Revealing uncertainty in the status of biodiversity change.

Biodiversity faces unprecedented threats from rapid global change1. Signals of biodiversity change come from time-series abundance datasets for thousands of species over large geographic and temporal scales. Analyses of these biodiversity datasets have pointed to varied trends in abundance, including increases and decreases. However, these analyses have not fully accounted for spatial, temporal and phylogenetic structures in the data. Here, using a new statistical framework, we show across ten high-profile biodiversity datasets2-11 that increases and decreases under existing approaches vanish once spatial, temporal and phylogenetic structures are accounted for. This is a consequence of existing approaches severely underestimating trend uncertainty and sometimes misestimating the trend direction. Under our revised average abundance trends that appropriately recognize uncertainty, we failed to observe a single increasing or decreasing trend at 95% credible intervals in our ten datasets. This emphasizes how little is known about biodiversity change across vast spatial and taxonomic scales. Despite this uncertainty at vast scales, we reveal improved local-scale prediction accuracy by accounting for spatial, temporal and phylogenetic structures. Improved prediction offers hope of estimating biodiversity change at policy-relevant scales, guiding adaptive conservation responses.

Drug metabolic enzyme genotype-phenotype discrepancy: High phenoconversion rate in patients treated with antidepressants.

Cytochromes from the P450 family (CYP) play a central role in the primary metabolism of frequently prescribed antidepressants, potentially affecting their efficacy and tolerance. There are however important differences in the drug metabolic capacities of each individual resulting from a combination of intrinsic and environmental factors. This variability can present an important risk for patients and increases the difficulty of drug prescription in clinical practice. Pharmacogenetic studies have uncovered a number of alleles defining the intrinsic metabolizer status, however, additional factors affecting cytochrome activity can modify this activity and result in a phenoconversion. The present study investigates the discrepancy between the genetically predicted and actually measured activities for the six most important liver cytochromes (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in a cohort of patients under antidepressant treatment, previously shown to have a high proportion of patients with low metabolizing activities. We now performed the genetic characterization of this cohort to determine the extent of the genetic versus environmental contribution in these decreased activities. For all enzyme tested, we observed an important rate of phenoconversion, affecting between 33 % and 65 % of the patients, as well as a significant (p < 1E-06) global reduction in the effective but not predicted activities of CYP2D6, CYP2C9 and CYP2C19 compared to the general population. Our results highlight the advantages of phenotyping versus genotyping as well as the increased risk of treatment failure or adverse effect occurrence in a polymedicated population.

Live fast, die young: Behavioural and physiological impacts of light pollution on a marine fish during larval recruitment.

Artificial light at night (ALAN) is a recently acknowledged form of anthropogenic pollution of growing concern to the biology and ecology of exposed organisms. Though ALAN can have detrimental effects on physiology and behaviour, we have little understanding of how marine organisms in coastal areas may be impacted. Here, we investigated the effects of ALAN exposure on coral reef fish larvae during the critical recruitment stage, encompassing settlement, metamorphosis, and post-settlement survival. We found that larvae avoided illuminated settlement habitats, however those living under ALAN conditions for 10 days post-settlement experienced changes in swimming behaviour and higher susceptibility to nocturnal predation. Although ALAN-exposed fish grew faster and heavier than control fish, they also experienced significantly higher mortality rates by the end of the experimental period. This is the first study on the ecological impacts of ALAN during the early life history of marine fish.

Reactivity of shape-controlled crystals and metadynamics simulations locate the weak spots of alumina in water.

The kinetic stability of any material in water relies on the presence of surface weak spots responsible for chemical weathering by hydrolysis. Being able to identify the atomistic nature of these sites and the first steps of transformation is therefore critical to master the decomposition processes. This is the challenge that we tackle here: combining experimental and modeling studies we investigate the stability of alumina in water. Exploring the reactivity of shape-controlled crystals, we identify experimentally a specific facet as the location of the weak spots. Using biased ab initio molecular dynamics, we recognize this weak spot as a surface exposed tetra-coordinated Al atom and further provide a detailed mechanism of the first steps of hydrolysis. This understanding is of great importance to heterogeneous catalysis where alumina is a major support. Furthermore, it paves the way to atomistic understanding of interfacial reactions, at the crossroad of a variety of fields of research.

