27 research outputs found

    Tectonic deformation of the Andes and the configuration of the subducted slab in central Peru: Results from a micro-seismic experiment

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    The vast majority of the microearthquakes recorded occurred to the east: on the Huaytapallana fault in the Eastern Cordillera or in the western margin of the sub-Andes. The sub-Andes appear to be the physiographic province subjected to the most intense seismic deformation. Focal depths for the crustal events here are as deep as 50 km, and the fault plane solutions, show thrust faulting on steep planes oriented roughly north-south. The Huaytapallana fault in the Cordillera Oriental also shows relatively high seismicity along a northeast-southwest trend that agrees with the fault scarp and the east dipping nodal plane of two large earthquakes that occurred on this fault in 1969. The recorded microearthquakes of intermediate depth show a flat seismic zone about 25 km thick at a depth of about 100 km. This agrees with the suggestion that beneath Peru the slab first dips at an angle of 30 deg to a depth of 100 km and then flattens following a quasi-horizontal trajectory. Fault plane solutions of intermediate depth microearthquakes have horizontal T axes oriented east-west

    The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin.

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    Trypanosoma cruzi glutathione-dependent peroxidase I (TcGPXI) can reduce fatty acid, phospholipid, and short chain organic hydroperoxides utilizing a novel redox cycle in which enzyme activity is linked to the reduction of trypanothione, a parasite-specific thiol, by glutathione. Here we show that TcGPXI activity can also be linked to trypanothione reduction by an alternative pathway involving the thioredoxin-like protein tryparedoxin. The presence of this new pathway was first detected using dialyzed soluble fractions of parasite extract. Tryparedoxin was identified as the intermediate molecule following purification, sequence analysis, antibody studies, and reconstitution of the redox cycle in vitro. The system can be readily saturated by trypanothione, the rate-limiting step being the interaction of trypanothione with the tryparedoxin. Both tryparedoxin and TcGPXI operate by a ping-pong mechanism. Overexpression of TcGPXI in transfected parasites confers increased resistance to exogenous hydroperoxides. TcGPXI contains a carboxyl-terminal tripeptide (ARI) that could act as a targeting signal for the glycosome, a kinetoplastid-specific organelle. Using immunofluorescence, tagged fluorescent proteins, and biochemical fractionation, we have demonstrated that TcGPXI is localized to both the glycosome and the cytosol. The ability of TcGPXI to use alternative electron donors may reflect their availability at the corresponding subcellular sites

    Common mouse models of tauopathy reflect early but not late human disease

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    BACKGROUND: Mouse models that overexpress human mutant Tau (P301S and P301L) are commonly used in preclinical studies of Alzheimer’s Disease (AD) and while several drugs showed therapeutic effects in these mice, they were ineffective in humans. This leads to the question to which extent the murine models reflect human Tau pathology on the molecular level. METHODS: We isolated insoluble, aggregated Tau species from two common AD mouse models during different stages of disease and characterized the modification landscape of the aggregated Tau using targeted and untargeted mass spectrometry-based proteomics. The results were compared to human AD and to human patients that suffered from early onset dementia and that carry the P301L Tau mutation. RESULTS: Both mouse models accumulate insoluble Tau species during disease. The Tau aggregation is driven by progressive phosphorylation within the proline rich domain and the C-terminus of the protein. This is reflective of early disease stages of human AD and of the pathology of dementia patients carrying the P301L Tau mutation. However, Tau ubiquitination and acetylation, which are important to late-stage human AD are not represented in the mouse models. CONCLUSION: AD mouse models that overexpress human Tau using risk mutations are a suitable tool for testing drug candidates that aim to intervene in the early formation of insoluble Tau species promoted by increased phosphorylation of Tau. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13024-023-00601-y

    Etude des potentialites aromatiques de ferments de fromagerie

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    SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 81970 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

    Synthesis of the C-disaccharide alpha-C(1 -> 3)-L-fucopyranoside of N-acetylgalactosamine

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    Radical C-glycosidation of racemic 5-exo-benzeneselenyl-6-endo-chloro-3-methylidene-7-oxabicyclo[2.2.1]hept an-2-one ((+/-)-2) with alpha -acetobromofucose (3) provided a mixture of alpha -C-fucosides that were reduced with NaBH4 to give two diastereomeric alcohols that were separated readily. One of them ((-)-6) was converted into (-)-methyl 2-acetamido-4-O-acetyl-2,3-dideoxy-3-C(3',4',5'-tri-O-acetyl-2',6'-anhyd ro- 1',7'-dideoxy-alpha -L-glycero-D-galacto-heptitol-1'-C-yl)-alpha -D-galactopyranuronate ((-)-11) and then into (-)-methyl 2-acetamido-2,3-dideoxy-3-C-(2',6'-anhydro- 1',7'-dideoxy-alpha -L-glycero-D-galacto-heptitol- 1'-C-yl)-beta -D-galactopyranoside a new alpha -C(1 -->3)-L-fucopyranoside of N-acetylgalactosamine. Its H-1 NMR data shows that this C-disaccharide (alpha -L-Fucp-(1 -->3)CH2-beta -D-GaINAc-OMe) adopts a major conformation in solution similar to that expected for the corresponding O-linked disaccharide, i.e., with antiperiplanar sigma (C-3',C-2') and sigma (C-1',C-3) bonds

    Stratégies de coping et sentiment de compétence parentale des parents d’enfants atteints de troubles autistiques

