Implications physiopathologiques de la Nestine lors du remodelage pulmonaire et cardiaque à la suite de l’infarctus du myocarde, du diabète et de l’hypertension pulmonaire

Il est reconnu que la protéine filamenteuse intermédiaire Nestine est exprimée lors du processus de cicatrisation et du remodelage fibrotique. De plus, nous avons identifié l’expression de la Nestine au sein de deux populations distinctes qui sont directement impliquées dans les réponses de fibroses réparative et réactive. Ainsi, une population de cellules souches neurales progénitrices résidentes du coeur de rat adulte exprime la Nestine et a été identifiée à titre de substrat de l’angiogenèse et de la neurogenèse cardiaque. Également, la Nestine est exprimée par les myofibroblastes cicatriciels cardiaques et il a été établi que la protéine filamenteuse intermédiaire joue un rôle dans la prolifération de ces cellules. Ainsi, l’objectif général de cette thèse était de mieux comprendre les évènements cellulaires impliqués dans la réponse neurogénique des cellules souches neurales progénitrices résidentes cardiaques Nestine(+) (CSNPRCN(+)) lors de la fibrose réparative cardiaque et d’explorer si l’apparition de fibroblastes Nestine(+) est associée avec la réponse de fibrose réactive secondaire du remodelage pulmonaire. Une première publication nous a permis d’établir qu’il existe une régulation à la hausse de l’expression de la GAP43 (growth associated protein 43) et que cet événement transitoire précède l’acquisition d’un phénotype neuronal par les CSNPRCN(+) lors du processus de cicatrisation cardiaque chez le rat ayant subi un infarctus du myocarde. De plus, la surimposition de la condition diabétique de type 1, via l’injection unique de Streptozotocine chez le rat, abolit la réponse neurogénique des CSNPRCN(+), qui est normalement induite à la suite de l’ischémie cardiaque ou de l’administration de 6-hydroxydopamine. Le second article a démontré que le développement aigu de la fibrose pulmonaire secondaire de l’infarctus du myocarde chez le rat est associé avec une augmentation de l’expression protéique de la Nestine et de l’apparition de myofibroblastes pulmonaires Nestine(+). Également, le traitement de fibroblastes pulmonaires avec des facteurs de croissances peptidiques pro-fibrotiques a augmenté l’expression de la Nestine par ces cellules. Enfin, le développement initial de la condition diabétique de type 1 chez le rat est associé avec une absence de fibrose réactive pulmonaire et à une réduction significative des niveaux protéiques et d’ARN messager de la Nestine pulmonaire. Finalement, la troisième étude représentait quant à elle un prolongement de la deuxième étude et a alors examiné le remodelage pulmonaire chronique chez un modèle établi d’hypertension pulmonaire. Ainsi, les poumons de rats adultes mâles soumis à l’hypoxie hypobarique durant 3 semaines présentent un remodelage vasculaire, une fibrose réactive et une augmentation des niveaux d’ARN messager et de la protéine Nestine. De plus, nos résultats ont démontré que la Nestine, plutôt que l’alpha-actine du muscle lisse, est un marqueur plus approprié des diverses populations de fibroblastes pulmonaires activés. Également, nos données suggèrent que les fibroblastes pulmonaires activés proviendraient en partie de fibroblastes résidents, ainsi que des processus de transition épithélio-mésenchymateuse et de transition endothélio-mésenchymateuse. Collectivement, ces études ont démontré que des populations distinctes de cellules Nestine(+) jouent un rôle majeur dans la fibrose réparative cardiaque et la fibrose réactive pulmonaire.

