188 research outputs found

    Agglomeration externalities, innovation and regional growth: Theoretical perspectives and meta-analysis

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    Technological change and innovation and are central to the quest for regional development. In the globally-connected knowledge-driven economy, the relevance of agglomeration forces that rely on proximity continues to increase, paradoxically despite declining real costs of information, communication and transportation. Globally, the proportion of the population living in cities continues to grow and sprawling cities remain the engines of regional economic transformation. The growth of cities results from a complex chain that starts with scale, density and geography, which then combine with industrial structure characterised by its extent of specialisation, competition and diversity, to yield innovation and productivity growth that encourages employment expansion, and further urban growth through inward migration. This paper revisits the central part of this virtuous circle, namely the Marshall-Arrow-Romer externalities (specialisation), Jacobs externalities (diversity) and Porter externalities (competition) that have provided alternative explanations for innovation and urban growth. The paper evaluates the statistical robustness of evidence for such externalities presented in 31 scientific articles, all building on the seminal work of Glaeser et al. (1992). We aim to explain variation in estimation results using study characteristics by means of ordered probit analysis. Among the results, we find that the impact of diversity depends on how it is measured and that diversity is important for the high-tech sector. High population density increases the chance of finding positive effects of specialisation on growth. More recent data find more positive results for both specialization and diversity, suggesting that agglomeration externalities become more important over time. Finally, primary study results depend on whether or not the externalities are considered jointly and on other features of the regression model specification

    Perspectives on the dynamics of third spaces

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    While coworking spaces (CSs) were traditionally viewed as a necessity for self-employed workers and freelancers, we outline how different users have also adopted the concept, even more so during the pandemic. The range of users has now expanded with employees from all sorts of companies who need to balance remote working with their private lives at home. We indicate avenues for future growth, in particular when the use of a CS becomes a lifestyle choice, and present paths for future research on CS users

    Enhancing faba bean (Vicia faba L.) genome resources

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    Grain legume improvement is currently impeded by a lack of genomic resources. The paucity of genome information for faba bean can be attributed to the intrinsic difficulties of assembling/annotating its giant (~13Gb) genome. In order to address this challenge, RNA-seq analysis was performed on faba bean (cv Wizard) leaves. Read alignment to the faba bean reference transcriptome identified 16,300 high quality unigenes. In addition, Illumina paired-end sequencing was used to establish a baseline for genomic information assembly. Genomic reads were assembled de novo into contigs with a size range of 50-5000 bp. Over 85% of sequences did not align to known genes, of which ~10 % could be aligned to known repetitive genetic elements. Over 26,000 of the reference transcriptome unigenes could be aligned to DNA-seq reads with high confidence. Moreover, this comparison identified 56,668 potential splice points in all identified unigenes. Sequence length data was extended at 461 putative loci through alignment of DNA-seq contigs to full length, publically available linkage marker sequences. Reads also yielded coverages of 3466x and 650x for the chloroplast and mitochondrial genomes respectively. Inter- and intra-species organelle genome comparisons established core legume organelle gene sets, and revealed polymorphic regions of faba bean organelle genomes

    Suramin Inhibits Chikungunya Virus Replication by Interacting with Virions and Blocking the Early Steps of Infection

