Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 0003-4975

hal-01563338
http://hal.univ-brest.fr/hal-01563338
DOI : 10.1016/j.athoracsur.2016.03.093
PUBMED : 27262916

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
DNase I requires Ca²+ and Mg²+ for hydrolyzing double-stranded DNA. However, the number and the location of DNase I ion-binding sites remain unclear, as well as the role of these counter-ions. Using molecular dynamics simulations, we show that bovine pancreatic (bp) DNase I contains four ion-binding pockets. Two of them strongly bind Ca²+ while the other two sites coordinate Mg²+. These theoretical results are strongly supported by revisiting crystallographic structures that contain bpDNase I. One Ca²+ stabilizes the functional DNase I structure. The presence of Mg²+ in close vicinity to the catalytic pocket of bpDNase I reinforces the idea of a cation-assisted hydrolytic mechanism. Importantly, Poisson-Boltzmann-type electrostatic potential calculations demonstrate that the divalent cations collectively control the electrostatic fit between bpDNase I and DNA. These results improve our understanding of the essential role of cations in the biological function of bpDNase I. The high degree of conservation of the amino acids involved in the identified cation-binding sites across DNase I and DNase I-like proteins from various species suggests that our findings generally apply to all DNase I-DNA interactions.
ISSN: 1553-734X

hal-00645165
https://hal.archives-ouvertes.fr/hal-00645165
https://hal.archives-ouvertes.fr/hal-00645165/document
https://hal.archives-ouvertes.fr/hal-00645165/file/journal.pcbi.1001000.pdf
DOI : 10.1371/journal.pcbi.1001000

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Carbon is transported from Earth's surface into its interior at subduction zones. Carbonates in sediments overlying hydrothermally altered rocks (including serpentinites) within the subducted slab are the main carriers of this carbon1. Part of the carbon is recycled back to the surface by volcanism, but some is transferred to the deep Earth1, 2. Redox transformations during shallow subduction control the transfer and long-term fate of carbon, but are poorly explored1, 3. Here we use carbon stable isotopes and Raman spectroscopy to analyse the reduction of carbonate in an exhumed serpentinite-sediment contact in Alpine Corsica, France. We find that highly crystalline graphite was formed during subduction metamorphism and was concentrated in the sediment, within a reaction zone in direct contact with the serpentinite. The graphite in this reaction zone has a carbon isotopic signature (δ13C) of up to 0.8±0.1‰, similar to that of the original calcite that composed the sediments, and is texturally associated with the calcium-bearing mineral wollastonite that is also formed in the process. We use mass-balance calculations to show that about 9% of the total carbonaceous matter in the sedimentary unit results from complete calcite reduction in the reaction zone. We conclude that graphite formation, under reducing and low-temperature conditions, provides a mechanism to retain carbon in a subducting slab, aiding transport of carbon into the deeper Earth.
ISSN: 1752-0894

hal-00903464
https://hal.archives-ouvertes.fr/hal-00903464
DOI : 10.1038/NGEO1827

Éditeur(s) : HAL CCSD
Résumé : National audience
Congrès de la SPTC - Société de Pharmaco-Toxicologie Cellulaire
Paris, France

hal-01122677
https://hal.archives-ouvertes.fr/hal-01122677

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Aims: The aims of this study were to compare short-and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy.Methods: Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short-and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics.Results: No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short-or long-term outcomes.Conclusion: The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery.
ISSN: 0959-8049

hal-01666517
https://hal.univ-lorraine.fr/hal-01666517
DOI : 10.1016/j.ejca.2015.11.024

Éditeur(s) : HAL CCSD European Respiratory Society
Résumé : International audience
Telomerase reverse transcriptase (TERT) or telomerase RNA (TERC) gene mutation is a major monogenic cause of pulmonary fibrosis. Sequencing of TERT/TERC genes is proposed to patients with familial pulmonary fibrosis. Little is known about the possible predictors of this mutation and its impact on prognosis. We retrospectively analysed all the genetic diagnoses made between 2007-2014 in patients with pulmonary fibrosis. We evaluated the prevalence of TERT/TERC disease-Associated variant (DAV), factors associated with a DAV, and the impact of the DAV on survival. 237 patients with pulmonary fibrosis (153 with familial pulmonary fibrosis, 84 with telomere syndrome features without familial pulmonary fibrosis) were tested for TERT/TERC DAV. DAV was diagnosed in 40 patients (16.8%), including five with non-idiopathic interstitial pneumonia. Prevalence of TERT/TERC DAV did not significantly differ between patients with familial pulmonary fibrosis or with only telomere syndrome features (18.2% versus 16.4%). Young age, red blood cell macrocytosis, and low platelet count were associated with the presence of DAV; the probability of DAV was increased for patients 40-60 years. Transplant-free survival was lower with than without TERT/TERC DAV (4.2 versus 7.2 years; p=0.046). TERT/TERC DAV were associated with specific clinical and biological features and reduced transplantfree survival. ©ERS 2016.
ISSN: 0903-1936

hal-01467555
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467555/file/Prevalence%20and%20characteristics%20of%20TERT.pdf
DOI : 10.1183/13993003.02115-2015

