Time-scale and other invariants of integrative mechanical behavior in living cells.

In dealing with systems as complex as the cytoskeleton, we need organizing principles or, short of that, an empirical framework into which these systems fit. We report here unexpected invariants of cytoskeletal behavior that comprise such an empirical framework. We measured elastic and frictional moduli of a variety of cell types over a wide range of time scales and using a variety of biological interventions. In all instances elastic stresses dominated at frequencies below 300 Hz, increased only weakly with frequency, and followed a power law; no characteristic time scale was evident. Frictional stresses paralleled the elastic behavior at frequencies below 10 Hz but approached a Newtonian viscous behavior at higher frequencies. Surprisingly, all data could be collapsed onto master curves, the existence of which implies that elastic and frictional stresses share a common underlying mechanism. Taken together, these findings define an unanticipated integrative framework for studying protein interactions within the complex microenvironment of the cell body, and appear to set limits on what can be predicted about integrated mechanical behavior of the matrix based solely on cytoskeletal constituents considered in isolation. Moreover, these observations are consistent with the hypothesis that the cytoskeleton of the living cell behaves as a soft glassy material, wherein cytoskeletal proteins modulate cell mechanical properties mainly by changing an effective temperature of the cytoskeletal matrix. If so, then the effective temperature becomes an easily quantified determinant of the ability of the cytoskeleton to deform, flow, and reorganize.

Integrative analysis of the Regulatory Region of the FGFR3 Oncogene

The study of transcriptional regulation often needs the integration of diverse yet independent data. In the present work, sequence conservation, predic-tion of transcription factor binding sites (TFBS) and gene expression analysis have been applied to the detection of putative transcription factor (TF) modules in the regulatory region of the FGFR3 oncogene. Several TFs with conserved binding sites in the FGFR3 regulatory region have shown high positive or negative corre-lation with FGFR3 expression both in urothelial carcinoma and in benign nevi. By means of conserved TF cluster analysis, two different TF modules have been iden-tified in the promoter and first intron of FGFR3 gene. These modules contain acti-vating AP2, E2F, E47 and SP1 binding sites plus motifs for EGR with possible repressor function.

An integrative computational analysis provides evidence for FBN1-associated network deregulation in trisomy 21

Although approximately 50% of Down Syndrome (DS) patients have heart abnormalities, they exhibit an overprotection against cardiac abnormalities related with the connective tissue, for example a lower risk of coronary artery disease. A recent study reported a case of a person affected by DS who carried mutations in FBN1, the gene causative for a connective tissue disorder called Marfan Syndrome (MFS). The fact that the person did not have any cardiac alterations suggested compensation effects due to DS. This observation is supported by a previous DS meta-analysis at the molecular level where we have found an overall upregulation of FBN1 (which is usually downregulated in MFS). Additionally, that result was cross-validated with independent expression data from DS heart tissue. The aim of this work is to elucidate the role of FBN1 in DS and to establish a molecular link to MFS and MFS-related syndromes using a computational approach. To reach that, we conducted different analytical approaches over two DS studies (our previous meta-analysis and independent expression data from DS heart tissue) and revealed expression alterations in the FBN1 interaction network, in FBN1 co-expressed genes and FBN1-related pathways. After merging the significant results from different datasets with a Bayesian approach, we prioritized 85 genes that were able to distinguish control from DS cases. We further found evidence for several of these genes (47%), such as FBN1, DCN, and COL1A2, being dysregulated in MFS and MFS-related diseases. Consequently, we further encourage the scientific community to take into account FBN1 and its related network for the study of DS cardiovascular characteristics.

An integrative computational analysis provides evidence for FBN1-associated network deregulation in trisomy 21

Although approximately 50% of Down Syndrome (DS) patients have heart abnormalities, they exhibit an overprotection against cardiac abnormalities related with the connective tissue, for example a lower risk of coronary artery disease. A recent study reported a case of a person affected by DS who carried mutations in FBN1, the gene causative for a connective tissue disorder called Marfan Syndrome (MFS). The fact that the person did not have any cardiac alterations suggested compensation effects due to DS. This observation is supported by a previous DS meta-analysis at the molecular level where we have found an overall upregulation of FBN1 (which is usually downregulated in MFS). Additionally, that result was cross-validated with independent expression data from DS heart tissue. The aim of this work is to elucidate the role of FBN1 in DS and to establish a molecular link to MFS and MFS-related syndromes using a computational approach. To reach that, we conducted different analytical approaches over two DS studies (our previous meta-analysis and independent expression data from DS heart tissue) and revealed expression alterations in the FBN1 interaction network, in FBN1 co-expressed genes and FBN1-related pathways. After merging the significant results from different datasets with a Bayesian approach, we prioritized 85 genes that were able to distinguish control from DS cases. We further found evidence for several of these genes (47%), such as FBN1, DCN, and COL1A2, being dysregulated in MFS and MFS-related diseases. Consequently, we further encourage the scientific community to take into account FBN1 and its related network for the study of DS cardiovascular characteristics.

