Regional Innovation Policy: Effect on SMEs in Five EU-Regions

Valtaosa eurooppalaisista yrityksistä on pk-yrityksiä, mutta tästä huolimatta seudullisen innovaatiopolitiikan vaikutusta juuri pk-yrityksiin on tutkittu melko vähän. Tämän tutkimuksen tarkoituksena on luoda yleiskuva pk-yritysten näkemykseen oman seutunsa innovaatiopolitiikasta viidellä EU:n alueella sijaitsevalla seudulla. Kirjallisuuden perusteella rakennettiin seudullista innovaatiopolitiikkaa kuvaava kysely, johon joukko pk-yrityksiä viideltä seudulta vastasi. Kyselyn tulokset kuvailtiin graafisesti, minkä lisäksi etsittiin vastauksiin vaikuttaneita tekijöitä ja yhteyksiä yritysten vastausten välillä. Tutkimus oli luonteeltaan lähinnä kvantitatiivinen. Tutkimus osoittaa, että seudullisessainnovaatiopolitiikassa on vielä paljon kehitettävää, jotta se tavoittaisi kattavasti pk-yritykset. Pk-yritysten tietoisuutta tulisi lisätä, sillä nämä eivät yleisesti ottaen näytä pitävän seudullista innovaatiopolitiikkaa menetykseen vaikuttavana tekijänä tai siihen liittyviä yhteistyömahdollisuuksia tärkeinä omalle toiminnalleen. Erot innovaatiotoiminnan seudullisessa roolissa tulivat esiin tuloksissa. Yritysten vastauksia selittäviä tekijöitä löydettiin, samoin yhteyksiä vastausten välillä, mutta varsinaisten johtopäätösten tekeminen edellyttänee laajempaa tutkimusta

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.

Genome-wide prediction of matrix attachment regions that increase gene expression in mammalian cells.

Gene transfer in eukaryotic cells and organisms suffers from epigenetic effects that result in low or unstable transgene expression and high clonal variability. Use of epigenetic regulators such as matrix attachment regions (MARs) is a promising approach to alleviate such unwanted effects. Dissection of a known MAR allowed the identification of sequence motifs that mediate elevated transgene expression. Bioinformatics analysis implied that these motifs adopt a curved DNA structure that positions nucleosomes and binds specific transcription factors. From these observations, we computed putative MARs from the human genome. Cloning of several predicted MARs indicated that they are much more potent than the previously known element, boosting the expression of recombinant proteins from cultured cells as well as mediating high and sustained expression in mice. Thus we computationally identified potent epigenetic regulators, opening new strategies toward high and stable transgene expression for research, therapeutic production or gene-based therapies.

Interhemispheric coupling between the posterior sylvian regions impacts successful auditory temporal order judgment.

Accurate perception of the temporal order of sensory events is a prerequisite in numerous functions ranging from language comprehension to motor coordination. We investigated the spatio-temporal brain dynamics of auditory temporal order judgment (aTOJ) using electrical neuroimaging analyses of auditory evoked potentials (AEPs) recorded while participants completed a near-threshold task requiring spatial discrimination of left-right and right-left sound sequences. AEPs to sound pairs modulated topographically as a function of aTOJ accuracy over the 39-77ms post-stimulus period, indicating the engagement of distinct configurations of brain networks during early auditory processing stages. Source estimations revealed that accurate and inaccurate performance were linked to bilateral posterior sylvian regions activity (PSR). However, activity within left, but not right, PSR predicted behavioral performance suggesting that left PSR activity during early encoding phases of pairs of auditory spatial stimuli appears critical for the perception of their order of occurrence. Correlation analyses of source estimations further revealed that activity between left and right PSR was significantly correlated in the inaccurate but not accurate condition, indicating that aTOJ accuracy depends on the functional decoupling between homotopic PSR areas. These results support a model of temporal order processing wherein behaviorally relevant temporal information--i.e. a temporal 'stamp'--is extracted within the early stages of cortical processes within left PSR but critically modulated by inputs from right PSR. We discuss our results with regard to current models of temporal of temporal order processing, namely gating and latency mechanisms.

