Characterization of human gene expression changes after olive oil ingestion: an exploratory approach

Olive oil consumption is protective against risk factors for cardiovascular and cancer diseases. A nutrigenomic approach was performed to assess whether changes in gene expression could occur in human peripheral blood mononuclear cells after oli ve oil ingestion at postprandial state. Six healthy male volunteers ingested, at fasting state, 50 ml of olive oil. Prior to intervention a 1-week washout period with a controlled diet and sunflower oil as the only source of fat was followed. During the 3 days before and on the intervention day, a very low-phenolic compound diet was followed. At baseline (0 h) and at post-ingestion (6 h), total RNA was isolated and gene expression (29,082 genes) was evaluated by microarray. From microarray data, nutrient-gene interactions were observed in genes related to metabolism, cellular processes, cancer, and atherosclerosis (e.g. USP48 by 2.16; OGT by 1.68-fold change) and associated processes such as inflammation (e.g. AKAP13 by 2.30; IL-10 by 1.66-fold change) and DNA damage (e.g. DCLRE1C by 1.47; POLK by 1.44- fold change). When results obtained by microarray were verified by qRT-PCR in nine genes, full concordance was achieved only in the case of up-regulated genes. Changes were observed at a real-life dose of olive oil, as it is daily consumed in some Mediterranean areas. Our results support the hypothesis that postprandial protective changes related to olive oil consumption could be mediated through gene expression changes.

Updated survival data of the phase iii clinical trial of novottf-100a versus best standard chemotherapy for recurrent glioblastoma

NovoTTF-100A (TTF) is a portable device delivering low-intensity, intermediate-frequency, alternating electric fields using noninvasive, disposable scalp electrodes. TTF interferes with tumor cell division, and it has been approved by the US Food and Drug Administration (FDA) for the treatment of recurrent glioblastoma (rGBM) based on data from a phase III trial. This presentation describes the updated survival data 2 years after completing recruitment. Adults with rGBM (KPS ≥ 70) were randomized (stratified by surgery and center) to either continuous TTF (20-24 h/day, 7 days/week) or efficacious chemotherapy based on best physician choice (BPC). The primary endpoint was overall survival (OS), and secondary endpoints were PFS6, 1-year survival, and QOL. Patients were randomized (28 US and European centers) to either TTF alone (n ¼ 120) or BPC (n ¼ 117). Patient characteristics were balanced, median age was 54 years (range, 23-80 years), and median KPS was 80 (range, 50-100). One quarter of the patients had debulking surgery, and over half of the patients were at their second or later recurrence. OS in the intent-to-treat (ITT) population was equivalent in TTF versus BPC patients (median OS, 6.6vs. 6.0 months; n ¼ 237; p ¼ 0.26; HR ¼ 0.86). With a median follow-up of 33.6 months, long-term survival in the TTF group was higher than that in the BPC group at 2, 3, and 4 years of follow-up (9.3% vs. 6.6%; 8.4% vs. 1.4%; 8.4% vs. 0.0%, respectively). Analysis of patients who received at least one treatment course demonstrated a survival benefit for TTF patients compared to BPC patients (median OS, 7.8 vs. 6.0 months; n ¼ 93 vs. n ¼ 117; p ¼ 0.012; HR ¼ 0.69). In this group, 1-year survival was 28% vs. 20%, and PFS6 was 26.2% vs. 15.2% (p ¼ 0.034). TTF, a noninvasive, novel cancer treatment modality shows significant therapeutic efficacy with promising long-term survival results. The impact of TTF was more pronounced when comparing only patients who received the minimal treatment course. A large-scale phase III trial in newly diagnosed GBM is ongoing.

Growth arrest-specific gene 6 (GAS6) as an intra-hospital mortality predictor for patients in septic shock

Aim: Gas6 is known to be elevated in sepsis, correlating with the severity of infection and organ failure. We aimed to investigate the performance of Gas6 plasma levels at admission to predict the risk of mortality in a cohort of septic patients.Methods: We used prospectively collected data and plasma samples from the 'Sepsis Cohorte Romande'. Gas6 level was measured by ELISA at admission and expressed in percentage relative to its level in a pool of normal plasma.Results: Non-survivors (n = 19) presented higher Gas6 levels than survivors (n = 78; median 287% vs. 158%, IQR 182 and 119 respectively; P = 0.0003). Gas6 correlated positively with different cytokine and was the best mortality predictor, as shown by the ROC curves area (Fig. 1). In patients with septic shock (n = 67), using 249% as a cut-off value, Gas6 measurement had a specificity of 81% and a sensitivity of 68% for predicting mortality. ROC curve area was 0.76. Positive and negative predictive values were 59% and 87%, respectively.Conclusion: Thus, Gas6 plasma level at admission might be a useful tool to predict mortality in patients with septic shock. Nevertheless, independent association of Gas6 level with mortality still needs to be assessed. Although Gas6 hold promise as an early sepsis marker, its precise implication in sepsis remains to be elucidated.

