Changement global : état de la notion dans les différents champs disciplinaires et plus spécifiquement en SHS: Note de synthèse bibliographique

Cet état de l’art sur la notion de changement global s’inscrit dans les actions de recherches prévues dans laprogrammation scientifique du Labex Item et a bénéficié d’une aide de l’Etat gérée par l'Agence Nationale de la Recherche au titre du programme « Investissements d’avenir » Labex ITEM - ANR-10-LABX-50-01.Au sein du Labex ITEM, le groupe de travail WP1 intitulé « Changement Global – Montagne » a engagé une réflexion sur la thématique du changement global en territoires de montagne, et les premiers échanges ont montré la nécessité de procéder à un état des lieux bibliographique préalable, afin de cerner les positionnements de chaque discipline sur le sujet, mais aussi d’identifier des verrous méthodologiques et des axes de travail.La démarche suivie a consisté en une interrogation de portails de ressources disciplinaires via une série de mots clés, enrichie progressivement suite aux premiers échanges avec le groupe de travail.Le changement global est une notion bien appropriée par les géosciences et les sciences de l’environnement, mais sous une définition partielle (changement climatique seulement), par rapport à celle que nous entendons. En effet, force est de constater que la bibliographie relative au changement global (c’est-à-dire croisant les différentes composantes du changement), comporte actuellement peu d’éléments, ou des éléments très segmentés. Son emploi pour désigner l’ensemble des changements : environnementaux (écologique / climatique), économique, énergétique, démographique, sociétal et culturel est d’un usage récent (Griffon 2007). Actuellement, peu (voire pas) de disciplines traitent du changement global en ne considérant pas seulement le changement climatique, mais aussi les mutations socio-économiques et leurs interactions.Néanmoins, la notion de changement global est présente dans les déclarations d’intention ou les documents de prospectives des organismes de recherche, même si son étude de manière croisée est encore peu abordée dans les SHS. En terme de changement, il apparaît que c’est essentiellement le changement climatique qui est traité, voire le changement social ou spatial.Cela conforte le positionnement du WP1 et l’intérêt de fournir une production scientifique sur le changement global appliqué aux territoires de montagne

L'outil-frise : une expérimentation interdisciplinaire: Comment représenter des processus de changements en territoires de montagne ?

Ont également contribué à cette publication : Denis Laforgue ; Sandrine Tolazzi ; Sophie Madelrieux ; Pénélope Lamarque ; Sabine Girard ; Mélanie Duval ; Suzanne Berthier-Foglar ; Philippe Bourdeau ; Anouk Bonnemains ; Hugues FrançoisInternational audienceLe LabEx Innovation et Territoires de Montagne a pour ambition de construire une communauté de recherche en sciences humaines et sociales travaillant sur la montagne. Dans cette dynamique, un collectif de chercheurs issus de différents champs disciplinaires et de parcours variés s’est proposé de développer une démarche de recherche qui dépasse les clivages disciplinaires par la formalisation d’un outil de dialogue sur le changement territorial. Ce carnet expose la construction, les enjeux et les résultats d’une telle démarche. Celle-ci a conduit à la mise en place d’un dispositif comprenant l’élaboration de documents-ressources, l’expérimentation collective d’une méthode sur différents systèmes territoriaux de montagne, l’échange en séminaires, ainsi que les retours critiques individuels et collectifs sur les apports d’une telle expérimentation. Au cœur de ce dispositif, « l’outil-frise », un outil de représentation synthétique et globale des changements territoriaux, qui permet de visualiser les co-évolutions et les interactions des composantes d’un processus complexe. Il implique une mise en perspective processuelle de l’objet d’étude, à savoir l’identification de la nature des mouvements et des moteurs facteurs de changements. Les enjeux épistémologiques et méthodologiques des différentes approches disciplinaires du changement ont ainsi pu être abordés, et notamment les concepts de rupture, de bifurcation, d’adaptation ou de transition territoriales

Prevention of post-mastectomy neuropathic pain with memantine: study protocol for a randomized controlled trial

International audienceBackground: N-methyl-D-aspartate receptor antagonists are potential therapies for neuropathic pain, and memantine has a good tolerance profile. A preclinical study recently reported that presurgery memantine may prevent neuropathic pain development and cognition dysfunction. Considering the high prevalence of breast cancer and of post-mastectomy neuropathic pain, a clinical trial is carried out to evaluate if memantine may prevent neuropathic pain development and maintain cognitive function and quality of life in cancer patients. Methods/Design: A randomized clinical trial (NCT01536314) includes 40 women with breast cancer undergoing mastectomy at the Oncology Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) is administered for 4 weeks starting 2 weeks before surgery. Intensity of pain, cognitive function, quality of life and of sleep, anxiety and depression are evaluated with questionnaires. The primary endpoint is pain intensity on a 0 to 10) numerical scale at 3 months post-mastectomy. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at α = 0.05. Discussion: The hypothesis of this translational approach is to confirm in patients the beneficial prophylactic effect of memantine observed in animals. Such a protective action of memantine against neuropathic pain and cognitive dysfunction would greatly improve the quality of life of cancer patients. Trial registration: ClinicalTrials.gov: NCT01536314 on 16 February 201

