Showing papers by "University of Bordeaux published in 2009"
TL;DR: The Large Area Telescope (Fermi/LAT) as mentioned in this paper is the primary instrument on the Fermi Gamma-ray Space Telescope, which is an imaging, wide field-of-view, high-energy gamma-ray telescope, covering the energy range from below 20 MeV to more than 300 GeV.
Abstract: (Abridged) The Large Area Telescope (Fermi/LAT, hereafter LAT), the primary instrument on the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy gamma-ray telescope, covering the energy range from below 20 MeV to more than 300 GeV. This paper describes the LAT, its pre-flight expected performance, and summarizes the key science objectives that will be addressed. On-orbit performance will be presented in detail in a subsequent paper. The LAT is a pair-conversion telescope with a precision tracker and calorimeter, each consisting of a 4x4 array of 16 modules, a segmented anticoincidence detector that covers the tracker array, and a programmable trigger and data acquisition system. Each tracker module has a vertical stack of 18 x,y tracking planes, including two layers (x and y) of single-sided silicon strip detectors and high-Z converter material (tungsten) per tray. Every calorimeter module has 96 CsI(Tl) crystals, arranged in an 8 layer hodoscopic configuration with a total depth of 8.6 radiation lengths. The aspect ratio of the tracker (height/width) is 0.4 allowing a large field-of-view (2.4 sr). Data obtained with the LAT are intended to (i) permit rapid notification of high-energy gamma-ray bursts (GRBs) and transients and facilitate monitoring of variable sources, (ii) yield an extensive catalog of several thousand high-energy sources obtained from an all-sky survey, (iii) measure spectra from 20 MeV to more than 50 GeV for several hundred sources, (iv) localize point sources to 0.3 - 2 arc minutes, (v) map and obtain spectra of extended sources such as SNRs, molecular clouds, and nearby galaxies, (vi) measure the diffuse isotropic gamma-ray background up to TeV energies, and (vii) explore the discovery space for dark matter.
3,666 citations
TL;DR: This critical review provides an overall survey of the basic concepts and up-to-date literature results concerning the very promising use of gold nanoparticles (AuNPs) for medicinal applications.
Abstract: This critical review provides an overall survey of the basic concepts and up-to-date literature results concerning the very promising use of gold nanoparticles (AuNPs) for medicinal applications. It includes AuNP synthesis, assembly and conjugation with biological and biocompatible ligands, plasmon-based labeling and imaging, optical and electrochemical sensing, diagnostics, therapy (drug vectorization and DNA/gene delivery) for various diseases, in particular cancer (also Alzheimer, HIV, hepatitis, tuberculosis, arthritis, diabetes) and the essential in vitro and in vivo toxicity. It will interest the medicine, chemistry, spectroscopy, biochemistry, biophysics and nanoscience communities (211 references).
2,499 citations
TL;DR: In this paper, the authors used excitation-emission matrix (EEM) spectroscopy, a sensitive technique that allows direct analysis of water samples, to better characterize DOM in the Gironde Estuary (southwestern France).
1,180 citations
TL;DR: Results implicate IDO as a critical molecular mediator of inflammation-induced depressive-like behavior, probably through the catabolism of tryptophan along the kynurenine pathway.
Abstract: Although elevated activity of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) has been proposed to mediate comorbid depression in inflammatory disorders, its causative role has never been tested. We report that peripheral administration of lipopolysaccharide (LPS) activates IDO and culminates in a distinct depressive-like behavioral syndrome, measured by increased duration of immobility in both the forced-swim and tail suspension tests. Blockade of IDO activation either indirectly with the anti-inflammatory tetracycline derivative minocycline, that attenuates LPS-induced expression of proinflammatory cytokines, or directly with the IDO antagonist 1-methyltryptophan (1-MT), prevents development of depressive-like behavior. Both minocycline and 1-MT normalize the kynurenine/tryptophan ratio in the plasma and brain of LPS-treated mice without changing the LPS-induced increase in turnover of brain serotonin. Administration of L-kynurenine, a metabolite of tryptophan that is generated by IDO, to naive mice dose dependently induces depressive-like behavior. These results implicate IDO as a critical molecular mediator of inflammation-induced depressive-like behavior, probably through the catabolism of tryptophan along the kynurenine pathway.
1,069 citations
TL;DR: In this article, the authors prove that the nonlinear dispersive partial differential equations (NPDPDE) and Korteweg-de Vries (KDE) arise in the modeling of the propagation of shallow water waves over a flat bed.