Study of tergal glands morphogenesis through an integrative analysis of genomic data

About 50% of living species are holometabolan insects. Therefore, unraveling the ori- gin of insect metamorphosis from the hemimetabolan (gradual metamorphosis) to the holometabolan (sudden metamorphosis at the end of the life cycle) mode is equivalent to explaining how all this biodiversity originated. One of the problems with studying the evolution from hemimetaboly to holometaboly is that most information is available only in holometabolan species. Within the hemimetabolan group, our model, the cock- roach Blattella germanica, is the most studied species. However, given that the study of adult morphogenesis at organismic level is still complex, we focused on the study of the tergal gland (TG) as a minimal model of metamorphosis. The TG is formed in tergites 7 and 8 (T7-8) in the last days of the last nymphal instar (nymph 6). The comparative study of four T7-T8 transcriptomes provided us with crucial keys of TG formation, but also essential information about the mechanisms and circuitry that allows the shift from nymphal to adult morphogenesis.

Identificaci�� de variables d'estat del sistema costaner sensibles a la c��rrega de nutrients

Projecte de recerca elaborat a partir d���una estada a la Napier University, Gran Bretanya, des d���octubre del 2006 a febrer del 2007. Els ecosistemes marins costaners s��n sistemes complexos, tant pel que fa a l���estructura de les comunitats que hi viuen com per la seva din��mica, amb processos que impliquen m��ltiples escales d���espai i de temps. Aquesta complexitat natural s���ha incrementat al llarg de les darreres d��cades com a conseq����ncia directa del creixement urb�� al litoral. L���augment de poblaci�� a les zones costaneres ha comportat no nom��s un augment generalitzat en l���aport de nutrients inorg��nics al mar, sin�� tamb�� una forta intervenci�� sobre la l��nia de costa ���construcci�� de ports, dics- i canvis en el moviment de les masses d���aigua. En aquest context, la interacci�� entre els factors turbul��ncia-nutrients a la zona costanera pot ser clau per a millorar la nostra comprensi�� sobre el funcionament dels sistemes planct��nics i, en darrer terme, per a derivar-ne mesures de gesti��. A difer��ncia de treballs experimentals previs, que adrecen els efectes de la turbul��ncia i/o els nutrients sobre grups espec��fics de pl��ncton, per avaluar la resposta conjunta de la comunitat necessitem par��metres integradors, que relacionin diversos processos i donin una idea general de l���estat i funcionament de l���ecosistema. Durant l���estada de recerca alguns dels algoritmes que es fan servir per la costa escocesa van reformular-se i recalcular-se amb dades de la Mediterr��nia (dades procedents de la badia de Blanes i de la costa de Barcelona). Els resultats mostren una capacitat de resposta molt r��pida del pl��ncton als increments de nutrients, una variabilitat anual marcada (quant a diversitat d���organismes planct��nics) i apunten el f��sfor com a principal limitant del creixement dels organismes en aquesta zona de la Mediterr��nia.

Determinants of the educational use of digital learning materials: The mediating role of self-efficacy, perceived norm and attitude

Initiatives to stimulate the development and propagation of open educational resources (OER) need a sufficiently large community that can be mobilized to participate in this endeavour. Failure to achieve this could lead to underuse of OER. In the context of the Wikiwijs initiative a large scale survey was undertaken amongst primary and secondary school teachers to explore possible determinants of the educational use of digital learning materials (DLMs). Basing on the Integrative Model of Behaviour Prediction it was conjectured that self-efficacy, attitude and perceived norm would take a central role in explaining the intention to use DLMs. Several other predictors were added to the model as well whose effects were hypothesized to be mediated by the three central variables.All conjectured relationships were found using path analysis on survey data from 1484 teachers. Intention to DLMs was most strongly determined by self-efficacy, followed by attitude. ICT proficiency was in its turn the strongest predictor of self-efficacy. Perceived norm played only a limited role in the intention to use DLMs. Concluding, it seems paramount for the success of projects such as Wikiwijs to train teachers in the use of digital learning materials and ICT (e.g. the digital blackboard) and to impact on their attitude.

