Etude in vitro de l'activité électrique du tissu nerveux obtenu par culture de biopsies cérébrales humaines adultes

Récemment encore, la neuro-genèse chez le primate adulte était supposée limitée aux régions précises que sont le bulbe olfactif, la zone sous-granulaire de l'hippocampe et la région sous- ventriculaire. Depuis lors, des cellules neurales progénitrices distribuées dans l'ensemble du cortex du primate adulte furent mises en évidence. Cultivées in vitro, ces cellules forment des écosystèmes cellulaires nerveux constitués de progéniteurs neuronaux, d'astrocytes et d'oligo- dendrocytes. Transplantés sur un modèle de primate parkinsonien, certains progéniteurs complètent leur différentiation en neurones matures et développent des propriétés neuro- trophiques et neuro-protectrices. Injectées aux environs d'une lésion cérébrale, ces cellules offrent un bénéfice fonctionnel et comportemental significatif. Le présent projet mesure l'activité électro-physiologique du tissu nerveux obtenu par culture de biopsies corticales humaines adultes, de sorte à déterminer son aptitude à intégrer l'information. Des biopsies corticales humaines adultes furent cultivées in vitro avec succès sur un support Micro-Electrode-Array. Cette technologie permet l'acquisition d'enregistrements électro- physiologiques à l'échelle des circuits, au sein d'un tissu maintenu en culture. En parallèle, une mesure de l'activité à l'échelle cellulaire fut obtenue par l'application du Patch Clamp à des cellules cultivées sur un support de verre. Malgré une culture prolongée et l'induction d'une différentiation neuronale, aucune activité électro-physiologique significative ne put être démontrée. Une analyse phénotypique à un stade intermédiaire de culture montra l'expression prometteuse du marqueur neuronal précoce β-Tubulin-III. Cependant, après l'induction d'une différenciation neuronale, la surprenante co-expression de marqueurs astroglial (GFAP) et neuronal (MAP2) fut constatée. Le silence électro-physiologique issu des enregistrements sur MEA peut être l'oeuvre d'un isolement des cellules électriquement actives, et d'un défaut d'organisation en réseau. Une interposition de tissu glial entre neurones et électrodes peut également absorber le signal. Par ailleurs, les cellules enregistrées par Patch Clamp furent déterminées selon le seul critère morphologique ; leur nature exacte demeure inconnue. Les analyses phénotypiques laissent supposer l'entrée dans une voie de maturation neuronale par l'expression du marqueur β- Tubulin-III. Toutefois le phénotype exprimé au terme du processus de culture reste incertain. Des facteurs de maturation ou environnementaux semblent faire défaut à la complétion d'une différentiation neuronale. La culture de neurones bien différenciés et électriquement actifs appelle de nouvelles études in vivo, ainsi qu'une analyse fine des voies intracellulaires de maturation.

Lamellarin D bioconjugates II: synthesis and cellular internalization of dendrimer and nuclear location signal derivatives

The design and synthesis of Lamellarin D conjugates with a nuclear localization signal peptide and a poly(ethylene glycol)-based dendrimer are described. Conjugates 1-4 were obtained in 8-84% overall yields from the corresponding protected Lamellarin D. Conjugates 1 and 4 are 1.4 to 3.3-fold more cytotoxic than the parent compound against three human tumor cell lines(MDA-MB-231 breast, A-549 lung, and HT-29 colon). Besides, conjugates 3, 4 showed a decrease in activity potency in BJ skin fibroblasts, a normal cell culture. Cellular internalization was analyzed and nuclear distribution pattern was observed for 4, which contains a nuclear localization signalling sequence.

Re-visiting the health care luxury good hypothesis: Aggregation, precision, and publication biases?

[cat] Mentre que una creixent literatura que ha examinat la relació entre la renda i la despesa sanitària suggereix que els serveis sanitaris són un be de luxe (elasticitat renda superior a la unitat), aquesta conclusió es contínuament debatuda atesa l'heterogeneïtat dels resultats. Aquest article testa la hipòtesis dels serveis sanitaris com bens de luxe fent server anàlisi de meta- regressió, particularment analitzant l'existència de biaixos de selecció de publicació, precisió així com biaixos d'agregació. Els resultats apunten l'existència d'un biaix de publicació, robust independentment dels controls analitzats. Els biaixos de precisió i agregació semblen tenir un paper en la generació de les estimacions de l'elasticitat renda. Els nostres resultat suggereixen que l'elasticitat renda dels serveis sanitaris un cop corregir pels biaixos esmentat varien entre 0.26 i 0.84, però no podem rebutjar que la elasticitat renda es igual a la unitat en algunes estimacions de l'elasticitat corregides.

