Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection due to Aspergillus fumigatus and other Aspergillus spp. Drugs targeting the fungal cell membrane (triazoles, amphotericin B) or cell wall (echinocandins) are currently the sole therapeutic options against IA. Their limited efficacy and the emergence of resistance warrant the identification of new antifungal targets. Histone deacetylases (HDACs) are enzymes responsible of the deacetylation of lysine residues of core histones, thus controlling chromatin remodeling and transcriptional activation. HDACs also control the acetylation and activation status of multiple non-histone proteins, including the heat shock protein 90 (Hsp90), an essential molecular chaperone for fungal virulence and antifungal resistance. This review provides an overview of the different HDACs in Aspergillus spp. as well as their respective contribution to total HDAC activity, fungal growth, stress responses, and virulence. The potential of HDAC inhibitors, currently under development for cancer therapy, as novel alternative antifungal agents against IA is discussed.

Rentabilidade da cultura da macieira cultivar Gala em duas densidades de plantio

O presente trabalho discute, com base em um estudo de caso, a viabilidade econômica de ampliar a densidade de plantio de macieiras cultivar Gala de 1.000 plantas por hectare para 3.378 plantas por hectare. Os resultados mostraram que a taxa interna de retorno não variou (próxima de 1,61% ao mês), independentemente da densidade utilizada, o que sugere o uso da menor densidade de plantio, uma vez que esta requer um menor volume de recursos financeiros. O custo unitário de produção também se mantém praticamente o mesmo ao se variar a densidade de plantio.

Evaluación competencial de los estudiantes de trabajo social

Con la finalidad de evaluar la implementación de los grados de Trabajo Social y de Educación Social, una vez han sido desplegados en su totalidad, desde el Equipo de Coordinación de Grado de la Facultad de Educación Social y Trabajo Social Pere Tarrés de la Universidad Ramón Llull (Barcelona) nos planteamos la necesidad de evaluar los resultados obtenidos. En esta comunicación presentamos una de las acciones que consiste en evaluar la percepción de los estudiantes sobre la adquisición de las competencias del prácticum, las propuestas de mejora para las titulaciones, y los resultados obtenidos en el Grado de Trabajo Social.

Expression of genes encoding the pre-TCR and CD3 complex during thymus development.

The mature TCR is composed of a clonotypic heterodimer (alpha beta or gamma delta) associated with the invariant CD3 components (gamma, delta, epsilon and zeta). There is now considerable evidence that more immature forms of the TCR-CD3 complex (consisting of either CD3 alone or CD3 associated with a heterodimer of TCR beta and pre-T alpha) can be expressed at the cell surface on early thymocytes. These pre-TCR complexes are believed to be necessary for the ordered progression of early T cell development. We have analyzed in detail the expression of both the pre-TCR and CD3 complex at various stages of adult thymus development. Our data indicate that all CD3 components are already expressed at the mRNA level by the earliest identifiable (CD4lo) thymic precursor. In contrast, genes encoding the pre-TCR complex (pre-T alpha and fully rearranged TCR beta) are first expressed at the CD44loCD25+CD4-CD8- stage. Detectable surface expression of both CD3 and TCR beta are delayed relative to expression of the corresponding genes, suggesting the existence of other (as yet unidentified) components of the pre-TCR complex.

Les Estratègies d'accés a la universitat via cicle formatiu de grau superior

Les inèrcies de la institució educativa avancen a un ritme més pausat que els reptes socials que es plantegen, donant com a una de les conseqüències el fet que l'origen social continua sent un factor explicatiu de l'èxit educatiu.Són moltes les teories que apunten que l'economia global en la qual estem immersos requereix d'un augment dels requeriments educatius col•lectius. És en aquest context en el qual analitzarem l'accés a la Universitat des dels Cicles Formatius de Grau Superior partint de la hipòtesi que aquesta és una via que afavoreix la consecució del'objectiu d'augmentar els titulats superiors, sota un prisma d'equitat d'oportunitats.

El Acceso a la universidad en el estado español en 2009: los condicionantes en el acceso y la dimensión transicional

Presentamos una actualización del análisis del acceso a la universidad española a partir de datos del módulo de la EPA 2009, un módulo que nos permite analizar también a los jóvenes independizados. Identificamos los principales condicionantes considerados y construimos un modelo de elección, añadiendo además aspectos biográficos en el análisis para mostrar la importancia de la trayectoria vital del joven en el acceso a la universidad. Las desigualdades de acceso están presentes en 2009 y tienen un impacto en la equidad social.

Meédicaments: une cause sous-estimée d'hypertension artérielle [Drugs: an underestimated cause of arterial hypertension].

