Systèmes agraires et changement climatique au Sud

À partir de l’étude détaillée et de la comparaison d’une douzaine de situations locales contrastées en Afrique sub-saharienne et en Asie du Sud-Est, les auteurs mettent en évidence les processus et les trajectoires qui expliquent la forte exposition aux aléas des différents groupes d’agriculteurs, ainsi que leur inégale capacité d’adaptation. Ils expliquent les ressorts de cette vulnérabilité et illustrent le poids des choix passés et actuels en matière de politiques agricole, environnementale et commerciale. Enfin, ils présentent les modalités d’ajustement et les transformations passées et en cours des pratiques paysannes allant dans le sens d’une réduction de l’exposition à l’aléa, d’une atténuation de la vulnérabilité, et d’une meilleure adaptation aux changements globaux : dérèglement climatique bien sûr, mais aussi accroissement démographique, compétition accrue pour l’accès aux ressources, évolution des prix relatifs et fluctuations des marchés, dérégulation et baisse des soutiens publics, etc. Ils esquissent en conclusion les chemins possibles en matière d’adaptation et des propositions de mesures politiques pour accompagner les producteurs.Pour des raisons de différences de fabrication, les figures et photos en couleurs de la présente version sont disséminées au sein des différents chapitres, mais sont réunies à la fin du chapitre 4 de la version PDF

Phrenic nerve stimulation in an ovine model with temporary removable pacing leads

International audienceBackground: The objective of this study was to assess the feasibility and safety of a novel, removable, surgically implanted, temporary neurostimulation approach involving the distal portion of the phrenic nerve.Methods: Temporary phrenic nerve pacing electrodes were implanted surgically using an ovine model (4 animals). The primary endpoint was the ability to successfully match the animal's minute-ventilation upon implantation of both phrenic nerve pacers on day 1. Secondary endpoints were successful phrenic neurostimulation by both electrodes 15 and 30 days after initial implantation. We also assessed safe removal of the electrodes at 15 and 30 days after implementation.Results: In 3 of 4 animals, electrodes were successfully implanted in both right and left phrenic nerves. On day 1, median ventilation-minute induced by neurostimulation was not significantly different from baseline ventilation-minute [4.9 L·min-1 (4.4-5.5) vs. 4.4 L·min-1 (4.3-5.2); P=0.4] after 15 minutes. Neurostimulation was still possible 15 and 30 days after implementation in all left side phrenic nerves. On the right side, stimulation was possible at all times in 1 animal but not in the remaining 3 animals for at least one time point, possibly due to lead displacement. Analysis of pathology after percutaneous electrode removal showed integrity of the distal portion of all phrenic nerves.Conclusions: Efficient temporary neurostimulation through the distal portion of the phrenic nerve was possible at baseline. The main complication was the displacement of electrodes on the right phrenic nerve on two occasions, which was due to the anatomy of the ovine model. It compromised diaphragm pacing on day 15 and day 30. The electrodes could be safely removed percutaneously without damage to the phrenic nerves

New mechanistic insights of integrin β1 in breast cancer bone colonization

Bone metastasis is a frequent and life-threatening complication of breast cancer. The molecular mechanisms supporting the establishment of breast cancer cells in the skeleton are still not fully understood, which may be attributed to the lack of suitable models that interrogate interactions between human breast cancer cells and the bone microenvironment. Although it is well-known that integrins mediate adhesion of malignant cells to bone extracellular matrix, their role during bone colonization remains unclear. Here, the role of β1 integrins in bone colonization was investigated using tissue-engineered humanized in vitro and in vivo bone models. In vitro, bone-metastatic breast cancer cells with suppressed integrin β1 expression showed reduced attachment, spreading, and migration within human bone matrix compared to control cells. Cell proliferation in vitro was not affected by β1 integrin knockdown, yet tumor growth in vivo within humanized bone microenvironments was significantly inhibited upon β1 integrin suppression, as revealed by quantitative in/ex vivo fluorescence imaging and histological analysis. Tumor cells invaded bone marrow spaces in the humanized bone and formed osteolytic lesions; osteoclastic bone resorption was, however, not reduced by β1 integrin knockdown. Taken together, we demonstrate that β1 integrins have a pivotal role in bone colonization using unique tissue-engineered humanized bone models

Iron- and Hepcidin-Independent Downregulation of the Iron Exporter Ferroportin in Macrophages during Salmonella Infection

