CELL POLARITY REGULATES ORGAN GROWTH THROUGH THE HIPPO PATHWAY

Defects in apical-basal cell polarity and abnormal expression of cell polarity determinants are linked to human cancer. Loss of polarity is highly correlated with malignancy. In Drosophila, perturbation of apical-basal polarity, including overexpressing the apical determinant Crumbs, can lead to uncontrolled tissue growth. Cells mutant for the basolateral determinant scribble overproliferate and can form neoplastic tumors. Interestingly, scribble mutant clones that arise in wild-type tissues are eliminated and therefore do not manifest their tumorigenic potential. However, the mechanisms by which cell polarity coordinates with growth control pathways in developing organs to achieve appropriate organ size remain obscure. To investigate the function of apical determinants in growth regulation, I investigated the mechanism by which the apical determinant Crumbs affects growth in Drosophila imaginal discs. I found that crumbs gain and loss of function cause overgrowth and induction of Hippo target genes. In addition, Crumbs is required for the proper localization of Expanded, an upstream component of the Hippo pathway. Furthermore, we uncoupled the cell polarity and growth control function of Crb through structure-functional analysis. Taken together, our data identify a role of Crb in growth regulation specifically through modulation of the Hippo pathway. To further explore the role of polarity in growth control, I investigated how cells mutant for basolateral determinants are eliminated by using patches of cells mutant for scribble (scribble mutant clones) as a model system. We found that competitive cell-cell interactions eliminate tumorigenic scribble cells by modulation of the Hippo pathway. The regulation of Hippo signaling is required and sufficient to restrain the tumorous growth of scribble mutant cells. Artificially increasing the relative fitness of scribble mutant cells unleashes their tumorigenic potential. Therefore, we have identified a novel tumor-suppression mechanism that depends on signaling between normal and tumorigenic cells. These data identify evasion of cell competition as a critical step toward malignancy and illustrate a role for wild-type tissue in eliminating abnormal cells and preventing the formation of tumors.

ADHERENS JUNCTIONS AND THE ACTOMYOSIN NETWORK REGULATE ORGAN GROWTH BY MODULATING HIPPO PATHWAY ACTIVITY IN DROSOPHILA

Adherens junctions (AJs) and basolateral modules are important for the establishment and maintenance of apico-basal polarity. Loss of AJs and basolateral module members lead to tumor formation, as well as poor prognosis for metastasis. Recently, in mammalian studies it has been shown that loss of either AJ or basolateral module members deregulate Yorkie activity, the downstream transcriptional effector of the Hippo pathway. Importantly, it is unclear if AJ and basolateral components act through the same or parallel mechanisms to regulate Yorkie activity. Here, we dissect how loss of AJ and basolateral components affects Hippo signaling in Drosophila. Surprisingly, while scrib knock-down tissue displays increased reporter activity autonomously, α-cat knock-down tissue shows a cell autonomous decrease and a cell non-autonomous increase of Hippo reporter activity. We provided several lines of evidence to show the differential regulation in polarity protein localizations and oncogenic cooperative overgrowth by AJs and basolateral complexes. Finally, we show that Hippo pathway activity is induced in α-cat and scrib double knocked-down tissue. Taken together, our results provide evidence to show that basolateral modules and AJs act in parallel to modulate Hippo pathway activity. Non-muscle myosin II is an actomyosin component that interacts with the actin. Non-muscle myosin II also interacts with lgl, though the function of this interaction is not clear. Our lab demonstrated that modulating F-actin regulates Hippo pathway activity, and lgl also has been described as a Hippo pathway regulator. Therefore we suspect that myosin II is also involved in Hippo pathway regulation. We first characterized non-muscle Myosin II as a novel tumor suppressor gene by affecting Hippo pathway activity. Upstream regulators of Myosin II, members in the Rho signaling pathway, also displayed similar phenotypes as the Myosin II knock-down tissues. Apoptosis is also induced in myosin II knock-down tissues, however, blocking cell death does not affect myosin II knock-down induced Hippo activation. Our data suggested hyperactivating myosin II induced F-actin accumulation so therefore induces Hippo target activation. Unexpectedly, we also observed that reducing F-actin activity induced Hippo target activation in vivo. These controversial data indicated that actomyosin may regulate the Hippo pathway through multiple mechanisms.