Éditeur(s) : HAL CCSD American Society of Hematology
Résumé : International audience
Polycythemia vera (PV) is characterized by an increased RBC mass, spontaneous erythroid colony formation, and the JAK2V617F mutation. PV is associated with a high risk of mesenteric and cerebral thrombosis. PV RBC adhesion to endothelial laminin is increased and mediated by phosphorylated erythroid Lu/BCAM. In the present work, we investigated the mechanism responsible for Lu/BCAM phosphorylation in the presence of JAK2V617F using HEL and BaF3 cell lines as well as RBCs from patients with PV. High levels of Rap1-GTP were found in HEL and BaF3 cells expressing JAK2V617F compared with BaF3 cells with wild-type JAK2. This finding was associated with increased Akt activity, Lu/BCAM phosphorylation, and cell adhesion to laminin that were inhibited by the dominant-negative Rap1S17N or by the specific Rap1 inhibitor GGTI-298. Surprisingly, knocking-down EpoR in HEL cells did not alter Akt activity or cell adhesion to laminin. Our findings reveal a novel EpoR-independent Rap1/Akt signaling pathway that is activated by JAK2V617F in circulating PV RBCs and responsible for Lu/BCAM activation. This new characteristic of JAK2V617F could play a critical role in initiating abnormal interactions among circulating and endothelial cells in patients with PV.
ISSN: 0006-4971

inserm-00821109
http://www.hal.inserm.fr/inserm-00821109
http://www.hal.inserm.fr/inserm-00821109/document
http://www.hal.inserm.fr/inserm-00821109/file/De_Grandis_Blood_2013.pdf
DOI : 10.1182/blood-2012-07-440487

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
ISSN: 1471-2407

hal-01638193
https://hal.archives-ouvertes.fr/hal-01638193
DOI : 10.1186/1471-2407-14-7
PUBMED : 24393405

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
Among 103 patients with multidrug-resistant HIV who initiated raltegravir, etravirine, and darunavir/ritonavir-containing regimen in the ANRS 139 TRIO trial, 100 participated in extended follow-up and continued study treatment until week 96. Among them, 87 (87%) received an optimized background therapy including either nucleoside reverse transcriptase inhibitors or enfuvirtide, they were 78 (78%) at week 96. At week 96, 88% achieved durable virologic response (<50 copies/mL). CD4 response was maintained (median change of +150 cells/mm(3)). No major toxicity was reported. This triple drug combination showed sustained efficacy and thus should be strongly considered for patients with multiclass-resistant virus.
ISSN: 1525-4135

hal-00875207
https://hal.archives-ouvertes.fr/hal-00875207
DOI : 10.1097/QAI.0b013e31824bb720
PUBMED : 22293546

Éditeur(s) : HAL CCSD Springer
Résumé : International audience
Diabetologia
Stockholm, Sweden

hal-01204766
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01204766
DOI : 10.1007/s00125-015-3687-4

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
ISSN: 0007-1048

hal-01668324
https://hal.univ-antilles.fr/hal-01668324
DOI : 10.1111/bjh.14064

Éditeur(s) : HAL CCSD
Résumé : Travaux Pratiques de Biochimie, IUT 2e année. Mise en place d'un réacteur enzymatique. Beta galactosidase. Transformation de l'oNPG en orthonitrophénol et galactose.
https://medihal.archives-ouvertes.fr/medihal-00459248
Terre Sainte, France

Droits : http://creativecommons.org/licenses/by-nc/
medihal-00459248
https://medihal.archives-ouvertes.fr/medihal-00459248
https://medihal.archives-ouvertes.fr/medihal-00459248/image
https://medihal.archives-ouvertes.fr/medihal-00459248/file/tp_biochimie_iut15.jpg

Éditeur(s) : HAL CCSD
Résumé : Travaux Pratiques de Biochimie, IUT 2e année. Mise en place d'un réacteur enzymatique. Beta galactosidase. Transformation de l'oNPG en orthonitrophénol et galactose.
https://medihal.archives-ouvertes.fr/medihal-00459247
Terre Sainte, France

