Covalent labeling of Matrix Metalloproteases with affinity-based probes containing tuned reactive N-acyl-N-alkyl sulfonamide cleavable linkers.

Original covalent probes with an N-acyl-N-alkyl sulfonamide cleavable linker were developed to target a broad set of human Matrix Metalloproteases (MMPs). The electrophilicity of this cleavable linker was modulated to improve the selectivity of the probes as well as reduce their unspecific reactivity in complex biological matrices. We first demonstrated that targeting the S3 subsite of MMPs enables access to broad-spectrum affinity-based probes that exclusively react with the active version of these proteases. The probes were further assessed in proteomes of varying complexity, where human MMP-13 was artificially introduced at known concentration and the resulting labeled MMP was imaged by in-gel fluorescence imaging. We showed that the less reactive probe was still able to covalently modify MMP-13 while exhibiting reduced off-target unspecific reactivity. This study clearly demonstrated the importance of finely controlling the reactivity of the NASA warhead to improve the selectivity of covalent probes in complex biological systems.

Analyzing the impacts of climate change on ecosystem services provided by apple orchards in Southeast France using a process-based model.

We know that fruit production, especially in the Mediterranean, will need to adapt to climate change to ensure the sustainability of fruit tree-based agroecosystems. However, there is a lack of evidence on the long-term effects of this change on sustainability indicators. To fill this gap, we used a fruit tree model, QualiTree, to analyze the impacts ofclimate change on the ecosystem services provided by apple orchards in south-eastern France. To do this, a blooming model was parameterized to simulate blooming date on the basis of climate data, and QualiTree was supplemented with a model of nitrogen processes in the tree and a soil module describing resource input (irrigation, mineral and organic fertilization), transfer in the soil (water and nitrogen) and metabolic transformation-immobilization (mineralization, (de)nitrification). This type of extension makes it possible to simulate a wide array of ecosystem services, including C sequestration, nitrate leaching and nitrous oxide emissions. The model was compared with data from an apple orchard in southeastern France. The predicted daily mean and variability over time of fruit growth, composition and soil water content were consistent with observed data. QualiTree was then used to assess the potential impacts of climate change on the ecosystem services supplied by apple orchards. For this purpose, weather variables from 2020 to 2100 were generated for three contrasted greenhouse gas emission scenarios, and simulations were performed under two irrigation schemes (no restriction and restricted use of water). Model outputs indicated that, on average, marketable apple yields would increase until 2050 and then subsequently decrease. The fruit refractometric index, an indicator of fruit quality, was projected to sharply decrease with the intensity of climate change. Ecosystem services such as C sequestration by the orchard will decrease with climate change severity, mainly due to a higher mineralization of soil humus, whereas N2O emissions will increase with larger denitrification rates. Soil water availability, fertility, drainage and leaching were predicted to depend more on the irrigation strategy than on climate change severity. The new functions performed in QualiTree broadened its predictive capabilities and allowed for a better understanding of ecosystem service delivery in fruit orchards under varying climate conditions.

Comparison of 17ß-estradiol, bisphenol-A and caffeine concentration levels before and after the water treatment plant.

This article compares the concentration levels of 17ß-estradiol (E2), bisphenol-A (BPA) and caffeine (CAF) in the Sinos River, Brazil, which is a source of drinking water and the presence of contaminants after the conventional treatment in a municipal water treatment plant (WTP). A total of nine sampling campaigns were carried out, with sample collection in the Sinos River, upstream and downstream of the WTP, in addition to a drinking water sample (DW). The samples were extracted with solid phase extraction (SPE) and the concentration by liquid chromatography coupled to mass spectrometry (LC-MS). The maximum concentration in the Sinos River was 6,127.99 ng·L-1 for E2, 3,294.63 ng·L-1 for BPA and 1,221.95 ng·L-1 for CAF. In drinking water, the concentration range of E2, BPA and CAF was from less than the Detection Limit (DL) up to 437.50 ng·L-1,

IPSIM-Web, An Online Resource for Promoting Qualitative Aggregative Hierarchical Network Models to Predict Plant Disease Risk: Application to Brown Rust on Wheat.