Ni lo mismo ni lo otro : sobre conocimiento y semejanza en la noética de Tomás de Aquino : antecedentes agustinianos, debates actuales

La noción de semejanza — similitudo — suele resultarle útil a Tomás de Aquino para explicar en qué consiste conocer. Recurre a ella para describir qué es la especie tanto inteligible como sensible así como el verbo mental. Sin embargo, el protagonismo de esta noción lleva anejos, al menos, dos problemas. Frecuentemente los especialistas pretenden explicarlo postulando un presunto precedente aristotélico. No obstante, examinada cuidadosamente, la obra del Estagirita proporciona escasas apariciones de la noción. En este trabajo examino la viabilidad de un precedente agustiniano para las recurrentes semejanzas del Aquinate. Y hay un segundo problema. ¿Cómo conciliar estas preponderantes semejanzas con el supuesto realismo directo que canónicamente se le ha imputado a Tomás? Con respecto a esto, critico algunas interpretaciones que anulan la semejanza tomándola como mero sinónimo de la identidad simpliciter. Finalmente, argumento la tesis de que, según Tomás, la eficacia noética de la semejanza estriba más en la diferencia que en la identidad.

El De Genesi ad litteram de San Agustín en el marco de la literatura hexameral desarrollada por San Basilio, San Ambrosio y San Buenaventura

El artículo desarrolla en perspectiva filosófica y teológica las semejanzas entre los comentarios al Génesis de San Basilio, San Ambrosio y San Buenaventura, teniendo como texto base el comentario de San Agustín. El análisis detallado de las fuentes constata puntos de encuentro, influencias y continuidad en la tradición hexameral aquí representada.

Sundrypeices of the Plate given to the College, 1736 September 18

One-page inventory of the silver, including the weight of each object, donor, and dates; one passage is crossed out, and written diagonal to the inventory are the words "Fort London Farmer London." Docketed on the verso with an address to the Right Honorable Samuel Bishop of York.

Report of Her Majesty's Commissioners appointed to inquire into the state, discipline, studies, and revenues of the University of Dublin, and of Trinity College : together with appendices, containing evidence, suggestions, and correspondence. /

Title is preceded on title page by: Dublin University Commission.

The Aleut language, the elements of Aleut grammar with a dictionary in two parts containing basic vocabularies of Aleut and English,

"Aleut-English dictionary, compiled by Richard Henry Geoghegan. A vocabulary of the Aleutian or Unangan language as spoken on the eastern Aleutian Islands and on the Alaska Peninsula, being a translation of the Russian, 'Slovarʹ aleutsko-lisʹevskago yazyka' or 'Dictionary of the Aleut-Fox language', by Ivan Veniaminov, 1834, with additions and annotations by the compiler": p. 89-124.

The legend of Cathleen and Kevin : a poem /

Sometimes attributed to H.J.M. Mason.

In defense of Harriet Shelley : and other essays /

In defense of Harriet Shelley.--Fenimore Cooper's literary offenses.--Traveling with a reformer.--Private history of the "Jumping frog" story.--Mental telegraphy.--Mental telegraphy again.--What Paul Bourget thinks of us.--A little note to M. Paul Bourget.--The invalid's story.--Stirring times in Austria.--The German Chicago.--Concerning the Jews.--About all kinds of ships.--From the "London times" of 1904.--A majestic literary fossil.--At the appetite cure.--Saint Joan of Arc.--In memoriam.--A biographical sketch.

La règle de Saint Benoît.

Latin and French texts on opposite pages.

Un inédit de saint Anselme? : le traité De unitate divinae essentiae et pluralitate creaturarum d'après Jean de Ripa /

"Le manuscrit B. N. lat. 15.369 nous fournira notre texte de base." - p. 16.

Débat entre un luciférien et un orthodoxe = Altercatio luciferiani et orthodoxi /

Published with the help of the Conseil général du Rhône; the GDR 2135, "Textes pour l'histoire de l'Antiquité tardive" and l'Institut des "Sources Chretiennes" (U.M.R. 5035 du Centre National de la Recherche Scientifique).

Reports on the violation of the rights of nations and of the laws ans customs of war in Belgium.

[Vol. I] includes a preface by J. van den Heuvel, minister of state, reports 1-12, and extracts from the pastoral letter of Cardinal Mercier, archbishop of Malines; vol. II includes reports 13-22, with facsimiles of German soldiers' diaries, correspondence between Cardinal Mercier and the German authorities, the protest of Mgr. Heylen, bishop of Namur, etc., etc., appended.

An examen of the calendar or catalogue of protestan saincts, martyrs, and consellors, deuised by Ion Fox, and prefixed before his great volume, of Acts and monuments ... The first six monethes. This tome appertayneth to the third part of a late treatise of three conuersions of England ... /

Comienza con un doble calendario de enero a mayo, con los santos católicos en el verso y los mártires protestantes en el recto, impreso a doble tinta.

The works of the Reverend William Law, M.A. ...

"Prefatory memoir" signed: G.B.M. [i.e. G. B. Morgan]