Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: Invasive fungal disease (IFD) remains a major concern in patients with haematological conditions. We describe diagnoses, therapeutic management and outcomes in unselected consecutive patients from haematological facilities treated for suspected or documented IFD. METHODS: In this observational prospective study, children/adults with haematological conditions or haematopoietic stem cell transplantation (HSCT) were recruited upon start of non-prophylactic systemic antifungal treatment in 37 French haematological facilities (December 2007 to December 2008). IFD episodes were classified according to the 2008 EORTC/MSG criteria. RESULTS: The cohort included 419 patients (298 adults and 121 children): 88% haematological malignancies, 28% HSCT recipients and 68% neutropenic. Patients had 423 IFD episodes: 21% mycologically documented (59% probable/proven aspergillosis, 32% proven candidiasis and 9% probable/proven other IFD) and 20% classified as possible IFD. The remaining cases were assigned to two groups: febrile neutropenia (34%) and unclassified (25%), 9% of which were classified as possible/probable/proven IFD by day 7. Treatment was thus initiated early in 59% of patients; liposomal amphotericin B and caspofungin were the most common single-agent therapies. The 12 week mortality was 18% for probable/proven aspergillosis, 15% for proven candidiasis, 10% for probable/proven other IFD, 9% for possible IFD, 3% for febrile neutropenia and 12% for unclassified episodes (log rank P = 0.016); it was dependent on age, complete remission of underlying haematological disease and mechanical ventilation. CONCLUSIONS: In this comprehensive sample of haematological patients receiving antifungal treatment, we observe a widespread resort to early therapy and a low mortality rate, including in patients with probable or proven IFD.
ISSN: 0305-7453

hal-00874741
https://hal.archives-ouvertes.fr/hal-00874741
DOI : 10.1093/jac/dks266
PUBMED : 22850692

Éditeur(s) : HAL CCSD National Academy of Sciences
Résumé : International audience
We applied single-molecule photobleaching to investigate the stoichiometry of human Orai1 and Orai3 channels tagged with eGFP and expressed in mammalian cells. Orai1 was detected predominantly as dimers under resting conditions and as tetramers when coexpressed with C-STIM1 to activate Ca(2+) influx. Orai1 was also found to be tetrameric when coexpressed with STIM1 and evaluated following fixation. We show that fixation rapidly causes release of Ca(2+), redistribution of STIM1 to the plasma membrane, and STIM1/Orai1 puncta formation, and may cause the channel to be in the activated state. Consistent with this possibility, Orai1 was found predominantly as a dimer when coexpressed with STIM1 in living cells under resting conditions. We further show that Orai3, like Orai1, is dimeric under resting conditions and is predominantly tetrameric when activated by C-STIM1. Interestingly, a dimeric Orai3 stoichiometry was found both before and during application of 2-aminoethyldiphenyl borate (2-APB) to activate a nonselective cation conductance in its STIM1-independent mode. We conclude that the human Orai1 and Orai3 channels undergo a dimer-to-tetramer transition to form a Ca(2+)-selective pore during store-operated activation and that Orai3 forms a dimeric nonselective cation pore upon activation by 2-APB.
ISSN: 0027-8424

hal-00873833
https://hal.archives-ouvertes.fr/hal-00873833
DOI : 10.1073/pnas.1114814108
PUBMED : 21987805

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
The organogenesis, histogenesis and growth of larvae of the fighting conch Strombus pugilis (Linne, 1758) were studied over a period of 30 d after hatching in laboratory culture. Early development of S. pugilis was examined by light and scanning electron microscopy. Rearing was conducted at 27 +/- 1 degrees C. Veligers were reared at 200 larvae l(-1) in 4-l containers. Larvae were fed with the microalgae Isochrysis galbana and Nanochloropsis oculata at a concentration of 1,000 cell l(-1). The protoconch at hatching measured 212 +/- 12.14 mu m in length and the shell reached 1,100 +/- 29.11 mu m 29 d after hatching. Development characteristics are described from hatching to settlement. Newly hatched veligers possess two velar lobes, a larval shell consisting of 1.5 whorls, eyespots and a single right tentacle. Late veligers (5-d old larvae) have four velar lobes and two shell whorls and the left tentacle appears. Pediveligers show a functional adult heart at 11 d. Crawling behaviour and settlement were observed from 27 to 31 d. Plantigrades were observed after 29 d, when a functioning proboscis is observed and the velar lobes are lost. This study will facilitate the identification of gastropod larval shells in the plankton and of juveniles in the meiobenthos and will aid aquaculture of Strombus species.
ISSN: 0260-1230

hal-01545910
https://hal.archives-ouvertes.fr/hal-01545910
DOI : 10.1093/mollus/eyv011

