Baronnies Provençales Regional Nature Park Pilot Action Region: The Benefit of Large-Scale Rockfall Modelling for Developing Efficient Forest-Based Integrative Management of an Alpine Territory

The choice of a natural risk prevention strategy must be considered at the scale of a territory in order to take into account all its components. Since 2015, France has developed integrated natural risk management (INRM) approaches in Alpine territories. The challenge of INRM lies in the definition and implementation of innovative projects for initiating synergies with respect to natural risks while seeking to increase resilience through the new and different involvement of the territorial actors. The Baronnies Provençales Regional Nature Park is one of the pilot territories for the operational implementation of this approach, with a particular focus on forest-based solutions. For this reason it has been chosen as the French Pilot Action Region (PAR) of the Interreg Alpine Space project GreenRisk4Alps. In this article we present an example of good practice related to the benefit of large-scale rockfall risk modeling, the analysis of potential cascading effects and the added value of a territorial perspective

Shared molecular targets confer resistance over short and long evolutionary timescales

Pre-existing and de novo genetic variants can both drive adaptation to environmental changes, but their relative contributions and interplay remain poorly understood. Here we investigated the evolutionary dynamics in drug-treated yeast populations with different levels of pre-existing variation by experimental evolution coupled with time-resolved sequencing and phenotyping. We found a doubling of pre-existing variation alone boosts the adaptation by 64.1% and 51.5% in hydroxyurea and rapamycin respectively. The causative pre-existing and de novo variants were selected on shared targets: RNR4 in hydroxyurea and TOR1, TOR2 in rapamycin. Interestingly, the pre-existing and de novo TOR variants map to different functional domains and act via distinct mechanisms. The pre-existing TOR variants from two domesticated strains exhibited opposite rapamycin resistance effects, reflecting lineage-specific functional divergence. This study provides a dynamic view on how pre-existing and de novo variants interactively drive adaptation and deepens our understanding of clonally evolving populations

Characterization, sources and reactivity of volatile organic compounds (VOCs) in Seoul and surrounding regions during KORUS-AQ

The Korea-United States Air Quality Study (KORUS-AQ) took place in spring 2016 to better understand air pollution in Korea. In support of KORUS-AQ, 2554 whole air samples (WAS) were collected aboard the NASA DC-8 research aircraft and analyzed for 82 C₁–C₁₀ volatile organic compounds (VOCs) using multi-column gas chromatography. Together with fast-response measurements from other groups, the air samples were used to characterize the VOC composition in Seoul and surrounding regions, determine which VOCs are major ozone precursors in Seoul, and identify the sources of these reactive VOCs. (1) The WAS VOCs showed distinct signatures depending on their source origins. Air collected over Seoul had abundant ethane, propane, toluene and n-butane while plumes from the Daesan petrochemical complex were rich in ethene, C₂–C₆ alkanes and benzene. Carbonyl sulfide (COS), CFC-113, CFC-114, carbon tetrachloride (CCl₄) and 1,2-dichloroethane were good tracers of air originating from China. CFC-11 was also elevated in air from China but was surprisingly more elevated in air over Seoul. (2) Methanol, isoprene, toluene, xylenes and ethene were strong individual contributors to OH reactivity in Seoul. However methanol contributed less to ozone formation based on photochemical box modeling, which better accounts for radical chemistry. (3) Positive Matrix Factorization (PMF) and other techniques indicated a mix of VOC source influences in Seoul, including solvents, traffic, biogenic, and long-range transport. The solvent and traffic sources were roughly equal using PMF, and the solvents source was stronger in the KORUS-AQ emission inventory. Based on PMF, ethene and propene were primarily associated with traffic, and toluene, ethylbenzene and xylenes with solvents, especially non-paint solvents for toluene and paint solvents for ethylbenzene and xylenes. This suggests that VOC control strategies in Seoul could continue to target vehicle exhaust and paint solvents, with additional regulations to limit the VOC content in a variety of non-paint solvents

