Reinforcement versus Fluidization in Cytoskeletal Mechanoresponsiveness

Every adherent eukaryotic cell exerts appreciable traction forces upon its substrate. Moreover, every resident cell within the heart, great vessels, bladder, gut or lung routinely experiences large periodic stretches. As an acute response to such stretches the cytoskeleton can stiffen, increase traction forces and reinforce, as reported by some, or can soften and fluidize, as reported more recently by our laboratory, but in any given circumstance it remains unknown which response might prevail or why. Using a novel nanotechnology, we show here that in loading conditions expected in most physiological circumstances the localized reinforcement response fails to scale up to the level of homogeneous cell stretch; fluidization trumps reinforcement. Whereas the reinforcement response is known to be mediated by upstream mechanosensing and downstream signaling, results presented here show the fluidization response to be altogether novel: it is a direct physical effect of mechanical force acting upon a structural lattice that is soft and fragile. Cytoskeletal softness and fragility, we argue, is consistent with early evolutionary adaptations of the eukaryotic cell to material properties of a soft inert microenvironment.

För Alexander [Stemmat]

Soitinnus: orkesteri, sekakuoro.

Reversal of a full-length mutant huntingtin neuronal cell phenotypeby chemical inhibitors of polyglutamine-mediated aggregation

Background: Huntington's disease (HD) is an inherited neurodegenerative disorder triggered by an expanded polyglutamine tract in huntingtin that is thought to confer a new conformational property on this large protein. The propensity of small amino-terminal fragments with mutant, but not wild-type, glutamine tracts to self-aggregate is consistent with an altered conformation but such fragments occur relatively late in the disease process in human patients and mouse models expressing full-length mutant protein. This suggests that the altered conformational property may act within the full-length mutant huntingtin to initially trigger pathogenesis. Indeed, genotypephenotype studies in HD have defined genetic criteria for the disease initiating mechanism, and these are all fulfilled by phenotypes associated with expression of full-length mutant huntingtin, but not amino-terminal fragment, in mouse models. As the in vitro aggregation of amino-terminal mutant huntingtin fragment offers a ready assay to identify small compounds that interfere with the conformation of the polyglutamine tract, we have identified a number of aggregation inhibitors, and tested whether these are also capable of reversing a phenotype caused by endogenous expressionof mutant huntingtin in a striatal cell line from the HdhQ111/Q111 knock-in mouse. Results: We screened the NINDS Custom Collection of 1,040 FDA approved drugs and bioactive compounds for their ability to prevent in vitro aggregation of Q58-htn 1¿171 amino terminal fragment. Ten compounds were identified that inhibited aggregation with IC50 < 15 ¿M, including gossypol, gambogic acid, juglone, celastrol, sanguinarine and anthralin. Of these, both juglone and celastrol were effective in reversing the abnormal cellular localization of full-length mutant huntingtin observed in mutant HdhQ111/Q111 striatal cells. Conclusions: At least some compounds identified as aggregation inhibitors also prevent a neuronal cellular phenotype caused by full-length mutant huntingtin, suggesting that in vitro fragment aggregation can act as a proxy for monitoring the disease-producing conformational property in HD. Thus, identification and testing of compounds that alter in vitro aggregation is a viable approach for defining potential therapeutic compounds that may act on the deleterious conformational property of full-length mutant huntingtin.

L'Intrusisme professional a principis del segle XX. El Dr. James M. Munyon.

RESUM: Presentem al Dr. James M. Munyon, qui a principis del segle passat es dedicà a la manufactura i patent de remeis homeopàtics. Va ser perseguit per frau en múltiples ocasions però la seva gran fortuna li va permetre estendre el seu negoci fins a casa nostra, arribant a assolir grans cotes de popularitat. La revista ¡Cu-Cut! li dedicà tres caricatures els anys 1902 i 1903. A través de l"estudi de les mateixes hem pogut conèixer el Dr. Munyon, un intrús professional de principis del segle XX.