Éditeur(s) : HAL CCSD
Résumé : Since its apparition at the end of the second world word, the practice of sport for people suffering with motor deficiency has known numerous and quick evolutions. Initially conceived in the science of rehabilitation therapy, it now integrates more and more the principle of performance by getting closer to “ordinary” sport movements. However, this process of sportivisation is variable depending on the social and cultural context in which it is taking place. Initiated at the start of the 1970’s, Guadeloupe’s Movement for Sport for People with motor impairments has been meeting recurring difficulties in how to organise and federate itself. During this work, we have conducted a survey directly with the local disabled sport associations. Meetings with the principal actors of this movement had been taking place, archives had been gathered and both direct and participative observations had been carried out in order to retrace the collective history and to identify the individual theories utilised in the formation of Guadeloupe’s Movement for Sport for Disabled People. For this we have used the tools of the socio-history and of the organizational analysis and handled the speeches with an analyse of the relationship by opposition (ARO). The main results bring to light that the associative dynamics which structure the sport practices of Guadeloupe’s disabled people are impregnated by a sport logic combined with social, cultural and identity stakes. Therefore the principal thesis defended in the process of the research is that the organisation of Guadeloupe’s Movement for Sport for Disabled People is impregnated by the highly contextual strategies where the identities -sport, Caribbean, disabled- produces some very particular adjustments.
Depuis son apparition à la fin de la seconde guerre mondiale, la pratique sportive des personnes atteintes de déficiences motrices a connu de nombreuses et rapides évolutions. Conçue initialement dans une logique rééducative, elle intègre de plus en plus le principe de performance en se rapprochant du mouvement sportif « ordinaire ». Toutefois, ce processus de sportivisation est variable selon l’espace social et culturel dans lequel il se réalise. Initié dans les années 1970, le mouvement handisportif guadeloupéen rencontre des difficultés récurrentes à s’organiser et à se fédérer. Au cours de ce travail, nous avons réalisé une enquête de terrain auprès des associations handisportives locales. Des entretiens avec les acteurs principaux de ce mouvement ont été conduits, des archives recueillies et des observations directes et participantes effectuées afin de retracer l’histoire collective et de repérer les logiques individuelles mobilisées dans la structuration du mouvement handisport en Guadeloupe. Pour cela nous avons utilisé des outils de la socio-histoire et de l’analyse organisationnelle et traité les discours au travers d’une analyse des relations par opposition (ARO). Les principaux résultats mettent en évidence que les dynamiques associatives structurant la pratique sportive des personnes handicapées motrices en Guadeloupe sont imprégnées par une logique sportive doublée d’enjeux sociaux, culturels et identitaires. Ainsi, la thèse principale défendue au terme de cette recherche est que l’organisation du mouvement handisport en Guadeloupe est marquée par des stratégies fortement contextualisées où la conjugaison des identités – sportive, antillaise, de personne handicapée - produit des ajustements singuliers.
https://hal.archives-ouvertes.fr/tel-01682717

Droits : info:eu-repo/semantics/OpenAccess
tel-01682717
https://hal.archives-ouvertes.fr/tel-01682717
https://hal.archives-ouvertes.fr/tel-01682717/document
https://hal.archives-ouvertes.fr/tel-01682717/file/Approche%20socio-historique%20du%20mouvement%20handisport%20en%20Guadeloupe.pdf

