in apparent contradiction with low present-day strain rates. We further show that the low present-day strain rate along the southern edge of the Aegean micro-plate requires substantial aseismic slip along the plate interface below Crete, consistent with the low level of historic, subduction-type earthquakes along this segment of the subduction zone.
ISSN: 0040-1951

hal-00512634
https://hal.archives-ouvertes.fr/hal-00512634
DOI : 10.1016/j.tecto.2009.05.027

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
We develop a block model for the Aegean and surrounding areas, constrained by Global Positioning System (GPS), in order to investigate the degree of coupling on the Hellenic subduction interface (i.e., the fraction of the motion across the plate boundary accommodated by elastic strain accumulation). We use previously published models, and seismicity to define the geometry of the interface separating the down-going Nubian slab from the overriding Aegean. This model provides a good fit to the GPS observations; for the ∼200,000 km2 Aegean block the wrms of the residual velocities is 1.4 mm/yr for 80 GPS velocity estimates, approximately the 95% level of the GPS velocity uncertainties. We investigate the degree of coupling on the seismically active plate interface, the Hellenic trench splay fault (believed to be the source of the 365 AD Great Crete Earthquake and Tsunami), and the Kephalonia transform fault by comparing the modeled GPS residual velocity field for a range of coupling values. The GPS observations are almost insensitive to coupling on the Kephalonia transform fault, because of the vertical dip of the fault that creates interseismic deformation only close to the fault where few GPS sites exist. The absence of resolvable shortening of the leading edge of the Aegean Plate precludes coupling of more than 0.2 (20% of the full Nubia-Aegean convergence rate) on the modeled plate interface. Because of the shallow dip of the plate interface and trench splay fault, and high rate of convergence, if these boundaries were fully coupled, high elastic strain rates would be expected to extend well into the overriding Aegean plate. Based on our preferred value for the degree of coupling (0.1), and assuming characteristic earthquake behavior, we estimate a recurrence time for great earthquakes with slip similar to that for the 365 Crete event of 5700-8300 yr, consistent with the absence of subsequent great earthquakes on this segment of the subduction zone.
ISSN: 0012-821X

hal-01053486
https://hal.archives-ouvertes.fr/hal-01053486
DOI : 10.1016/j.epsl.2013.10.018

Éditeur(s) : HAL CCSD Météo et Climat
Résumé : International audience
D'initiative française, le projet international HyMeX a pour objectif d'améliorer la compréhension du cycle de l'eau en Méditerranée, de sa variabilité, de l'échelle de l'événement météorologique aux échelles saisonnières et interannuelles, et de ses caractéristiques sur une décennie, dans un contexte de changement global. Le projet est motivé par le rôle déterminant des processus de mésoéchelle, couplés entre l'atmosphère, la mer et la terre, sur la variabilité du système climatique et sur le déclenchement d'événements hydrométéorologiques extrêmes (précipitations et inondations, vents forts et convection océanique, canicules et sécheresses). Le projet vise enfin à évaluer les conséquences de ces événements extrêmes sur la vulnérabilité sociale et économique de cette région et sa capacité d'adaptation.
ISSN: 0026-1181

hal-00828758
https://hal.archives-ouvertes.fr/hal-00828758
https://hal.archives-ouvertes.fr/hal-00828758/document
https://hal.archives-ouvertes.fr/hal-00828758/file/meteo_2013_80_23%20%281%29.pdf
DOI : 10.4267/2042/48792