Droits : http://creativecommons.org/licenses/by-nc/
medihal-00459247
https://medihal.archives-ouvertes.fr/medihal-00459247
https://medihal.archives-ouvertes.fr/medihal-00459247/image
https://medihal.archives-ouvertes.fr/medihal-00459247/file/tp_biochimie_iut14.jpg

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Objectif Analyser les caractéristiques virologiques et les complications des syndromes grippaux chez les diabétiques en période hivernale. Patients et Méthodes Étude conduite dans 6 hôpitaux (Montpellier, Lyon, Cochin, Bichat, Limoges, Rennes) au cours de 3 saisons grippales (2012-2013, 2013-2014 et 2014-2015), sur 1 451 adultes hospitalisés avec syndrome grippal récent (début ≤ 7 jours), associant un signe respiratoire (toux, dys-pnée) et un signe systémique (fièvre, céphalées, malaise, myalgies). Les virus respiratoires étaient recherchés par RT-PCR sur prélèvement naso-pharyngé ou LBA (Centre National de Référence, Lyon). La vaccination anti-grippale, la présence d'un diabète, les comorbidités, les complications en cours d'hospitalisation (insuffisance rénale, cardiaque, respiratoire, pneumonie, décès) et la durée moyenne de séjour (DMS) étaient enregistrées. Les facteurs de risque de complications ont été étudiés par régression logistique multivariée ajustée sur âge, sexe, infection grippale, vaccination, diabète et antécédents de pathologies rénale, cardiaque ou respiratoire. Résultats Les hospitalisations ont eu lieu dans des services de maladies respiratoires, médecine interne, MIT et réanimation. Un diabète était présent chez 368 sujets (non traités : 15 %, ADO : 41 %, insuline : 27 %, mixte : 17 %). Les diabétiques étaient plus âgés (71 ± 15 vs 65 ± 20 ans, P < 0,001) et présentaient plus souvent un antécédent de pathologie rénale (18 % vs 8 %, P < 0,00001) ou cardiaque (19 % vs 11 %, P < 0,001). Leur couverture vaccinale était meilleure (60 % vs 46 %). Les données virologiques étaient comparables : grippe 38,9 % (76,1 % type A) vs 39,2 % ; (74,1 % type A) ; autres virus respiratoires : 17,0 % vs 19,9 %. La DMS était un peu plus élevée chez les diabétiques (9,1 ± 9 vs 8,9 ± 11, P = 0,015), avec une tendance à un risque de décès plus élevé (6,25 % vs 3,97 %, P 0,07). En analyse multivariée, le diabète était un facteur de risque de complications à type d'insuffisance rénale (OR : 1,66, IC 95 % : 1,10-2,52) mais pas d'insuffisance cardiaque, respiratoire ou de décès. Les complications n'étaient pas modi-fiées par les résultats virologiques. Conclusions Le diabète est un facteur de risque de complications rénales chez les patients hospitalisés avec syndrome grippal
ISSN: 1262-3636

hal-01300779
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01300779
DOI : 10.1016/S1262-3636(16)30020-9

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
The aim of the present study was to test the effects of hydroxyurea (HU) therapy on clinical, hematological and hemorheological parameters in adult patients with sickle cell anemia (SCA). Hematological and hemorheological parameters were measured in 28 SCA patients before HU therapy (i.e., baseline) and at 6, 12 and 24 months of treatment. RBC deformability was determined by ektacytometry at 30 Pa. RBC aggregation properties were investigated by light-backscatter method. Blood viscosity was measured at 225 s-1 by a cone-plate viscometer. The rates of vaso-occlusive crises and acute chest syndrome were lower at 1 and 2 years of HU therapy compared to baseline. The proportion of patients with leg ulcers tended to decrease after 2 years of treatment. Hemoglobin oxygen saturation improved with HU therapy. HU therapy induced a decrease of platelet and white blood cell counts and a rise in fetal hemoglobin level and mean cell volume. While hemoglobin concentrations increased under HU, blood viscosity remained unchanged all along the study. RBC deformability increased over baseline values at 6 months of HU therapy and continued to rise until the end of the follow-up period. In conclusion, the improvement in RBC deformability probably compensates the increase of hemoglobin on blood viscosity and participates to the improvement of the clinical status of patients.
ISSN: 1386-0291