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    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause a debilitating disease that is primarily characterized by persistent joint pain. CHIKV has been emerging globally, while neither a vaccine nor antiviral medication is available. The anti-parasitic drug suramin was previously shown to inhibit CHIKV replication. In this study we aimed to obtain more detailed insight into its mechanism of action. We found that suramin interacts with virions and can inhibit virus binding to cells. It also appeared to inhibit post-attachment steps of the infection process, likely by preventing conformational changes of the envelope glycoproteins required for fusion and the progression of infection. Suramin-resistant CHIKV strains were selected and genotyping and reverse genetics experiments indicated that mutations in E2 were responsible for resistance. The substitutions N5R and H18Q were reverse engineered in the E2 glycoprotein in order to understand their role in resistance. The binding of suramin-resistant viruses with these two E2 mutations was inhibited by suramin like that of wild-type virus, but they appeared to be able to overcome the post-attachment inhibitory effect of suramin. Conversely, a virus with a G82R mutation in E2 (implicated in attenuation of vaccine strain 181/25), which renders it dependent on the interaction with heparan sulfate for entry, was more sensitive to suramin than wild-type virus. Using molecular modelling studies, we predicted the potential suramin binding sites on the mature spikes of the chikungunya virion. We conclude that suramin interferes with CHIKV entry by interacting with the E2 envelope protein, which inhibits attachment and also interferes with conformational changes required for fusion

    Інноваційна діяльність через впровадження технопарків

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    Досвід усього світу показує, що економічне зростання країн вже давно базується на використанні сфери знань і високих технологій, а їх ефективне поєднання гарантує прогресивний розвиток нації та людства. Однією з найбільш вдалих форм такої інтеграції є технопарки. Саме тому розвитку технопарків на сьогоднішній день приділяють увагу вчені та економісти. Основною метою статті є інноваційна діяльність через впровадження технологічних парків, їх призначення та вплив на розвиток країни

    Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients

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    Introduction: In dystonia, dopaminergic alterations are considered to be responsible for the motor symptoms. Recent attention for the highly prevalent non-motor symptoms suggest also a role for serotonin in the pathophysiology. In this study we investigated the dopaminergic, serotonergic and noradrenergic metabolism in blood samples of dystonia patients and its relation with (non-)motor manifestations. Methods: Concentrations of metabolites of dopaminergic, serotonergic and noradrenergic pathways were measured in platelet-rich plasma in 41 myoclonus-dystonia (M-D), 25 dopa-responsive dystonia (DRD), 50 cervical dystonia (CD) patients and 55 healthy individuals. (Non-)motor symptoms were assessed using validated instruments, and correlated with concentrations of metabolites. Results: A significantly higher concentration of 3-methoxytyramine (0.03 vs. 0.02 nmol/L, p < 0.01), a metabolite of dopamine, and a reduced concentration of tryptophan (50 vs. 53 μmol/L, p = 0.03), the precursor of serotonin was found in dystonia patients compared to controls. The dopamine/levodopa ratio was higher in CD patients compared to other dystonia groups (p < 0.01). Surprisingly, relatively high concentrations of levodopa were found in the untreated DRD patients. Low concentrations of levodopa were associated with severity of dystonia (rs = −0.3, p < 0.01), depression (rs = −0.3, p < 0.01) and fatigue (rs = −0.2, p = 0.04). Conclusion: This study shows alterations in the dopaminergic and serotonergic metabolism of patients with dystonia, with dystonia subtype specific changes. Low concentrations of levodopa, but not of serotonergic metabolites, were associated with both motor and non-motor symptoms. Further insight into the dopaminergic and serotonergic systems in dystonia with a special attention to the kinetics of enzymes involved in these pathways, might lead to better treatment options

    Tomatidine reduces chikungunya virus progeny release by controlling viral protein expression