Éditeur(s) : HAL CCSD European Geosciences Union
Résumé : International audience
The exchanges of carbon, water and energy between the atmosphere and the Amazon basin have global implications for the current and future climate. Here, the global atmospheric inversion system of the Monitoring of Atmospheric Composition and Climate (MACC) service is used to study the seasonal and interannual variations of biogenic CO 2 fluxes in Amazonia during the period 2002–2010. The system assimilated surface measurements of atmospheric CO 2 mole fractions made at more than 100 sites over the globe into an atmospheric transport model. The present study adds measurements from four surface stations located in tropical South America, a region poorly covered by CO 2 observations. The estimates of net ecosystem exchange (NEE) optimized by the inversion are compared to an independent estimate of NEE upscaled from eddy-covariance flux measurements in Amazonia. They are also qualitatively evaluated against reports on the seasonal and interannual variations of the land sink in South America from the scientific literature. We attempt at assessing the impact on NEE of the strong droughts in 2005 and 2010 (due to severe and longer-than-usual dry seasons) and the extreme rainfall conditions registered in 2009. The spatial variations of the seasonal and in-terannual variability of optimized NEE are also investigated. While the inversion supports the assumption of strong spatial heterogeneity of these variations, the results reveal critical limitations of the coarse-resolution transport model, the surface observation network in South America during the recent years and the present knowledge of modelling uncertainties in South America that prevent our inversion from capturing the seasonal patterns of fluxes across Amazonia. However, some patterns from the inversion seem consistent with the anomaly of moisture conditions in 2009.
ISSN: 1680-7316

hal-01557375
https://hal.univ-lorraine.fr/hal-01557375
https://hal.univ-lorraine.fr/hal-01557375/document
https://hal.univ-lorraine.fr/hal-01557375/file/acp-15-8423-2015.pdf
DOI : 10.5194/acp-15-8423-2015-supplement

Éditeur(s) : HAL CCSD American Geophysical Union
Résumé : International audience
GPS measurements adjacent to the southern Red Sea and Afar Triple Junction, indicate that the Red Sea Rift bifurcates south of 17 degrees N latitude with one branch following a continuation of the main Red Sea Rift (similar to 150 degrees Az.) and the other oriented more N-S, traversing the Danakil Depression. These two rift branches account for the full Arabia-Nubia relative motion. The partitioning of extension between rift branches varies approximately linearly along strike; north of similar to 16 degrees N latitude, extension (similar to 15 mm/yr) is all on the main Red Sea Rift while at similar to 13 degrees N, extension (similar to 20 mm/yr) has transferred completely to the Danakil Depression. The Danakil Block separates the two rifts and rotates in a counterclockwise sense with respect to Nubia at a present-day rate of 1.9 +/- 0.1 degrees/Myr around a pole located at 17.0 +/- 0.2 degrees N, 39.7 +/- 0.2 degrees E, accommodating extension along the rifts and developing the roughly triangular geometry of the Danakil Depression. Rotating the Danakil Block back in time to close the Danakil Depression, and assuming that the rotation rate with respect to Nubia has been roughly constant, the present width of the Danakil Depression is consistent with initiation of block rotation at 9.3 +/- 4 Ma, approximately coincident with the initiation of ocean spreading in the Gulf of Aden, and a concomitant similar to 70% increase in the rate of Nubia-Arabia relative motion.
ISSN: 0094-8276

hal-00475536
https://hal.archives-ouvertes.fr/hal-00475536
DOI : 10.1029/2009GL041127

Éditeur(s) : HAL CCSD
Résumé : This study assesses the place of MSEs in Haiti and gives a brief description of the relevant economic, regulatory and technological instruments of economic development and environmental protection. The discussions suggest that the application of such instruments will encourage and improve economic development in Haiti. The infrastructure necessary for MSEs drives growth and offers added value to economic development in Haiti. With an overview of Haitian MSEs we have been able to identify and palliate insufficiencies in the legislative framework regulating the operation of MSEs, as well as, understand their involvement in economic growth. MSEs are a powerful tool to reduce poverty, facilitate economic development and reinforce policies supporting environmental protection.
Ce travail dresse un bilan sur la situation des TPE en Haïti et propose une analyse succincte de l’impact des instruments économiques, règlementaires et technologique au développement économique et à la protection de l’environnement. Les discussions menées ont permis de découvrir que l’application de ces instruments est une perspective d’amélioration du développement économique des TPE.La structuration des TPE reste la principale action stratégique de croissance et représente une grande valeur ajoutée pour le développement économique du pays. Le panorama des TPE haïtiennes nous a permis de compléter les insuffisances du cadre légal réglementant le fonctionnement des TPE et de comprendre leur participation à la croissance économique du pays. Ce sont des outils indispensables pour réduire la pauvreté, faciliter le développement économique et renforcer les politiques de protection de l’environnement à travers le pays.
https://hal.univ-antilles.fr/hal-01292918