Abstract: In recent years two nonlinear dispersive partial differential equations have attracted a lot of attention due to their integrable structure. We prove that both equations arise in the modeling of the propagation of shallow water waves over a flat bed. The equations capture stronger nonlinear effects than the classical nonlinear dispersive Benjamin-Bona-Mahoney and Korteweg-de Vries equations. In particular, they accomodate wave breaking phenomena.
989 citations
World Health Organization1, Brigham and Women's Hospital2, University of Bordeaux3, Stanford University4, Centers for Disease Control and Prevention5, Brown University6, Tufts University7, Rega Institute for Medical Research8, Public Health Agency of Canada9, Utrecht University10, Erasmus University Rotterdam11, University College London12
TL;DR: This paper follows the same procedures described previously to develop an updated list of SDRMs that are likely to be useful for ongoing and future studies of transmitted drug resistance and concludes that the updated SDRM list has 93 mutations.
Abstract: Programs that monitor local, national, and regional levels of transmitted HIV-1 drug resistance inform treatment guidelines and provide feedback on the success of HIV-1 treatment and prevention programs. To accurately compare transmitted drug resistance rates across geographic regions and times, the World Health Organization has recommended the adoption of a consensus genotypic definition of transmitted HIV-1 drug resistance. In January 2007, we outlined criteria for developing a list of mutations for drug-resistance surveillance and compiled a list of 80 RT and protease mutations meeting these criteria (surveillance drug resistance mutations; SDRMs). Since January 2007, several new drugs have been approved and several new drug-resistance mutations have been identified. In this paper, we follow the same procedures described previously to develop an updated list of SDRMs that are likely to be useful for ongoing and future studies of transmitted drug resistance. The updated SDRM list has 93 mutations including 34 NRTI-resistance mutations at 15 RT positions, 19 NNRTI-resistance mutations at 10 RT positions, and 40 PI-resistance mutations at 18 protease positions.
870 citations
TL;DR: These findings establish high harmonic interferometry as an effective approach to resolving multi-electron dynamics with sub-Ångström spatial resolution arising from the de Broglie wavelength of the recombining electron, and attosecond temporal resolution arisen from the timescale ofThe recombination event.
Abstract: High harmonic emission occurs when an electron, liberated from a molecule by an incident intense laser field, gains energy from the field and recombines with the parent molecular ion. The emission provides a snapshot of the structure and dynamics of the recombining system, encoded in the amplitudes, phases and polarization of the harmonic light. Here we show with CO2 molecules that high harmonic interferometry can retrieve this structural and dynamic information: by measuring the phases and amplitudes of the harmonic emission, we reveal ‘fingerprints’ of multiple molecular orbitals participating in the process and decode the underlying attosecond multi-electron dynamics, including the dynamics of electron rearrangement upon ionization. These findings establish high harmonic interferometry as an effective approach to resolving multi-electron dynamics with sub-Angstrom spatial resolution arising from the de Broglie wavelength of the recombining electron, and attosecond temporal resolution arising from the timescale of the recombination event. The high harmonic emission that accompanies the recombination of an electron with its parent molecular ion in an intense laser field provides a snapshot of the structure and dynamics of the recombining system. Experiments with CO2 molecules now show that high harmonic interferometry can retrieve this structural and dynamic information by measuring the phases and amplitudes of the harmonic emission. The resulting 'fingerprints' of the multiple molecular orbitals participating in the process can be used to decode the underlying attosecond multi-electron dynamics, including the dynamics of electron rearrangement upon ionization. The light emitted from the system contains images of moving electrons that can be processed into a movie. These findings establish high harmonic interferometry as an effective approach to resolving multi-electron dynamics with sub-Angstrom spatial resolution arising from the de-Broglie wavelength of the recombining electron, and attosecond temporal resolution arising from the timescale of the recombination event. The high harmonic emission that accompanies the recombination of an electron with its parent molecular ion in an intense laser field provides a snapshot of the structure and dynamics of the recombining system. Experiments on CO2 molecules now show how to extract information from the properties of the emitted light about the underlying multi-electron dynamics with sub-Angstrom spatial resolution and attosecond temporal resolution
840 citations
TL;DR: It is clear that in spite of a growing public and commercial interest and the success of several pilot studies and field scale applications more fundamental research still is needed to better exploit the metabolic diversity of the plants themselves, but also to better understand the complex interactions between contaminants, soil, plant roots, and microorganisms in the rhizosphere.