Effect of production quotas on economic and environmental values of growth rate and feed efficiency in sea cage fish farming.

In sea cage fish farming, production quotas aim to constrain the impact of fish farming on the surrounding ecosystem. It is unknown how these quotas affect economic profitability and environmental impact of genetic improvement. We combined bioeconomic modelling with life cycle assessment (LCA) to calculate the economic (EV) and environmental (ENV) values of thermal growth coefficient (TGC) and feed conversion ratio (FCR) of sea bass reared in sea cages, given four types of quota commonly used in Europe: annual production (Qprod), annual feed distributed (Qannual_feed), standing stock (Qstock), and daily feed distributed (Qdaily_feed). ENV were calculated for LCA impact categories climate change, eutrophication and acidification. ENV were expressed per ton of fish produced per year (ENV(fish)) and per farm per year (ENV(farm)). Results show that irrespective of quota used, EV of FCR as well as ENV(fish) and ENV(farm) were always positive, meaning that improving FCR increased profit and decreased environmental impacts. However, the EV and the ENV(fish) of TGC were positive only when quota was Qstock or Qdaily_feed. Moreover, the ENV(farm) of TGC was negative in Qstock and Qdaily_feed quotas, meaning that improving TGC increased the environmental impact of the farm. We conclude that Qstock quota and Qdaily_feed quota are economically favorable to a genetic improvement of TGC, a major trait for farmers. However, improving TGC increases the environmental impact of the farm. Improving FCR represents a good opportunity to balance out this increase but more information on its genetic background is needed to develop breeding programs improving FCR.

Habitat selection by marine larvae in changing chemical environments.

The replenishment and persistence of marine species is contingent on dispersing larvae locating suitable habitat and surviving to a reproductive stage. Pelagic larvae rely on environmental cues to make behavioural decisions with chemical information being important for habitat selection at settlement. We explored the sensory world of crustaceans and fishes focusing on the impact anthropogenic alterations (ocean acidification, red soil, pesticide) have on conspecific chemical signals used by larvae for habitat selection. Crustacean (Stenopus hispidus) and fish (Chromis viridis) larvae recognized their conspecifics via chemical signals under control conditions. In the presence of acidified water, red soil or pesticide, the ability of larvae to chemically recognize conspecific cues was altered. Our study highlights that recruitment potential on coral reefs may decrease due to anthropogenic stressors. If so, populations of fishes and crustaceans will continue their rapid decline; larval recruitment will not replace and sustain the adult populations on degraded reefs.

From impulses to maladaptive actions: the insula is a neurobiological gate for the development of compulsive behavior.

Impulsivity is an endophenotype of vulnerability for compulsive behaviors. However, the neural mechanisms whereby impulsivity facilitates the development of compulsive disorders, such as addiction or obsessive compulsive disorder, remain unknown. We first investigated, in rats, anatomical and functional correlates of impulsivity in the anterior insular (AI) cortex by measuring both the thickness of, and cellular plasticity markers in, the AI with magnetic resonance imaging and in situ hybridization of the immediate early gene zif268, respectively. We then investigated the influence of bilateral AI cortex lesions on the high impulsivity trait, as measured in the five-choice serial reaction time task (5-CSRTT), and the associated propensity to develop compulsivity as measured by high drinking levels in a schedule-induced polydipsia procedure (SIP). We demonstrate that the AI cortex causally contributes to individual vulnerability to impulsive-compulsive behavior in rats. Motor impulsivity, as measured by premature responses in the 5-CSRTT, was shown to correlate with the thinness of the anterior region of the insular cortex, in which highly impulsive (HI) rats expressed lower zif268 mRNA levels. Lesions of AI reduced impulsive behavior in HI rats, which were also highly susceptible to develop compulsive behavior as measured in a SIP procedure. AI lesions also attenuated both the development and the expression of SIP. This study thus identifies the AI as a novel neural substrate of maladaptive impulse control mechanisms that may facilitate the development of compulsive disorders.