A qualitative pest modeling platform, named Injury Profile Simulator (IPSIM), provides a tool to design aggregative hierarchical network models to predict the risk of pest injuries, including diseases, on a given crop based on variables related to cropping practices as well as soil and weather environment at the field level. The IPSIM platform enables modelers to combine data from various sources (literature, survey, experiments, and so on), expert knowledge, and simulation to build a network-based model. The overall structure of the platform is fully described at the IPSIM-Web website ( www6.inra.fr/ipsim ). A new module called IPSIM-Wheat-brown rust is reported in this article as an example of how to use the system to build and test the predictive quality of a prediction model. Model performance was evaluated for a dataset comprising 1,788 disease observations at 13 French cereal-growing regions over 15 years. Accuracy of the predictions was 85% and the agreement with actual values was 0.66 based on Cohen's κ. The new model provides risk information for farmers and agronomists to make scientifically sound tactical (within-season) decisions. In addition, the model may be of use for ex post diagnoses of diseases in commercial fields. The limitations of the model such as low precision and threshold effects as well as the benefits, including the integration of different sources of information, transparency, flexibility, and a user-friendly interface, are discussed.

Spatially explicit estimates of N2 O emissions from croplands suggest climate mitigation opportunities from improved fertilizer management.

With increasing nitrogen (N) application to croplands required to support growing food demand, mitigating N2 O emissions from agricultural soils is a global challenge. National greenhouse gas emissions accounting typically estimates N2 O emissions at the country scale by aggregating all crops, under the assumption that N2 O emissions are linearly related to N application. However, field studies and meta-analyses indicate a nonlinear relationship, in which N2 O emissions are relatively greater at higher N application rates. Here, we apply a super-linear emissions response model to crop-specific, spatially explicit synthetic N fertilizer and manure N inputs to provide subnational accounting of global N2 O emissions from croplands. We estimate 0.66 Tg of N2 O-N direct global emissions circa 2000, with 50% of emissions concentrated in 13% of harvested area. Compared to estimates from the IPCC Tier 1 linear model, our updated N2 O emissions range from 20% to 40% lower throughout sub-Saharan Africa and Eastern Europe, to >120% greater in some Western European countries. At low N application rates, the weak nonlinear response of N2 O emissions suggests that relatively large increases in N fertilizer application would generate relatively small increases in N2 O emissions. As aggregated fertilizer data generate underestimation bias in nonlinear models, high-resolution N application data are critical to support accurate N2 O emissions estimates.

Monitoring the phenology of plant pathogenic fungi: why and how?

Phenology is a key adaptive trait of organisms, shaping biotic interactions in response to the environment. It has emerged as a critical topic with implications for societal and economic concerns due to the effects of climate change on species' phenological patterns. Fungi play essential roles in ecosystems, and plant pathogenic fungi have significant impacts on global food security. However, the phenology of plant pathogenic fungi, which form a huge and diverse clade of organisms, has received limited attention in the literature. This diversity may have limited the use of a common language for comparisons and the integration of phenological data for these taxonomic groups. Here, we delve into the concept of 'phenology' as applied to plant pathogenic fungi and explore the potential drivers of their phenology, including environmental factors and the host plant. We present the PhenoFun scale, a phenological scoring system suitable for use with all fungi and fungus-like plant pathogens. It offers a standardised and common tool for scientists studying the presence, absence, or predominance of a particular phase, the speed of phenological phase succession, and the synchronism shift between pathogenic fungi and their host plants, across a wide range of environments and ecosystems. The application of the concept of 'phenology' to plant pathogenic fungi and the use of a phenological scoring system involves focusing on the interacting processes between the pathogenic fungi, their hosts, and their biological, physical, and chemical environment, occurring during the life cycle of the pathogen. The goal is to deconstruct the processes involved according to a pattern orchestrated by the fungus's phenology. Such an approach will improve our understanding of the ecology and evolution of such organisms, help to understand and anticipate plant disease epidemics and their future evolution, and make it possible to optimise management models, and to encourage the adoption of cropping practices designed from this phenological perspective.