Influencia del estr��s en el padecimiento de la migra��a

La migrafia es una cefalea en cuya etiologia intervienen factores muy diversos. En este trabajo, se revisan 10s resultados de diferentes investigaciones y se proponen pautas para un modelo integrador en el que 10s factores precipitantes del ataque de migra��a ('a sean nerviosos, endocrinos, metab��licos o inmunol��gicos) ven facilitado su poder como desencadenantes a causa de la existencia de un estado de estr��s cr��nico en el paciente

Improved earthquake response via simulation and integrated space- and ground-based technologies: the TREMOR proposal

Earthquakes occurring around the world each year cause thousands ofdeaths, millions of dollars in damage to infrastructure, and incalculablehuman suffering. In recent years, satellite technology has been asignificant boon to response efforts following an earthquake and itsafter-effects by providing mobile communications between response teamsand remote sensing of damaged areas to disaster management organizations.In 2007, an international team of students and professionals assembledduring theInternational Space University���s Summer Session Program in Beijing, Chinato examine how satellite and ground-based technology could be betterintegrated to provide an optimised response in the event of an earthquake.The resulting Technology Resources for Earthquake MOnitoring and Response(TREMOR) proposal describes an integrative prototype response system thatwill implement mobile satellite communication hubs providing telephone anddata links between response teams, onsite telemedicine consultation foremergency first-responders, and satellite navigation systems that willlocate and track emergency vehicles and guide search-and-rescue crews. Aprototype earthquake simulation system is also proposed, integratinghistorical data, earthquake precursor data, and local geomatics andinfrastructure information to predict the damage that could occur in theevent of an earthquake. The backbone of these proposals is a comprehensiveeducation and training program to help individuals, communities andgovernments prepare in advance. The TREMOR team recommends thecoordination of these efforts through a centralised, non-governmentalorganization.

Predicting cancer involvement of genes from heterogeneous data

Background: Systematic approaches for identifying proteins involved in different types of cancer are needed. Experimental techniques such as microarrays are being used to characterize cancer, but validating their results can be a laborious task. Computational approaches are used to prioritize between genes putatively involved in cancer, usually based on further analyzing experimental data. Results: We implemented a systematic method using the PIANA software that predicts cancer involvement of genes by integrating heterogeneous datasets. Specifically, we produced lists of genes likely to be involved in cancer by relying on: (i) protein-protein interactions; (ii) differential expression data; and (iii) structural and functional properties of cancer genes. The integrative approach that combines multiple sources of data obtained positive predictive values ranging from 23% (on a list of 811 genes) to 73% (on a list of 22 genes), outperforming the use of any of the data sources alone. We analyze a list of 20 cancer gene predictions, finding that most of them have been recently linked to cancer in literature. Conclusion: Our approach to identifying and prioritizing candidate cancer genes can be used to produce lists of genes likely to be involved in cancer. Our results suggest that differential expression studies yielding high numbers of candidate cancer genes can be filtered using protein interaction networks.

Mononuclear cell transcriptome response after sustained virgin olive oil consumption in humans: an exploratory nutrigenomics study

Virgin olive oil (VOO) is considered to be one of the main components responsible for the health benefits of the Mediterranean diet, particularly against atherosclerosis where peripheral blood mononuclear cells (PBMNCs) play a crucial role in atherosclerosis development and progression. The objective of this article was to identify the PBMNC genes that respond to VOO consumption in order to ascertain the molecular mechanisms underlying the beneficial action of VOO in the prevention of atherosclerosis. Gene expression profiles of PBMNCs from healthy individuals were examined in pooled RNA samples by microarrays after 3 weeks of moderate and regular consumption of VOO, as the main fat source in a diet controlled for antioxidant content. Gene expression was verified by qPCR. The response to VOO consumption was confirmed for individual samples (n = 10) by qPCR for 10 upregulated genes (ADAM17, ALDH1A1, BIRC1, ERCC5, LIAS, OGT, PPARBP, TNFSF10, USP48, and XRCC5). Their putative role in the molecular mechanisms involved in atherosclerosis development and progression is discussed, focusing on a possible relation with VOO consumption. Our data support the hypothesis that 3 weeks of nutritional intervention with VOO supplementation, at doses common in the Mediterranean diet, can alter the expression of genes related to atherosclerosis development and progression.