In Switzerland, as in other Occidental countries, the prevalence of arterial hypertension (AHT) in the adult population is around 30-40%. Among the causes of secondary AHT, drug induced hypertension is sometimes omitted. Many molecules can induce AHT or worsen it due to an interaction with anti hypertensive drugs. Among these, NSAIDs and anti depressants, widely prescribed, should be used with caution, particularly in patients at risk, namely: those with preexisting AHT, the elderly, or patients suffering from kidney disease, diabetes, and/or heart failure. Increases in blood pressure have also been described with anti-vascular endothelial growth factor (VEGF) drugs, used in the treatment of (metastatic) cancer. A thorough anamnesis of drugs, including over the counter ones, should be performed in every hypertensive patient, and can avoid cumbersome and unnecessary investigations and therapy.

Mortality rates in by-caught loggerhead turtle Caretta caretta in the Mediterranean Sea and implications for the Atlantic populations

Reliable estimates of the post-release mortality probability of marine turtles after incidental by-catch are essential for assessing the impact of longline fishing on these species.Large numbers of loggerhead turtles Caretta caretta from rookeries in the northwestern Atlantic Ocean have been by-caught annually in the southwestern Mediterranean Sea since the 1980s, but nothing is known about their post-release mortality probability under natural conditions. Pop-up archival transmitting tags were attached to 26 loggerhead turtles following incidental capture by Spanish longliners. Hooks were not removed, and 40 cm of line was left in place. The post-release mortality probability during the 90 d following release ranged from 0.308 to 0.365, and was independent of hook location. When the post-release mortality probability was combined with previously reported estimates of the mortality probability before hauling, the aggregated by-catch mortality probability ranged from 0.321 to 0.378. Assuming a total annual by-catch of 10656 loggerhead turtles by the Spanish longline fleet operating in the southwestern Mediterranean, by-catch results in 3421 to 4028 turtle deaths annually. This range is equivalent to 8.5−10.1% of the approximately 40000 turtles inhabiting the fishing grounds used by Spanish longliners, most of them from rookeries in the northwestern Atlantic. As a consequence, the accumulated mortality during the oceanic stage is expected to be larger for those loggerhead turtles of Atlantic origin that spend several years in the Mediterranean Sea than for turtles of the same cohort that remain in the Atlantic. For this reason, the Mediterranean can be considered a dead end for loggerhead turtle populations nesting in the Atlantic, although the actual demographic relevance of by-catch mortality of loggerhead turtles in the Mediterranean remains unknown.

Précis du procès de M. le comte de Morangiès, contre la famille Verron

[Factum. Morangiès, Jean-François-Charles de Molette (comte de)]

Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells.

Pluripotency in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is regulated by three transcription factors-OCT3/4, SOX2, and NANOG. To fully exploit the therapeutic potential of these cells it is essential to have a good mechanistic understanding of the maintenance of self-renewal and pluripotency. In this study, we demonstrate a powerful systems biology approach in which we first expand literature-based network encompassing the core regulators of pluripotency by assessing the behavior of genes targeted by perturbation experiments. We focused our attention on highly regulated genes encoding cell surface and secreted proteins as these can be more easily manipulated by the use of inhibitors or recombinant proteins. Qualitative modeling based on combining boolean networks and in silico perturbation experiments were employed to identify novel pluripotency-regulating genes. We validated Interleukin-11 (IL-11) and demonstrate that this cytokine is a novel pluripotency-associated factor capable of supporting self-renewal in the absence of exogenously added bFGF in culture. To date, the various protocols for hESCs maintenance require supplementation with bFGF to activate the Activin/Nodal branch of the TGFβ signaling pathway. Additional evidence supporting our findings is that IL-11 belongs to the same protein family as LIF, which is known to be necessary for maintaining pluripotency in mouse but not in human ESCs. These cytokines operate through the same gp130 receptor which interacts with Janus kinases. Our finding might explain why mESCs are in a more naïve cell state compared to hESCs and how to convert primed hESCs back to the naïve state. Taken together, our integrative modeling approach has identified novel genes as putative candidates to be incorporated into the expansion of the current gene regulatory network responsible for inducing and maintaining pluripotency.

Agréments+ de la campagne, ou Remarques particulieres sur la construction des maisons de campagne plus ou moins magnifiques; des jardins de plaisance & des plantages...

Titre original : # Byzondere # + Bijzondere + # aenmerkingen over het aenleggen van pragtige en gemeene landhuizen # + aanmerkingen over het aanleggen van prachtige en gemeene landhuisen + , lusthoven, plantagien