Miracle-dz/UniFAR-FTUs huggingface dataset:
Approche intégrative de la réponse d'un organisme marin face au changement climatique : la coquille Saint-Jacques Pecten maximus et les stress thermique et hypoxique

Les ecosystemes cotiers sont parmi les plus vulnerables aux changements globaux actuels, qui entrainent notamment une augmentation de la temperature de l'eau, ainsi que de la frequence des episodes hypoxiques. La coquille Saint-Jacques, Pecten maximus, est une espece subtidale evoluant a des profondeurs de 2 a 210 m. Malgre son interet commercial et un interet ecologique majeur, cette espece n'a fait l'objet que de peu d'etudes au niveau moleculaire. L'objectif de cette these etait de caracteriser les mecanismes moleculaires regissant l'acclimatation de cette espece aux contraintes thermique et hypoxique. Nous avons dans un premier temps caracterise les modifications d'expression des genes/proteines, par des approches transcriptomiques (RNAseq) et proteomiques (2-DE), dans un tissu, le manteau, d'animaux exposes a une contrainte thermique prolongee (56 jours). Nous avons ainsi pu identifier les voies majeures de regulation (eg., AP-1), les grandes fonctions (eg., cytosquelette) et processus (eg., apoptose) impliques dans la reponse, mais egalement d'observer les grandes orientations du metabolisme (eg., degradation des lipides de reserve). La reponse des organismes a l'hypoxie depend de leur maniere de gerer les faibles teneurs en oxygene. Nous avons d'abord, par une approche comparative avec une espece intertidale, la moule (Mytilus spp.), caracterisee la reponse physiologique de la coquille Saint-Jacques a l'hypoxie. Nous avons pu ainsi determiner ses parametres d'oxyregulation, plus particulierement son Point critique en 02 (Pc02). Le developpement d'une approche proteomique, couplant l'effet de la temperature et de l'hypoxie, nous a ensuite permis d'identifier plusieurs proteines (CK2, GLN, etc.) potentiellement impliquees dans la reponse au niveau moleculaire. Enfin, dans l'optique de mieux comprendre la physiologie particuliere de ces mollusques dans leur environnement naturel, nous avons compare les signatures proteomiques de deux populations de P. maximus evoluant dans des ecosystemes contrastes, i.e. en limite nord- (Norvege) et au centre- (Brest) de l'aire de repartition de l'espece. Les resultats suggerent des differences majeures entre les deux populations au niveau du cytosquelette. En conclusion, ce travail ouvre des perspectives nouvelles pour la comprehension des mecanismes moleculaires regissant l'adaptation des mollusques aux contraintes thermiques et hypoxiques, deux stress particulierement importants pour les organismes marins dans le contexte du changement global.
Glioblastome et angiogenèse : profils évolutifs, interaction avec l'invasivité et implications thérapeutiques

Les glioblastomes sont les tumeurs primitives cerebrales les plus agressives de l’adulte. Elles sont caracterisees par une importante neo-angiogenese, conduisant au developpement des anti-VEGF chez ces patients. L’objectif de cette these etait d’identifier de potentiels marqueurs predictifs de l’activite du bevacizumab et d’analyser le profil evolutif des facteurs de l’angiogenese. En situation de recidive d’un gliome de haut grade, si aucun facteur clinique ne semble permettre d’identifier un sous-groupe de patients beneficiant particulierement du bevacizumab, les taux plasmatiques avant traitement de MMP2 et MMP9, inversement correles entre eux suggerant un role biologique distinct mais relie, semblent associes a la reponse, la survie sans progression et la survie globale de patients porteurs de gliome de haut grade traites a la recidive par bevacizumab. Le role potentiel de ces marqueurs est renforce par la cinetique de leurs taux plasmatiques observe sous traitement, Nous avons mis en evidence des resultats superposables chez des patientes porteuses de cancers du sein inflammatoires traites par bevacizumab en situation neo-adjuvante, renforcant l’interet de ces marqueurs. Par ailleurs, l’analyse de la signature angiogenique tissulaire des glioblastomes nouvellement diagnostiques et recidivants nous a permis d’observer une modification de l’expression des facteurs de l’angiogenese avec un possible switch de la voie VEGFR2-HIF1α en faveur de la voie CXCL12-CXCR4 a la recidive. Ces differents resultats permettent d’ouvrir de nouvelles perspectives dans le ciblage de l’angiogenese et dans l’approche therapeutique de patients porteurs de gliome de haut grade.
Objective predictors of response for staple versus laser emphysematous lung reduction.