hal-01668327
https://hal.univ-antilles.fr/hal-01668327
DOI : 10.3233/CH-170280

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: The aims of the study were to assess in patients with advanced HIV disease receiving antiretroviral therapy (ART) intensification with enfuvirtide (i) resistance at virological failure (VF), (ii) impact of baseline tropism on immunovirological response, and (iii) HIV-1 DNA tropism evolution during ART. METHODS: The ANRS 130 APOLLO randomized trial evaluated in naive patients the immunovirological impact of standard ART without (control arm) or with enfuvirtide. Tropism was determined on RNA and DNA by V3-loop sequencing interpreted using the Geno2Pheno algorithm. RESULTS: At baseline the median CD4 cell count was 30 cells/mm(3). Among the 170 patients assessable in this virological substudy, HIV-1 RNA tropism was as follows: 60% of viruses were R5 and 40% were R5X4/X4. HIV-1 DNA tropism was as follows: 54% were R5 and 46% were R5X4/X4. At week 24, 39% and 49% of patients experienced VF in the enfuvirtide and control arms, respectively. In the enfuvirtide arm, only resistance-associated mutations to enfuvirtide were detected. In the control arm, two patients displayed drug-resistant viruses at the time of VF. No impact of baseline tropism was observed on immunovirological response, regardless of the study arm. Among the 25 patients experiencing DNA tropism switch between baseline and week 24, 16 (64%) switched from R5 to R5X4/X4. These latter were mostly successfully suppressed patients receiving enfuvirtide and exhibiting poorer immunological response. CONCLUSIONS: Baseline RNA tropism had no impact on the immunovirological response. Drug resistance mutations were only detected for the fusion inhibitor. Finally, the mechanism of replenishment of the viral cellular reservoir with X4 viruses observed needs to be further analysed.
ISSN: 0305-7453

hal-00875130
https://hal.archives-ouvertes.fr/hal-00875130
DOI : 10.1093/jac/dks455
PUBMED : 23152480

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways
ISSN: 1553-7366

Droits : http://creativecommons.org/licenses/by/
hal-01207287
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287/file/journal.ppat.1005153.pdf
DOI : 10.1371/journal.ppat.1005153

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Whilst it used to affect mostly intravenous drug users and patients who underwent valvular surgery with suboptimal infection control procedures, fungal endocarditis is now mostly observed in patients with severe immunodeficiency (onco-haematology), in association with chronic central venous access and broad-spectrum antibiotic use. The incidence of fungal endocarditis has probably decreased in most developed countries with access to harm-reduction policies (i.e. needle exchange programmes) and with improved infection control procedures during cardiac surgery. Use of specific blood culture bottles for diagnosis of fungal endocarditis has decreased due to optimisation of media and automated culture systems. Meanwhile, the advent of rapid techniques, including fungal antigen detection (galactomannan, mannan/anti-mannan antibodies and β-1,3-d-glucans) and PCR (e.g. universal fungal PCR targeting 18S rRNA genes), shall improve sensitivity and reduce diagnostics delays, although limited data are available on their use for the diagnosis of fungal endocarditis. New antifungal agents available since the early 2000s may represent dramatic improvement for fungal endocarditis: (i) a new class, the echinocandins, has the potential to improve the management of Candida endocarditis owing to its fungicidal effect on yeasts as well as tolerability of increased dosages; and (ii) improved survival in patients with invasive aspergillosis with voriconazole compared with amphotericin B, and this may apply to Aspergillus sp. endocarditis as well, although its prognosis remains dismal. These achievements may allow selected patients to be cured with prolonged medical treatment alone when surgery is considered too risky.
ISSN: 0924-8579

hal-01118441
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118441
DOI : 10.1016/j.ijantimicag.2014.07.003
PUBMED : 25178919

Éditeur(s) : HAL CCSD
Résumé : Travaux Pratiques de Biochimie, IUT 2e année. Mise en place d'un réacteur enzymatique. Beta galactosidase. Transformation de l'oNPG en orthonitrophénol et galactose.
https://medihal.archives-ouvertes.fr/medihal-00459240
Terre Sainte, France

Droits : http://creativecommons.org/licenses/by-nc/
medihal-00459240
https://medihal.archives-ouvertes.fr/medihal-00459240
https://medihal.archives-ouvertes.fr/medihal-00459240/image
https://medihal.archives-ouvertes.fr/medihal-00459240/file/tp_biochimie_iut07.jpg

Éditeur(s) : HAL CCSD
Résumé : International audience
o abstract
Revue Des Maladies Respiratoires

hal-01647076
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647076
DOI : 10.1016/j.rmr.2017.07.022
PUBMED : 28935495