Characterization, sources and reactivity of volatile organic compounds (VOCs) in Seoul and surrounding regions during KORUS-AQ

The Korea-United States Air Quality Study (KORUS-AQ) took place in spring 2016 to better understand air pollution in Korea. In support of KORUS-AQ, 2554 whole air samples (WAS) were collected aboard the NASA DC-8 research aircraft and analyzed for 82 C₁–C₁₀ volatile organic compounds (VOCs) using multi-column gas chromatography. Together with fast-response measurements from other groups, the air samples were used to characterize the VOC composition in Seoul and surrounding regions, determine which VOCs are major ozone precursors in Seoul, and identify the sources of these reactive VOCs. (1) The WAS VOCs showed distinct signatures depending on their source origins. Air collected over Seoul had abundant ethane, propane, toluene and n-butane while plumes from the Daesan petrochemical complex were rich in ethene, C₂–C₆ alkanes and benzene. Carbonyl sulfide (COS), CFC-113, CFC-114, carbon tetrachloride (CCl₄) and 1,2-dichloroethane were good tracers of air originating from China. CFC-11 was also elevated in air from China but was surprisingly more elevated in air over Seoul. (2) Methanol, isoprene, toluene, xylenes and ethene were strong individual contributors to OH reactivity in Seoul. However methanol contributed less to ozone formation based on photochemical box modeling, which better accounts for radical chemistry. (3) Positive Matrix Factorization (PMF) and other techniques indicated a mix of VOC source influences in Seoul, including solvents, traffic, biogenic, and long-range transport. The solvent and traffic sources were roughly equal using PMF, and the solvents source was stronger in the KORUS-AQ emission inventory. Based on PMF, ethene and propene were primarily associated with traffic, and toluene, ethylbenzene and xylenes with solvents, especially non-paint solvents for toluene and paint solvents for ethylbenzene and xylenes. This suggests that VOC control strategies in Seoul could continue to target vehicle exhaust and paint solvents, with additional regulations to limit the VOC content in a variety of non-paint solvents

The role of RelA (p65) threonine 505 phosphorylation in the regulation of cell growth, survival, and migration

The NF-κB family of transcription factors is a well-established regulator of the immune and inflammatory responses and also plays a key role in other cellular processes, including cell death, proliferation, and migration. Conserved residues in the trans-activation domain of RelA, which can be posttranslationally modified, regulate divergent NF-κB functions in response to different cellular stimuli. Using rela(−/−) mouse embryonic fibroblasts reconstituted with RelA, we find that mutation of the threonine 505 (T505) phospho site to alanine has wide-ranging effects on NF-κB function. These include previously described effects on chemotherapeutic drug-induced apoptosis, as well as new roles for this modification in autophagy, cell proliferation, and migration. This last effect was associated with alterations in the actin cytoskeleton and expression of cellular migration–associated genes such as WAVE3 and α-actinin 4. We also define a new component of cisplatin-induced, RelA T505–dependent apoptosis, involving induction of NOXA gene expression, an effect explained at least in part through induction of the p53 homologue, p73. Therefore, in contrast to other RelA phosphorylation events, which positively regulate NF-κB function, we identified RelA T505 phosphorylation as a negative regulator of its ability to induce diverse cellular processes such as apoptosis, autophagy, proliferation, and migration

L’oncogenèse entretenue par une boucle de transformation autocrine

International audienceNo abstract availabl

Circulating miRNAs as new activators of the JAK-STAT3 pathway

International audienceCell communication is well known to rely on direct contacts or on secreted factors that bind to receptors located on the surface of their target cells. In addition to this classical pathway, recent results have shown that cells produce microvesicles that contain functional DNA, RNA and proteins that can be directly transferred to recipient cells. This induces proliferation, differentiation or cell death to the same extent as classical soluble factors. New data obtained from the laboratory of Napoleone Ferrara show that these microvesicles also contain miRNAs that can induce angiogenic activities in neighboring endothelial cells. When secreted from cancer cells, these miRNA-loaded vesicles penetrate recipient cells where they activate the JAK-STAT pathway. This represents a new type of intercellular signaling and a new way of activating the STAT transcription factors that could be of interest for the design of cancer treatments.</p