Recently described surgical approaches to the treatment of emphysema, including buttressed stapled volume reduction and laser coagulation, are associated with variable clinical outcomes. We examined objective preoperative factors as predictors of response to treatment in patients enrolled in a randomized trial of staple versus laser volume-reduction surgery in order to help define patient selection criteria for these procedures. Seventy-two patients with severe symptomatic emphysema without bullae were entered into the protocol (39 staple, 33 laser). Preoperative objective variables (pulmonary function tests, smoking history, demographics, and graded chest computed tomographic [CT] scans) were evaluated as predictors of response to treatment (defined as a change in FEV1) at 3- to 6-mo follow-up, using linear and multivariate regression analysis. Follow-up pulmonary function was obtained on 90% of the 68 patients surviving at 6 mo. Overall improvement was significant only for staple-treated patients, and improved outcome correlated with greater smoking history and younger age for staple-treated patients. When physiologic variables were analyzed, greater smoking history, lower DL(CO), and younger age predicted improved outcome for laser-treated patients. Preoperative FEV1 and gas-exchange variables did not predict outcome in staple-treated patients. When CT scan grading was included in multivariate regression analysis, hyperinflation (increased thoracic gas volume) was the primary predictor of response for laser-treated patients. These findings suggest that younger patients with evidence of advanced emphysematous lung disease and hyperinflation are optimal candidates for lung-volume-reduction surgery, particularly by staple-reduction techniques. Additional studies with long-term follow-up, bilateral procedures, and assessment of other outcome measures must be performed to further define operative criteria for lung-volume-reduction surgery for emphysema.
Lessons from the bare lymphocyte syndrome: molecular mechanisms regulating MHC class II expression

Major histocompatibility complex class II (MHCII) molecules drive the development, activation and homeostasis of CD4* T-helper cells. They play a central role in key processes of the adaptive immune system, such as the generation of T-cell-mediated immune responses, the regulation of antibody production and the development and maintenance of tol erance. It is thus not surprising that the absence of MHCII expression results in a severe primary immunodeficiency disease (the bare lymphocyte syndrome (BLS)). The genetic defects responsible for BLS do not lie within the MHCII locus, but in genes encoding transcription factors required for MHCII expression. A great deal of our current knowledge about the mechanisms regulating expression of MHCII genes has been derived from the study of BLS. Four different MHCII regulatory genes have been identified. These genes encode RFXANK, RFXS, RFXAP and CIITA. The first three are subunits of RFX, a ubiquitously expressed factor that binds to the promoters of all MHCII genes. RFX binds co-operatively with other factors to form a highly stable multiprotein complex referred to as the MHCII enhanceosome. This enhanceosome serves as a landing pad for the co-activator CIITA, which is recruited via protein-protein interactions CIITA is the master control factor for MHCII expression. The highly regulated expression pattern of CIITA ultimately dictates the cell type specificity, induction and level of MHCII expression.
The Efficacy of a Semirigid Ankle Stabilizer to Reduce Acute Ankle Injuries in Basketball

This randomized clinical study was designed to pro spectively determine the efficacy of a semirigid ankle stabilizer in reducing the frequency and severity of acute ankle injuries in basketball. Athletic shoe, playing surface, athlete-exposure, ankle injury history, and brace assignment were either statistically or experimen tally controlled. Participants in the study were 1601 United States Military Academy cadets with no prepar ticipation, clinical, functional, or radiographic evidence of ankle instability. Subjects experienced a total of 13,430 athlete-exposures in the 1990 and 1991 intra mural basketball seasons. Ankle injury was defined as acute trauma to the ankle ligaments that resulted in an athlete's inability to participate in basketball 1 day after the injury. Use of ankle stabilizers significantly reduced the frequency of ankle injuries. Reduction in ankle in juries, however, depended on the nature of injury (fewer contact injuries occurred among those who wore braces). Injury severity was not statistically reduced, and wearing the ankle stabilizer did not affect the fre quency of knee injuries. Attitude toward ankle stabilizer use improved as use of the stabilizer increased.
A preliminary evaluation of next-generation sequencing as a screening tool for targeted genotyping of erythrocyte and platelet antigens in blood donors.

