Genomic organization of α1 and β1 subunits of the mammalian soluble guanylyl cyclase genes

The structures of the genes encoding the α1 and β1 subunits of murine soluble guanylyl cyclase (sGC) were determined. Full-length cDNAs isolated from mouse lungs encoding the α1 (2.5 kb) and β1 (3.3 kb) subunits are presented in this report. The α1 sGC gene is approximately 26.4 kb and contains nine exons, whereas the β1 sGC gene spans 22 kb and consists of 14 exons. The positions of exon/intron boundaries and the sizes of introns for both genes are described. Comparison of mouse genomic organization with the Human Genome Database predicted the exon/intron boundaries of the human genes and revealed that human and mouse α1 and β1 sGC genes have similar structures. Both mouse genes are localized on the third chromosome, band 3E3-F1, and are separated by a fragment that is 2% of the chromosomal length. The 5′ untranscribed regions of α1 and β1 subunit genes were subcloned into luciferase reporter constructs, and the functional analysis of promoter activity was performed in murine neuroblastoma N1E-115 cells. Our results indicate that the 5′ untranscribed regions for both genes possess independent promoter activities and, together with the data on chromosomal localization, suggest independent regulation of both genes.

Structure of the recombinant full-length hamster prion protein PrP(29–231): The N terminus is highly flexible

The prion diseases seem to be caused by a conformational change of the prion protein (PrP) from the benign cellular form PrPC to the infectious scrapie form PrPSc; thus, detailed information about PrP structure may provide essential insights into the mechanism by which these diseases develop. In this study, the secondary structure of the recombinant Syrian hamster PrP of residues 29–231 [PrP(29–231)] is investigated by multidimensional heteronuclear NMR. Chemical shift index analysis and nuclear Overhauser effect data show that PrP(29–231) contains three helices and possibly one short β-strand. Most striking is the random-coil nature of chemical shifts for residues 30–124 in the full-length PrP. Although the secondary structure elements are similar to those found in mouse PrP fragment PrP(121–231), the secondary structure boundaries of PrP(29–231) are different from those in mouse PrP(121–231) but similar to those found in the structure of Syrian hamster PrP(90–231). Comparison of resonance assignments of PrP(29–231) and PrP(90–231) indicates that there may be transient interactions between the additional residues and the structured core. Backbone dynamics studies done by using the heteronuclear [1H]-15N nuclear Overhauser effect indicate that almost half of PrP(29–231), residues 29–124, is highly flexible. This plastic region could feature in the conversion of PrPC to PrPSc by template-assisted formation of β-structure.

Modular cis-regulatory organization of developmentally expressed genes: two genes transcribed territorially in the sea urchin embryo, and additional examples.

The cis-regulatory systems that control developmental expression of two sea urchin genes have been subjected to detailed functional analysis. Both systems are modular in organization: specific, separable fragments of the cis-regulatory DNA each containing multiple transcription factor target sites execute particular regulatory subfunctions when associated with reporter genes and introduced into the embryo. The studies summarized here were carried out on the CyIIIa gene, expressed in the embryonic aboral ectoderm and on the Endo16 gene, expressed in the embryonic vegetal plate, archenteron, and then midgut. The regulatory systems of both genes include modules that control particular aspects of temporal and spatial expression, and in both the territorial boundaries of expression depend on a combination of negative and positive functions. In both genes different regulatory modules control early and late embryonic expression. Modular cis-regulatory organization is widespread in developmentally regulated genes, and we present a tabular summary that includes many examples from mouse and Drosophila. We regard cis-regulatory modules as units of developmental transcription control, and also of evolution, in the assembly of transcription control systems.

A long-range regulatory element of Hoxc8 identified by using the pClasper vector.