Mapping the race between crop phenology and climate risks for wheat in France under climate change.

Climate change threatens food security by affecting the productivity of major cereal crops. To date, agroclimatic risk projections through indicators have focused on expected hazards exposure during the crop's current vulnerable seasons, without considering the non-stationarity of their phenology under evolving climatic conditions. We propose a new method for spatially classifying agroclimatic risks for wheat, combining high-resolution climatic data with a wheat's phenological model. The method is implemented for French wheat involving three GCM-RCM model pairs and two emission scenarios. We found that the precocity of phenological stages allows wheat to avoid periods of water deficit in the near future. Nevertheless, in the coming decades the emergence of heat stress and increasing water deficit will deteriorate wheat cultivation over the French territory. Projections show the appearance of combined risks of heat and water deficit up to 4 years per decade under the RCP 8.5 scenario. The proposed method provides a deep level of information that enables regional adaptation strategies: the nature of the risk, its temporal and spatial occurrence, and its potential combination with other risks. It's a first step towards identifying potential sites for breeding crop varieties to increase the resilience of agricultural systems.

European scale assessment of the potential of ozonation and activated carbon treatment to reduce micropollutant emissions with wastewater.

Micropollutants (MPs) in wastewater pose a growing concern for their potential adverse effects on the receiving aquatic environment, and some countries have started requiring that wastewater treatment plants remove them to a certain extent. Broad spectrum advanced treatment processes, such as ozonation, activated carbon or their combination, are expected to yield a significant reduction in the toxicity of effluents. Here we quantify the reduction of effluent toxicity potentially achieved by implementing these advanced treatment solutions in a selection of European wastewater treatment plants. To this end, we refer to a list of "total pollution proxy substances" (TPPS) composed of 1337 chemicals commonly found in wastewater effluents according to a compilation of datasets of measured concentrations. We consider these substances as an approximation of the "chemical universe" impinging on the European wastewater system. We evaluate the fate of the TPPS in conventional and advanced treatment plants using a compilation of experimental physicochemical properties that describe their sorption, volatilization and biodegradation during activated sludge treatment, as well as known removal efficiency in ozonation and activated carbon treatment, while filling the gaps through in silico prediction models. We estimate that the discharge of micropollutants with wastewater effluents in the European Union has a cumulative MP toxicity to the environment equal to the discharge of untreated wastewater of ca. 160 million population equivalents (PE), i.e. about 30 % of the generated wastewater in the EU. If all plants above a capacity of 100,000 PE were equipped with advanced treatment, we show that this load would be reduced to about 95 million PE. In addition, implementing advanced treatment in wastewater plants above 10,000 PE discharging to water bodies with an average dilution ratio smaller than 10 would yield a widespread improvement in terms of exposure of freshwater ecosystems to micropollutants, almost halving the part of the stream network exposed to the highest toxic risks. Our analysis provides background for a cost-effectiveness appraisal of advanced treatment "at the end of the pipe", which could lead to optimized interventions. This should not be regarded as a stand-alone solution, but as a complement to policies for the control of emissions at the source for the most problematic MPs.

Prevalence of tobacco smoking in teachers following anti-smoking policies: results from two French surveys (1999 and 2005).

