Long-term treatment with insulin induces apoptosis in brown adipocytes: role of oxidative stress

Trying to define the precise role played by insulin regulating the survival of brown adipocytes, we have used rat fetal brown adipocytes maintained in primary culture. The effect of insulin on apoptosis and the mechanisms involved were assessed. Different from the known effects of insulin as a survival factor, we have found that long-term treatment (72 h) with insulin induces apoptosis in rat fetal brown adipocytes. This process is dependent on the phosphatidylinositol 3-kinase/mammalian target of rapamycin/p70 S6 kinase pathway. Short-term treatment with the conditioned medium from brown adipocytes treated with insulin for 72 h mimicked the apoptotic effect of insulin. During the process, caspase 8 activation, Bid cleavage, cytochrome c release, and activation of caspases 9 and 3 are sequentially produced. Treatment with the caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (Z-VAD), prevents activation of this apoptotic cascade. The antioxidants, ascorbic acid and superoxide dismutase, also impair this process of apoptosis. Moreover, generation of reactive oxygen species (ROS), probably through reduced nicotinamide adenine dinucleotide phosphate oxidases, and a late decrease in reduced glutathione content are produced. According to this, antioxidants prevent caspase 8 activation and Bid cleavage, suggesting that ROS production is an important event mediating this process of apoptosis. However, the participation of uncoupling protein-1, -2, and -3 regulating ROS is unclear because their levels remain unchanged upon insulin treatment for 72 h. Our data suggest that the prolonged hyperinsulinemia might cause insulin resistance through the loss of brown adipose tissue.

Présentation du dossier

Présentation du dossier Spinoza politique - Penser la puissance de la multitude Présentation effectuée à titre d'éditeur scientifique du dossier comprenant les articles suivants: - Laurent Bove, A quoi est tenu le corps d'une multitude afin d'échapper à la domination? La leçon de Spinoza dans le Traité politique - Charles Ramond, Le Traité politique de Spinoza - vers une démocratie sans valeurs? - Chantal Jaquet, L'accord affectif de la multitude. Le désir (desiderium) de vengeance comme principe du corps politique - Hugues Poltier, Multitude libre/Multitude serve. Pour une lecture du Traité politique de Spinoza - Jack Stetter, L'Etat comme âme, le citoyen comme soumis et comme résistant

Local effects drive heterozygosity-fitness correlations in an outcrossing long-lived tree.

Heterozygosity-fitness correlations (HFCs) have been used to understand the complex interactions between inbreeding, genetic diversity and evolution. Although frequently reported for decades, evidence for HFCs was often based on underpowered studies or inappropriate methods, and hence their underlying mechanisms are still under debate. Here, we used 6100 genome-wide single nucleotide polymorphisms (SNPs) to test for general and local effect HFCs in maritime pine (Pinus pinaster Ait.), an iconic Mediterranean forest tree. Survival was used as a fitness proxy, and HFCs were assessed at a four-site common garden under contrasting environmental conditions (total of 16 288 trees). We found no significant correlations between genome-wide heterozygosity and fitness at any location, despite variation in inbreeding explaining a substantial proportion of the total variance for survival. However, four SNPs (including two non-synonymous mutations) were involved in significant associations with survival, in particular in the common gardens with higher environmental stress, as shown by a novel heterozygosity-fitness association test at the species-wide level. Fitness effects of SNPs involved in significant HFCs were stable across maritime pine gene pools naturally growing in distinct environments. These results led us to dismiss the general effect hypothesis and suggested a significant role of heterozygosity in specific candidate genes for increasing fitness in maritime pine. Our study highlights the importance of considering the species evolutionary and demographic history and different spatial scales and testing environments when assessing and interpreting HFCs.