Regional Innovation Policy: Effect on SMEs in Five EU-Regions

Valtaosa eurooppalaisista yrityksistä on pk-yrityksiä, mutta tästä huolimatta seudullisen innovaatiopolitiikan vaikutusta juuri pk-yrityksiin on tutkittu melko vähän. Tämän tutkimuksen tarkoituksena on luoda yleiskuva pk-yritysten näkemykseen oman seutunsa innovaatiopolitiikasta viidellä EU:n alueella sijaitsevalla seudulla. Kirjallisuuden perusteella rakennettiin seudullista innovaatiopolitiikkaa kuvaava kysely, johon joukko pk-yrityksiä viideltä seudulta vastasi. Kyselyn tulokset kuvailtiin graafisesti, minkä lisäksi etsittiin vastauksiin vaikuttaneita tekijöitä ja yhteyksiä yritysten vastausten välillä. Tutkimus oli luonteeltaan lähinnä kvantitatiivinen. Tutkimus osoittaa, että seudullisessa innovaatiopolitiikassa on vielä paljon kehitettävää, jotta se tavoittaisi kattavasti pk-yritykset. Pk-yritysten tietoisuutta tulisi lisätä, sillä nämä eivät yleisesti ottaen näytä pitävän seudullista innovaatiopolitiikkaa menetykseen vaikuttavana tekijänä tai siihen liittyviä yhteistyömahdollisuuksia tärkeinä omalle toiminnalleen. Erot innovaatiotoiminnan seudullisessa roolissa tulivat esiin tuloksissa. Yritysten vastauksia selittäviä tekijöitä löydettiin, samoin yhteyksiä vastausten välillä, mutta varsinaisten johtopäätösten tekeminen edellyttänee laajempaa tutkimusta.

Copy number variation in the porcine genome inferred from a 60 k SNP BeadChip

Background: Recent studies in pigs have detected copy number variants (CNVs) using the Comparative Genomic Hybridization technique in arrays designed to cover specific porcine chromosomes. The goal of this study was to identify CNV regions (CNVRs) in swine species based on whole genome SNP genotyping chips. Results: We used predictions from three different programs (cnvPartition, PennCNV and GADA) to analyze data from the Porcine SNP60 BeadChip. A total of 49 CNVRs were identified in 55 animals from an Iberian x Landrace cross (IBMAP) according to three criteria: detected in at least two animals, contained three or more consecutive SNPs and recalled by at least two programs. Mendelian inheritance of CNVRs was confirmed in animals belonging to several generations of the IBMAP cross. Subsequently, a segregation analysis of these CNVRs was performed in 372 additional animals from the IBMAP cross and its distribution was studied in 133 unrelated pig samples from different geographical origins. Five out of seven analyzed CNVRs were validated by real time quantitative PCR, some of which coincide with well known examples of CNVs conserved across mammalian species. Conclusions: Our results illustrate the usefulness of Porcine SNP60 BeadChip to detect CNVRs and show that structural variants can not be neglected when studying the genetic variability in this species.

Genomic evidence for role of inversion 3RP of Drosophila melanogaster in facilitating climate change adaptation.

Chromosomal inversion polymorphisms are common in animals and plants, and recent models suggest that alternative arrangements spread by capturing different combinations of alleles acting additively or epistatically to favour local adaptation. It is also thought that inversions typically maintain favoured combinations for a long time by suppressing recombination between alternative chromosomal arrangements. Here, we consider patterns of linkage disequilibrium and genetic divergence in an old inversion polymorphism in Drosophila melanogaster (In(3R)Payne) known to be associated with climate change adaptation and a recent invasion event into Australia. We extracted, karyotyped and sequenced whole chromosomes from two Australian populations, so that changes in the arrangement of the alleles between geographically separated tropical and temperate areas could be compared. Chromosome-wide linkage disequilibrium (LD) analysis revealed strong LD within the region spanned by In(3R)Payne. This genomic region also showed strong differentiation between the tropical and the temperate populations, but no differentiation between different karyotypes from the same population, after controlling for chromosomal arrangement. Patterns of differentiation across the chromosome arm and in gene ontologies were enhanced by the presence of the inversion. These data support the notion that inversions are strongly selected by bringing together combinations of genes, but it is still not clear if such combinations act additively or epistatically. Our data suggest that climatic adaptation through inversions can be dynamic, reflecting changes in the relative abundance of different forms of an inversion and ongoing evolution of allelic content within an inversion.