Innate immune response to poxvirus vectors

Summary : A large body of evidence indicates that the innate immune system plays a key role in host response to viral infection. Recently, Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and NOD-like receptor receptors (NLRs) have emerged as key innate immune sensors of microbial products, eliciting intracellular signaling and leading to the production of chemokines, cytokines and interferons (IFNs) that shape innate immune responses and coordinate the development of adaptive immunity. Poxviruses are currently developed as vaccines vectors for infectious diseases such as HIV, tuberculosis and malaria. Modified vaccinia virus Ankara (MVA) and New York vaccinia virus (NWAC) are attenuated, replication deficient strains of poxvirus. The mechanisms underlying innate immune responses to MVA and NYVAC are poorly characterized. Thus, the objectives of the project were to determine the innate immune profile stimulated by poxviruses in innate immune cells and to evaluate the impact of modifications in the viral genome on MVA and NYVAC immunogenicity. MVA stimulated the production of abundant amounts of chemokines and IFNß but low levels of cytokines by human macrophages. In contrast, NYVAC weakly stimulated the production of all mediators. Interestingly, MVA and NYVAC strongly stimulated innate immune responses in vivo and in human whole blood, suggesting that a soluble factors}, possibly a complement component, was required for optimal activation of innate immune cells by poxviruses. Modified MVA and NYVAC produced by single or multiple deletions of viral genes targeting crucial pathways of host innate immunity, and mutant poxviruses with limited replication capacity, increased the production of pro-inflammatory molecules by human whole blood. Gene expression profiling in human macrophages confirmed the increased immunologic stimulatory capacity of modified poxviruses. The pathways activated by MVA and NYVAC in innate immune cells were described by analysing the response of knockdown or shRNA transduced macrophages with impaired expression of TLRs and their adaptors (MyD8$ and TRIF), RLRs (RIG-I, MDA-5 and the adaptor IPS-1) and the NALP3 inflammasome composed óf the NLR NALP3, caspase-1 and ASC. These experiments revealed a critical role for TLR2-TLR6-MyD88 in the production of tFNß-independent chemokines and of MDA-5-IPS-1 in the production of IFNß and IFNßdependent chemokines. The transcription of the iL1b gene encoding for the IL-1ß cytokine was initiated through TLR2-MyD88, whereas the maturation and the secretion of IL-1ß were controlled by the NALP3 inflammasome. Finally, we analyzed the role of macrophage migration inhibitory factor (MIF), a mediator of inflammation and innate immune responses, in MVA infection. We observed that MVA infection increased MIF production by innate immune cells and that MIF deficiency impaired macrophage and dendritic cell responses (ie migration, maturation, cytokine and IFN production) to MVA infection in vitro and in vivo. Moreover, MIF-deficiency resulted in delayed anti-MVA specific antibody production in mice immunized with the virus. In conclusion, we demonstrate. that poxviruses can be modified genetically to improve their immunogenicity. We also report the first comprehensive analysis of poxvirus sensing by innate immune cells, showing that the TLR, RLR and NLR pathways play specific and coordinated roles in regulating cytokine, chemokine and IFN response to poxvirus infection. Finally, we show that MIF is an integral host component involved in innate and adaptive immune responses to MVA infection. The present findings provide important information relevant to the study of the pathogenesis of poxvirus infections and allow a better understanding of the immunogenic potential of vaccine vectors, which is required for the development of optimized modìfied pox-vaccine vectors.

IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction.

Approximately 3% of the world population is chronically infected with the hepatitis C virus (HCV), with potential development of cirrhosis and hepatocellular carcinoma. Despite the availability of new antiviral agents, treatment remains suboptimal. Genome-wide association studies (GWAS) identified rs12979860, a polymorphism nearby IL28B, as an important predictor of HCV clearance. We report the identification of a novel TT/-G polymorphism in the CpG region upstream of IL28B, which is a better predictor of HCV clearance than rs12979860. By using peripheral blood mononuclear cells (PBMCs) from individuals carrying different allelic combinations of the TT/-G and rs12979860 polymorphisms, we show that induction of IL28B and IFN-γ-inducible protein 10 (IP-10) mRNA relies on TT/-G, but not rs12979860, making TT/-G the only functional variant identified so far. This novel step in understanding the genetic regulation of IL28B may have important implications for clinical practice, as the use of TT/G genotyping instead of rs12979860 would improve patient management.