Enterografia por tomografia computadorizada: uma avaliação de diferentes contrastes orais neutros

OBJETIVO: O objetivo deste estudo foi avaliar o desempenho de contrastes orais neutros, comparando a capacidade de distensão intestinal, a distinção da parede intestinal, a aceitação e os efeitos colaterais. MATERIAIS E MÉTODOS: Estudo prospectivo, randomizado e duplo-cego em 30 pacientes submetidos a tomografia computadorizada de abdome e pelve com administração de contraste oral neutro, divididos em três grupos: leite, água e polietilenoglicol. Os exames foram analisados quanto ao grau de distensão intestinal e distinção da parede intestinal por dois examinadores em consenso. Os pacientes responderam a um questionário referente ao sabor da solução ingerida e efeitos colaterais. Foram utilizados os testes Kruskal-Wallis e qui-quadrado para as análises estatísticas. RESULTADOS: Distensão intestinal adequada (calibre da alça maior que 2 cm) foi observada em 14 segmentos dos 40 estudados (35%) no grupo leite, em 10 segmentos (25%) no grupo água e em 23 segmentos (57%) no grupo polietilenoglicol (p = 0,01). O preparo com polietilenoglicol resultou na melhor distensão intestinal, porém apresentou o pior sabor e maior incidência de diarreia, referidos pelos pacientes. CONCLUSÃO: O preparo oral com polietilenoglicol promove maior grau de distensão intestinal do que quando se utiliza água ou leite, mas tem pior aceitação, relacionada ao seu sabor e frequência de diarreia.

Postmating-prezygotic isolation between two allopatric populations of Drosophila montana: fertilisation success differs under sperm competition

Postmating but prezygotic (PMPZ) interactions are increasingly recognized as a potentially important early-stage barrier in the evolution of reproductive isolation. A recent study described a potential example between populations of the same species: single matings between Drosophila montana populations resulted in differential fertilisation success because of the inability of sperm from one population (Vancouver) to penetrate the eggs of the other population (Colorado). As the natural mating system of D. montana is polyandrous (females remate rapidly), we set up double matings of all possible crosses between the same populations to test whether competitive effects between ejaculates influence this PMPZ isolation. We measured premating isolation in no-choice tests, female fecundity, fertility and egg-to-adult viability after single and double matings as well as second-male paternity success (P-2). Surprisingly, we found no PMPZ reproductive isolation between the two populations under a competitive setting, indicating no difficulty of sperm from Vancouver males to fertilize Colorado eggs after double matings. While there were subtle differences in how P-2 changed over time, suggesting that Vancouver males' sperm are somewhat less competitive in a first-male role within Colorado females, these effects did not translate into differences in overall P-2. Fertilisation success can thus differ dramatically between competitive and noncompetitive conditions, perhaps because the males that mate second produce higher quality ejaculates in response to sperm competition. We suggest that unlike in more divergent species comparisons, where sperm competition typically increases reproductive isolation, ejaculate tailoring can reduce the potential for PMPZ isolation when recently diverged populations interbreed.

Optimisation d'une approche pour l'analyse de l'expression de gènes au niveau unicellulaire chez des sous-populations spécialisées de lymphocytes T CD4+ humaines