Abstract: The use of plants and associated microorganisms to remove, contain, inactivate, or degrade harmful environmental contaminants (generally termed phytoremediation) and to revitalize contaminated sites is gaining more and more attention. In this review, prerequisites for a successful remediation will be discussed. The performance of phytoremediation as an environmental remediation technology indeed depends on several factors including the extent of soil contamination, the availability and accessibility of contaminants for rhizosphere microorganisms and uptake into roots (bioavailability), and the ability of the plant and its associated microorganisms to intercept, absorb, accumulate, and/or degrade the contaminants. The main aim is to provide an overview of existing field experience in Europe concerning the use of plants and their associated microorganisms whether or not combined with amendments for the revitalization or remediation of contaminated soils and undeep groundwater. Contaminations with trace elements (except radionuclides) and organics will be considered. Because remediation with transgenic organisms is largely untested in the field, this topic is not covered in this review. Brief attention will be paid to the economical aspects, use, and processing of the biomass. It is clear that in spite of a growing public and commercial interest and the success of several pilot studies and field scale applications more fundamental research still is needed to better exploit the metabolic diversity of the plants themselves, but also to better understand the complex interactions between contaminants, soil, plant roots, and microorganisms (bacteria and mycorrhiza) in the rhizosphere. Further, more data are still needed to quantify the underlying economics, as a support for public acceptance and last but not least to convince policy makers and stakeholders (who are not very familiar with such techniques).
786 citations
TL;DR: A review of studies of introgression in species with sex-biased dispersal largely confirms that species delimitation should be more effective with markers experiencing high levels of gene flow, a simple but not widely appreciated prediction.
Abstract: A defining feature of species is that their constituting populations are connected by gene flow. However, interspecific gene flow (introgression) can affect species integrity. If some genome components were less prone to introgression than others, they should be particularly suitable to delimitate species. Recent simulation studies have predicted a negative correlation between intra- and interspecific gene flow, suggesting that markers associated with the most dispersing sex should better delimitate species. A review of studies of introgression in species with sex-biased dispersal largely confirms this prediction. Hence, species delimitation should be more effective with markers experiencing high levels of gene flow, a simple but not widely appreciated prediction.
710 citations
TL;DR: The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gammaray energy, with the largest apparent energy release yet measured.
Abstract: Gamma-ray bursts (GRBs) are highly energetic explosions signaling the death of massive stars in distant galaxies. The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gamma-ray energy. In September 2008, Fermi observed the exceptionally luminous GRB 080916C, with the largest apparent energy release yet measured. The high-energy gamma rays are observed to start later and persist longer than the lower energy photons. A simple spectral form fits the entire GRB spectrum, providing strong constraints on emission models. The known distance of the burst enables placing lower limits on the bulk Lorentz factor of the outflow and on the quantum gravity mass.
651 citations
TL;DR: The detection of emission up to ∼31 GeV from the distant and short GRB, and no evidence for the violation of Lorentz invariance is found, which disfavour quantum-gravity theories in which the quantum nature of space–time on a very small scale linearly alters the speed of light.
Abstract: A cornerstone of Einstein's special relativity is Lorentz invariance-the postulate that all observers measure exactly the same speed of light in vacuum, independent of photon-energy. While special relativity assumes that there is no fundamental length-scale associated with such invariance, there is a fundamental scale (the Planck scale, l(Planck) approximate to 1.62 x 10(-33) cm or E(Planck) = M(Planck)c(2) approximate to 1.22 x 10(19) GeV), at which quantum effects are expected to strongly affect the nature of space-time. There is great interest in the (not yet validated) idea that Lorentz invariance might break near the Planck scale. A key test of such violation of Lorentz invariance is a possible variation of photon speed with energy(1-7). Even a tiny variation in photon speed, when accumulated over cosmological light-travel times, may be revealed by observing sharp features in gamma-ray burst (GRB) light-curves(2). Here we report the detection of emission up to similar to 31GeV from the distant and short GRB090510. We find no evidence for the violation of Lorentz invariance, and place a lower limit of 1.2E(Planck) on the scale of a linear energy dependence (or an inverse wavelength dependence), subject to reasonable assumptions about the emission (equivalently we have an upper limit of l(Planck)/1.2 on the length scale of the effect). Our results disfavour quantum-gravity theories(3,6,7) in which the quantum nature of space-time on a very small scale linearly alters the speed of light.