hal-01292918
https://hal.univ-antilles.fr/hal-01292918
https://hal.univ-antilles.fr/hal-01292918/document
https://hal.univ-antilles.fr/hal-01292918/file/Final-IER_Article%20P.%20SIMON.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
We present GPS observations in Morocco and adjacent areas of Spain from 15 continuous (CGPS) and 31 survey-mode (SGPS) sites extending from the stable part of the Nubian plate to central Spain. We determine a robust velocity field for the W Mediterranean that we use to constrain models for the Iberia-Nubia plate boundary. South of the High Atlas Mountain system, GPS motions are consistent with Nubia plate motions from prior geodetic studies. We constrain shortening in the Atlas system to <1.5 mm/yr. 95% confidence level. North of the Atlas Mountains, the GPS velocities indicate Nubia motion with respect to Eurasia, but also a component of motion normal to the direction of Nubia-Eurasia motion, consisting of southward translation of the Rif Mountains in N Morocco at rates exceeding 5 mm/yr. This southward motion appears to be directly related to Miocene opening of the Alboran Sea. The Betic Mountain system north of the Alboran Sea is characterized by WNW motion with respect to Eurasia at 1-2 mm/yr. paralleling Nubia-Eurasia relative motion. In addition, sites located in the Betics north of the southerly moving Rif Mountains also indicate a component of southerly motion with respect to Eurasia. We interpret this as indicating that deformation associated with Nubia-Eurasia plate motion extends into the southern Betics, but also that the Betic system may be affected by the same processes that are causing southward motion of the Rif Mountains south of the Alboran Sea. Kinematic modeling indicates that plate boundary geometries that include a boundary through the Straits of Gibraltar are most compatible with the component of motion in the direction of relative plate motion, but that two additional blocks (Alboran-Rif block, Betic Mountain block), independent of both Nubia and Eurasia are needed to account for the motions of the Rif and Betic Mountains normal to the direction of relative plate motion. We speculate that the southward motions of the Alboran-Rif and Betic blocks may be related to mantle flow, possibly induced by southward rollback of the subducted Nubian plate beneath the Alboran Sea and Rif Mountains.
ISSN: 0264-3707

hal-00475538
https://hal.archives-ouvertes.fr/hal-00475538
DOI : 10.1016/j.jog.2009.10.007

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Despite the dramatic reductions in children's blood lead levels (BLLs), there is considerable evidence that low-level lead exposure is associated with intellectual deficits and behavioral problems, without apparent threshold. There are limited data, however, about the contribution of residential sources of lead to contemporary children's blood lead levels. The aim of this study is to calculate the contributions of residential sources of lead to assess the potential impact of setting new standards for lead levels in residential dust, soil and water. We enrolled 484 French children aged from 6 months to 6 years, and collected data on social, housing and individual characteristics. Lead concentrations in blood and environmental samples (water, soils, and dusts) were measured using inductively coupled plasma mass spectrometry. Data were analyzed using a multivariate generalized additive model accounting for the sampling design and the sampling weights. We found that exceedingly low concentrations of lead in dust, soil and water were significant predictors of children's BLLs, after adjustment for potential confounding variables. Lead-contaminated floor dust was the main source of lead in blood. BLLs (GM: 14μg/L) increased by 65%, 13%, 25%, and 5% when lead content in floor dust, loose soil, hard soil and water increased from their 25th percentile to their 95th percentile, respectively. We also observed that the steepest increase in BLLs occurred at the lowest levels of lead-contaminated floor dust, which indicates that lead contamination should be kept as low as possible. Impact of different possible standards on children's BLLs was also tabulated and indicated that unless standards are set low, they will only benefit a small proportion of children who have the highest exposures.
ISSN: 1438-4639

inserm-00821999
http://www.hal.inserm.fr/inserm-00821999
DOI : 10.1016/j.ijheh.2013.02.007
PUBMED : 23528234