High elevation Plantago lanceolata plants are less resistant to herbivory than their low elevation conspecifics: is it just temperature?

Traits that mediate species interactions are evolutionarily shaped by biotic and abiotic drivers, yet we know relatively little about the relative importance of these factors. Herbivore pressure, along with resource availability and third-party' mutualists, are hypothesized to play a major role in the evolution of plant defence traits. Here, we used the model system Plantago lanceolata, which grows along steep elevation gradients in the Swiss Alps, to investigate the effect of elevation, herbivore pressure, mycorrhizal inoculation and temperature on plant resistance. Over a 1200 m elevation gradient, the levels of herbivory and iridoid glycosides (IGs) declined with increasing elevation. By planting seedlings at three different elevations, we further showed that both low-elevation growing conditions and mycorrhizal inoculation resulted in increased plant resistance to herbivores. Finally, using a temperature-controlled experiment comparing high- and low-elevation ecotypes, we showed that high-elevation ecotypes are less resistant to herbivory, and that lower temperatures impair IGs deployment after herbivore attack. We thus propose that both lower herbivore pressure, and colder temperatures relax the defense syndrome of high elevation plants.

Especificitats de la narrativa audiovisual informativa a Internet: anàlisi de les rutines de producció i dels vídeos produïts per La Vanguardia Digital, VilaWeb i 3cat24.cat

El present projecte d’investigació és el treball de recerca del Doctorat en Comunicació Pública (bienni 2007-2009) i es proposa de desenvolupar-lo com a tesi doctoral. Vol estudiar les especificitats de la narrativa audiovisual informativa a Internet de tres mitjans digitals decomunicació catalans. Per a fer-ho es proposa una metodologia qualitativa dividida en dos blocs: el primer, a partir de l'observació, entrevistes en profunditat i enquestes, vol investigar les novesrutines de producció audiovisual en aquests tres mitjans, condicionades per un nou entorn digital; el segon, a partir de la narratologia, vol analitzar els efectes d'aquestes rutines i d'aquest nou entorn enel producte audiovisual resultant

Shifts in species and phylogenetic diversity between sapling and tree communities indicate negative density dependence in a lowland rain forest

1. As trees in a given cohort progress through ontogeny, many individuals die. This risk of mortality is unevenly distributed across species because of many processes such as habitat filtering, interspecific competition and negative density dependence. Here, we predict and test the patterns that such ecological processes should inscribe on both species and phylogenetic diversity as plants recruit from saplings to the canopy. 2. We compared species and phylogenetic diversity of sapling and tree communities at two sites in French Guiana. We surveyed 2084 adult trees in four 1-ha tree plots and 943 saplings in sixteen 16-m2 subplots nested within the tree plots. Species diversity was measured using Fisher's alpha (species richness) and Simpson's index (species evenness). Phylogenetic diversity was measured using Faith's phylogenetic diversity (phylogenetic richness) and Rao's quadratic entropy index (phylogenetic evenness). The phylogenetic diversity indices were inferred using four phylogenetic hypotheses: two based on rbcLa plastid DNA sequences obtained from the inventoried individuals with different branch lengths, a global phylogeny available from the Angiosperm Phylogeny Group, and a combination of both. 3. Taxonomic identification of the saplings was performed by combining morphological and DNA barcoding techniques using three plant DNA barcodes (psbA-trnH, rpoC1 and rbcLa). DNA barcoding enabled us to increase species assignment and to assign unidentified saplings to molecular operational taxonomic units. 4. Species richness was similar between saplings and trees, but in about half of our comparisons, species evenness was higher in trees than in saplings. This suggests that negative density dependence plays an important role during the sapling-to-tree transition. 5. Phylogenetic richness increased between saplings and trees in about half of the comparisons. Phylogenetic evenness increased significantly between saplings and trees in a few cases (4 out of 16) and only with the most resolved phylogeny. These results suggest that negative density dependence operates largely independently of the phylogenetic structure of communities. 6. Synthesis. By contrasting species richness and evenness across size classes, we suggest that negative density dependence drives shifts in composition during the sapling-to-tree transition. In addition, we found little evidence for a change in phylogenetic diversity across age classes, suggesting that the observed patterns are not phylogenetically constrained.