Chez les patients cancéreux, les cellules malignes sont souvent reconnues et détruites par les cellules T cytotoxiques du patient. C'est pourquoi, depuis plusieurs années, des recherches visent à produire des vaccins sensibilisant les cellules de l'immunité adaptative, afin de prévenir certains cancers. Bien que les vaccins ciblant les cellules T CD8+ (cytotoxiques) ont une efficacité in-vitro élevée, un vaccin pouvant cibler les cellules T CD8+ et CD4+ aurait une plus grande efficacité (1-3). En effet, les cellules T helper (CD4+) favorisent la production et la maintenance des cellules T CD8+ mémoires à longue durée de vie. Il existe un grand nombre de sous-types de cellules T CD4+ et leur action envers les cellules cancéreuses est différente. Par exemple, les lymphocytes Treg ont une activité pro-tumorale importante (4) et les lymphocytes Th1 ont une activité anti-tumorale (5). Cependant, le taux naturel des différents sous-types de cellules T CD4+ spécifiques aux antigènes tumoraux est variable. De plus, une certaine flexibilité des différents sous-types de cellules T CD4+ a été récemment démontrée (6). Celle-ci pourrait être ciblée par des protocoles de vaccination avec des antigènes tumoraux administrés conjointement à des adjuvants définis. Pour cela, il faut approfondir les connaissances sur le rôle des cellules T CD4+ spécifiques aux antigènes dans l'immunité anti-tumorale et connaître précisément la proportion des sous-types de cellules T CD4+ activées avant et après la vaccination. L'analyse des cellules T, par la cytométrie de flux, est très souvent limité par le besoin d'un nombre très élevé de cellules pour l'analyse de l'expression protéique. Or dans l'analyse des cellules T CD4+ spécifiques aux antigènes tumoraux cette technique n'est souvent pas applicable, car ces cellules sont présentes en très faible quantité dans le sang et dans les tissus tumoraux. C'est pourquoi, une approche basée sur l'analyse de la cellule T individuelle a été mise en place afin d'étudier l'expression du profil génétique des cellules T CD8+ et CD4+. (7,8) Méthode : Ce nouveau protocole (« single cell ») a été élaboré à partir d'une modification du protocole PCR-RT, qui permet la détection spécifique de l'ADN complémentaire (ADNc) après la transcription globale de l'ARN messager (ARNm) exprimé par une cellule T individuelle. Dans ce travail, nous optimisons cette nouvelle technique d'analyse pour les cellules T CD4+, en sélectionnant les meilleures amorces. Tout d'abord, des clones à profils fonctionnels connus sont générés par cytométrie de flux à partir de cellules T CD4+ d'un donneur sain. Pour cette étape d'optimisation des amorces, la spécificité des cellules T CD4+ n'est pas prise en considération. Il est, donc, possible d'étudier et de trier ces clones par cytométrie de flux. Ensuite, grâce au protocole « single cell », nous testons par PCR les amorces des différents facteurs spécifiques de chaque sous-type des T CD4+ sur des aliquotes issus d'une cellule provenant des clones générés. Nous sélectionnons les amorces dont la sensibilité, la spécificité ainsi que les valeurs prédictives positives et négatives des tests sont les meilleures. (9) Conclusion : Durant ce travail nous avons généré de l'ADNc de cellules T individuelles et sélectionné douze paires d'amorces pour l'identification des sous-types de cellules T CD4+ par la technique d'analyse PCR « single cell ». Les facteurs spécifiques aux cellules Th2 : IL-4, IL-5, IL-13, CRTh2, GATA3 ; les facteurs spécifiques aux cellules Th1 : TNFα, IL-2 ; les facteurs spécifiques aux cellules Treg : FOXP3, IL-2RA ; les facteurs spécifiques aux cellules Th17 : RORC, CCR6 et un facteur spécifique aux cellules naïves : CCR7. Ces amorces peuvent être utilisées dans le futur en combinaison avec des cellules antigènes-spécifiques triées par marquage des multimères pMHCII. Cette méthode permettra de comprendre le rôle ainsi que l'amplitude et la diversité fonctionnelle de la réponse de la cellule T CD4+ antigène-spécifique dans les cancers et dans d'autres maladies. Cela afin d'affiner les recherches en immunothérapie oncologique. (8)

Estudi tècnic dels Cartells de la Festa Major de Vilafranca del Penedès del VINSEUM

L'octubre de 2010 es va iniciar un estudi sobre els cartells de la Festa Majar de Vilafranca que esconserven al Centre de Documentació del Museu de les Cultures del Vi de Catalunya (CDV i VINSEUM)de Vilafranca del Penedes. Aquests cartells són part de la documentació grafica que genera aquestafesta i cronológicament se situen entre el 1907 i el 2007.El treball es va dur a terme mitjanc;ant conven i entre el Museu i la Universitat de Barcelona per ala real ització del Practicum del Máster en Direcció de Projectes de Conservació-Restauració ambI'objectiu d'estudiar I'estat de conservació de la Col·lecció de Cartells del CDV i propasar un seguit derecomanacions practiques per a la seva preservació futura.L'interes que va generar aquest primer estudi va donar pas a la necessitat d'aprofundir en lescaracterístiques tecniques deis Cartells de la Col ·lecció. A més, el fet de poder estudiar una col·leccióde cartells cronológicament correlatius i fets en un mateix Iloc geografic, Catalunya, permetria coneixerI'evo!ució tant de les tecniques d'impressió com deis materials utilitzats en la producció de cartells.En I'estudi es plantejaven dos obj ectius principals: en primer lIoc, recollir el maxim d'informaciósobre els mat erials i les tecniques deis cartells; i en segon, plantej ar la possibi litat de relacionarels diferents materials deis cartells amb el seu estat de conservació, intent ant posar de manifest sirealment els elements constitutius del paper I'havien afectat i si ho feien de la mateixa manera endiferents exemplars.

