Adjustments in the forcing-feedback framework for understanding climate change

The traditional forcing-feedback framework has provided an indispensable basis for discussing global climate changes. However, as analysis of model behavior has become more detailed, shortcomings and ambiguities in the framework have become more evident and physical effects unaccounted for by the traditional framework have become interesting. In particular, the new concept of adjustments, which are responses to forcings that are not mediated by the global mean temperature, has emerged. This concept, related to the older ones of climate efficacy and stratospheric adjustment, is a more physical way of capturing unique responses to specific forcings. We present a pedagogical review of the adjustment concept, why it is important, and how it can be used. The concept is particularly useful for aerosols, where it helps to organize what has become a complex array of forcing mechanisms. It also helps clarify issues around cloud and hydrological response, transient vs. equilibrium climate change, and geoengineering

Taxonomic and Functional Microbial Signatures of the Endemic Marine Sponge Arenosclera brasiliensis

The endemic marine sponge Arenosclera brasiliensis (Porifera, Demospongiae, Haplosclerida) is a known source of secondary metabolites such as arenosclerins A-C. In the present study, we established the composition of the A. brasiliensis microbiome and the metabolic pathways associated with this community. We used 454 shotgun pyrosequencing to generate approximately 640,000 high-quality sponge-derived sequences (∼150 Mb). Clustering analysis including sponge, seawater and twenty-three other metagenomes derived from marine animal microbiomes shows that A. brasiliensis contains a specific microbiome. Fourteen bacterial phyla (including Proteobacteria, Cyanobacteria, Actinobacteria, Bacteroidetes, Firmicutes and Cloroflexi) were consistently found in the A. brasiliensis metagenomes. The A. brasiliensis microbiome is enriched for Betaproteobacteria (e.g., Burkholderia) and Gammaproteobacteria (e.g., Pseudomonas and Alteromonas) compared with the surrounding planktonic microbial communities. Functional analysis based on Rapid Annotation using Subsystem Technology (RAST) indicated that the A. brasiliensis microbiome is enriched for sequences associated with membrane transport and one-carbon metabolism. In addition, there was an overrepresentation of sequences associated with aerobic and anaerobic metabolism as well as the synthesis and degradation of secondary metabolites. This study represents the first analysis of sponge-associated microbial communities via shotgun pyrosequencing, a strategy commonly applied in similar analyses in other marine invertebrate hosts, such as corals and algae. We demonstrate that A. brasiliensis has a unique microbiome that is distinct from that of the surrounding planktonic microbes and from other marine organisms, indicating a species-specific microbiome

EuReCa ONE—27 Nations, ONE Europe, ONE Registry A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe

AbstractIntroductionThe aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.MethodsThis was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.ResultsData on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.ConclusionThe results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe.EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Brazil's landless movement and rights 'from below'

Recent literature has recognised the value of food sovereignty and human rights frameworks in agrarian struggles. Relatively little attention has gone toward how agrarian movements develop and apply their own rights discourses to further demands for social justice. This study considers Brazil's landless movement (MST) between 1984 and 1995, revealing three distinct rights discourses that recruited and mobilised protest by linking local issues to the movement's broader political project. The findings illustrate the value of rights, frames and ideology as analytical tools, shedding light on how movement-generated rights emerge through processes of reflexivity and in response to dynamic social-political contexts

Deregulation of cell death in rhabdomyosarcoma : analysis of the role of the mitochondrial transporter ANT1