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    International audienceIntroductionNumerous studies have been done about the impact of the diagnosis of autism spectrum disorder on the parents’ quality of life and the family as a whole. Confronting child suffering, day-to-day disability management and difficulties in integrating the child have an impact on the physical and mental well-being of parents. Parenting with a child suffering from a disability requires significant cognitive, emotional and behavioral adjustments by the parents. New knowledge in this field would make possible to adjust as much as possible the therapeutic management, in particular in the accompaniment of parents experience and parenting role. The main objective of this study is to identify links between coping strategies of parents to deal with the stressful events induced by the child's disability and their sense of parental competence. The second objective is to observe whether the integration of parents into the therapeutic management of the child has an impact on well-being.MethodThirty-three parents of children with autism spectrum disorder completed the WCC-R, PANAS, QAECEP and ASR. We have studied the links between coping strategies adopted by parents to deal with the stressful events induced by the child's disability and their sense of parental competence, a factor influencing their subjective well-being. We were interested in the consequences of the integration by the professional team of the parent in the care of the child on the feeling of parental competence.ResultsCoping strategies centered on emotions disrupt feelings of parental satisfaction. In addition, parents who are satisfied with their role tend to express a better sense of subjective well-being and parental skill than the less satisfied parents. Finally, the integration of the parent in the child care process promotes the sense of parental competence.ConclusionIt seems important to note that the better the feeling of parental competence, the less the depressive symptomatology is high. The results confirm the need for professional teams in charge of the autism spectrum disorder child to integrate, support and help parents in their parenting role. This support allows them to develop a good sense of parental competence and fosters their sense of well-being.IntroductionLe présent article a pour objectif d’étudier les répercussions de l’autisme de l’enfant sur le bien-être psychique des parents. La parentalité auprès d’un enfant handicapé nécessite d’importants ajustements cognitifs, émotionnels et comportementaux de la part des parents. L’hypothèse principale est que des difficultés d’adaptation dans ces différents domaines pourraient générer de la souffrance et impacter le sentiment de bien-être des parents. De nouvelles connaissances dans ce champ permettraient d’ajuster au mieux les prises en charge thérapeutiques, notamment dans l’accompagnement du parent dans son vécu et son rôle parental.MéthodeTrente-trois parents d’enfants atteints de troubles autistiques ont rempli la WCC-R, la PANAS, le QAECEP et l’ASR. Nous avons étudié les liens existants entre les stratégies de coping adoptées par les parents pour faire face aux évènements stressants induits par le handicap de l’enfant et leur sentiment de compétence parentale, facteur influençant leur bien-être subjectif. Nous nous sommes intéressés aux conséquences de l’intégration, par l’équipe professionnelle, du parent dans la prise en charge de l’enfant sur le sentiment de compétence parentale.RésultatsLes stratégies de coping centré sur les émotions perturbent le sentiment de satisfaction parentale. De plus, les parents satisfaits dans leur rôle ont tendance à exprimer un meilleur sentiment de bien-être subjectif que les parents se disant moins satisfaits. Enfin, l’intégration du parent dans le processus de soin de l’enfant favorise son sentiment de compétence parentale.ConclusionLe soutien des parents leur permettrait de développer un bon sentiment de compétence parentale et de favoriser leur sentiment de bien-être

    Surgical resection of incidental diffuse gliomas involving eloquent brain areas. Rationale, functional, epileptological and oncological outcomes

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    International audienceOBJECTIVE:Incidentally discovered diffuse low-grade gliomas progress in a fashion similar to their symptomatic counterparts. Their early detection allows more effective pre-emptive and individualized oncological treatment. We assessed the safety and efficacy of maximal safe resection according to functional boundaries for incidental diffuse low-grade gliomas in eloquent areas.MATERIAL AND METHODS:Two-centre retrospective series of adult patients with incidental diffuse low-grade gliomas located within/close to eloquent areas in the dominant hemisphere, treated with maximal surgical resection according to functional boundaries under intraoperative functional cortico-subcortical monitoring under awake conditions, and with a minimal follow-up of 24months.RESULTS:The series included 19 patients (8 men, 11 women) with no preoperative neurological deficit but with a radiologically enlarged glioma. No intraoperative seizure, postoperative infection, haematoma or wound-healing problem was observed. In the immediate postsurgical period, a transient neurological worsening occurred in 10 patients. The resection (mean rate 96.4%; range, 82.4-100) was supratotal in 5 cases, total in 5 cases, subtotal in 7 cases, and partial in 2 cases. Six months after surgery, all patients recovered after functional rehabilitation, with no permanent neurological deficit, Karnofsky Performance Status was 100 (except for one patient who received early postoperative radiotherapy) and no seizures were observed. The survival without progression requiring oncological treatment was significantly longer in patients with a total/supratotal resection than in patients with a partial/subtotal resection.CONCLUSIONS:These results suggest the reproducibility, safety, and effectiveness of an early maximal functionally based resection within cortico-subcortical functional boundaries for incidental diffuse low-grade gliomas in adults in centres hyperspecialized in surgical neuro-oncology

    A simple, time- and cost-effective, high-throughput depletion strategy for deep plasma proteomics

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    We introduce a cost-effective, robust high-throughput-compatible plasma depletion method enabling in-depth profiling of plasma that detects >1300 proteins per run with a throughput of 60 samples per day. The method has been fully validated by processing >3000 samples with no apparent batch effect at a cost for the depletion step of similar to$2.5 per sample
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