Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription.

Lipophilic compounds such as retinoic acid and long-chain fatty acids regulate gene transcription by activating nuclear receptors such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptors (PPARs). These compounds also bind in cells to members of the family of intracellular lipid binding proteins, which includes cellular retinoic acid-binding proteins (CRABPs) and fatty acid binding proteins (FABPs). We previously reported that CRABP-II enhances the transcriptional activity of RAR by directly targeting retinoic acid to the receptor. Here, potential functional cooperation between FABPs and PPARs in regulating the transcriptional activities of their common ligands was investigated. We show that adipocyte FABP and keratinocyte FABP (A-FABP and K-FABP, respectively) selectively enhance the activities of PPARgamma and PPARbeta, respectively, and that these FABPs massively relocate to the nucleus in response to selective ligands for the PPAR isotype which they activate. We show further that A-FABP and K-FABP interact directly with PPARgamma and PPARbeta and that they do so in a receptor- and ligand-selective manner. Finally, the data demonstrate that the presence of high levels of K-FABP in keratinocytes is essential for PPARbeta-mediated induction of differentiation of these cells. Taken together, the data establish that A-FABP and K-FABP govern the transcriptional activities of their ligands by targeting them to cognate PPARs in the nucleus, thereby enabling PPARs to exert their biological functions.

Cooperation and game theory, free software or the #15m movement: Two examples for universities

Closing talk of the Open Access Week 2011 at the UOC, by Josep Jover. Why do altruistic strategies beat selfish ones in the spheres of both free software and the #15m movement? The #15m movement, like software but unlike tangible goods, cannot be owned. It can be used (by joining it) by an indeterminate number of people without depriving anyone else of the chance to do the same. And that turns everything on its head: how universities manage information and what their mission is in this new society. In the immediate future, universities will be valued not for the information they harbour, which will always be richer and more extensive beyond their walls, but rather for their capacity to create critical masses, whether of knowledge research, skill-building, or networks of peers... universities must implement the new model or risk becoming obsolete.

Determinants of science-based cooperation: evidence in a sample of small and micro firms

We study the determining factors of cience-based cooperation in the case of small and micro firms. In this research, we propose an analytical framework based on the resource-based view of the firm and we identify a set of organisational characteristics, which we classify as internal, external and structural factors. Each factor can be linked to at least one reason, from the firm¿s point of view, to cooperate with universities and public research centres. Each reason can, in turn, be used as an indicator of a firm¿s organisational needs or organisational capacities. In order to validate the theoretical model, we estimate a logistic regression that models the propensity to participate in science-based cooperation activities within a sample of 285 small and micro firms located in Barcelona. The results show the key role played by the absorptive capacity of new and small companies.

Distribuição horizontal e vertical de fósforo em sistemas de cultivos exclusivos de soja e de integração lavoura-pecuária-floresta

O objetivo deste trabalho foi avaliar a distribuição horizontal e vertical do fósforo no solo e a produtividade de soja em sistemas de cultivos exclusivos e de integração lavoura-pecuária-floresta (ILPF). Foram avaliados os tratamentos: floresta plantada de eucalipto; lavoura de soja e milho safrinha consorciado com Urochloa brizantha 'Marandu'; pastagem de U. brizantha; sistema de ILPF; e duas áreas controle, com floresta nativa e pousio. O solo foi coletado nas camadas de 0-5, 5-10, 10-20 e 20-30 cm, para determinação das características químicas. As avaliações foram realizadas no segundo ano agrícola após a implantação do experimento. No sistema de ILPF, solo e produtividade foram avaliados em quatro transectos equidistantes, no centro do renque e a 3, 6, 10 e 15 m do renque, nas faces norte e sul. Os teores de P disponível (Mehlich-1) foram maiores nas camadas superficiais do solo, nos sistemas com soja/milho safrinha e com ILPF. No ILPF, os teores de P disponível não diferiram entre as distâncias do renque das árvores, e a produtividade de soja não diferiu da observada no sistema com soja/milho safrinha. Portanto, com dois anos de implantação, o sistema ILPF ainda não é capaz de interferir marcadamente nas características químicas do solo e na produtividade da soja.

Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.

Inherited mutations in human PALB2 are associated with a predisposition to breast and pancreatic cancers. PALB2's tumor-suppressing effect is thought to be based on its ability to facilitate BRCA2's function in homologous recombination. However, the biochemical properties of PALB2 are unknown. Here we show that human PALB2 binds DNA, preferentially D-loop structures, and directly interacts with the RAD51 recombinase to stimulate strand invasion, a vital step of homologous recombination. This stimulation occurs through reinforcing biochemical mechanisms, as PALB2 alleviates inhibition by RPA and stabilizes the RAD51 filament. Moreover, PALB2 can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion. Finally, we show that PALB2-deficient cells are sensitive to PARP inhibitors. Our studies provide the first biochemical insights into PALB2's function with piBRCA2 as a mediator of homologous recombination in DNA double-strand break repair.

