The metastasis inducer CCN1 (CYR61) activates the fatty acid synthase (FASN)-driven lipogenic phenotype in breast cancer cells

The angiogenic inducer CCN1 (Cysteine-rich 61, CYR61) is differentially activated in metastatic breast carcinomas. However, little is known about the precise mechanisms that underlie the pro-metastatic actions of CCN1. Here, we investigated the impact of CCN1 expression on fatty acid synthase (FASN), a metabolic oncogene thought to provide cancer cells with proliferative and survival advantages. Forced expression of CCN1 in MCF-7 cells robustly up-regulated FASN protein expression and also significantly increased FASN gene promoter activity 2- to 3-fold, whereas deletion of the sterol response element-binding protein (SREBP) binding site in the FASN promoter completely abrogated CCN1-driven transcriptional activation. Pharmacological blockade of MAPK or PI-3´K activation similarly prevented the ability of CCN1 to induce FASN gene activation. Pharmacological inhibition of FASN activity with the mycotoxin cerulenin or the small compound C75 reversed CCN1-induced acquisition of estrogen independence and resistance to hormone therapies such as tamoxifen and fulvestrant in anchorage-independent growth assays. This study uncovers FASNdependent endogenous lipogenesis as a new mechanism controlling the metastatic phenotype promoted by CCN1. Because estrogen independence and progression to a metastatic phenotype are hallmarks of therapeutic resistance and mortality in breast cancer, this previously unrecognized CCN1-driven lipogenic phenotype represents a novel metabolic target to clinically manage metastatic disease progression.Fil: Menendez, Javier A.. Instituto Catalán de Oncología; España. Institut d; EspañaFil: Vellón, Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Espinoza, Ingrid. University Of Mississippi; Estados UnidosFil: Lupu, Ruth. Mayo Clinic Cancer Center; Estados Unido

Introducing alternative-based thresholding for defining functional regions of interest in fMRI

In fMRI research, one often aims to examine activation in specific functional regions of interest (fROIs). Current statistical methods tend to localize fROIs inconsistently, focusing on avoiding detection of false activation. Not missing true activation is however equally important in this context. In this study, we explored the potential of an alternative-based thresholding (ABT) procedure, where evidence against the null hypothesis of no effect and evidence against a prespecified alternative hypothesis is measured to control both false positives and false negatives directly. The procedure was validated in the context of localizer tasks on simulated brain images and using a real data set of 100 runs per subject. Voxels categorized as active with ABT can be confidently included in the definition of the fROI, while inactive voxels can be confidently excluded. Additionally, the ABT method complements classic null hypothesis significance testing with valuable information by making a distinction between voxels that show evidence against both the null and alternative and voxels for which the alternative hypothesis cannot be rejected despite lack of evidence against the null

Feasibility and reliability of a Physical Fitness test battery in individuals with Down Syndrome

Background: Down syndrome (DS) is a genetic disorder that occurs because of an abnormal division between cells that results in an extra copy of chromosome 21. Some studies show that physical exercise in people with DS increases some cognitive capacities, such as memory, and improves the quality of life. Aim: The main aim of this study was to perform an analysis of the reliability and feasibility of the SAMU-Disability Fitness (DISFIT) battery in adults with DS. Methods: A cross-sectional study with a test–retest design was performed in a maximum interval of 2 weeks in 37 subjects (11 women and 26 men) aged between 21 and 58 years old with DS. Eight field-based fitness tests were proposed to assess the physical fitness (PF) of adults with DS: Body Mass Index (BMI), Waist Circumference (WC), the Timed Up and Go test (TUG), the Deep Trunk Flexibility test (DTF), the Hand Grip test (HG), the Timed Stand Test (TST), the 30-s Sit-Up (SUP) and the 6-Min Walk Test (6MWT). Results: The intra-class correlation coefficient (ICC) in all the tests was good and high (>0.80), except for the 6MWT, whose reliability was fair. Conclusion: The SAMU-DISFIT battery is a reliable and feasible physical fitness battery which has been created with the purpose of establishing tests which measure the four basic components of PF (flexibility, cardiorespiratory fitness, musculoskeletal fitness and motor fitness) in adults with D

Multi-criteria decision analysis tools for prioritising emerging or re-emerging infectious diseases associated with climate change in Canada