Breeding, genetic and genomic of citrus for disease resistance

Although the citriculture is one of the most important economic activities in Brazil, it is based on a small number of varieties. This fact has contributed for the vulnerability of the culture regarding the phytosanitary problems. A higher number of varieties/genotypes with potential for commercial growing, either for the industry or fresh market, has been one of the main objectives of citrus breeding programs. The genetic breeding of citrus has improved, in the last decades, due to the possibility of an association between biotechnological tools and classical methods of breeding. The use of molecular markers for early selection of zygotic seedlings from controlled crosses resulted in the possibility of selection of a high number of new combination and, as a consequence, the establishment of a great number of hybrids in field experiments. The faster new tools are incorporated in the program, the faster is possibility to reach new genotypes that can be tested as a new variety. Good traits should be kept or incorporate, whereas bad traits have to be excluded or minimized in the new genotype. Scion and rootstock can not be considered separately, and graft compatibility, fruit quality and productivity are essential traits to be evaluated in the last stages of the program. The mapping of QTLs has favored breeding programs of several perennial species and in citrus it was possible to map several characteristics with qualitative and quantitative inheritance. The existence of linkage maps and QTLs already mapped, the development of EST and BAC library and the sequencing of the Citrus complete genome altogether make very demanding and urgent the exploration of such data to launch a wider genetic study of citrus. The rising of information on genome of several organisms has opened new approaches looking for integration between breeding, genetic and genome. Genome assisted selection (GAS) involves more than gene or complete genome sequencing and is becoming an import support in breeding programs of annual and perennial species. An huge information amount can be derivate from genome analysis. The use and benefit of such informations will depend on the genetic basis of the breeding program.

Patterns of nucleotide diversity at the regions encompassing the Drosophila insulin-like peptide (dilp) genes: demography vs positive selection in Drosophila melanogaster.

In Drosophila, the insulin-signaling pathway controls some life history traits, such as fertility and lifespan, and it is considered to be the main metabolic pathway involved in establishing adult body size. Several observations concerning variation in body size in the Drosophila genus are suggestive of its adaptive character. Genes encoding proteins in this pathway are, therefore, good candidates to have experienced adaptive changes and to reveal the footprint of positive selection. The Drosophila insulin-like peptides (DILPs) are the ligands that trigger the insulin-signaling cascade. In Drosophila melanogaster, there are several peptides that are structurally similar to the single mammalian insulin peptide. The footprint of recent adaptive changes on nucleotide variation can be unveiled through the analysis of polymorphism and divergence. With this aim, we have surveyed nucleotide sequence variation at the dilp1-7 genes in a natural population of D. melanogaster. The comparison of polymorphism in D. melanogaster and divergence from D. simulans at different functional classes of the dilp genes provided no evidence of adaptive protein evolution after the split of the D. melanogaster and D. simulans lineages. However, our survey of polymorphism at the dilp gene regions of D. melanogaster has provided some evidence for the action of positive selection at or near these genes. The regions encompassing the dilp1-4 genes and the dilp6 gene stand out as likely affected by recent adaptive events.

Patent claims in certain geographical regions

Työn tavoitteena oli käsitellä mahdollisuutta laatia patenttihakemuksen vaatimuksia siten, että patenttihakemukset toimisivat eri oikeusalueilla, jotka ovat tässä Eurooppa, Suomi ja USA. Aluksi käsiteltiin patentointia ja eri patenttijärjestelmiä yleisesti, jonka jälkeen käsiteltiin lähemmin patenttivaatimuksia, niiden muotoja ja eri vaatimusten edellytyksiä, joita vaaditaan Euroopan patenttisopimuksessa, suomalaisessa ja USA:laisessa patenttijärjestelmässä. Vaikka uutuus, keksinnöllisyys ja teollinen käyttökelpoisuus ovat tärkeimmät edellytykset kun määritetään patenttivaatimuksia, niitä ei käsitelty työn empiirisessä osassa. Työn empiirinen osuus osoittaa selvästi, että erilaiset muodolliset vaatimukset Euroopan patenttisopimuksessa, suomalaisessa ja USA:laisessa patenttijärjestelmässä hankaloittavat patenttivaatimusten laatimista siten että ne toimisivat yhdessä patenttihakemuksessa yllä mainituissa patenttijärjestelmissä. Empiirisen tutkimuksen ja eri oikeusalueilla patenttivaatimusten edellytysten perusteella, ei ole yksinkertaista ratkaisua laatia patenttivaatimuksia (ja myös patenttiselostuksia), jotka toimisivat monilla oikeusalueilla. Eräs ratkaisu ongelmaan on laatia yksi sarja patenttivaatimuksia, jotka täyttävät Euroopan patenttisopimuksen käytännön mukaiset edellytykset (täyttävät myös Suomalaisen patenttijärjestelmän edellytykset) ja toinen sarja patenttivaatimuksia, jotka täyttävät USA:laisen patenttijärjestelmän edellytykset samassa patenttihakemuksessa. Hakemuksen käsittelyvaiheessa hakija voi pudottaa patenttivaatimukset, jotka eivät täytä kansallisen patenttijärjestelmän edellytyksiä patenttihakemuksesta.

Sciatic and femoral nerve sensory neurones occupy different regions of the L4 dorsal root ganglion in the adult rat.

