L1 and HERV-W retrotransposons are hypomethylated in human ovarian carcinomas

Wide-spread hypomethylation of CpG dinucleotides is characteristic of many cancers. Retrotransposons have been identified as potential targets of hypomethylation during cellular transformation. We report the results of an preliminary examination of the methylation status of CpG dinucleotides associated with the L1 and HERV-W retrotransposons in benign and malignant human ovarian tumors. We find a reduction in the methylation of CpG dinucleotides within the promoter regions of these retroelements in malignant relative to non-malignant ovarian tissues. Consistent with these results, we find that relative L1 and HERV-W expression levels are elevated in representative samples of malignant vs. non-malignant ovarian tissues

Ciliary adenylyl cyclases control the Hedgehog pathway

Protein kinase A (PKA) accumulates at the base of the cilium where it negatively regulates the Hedgehog (Hh) pathway. Although PKA activity is essentially controlled by the cAMP produced by adenylyl cyclases, the influence of these enzymes on the Hh pathway remains unclear. Here, we show that adenylyl cyclase 5 and adenylyl cyclase 6 (AC5 and AC6, also known as ADCY5 and ADCY6, respectively) are the two isoforms most strongly expressed in cerebellar granular neuron precursors (CGNPs). We found that overexpression of AC5 and AC6 represses, whereas their knockdown activates, the Hh pathway in CGNPs and in the embryonic neural tube. Indeed, AC5 and AC6 concentrate in the primary cilium, and mutation of a previously undescribed cilium-targeting motif in AC5 suppresses its ciliary location, as well as its capacity to inhibit Hh signalling. Stimulatory and inhibitory Gα proteins, which are engaged by the G-protein-coupled receptors (GPCRs), control AC5 and AC6 activity and regulate the Hh pathway in CGNPs and in the neural tube. Therefore, we propose that the activity of different ciliary GPCRs converges on AC5 and AC6 to control PKA activity and, hence, the Hh pathwayThis work was supported by Spanish and Catalan ministries of Science [grant numbers BFU2008-02424/BFI, BFU2011-24099 and SGR200821A333 to S.P.]Peer Reviewe

A linear domain decomposition method for two-phase flow in porous media

This article is a follow up of our submitted paper [11] in which a decomposition of the Richards equation along two soil layers was discussed. A decomposed problem was formulated and a decoupling and linearisation technique was presented to solve the problem in each time step in a fixed point type iteration. This article extends these ideas to the case of two-phase in porous media and the convergence of the proposed domain decomposition method is rigorously shown.Comment: 8 page

AUTOMATICALLY TAG WHITEBOARD AUTHORS

Techniques are provided for identifying and tagging authors of whiteboard content. A neural network is used to detect the most likely person or persons currently drawing on the whiteboard. The neural network works together with face recognition or other methods to tag and save the authors of each stroke in the whiteboard metadata

Design guidelines for self-assessment support for adult academic distance learning

Menendez Blanco, M., Van der Veer, G., Benvenuti, L., & Kirschner, P. A. (2011). Design guidelines for self-assessment support for adult academic distance learning. In H-J Shalin (Ed.), Constructing self-discovery learning spaces online: scaffolding and decision making technologies (pp. 169-198). Hershey, PA: IGI Global.This contribution focuses on adult distance learning. Based on experiences at the Open University of the Netherlands we investigate specific problems that our students have with self-assessment and metacognition while studying. Starting from a literature review and complementing this with available student data from our teaching research center, we developed a conceptual framework that was iteratively adjusted and assessed by a questionnaire study and interviews. This allowed us to develop design guidelines for self-assessment support in distance learning environments. These guidelines were reviewed by experts. The input from the experts was used to modify the guidelines and iterate until they were considered complete. Tangible designs (i.e., mock-ups) for each of the self-assessment methods were proposed. These tangible designs were prototyped for later evaluation. Finally, we provide our conclusions and propose recommendations for actual application and systematic design

Policy Change and Differentiated Integration: Implementing Spanish Higher Education Reforms

Over the last two decades, the Spanish higher education and research sector has undergone profound changes, but little is known about the implementation of recent reforms and how university actors responded to policy change and institutional pressures within a changing resource environment. Drawing on the insights from institutional and resource-dependence theory, we show how Spanish public universities have coped and implemented their human resources policy over the past 15 years and whether individual universities converged in their employment behaviour. The aggregate evolution of university employment trends reveals adaptation to the institutional normative pressures and financial constraints. Our results also show that some universities are more responsive to changes in the resource environment than others, and that compliance is not the only strategic response. In so doing, we aim to contribute to existing research on strategic behaviour of actors and coalitions facing policy change, and to the construction of analytical bridges between environmental changes (institutional and economic) and organisational dynamics underlying policy implementation