La Gestió econòmico-empresarial d'un club de futbol

Hi ha records que perduraran sempre; el gol d’Iniesta contra el Chelsea, la boleia de Zidane a Hampden Park… Aquests moments memorables que queden gravats a les retines de tots nosaltres i produeixen una immensa felicitat a l’ésser humà, que l’emocionen, que el fan casi plorar. Tot això es produeix gràcies a un esport de masses molt present en les nostres vides, el futbol. Una activitat merament esportiva que s’ha convertit, amb el pas dels anys, en quelcom més que un esport, ha travessat l’àmbit purament sentimental d’una regió fins a assolir nivells d’autèntica globalització arreu del món. I és precisament el fet que el futbol porta una immensa passió a tots els racons de la societat, el que fa plantejar-nos el funcionament d’aquesta gran indústria de l’entreteniment.La realitat, tanmateix, revela l’existència de tot un món econòmico-empresarial que s’amaga darrere aquest espectacle, del qual, els veritables protagonistes són els clubs de futbol. Sense ells no es produiria mai l’espectacle. És per aquest motiu, que centrarem el nostre anàlisi sobre aquestes entitats esportives: veure el seu funcionament en la seva vessant més econòmica (1).En el present estudi s’analitzarà tot el funcionament intern d’un club, des del seu marc legal fins a l’econòmic, parant molta atenció en el que és el mercat futbolístic, el qual, al cap i a la fi, acaba relacionant la part més esportiva amb l’empresarial. A partir d’aquí intentarem extrapolar aquest entramat al que és el món futbolístic en general.Amb això, intentarem qüestionar-nos el perquè del gran moviment de divises existent, actualment, en aquest esport. Com pot ser que un club inverteixi més de 30 milions d’euros (2) només en el que seria contractar un nou treballador? Com es podengenerar tants recursos per després gastar-los en nòmines astronòmiques pels jugadors?Doncs aquest seguit de qüestions es el que pretenem respondre en aquest treball, de la forma més amena i clara possible, amb els gràfics i taules més adients.(1) Com que de clubs de futbol n’hi ha molts i no els podem analitzar tots un per un, partirem de la based’agafar-ne un com a model, en aquest cas, per la seva proximitat i facilitat d’obtenció de dades hemescollit el FC Barcelona.(2) Quantitat que equival, ni més ni menys, a 500 vegades el sou d’un treballador mitjà al llarg de tota la seva vida

Instal·lació fotovoltaica a la UPF : projecte de viabilitat

És viable portar a terme la instal·lació de panells solars fotovoltaics a la UniversitatPompeu Fabra? Està dins dels objectius de la universitat? Per què encara no s’ha portat a terme un projecte com aquest en cap campus de la UPF? Aquest treball busca donar resposta a totes aquestes preguntes i fer-ho de manera realista i imparcial.Primer de tot, hem de destacar que fer una instal·lació solar en un edifici és, a diferència del que ens ve al cap primerament, una inversió. Amb això volem dir que l’energia generada per cada panell solar no es dedica al consum de la niversitat, sinó que es ven a la xarxa elèctrica a un preu fixat per llei. Així que el que tenim entre mans és clarament una inversió i, evidentment, ens pot fer guanyar diners.L’espina dorsal del treball és un estudi exhaustiu de la viabilitat econòmica que tindria aquesta inversió en diferents escenaris. Hem centrat l’estudi en el Campus de la Ciutadella de la UPF, concretament sobre les cobertes dels edificis Roger de Llúria i Jaume Primer; i hem calculat el VAN, TIR i pay-back de la inversió sota diferents circumstàncies per mostrar un panorama complert de la situació. Tot i això, el treball no es queda aquí. Emmarcant l’estudi de la inversió, s’ha situat lesenergies renovables en l’actualitat, concretament la solar fotovoltaica, s’ha comparat la ideologia de la UPF amb les ideologies d’altres universitats catalanes que compten amb instal·lacions solars, s’ha comparat els projectes de diverses d’aquestesuniversitats amb el que seria el projecte de la UPF i, per últim, s’ha plantejat unaproposta d’obtenció d’ingressos per tal de millorar la inversió o participar en altresprojectes ecològics. La nostra opinió és que aquest tema té un gran rerefons, ja que neix conceptes relacionats amb la economia, la imatge, la responsabilitat social o l’evolució. Per tant, animem al lector a continuar llegint i descobrir la resposta a tots aquests interrogants.