Economic values of growth and feed efficiency for fish farming in recirculating aquaculture system with density and nitrogen output limitations: a case study with African catfish (Clarias gariepinus).

In fish farming, economic values (EV) of breeding goal traits are lacking, even though they are key parameters when defining selection objectives. The aim of this study was to develop a bioeconomic model to estimate EV of 2 traits representing production performances in fish farming: the thermal growth coefficient (TGC) and the feed conversion ratio (FCR). This approach was applied to a farm producing African catfish (Clarias gariepinus) in a recirculating aquaculture system (RAS). In the RAS, 2 factors could limit production level: the nitrogen treatment capacity of the biofilter or the fish density in rearing tanks at harvest. Profit calculation includes revenue from fish sales, cost of juveniles, cost of feed, cost of waste water treatment, and fixed costs. In the reference scenario, profit was modeled to zero. EV were calculated as the difference in profit per kilogram of fish between the current population mean for both traits (µt) and the next generation of selective breeding (µt+Δt) for either TGC or FCR. EV of TGC and FCR were calculated for three generations of hypothetical selection on either TGC or FCR (respectively 6.8% and 7.6% improvement per generation). The results show that changes in TGC and FCR can affect both the number of fish that can be stocked (number of batches per year and number of fish per batch) and the factor limiting production. The EV of TGC and FCR vary and depend on the limiting factors. When dissolved NH3-N is the limiting factor for both µt and µt+Δt, increasing TGC decreases the number of fish that can be stocked but increases the number of batches that can be grown. As a result, profit remains constant and EVTGC is zero. Increasing FCR, however, increases the number of fish stocked and the ratio of fish produced per kilogram of feed consumed ("economic efficiency"). The EVFCR is 0.14 €/kg of fish, and profit per kilogram of fish increases by about 10%. When density is the limiting factor for both µt and µt+Δt, the number of fish stocked per batch is fixed; therefore, extra profit is obtained by increasing either TGC, which increases the annual number of batches, or by decreasing FCR, which decreases annual feed consumption. EVTGC is 0.03 €/kg of fish and EVFCR is 0.05-0.06 €/kg of fish. These results emphasize the importance of calculating economic values in the right context to develop efficient future breeding programs in aquaculture.

"All that glitters is not alone". Congruity effects in highly and less predictable sentence contexts.

CONTEXT: Using natural connected speech, the aim of the present study was to examine the semantic congruity effect (i.e. the difference between semantically incongruous and congruous words) in sentence contexts that generate high or moderate final word expectancies. METHODS: We used sentences with two levels of word expectancy in the auditory modality: familiar proverbs (that generate high final word expectancy), and unfamiliar sentences (that generate only moderate final word expectancy). RESULTS: Results revealed an early congruity effect (0-200 ms) that developed across all scalp sites for familiar proverbs but not for unfamiliar sentences. By contrast, typical centro-parietal N400 and Late Positivity Component congruity effects developed later (200-500 ms and 600-900 ms ranges) for both familiar proverbs and unfamiliar sentences. DISCUSSION: We argue that the early congruity effect for proverbs comprises both a Phonological Mismatch Negativity, reflecting the processing of the acoustic/phonological mismatch between the expected (congruous) and unexpected (incongruous) sentence completions and a typical N400 semantic congruity effect with an unusual short latency because final words can be predicted from the unusually high contextual constraints of familiar proverbs. These results are considered in the light of current views of anticipation and prediction processes in sentence contexts.