BACKGROUND: French public health policies aimed at reducing smoking were reinforced in France between 1999 and 2004 to decrease tobacco consumption. The consequences of these policies are of particular interest to teachers who play a role model for young people. Depression and alcohol problems were particularly studied as they may influence smoking behaviour. METHODS: Two large cross-sectional health surveys conducted in 1999 (N = 2931) and 2005 (N = 3702) included teachers, aged 20-59 years. Smoking status, socio-demographic characteristics, history of depressive episode in the previous year and problems with alcohol were collected using self-administered postal questionnaires. RESULTS: From 1999 to 2005, the prevalence of smoking decreased significantly from 25.7 to 18.2% for men (P < 0.001), from 20.0 to 16.5% (P < 0.001) for women; and the proportion of never-smokers increased. In smokers, the number of cigarettes consumed per day decreased significantly. Multivariate analysis revealed a significant decrease of the risk of being a smoker in 2005 compared with 1999 [odds ratio (OR) = 0.68 for men; OR = 0.78 for women]. Risk factors of smoking were: men aged 20-34 years (OR = 1.81), CAGE score > or =2, (OR = 1.95 for men, 2.12 for women) history of a major depressive episode in the previous 12 months (OR = 1.46 for men, 1.44 for women). CONCLUSION: Anti-smoking policies resulted in a decrease of teachers' tobacco consumption between 1999 and 2005. However, people with more difficulties in quitting smoking, in particular people with depressive episodes or problems with alcohol, might benefit from comprehensive programmes, including training of health professionals.

Organic micropollutants discharged by combined sewer overflows - Characterisation of pollutant sources and stormwater-related processes.

To characterise emissions from combined sewer overflows (CSOs) regarding organic micropollutants, a monitoring study was undertaken in an urban catchment in southwest Stuttgart, Germany. The occurrence of 69 organic micropollutants was assessed at one CSO outfall during seven rain events as well as in the sewage network at the influent of the wastewater treatment plant (WWTP) and in the receiving water. Several pollutant groups like pharmaceuticals and personal care products (PPCPs), urban biocides and pesticides, industrial chemicals, organophosphorus flame retardants, plasticisers and polycyclic aromatic hydrocarbons (PAHs) were chosen for analysis. Out of the 69 monitored substances, 60 were detected in CSO discharges. The results of this study show that CSOs represent an important pathway for a wide range of organic micropollutants from wastewater systems to urban receiving waters. For most compounds detected in CSO samples, event mean concentrations varied between the different events in about one order of magnitude range. When comparing CSO concentrations with median wastewater concentrations during dry weather, two main patterns could be observed depending on the source of the pollutant: (i) wastewater is diluted by stormwater; (ii) stormwater is the most important source of a pollutant. Both wastewater and stormwater only play an important role in pollutant concentration for a few compounds. The proportion of stormwater calculated with the conductivity is a suitable indicator for the evaluation of emitted loads of dissolved wastewater pollutants, but not for all compounds. In fact, this study demonstrates that remobilisation of in-sewer deposits contributed from 10% to 65% to emissions of carbamazepine in CSO events. The contribution of stormwater to CSO emitted loads was higher than 90% for all herbicides as well as for PAHs. Regarding the priority substance di(2-ethylhexyl)phthalate (DEHP), this contribution varied between 39% and 85%. The PAH concentrations found along the river indicate environmental risk, especially during rainfall events.

Pesticide fate modeling in soils with the crop model STICS: Feasibility for assessment of agricultural practices.

Numerous pesticide fate models are available, but few of them are able to take into account specific agricultural practices, such as catch crop, mixing crops or tillage in their predictions. In order to better integrate crop management and crop growth in the simulation of diffuse agricultural pollutions, and to manage both pesticide and nitrogen pollution, a pesticide fate module was implemented in the crop model STICS. The objectives of the study were: (i) to implement a pesticide fate module in the crop model STICS; (ii) to evaluate the model performance using experimental data from three sites with different pedoclimatic contexts, one in The Netherlands and two in northern France; (iii) to compare the simulations with several pesticide fate models; and (iv) to test the impact of specific agricultural practices on the transfer of the dissolved fraction of pesticides. The evaluations were carried out with three herbicides: bentazone, isoproturon, and atrazine. The strategy applied in this study relies on a noncalibration approach and sensitivity test to assess the operating limits of the model. To this end, the evaluation was performed with default values found in the literature and completed by sensitivity tests. The extended version of the STICS named STICS-Pest, shows similar results with other pesticide fate models widely used in the literature. Moreover, STICS-Pest was able to estimate realistic crop growth and catch crop dynamic, which thus illustrate agricultural practices leading to a reduction of nitrate and a change in pesticide leaching. The dynamic plot-scale model, STICS-Pest is able to simulate nitrogen and pesticide fluxes, when the hydrologic context is in the validity range of the reservoir (or capacity) model. According to these initial results, the model may be a relevant tool for studying the effect of long-term agricultural practices on pesticide residue dynamics in soil and the associated diffuse pollution transfer.

