Flower Forms an Extracellular Code that Reveals the Fitness of a Cell to its Neighbors in Drosophila

SummaryCell competition promotes the elimination of weaker cells from a growing population. Here we investigate how cells of Drosophila wing imaginal discs distinguish “winners” from “losers” during cell competition. Using genomic and functional assays, we have identified several factors implicated in the process, including Flower (Fwe), a cell membrane protein conserved in multicellular animals. Our results suggest that Fwe is a component of the cell competition response that is required and sufficient to label cells as “winners” or “losers.” In Drosophila, the fwe locus produces three isoforms, fweubi, fweLose-A, and fweLose-B. Basal levels of fweubi are constantly produced. During competition, the fweLose isoforms are upregulated in prospective loser cells. Cell-cell comparison of relative fweLose and fweubi levels ultimately determines which cell undergoes apoptosis. This “extracellular code” may constitute an ancient mechanism to terminate competitive conflicts among cells

Chemoenzymatic synthesis of optically active 2-(2- or 4-substituted-1H-imidazol-1-yl)cycloalcanols. Chiral additives for (L)-proline

Enantiopure substituted imidazoles obtained by enzymatic kinetic resolution can be promising candidates as co-catalysts for aldol reactions catalysed by (L)-proline. These additives seem to form supramolecular complexes with the catalyst through the formation of H-bonds, leading to significant improvement in both the reaction rates and selectivity of the reaction. Herein, we present our results on the use of these substituted trans-2-imidazoyl-cycloalkanols as additives for the (L)-proline catalyzed direct aldol reaction between ketones and aromatic aldehydes

Simultaneous inhibition of pan-phosphatidylinositol-3-kinases and MEK as a potential therapeutic strategy in peripheral T-cell lymphomas

Obtained from Haematologica/the Hematology Journal website http://www.haematologica.orgPeripheral T-cell lymphomas are very aggressive hematologic malignancies for which there is no targeted therapy. New, rational approaches are necessary to improve the very poor outcome in these patients. Phosphatidylinositol- 3-kinase is one of the most important pathways in cell survival and proliferation. We hypothesized that phosphatidylinositol- 3-kinase inhibitors could be rationally selected drugs for treating peripheral T-cell lymphomas. Several phosphatidylinositol-3-kinase isoforms were inhibited genetically (using small interfering RNA) and pharmacologically (with CAL-101 and GDC-0941 compounds) in a panel of six peripheral and cutaneous T-cell lymphoma cell lines. Cell viability was measured by intracellular ATP content; apoptosis and cell cycle changes were checked by flow cytometry. Pharmacodynamic biomarkers were assessed by western blot. The PIK3CD gene, which encodes the δ isoform of phosphatidylinositol-3-kinase, was overexpressed in cell lines and primary samples, and correlated with survival pathways. However, neither genetic nor specific pharmacological inhibition of phosphatidylinositol-3-kinase δ affected cell survival. In contrast, the pan-phosphatidylinositol-3-kinase inhibitor GDC-0941 arrested all T-cell lymphoma cell lines in the G1 phase and induced apoptosis in a subset of them. We identified phospho-GSK3b and phospho-p70S6K as potential biomarkers of phosphatidylinositol-3-kinase inhibitors. Interestingly, an increase in ERK phosphorylation was observed in some GDC-0941-treated T-cell lymphoma cell lines, suggesting the presence of a combination of phosphatidylinositol-3-kinase and MEK inhibitors. A highly synergistic effect was found between the two inhibitors, with the combination enhancing cell cycle arrest at G0/G1 in all T-cell lymphoma cell lines, and reducing cell viability in primary tumor T cells ex vivo. These results suggest that the combined treatment of pan-phosphatidylinositol-3-kinase + MEK inhibitors could be more effective than single phosphatidylinositol-3-kinase inhibitor treatment, and therefore, that this combination could be of therapeutic value for treating peripheral and cutaneous T-cell lymphomas.This work was supported by grants from the Asociación Española Contra el Cáncer, Fondo de Investigaciones Sanitarias (PI051623, PI052800 and PI080856), RTICC (RD06/0020/0107) and Ministerio de Ciencia e Innovación (SAF2008-0387-1). EMS is supported by a grant from the Department of Education, Universities and Research of the Basque Government (BFI08.207). MSB is supported by a Contract Miguel Servet from Fondo de Investigaciones Sanitarias (CP11/00018