Reduced parathyroid functional mass after successful kidney transplantation

Reduced parathyroid functional mass after successful kidney transplantation.BackgroundChronic uremia is responsible for secondary hyperparathyroidism (HPT II). Parathyroid secretion usually tends to normalize after kidney transplantation (KT), but the parameters of the reversibility of HPT II remain poorly defined, particularly the intrinsic mechanisms underlying the improvement of parathyroid function.MethodsThe kinetic functional parameters of the ionized calcium (iCa)/parathormone (PTH) relationship curve were studied in 11 patients with mild to moderate HPT II one and six months after successful KT. Hypercalcemia and hypocalcemia were induced, respectively, by CaCl2 and Na2-ethylenediaminetetraacetic acid (Na2-EDTA) infusions.ResultsThe mean glomerular filtration rate remained stable during follow-up. Basal PTH decreased from 195 ± 54 pg/ml before KT to 70 ± 12 pg/ml six months later (P < 0.005). During the tests, mean PTH levels decreased significantly between the two measured times for all iCa levels, indicating an improved parathyroid function. An analysis of the kinetic parameters of the curves showed significant decreases of the mean maximal and minimal PTH levels, respectively, from 340 ± 91 to 220 ± 30 pg/ml (P = 0.03) and from 25 ± 6 to 15 ± 5 pg/ml (P = 0.005). On the other hand, no change was noted in the parathyroid-cell calcium-sensitivity parameters (slope, set point) assessed using two different approaches, either the entire curve or the limited calcium-mediated suppression curve.ConclusionImprovement of the parathyroid function between the first and sixth months post-KT seems mainly attributable to a reduction of the parathyroid functional mass

Aberrant Splicing Is the Pathogenicity Mechanism of the p.Glu314Lys Variant in CYP11A1 Gene

Context: The cholesterol side chain cleavage enzyme (CYP11A1) catalyzes the conversion of cholesterol to pregnenolone, the first rate-limiting step of steroidogenesis. CYP11A1 mutations are associated with primary adrenal insufficiency (PAI) as well as disorders of sex development (DSD) in 46,XY patients.Objective: To define the pathogenicity mechanism for the p.Glu314Lys variant, previously reported, and found in four additional patients with CYP11A1 deficiency.Subjects and Methods: DNA of four patients presenting with delayed PAI and/or 46,XY DSD were studied by Sanger or Massively Parallel sequencing. Three CYP11A1 mutations were characterized in vitro and in silico, and one by mRNA analysis on testicular tissue.Results: All patients were compound heterozygous for the previously described p.Glu314Lys variant. In silico studies predicted this mutation as benign with no effect on splicing but mRNA analysis found that it led to incomplete exon 5 skipping. This mechanism was confirmed by minigene experiment. The protein carrying this mutation without exon skipping should conserve almost normal activity, according to in vitro studies. Two other mutations found in trans, the p.Arg120Gln and p.Arg465Trp, had similar activity compared to negative control, consistent with the in silico studies.Conclusions: We provide biological proof that the p. Glu314Lys variant is pathogenic due to its impact on splicing and seems responsible for the moderate phenotype of the four patients reported herein. The present study highlights the importance of considering the potential effect of a missense variant on splicing when it is not predicted to be disease causing

Loss of LGR4/GPR48 causes severe neonatal salt-wasting due to disrupted WNT signaling altering adrenal zonation.

Disorders of isolated mineralocorticoid deficiency causing potentially life-threatening salt-wasting crisis early in life have been associated with gene variants of aldosterone biosynthesis or resistance, but in some patients no such variants are found. WNT/β-catenin signaling is crucial for differentiation and maintenance of the aldosterone producing adrenal zona glomerulosa (zG). We describe a highly consanguineous family with multiple perinatal deaths or infants presenting at birth with failure to thrive, severe salt-wasting crises associated with isolated hypoaldosteronism, nail anomalies, short stature, and deafness. Whole exome sequencing revealed a homozygous splice variant in the R-SPONDIN receptor LGR4 gene (c.618-1G>C) regulating WNT signaling. The resulting transcripts affected protein function and stability, and resulted in loss of Wnt/β-catenin signaling in vitro. The impact of LGR4 inactivation was analyzed by adrenal cortex specific ablation of Lgr4, using Lgr4Flox/Flox mated with Sf1:Cre mice. Inactivation of Lgr4 within the adrenal cortex in the mouse model caused decreased WNT signaling, aberrant zonation with deficient zG and reduced aldosterone production. Thus, human LGR4 mutations establish a direct link between LGR4 inactivation and decreased canonical WNT signaling with abnormal zG differentiation and endocrine function. Therefore, variants in WNT signaling and its regulators should systematically be considered in familial hyperreninemic hypoaldosteronism

Conserved white-rot enzymatic mechanism for wood decay in the Basidiomycota genus Pycnoporus

White-rot (WR) fungi are pivotal decomposers of dead organic matter in forest ecosystems and typically use a large array of hydrolytic and oxidative enzymes to deconstruct lignocellulose. However, the extent of lignin and cellulose degradation may vary between species and wood type. Here, we combined comparative genomics, transcriptomics and secretome proteomics to identify conserved enzymatic signatures at the onset of wood-decaying activity within the Basidiomycota genus Pycnoporus. We observed a strong conservation in the genome structures and the repertoires of protein-coding genes across the four Pycnoporus species described to date, despite the species having distinct geographic distributions. We further analysed the early response of P. cinnabarinus, P. coccineus and P. sanguineus to diverse (ligno)-cellulosic substrates. We identified a conserved set of enzymes mobilized by the three species for breaking down cellulose, hemicellulose and pectin. The co-occurrence in the exo-proteomes of H2O2-producing enzymes with H2O2-consuming enzymes was a common feature of the three species, although each enzymatic partner displayed independent transcriptional regulation. Finally, cellobiose dehydrogenase-coding genes were systematically co-regulated with at least one AA9 lytic polysaccharide monooxygenase gene, indicative of enzymatic synergy in vivo. This study highlights a conserved core white-rot fungal enzymatic mechanism behind the wood-decaying process.Peer reviewe

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.N