First outbreak of community-acquired MRSA USA300 in France: failure to suppress prolonged MRSA carriage despite decontamination procedures.

The first French outbreak of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 clone was investigated. After outbreak investigation, hygiene measures were implemented in all family households and childminders' homes. Several decontamination procedures were performed, which used a combination of topical mupirocin, total body application of chlorhexidine, chlorhexidine gargle (if >6 years old) and a course of antibiotic therapy in cases of infection or decontamination failure. Patients were followed up for MRSA skin and soft tissue infections (SSTIs) and carriage. Strains were characterised by antimicrobial drug resistance profile, pulsed-field gel electrophoresis (PFGE) and DNA microarrays. Between June 2011 and June 2012, six children and six adults among the ten corresponding relatives developed 28 SSTIs. None of the family members, including the index case, had any contact with foreigners or individuals known to have SSTIs. After infection control measures and prolonged decontamination have been implemented with a high adherence, six patients remained sustained CA-MRSA USA300 carriers, including one who developed mupirocin resistance and six who experienced minor CA-MRSA-related SSTIs. A baby was identified as an MRSA carrier 2 months after delivery. CA-MRSA decontamination using mupirocin and chlorhexidine in the community setting may also be a questionable strategy, associated with failure and resistance to both agents. Close monitoring of CA-MRSA SSTIs is required in France and in other European countries where MRSA USA300 has recently emerged. We showed that a closed management based on hygiene measures reinforcement, decolonisation and extended screening may fail to suppress CA-MRSA carriage and subsequent infections.

[Electrophysiology and schizophrenic vulnerability: the N400 component as endophenotype candidate?]. / Électrophysiologie et vulnérabilité schizophrénique: la composante N400 comme endophénotype candidat?

Research on early stages of schizophrenia aims to provide early, objective, and stable markers of vulnerability. In this review, we first briefly describe the notion of such markers, or endophenotypes, notably in terms of stability, specificity and heritability. Among other empirical approaches, event-related potentials (ERPs) have been recently considered as putative endophenotypes. The N400 component is an event-related brain potential classically elicited during semantic processing, as suggested by a growing body of empirical studies with a large variety of paradigms. We provide here a short account of its typical descriptions and the interpretations of its functional significance. Then we describe the main current results about schizophrenic alterations of the N400 component. Two levels of semantic processing (automatic spreading and controlled mechanisms) are disturbed in schizophrenia, even if the underlying mechanisms remain unclear or discussed. Several controversial issues may also need further research, such as the influence of symptomatology and evolution of schizophrenia. Another crucial topic concerns the putative schizophrenic specificity, and only little is known about possible alterations of N400 in affective disorders. We discuss the notion of heritability, mainly explored in current literature among people with schizotypal personality. Finally, even if N400 studies contribute to a better understanding of linguistic disturbances in schizophrenia, it appears difficult to consider the N400 component as a relevant schizophrenic endophenotype, given the current paucity of results on its stability, its heritability (clinical and genetic vulnerability) and its schizophrenic specificity.

Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement.

Smoking is the most important preventable cause of mortality and morbidity worldwide. This nicotine addiction is mediated through the nicotinic acetylcholine receptor (nAChR), expressed on most neurons, and also many other organs in the body. Even within the ventral tegmental area (VTA), the key brain area responsible for the reinforcing properties of all drugs of abuse, nicotine acts on several different cell types and afferents. Identifying the precise action of nicotine on this microcircuit, in vivo, is important to understand reinforcement, and finally to develop efficient smoking cessation treatments. We used a novel lentiviral system to re-express exclusively high-affinity nAChRs on either dopaminergic (DAergic) or γ-aminobutyric acid-releasing (GABAergic) neurons, or both, in the VTA. Using in vivo electrophysiology, we show that, contrary to widely accepted models, the activation of GABA neurons in the VTA plays a crucial role in the control of nicotine-elicited DAergic activity. Our results demonstrate that both positive and negative motivational values are transmitted through the dopamine (DA) neuron, but that the concerted activity of DA and GABA systems is necessary for the reinforcing actions of nicotine through burst firing of DA neurons. This work identifies the GABAergic interneuron as a potential target for smoking cessation drug development.