Guía de saúde infantil : actividades preventivas e de promoción da saúde en pediatría de atención primaria

Se trata de una guía de salud infantil dirigida a los profesionales que trabajan en el ámbito de la asistencia sanitaria a los niños y adolescentes en atención primaria del Sistema Público de Salud de Galicia.Trátase dunha guía de saúde infantil dirixida aos profesionais que traballan no ámbito da asistencia sanitaria aos nenos e adolescentes na atención primaria do Sistema Público de Saúde de Galicia

Política y ética en Aristóteles y Maquiavelo: un contrapunto para pensar la felicidad política.

Este artículo se centra en el trabajo comparativo de  las obras de Aristóteles y Maquiavelo, considerando al concepto de felicidad como su eje principal. Si bien las consideraciones del estagirita en torno a la eudaimonia son ampliamente conocidas, no ocurre lo mismo en el caso del florentino. En consecuencia, partiremos de la formulación de la siguiente hipótesis: el pensamiento de Maquiavelo efectivamente presenta una reflexión en torno a la “felicidad”, aunque de manera soslayada si tomamos como referencia la profundidad que la cuestión adquiere en Aristóteles. A partir del análisis comparativo entre los dos autores proponemos asirnos con un nuevo concepto, el de “felicidad política”.A estos fines, nuestra presentación se articula en tres partes centrales. En la primera, ubicamos brevemente la categoría de eudaimonía en el marco de la filosofía aristotélica, para luego presentar el problema de la felicidad en Maquiavelo. En la segunda parte, nos adentramos en la posibilidad de pensar la categoría “felicidad política” a partir de la comparación entre algunos de los elementos centrales de la eudaimonía aristotélica y la  felicidad política maquiaveliana. Dado este paso, ubicamos a la felicidad política en el marco más amplio del quiebre entre moral religiosa y moral política.

Politics and ethics in Aristotle and Machiavelli: a counterpoint to think political happiness

Este artículo se centra en el trabajo comparativo de las obras de Aristóteles y Maquiavelo, considerando al concepto de felicidad como su eje principal. Si bien las consideraciones del estagirita en torno a la eudaimonia son ampliamente conocidas, no ocurre lo mismo en el caso del florentino. En consecuencia, partiremos de la formulación de la siguiente hipótesis: el pensamiento de Maquiavelo efectivamente presenta una reflexión en torno a la “felicidad”, aunque de manera soslayada si tomamos como referencia la profundidad que la cuestión adquiere en Aristóteles. A partir del análisis comparativo entre los dos autores proponemos asirnos con un nuevo concepto, el de “felicidad política”. A estos fines, nuestra presentación se articula en tres partes centrales. En la primera, ubicamos brevemente la categoría de eudaimonía en el marco de la filosofía aristotélica, para luego presentar el problema de la felicidad en Maquiavelo. En la segunda parte, nos adentramos en la posibilidad de pensar la categoría “felicidad política” a partir de la comparación entre algunos de los elementos centrales de la eudaimonía aristotélica y la felicidad política maquiaveliana. Dado este paso, ubicamos a la felicidad política en el marco más amplio del quiebre entre moral religiosa y moral política.This article centers on the comparative analysis between the works of Aristotle and Machiavelli, taking into account the notion of happiness as its backbone. Although the Stagirite’s remarks regarding eudaimonia are widely known, we can’t state the same about the Florentine. Hence, our point of departure will be the formulation of a brand new hypothesis: Machiavelli’s thought involves a consideration of happiness, though in a shaded fashion if we compare it with the thorough approach developed by the Stagirite. The comparative analysis between both authors is how we intend to grasp this new conception, political happiness. To this end, our paper is articulated in three main sections. In the first one, we briefly recount the category of eudaimonia within the Aristotelic philosophy in order to introduce the issue of happiness in Machiavelli. In the second part, we take a few steps into the prospect of thinking the category of political happiness by relating some of the essential inputs of both Aristotle’s eudaimonia and Machiavelli’s thoughts on happiness. At this stage, we place the political happiness in the frame of the broader scenery of the schism between religious morality and political morality.Fil: Grimmer, Luis Santiago. Universidad Nacional de San Martín. Instituto de Altos Estudios Sociales; ArgentinaFil: Lombardía, Federico Nicolás. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones "Gino Germani"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones "Gino Germani"; Argentin