Pulmonary arterial dysfunction in insulin resistant obese Zucker rats

<p>Abstract</p> <p>Background</p> <p>Insulin resistance and obesity are strongly associated with systemic cardiovascular diseases. Recent reports have also suggested a link between insulin resistance with pulmonary arterial hypertension. The aim of this study was to analyze pulmonary vascular function in the insulin resistant obese Zucker rat.</p> <p>Methods</p> <p>Large and small pulmonary arteries from obese Zucker rat and their lean counterparts were mounted for isometric tension recording. mRNA and protein expression was measured by RT-PCR or Western blot, respectively. K_Vcurrents were recorded in isolated pulmonary artery smooth muscle cells using the patch clamp technique.</p> <p>Results</p> <p>Right ventricular wall thickness was similar in obese and lean Zucker rats. Lung BMPR2, K_V1.5 and 5-HT_2Areceptor mRNA and protein expression and K_Vcurrent density were also similar in the two rat strains. In conductance and resistance pulmonary arteries, the similar relaxant responses to acetylcholine and nitroprusside and unchanged lung eNOS expression revealed a preserved endothelial function. However, in resistance (but not in conductance) pulmonary arteries from obese rats a reduced response to several vasoconstrictor agents (hypoxia, phenylephrine and 5-HT) was observed. The hyporesponsiveness to vasoconstrictors was reversed by L-NAME and prevented by the iNOS inhibitor 1400W.</p> <p>Conclusions</p> <p>In contrast to rat models of type 1 diabetes or other mice models of insulin resistance, the obese Zucker rats did not show any of the characteristic features of pulmonary hypertension but rather a reduced vasoconstrictor response which could be prevented by inhibition of iNOS.</p

Wells’ Syndrome Successfully Treated with Colchicine

La celulitis eosinofílica es un trastorno infrecuente, inflamatorio y crónico de etiología desconocida. Actualmente, se considera que los corticosteroides son el tratamiento de primera línea, pero no carecen de desventajas significativas, como las contraindicaciones en los casos resistentes a esteroides y los pacientes con recidivas frecuentes. Divulgamos a un paciente que sufre del síndrome de Wells con una historia de 24 años de lesiones cutáneas sintomáticas y generalizadas. Después de la consulta en nuestro servicio, se prescribió tratamiento con colchicina 1 mg / día, lo que resultó en una gran mejoría clínica. No se han registrado efectos secundarios. Hasta donde sabemos, este es un enfoque de enfermedad original. Aunque pequeña, nuestra experiencia clínica respalda la inclusión de colchicina en el arsenal farmacológico cuando se trata a pacientes con síndrome de Wells. De hecho, su excelente perfil de seguridad lo hace muy atractivo para los pacientes con episodios recurrentes frecuentes que necesitan opciones seguras para el control de la enfermedad a mediano y largo plazoA celulitis eosinofílica é un trastorno infrecuente, inflamatorio e crónico de etioloxía descoñecida. Actualmente, considérase que os corticosteroides son o tratamento de primeira liña, pero non carecen de desvantaxes significativas, como as contraindicacións nos casos resistentes a esteroides e os pacientes con recidivas frecuentes. Divulgamos a un paciente que sofre da síndrome de Wells cunha historia de 24 anos de lesións cutáneas sintomáticas e xeneralizadas. Despois da consulta no noso servizo, prescribiuse tratamento con colchicina 1 mg / día, o que resultou nunha gran melloría clínica. Non se rexistraron efectos secundarios. Ata onde sabemos, este é un enfoque da enfermidade orixinal. Aínda que pequena, a nosa experiencia clínica apoia a inclusión de colchicina no arsenal farmacolóxico cando se trata a pacientes con síndrome de Wells. De feito, o seu excelente perfil de seguridade faio moi atractivo para os pacientes con episodios recorrentes frecuentes que necesitan opcións seguras para o control da enfermidade a mediano e longo prazoEosinophilic cellulitis is an uncommon, inflammatory and chronic disorder of unknown etiology. Corticosteroids are currently considered as the first-line treatment but they are not without significant disadvantages such as contraindications in steroid-resistant cases and patients with frequent recurrences. We report a patient suffering from Wells’ syndrome with a 24-year history of symptomatic and generalized skin lesions. After consultation in our department, treatment with colchicine 1 mg/day was prescribed resulting in large clinical improvement. No side effects have been recorded. To our knowledge, this is an original disease approach. Although small, our clinical experience supports the inclusion of colchicine in the drug armamentarium when treating patients suffering from Wells’ syndrome. Indeed, its excellent safety profile makes it very attractive for patients with frequent recurrent episodes who need secure options for the medium- and long-term disease contro