Global climate change is known to result in the emergence or re-emergence of some infectious diseases. Reliable methods to identify the infectious diseases of humans and animals and that are most likely to be influenced by climate are therefore required. Since different priorities will affect the decision to address a particular pathogen threat, decision makers need a standardised method of prioritisation. Ranking methods and Multi-Criteria Decision approaches provide such a standardised method and were employed here to design two different pathogen prioritisation tools. The opinion of 64 experts was elicited to assess the importance of 40 criteria that could be used to prioritise emerging infectious diseases of humans and animals in Canada. A weight was calculated for each criterion according to the expert opinion. Attributes were defined for each criterion as a transparent and repeatable method of measurement. Two different Multi-Criteria Decision Analysis tools were tested, both of which used an additive aggregation approach. These were an Excel spreadsheet tool and a tool developed in software 'M-MACBETH'. The tools were trialed on nine 'test' pathogens. Two different methods of criteria weighting were compared, one using fixed weighting values, the other using probability distributions to account for uncertainty and variation in expert opinion. The ranking of the nine pathogens varied according to the weighting method that was used. In both tools, using both weighting methods, the diseases that tended to rank the highest were West Nile virus, Giardiasis and Chagas, while Coccidioidomycosis tended to rank the lowest. Both tools are a simple and user friendly approach to prioritising pathogens according to climate change by including explicit scoring of 40 criteria and incorporating weighting methods based on expert opinion. They provide a dynamic interactive method that can help to identify pathogens for which a full risk assessment should be pursued

The use of expert opinion to assess the risk of emergence or re-emergence of infectious diseases in Canada associated with climate change

Global climate change is predicted to lead to an increase in infectious disease outbreaks. Reliable surveillance for diseases that are most likely to emerge is required, and given limited resources, policy decision makers need rational methods with which to prioritise pathogen threats. Here expert opinion was collected to determine what criteria could be used to prioritise diseases according to the likelihood of emergence in response to climate change and according to their impact. We identified a total of 40 criteria that might be used for this purpose in the Canadian context. The opinion of 64 experts from academic, government and independent backgrounds was collected to determine the importance of the criteria. A weight was calculated for each criterion based on the expert opinion. The five that were considered most influential on disease emergence or impact were: potential economic impact, severity of disease in the general human population, human case fatality rate, the type of climate that the pathogen can tolerate and the current climatic conditions in Canada. There was effective consensus about the influence of some criteria among participants, while for others there was considerable variation. The specific climate criteria that were most likely to influence disease emergence were: an annual increase in temperature, an increase in summer temperature, an increase in summer precipitation and to a lesser extent an increase in winter temperature. These climate variables were considered to be most influential on vector-borne diseases and on food and water-borne diseases. Opinion about the influence of climate on air-borne diseases and diseases spread by direct/indirect contact were more variable. The impact of emerging diseases on the human population was deemed more important than the impact on animal populations

Análisis de la satisfacción laboral percibida por los trabajadores pertenecientes al sector deportivo: una revisión sistemática

The aim of this research was to carry out a systematic review of the existing scientific information on job satisfaction as perceived by workers or professionals in sports organisations. This systematic review followed the considerations established by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The present systematic review included published research papers whose subject matter was related to the job satisfaction of the worker or professional in the field of sport and especially in municipal sports services. After an initial papers analysis of 168 articles, we excluded those that did not meet the inclusion criteria (n = 147); thereby, we obtained the final selection of 18 articles. The results of this study seem to indicate that the job satisfaction of workers or professionals in sports organisations is fairly moderate and that there may also be differences depending on gender, type of work and the sector (public or private) to which they belong. Furthermore, the results analysed in this systematic review show that there is no uniformity in the evaluation systems for measuring workers' job satisfaction.El objetivo de esta investigación fue realizar una revisión sistemática sobre de la información científica existente referente a la satisfacción laboral percibida por el trabajador o profesional de entidades deportivas. La presente revisión sistemática siguió las consideraciones establecidas por Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). En la presente revisión sistemática se incluyeron los estudios publicados cuya temática estuviera relacionada con la satisfacción laboral del trabajador o profesional en el ámbito deportivo y especialmente en los servicios deportivos municipales. Tras un primer análisis de trabajos donde se identificaron 168 artículos, se excluyeron aquellos que no cumplieran los criterios de inclusión (n = 147) y así, se obtuvo la selección definitiva de 18 artículos. Los resultados de este estudio parecen indicar que la satisfacción laboral de los trabajadores o profesionales de entidades deportivas en su mayoría es moderada, y que además pueden existir diferencias en función del sexo, del tipo de trabajo y del sector (público o privado) al que pertenezcan. Por otro lado, de los resultados analizados en la presente revisión sistemática se desprende que no existe uniformidad en los sistemas de evaluación para medir la satisfacción laboral de los trabajadores.&nbsp