SOSelectiva

Este trabajo nace de la idea de que el sistema de recogida selectiva de residuos en Barcelona puede mejorarse. Para respaldar esta hipótesis previa, hemos utilizado tanto datos de organismos oficiales (La EMMA o el Ayuntamiento de BCN por citar algunos de los más relevantes) como encuestas realizados por nosotros mismos y que han sido distribuidas a una muestra de aproximadamente 180 personas de la ciudadcondal.Con la información obtenida de estas fuentes, podemos afirmar que, definitivamente, estábamos en lo correcto: el sistema puede mejorarse.En este punto es necesario ser precisos y explicar qué entendemos por mejorar.Concretamente, lo que nosotros queremos hacer es incrementar el porcentaje de cantidad recogida de papel-cartón, vidrio y envases ligeros sobre el total consumido deestos materiales. Este será nuestro objetivo durante todo el estudio. Y, como el lectordescubrirá, hemos propuesto dos vías para conseguir tal cosa: incrementar el número decontenedores (método extensivo) o implementar una nueva tecnología (métodointensivo). El planteamiento y desarrollo de estas dos propuestas será la piedra angulardel trabajo.Ahora bien, a modo de anticipo, ¿qué podemos decirle al lector sobre estas vías?¿Consiguen el objetivo que se proponen? ¿Son aplicables? La respuesta es que, como severá a lo largo de estas páginas, el método extensivo consigue efectivamente incrementar el porcentaje de cantidad recogida mientras que la vía intensiva, aunque tiene la ventaja de que es capaz de reducir los costes que se derivan del proceso (costesde transporte…) y es consecuente con políticas de sostenibilidad medioambiental (higieniza los residuos, reduce enormemente los desechos destinados a depósitoscontrolados e incineradoras) presenta la gran desventaja de que precisamente por seruna tecnología nueva, no hay suficientes datos para estudiar su comportamiento en unperiodo de tiempo largo. Por tanto, en este estudio se abogará por la estrategia extensiva, en pos de mostrar un análisis más coherente y de implementación rápida.

Economia digital : una sortida per a múltiples sistemes comercials

Economia Digital: Una sortida per a múltiples sistemes comercials, és un treball de recerca que tracta sobre el comerç electrònic en tots els seus aspectes, partint d’un anàlisi teòric que estableix les bases d’aquest sistema comercial; seguit d’un estudi de dos casos concrets d’empreses que han introduït Internet en la seva activitat. Per una banda, una d’aquestes empreses, Destil·leries Julián Segarra, s’ha servit de les noves tecnologies, amb un ús publicitari, per tal de donar-se a conèixer però sense oferir la possibilitat de venda online. D’altra banda, Surfdevils S.L. no només utilitza els recursos que ofereix la xarxa de manera informativa, sinó que va més enllà i permet adquirir els seus productes mitjançant el seu espai web. A més es realitza un breu estudi sobre els hàbits de compra per Internet, mitjançant una enquesta efectuada a una mostra de la població.Tot aquest estudi, serveix per arribar a la conclusió que introduir el comerç electrònic dins del seu funcionament és rentable per a les empreses i beneficiós pels consumidors, ja que els ofereix la possibilitat d’adquirir els productes en un mercat més ampli, transparent i competitiu.

Histone deacetylase inhibitors repress macrophage migration inhibitory factor (MIF) expression by targeting MIF gene transcription through a local chromatin deacetylation.

The cytokine macrophage migration inhibitory factor plays a central role in inflammation, cell proliferation and tumorigenesis. Moreover, macrophage migration inhibitory factor levels correlate with tumor aggressiveness and metastatic potential. Histone deacetylase inhibitors are potent antitumor agents recently introduced in the clinic. Therefore, we hypothesized that macrophage migration inhibitory factor would represent a target of histone deacetylase inhibitors. Confirming our hypothesis, we report that histone deacetylase inhibitors of various chemical classes strongly inhibited macrophage migration inhibitory factor expression in a broad range of cell lines, in primary cells and in vivo. Nuclear run on, transient transfection with macrophage migration inhibitory factor promoter reporter constructs and transduction with macrophage migration inhibitory factor expressing adenovirus demonstrated that trichostatin A (a prototypical histone deacetylase inhibitor) inhibited endogenous, but not episomal, MIF gene transcription. Interestingly, trichostatin A induced a local and specific deacetylation of macrophage migration inhibitory factor promoter-associated H3 and H4 histones which did not affect chromatin accessibility but was associated with an impaired recruitment of RNA polymerase II and Sp1 and CREB transcription factors required for basal MIF gene transcription. Altogether, this study describes a new molecular mechanism by which histone deacetylase inhibitors inhibit MIF gene expression, and suggests that macrophage migration inhibitory factor inhibition by histone deacetylase inhibitors may contribute to the antitumorigenic effects of histone deacetylase inhibitors.

Estradiol and progesterone strongly inhibit the innate immune response of mononuclear cells in newborns.

Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period.