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: The Ras/Raf/MEK/ERK signaling pathway is involved in essential cell processes and it is abnormally activated in similar to 30 % of cancers and cognitive disorders. Two ERK isoforms have been described, ERK1 and ERK2; ERK2 being regarded by many as essential due to the embryonic lethality of ERK2 knock-out mice, whereas mice lacking ERK1 are viable and fertile. The controversial question of why we have two ERKs and whether they have differential functions or display functional redundancy has not yet been resolved. Results: To investigate this question we used a novel approach based on comparing the evolution of ERK isoforms' sequences and protein expression across vertebrates. We gathered and cloned erk1 and erk2 coding sequences and we examined protein expression of isoforms in brain extracts in all major clades of vertebrate evolution. For the first time, we measured each isoforms' relative protein level in phylogenetically distant animals using anti-phospho antibodies targeting active ERKs. We demonstrate that squamates (lizards, snakes and geckos), despite having both genes, do not express ERK2 protein whereas other tetrapods either do not express ERK1 protein or have lost the erk1 gene. To demonstrate the unexpected squamates' lack of ERK2 expression, we targeted each ERK isoform in lizard primary fibroblasts by specific siRNA-mediated knockdown. We also found that undetectable expression of ERK2 in lizard is compensated by a greater strength of lizard's erk1 promoter. Finally, phylogenetic analysis revealed that ERK1 amino acids sequences evolve faster than ERK2' s likely due to genomic factors, including a large difference in gene size, rather than from functional differences since amino acids essential for function are kept invariant. Conclusions: ERK isoforms appeared by a single gene duplication at the onset of vertebrate evolution at least 400 Mya. Our results demonstrate that tetrapods can live by expressing either one or both ERK isoforms, supporting the notion that ERK1/2 act interchangeably. Substrate recognition sites and catalytic cleft are nearly invariant in all vertebrate ERKs further suggesting functional redundancy. We suggest that future ERK research should shift towards understanding the role and regulation of total ERK quantity, especially in light of newly described erk2 gene amplification identified in tumors.
ISSN: 1471-2148

hal-01546165
https://hal.archives-ouvertes.fr/hal-01546165
DOI : 10.1186/s12862-015-0450-x

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: The TGF-β transforming growth factor is the most pleiotropic cytokine controlling a broad range of cellular responses that include proliferation, differentiation and apoptosis. The context-dependent multifunctional nature of TGF-β is associated with complex signaling pathways. Differential models describe the dynamics of the TGF-β canonical pathway, but modeling the non-canonical networks constitutes a major challenge. Here, we propose a qualitative approach to explore all TGF-β-dependent signaling pathways. RESULTS: Using a new formalism, CADBIOM, which is based on guarded transitions and includes temporal parameters, we have built the first discrete model of TGF-β signaling networks by automatically integrating the 137 human signaling maps from the Pathway Interaction Database into a single unified dynamic model. Temporal property-checking analyses of 15934 trajectories that regulate 145 TGF-β target genes reveal the association of specific pathways with distinct biological processes. We identify 31 different combinations of TGF-β with other extracellular stimuli involved in non-canonical TGF-β pathways that regulate specific gene networks. Extensive analysis of gene expression data further demonstrates that genes sharing CADBIOM trajectories tend to be co-regulated. CONCLUSIONS: As applied here to TGF-β signaling, CADBIOM allows, for the first time, a full integration of highly complex signaling pathways into dynamic models that permit to explore cell responses to complex microenvironment stimuli.
ISSN: 1752-0509

inserm-00978313
http://www.hal.inserm.fr/inserm-00978313
http://www.hal.inserm.fr/inserm-00978313/document
http://www.hal.inserm.fr/inserm-00978313/file/1752-0509-8-30.pdf
DOI : 10.1186/1752-0509-8-30

Éditeur(s) : HAL CCSD
Résumé : International audience
Seven individuals of a single morphotype of mussels (Bivalvia: Mytilidae) were found attached to a naturally sunken whale intervertebral disk collected in Guadeloupe (Caribbean) at 800 m depth. These specimens resemble small Idas mussels which are found worldwide at cold seeps and hydrothermal vents, and typically harbor ectosymbiotic bacteria on their gills upon which they depend for nutrition. Based on multi-locus gene sequencing, these specimens appear to belong to a new species closely related to two species now included within the genus Terua. Unexpectedly, its closest relatives are found in the Pacific, questioning how this species has reached the Antilles arc. Based on marker gene sequence analysis, electron and fluorescence microscopy, Terua n. sp. harbors two distinct and abundant extracellular bacterial symbionts located between microvilli at the apical surface of host gill epithelial cells. One is a sulfur-oxidizing bacterium similar to the symbionts previously identified in several deep-sea mussels, while the other is related to Colwellia species, a group of cold-adapted heterotrophic bacteria able to degrade organic compounds. This study provides the first evidence for the existence of a dual symbiosis in mussels from whale fall ecosystems in the Caribbean. The evolutionary history of Terua n. sp. and potential role of its Colwellia symbionts are discussed.
Deep Sea Research Part I: Oceanographic Research Papers

hal-01336943
http://hal.upmc.fr/hal-01336943
http://hal.upmc.fr/hal-01336943/document
http://hal.upmc.fr/hal-01336943/file/Duperron_Colwellia_and.pdf
DOI : 10.1016/j.dsr.2016.05.012