Fischer-Tropsch Slurry Bubble Column Reactor Modeling

The literature part of the work reviews overall Fischer-Tropsch process, Fischer-Tropsch reactors and catalysts. Fundamentals of Fischer-Tropsch modeling are also presented. The emphasis is on the reactor unit. Comparison of the reactors and the catalysts is carried out to choose the suitable reactor setup for the modeling work. The effects of the operation conditions are also investigated. Slurry bubble column reactor model operating with cobalt catalyst is developed by taking into account the mass transfer of the reacting components (CO and H2) and the consumption of the reactants in the liquid phase. The effect of hydrostatic pressure and the change in total mole flow rate in gas phase are taken into account in calculation of the solubilities. The hydrodynamics, reaction kinetics and product composition are determined according to literature. The cooling system and furthermore the required heat transfer area and number of cooling tubes are also determined. The model is implemented in Matlab software. Commercial scale reactor setup is modeled and the behavior of the model is investigated. The possible inaccuraries are evaluated and the suggestions for the future work are presented. The model is also integrated to Aspen Plus process simulation software, which enables the usage of the model in more extensive Fischer-Tropsch process simulations. Commercial scale reactor of diameter of 7 m and height of 30 m was modeled. The capacity of the reactor was calculated to be about 9 800 barrels/day with CO conversion of 75 %. The behavior of the model was realistic and results were in the right range. The highest uncertainty to model was estimated to be caused by the determination of the kinetic rate.

Ultralujasta teräksestä valmistetun henkilönostimen teleskooppipuomin kehittäminen

Tässä työssä kehitettiin palo- ja pelastuskäyttöön tarkoitettuun henkilönostimeen teleskooppipuomin profiilit. Profiilien valmistusmateriaalina oli kuumavalssattu, ultraluja säänkestävä rakenneteräs. Työssä kehitettiin standardien ja ohjeiden pohjalta laskentapohja, jolla voidaan tutkia teleskooppipuomin jaksojen tukireaktioita, taivutus- ja vääntömomentteja ja leikkaus ja normaalivoimia. Laskentapohjassa voidaan varioida eri kuormitusten suuntia, teleskooppipuomin sivusuuntaista ulottumaa ja nostokulmaa. Profiilien alustavassa mitoituksessa hyödynnettiin paikallisen lommahduksen huomioon ottavia standardeja ja suunnitteluohjeita. Eri poikkileikkausten ominaisuuksia verrattiin keskenään ja profiili valittiin yhdessä kohdeyrityksen kanssa. Alustavan mitoituksen yhteydessä muodostettiin apuohjelma valitulle poikkileikkaukselle, jolla voitiin tutkia profiilin eri muuttujien vaikutusta mm. paikalliseen lommahdukseen ja jäykkyyteen. Laskentapohjaan sisällytettiin myös optimointirutiini, jolla voitiin minimoida poikkileikkauksen pinta-ala ja tätä kautta profiilin massa. Lopullinen mitoitus suoritettiin elementtimenetelmällä. Mitoituksessa tutkittiin alustavasti mitoitettujen profiilien paikallista lommahdusta lineaarisen stabiilius- ja epälineaarisen analyysin pohjalta. Profiilien jännityksiä tutkittiin tarkemmin mm. varioimalla kuormituksia ja osittelemalla elementtien normaalijännityksiä. Diplomityössä kehitetyllä ja analysoidulla teleskooppipuomilla voitiin keventää jaksojen painoja 15-30 %. Sivusuuntainen ulottuma parani samalla lähes 20 % ja nimelliskuorma kasvoi 25 %.