University of Bremen1, University of Tübingen2, Autonomous University of Barcelona3, University of Kiel4, Oregon State University5, Alfred Wegener Institute for Polar and Marine Research6, Commonwealth Scientific and Industrial Research Organisation7, Aix-Marseille University8, Cardiff University9, Australian National University10, University of Barcelona11, National Taiwan Ocean University12, University of Bordeaux13, Université du Québec à Montréal14, University of Bergen15, University of Cambridge16, University of Limerick17, Newcastle University18, University of Sfax19, Dalhousie University20, University of Liverpool21, Université du Québec22, National Oceanography Centre23, Geoscience Australia24, University of California, Davis25
TL;DR: This article presented an updated synthesis of sea surface temperatures during the Last Glacial Maximum, rigorously defined as the period between 23 and 19 thousand years before present, from the Multiproxy Approach for the Reconstruction of the Glacial Ocean Surface (MARGO) project.
Abstract: Observation-based reconstructions of sea surface temperature from relatively stable periods in the past, such as the Last Glacial Maximum, represent an important means of constraining climate sensitivity and evaluating model simulations1. The first quantitative global reconstruction of sea surface temperatures during the Last Glacial Maximum was developed by the Climate Long-Range Investigation, Mapping and Prediction (CLIMAP) project in the 1970s and 1980s (refs 2, 3). Since that time, several shortcomings of that earlier effort have become apparent4. Here we present an updated synthesis of sea surface temperatures during the Last Glacial Maximum, rigorously defined as the period between 23 and 19 thousand years before present, from the Multiproxy Approach for the Reconstruction of the Glacial Ocean Surface (MARGO) project5. We integrate microfossil and geochemical reconstructions of surface temperatures and include assessments of the reliability of individual records. Our reconstruction reveals the presence of large longitudinal gradients in sea surface temperature in all of the ocean basins, in contrast to the simulations of the Last Glacial Maximum climate available at present6, 7.
TL;DR: Replication experiments and analysis of artifacts suggest that humans in South Africa at this time, and perhaps earlier, systematically heated stone materials, including silcrete to improve its flaking properties in making tools.
Abstract: The controlled use of fire was a breakthrough adaptation in human evolution. It first provided heat and light and later allowed the physical properties of materials to be manipulated for the production of ceramics and metals. The analysis of tools at multiple sites shows that the source stone materials were systematically manipulated with fire to improve their flaking properties. Heat treatment predominates among silcrete tools at ~72 thousand years ago (ka) and appears as early as 164 ka at Pinnacle Point, on the south coast of South Africa. Heat treatment demands a sophisticated knowledge of fire and an elevated cognitive ability and appears at roughly the same time as widespread evidence for symbolic behavior.
TL;DR: It is shown that transgenic animals, in which adult hippocampal neurogenesis has been specifically impaired, exhibit a striking increase in anxiety-related behaviors, which indicates that neuroGenesis plays an important role in the regulation of affective states and could be the target of new treatments for anxiety disorders.
Abstract: Adult hippocampal neurogenesis is a unique example of structural plasticity, the functional role of which has been a matter of intense debate. New transgenic models have recently shown that neurogenesis participates in hippocampus-mediated learning. Here, we show that transgenic animals, in which adult hippocampal neurogenesis has been specifically impaired, exhibit a striking increase in anxiety-related behaviors. Our results indicate that neurogenesis plays an important role in the regulation of affective states and could be the target of new treatments for anxiety disorders.
TL;DR: The LAT Bright AGN Sample (LBAS) as discussed by the authors contains two radio galaxies, namely Centaurus A and NGC 1275, and 104 blazars consisting of 57 flat spectrum radio quasars (FSRQs), 42 BL Lac objects, and 5 BLazars with uncertain classification.