Re-visiting the health care luxury good hypothesis: Aggregation, precision, and publication biases?

[cat] Mentre que una creixent literatura que ha examinat la relació entre la renda i la despesa sanitària suggereix que els serveis sanitaris són un be de luxe (elasticitat renda superior a la unitat), aquesta conclusió es contínuament debatuda atesa l'heterogeneïtat dels resultats. Aquest article testa la hipòtesis dels serveis sanitaris com bens de luxe fent server anàlisi de meta- regressió, particularment analitzant l'existència de biaixos de selecció de publicació, precisió així com biaixos d'agregació. Els resultats apunten l'existència d'un biaix de publicació, robust independentment dels controls analitzats. Els biaixos de precisió i agregació semblen tenir un paper en la generació de les estimacions de l'elasticitat renda. Els nostres resultat suggereixen que l'elasticitat renda dels serveis sanitaris un cop corregir pels biaixos esmentat varien entre 0.26 i 0.84, però no podem rebutjar que la elasticitat renda es igual a la unitat en algunes estimacions de l'elasticitat corregides.

Espectrometria de absorção atômica com atomização eletrotérmica em filamento de tungstênio: uma re-visão crítica

In this review it is presented some aspects of electrothermal atomic absorption spectrometry with tungsten coil (ETAW-AAS) since its beginning until the present days as well as the perspectives for this technique. Some aspects concerning its development and theoretical concepts are discussed. The analytical figures of merit such as limit of detection (LD), characteristic mass (m0), relative standard deviation (RSD), accuracy and precision are evaluated, compared and discussed considering published works. It is also evaluated its advantages, applications, limitations and instrumental development. The use of diode laser as radiation source and its perspectives to ETAW are also discussed.

β1 integrin regulation

Integrins are heterodimeric adhesion receptors mediating adhesion to extracellular matrix proteins and to other cells. Integrins are important in embryonic development, structural integrity of connective tissue, blood thrombus formation, and immune defense system. Integrins are transmembrane proteins whose ligand binding capacity (activity) is regulated by large conformational changes. Extracellular ligand binding or intracellular effector binding to integrin cytoplasmic face regulate integrin activity. Integrins are thus able to mediate bi-directional signaling. Integrin function is also regulated by intracellular location. Integrins are constantly recycled from endocytic vesicles to plasma membrane, and this has been shown to be important for cell migration and invasion as well. Deregulation of integrin functionality can lead to deleterious illnesses, such as bleeding or inflammatory disorders. It is also evident that integrin deregulation is associated with cancer progression. In this study, a novel Beta1 integrin associating protein, Rab21, was characterized. Rab21 binding to integrin cytoplasmic tail was shown to be important for Beta1 integrin endo- and exocytosis – intracellular trafficking. It was furher shown that this interaction has an important role in cell adhesion, migration, as well as in the final step of cell division, cytokinesis. This work showed that abrogation of Rab21 function or β1 integrin endocytic traffic, can lead to defects in cell division and results in formation of multinucleated cells. Multinucleation and especially tetraploidy can be a transient pathway to aneuploidy and tumorigenesis. This work characterized chromosomal deletions in rab21 locus in ovarian and prostate cancer samples and showed that a cell line with rab21 deletion also had impairment in cell division, which could be rescued by Rab21 re-expression. The work demonstrates an important role for Rab21 and Beta1 integrin traffic regulation in cell adhesion and division, and suggests a probable associaton with tumorigenesis. In this study, Beta1 integrin activity regulation was also addressed. A novel cell array platform for genome-scale RNAi screenings was characterized here. More than 4500 genes were knocked-down in prostate cancer cells using siRNA-mediated silencing. The effects on Beta1 integrin activity were analyzed upon knock-downs. The screen identified more that 400 putative regulators of Beta1 integrin activity in prostate cancer. In conclusion, this work will help us to understand complex regulatory pathways involved in cancer cell adhesion and migration.

Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial

Background: Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods: We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results: Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality.

El reposicionamiento: análisis conceptual y causal del fenómeno desde su origen hasta el (re)planteamiento actual

El present estudi té com a finalitat estudiar què és el reposicionament i quins són els factors que l’envolten. Pretén establir quines són les principals causes que condueixen a reposicionar una marca, així com també analitzar si el reposicionament és equivalent que quan va sorgir, o si pel contrari ha evolucionat, i com ho ha fet. Amb aquest estudi intentarem esbrinar com es reposicionen les marques en l’actualitat.

Patriarchal hauntings : re-reading villainy and gender in Daphne du Maurier’s 'Rebecca'

Daphne du Maurier’s popular classic Rebecca (1938) was traditionally marketed as a Gothic romance in which two lovers conquered the evil women that separated them. In more recent years, some feminist critics have provided a very different view of the story as a Gothic narrative about the dangers women suffer under patriarchal control. In this thesis, I propose, through a Gothic Studies and a Gender Studies reading, that the victim/abuser statuses in du Maurier’s novel cannot be equated to femininity and masculinity, respectively. Instead, I argue that villainy in Rebecca comes from being in a powerful position within patriarchy—a position that is occupied by both male and female characters

Creative Industries: a Preliminary Insight to their Location Determinants

This paper is about location decisions of Creative Industries and the role played by existent spatial distribution and agglomeration economies of these kinds of activities in order to analyse their location determinants. Our main statistical source is the REIC (Catalan Manufacturing Establishments Register), which has plant-level microdata on location of new plants. Using Count Data Models, our main results show that location determinants are quite similar between both industries and also both non-creative and creative firms are positively influenced by the specialisation level in Creative Industries of municipalities. Moreover, our results provide evidence that the unobserved ‘creative milieu’ has a limited impact on attracting firms. Keywords: creative industries, creative milieu, count data models, industrial location, agglomeration economies

Minimization of the experimental workload for the prediction of pollutants propagation in rivers. Mathematical modelling and knowledge re-use

The present thesis in focused on the minimization of experimental efforts for the prediction of pollutant propagation in rivers by mathematical modelling and knowledge re-use. Mathematical modelling is based on the well known advection-dispersion equation, while the knowledge re-use approach employs the methods of case based reasoning, graphical analysis and text mining. The thesis contribution to the pollutant transport research field consists of: (1) analytical and numerical models for pollutant transport prediction; (2) two novel techniques which enable the use of variable parameters along rivers in analytical models; (3) models for the estimation of pollutant transport characteristic parameters (velocity, dispersion coefficient and nutrient transformation rates) as functions of water flow, channel characteristics and/or seasonality; (4) the graphical analysis method to be used for the identification of pollution sources along rivers; (5) a case based reasoning tool for the identification of crucial information related to the pollutant transport modelling; (6) and the application of a software tool for the reuse of information during pollutants transport modelling research. These support tools are applicable in the water quality research field and in practice as well, as they can be involved in multiple activities. The models are capable of predicting pollutant propagation along rivers in case of both ordinary pollution and accidents. They can also be applied for other similar rivers in modelling of pollutant transport in rivers with low availability of experimental data concerning concentration. This is because models for parameter estimation developed in the present thesis enable the calculation of transport characteristic parameters as functions of river hydraulic parameters and/or seasonality. The similarity between rivers is assessed using case based reasoning tools, and additional necessary information can be identified by using the software for the information reuse. Such systems represent support for users and open up possibilities for new modelling methods, monitoring facilities and for better river water quality management tools. They are useful also for the estimation of environmental impact of possible technological changes and can be applied in the pre-design stage or/and in the practical use of processes as well.

De re vestiaria

Invocatio: Q.F.F.Q.S.

Aerosol particle size distributions at a traffic exposed site and an urban background location in Oporto, Portugal

Aerosol size distributions from 6 to 700 nm were measured simultaneously at an urban background site and a roadside station in Oporto. The particle number concentration was higher at the traffic exposed site, where up to 90% of the size spectrum was dominated by the nucleation mode. Larger aerosol mode diameters were observed in the urban background site possibly due to the coagulation processes or uptake of gases during transport. Factor analysis has shown that road traffic and the neighbour stationary sources localised upwind affect the urban area thought intra-regional pollutant transport.