High Styrene–Rubber Ionomers, an Alternative to Thermoplastic Elastomers

High styrene rubber ionomers were prepared by sulfonating styrene–butadiene rubber of high styrene content (high styrene rubber) in 1,2-dichloroethane using acetyl sulfate reagent, followed by neutralization of the precursor acids using methanolic zinc acetate. The ionomers were characterized using X-ray fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), dynamic mechanical analysis (DMA), and also by the evaluation of mechanical properties. The FTIR studies of the ionomer reveal that the sulfonate groups are attached to the benzene ring. The NMR spectra give credence to this observation. Results of DMA show an ionic transition (Ti) in addition to glass–rubber transition (Tg). Incorporation of ionic groups results in improved mechanical properties as well as retention of properties after three cycles of processing

Senescence-associated β-galactosidase activity in the in vitro ovarian stromal fibroblasts

Introduction: A growing biological research field is the cellular senescence, a mechanism that has been associated, under certain circumstances, with malignant transformation. Given the high incidence of ovarian cancer and its main origin from the ovarian surface epithelium, as well as the possibility that an epithelial-mesenchymal transition occurs, we evaluated both the in vitro growth of stromal fibroblasts from the ovarian cortex and their β-galactosidase activity at pH 6, enzyme whose expression is considered as a marker of replicative senescence. Methods: 48 samples of ovarian cortical fibroblasts from donors without a history of cancer were serially cultured until the end of their replicative life. β-galactosidase activity at pH 6 was quantified in each passage by the chemiluminiscent method. As control, we used ovarian epithelial cell cultures from the same donors. The enzyme activity was also evaluated in fibroblasts previously induced to senescence by exposure to hydrogen peroxide. Results: The analysis of the enzyme activity and the replicative capacity taken together showed that the fibroblast cultures reached the senescent state at passages 4-5, as what happened with the control epithelial cells. Fibroblasts induced to senescence showed high variability in the values of enzymatic activity. Conclusions: The similarity between both types of cells in reaching the senescent state deserves to be taken into account in relation to the epithelialmesenchymal transition that has been proposed to explain their behavior in the genesis of cancer arising from ovarian surface epithelium. Low β-galactosidase activity values at pH 6 would suggest possible inactivation of the response pathways to oxidative stress.

Relationships between transition period diet, metabolic parameters and fertility in lactating dairy cows

Cows in severe negative energy balance after calving have reduced fertility, mediated by metabolic signals influencing the reproductive system. We hypothesised that transition diet could alter metabolic status after calving, and thus influence fertility. Multiparous dairy cows were assigned to four transition groups 6 weeks pre-calving and fed: (a) basal control diet (n = 10); (b) basal diet plus barley (STARCH, n = 10); (c) basal diet plus Soypass (high protein, HiPROT, n = 11); or (d) no transition management (NoTRANS, n = 9). All cows received the same lactational diet. Blood samples, body weights and condition scores (BCS) were collected weekly. Fertility parameters were monitored using milk progesterone profiles and were not affected by transition diet. Data from all cows were then combined and analysed according to the pattern of post-partum ovarian activity. Cows with low progesterone profiles had significantly lower insulin-like growth factor-I (IGF-I) and insulin concentrations accompanied by reduced dry matter intakes (DMIs), BCS and body weight. Cows with prolonged luteal activity (PLA) were older and tended to have lower IGF-I. Analysis based on the calving to conception interval revealed that cows which failed to conceive (9/40) also had reduced IGF-I, BCS and body weight. Fertility was, therefore, decreased in cows which were in poor metabolic status following calving. This was reflected in reduced circulating IGF-I concentrations and compromised both ovarian activity and conception. There was little effect of the transition diets on these parameters. (C) 2003 Elsevier Science Inc. All rights reserved.

Dielectric relaxation around the nematic-isotropic transition of liquid crystalline polymers

This study is concerned with a series of acrylate based side-chain liquid crystalline (LC) polymers. Previous studies have shown that these LC polymers have a preference for parallel or perpendicular alignment with respect to the polymer chain which depends on the length of the coupling chain joining the mesogenic unit to the polymer backbone. On the other hand, the dielectric relaxation of these side-chain LC polymers shows a strong relaxation associated to the mesogenic unit dynamics. For samples with parallel alignment, it was found that the dielectric relaxation of the nematic is weaker and broader than the relaxation of the isotropic. By contrast, for samples with perpendicular alignment, the isotropic to nematic transition reduces the broadening the relaxation and increases the relaxation strength. These two features are more evident for samples with short coupling units for which the dielectric relaxation observed appears to be strongly coupled with the backbone dynamics.