Abstract: The first three months of sky-survey operation with the Fermi Gamma Ray Space Telescope (Fermi) Large Area Telescope (LAT) reveals 132 bright sources at |b|>10 deg with test statistic greater than 100 (corresponding to about 10 sigma). Two methods, based on the CGRaBS, CRATES and BZCat catalogs, indicate high-confidence associations of 106 of these sources with known AGNs. This sample is referred to as the LAT Bright AGN Sample (LBAS). It contains two radio galaxies, namely Centaurus A and NGC 1275, and 104 blazars consisting of 57 flat spectrum radio quasars (FSRQs), 42 BL Lac objects, and 5 blazars with uncertain classification. Four new blazars were discovered on the basis of the LAT detections. Remarkably, the LBAS includes 10 high-energy peaked BL Lacs (HBLs), sources which were so far hard to detect in the GeV range. Another 10 lower-confidence associations are found. Only thirty three of the sources, plus two at |b|>10 deg, were previously detected with EGRET, probably due to the variable nature of these sources. The analysis of the gamma-ray properties of the LBAS sources reveals that the average GeV spectra of BL Lac objects are significantly harder than the spectra of FSRQs. No significant correlation between radio and peak gamma-ray fluxes is observed. Blazar log N - log S and luminosity functions are constructed to investigate the evolution of the different blazar classes, with positive evolution indicated for FSRQs but none for BLLacs. The contribution of LAT-blazars to the total extragalactic gamma-ray intensity is estimated.
TL;DR: In this article, the authors presented the initial results for energies above 100 MeV for the 205 most significant (statistical significance greater than 10-sigma) gamma-ray sources in early-mission data.
Abstract: Following its launch in June 2008, the Fermi Gamma-ray Space Telescope (Fermi) began a sky survey in August. The Large Area Telescope (LAT) on Fermi in 3 months produced a deeper and better-resolved map of the gamma-ray sky than any previous space mission. We present here initial results for energies above 100 MeV for the 205 most significant (statistical significance greater than 10-sigma) gamma-ray sources in these data. These are the best-characterized and best-localized gamma-ray sources in the early-mission data.
TL;DR: Thirteen additional pieces of incised ochre recovered from c.
TL;DR: Community- Acquired ESBL-producing Enterobacteriaceae are now prevalent worldwide, necessitating international collaboration and novel approaches are required to adequately address issues such as empirical treatment for severe community-acquired infection and infection control.
Abstract: Infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are increasing in frequency and are associated with high mortality rates. Circulation of CTX-M-type ESBLs in the community is of particular concern, because it may confound standard infection-control measures.
TL;DR: Among postmenopausal women with endocrine-responsive breast cancer, sequential treatment with letrozole and tamoxifen, as compared with let rozole monotherapy, did not improve disease-free survival.
Abstract: BACKGROUND: The aromatase inhibitor letrozole, as compared with tamoxifen, improves disease-free survival among postmenopausal women with receptor-positive early breast cancer. It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone. METHODS: In this randomized, phase 3, double-blind trial of the treatment of hormone-receptor-positive breast cancer in postmenopausal women, we randomly assigned women to receive 5 years of tamoxifen monotherapy, 5 years of letrozole monotherapy, or 2 years of treatment with one agent followed by 3 years of treatment with the other. We compared the sequential treatments with letrozole monotherapy among 6182 women and also report a protocol-specified updated analysis of letrozole versus tamoxifen monotherapy in 4922 women. RESULTS: At a median follow-up of 71 months after randomization, disease-free survival was not significantly improved with either sequential treatment as compared with letrozole alone (hazard ratio for tamoxifen followed by letrozole, 1.05; 99% confidence interval [CI], 0.84 to 1.32; hazard ratio for letrozole followed by tamoxifen, 0.96; 99% CI, 0.76 to 1.21). There were more early relapses among women who were assigned to tamoxifen followed by letrozole than among those who were assigned to letrozole alone. The updated analysis of monotherapy showed that there was a nonsignificant difference in overall survival between women assigned to treatment with letrozole and those assigned to treatment with tamoxifen (hazard ratio for letrozole, 0.87; 95% CI, 0.75 to 1.02; P=0.08). The rate of adverse events was as expected on the basis of previous reports of letrozole and tamoxifen therapy. CONCLUSIONS: Among postmenopausal women with endocrine-responsive breast cancer, sequential treatment with letrozole and tamoxifen, as compared with letrozole monotherapy, did not improve disease-free survival. The difference in overall survival with letrozole monotherapy and tamoxifen monotherapy was not statistically significant. (ClinicalTrials.gov number, NCT00004205.)
TL;DR: In this article, the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) instruments on-board the Fermi observatory were used to observe the long gamma-ray burst, GRB 090902B.
Abstract: We report on the observation of the bright, long gamma-ray burst (GRB), GRB 090902B, by the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) instruments on-board the Fermi observatory. ...