BACKGROUND Matching the compatibility of donor blood with the recipient's antigens prevents alloimmunisation. Next-generation sequencing (NGS) technology is a promising method for extensive blood group and platelet antigen genotyping of blood donors. It circumvents the limitations of detecting known alleles based on predefined polymorphisms and enables targeted sequencing on a massive scale. The aim of this study was to evaluate the NGS AmpliSeq application on the Ion Torrent platform as a screening tool for genotyping blood donors' erythrocyte/platelet antigens. MATERIALS AND METHODS Primers for regions encoding antigens RhD (exons 5, 7), Rhc, RhE/e, Fya/b, Jka/b, M/N, S/s, HPA-1, 2, 3, 5, 15 were designed with Ion AmpliSeq Designer with manual inclusion of RHCE*C primers. DNA libraries of 57 regular blood donors with determined phenotype/genotype (prepared using the Ion AmpliSeq Library Kit and 14 primer pairs) were sequenced on the Ion Torrent PGM using 316v2 chips and 200 bp chemistry. RESULTS Sequencing was successful in all but the MN and HPA-5 regions. Mean sequencing coverage in one experiment was 4,606 reads, except for the RHCE*C region (mean 568 reads). NGS results agreed with the known phenotype/genotype of donors except in one phenotypically Fy(a+b-) case in whom FY*A/FY*B alleles were found. Reading rates for homozygotes were 97-100%, while they were around 50% for heterozygotes. NGS of RHD regions led to identification of mutations in two RhD negative donors. DISCUSSION NGS can be performed as a screening test to determine erythrocyte/platelet antigens in blood donors. This method allowed testing of 48 donors for 14 features (200 bp long) with the depth of a few thousand reads simultaneously, and the estimation of natural chimerism or hemi/homozygotic status. NGS screening can be adjusted to the genetic background of a given tested population.
Expression of the Ets-1 Proto-Oncogene in Melanocytic Lesions

Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in melanocytic lesions. A series of 10 cutaneous melanomas and 24 benign melanocytic lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle upon Tyne, UK) was scored by an average of the mean labeling intensity; no nuclear staining = 0, weak nuclear staining = 1, moderate = 2, and intense = 3. Ets-1 expression was statistically assessed by the one-way analysis of variance (ANOVA) comparing the mean labeling intensity of melanoma to benign melanocytic nevi. All of the benign melanocytic lesions exhibited negative to weak nuclear staining, with an average mean labeling intensity of 0.4. Melanoma in situ exhibited moderate nuclear staining, for a mean labeling intensity of 2.0, whereas all conventional invasive melanomas exhibited moderate to strong nuclear staining, with a mean labeling intensity of 2.7. Metastatic melanoma exhibited very strong nuclear staining, with a mean labeling intensity of 3.0. Invasive desmoplastic melanoma, like melanoma in situ, showed moderate nuclear staining with a mean labeling intensity of 2.1. There was a trend toward more intense staining with melanoma progression. A statistically significant difference in the mean labeling intensity of Ets-1 was seen between invasive melanoma and benign melanocytic nevi (P < .0001). Ets-1 oncoprotein expression, however, does not distinguish among benign melanocytic lesions. Staining intensity and pattern might be a useful adjunct with histomorphology in distinguishing invasive melanoma from benign melanocytic nevi. Furthermore, Ets-1 expression may be an important pathogenic mechanism and predictor of aggressive biologic behavior of cutaneous melanoma, with a trend toward staining intensity increasing as Clark stage increases.
Studies on the Neurotoxicity of 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine: Inhibition of NAD‐Linked Substrate Oxidation by Its Metabolite, 1‐Methyl‐4‐Phenylpyridinium

Abstract: The effects of the parkinsonism‐inducing neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) and its 4‐electron oxidation product 1‐methyl‐4‐phenylpyridinium (MPP+) were studied in isolated mitochondria and in mouse brain striatal slices. ADP‐stimulated oxidation of NAD‐linked substrates was inhibited in a time‐dependent manner by MPP+ (0.1–0.5 mM), but not MPTP, in mitochondria prepared from rat brain, mouse brain, or rat liver. Under identical conditions, succinate oxidation was relatively unaffected. In neostriatal slices prepared from the mouse, a species susceptible to the dopaminergic neurotoxicity of MPTP, incubation with either MPP+ or MPTP caused metabolic changes consistent with inhibition of mitochondnial oxidation, i.e., an increase in the formation of lactate and accumulation of the amino acids glutamate and alanine with concomitant decreases in glutamine and aspartate levels. The changes resulting from incubation with MPTP were prevented by the monoamine oxidase inhibitor pargyline, which blocks formation of MPP+ from MPTP. The results suggest that compromise of mitochondrial function and its metabolic sequelae within dopaminergic neurons could be an important factor in the neurotoxicity observed after MPTP administration.
Polarity of Mature Human Odontoblasts