Una propuesta de la integración psicocorporal a través de la técnica Alexander y la danza movimiento terapia

Este trabajo es una propuesta de integración de la Técnica Alexander y la Danza Movimiento Terapia. Partiendo de la realidad de que ambas técnicas tienen como objetivo final la integración de la dimensión de la psique, del cuerpo y de la emoción, para restaurar el equilibrio integral del ser humano que como consecuencia aporta un estado de salud al individuo. Cada una de ellas se posiciona sobre un camino diferente hacia la curación, aunque comparten muchas bases en común. Una de ellas trata del aprendizaje de un método: la Técnica Alexander, y la otra es una forma de psicoterapia para realizar un proceso terapéutico: la Danza Movimiento Terápia. Una se focaliza en la reeducación del uso psicofísico del individuo y en su interacción con el mundo interno y externo (TA) y el otro en la expresión y despliegue psico / corporal / emocional para la transformación y el desarrollo personal, y la curación del trauma (DMT). Como cada una de ellas ha desarrollado un aspecto más profundamente que otro, en el caso de la TA: la estructura psicofísica primaria y estructural orgánica, y la DMT: la emoción: su expresión y capacidad para la transformación. Y es estos aspectos más desarrollados que pueden enriquecer y desarrollar a la otra. Este texto aporta un estudio comparativo entre ambos métodos, los objetivos y la teoría que comparten como los aspectos en los que divergen. Finalmente se propone una hipótesis de integración de la TA, como técnica base de formación psicocorporal del estudiante dentro de un programa de formación de la DMT, y la DMT como técnica psicoterapéutica de acompañamiento de los estudiantes en formación de profesores de la TA.

Lucia di Lammermoor

Pons, Lily (Lucia) ; Votipka, Thelma (Alisa) ; Tucker, Richard (Edgardo) ; Hayward, Thomas (Arturo) ; McCracken, James (Normanno) ; Guarrera, Frank (Enrico) ; Scott, Norman (Raimondo) ; Chorus and Orchestra of the Metropolitan Opera Association, Cleva, Fausto, joht.

História da química e da geologia: Joseph Black e James Hutton como referências para educação em ciências

The second half of eighteenth century is marked by the advancement of chemistry and geology. The first science acquired the law of conservation of mass and this science represented a important support to geology and mineralogy. We say that both became modern science that time. Our aim is to show up some interrelations between history of chemistry and history of geology by means of the study of Joseph Black's and James Hutton's works. We defend that it is positive to science education to understand and approach the relations among different and disciplinary areas of science.

Rebuilding Defenses: Explorations in Norman Fairclough’s Theory of Critical Discourse Analysis

Tutkielmassa eritellään Norman Faircloughin kriittisen diskurssianalyysin teoriaa ja siihen kohdistettua kritiikkiä. Pyrkimyksenä on sovittaa näitä erilaisia näkemyksiä keskenään ja tarjota ratkaisuja yhteen kiriittisen diskurssianalyysin keskeiseen ongelmaan eli emansipaation (sosiaalisten epäkohtien tunnistamisen ja ratkaisemisen) puutteellisuuteen. Teoriaosuudesta esiin nousevia mahdollisuuksia sovelletaan tekstianalyysiin. Tutkimuksen kohteena on teksti Rebuilding America’s Defenses: Strategy, Forces and Resources For a New Century ja jossain määrin sen tuottanut järjestö Project for the New American Century. Näitä tarkastellaan ennen kaikkea sosiaalisina ilmiöinä ja suhteessa toisiinsa. Faircloughin mallin suurimmiksi ongelmiksi muodostuvat perinteinen käsitys kielestä, jonka mukaan kielen järjestelmän abstraktit ja sisäiset suhteet ovat tärkeimpiä, sekä ideologinen vastakkainasettelu kritiikin lähtökohtana. Ensimmäinen johtaa kielellisten tutkimustulosten epätyydyttävään kykyyn selittää sosiaalisia havaintoja ja jälkimmäinen poliittiseen tai maailmankatsomukselliseen väittelyyn, joka ei mahdollista uusia näkemyksiä. Tutkielman lopputulema on, että keskittymällä asiasisältöön kielen rakenteen sijasta ja ymmärtämällä tekstin tuottaja yksittäisenä, rajattuna sosiaalisena toimijana voidaan analyysiin saada avoimuutta ja täsmällisyyttä. Kriittiinen diskurssianalyysi kaipaa tällaista näkemystä kielellisten analyysien tueksi ja uudenlaisen relevanssin löytääkseen.