Success and failure of grassroots innovations for addressing climate change: the case of the Transition Movement

Grassroots innovations emerge as networks generating innovative solutions for climate change adaptation and mitigation. However, it is unclear if grassroots innovations can be successful in responding to climate change. Little evidence exists on replication, international comparisons are rare, and research tends to overlook discontinued responses in favour of successful ones. We take the Transition Movement as a case study of a rapidly spreading transnational grassroots network, and include both active and non-active local transition initiatives. We investigate the replication of grassroots innovations in different contexts with the aim to uncover general patterns of success and failure, and identify questions for future research. An online survey was carried out in 23 countries (N=276). The data analysis entailed testing the effect of internal and contextual factors of success as drawn from the existing literature, and the identification of clusters of transition initiatives with similar internal and contextual factor configurations. Most transition initiatives consider themselves successful. Success is defined along the lines of social connectivity and empowerment, and external environmental impact. We find that less successful transition initiatives might underestimate the importance of contextual factors and material resources in influencing success. We also find that their diffusion is linked to the combination of local-global learning processes, and that there is an incubation period during which a transition initiative is consolidated. Transition initiatives seem capable of generalising organisational principles derived from unique local experiences that seem to be effective in other local contexts. However, the geographical locations matter with regard to where transition initiatives take root and the extent of their success, and ‘place attachment’ may have a role in the diffusion of successful initatives. We suggest that longitudinal comparative studies can advance our understanding in this regard, as well as inform the changing nature of the definition of success at different stages of grassroots innovation development, and the dynamic nature of local and global linkages.

Climate perspective on the large-scale circulation associated with the transition of the first South Atlantic hurricane

The landfall of Cyclone Catarina on the Brazilian coast in March 2004 became known as the first documented hurricane in the South Atlantic Ocean, promoting a new view oil how large-scale features can contribute to tropical transition. The aim of this paper is to put the large-scale circulation associated with Catarina`s transition in climate perspective. This is discussed in the light of a robust pattern of spatial correlations between thermodynamic and dynamic variables of importance for hurricane formation. A discussion on how transition mechanisms respond to the present-day circulation is presented. These associations help in understanding why Catarina was formed in a region previously thought to be hurricane-free. Catarina developed over a large-scale area of thermodynamically favourable air/sea temperature contrast. This aspect explains the paradox that such a rare system developed when the sea surface temperature was slightly below average. But, although thermodynamics played an important role, it is apparent that Catarina would not have formed without the key dynamic interplay triggered by a high latitude blocking. The blocking was associated with an extreme positive phase of the Southern Annular Mode (SAM) both hemispherically and locally, and the nearby area where Catarina developed is found to be more cyclonic during the positive phase of the SAM. A conceptual model is developed and a `South Atlantic index` is introduced as a useful diagnostic of potential conditions leading to tropical transition in the area, where large-scale indices indicate trends towards more favourable atmospheric conditions for tropical cyclone formation. Copyright (c) 2008 Royal Meteorological Society

Vimentin Expression and Myofibroblast Infiltration Are Early Markers of Renal Dysfunction in Kidney Transplantation: An Early Stage of Chronic Allograft Dysfunction?