Le rhabdomyosarcome (RMS) est la forme la plus fréquente de sarcome des tissus mous chez l'enfant. On distingue 2 sous-types principaux: ERMS (embryonnaire) et ARMS (alvéolaire). Les traitements actuels sont basés sur la chimiothérapie, la chirurgie et la radiothérapie. Le taux de survie à 5 ans reste de 70% depuis 2000, malgré plusieurs essais cliniques. Il est donc essentiel de pouvoir mieux comprendre leurs bases moléculaires pour pouvoir dans l’avenir mieux les soigner. Mon projet de thèse s’est inscrit dans cette perspective, en cherchant à mieux définir les mécanismes à l’origine de la résistance à la mort cellulaire dans ces cancers. Les cellules tumorales de RMS proviennent de précurseurs du lignage musculaire. Au cours de la myogenèse, la différenciation des myoblastes primitifs en myotubes nécessite un « switch » métabolique pour répondre à la demande énergétique accrue associée à la contraction musculaire. Ce processus est notamment soutenu par l'expression de gènes impliqués dans la phosphorylation oxydative, tels que SLC25A4. Ce gène code pour une protéine mitochondriale nommée ANT1, qui présente une dualité fonctionnelle. En effet, elle intervient à la fois dans la régulation du métabolisme énergétique en régulant l’export d'ATP de la mitochondrie vers le cytosol, mais également dans l’induction de la mort cellulaire en participant à l’ouverture du pore de transition de perméabilité (mPTP) conduisant à la libération du cytochrome c en conditions de stress. Par analyse bioinformatique de bases de données transcriptomiques, nous avons observé que l’expression de SLC25A4 est diminuée dans les RMS. Afin d’étudier le rôle causal de cette altération dans la survenue de RMS, des modèles cellulaires de RMS génétiquement modifiés permettant la surexpression ou l’invalidation d’ANT1 de manière inductible ont été établis. A l’aide de ces modèles, nous avons montré que la perte d’ANT1 favorise un « switch » métabolique dans les cellules tumorales de RMS et/ou diminue la sensibilité à des stress de type chimiothérapie, selon le contexte cellulaire. Réciproquement, sa réexpression sensibilise les cellules à ces traitements in vitro, et suffit à freiner la croissance tumorale in vivo. Ces résultats indiquent que la perte d’ANT1 peut constituer un nouveau mécanisme oncogénique dans les cellules tumorales, et favoriser notamment la résistance aux chimiothérapies.Rhabdomyosarcoma (RMS) is the most frequent form of pediatric soft-tissue sarcoma. It is divided into 2 main subtypes: ERMS (embryonal) and ARMS (alveolar). Current treatments are based on chemotherapy, surgery and radiotherapy. 5-year survival rate remains of 70% since 2000, despite several clinical trials. There is then an urgent need to improve the understanding of their molecular etiology to improve their therapeutic management. My PhD project forms part of this perspective, by seeking to better define mechanisms triggering resistance to cell death in these cancers. RMS cells derive from muscle linage precursors. During myogenesis, primitive myoblasts diffentiation into myotubes requires a metabolic switch to support the increased energetic demand of contractile muscle. This process is notably supported by expression of genes involved in oxydative phosphorylation, such as SLC25a4. This gene encodes a mitochondrial protein named ANT1, which has a functional duality as it is involved both in metabolism via regulation of ATP release from mitochondria to cytosol, but also in apoptosis as part as the mPTP (mitochondria Permeability Transition Pore) leading to the release of cytochrome c under stress. By bioinformatic analysis of transcriptomic databases, we observed that SLC25A4 expression is downregulated in RMS. To deal with this result in depth, we designed modified RMS cells inactivated for ANT1 using CRISPR/CAS9 technology or overexpressing this protein, using a Tet-On system. Using these models, we have shown that loss of ANT1 favors a metabolic switch in RMS tumor cells and/or promotes resistance to death notably upon chemotherapeutic treatments, according to the cell context. Reciprocally, its reexpression sensitizes cells to these treatments in vitro and brakes tumor growth in vivo. These results indicate that ANT1 loss may constitute a new oncogenic mechanism in tumor cells, and may notably favor resistance to chemotherapies

Identification of quorum sensing-controlled genes in Burkholderia ambifaria.

International audienceThe Burkholderia cepacia complex (Bcc) comprises strains with a virulence potential toward immunocompromised patients as well as plant growth-promoting rhizobacteria (PGPR). Owing to the link between quorum sensing (QS) and virulence, most studies among Bcc species have been directed toward QS of pathogenic bacteria. We have investigated the QS of B. ambifaria, a PGPR only infrequently recovered from patients. The cepI gene, responsible for the synthesis of the main signaling molecule N-octanoylhomoserine lactone (C8 -HSL), was inactivated. Phenotypes of the B. ambifaria cepI mutant we observed, such as increased production of siderophores and decreased proteolytic and antifungal activities, are in agreement with those of other Bcc cepI mutants. The cepI mutant was then used as background strain for a whole-genome transposon-insertion mutagenesis strategy, allowing the identification of 20 QS-controlled genes, corresponding to 17 loci. The main functions identified are linked to antifungal and antimicrobial properties, as we have identified QS-controlled genes implicated in the production of pyrrolnitrin, burkholdines (occidiofungin-like molecules), and enacyloxins. This study provides insights in the QS-regulated functions of a PGPR, which could lead to beneficial potential biotechnological applications

Polycaprolactone / bioactive glass hybrid scaffolds for bone regeneration

International audienceBioactive glasses (BG) bond to bone and stimulate bone regeneration, but they are brittle. Inorganicorganic hybrids appear as promising bone substitutes since they associate the bone mineral forming ability of BG with the toughness of polymers. Hybrids comprised of polycaprolactone (PCL) and SiO 2 -CaO BG were produced by sol-gel chemistry and processed into porous scaffolds with controlled pore and interconnection sizes. The obtained scaffolds are highly flexible, meaning that PCL effectively introduces toughness. Apatite formation is observed within 24 hours of immersion in simulated body fluid (SBF) and is not limited to the surface as the entire hybrid progressively changes into bone-like minerals. The degradation rate is suitable for bone regeneration with a 13.2% weight loss after 8 weeks of immersion. Primary osteoblasts cultured in scaffolds demonstrate that the samples are not cytotoxic and provide good cell adhesion. The in vivo study confirms the bioactivity, biocompatibility and suitable degradation rate of the hybrid. A physiological bone made of trabeculae and bone marrow regenerates. The structure and kinetic of bone regeneration was similar to the implanted commercial standard based on bovine bone, demonstrating that this new synthetic PCL-BG hybrid could perform as well as animal-derived bone substitutes