The topographical distribution of sciatic and femoral nerve sensory neuronal somata in the L4 dorsal root ganglion of the adult rat was mapped after retrograde tracing with one or two of the dyes Fast Blue, Fluoro-Gold, or Diamidino Yellow. The tracers were applied to the proximal transected end of either nerve alone, or from both nerves in the same animal using separate tracers. Three-dimensional reconstructions of the distribution of labelled neurones were made from serial sections of the L4 dorsal root ganglion which is the only ganglion that these two nerves share. The results showed that with little overlap, femoral nerve neurones distribute dorsally and rostrally whereas sciatic nerve neurones distribute medially and ventrally. This finding indicates the existence of a somatotopical organisation for the representation of different peripheral nerves in dorsal root ganglia of adult animals.

Identification of potential HIV restriction factors by combining evolutionary genomic signatures with functional analyses.

BACKGROUND: Known antiretroviral restriction factors are encoded by genes that are under positive selection pressure, induced during HIV-1 infection, up-regulated by interferons, and/or interact with viral proteins. To identify potential novel restriction factors, we performed genome-wide scans for human genes sharing molecular and evolutionary signatures of known restriction factors and tested the anti-HIV-1 activity of the most promising candidates. RESULTS: Our analyses identified 30 human genes that share characteristics of known restriction factors. Functional analyses of 27 of these candidates showed that over-expression of a strikingly high proportion of them significantly inhibited HIV-1 without causing cytotoxic effects. Five factors (APOL1, APOL6, CD164, TNFRSF10A, TNFRSF10D) suppressed infectious HIV-1 production in transfected 293T cells by >90% and six additional candidates (FCGR3A, CD3E, OAS1, GBP5, SPN, IFI16) achieved this when the virus was lacking intact accessory vpr, vpu and nef genes. Unexpectedly, over-expression of two factors (IL1A, SP110) significantly increased infectious HIV-1 production. Mechanistic studies suggest that the newly identified potential restriction factors act at different steps of the viral replication cycle, including proviral transcription and production of viral proteins. Finally, we confirmed that mRNA expression of most of these candidate restriction factors in primary CD4+ T cells is significantly increased by type I interferons. CONCLUSIONS: A limited number of human genes share multiple characteristics of genes encoding for known restriction factors. Most of them display anti-retroviral activity in transient transfection assays and are expressed in primary CD4+ T cells.

The effects of unemployment benefits on migration in lagging regions

[spa] En este trabajo se analizan los efectos sobre la movilidad geográfica de una política pública (SIPTEA) que aumenta la protección por desempleo en Extremadura y Andalucía. Utilizando la discontinuidad geográfica en la política estudiada y datos de los Censos de Población de 1981 y 1991 a nivel municipal, se estima el efecto de SIPTEA en el crecimiento de la población y en las probabilidades de emigrar e inmigrar en áreas rurales que experimentan elevadas tasas de paro y de emigración. Los resultados del trabajo indican que la política mitigó estas pérdidas de población aunque los efectos son cuantitativamente moderados. También se exploran los efectos de dicha política en el ámbito laboral, encontrándose un incremento de la tasa del desempleo asociado a la implementación de la política de entre 10 y 13 puntos porcentuales.

The effects of unemployment benefits on migration in lagging regions

[spa] En este trabajo se analizan los efectos sobre la movilidad geográfica de una política pública (SIPTEA) que aumenta la protección por desempleo en Extremadura y Andalucía. Utilizando la discontinuidad geográfica en la política estudiada y datos de los Censos de Población de 1981 y 1991 a nivel municipal, se estima el efecto de SIPTEA en el crecimiento de la población y en las probabilidades de emigrar e inmigrar en áreas rurales que experimentan elevadas tasas de paro y de emigración. Los resultados del trabajo indican que la política mitigó estas pérdidas de población aunque los efectos son cuantitativamente moderados. También se exploran los efectos de dicha política en el ámbito laboral, encontrándose un incremento de la tasa del desempleo asociado a la implementación de la política de entre 10 y 13 puntos porcentuales.

Worldwide Population Structure, Long-Term Demography, and Local Adaptation of Helicobacter pylori.

Helicobacter pylori is an important human pathogen associated with serious gastric diseases. Owing to its medical importance and close relationship with its human host, understanding genomic patterns of global and local adaptation in H. pylori may be of particular significance for both clinical and evolutionary studies. Here we present the first such whole genome analysis of 60 globally distributed strains, from which we inferred worldwide population structure and demographic history and shed light on interesting global and local events of positive selection, with particular emphasis on the evolution of San-associated lineages. Our results indicate a more ancient origin for the association of humans and H. pylori than previously thought. We identify several important perspectives for future clinical research on candidate selected regions that include both previously characterized genes (e.g., transcription elongation factor NusA and tumor necrosis factor alpha-inducing protein Tipα) and hitherto unknown functional genes.