Introduction. The objective of this study was to show the morphologic characteristics of allograft renal biopsies in renal transplant patients with stable renal function, which can potentially be early markers of allograft dysfunction, after 5 years of follow-up. Methods. Forty-nine renal transplant patients with stable renal function were submitted to renal biopsies and simultaneous measurement of serum creatinine (Cr). Histology was evaluated using Banff scores, determination of interstitial fibrosis by Sirius red staining and immunohistochemical study of proximal tubule and interstitial compartment (using cytokeratin, vimentin, and myofibroblasts as markers). Biopsies were evaluated according to the presence or absence of the epitheliomesenchymal transition (EMT). The interstitial presence of myofibroblasts and tubular presence of vimentin was also analyzed simultaneously. Renal function was measured over the follow-up period to estimate the reduction of graft function. Results. Median posttransplant time at enrollment was 105 days. Patients were followed for 64.3 +/- 8.5 months. The mean Cr at biopsy time was 1.44 +/- 0.33 mg/dL, and after the follow-up it was 1.29 +/- 0.27 mg/dL. Nine patients (19%) had a reduction of their graft function. Eleven biopsies (22%) had tubulointerstitial alterations according to Banff score. Seventeen biopsies (34%) presented EMT. Fifteen biopsies (32%) had high interstitial expression of myofibroblasts and tubular vimentin. Using Cox multivariate analysis, HLA and high expression of interstitial myofibroblasts and tubular vimentin were associated with reduction of graft function, yielding a risk of 3.3 (P = .033) and 9.8 (P = .015), respectively. Conclusion. Fibrogenesis mechanisms occur very early after transplantation and are risk factors for long-term renal function deterioration.

In situ X-ray diffraction studies of phase transition in Pb1-x La x Zr0.40Ti0.60O3 ferroelectric ceramics

The temperature dependence of the crystalline structure and the lattice parameters of Pb1-xLaxZr0.40Ti0.60O3 ferroelectric ceramic system with 0.00 x 0.21 was determined. The samples with x 0.11 show a cubic-to-tetragonal phase transition at the maximum dielectric permittivity, Tmax. Above this amount and especially for the x = 0.12 sample, a spontaneous phase transition from a relaxor ferroelectric state (cubic phase) to a ferroelectric state (tetragonal phase) is observed upon cooling below the Tmax. Unlike what has been reported in other studies, the x = 0.13, 0.14, and 0.15 samples, which present a more pronounced relaxor behavior, also presents a spontaneous normal-to-relaxor transition, indicated by a cubic to tetragonal symmetry below the Tmax. The origin of this anomaly has been associated with an increase in the degree of tetragonality, confirmed by the measurements of the X-ray diffraction patterns. The differential thermal analysis (DSC) measurements also confirm the existence of these phase transitions.

Glypican-3 regulates migration, adhesion and actin cytoskeleton organization in mammary tumor cells through Wnt signaling modulation

Glypican-3 (GPC3) is a proteoglycan involved in migration, proliferation and cell survival modulation in several tissues. There are many reports demonstrating a downregulation of GPC3 expression in some human tumors, including mesothelioma, ovarian and breast cancer. Previously, we determined that GPC3 reexpression in the murine mammary adenocarcinoma LM3 cells induced an impairment of their in vivo invasive and metastatic capacities together with a higher susceptibility to in vitro apoptosis. Currently, the signaling mechanism of GPC3 is not clear. First, it was speculated that GPC3 regulates the insulin-like growth factor (IGF) signaling system. This hypothesis, however, has been strongly challenged. Recently, several reports indicated that at least in some cell types GPC3 serves as a selective regulator of Wnt signaling. Here we provide new data demonstrating that GPC3 regulates Wnt pathway in the metastatic adenocarcinoma mammary LM3 cell line. We found that GPC3 is able to inhibit canonical Wnt signals involved in cell proliferation and survival, as well as it is able to activate non canonical pathway, which directs cell morphology and migration. This is the first report indicating that breast tumor cell malignant properties can be reverted, at least in part, by GPC3 modulation of Wnt signaling. Our results are consistent with the potential role of GPC3 as a metastasis suppressor.

Overexpression of Vimentin in Canine Prostatic Carcinoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Superfluid Bose-Fermi mixture from weak coupling to unitarity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação da população de células tronco tumorais nas neoplasias da glândula mamária em cadelas

Pós-graduação em Ciência Animal - FMVA

Perfil de expressão dos mIRNAS da família mIR-200 e mIR-192 no rim total e glomérulos isolados de ratos submetidos à restrição protéica in útero

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

TGFβ, pSmad2, p53, p63, E-caderina e Vimentina como marcadores prognósticos em tumores espontâneos de mama de cadelas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)