Stochasticity and bistability in horizontal transfer control of a genomic island in Pseudomonas.

Genomic islands (GEI) comprise a recently recognized large family of potentially mobile DNA elements and play an important role in the rapid differentiation and adaptation of bacteria. Most importantly, GEIs have been implicated in the acquisition of virulence factors, antibiotic resistances or toxic compound metabolism. Despite detailed information on coding capacities of GEIs, little is known about the regulatory decisions in individual cells controlling GEI transfer. Here, we show how self-transfer of ICEclc, a GEI in Pseudomonas knackmussii B13 is controlled by a series of stochastic processes, the result of which is that only a few percent of cells in a population will excise ICEclc and launch transfer. Stochastic processes have been implicated before in producing bistable phenotypic transitions, such as sporulation and competence development, but never before in horizontal gene transfer (HGT). Bistability is instigated during stationary phase at the level of expression of an activator protein InrR that lays encoded on ICEclc, and then faithfully propagated to a bistable expression of the IntB13 integrase, the enzyme responsible for excision and integration of the ICEclc. Our results demonstrate how GEI of a very widespread family are likely to control their transfer rates. Furthermore, they help to explain why HGT is typically confined to few members within a population of cells. The finding that, despite apparent stochasticity, HGT rates can be modulated by external environmental conditions provides an explanation as to why selective conditions can promote DNA exchange.

An operon of three transcriptional regulators controls horizontal gene transfer of the integrative and conjugative element ICEclc in Pseudomonas knackmussii B13.

The integrative and conjugative element ICEclc is a mobile genetic element in Pseudomonas knackmussii B13, and an experimental model for a widely distributed group of elements in Proteobacteria. ICEclc is transferred from specialized transfer competent cells, which arise at a frequency of 3-5% in a population at stationary phase. Very little is known about the different factors that control the transfer frequency of this ICE family. Here we report the discovery of a three-gene operon encoded by ICEclc, which exerts global control on transfer initiation. The operon consists of three consecutive regulatory genes, encoding a TetR-type repressor MfsR, a MarR-type regulator and a LysR-type activator TciR. We show that MfsR autoregulates expression of the operon, whereas TciR is a global activator of ICEclc gene expression, but no clear role was yet found for MarR. Deletion of mfsR increases expression of tciR and marR, causing the proportion of transfer competent cells to reach almost 100% and transfer frequencies to approach 1 per donor. mfsR deletion also caused a two orders of magnitude loss in population viability, individual cell growth arrest and loss of ICEclc. This indicates that autoregulation is an important feature maintaining ICE transfer but avoiding fitness loss. Bioinformatic analysis showed that the mfsR-marR-tciR operon is unique for ICEclc and a few highly related ICE, whereas tciR orthologues occur more widely in a large variety of suspected ICE among Proteobacteria.

Interfirm Knowledge Transfer in Coopetitive Relationships

Tämä tutkimuskeskittyy yritysten väliseen samanaikaiseen kilpailuun ja yhteistyöhön. Suurin mielenkiinto tässä tutkimuksessa kohdistuu yritysten väliseen tietämyksen siirtoon. Tietämyksen siirto samanaikaisissa kilpailu- ja yhteistyösuhteissa voi olla erityisen hyödyllistä samankaltaisten toimintalogiikoiden ja ymmärryksen takia. Toisaalta, mahdollinen kriittisen tiedon vuotaminen kilpailevalle yritykselle onriski, joka täytyy ottaa huomioon, kun yhteistyötä kilpailijan kanssa suunnitellaan. Tämän tutkimuksen tavoitteena on selvittää, kuinka tietämystä siirretään samanaikaisissa kilpailu- ja yhteistyösuhteissa välttäen kuitenkin tähän liittyvät riskit. Tutkimuksen empiirinen osa sisältää kolme erilaista case-esimerkkiä samanaikaisista kilpailu- ja yhteistyösuhteista. Empiirisessä osassa tehdyt havainnot tukevat pääasiassa teoriaosuudessa käsiteltyjä asioita. Tietämyksen siirron motiivit, suhdekohtaiset tietämyksen omaksumiskyvyt, tietojohtamiskäytännöt ja luottamus ovat tekijöitä, jotka vaikuttavat tietämyksen siirron tehokkuuteen. Pääasialliset keinot tietämyksen siirron riskin välttämiseksi samanaikaisissa kilpailu- ja yhteistyösuhteissa ovat hierarkkisen hallintomuodon käyttäminen tai horisontaalisesti ja vertikaalisesti rajattu yhteistyön laajuus.