The pyramidal cell in cognition: A comparative study in human and monkey

Here we present evidence that the pyramidal cell phenotype varies markedly in the cortex of different anthropoid species. Regional and species differences in the size of, number of bifurcations in, and spine density of the basal dendritic arbors cannot be explained by brain size. Instead, pyramidal cell morphology appears to accord with the specialized cortical function these cells perform. Cells in the prefrontal cortex of humans are more branched and more spinous than those in the temporal and occipital lobes. Moreover, cells in the prefrontal cortex of humans are more branched and more spinous than those in the prefrontal cortex of macaque and marmoset monkeys. These results suggest that highly spinous, compartmentalized, pyramidal cells (and the circuits they form) are required to perform complex cortical functions such as comprehension, perception, and planning

The systemic governance influence of universal owners: evidence from an expectation document

Universal owners - large institutional investors with highly diversified and long-term portfolios spanning the entire global capital market - have multiple engagement mechanisms to influence their portfolio companies. Given the costly nature of firm-specific interventions, universal owners have also drawn on systemic governance mechanisms with a wide market effect and low cost such as expectation documents. We focus on Norway’s sovereign wealth fund and its release of an unforeseen key expectation Note in 2012 requesting explicit corporate governance practices from all its portfolio companies. We use this early example of an expectation Note as a natural experiment to examine whether expectation documents have impactful governance consequences for the entire market. We develop a new three-step decomposition approach to explore the effectiveness of expectation documents as an activism mechanism. First, we analyze how portfolio firms adapted to the fund’s new governance expectations and explore their heterogeneous response across ownership levels and firm characteristics. We find a stronger reaction by firms for which direct action is more costly to universal owners. Second, we show how the fund also changed its investment policy to meet its newly stated governance preferences, even at the expense of its financial returns. And finally, we illustrate the new correlation between the firms’ changes toward higher governance scores and the fund’s changes in the investment weights. With this study, we contribute to research on shareholder stewardship by examining a novel and effective governance engagement tactic which is becoming popular in an era of raising pressures for corporations to pursue purpose

Selective alterations of neurons and circuits related to early memory loss in Alzheimers's disease

This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permissionAprogressive loss of episodic memory is awell-known clinical symptom tha tcharacterizes Alzheimer’s disease(AD). The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal lcortex(EC). Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses.The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the performant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII→dentategyrus→CA3→CA1) and mono synaptic (ECIII→CA1) circuits. Thus, the study of the early pathological changes in these circuitsis of great interest. In this review,we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occu rin AD in relation to the possible differential alterations of these two main circuitsThis work wa ssupported by grants from the following entities: CIBERNED,Comunidad de Madrid (grant S2010/BMD-2331), Fundación CIEN, Fundación Ramón Areces and the Spanish Ministry of Economy and Competitiveness (SAF2011-24841, BFU2012-34963 and the Cajal Blue Brain Project, Spanish partner of the Blue Brain Project initiative from EPFL

Gigabit point to multipoint backhaul using Q-band

© 2014 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.This paper defines a Q-band point to multipoint backhaul architecture including Q-band disruptive technology that provides multi-gigabit capacity in a cost-effective manner as proposed in the EU FP7 SARABAND project. The small-scale field-trial of the network platform providing Gigabit Ethernet communication is also described.The European Commission is gratefully acknowledged for partial funding of the ICT-2011-288267 SARABAND project in the 7th Framework Programme.Vilar Mateo, R.; Martí Sendra, J.; Magne, F. (2014). Gigabit point to multipoint backhaul using Q-band. En European Conference on Networks and Communications Bologna, Italy, June 23/26, 2014. Institute of Electrical and Electronics Engineers (IEEE). 1-2. http://hdl.handle.net/10251/62767S1