Danos ao DNA promovidos por ácido 5-aminolevulínico: possível associação com o desenvolvimento de carcinoma hepatocelular em portadores de porfiria aguda intermitente

5-Aminolevulinic acid (ALA) is a heme precursor accumulated in acute intermittent porphyria (AIP), which might be associated with hepatocellular carcinoma (HCC) in symptomatic patients. Under metal catalyzed oxidation, ALA and its cyclic dimerization product, 3,6-dihydropyrazine-2,5-dipropanoic acid, produce reactive oxygen species that damage plasmid and calf thymus DNA bases, increase the steady state level of 8-oxo-7,8-dihydro-2´-deoxyguanosine in liver DNA and promote mitochondrial DNA damage. The final product of ALA, 4,5-dioxovaleric acid (DOVA), is able to alkylate guanine moieties, producing adducts. ALA and DOVA are mutagenic in bacteria. This review shows an up-to-date literature data that reinforce the hypothesis that the DNA damage induced by ALA may be associated with the development of HCC in AIP patients.

Profiles of Second Language Learners in Bilingual Education: A Comparative Study of the Characteristics of Finnish and American Students

The purpose of this comparative study is to profile second language learners by exploring the factors which have an impact on their learning. The subjects come from two different countries: one group comes from Milwaukee, US, and the other from Turku, Finland. The subjects have attended bilingual classes from elementary school to senior high school in their respective countries. In the United States, the subjects (N = 57) started in one elementary school from where they moved on to two high schools in the district. The Finnish subjects (N = 39) attended the same school from elementary to high school. The longitudinal study was conducted during 1994-2004 and combines both qualitative and quantitative research methods. A Pilot Study carried out in 1990-1991 preceded the two subsequent studies that form the core material of this research. The theoretical part of the study focuses first on language policies in the United States and Finland: special emphasis is given to the history, development and current state of bilingual education, and the factors that have affected policy-making in the provision of language instruction. Current language learning theories and models form the theoretical foundation of the research, and underpin the empirical studies. Cognitively-labeled theories are at the forefront, but sociocultural theory and the ecological approach are also accounted for. The research methods consist of questionnaires, compositions and interviews. A combination of statistical methods as well as content analysis were used in the analysis. The attitude of the bilingual learners toward L1 and L2 was generally positive: the subjects enjoyed learning through two languages and were motivated to learn both. The knowledge of L1 and parental support, along with early literacy in L1, facilitated the learning of L2. This was particularly evident in the American subject group. The American subjects’ L2 learning was affected by the attitudes of the learners to the L1 culture and its speakers. Furthermore, the negative attitudes taken by L1 speakers toward L2 speakers and the lack of opportunities to engage in activities in the L1 culture affected the American subjects’ learning of L2, English. The research showed that many American L2 learners were isolated from the L1 culture and were even afraid to use English in everyday communication situations. In light of the research results, a politically neutral linguistic environment, which the Finnish subjects inhabited, was seen to be more favorable for learning. The Finnish subjects were learning L2, English, in a neutral zone where their own attitudes and motivation dictated their learning. The role of L2 as a means of international communication in Finland, as opposed to a means of exercising linguistic power, provided a neutral atmosphere for learning English. In both the American and Finnish groups, the learning of other languages was facilitated when the learner had a good foundation in their L1, and the learning of L1 and L2 were in balance. Learning was also fostered when the learners drew positive experiences from their surroundings and were provided with opportunities to engage in activities where L2 was used.

Koulu, oppitunti

Ala-asteen oppitunti. Hiljaisuus. Yskimistä, pientä liikehtimistä, kuiskimista ja kiistelyä. Ei puheääniä.

Koulu, välitunti

Ala-aste. Välitunti loppuu. Kello soi ja lapset juoksevat jonoon. Jalkaralli kolisee.

Koulu, välitunti

Ala-aste. Lapset välitunnilla. Juoksua ja puhetta.