Variability and predictability of functional efficacy of botulinum toxin injection in leg spastic muscles.

Botulinum toxin injection reduces spasticity level. However, the effects on gait parameters and daily living activities remain controversial, and the prediction of results remains poorly evaluated. The aim of this open study was to investigate these effects, and the predictability of results. Forty-seven injections were given to 47 patients with stroke (males: 24; mean age: 51.7), in the soleus, gastrocnemius, tibialis posterior and anterior, and flexor digitorum longus, with a global dose of 300 U (Botox). Each was evaluated at day 1 (D1), day 15 (D15), month 2 (M2) and month 5 (M5). We observed a significant but moderate reduction in spasticity (Ashworth) of the ankle plantar flexors (0.72/5) and dorsiflexors, which was greater at D15, and an improvement in distal positioning in the upright situation. Upright balance and gait (Functional Ambulation Categories) were improved, especially at M2 and in the barefoot condition. Gait velocity and step length with usual aids (10 m) were discretely increased, and this was especially evident in about 15 patients. We also found improvement in the Rivermead Motor Assessment. Patients reported better foot positioning, facilitation in limb propulsion, and better static and dynamic balance. For each assessment, high variability in the effects was also shown. Improvement in functional tests was partially predicted by age (negative relation), delay since stroke (negative relation), gender (better in men), spasticity of hip adductors and knee extensors (negative relation), active ankle dorsiflexion (positive relation) and heel-ground distance (positive relation). In conclusion, the effects on spasticity, balance and gait were relatively modest, and with a large variability between patients. Functional improvement could be partially predicted by several general or specific factors, the knowledge of which is important in the selection of patients to be injected, and for future trials aiming to demonstrate the efficacy of botulinum toxin injection.

Smoking and the consumption of antidepressants, anxiolytics and hypnotic drugs: results of a large, French epidemiological study in 2005.

The aim of this study was to describe and analyse the links between the consumption of psychotropic drugs and smoking, based on data from individuals subscribing to a health insurance organisation (a mutuelle) in France in 2005. Data on smoking status, depression, anxiety and alcohol consumption from a large transversal epidemiological study carried out in 2005 were analysed in parallel to individual data concerning the reimbursement of medical prescriptions for psychotropic drugs. We compared reimbursement data for psychotropic drugs between individuals who had smoked for at least 15 years and continued to smoke and individuals who had stopped smoking after at least 15 years of smoking. This group of ex-smokers was subdivided into three subgroups on the basis of the number of years elapsed since the time point at which the individual had been smoking for 15 years: 1 to 9 years, 10 to 19 years and 20 years or more. "Ex-smoker" status was associated with a lower risk of psychotropic drug prescription than "current smoker" status (OR=0.81 for anxiolytics, OR=0.74 for antidepressants). Analysis of the subgroups of smokers and ex-smokers also showed that mean annual consumption of antidepressants and anxiolytics was significantly lower for individuals who had stopped smoking after at least 15 years of the habit than for those who continued to smoke (respectively 1.34 versus 0.65 for anxiolytics, and 1.17 versus 0.62 for antidepressants). Our findings suggest that stopping smoking is associated with a decrease in the consumption of psychotropic drugs. They highlight the need to evaluate the medium- and long-term effects of stopping smoking on psychotropic drug consumption in more detail, taking into account the anxious and depressive disorders to which smokers are particularly prone.