Proteomics-based validation of genomic data: applications in colorectal cancer diagnosis

13 p.-5 fig.-3 tab.Multiple factors are involved in the translation of functional genomic results into proteins for proteome research and target validation on tumoral tissues. In this report, genes were selected by using DNA microarrays on a panel of colorectal cancer (CRC) paired samples. A large number of up-regulated genes in colorectal cancer patients were investigated for cellular location, and those corresponding to membrane or extracellular proteins were used for a non-biased expression in Escherichia coli. We investigated different sources of cDNA clones for protein expression as well as the influence of the protein size and the different tags with respect to protein expression levels and solubility in E. coli. From 29 selected genes, 21 distinct proteins were finally expressed as soluble proteins with, at least, one different fusion protein. In addition, seven of these potential markers (ANXA3, BMP4, LCN2, SPARC, SPP1, MMP7, and MMP11) were tested for antibody production and/or validation. Six of the seven proteins (all except SPP1) were confirmed to be overexpressed in colorectal tumoral tissues by using immunoblotting and tissue microarray analysis. Although none of them could be associated to early stages of the tumor, two of them (LCN2 and MMP11) were clearly overexpressed in late Dukes' stages (B and C). This proteomic study reveals novel clues for the assembly of a robust and highly efficient high throughput system for the validation of genomic data. Moreover it illustrates the different difficulties and bottlenecks encountered for performing a quick conversion of genomic results into clinically useful proteins.This work was supported in part by Spanish Ministry of Science Grant BIO2003-01481. The costs of publication of this article were defrayed in part by the payment of page charges.Peer reviewe

MicroRNA-22 is induced by vitamin D and contributes to its antiproliferative, antimigratory and gene regulatory effects in colon cancer cells

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review.Vitamin D deficiency is associated with the high risk of colon cancer and a variety of other diseases. The active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates gene transcription via its nuclear receptor (VDR), and posttranscriptional regulatory mechanisms of gene expression have also been proposed. We have identified microRNA-22 (miR-22) and several other miRNA species as 1,25(OH)2D3 targets in human colon cancer cells. Remarkably, miR-22 is induced by 1,25(OH)2D3 in a time-, dose- and VDR-dependent manner. In SW480-ADH and HCT116 cells, miR-22 loss-of-function by transfection of a miR-22 inhibitor suppresses the antiproliferative effect of 1,25(OH)2D3. Additionally, miR-22 inhibition increases cell migration per se and decreases the antimigratory effect of 1,25(OH)2D3 in both cell types. In silico analysis shows a significant overlap between genes suppressed by 1,25(OH)2D3 and miR-22 putative target genes. Consistently, miR-22 inhibition abrogates the 1,25(OH)2D3-mediated suppression of NELL2, OGN, HNRPH1, RERE and NFAT5 genes. In 39 out of 50 (78%) human colon cancer patients, miR-22 expression was found lower in the tumour than in the matched normal tissue and correlated directly with that of VDR. Our results indicate that miR-22 is induced by 1,25(OH)2D3 in human colon cancer cells and it may contribute to its antitumour action against this neoplasia.This work was supported by the Ministerio de Ciencia e Innovación of Spain (SAF2010-18302), Comunidad de Madrid (Colomics2, S2011/BMD-2344) and Fondo Europeo de Desarrollo Regional-Instituto de Salud Carlos III (RD06/0020/0009 to A.M. and RD06/0020/0020 to F.B.).Peer reviewe