miR-514a regulates the tumour suppressor NF1 and modulates BRAFi sensitivity in melanoma

To identify ‘melanoma-specific’ microRNAs (miRNAs) we used an unbiased microRNA profiling approach to comprehensively study cutaneous melanoma in relation to other solid malignancies, which revealed 233 differentially expressed (≥ 2 fold, p < 0.05) miRNAs. Among the top 20 most significantly different miRNAs was hsa-miR-514a-3p. miR-514a is a member of a cluster of miRNAs (miR-506-514) involved in initiating melanocyte transformation and promotion of melanoma growth. We found miR-514a was expressed in 38/55 (69%) melanoma cell lines but in only 1/34 (3%) other solid cancers. To identify miR-514a regulated targets we conducted a miR-514a-mRNA ‘pull-down’ experiment, which revealed hundreds of genes, including: CTNNB1, CDK2, MC1R, and NF1, previously associated with melanoma. NF1 was selected for functional validation because of its recent implication inacquired resistance to BRAFV600E-targeted therapy. Luciferase-reporter assays confirmed NF1 as a direct target of miR-514a and over-expression of miR-514a in melanoma cell lines inhibited NF1 expression, which correlated with increased survival of BRAFV600E cells treated with PLX4032. These data provide another mechanism for the dysregulation of the MAPK pathway which may contribute to the profound resistance associated with current RAF-targeted therapies.

Portrait of Elly Goldschmidt and her children Ilse and Robert. Portraits Family

Digital Image

Ilse and Robert Goldschmidt with their parents Albert Goldschmidt and Elly nee Schoenbeck grandfather Albert Schoenbeck and great grandmother Sophie Schoenbeck nee Mahler. Portraits Family

Digital Image

Portrait of the engineer and geneologist Robert Goldschmidt Portraits Men

Digital Image

Albert Einstein with Robert Andrews Millikan, Albert Michelson and unidentified men; Pasadena, California Portraits Groups; Men

Digital Image

Portrait of Elly Goldschmidt and her children Ilse and Robert. Portraits Family

Digital Image

Ilse and Robert Goldschmidt with their parents Albert Goldschmidt and Elly nee Schoenbeck grandfather Albert Schoenbeck and great grandmother Sophie Schoenbeck nee Mahler. Portraits Family

Digital Image

Portrait of the engineer and geneologist Robert Goldschmidt Portraits Men

Digital Image

Solomon Robert Kagan papers undated, 1920-1955

Contains correspondence, printed material, and photographs relating to Jews in the medical profession, used as a basis for Kagan's several works on Jews in medicine, including the correspondence of members of the American Physicians Fellowship Committee of the Israel Medical Association; includes also correspondence relating to the Near East and the internationalization of Jerusalem, 1945-1954; and personal correspondence. Among the correspondents are Bernard M. Baruch and Christian A. Herter.

Faster Algorithms for Incremental Topological Ordering.Robert Tarjan

We present two online algorithms for maintaining a topological order of a directed acyclic graph as arcs are added, and detecting a cycle when one is created. Our first algorithm takes O(m 1/2) amortized time per arc and our second algorithm takes O(n 2.5/m) amortized time per arc, where n is the number of vertices and m is the total number of arcs. For sparse graphs, our O(m 1/2) bound improves the best previous bound by a factor of logn and is tight to within a constant factor for a natural class of algorithms that includes all the existing ones. Our main insight is that the two-way search method of previous algorithms does not require an ordered search, but can be more general, allowing us to avoid the use of heaps (priority queues). Instead, the deterministic version of our algorithm uses (approximate) median-finding; the randomized version of our algorithm uses uniform random sampling. For dense graphs, our O(n 2.5/m) bound improves the best previously published bound by a factor of n 1/4 and a recent bound obtained independently of our work by a factor of logn. Our main insight is that graph search is wasteful when the graph is dense and can be avoided by searching the topological order space instead. Our algorithms extend to the maintenance of strong components, in the same asymptotic time bounds.

An estimate of the number of tropical tree species

The high species richness of tropical forests has long been recognized, yet there remains substantial uncertainty regarding the actual number of tropical tree species. Using a pantropical tree inventory database from closed canopy forests, consisting of 657,630 trees belonging to 11,371 species, we use a fitted value of Fisher's alpha and an approximate pantropical stem total to estimate the minimum number of tropical forest tree species to fall between similar to 40,000 and similar to 53,000, i.e., at the high end of previous estimates. Contrary to common assumption, the Indo-Pacific region was found to be as species-rich as the Neotropics, with both regions having a minimum of similar to 19,000-25,000 tree species. Continental Africa is relatively depauperate with a minimum of similar to 4,500-6,000 tree species. Very few species are shared among the African, American, and the Indo-Pacific regions. We provide a methodological framework for estimating species richness in trees that may help refine species richness estimates of tree-dependent taxa.

Redescubrir la finalidad natural : Robert Spaemann y Tomás de Aquino

Resumen: En ocasión de la autobiografía de Robert Spaemann aparecida en 2012, este trabajo examina la lectura que Spaemann hace de la teleología en la doctrina de Santo Tomás de Aquino, especialmente en su obra Natürliche Ziele (2005) que prosigue la versión de 1981. En la primera parte, se estudia la historia de la teleología en el pensamiento filosófico y científico expuesta en «Fines naturales». La finalidad intrínseca en la naturaleza de los seres es conocida con profundidad creciente gracias a Platón, Aristóteles, al estoicismo y a la tradición cristiana. Estos aportes se integran en una estructura teleológica unitaria en el Aquinate. Después acontece una «inversión» de la teleología centrada en la conservación del propio ser y una consideración de los fines como algo externo a la realidad. Con la teoría evolucionista surge la teleonomía que se limita a las reglas del dinamismo, suprimiendo el fin. Con todo, los científicos no logran eliminar los términos «con el fin de» o «para» en su lenguaje. Eso permite proceder a un redescubrimiento de los fines naturales. En la segunda parte, se ve cómo Tomás de Aquino lleva el conocimiento de la finalidad más allá de Aristóteles, porque ella remite a una inteligencia creadora. La teleología implica una teología, aunque no queda del todo claro si es la teología filosófica o la cristiana. Spaemann tiene un planteo ontológico de tipo persuasivo, pero en algunos momentos siente dificultad para superar en el plano teorético a quien se limita a una teleonomía.

Carta enviada por el Dr. Robert Worms a Justo Garate

1 carta (manuscrita) ; 202x145mm.