TL;DR: In this article, the authors showed that the pro-Th2 cytokine thymic stromal lymphopoietin (TSLP), the thymus and activation-regulated chemokine are overexpressed in LEKTI-deficient epidermis.
Abstract: Netherton syndrome (NS) is a severe genetic skin disease with constant atopic manifestations that is caused by mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene, which encodes the protease inhibitor lymphoepithelial Kazal-type–related inhibitor (LEKTI). Lack of LEKTI causes stratum corneum detachment secondary to epidermal proteases hyperactivity. This skin barrier defect favors allergen absorption and is generally regarded as the underlying cause for atopy in NS. We show for the first time that the pro-Th2 cytokine thymic stromal lymphopoietin (TSLP), the thymus and activation-regulated chemokine, and the macrophage-derived chemokine are overexpressed in LEKTI-deficient epidermis. This is part of an original biological cascade in which unregulated kallikrein (KLK) 5 directly activates proteinase-activated receptor 2 and induces nuclear factor κB–mediated overexpression of TSLP, intercellular adhesion molecule 1, tumor necrosis factor α, and IL8. This proinflammatory and proallergic pathway is independent of the primary epithelial failure and is activated under basal conditions in NS keratinocytes. This cell-autonomous process is already established in the epidermis of Spink5−/− embryos, and the resulting proinflammatory microenvironment leads to eosinophilic and mast cell infiltration in a skin graft model in nude mice. Collectively, these data establish that uncontrolled KLK5 activity in NS epidermis can trigger atopic dermatitis (AD)–like lesions, independently of the environment and the adaptive immune system. They illustrate the crucial role of protease signaling in skin inflammation and point to new therapeutic targets for NS as well as candidate genes for AD and atopy.
TL;DR: The results establish a causal link between a specific neuronal subpopulation and memory expression, thereby identifying critical neurons within the memory trace, and identifies them as lateral amygdala neurons with increased cyclic adenosine monophosphate response element–binding protein (CREB).
Abstract: Memories are thought to be encoded by sparsely distributed groups of neurons. However, identifying the precise neurons supporting a given memory (the memory trace) has been a long-standing challenge. We have shown previously that lateral amygdala (LA) neurons with increased cyclic adenosine monophosphate response element-binding protein (CREB) are preferentially activated by fear memory expression, which suggests that they are selectively recruited into the memory trace. We used an inducible diphtheria-toxin strategy to specifically ablate these neurons. Selectively deleting neurons overexpressing CREB (but not a similar portion of random LA neurons) after learning blocked expression of that fear memory. The resulting memory loss was robust and persistent, which suggests that the memory was permanently erased. These results establish a causal link between a specific neuronal subpopulation and memory expression, thereby identifying critical neurons within the memory trace.
TL;DR: It is demonstrated that IFNγ, with TNFα, is necessary for induction of IDO and depressive-like behavior in mice after BCG infection and synergized to induce IDO in primary microglia.
Abstract: Although the tryptophan-degrading enzyme, indoleamine 2,3-dioxygenase (IDO), is a pivotal mediator of inflammation-induced depression, its mechanism of regulation has not yet been investigated in this context. Here, we demonstrate an essential role for interferon (IFN)gamma and tumor necrosis factor (TNF)alpha in the induction of IDO and depressive-like behaviors in response to chronic immune activation. Wild-type (WT) control mice and IFNgammaR(-/-) mice were inoculated with an attenuated form of Mycobacterium bovis, bacille Calmette-Guerin (BCG). Infection with BCG induced an acute episode of sickness that was similar in WT and IFNgammaR(-/-) mice. Increased immobility during the forced swim and tail suspension tests occurred in WT mice 7 d after BCG inoculation but was entirely absent in IFNgammaR(-/-) mice. In WT mice, these indices of depressive-like behavior were associated with chronic upregulation of IFNgamma, interleukin(IL)-1beta, TNFalpha, and IDO. Proinflammatory cytokine expression was elevated in BCG-infected IFNgammaR(-/-) mice as well, but upregulation of lung and brain IDO mRNA was completely abolished. This was accompanied by an attenuation of BCG-induced TNFalpha mRNA and the lack of an increase in plasma kynurenine/tryptophan ratio in the BCG-inoculated IFNgammaR(-/-) mice compared with WT controls. Pretreatment of mice with the TNFalpha antagonist, etanercept, partially blunted BCG-induced IDO activation and depressive-like behavior. In accordance with these in vivo data, IFNgamma and TNFalpha synergized to induce IDO in primary microglia. Together, these data demonstrate that IFNgamma, with TNFalpha, is necessary for induction of IDO and depressive-like behavior in mice after BCG infection.