Odontoblast polarization is based on histological appearance as columnar cells with asymmetric disposition of organelles and plasma membrane domains. However, little is known about the odontoblast plasma membrane organization. We investigated odontoblast membrane polarity using influenza virus hemagglutinin and vesicular stomatitis virus glycoprotein as model proteins in mature human odontoblast organ culture. We also examined the distribution patterns of aquaporin 4 and 5, which are basolateral and apical proteins in epithelial cells, respectively. Confocal microscopy immunofluorescence and electron microscopy demonstrated that the apical markers located at the surface toward pulp and basolateral markers located at the plasma membrane of odontoblast processes. Therefore, odontoblast plasma membrane polarity was different from that in epithelial cells. Also, certain lectins stained odontoblast processes while others stained the soma, reflecting the different natures of their membrane domains. Strong ZO-1 and weaker claudin expression suggest weak tight junctions in the odontoblasts. TGF-β1 showed a tendency to reinstate the expression of selected TJ genes, indicating that TGF-β1 may control odontoblast cell layer integrity by controlling tight junction protein expression.
Elevated testicular temperature modulates expression patterns of sperm proteins in Holstein bulls

The objective of this study was to determine the effects of elevated testicular temperature on the expression patterns of sperm proteins in bulls. Ejaculates were collected from sexually mature Holstein bulls (n = 6) twice weekly for 10 weeks. Testicular temperature was elevated in all bulls by scrotal insulation for 72 consecutive hours during Week 2. Triton X‐100 extracts of sperm proteins were prepared and subjected to SDS–PAGE. Sperm proteins in the 110 kDa range decreased from pre‐thermal insult to Day 28 (start of thermal insult = Day 0), concurrent with decreases in sperm concentration, motility, and morphology, and subsequently increased, approaching pre‐thermal insult values by Day 40. Based on mass spectrometry, this band was comprised of angiotensin converting enzyme (ACE), Hexokinase‐1, and the α‐4 subunit of Na+/K+ATPase. Changes in the expression patterns of these proteins were confirmed by immunoblotting, including the use of a custom antibody against the α‐4 subunit of Na+/K+ATPase (testis‐specific isoform). Furthermore, a 25 kDa sperm protein (identified as tissue inhibitor of metalloproteinase‐2; TIMP‐2), had a low expression level in pre‐thermal insult samples, increased to Day 28 of post‐thermal insult, and subsequently decreased to the pre‐thermal insult level by the end of the experimental period. In conclusion, we identified proteins that may serve as molecular markers of impaired sperm function due to elevated testicular temperature, with important implications for fertility predictions. To our knowledge, this is the first report of the identification of a testis‐specific isoform of Na+/K+ATPase in bovine sperm. Mol. Reprod. Dev. 76: 109–118, 2009. © 2008 Wiley‐Liss, Inc.
Registry for the Evaluation of the PROgnostic value of a novel integrated imaging approach combining Single Photon Emission Computed Tomography with coronary calcification imaging (REPROSPECT).

AIMS Although an added diagnostic and prognostic value of the global coronary artery calcification (CAC) score as an adjunct to single-photon emission computed tomography (SPECT)-myocardial perfusion image (MPI) has been repeatedly documented, none of the previous studies took advantage of the anatomic information provided by the unenhanced cardiac CT. Therefore, no co-registration has so far been used to match a myocardial perfusion defect with calcifications in the subtending coronary artery. To evaluate the prognostic value of integrating SPECT-MPI with CAC images were obtained from non-enhanced cardiac computed tomography (CT) for attenuation correction to predict major adverse cardiac events (MACE). METHODS AND RESULTS Follow-up was obtained in 462 patients undergoing a 1-day stress/rest (99m)Tc-teterofosmin SPECT and non-enhanced cardiac CT for attenuation correction. Survival free of MACE was determined using the Kaplan-Meier method. After integrating MPI and CT findings, patients were divided into three groups (i) MPI defect matched by calcification (CAC ≥ 1) in the subtending coronary artery (ii) unmatched MPI and CT finding (iii) normal finding by MPI and CT. At a mean follow-up of 34.5 ± 13 months, a MACE was observed in 80 patients (33 death, 6 non-fatal myocardial infarction, 9 hospitalizations due to unstable angina, and 32 revascularizations). Survival analysis revealed the most unfavourable outcome (P < 0.001 log-rank test) for patients with a matched finding. CONCLUSION In the present study, a novel approach using a combined integration of cardiac SPECT-CAC imaging allows for refined risk stratification, as a matched defect emerged as an independent predictor of MACE.
A sonic hedgehog signaling domain in the arterial adventitia supports resident Sca1+ smooth muscle progenitor cells