Un cas d’acidose pyroglutamique associé à la prise concomitante de cloxacilline et d’acétaminophène

RésuméObjectif : Décrire un cas clinique d’acidose pyroglutamique qui serait causé par la prise concomitante de cloxacilline et d’acétaminophène et discuter des étiologies possibles de ce type d’acidose métabolique avec une élévation du trou anionique.Résumé du cas : Une patiente de 83 ans, souffrant d’une infection, a développé une acidose métabolique avec une élévation du trou anionique et des lactates normaux lors du traitement à la cloxacilline d’un anévrisme mycotique à Staphylococcus aureus sensible à la méthicilline. La patiente recevait également de l’acétaminophène durant son hospitalisation. En retirant les agents causaux (cloxacilline et acétaminophène) et en instaurant un traitement de soutien et un protocole de N-Acétylcystéine, la patiente a récupéré rapidement sans subir de conséquence permanente.Discussion : L’acidose pyroglutamique résulte de l’accumulation de 5-oxoproline secondaire à des anomalies du cycle gammaglutamyl et à une déplétion en glutathion. Plusieurs rapports de cas décrivent différents facteurs de risque, dont certains médicaments (acétaminophène, cloxacilline, vigabatrin) et certaines comorbidités (atteinte rénale ou hépatique, sepsis, malnutrition). Selon les algorithmes de Naranjo et DIPS, il est probable que ce cas d’acidose pyroglutamique ait été causé par la combinaison de cloxacilline et d’acétaminophène. Bien qu’une valeur d’excrétion rénale de 5-oxoproline aurait permis de confirmer le diagnostic, la suspicion clinique demeure élevée après l’exclusion des autres causes potentielles.Conclusion : L’acidose pyroglutamique est une cause rare d’acidose métabolique avec une élévation du trou anionique, et on devrait penser à une telle acidose une fois que le diagnostic différentiel a éliminé les étiologies communes d’acidose. Ce cas souligne bien le rôle du pharmacien dans la détection des effets indésirables médicamenteux rares.AbstractObjective: To describe a clinical case of pyroglutamic acidosis apparently caused by the concomitant use of cloxacillin and acetaminophen and to discuss the possible etiologies of this type of metabolic acidosis accompanied by an elevated anion gap.Case summary: An 83-year-old female patient with an infection developed metabolic acidosis with an elevated anion gap and normal lactates while being treated with cloxacillin for a methicillin-sensitive Staphylococcus aureus mycotic aneurysm. The patient also received acetaminophen during her hospital stay. Upon the withdrawal of the causal agents (cloxacillin and acetaminophen) and the initiation of supportive treatment and an N-acetylcysteine protocol, the patient experienced a rapid recovery with no permanent sequelae.Discussion: Pyroglutamic acidosis results from a build-up of 5-oxoproline secondary to gamma-glutamyl cycle abnormalities and glutathione depletion. A number of case reports describe different risk factors, among which are certain drugs (acetaminophen, cloxacillin and vigabatrin) and certain comorbidities (hepatic or renal impairment, sepsis and malnutrition). Based on the Naranjo and Drug Interaction Probability Scale algorithms, this case of pyroglutamic acidosis was probably caused by the concomitant use of cloxacillin and acetaminophen. Although the diagnosis could have been confirmed from a urinary 5-oxoproline excretion value, clinical suspicion remained strong after ruling out the other possible causes.Conclusion: Pyroglutamic acidosis is a rare cause of metabolic acidosis accompanied by an elevated anion gap and should be considered once the differential diagnosis has ruled out the common etiologies of acidosis. This case underscores the pharmacist’s role in detecting rare drug adverse effects