01 Jan 2009
TL;DR: The major challenge in the coming years will be to prevent onset of smoking along with early detection of the disease in the general population.
Abstract: Chronic obstructive pulmonary disease (COPD) is responsible for early mortality, high death rates and significant cost to health systems. The projection for 2020 indicates that COPD will be the third leading cause of death worldwide (from sixth in 1990) and fifth leading cause of years lost through early mortality or handicap (disability-adjusted life years) (12th in 1990). Active smoking remains the main risk factor, but other factors are becoming better known, such as occupational factors, infections and the role of air pollution. Prevalence of COPD varies according to country, age and sex. This disease is also associated with significant comorbidities. COPD is a disorder that includes various phenotypes, the continuum of which remains under debate. The major challenge in the coming years will be to prevent onset of smoking along with early detection of the disease in the general population.
TL;DR: In this paper, a set of brine-CO 2 interfacial tension data at pressure, temperature and salinity conditions, representative of a CO 2 storage operation, is presented.
TL;DR: An overview about AQP structure, function and regulation in a broad range of living organisms is given, with emphasis on plant AQPs where the high number and diversity of these transport proteins make them behave more like multifunctional, highly adapted channels rather than simple water pores.
TL;DR: It is found that THC long-term memory deficits were mediated by CB1Rs expressed on GABAergic interneurons through a glutamatergic mechanism, as both the amnesic-like effects and p70S6K phosphorylation were reduced in GABA-CB1R knockout mice and by NMDA blockade.
Abstract: Cognitive impairment is one of the most important negative consequences associated with cannabis consumption. We found that CB1 cannabinoid receptor (CB1R) activation transiently modulated the mammalian target of rapamycin (mTOR)/p70S6K pathway and the protein synthesis machinery in the mouse hippocampus, which correlated with the amnesic properties of delta9-tetrahydrocannabinol (THC). In addition, non-amnesic doses of either the mTOR blocker rapamycin or the protein synthesis inhibitor anisomycin abrogated the amnesic-like effects of THC, pointing to a mechanism involving new protein synthesis. Moreover, using pharmacological and genetic tools, we found that THC long-term memory deficits were mediated by CB1Rs expressed on GABAergic interneurons through a glutamatergic mechanism, as both the amnesic-like effects and p70S6K phosphorylation were reduced in GABA-CB1R knockout mice and by NMDA blockade.
TL;DR: Comparing phenological sensitivities to temperature of seven woody species between each other and within-species between two geographical areas using both altitudinal and temporal gradients suggests that population sensitivity to global warming might be stable for a given species, in spite of its possible local adaptation.
TL;DR: It is suggested that long-term CHIKV rheumatic manifestations seem to be a frequent underlying post-epidemic condition and may be particularly useful in the development of future prevention and care strategies for this emerging virus infection.
Abstract: Although the acute manifestations of Chikungunya virus (CHIKV) illness are well-documented, few data exist about the long-term rheumatic outcomes of CHIKV-infected patients. We undertook between June and September 2006 a retrospective cohort study aimed at assessing the course of late rheumatic manifestations and investigating potential risk factors associated with the persistence of these rheumatic manifestations over 15 months. 147 participants (>16 yrs) with laboratory-confirmed CHIKV disease diagnosed between March 1 and June 30, 2005, were identified through a surveillance database and interviewed by telephone. At the 15-month-period evaluation after diagnosis, 84 of 147 participants (57%) self-reported rheumatic symptoms. Of these 84 patients, 53 (63%) reported permanent trouble while 31 (37%) had recurrent symptoms. Age > or=45 years (OR = 3.9, 95% CI 1.7-9.7), severe initial joint pain (OR = 4.8, 95% CI 1.9-12.1), and presence of underlying osteoarthritis comorbidity (OR = 2.9, 95% CI 1.1-7.4) were predictors of nonrecovery. Our findings suggest that long-term CHIKV rheumatic manifestations seem to be a frequent underlying post-epidemic condition. Three independent risk factors that may aid in early recognition of patients with the highest risk of presenting prolonged CHIKV illness were identified. Such findings may be particularly useful in the development of future prevention and care strategies for this emerging virus infection.