El Brasil de los populismos: de la construcci��n de la identidad nacional a la supuesta democracia racial

El autor estudia la creaci��n de una identidad nacional en Brasil durante los siglos XIX y XX, incidiendo en los intereses de las ��lites gobernantes para formular un determinado discurso integrador de lo ind��gena y lo africano. / L'autor estudia la creaci�� d'una identitat nacional al Brasil durant els segles XIX i XX, incidint en els interessos de les ��lits governants per formular un determinat discurs integrador d'all�� ind��gena i all�� afric��. / The author studies the creation of a national identity in Brazil during the 19th and 20th century, focus on the elites rulers interests to formulate a determined integrative speech of the ��native�� and the ��African��.

GSVA: gene set variation analysis for microarray and RNA-seq data

Gene set enrichment (GSE) analysis is a popular framework for condensing information from gene expression pro���les into a pathway or signature summary. The strengths of this approach over single gene analysis include noise and dimension reduction, as well as greater biological interpretability. As molecular pro���ling experiments move beyond simple case-control studies, robust and ���exible GSE methodologies are needed that can model pathway activity within highly heterogeneous data sets. To address this challenge, we introduce Gene Set Variation Analysis (GSVA), a GSE method that estimates variation of pathway activity over a sample population in an unsupervised manner. We demonstrate the robustness of GSVA in a comparison with current state of the art sample-wise enrichment methods. Further, we provide examples of its utility in di���erential pathway activity and survival analysis. Lastly, we show how GSVA works analogously with data from both microarray and RNA-seq experiments. GSVA provides increased power to detect subtle pathway activity changes over a sample population in comparison to corresponding methods. While GSE methods are generally regarded as end points of a bioinformatic analysis, GSVA constitutes a starting point to build pathway-centric models of biology. Moreover, GSVA contributes to the current need of GSE methods for RNA-seq data. GSVA is an open source software package for R which forms part of the Bioconductor project and can be downloaded at http://www.bioconductor.org.

G��nere i sexoafectivitat segons els adolescents dels usuaris dels centres oberts de la ciutat de Girona

L���objectiu d���aquest treball ��s con��ixer la percepci�� que tenen els adolescents usuaris dels centres oberts de la ciutat de Girona sobre la sexualitat, l���afectivitat, quins rols de g��nere se���n deriven i quines creences els sustenten. El disseny del treball ha estat qualitatiu, observacional, grups de discussi��. Pel que fa als subjectes i al m��tode, la poblaci�� seleccionada ha estat de 33 adolescents i joves d���edats compreses entre els 12 i els 22 anys, usuaris de quatre centres oberts de Girona: el centre obert de Taial��, el Centre Obert de Font de la P��lvora (Onyar), el Centre Obert de Santa Eug��nia i el Centre Obert del Barri Vell. Es van dur a terme grups de discussi�� d���una hora de duraci�� sense descans amb d���entre 6 i 8 persones a partir d���un gui�� format per diversos mites i frases en relaci�� a diversos temes (El festeig, la virginitat, la curiositat pel cos i per la sexualitat, els anticonceptius i les principals fonts d���informaci��) sobre les que havien de dir si estaven d���acord o no i qui creien que les deia (si un noi o una noia). Sobre els resultats del treball cal dir que s���ha observat la persist��ncia d���algunes creences del model del amor rom��ntic en relaci�� al rols de g��nere com la definici�� de la dona vinculada a papers de cura i prevenci��, una dona que t�� acc��s a la sexualitat per�� segueix estan catalogada per la viv��ncia d���aquesta essent una persona ���respectable��� o una ���puta���, que pren un rol m��s actiu en la iniciativa per�� no el l���assertivitat en les relacions; i un home, m��s impulsiu i sexual. En relaci�� als comportaments sexuals destacar l���embar��s no desitjat com la principal preocupaci�� de les relacions i el desconeixement/confusi�� entre els m��todes anticonceptius i de barrera disponibles a la xarxa de salut. Apareix la pornografia com a model emergent de relacions sexuals i models de relaci�� entre homes i dones, en contraposici�� a altres fonts de informaci�� i consulta tradicionals com els amics que segueixen essent la m��s significativa, la fam��lia, els serveis socials i educatius, i Internet. Com a conclusi�� cal dir que queda palesa la necessitat de incorporar una perspectiva de g��nere en la formaci�� curricular dels joves i el fet de seguir replantejant les millors estrat��gies d���intervenci�� per una concepci�� integradora de la sexualitat

Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal glial networks

Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT) and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR) heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT) and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT) and histamine striatal afferents, the cholinergic interneurons, and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal cellular networks