Involvement of the Drosophila taurine/aspartate transporter dEAAT2 in selective olfactory and gustatory perceptions.

Excitatory amino acid transporters (EAATs) are membrane proteins involved in the uptake of neurotransmitter amino acids in the nervous system. The Drosophila dEAAT2 gene was previously described to encode a taurine/aspartate transporter. To analyze further the expression pattern and physiological function of this protein, we generated transgenic flies containing either the dEAAT2 promoter region fused to GAL4 (dEAAT2-GAL4) or a transgene allowing expression of a dEAAT2::GFP fusion protein (UAS-dEAAT2::GFP). We observed that dEAAT2-GAL4 expresses green fluorescent protein (GFP) in neurons in central and peripheral structures of third-instar larvae and adult flies. Labeled neurons were found in olfactory and gustatory pathways, in which dEAAT2::GFP was detected from the dendrites of the sensory neurons up to the first- and second-order centers. dEAAT2-GAL4 is also expressed in mechanosensory neurons. We found that a viable piggyBac insertion strain disrupts dEAAT2 expression. This mutant appears morphologically normal and presents no locomotor or phototaxis impairments; however, its brain taurine level is significantly reduced compared with that of wild-type flies. The dEAAT2 mutant showed decreased avoidance behavior in the presence of high concentration of propionic acid compared with wild-type flies, but no modification of the avoidance response to benzaldehyde. In gustatory tests, both mutant and control flies were normally attracted to sucrose; however, the dEAAT2 mutant presented a higher salt sensitivity, being repulsed by low and high salt concentrations. Therefore, we conclude that dEAAT2 does function as a taurine transporter in vivo and that this protein is physiologically required for the sensory perception of specific environmental molecules.

Impact of genetic polymorphisms and drug-drug interactions on clopidogrel and prasugrel response variability.

Thienopyridine antiaggregating platelet agents (clopidogrel and prasugrel) act as irreversible P2Y12 receptor inhibitors. They are used with aspirin to prevent thrombotic complications after an acute coronary syndrome or percutaneous coronary intervention. A large interindividual variability in response to clopidogrel and to a lesser extent to prasugrel is observed and may be related to their metabolism. Clopidogrel and prasugrel are indeed prodrugs converted into their respective active metabolites by several cytochromes P450 (CYPs). Besides clopidogrel inactivation (85%) by esterases to the carboxylic acid, clopidogrel is metabolized by CYPs to 2-oxo-clopidogrel (15%) and further metabolized to an unstable but potent platelet-aggregating inhibitor. Prasugrel is more potent than clopidogrel with a better bioavailability and lower pharmacodynamic variability. Prasugrel is completely converted by esterases to an intermediate oxo-metabolite (R-95913) further bioactivated by CYPs. Numerous clinical studies have shown the influence of CYP2C19 polymorphism on clopidogrel antiplatelet activity. Moreover, unwanted drug-drug pharmacokinetic interactions influencing CYP2C19 activity and clopidogrel bioactivation such as with proton pump inhibitors remain a matter of intense controversy. Several studies have also demonstrated that CYP3A4/5 and CYP1A2 are important in clopidogrel bioactivation and should also be considered as potential targets for unwanted drug-drug interactions. Prasugrel bioactivation is mainly related to CYP3A4 and 2B6 activity and therefore the question of the effect of drug-drug interaction on its activity is open. The purpose of this review is to critically examine the current literature evaluating the influence of genetic and environmental factors such as unwanted drug-drug interaction affecting clopidogrel and prasugrel antiplatelet activity.