We characterize a sonic hedgehog (Shh) signaling domain restricted to the adventitial layer of artery wall that supports resident Sca1-positive vascular progenitor cells (AdvSca1). Using patched-1 (Ptc1lacZ) and patched-2 (Ptc2lacZ) reporter mice, adventitial Shh signaling activity was first detected at embryonic day (E) 15.5, reached the highest levels between postnatal day 1 (P1) and P10, was diminished in adult vessels, and colocalized with a circumferential ring of Shh protein deposited between the media and adventitia. In Shh−/− mice, AdvSca1 cells normally found at the aortic root were either absent or greatly diminished in number. Using a Wnt1-cre lineage marker that identifies cells of neural crest origin, we found that neither the adventitia nor AdvSca1 cells were labeled in arteries composed of neural crest-derived smooth muscle cells (SMCs). Although AdvSca1 cells do not express SMC marker proteins in vivo, they do express transcription factors thought to be required for SMC differentiation, including serum response factor (SRF) and myocardin family members, and readily differentiate to SMC-like cells in vitro. However, AdvSca1 cells also express potent repressors of SRF-dependent transcription, including Klf4, Msx1, and FoxO4, which may be critical for maintenance of the SMC progenitor phenotype of AdvSca1 cells in vivo. We conclude that a restricted domain of Shh signaling is localized to the arterial adventitia and may play important roles in maintenance of resident vascular SMC progenitor cells in the artery wall.
Steady‐state fluid filtration at different capillary pressures in perfused frog mesenteric capillaries.

1. The theory of steady‐state filtration through capillary walls (Michel, 1984) has been developed and investigated in experiments on single capillaries of the frog mesentery perfused with Ringer solutions containing bovine serum albumin (BSA) and Ficoll 70. 2. In each experiment, the micro‐occlusion technique of Michel, Mason, Curry, Tooke & Hunter (1974) has been used to investigate the relation between fluid movements per unit area of capillary wall (Jv/A) and capillary pressure (Pc) under two sets of conditions in the same vessel. First, the relation has been determined following brief perfusions, where the difference in oncotic pressure across the capillary wall approximated to the perfusate oncotic pressure at all values of Pc. These results are referred to as the transient data. Secondly, the relation was investigated by estimating Jv/A at values of Pc which had been maintained constant during at least 2 min of perfusion prior to the measurement. Under these conditions the concentration of macromolecules in the pericapillary fluid was determined by the steady‐state composition of the filtrate passing through the capillary wall, and these results are referred to as steady‐state data. 3. In all fifteen capillaries investigated, the relationship between Jv/A and Pc was linear for the transient data and conspicuously non‐linear in the steady state. When Pc exceeded the oncotic pressure of the perfusate, steady‐state values for Jv/A lay slightly above but parallel to the transient values for the same vessel. At values of Pc less than the perfusate oncotic pressure, the transient data showed reabsorption of fluid from the tissues, but in the steady state either fluid movements were so small as to be undetected or slight filtration was observed. The steady‐state data followed the pattern predicted by theory. 4. The transient data were used to estimate the reflection coefficient of the capillary wall (sigma) to the macromolecular solute. In seven vessels, the mean sigma to BSA was 0.76 (S.E. of mean +/‐ 0.04) and in eight different vessels mean sigma to Ficoll 70 in the presence of BSA (10 mg ml‐1) was 0.98 (S.E. of mean +/‐ 0.05). The steady‐state data were consistent with the prediction that the oncotic pressure opposing high filtration rates approximates to sigma 2 pi c in the steady state, where pi c is the perfusate oncotic pressure. (ABSTRACT TRUNCATED AT 400 WORDS)