Potential for enterprise cooperation between Southeast Finland and Northwest Russia

Tutkimus käsittelee Kaakkois-Suomen ja Luoteis-Venäjän yritysten nykyistä yhteistyötä ja arvioi sen tulevaisuuden mahdollisuuksia. Raportissa käydään läpi useita toimialoja, jotka ovat tärkeitä paikalliselle elinkeinoelämälle tai joissa Venäjän merkitys on korostunut. Tutkimukset kattamat alat ovat metsäteollisuus, elintarviketeollisuus, metalliteollisuus, tieto- ja viestintäteollisuus, logistiikka, matkailusekä energia ja ympäristö. Kaakkois-Suomen ja Luoteis-Venäjän väliset kauppa- ja taloussuhteet ovat perinteisesti olleet vilkkaat maantieteellisestä läheisyydestä johtuen. Pääpaino kanssakäymisessä on ollut kaupalla, mutta Neuvostoliiton hajottua yritysten välille on kehittynyt myös muita yhteistoiminnan muotoja kutenyhteistuotantoa ja alihankintaa. Kaakkois-Suomen yritysten näkökulmasta Venäjänedullinen kustannustaso houkuttelee siirtämään tuotannollisia toimintoja rajan taakse. Tuotannollisen yhteistoiminnan aloittamista ja menestyksellistä toteuttamista hankaloittaa kuitenkin yritysympäristön kehittymättömyys Venäjällä ja usein myös osapuolten näkemyserot toiminnan tavoitteista ja liiketoimintakäytännöistä. Raportin ensimmäisessä osassa arvioidaan yhteistyöpotentiaalia valituilla toimialoilla analysoimalla alojen nykytilaa Kaakkois-Suomessa ja Luoteis- Venäjällä. Nykytilakartoituksen avulla selvitetään yhteistyön motiiveja suomalaisten yritysten kannalta ja sen tuottamaa mahdollista kilpailuetua. Toisessa osassa kuvataan Luoteis-Venäjän muodollista liiketoimintaympäristöä, mukaan lukien lainsäädäntö, hallinto ja liiketoiminnan tukiorganisaatiot. Kolmannessa osassa esitetään suomalais-venäläistä yritysyhteistyötä koskevia kokemuksia ja odotuksia, verrataan eri osapuolten näkemyksiä keskenään ja kuvataan yhteistyön yleisimpiä rajoitteita ja ongelmia. Tutkimustulosten valossa vaikuttaa siltä, että Luoteis-Venäjällä tuotannosta saatu kustannushyöty on pienenemässä palkkojen ja energiakustannusten noustessa. Luoteis-Venäjän merkitys markkina-alueena on vastaavasti kasvussa. Tavaroiden viennin lisäksi talouskasvu ja paikalliset investoinnit esimerkiksilogistiikka- ja energiainfrastruktuuriin tarjoavat mahdollisuuksia suomalaisille palveluiden ja teknologian viejille. Toisaalta monikansallisten yritysten etabloituminen Luoteis-Venäjälle (esim. Ford ja IKEA) luovat kysyntää paikallisille alihankkijoille. Suomalaisyritykset voisivat ottaa siitä osansa investoimalla paikalliseen tuotantoon. Palvelualoilla, kuten logistiikkasektorilla ja matkailussa Luoteis-Venäjän merkitys Kaakkois-Suomen kilpailijana on kasvussa paikallisen infrastruktuurin kehittyessä. Näillä aloilla tulisikin keskittyä ei ainoastaan Suomen kilpailukyvyn ylläpitoon vaan myös liiketoimintayhteistyön kehittämiseen venäläisten toimijoiden kanssa.

Let's share perspectives! Mentalistic skills involved in cooperation = ¿A tu Izquierda o a la Mía? Habilidades Mentalistas Implicadas en la Cooperación

Previous research has found a link between theory of mind and cooperation. The aim of this study is to deepen into this relationship, to identify which theory of mind skills are more related to the cooperative capacity on a referential communication task. A total of 50 children from first and fifth grade completed a battery of theory of mind tasks, and also a cooperative task where children worked in pairs to build block models. Each pair was composed by a builder and a guide, who gave instructions to his partner about how to build a replica of the model. The results show a significant relationship between the theory of mind skills and cooperation. Specifically, we found that the second-order false-belief task was the variable most related to cooperation after controlling the effect of age. In addition, we observed that the mentalist skills were more important for cooperation in the builders than in the guides. Finally, we discuss the findings of this study and make suggestions for the future

Diagnostic and Prognostic Impact of pc-ASPECTS Applied to Perfusion CT in the Basilar Artery International Cooperation Study.

BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-APECTS) applied to CT angiography source images (CTA-SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic and prognostic impact of pc-ASPECTS applied to perfusion CT (CTP) in the BASICS registry population. METHODS: We applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal. RESULTS: CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI], 76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23 patients with a CBV pc-ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9-7.6). CONCLUSION: CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps. CBV pc-ASPECTS < 8 may indicate patients with high case fatality.