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    Author summaryChikungunya fever is a debilitating disease caused by the mosquito-borne Chikungunya virus. Over the past two decades the geographical spread of the virus and its mosquito vector has drastically increased thereby causing millions of infections. To date there is no antiviral drug and no vaccine available to treat/prevent Chikungunya virus infection. We recently showed that the natural steroidal alkaloid tomatidine has potent antiviral activity towards Chikungunya virus at submicromolar concentrations. In this study we dissected how tomatidine reduces the production of Chikungunya virus particles. We show that tomatidine lowers viral protein expression and we hypothesize that the effect of tomatidine on viral protein translation hampers the production of progeny viral RNA copies / number of infected cells thereby leading to a reduced production of secreted virus particles. Also, we show that Chikungunya virus does not readily become resistant to tomatidine. Collectively, we deciphered the mechanism by which tomatidine exerts antiviral activity to Chikungunya virus and our results strengthen the potential of tomatidine as an antiviral treatment strategy towards Chikungunya virus.Tomatidine, a natural steroidal alkaloid from unripe green tomatoes has been shown to exhibit many health benefits. We recently provided in vitro evidence that tomatidine reduces the infectivity of Dengue virus (DENV) and Chikungunya virus (CHIKV), two medically important arthropod-borne human infections for which no treatment options are available. We observed a potent antiviral effect with EC50 values of 0.82 mu M for DENV-2 and 1.3 mu M for CHIKV-LR. In this study, we investigated how tomatidine controls CHIKV infectivity. Using mass spectrometry, we identified that tomatidine induces the expression of p62, CD98, metallothionein and thioredoxin-related transmembrane protein 2 in Huh7 cells. The hits p62 and CD98 were validated, yet subsequent analysis revealed that they are not responsible for the observed antiviral effect. In parallel, we sought to identify at which step of the virus replication cycle tomatidine controls virus infectivity. A strong antiviral effect was seen when in vitro transcribed CHIKV RNA was transfected into Huh7 cells treated with tomatidine, thereby excluding a role for tomatidine during CHIKV cell entry. Subsequent determination of the number of intracellular viral RNA copies and viral protein expression levels during natural infection revealed that tomatidine reduces the RNA copy number and viral protein expression levels in infected cells. Once cells are infected, tomatidine is not able to interfere with active RNA replication yet it can reduce viral protein expression. Collectively, the results delineate that tomatidine controls viral protein expression to exert its antiviral activity. Lastly, sequential passaging of CHIKV in presence of tomatidine did not lead to viral resistance. Collectively, these results further emphasize the potential of tomatidine as an antiviral treatment towards CHIKV infection.Molecular basis of virus replication, viral pathogenesis and antiviral strategie

    Stronger diversity effects with increased environmental stress : a study of multitrophic interactions between oak, powdery mildew and ladybirds

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    Recent research has suggested that increasing neighbourhood tree species diversity may mitigate the impact of pests or pathogens by supporting the activities of their natural enemies and/or reducing the density of available hosts. In this study, we attempted to assess these mechanisms in a multitrophic study system of young oak (Quercus), oak powdery mildew (PM, caused by Erysiphe spp.) and a mycophagous ladybird (Psyllobora vigintiduo-punctata). We assessed ladybird mycophagy on oak PM in function of different neighbourhood tree species compositions. We also evaluated whether these species interactions were modulated by environmental conditions as suggested by the Stress Gradient Hypothesis. We adopted a complementary approach of a field experiment where we monitored oak saplings subjected to a reduced rainfall gradient in a young planted forest consisting of different tree species mixtures, as well as a lab experiment where we independently evaluated the effect of different watering treatments on PM infections and ladybird mycophagy. In the field experiment, we found effects of neighbourhood tree species richness on ladybird mycophagy becoming more positive as the target trees received less water. This effect was only found as weather conditions grew drier. In the lab experiment, we found a preference of ladybirds to graze on infected leaves from trees that received less water. We discuss potential mechanisms that might explain this preference, such as emissions of volatile leaf chemicals. Our results are in line with the expectations of the Natural Enemies Hypothesis and support the hypothesis that biodiversity effects become stronger with increased environmental stress

    Increased atherosclerosis in a mouse model of glycogen storage disease type 1a

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    Glycogen storage disease type 1a (GSD Ia) is an inborn error of carbohydrate metabolism. Despite severe hyperlipidemia, GSD Ia patients show limited atherogenesis compared to age-and-gender matched controls. Employing a GSD Ia mouse model that resembles the severe hyperlipidemia in patients, we here found increased atherogenesis in GSD Ia. These data provide a rationale for investigating atherogenesis in GSD Ia in a larger patient cohort.</p
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