Retention of iron in tissue macrophages via upregulation of hepcidin (HAMP) and downregulation of the iron exporter ferroportin (FPN) is thought to participate in the establishment of anemia of inflammation after infection. However, an upregulation of FPN has been proposed to limit macrophages iron access to intracellular pathogens. Therefore, we studied the iron homeostasis and in particular the regulation of FPN after infection with Salmonella enterica serovar Typhimurium in mice presenting tissue macrophages with high iron (AcB61), basal iron (A/J and wild-type mice), or low iron (Hamp knock out, Hamp(-/-)) levels. The presence of iron in AcB61 macrophages due to extravascular hemolysis and strong erythrophagocytosis activity favored the proliferation of Salmonella in the spleen and liver with a concomitant decrease of FPN protein expression. Despite systemic iron overload, no or slight increase in Salmonella burden was observed in Hamp(-/-) mice compared to controls. Importantly, FPN expression at both mRNA and protein levels was strongly decreased during Salmonella infection in Hamp(-/-) mice. The repression of Fpn mRNA was also observed in Salmonella-infected cultured macrophages. In addition, the downregulation of FPN was associated with decreased iron stores in both the liver and spleen in infected mice. Our findings show that during Salmonella infection, FPN is repressed through an iron and hepcidin-independent mechanism. Such regulation likely provides the cellular iron indispensable for the growth of Salmonella inside the macrophages

Astaxanthin Complexes to Attenuate Muscle Damage after In Vivo Femoral Ischemia-Reperfusion.

International audience(1) Background: Reperfusion injury refers to the cell and tissue damage induced, when blood flow is restored after an ischemic period. While reperfusion reestablishes oxygen supply, it generates a high concentration of radicals, resulting in tissue dysfunction and damage. Here, we aimed to challenge and achieve the potential of a delivery system based on astaxanthin, a natural antioxidant, in attenuating the muscle damage in an animal model of femoral hind-limb ischemia and reperfusion. (2) Methods: The antioxidant capacity and non-toxicity of astaxanthin was validated before and after loading into a polysaccharide scaffold. The capacity of astaxanthin to compensate stress damages was also studied after ischemia induced by femoral artery clamping and followed by varied periods of reperfusion. (3) Results: Histological evaluation showed a positive labeling for CD68 and CD163 macrophage markers, indicating a remodeling process. In addition, higher levels of Nrf2 and NQO1 expression in the sham group compared to the antioxidant group could reflect a reduction of the oxidative damage after 15 days of reperfusion. Furthermore, non-significant differences were observed in non-heme iron deposition in both groups, reflecting a cell population susceptible to free radical damage. (4) Conclusions: Our results suggest that the in situ release of an antioxidant molecule could be effective in improving the antioxidant defenses of ischemia/reperfusion (I/R)-damaged muscles

A phase I dose-escalation study of oxaliplatin delivered via a laparoscopic approach using pressurised intraperitoneal aerosol chemotherapy for advanced peritoneal metastases of gastrointestinal tract cancers

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Prevalence of K-RAS Codons 12 and 13 Mutations in Locally Advanced Head and Neck Squamous Cell Carcinoma and Impact on Clinical Outcomes

Background. RAS gene mutations have an impact on treatment response and overall prognosis for certain types of cancer. Objectives. To determine the prevalence and impact of K-RAS codons 12 and 13 mutations in patients with locally advanced HNSCC treated with primary or adjuvant chemo-radiation. Methods. 428 consecutive patients were treated with chemo-radiation therapy and followed for a median of 37 months. From these, 199 paraffin embedded biopsy or surgical specimens were retrieved. DNA was isolated and analyzed for K-RAS mutational status. Results. DNA extraction was successful in 197 samples. Of the 197 specimens, 3.5% presented K-RAS codon 12 mutations. For mutated cases and non-mutated cases, complete initial response to chemoradiation therapy was 71 and 73% (P=0.32). LRC was respectively 32 and 83% (P=0.03), DFS was 27 and 68% (P=0.12), distant metastasis-free survival was 100 and 81% (P=0.30) and OS was 57 and 65% (P=0.14) at three years. K-Ras codon 13 analysis revealed no mutation. Conclusion. K-RAS codon 12 mutational status, although not associated with a difference in response rate, may influence the failure pattern and the type of therapy offered to patients with HNSCC. Our study did not reveal any mutation of K-RAS codon 13