Supported noble metal catalysts in the catalytic wet air oxidation of industrial wastewaters and sewage sludges.

This paper reviews some catalytic wet air oxidation (CWAO) investigations of industrial wastewaters over platinum and ruthenium catalysts supported on TiO2 and ZrO2 formulated to be active and resistant to leaching, with particular focus on the stability of the catalyst. Catalyst recycling experiments were performed in batch reactors and long-term stability tests were conducted in trickle-bed reactors. The catalyst did not leach upon treatment of Kraft bleaching plant and olive oil mill effluents, and could be either recycled or used for long periods of time in continuous reactors. Conversely, these catalysts were rapidly leached when used to treat effluents from the production of polymeric membranes containing N,N-dimethylformamide. The intermediate formation of amines, such as dimethylamine and methylamine with a high complexing capacity for the metal, was shown to be responsible for the metal leaching. These heterogeneous catalysts also deactivated upon CWAO of sewage sludges due to the adsorption of the solid organic matter. Pre-sonication of the sludge to disintegrate the flocs and improve solubility was inefficient.

Naloxone-responsive acute dystonia and parkinsonism following general anaesthesia.

Various movement disorders such as dystonia may acutely develop during or at emergence from general anaesthesia in patients with or without pre-existing Parkinson disease. These movements are triggered by a variety of drugs including propofol, sevoflurane, anti-emetics, antipsychotics and opioids. The postulated mechanism involves an imbalance between dopaminergic and cholinergic neurotransmitters in the basal ganglia. We report an acute, severe and generalised dystonic reaction in an otherwise healthy woman at emergence from general anaesthesia, dramatically reversed by the administration of naloxone, pointing to a potential role of the fentanyl and morphine that the patient had received. Recent literature on the mechanisms of abnormal movements induced by opioids are discussed. The severity of the reaction with usual doses of opioids, in a patient with no prior history of parkinsonism, led to further investigation that demonstrated the possibility of an enhanced susceptibility to opioids, involving a genetically determined abnormal function of glycoproteine-P and catechol-O-methyltransferase.

[Frequency and epidemiology of primary epiploic appendagitis on CT in adults with abdominal pain]. / Fréquence et épidémiologie descriptive de l'appendicite épiploïque primitive par l'exploration tomodensitométrique des douleurs abdominales de l'adulte.

PURPOSE: Advances in medical imaging have improved the presurgical diagnosis of isolated epiploic appendagitis. The authors assess its relative frequency and define its main epidemiological criteria. PATIENTS AND METHODS: Study of an adult population presenting with abdominal pain and evaluated by CT over a 3 year period. Evaluation for the presence of an isolated fat density paracolic mass with hyperdense periphery. A review of the literature was performed as well. RESULTS: The frequency of epiploic appendagitis is estimated at 1.3% and its incidence at 8.8 cases/million/year. The typical patient profile is a young to middle aged male presenting with left flank and lower quadrant pain. Obesity, GI symptoms, fever, and leukocytosis are characteristically absent while elevation of the CRP is typical. CT shows the lesion along the anterolateral margin of the descending or sigmoid colon. Spontaneous resolution usually occurs within 8 days. CONCLUSION: Our results confirm epidemiological data from the literature. Knowledge of the imaging features of epiploic appendagitis will ensure conservative patients management and avoid unnecessary surgery.

[Self-medication amongst illegal Latino-American immigrants: necessary or inapropriate]. / Automédication chez les sans-papiers latino-americains: entre le nécessaire et l'inapproprié.

Self-medication is well known risk in Latin America. This situation can partly be explain by the difficult access to doctors and poorly regulated drug sales. Illegal Latino-American immigrants import their practice of self-medication and their drugs with them. The economic advantage of this practice makes it popular and confronts medical practitioners to question the benefice/risk of such behavior. Taking the particular situation of illegal Latino-American immigrants, this review discusses the necessity of abording systematically the question of self-medication during a medical consultation.