Hox genes are located in highly conserved clusters. The significance of this organization is unclear, but one possibility is that regulatory regions for individual genes are dispersed throughout the cluster and shared with other Hox genes. This hypothesis is supported by studies on several Hox genes in which even large genomic regions immediately surrounding the gene fail to direct the complete expression pattern in transgenic mice. In particular, previous studies have identified proximal regulatory regions that are primarily responsible for early phases of mouse Hoxc8 expression. To locate additional regulatory regions governing expression during the later periods of development, a yeast homologous recombination-based strategy utilizing the pClasper vector was employed. Using homologous recombination into pClasper, we cloned a 27-kb region around the Hoxc8 gene from a yeast artificial chromosome. A reporter gene was introduced into the coding region of the isolated gene by homologous recombination in yeast. This large fragment recapitulates critical aspects of Hoxc8 expression in transgenic mice. We show that the regulatory elements that maintain the anterior boundaries of expression in the neural tube and paraxial mesoderm are located between 11 and 19 kb downstream of the gene.

Recruitment and replacement of hippocampal neurons in young and adult chickadees: an addition to the theory of hippocampal learning.

We used [3H]thymidine to document the birth of neurons and their recruitment into the hippocampal complex (HC) of juvenile (4.5 months old) and adult blackcapped chickadees (Parus atricapillus) living in their natural surroundings. Birds received a single dose of [3H]thymidine in August and were recaptured and killed 6 weeks later, in early October. All brains were stained with Cresyl violet, a Nissl stain. The boundaries of the HC were defined by reference to the ventricular wall, the brain surface, or differences in neuronal packing density. The HC of juveniles was as large as or larger than that of adults and packing density of HC neurons was 31% higher in juveniles than in adults. Almost all of the 3H-labeled HC neurons were found in a 350-m-wide layer of tissue adjacent to the lateral ventricle. Within this layer the fraction of 3H-labeled neurons was 50% higher in juveniles than in adults. We conclude that the HC of juvenile chickadees recruits more neurons and has more neurons than that of adults. We speculate that juveniles encounter greater environmental novelty than adults and that the greater number of HC neurons found in juveniles allows them to learn more than adults. At a more general level, we suggest that (i) long-term learning alters HC neurons irreversibly; (ii) sustained hippocampal learning requires the periodic replacement of HC neurons; (iii) memories coded by hippocampal neurons are transferred elsewhere before the neurons are replaced.

Towards Better Use of Credit Reporting in Europe. CEPS-ECRI Task Force Report, September 2013

This report discusses how the current EU credit reporting systems meet the demands of the different stakeholders in the credit granting and management process, and what is needed to improve these systems. As credit reporting is a tool for responsible lending and for ensuring financial inclusion of consumers, it argues that the needs of EU credit markets and consumers should be the basis for assessing the current regulation and its functionality. How a creditor assesses the risk and the creditworthiness of a customer is at the core of successful and safe crediting. Facilitating this assessment process, within the boundaries of data protection laws, is a key building block for making well-informed credit decisions.

Legal shifts : shaping expectations of intellectual property protection in an open innovation industrial environment

Projet de recherche réalisé en 2014-2015 avec l'appui du Fonds de recherche du Québec – Société et culture.

Strategic knowledge serendipity and arbitrage & intellectual venture capitalists: An emerging breed of knowledge entrepreneurs; and Part II: Global and Local (GloCal) knowledge logistics for innovation and competitiveness. ACES Working Papers, August 2009

Strategic Knowledge: While entrepreneurship may occur as a natural result of personal drive, it occurs most often, most robustly and is most sustainable in an environment designed to encourage it. Potential entrepreneurs become active entrepreneurs when the conditions are most supportive of their commercial opportunities and their business thus helping channel the two key qualities they exhibit as individuals obsessed maniacs and clairvoyant oracles (Carayannis, GWU Lectures, 2000-2005) and (Carayannis et at, 2003a) towards the generation of sustainable wealth. So far, entrepreneurial scholars who turn into intellectual venture capitalists by founding knowledge-driven companies remain one of the least explored specie in the territory of entrepreneurship. GloCal: The increasing engagement of firms within global knowledge and production networks and their ability to source knowledge globally as well as locally (GloCally), for the development of innovation capacities will shape the future of UK's knowledge resources and its role in the global economy. Practices such as off-shoring R&D activities are widely adopted, creating challenging, and not very well understood, issues related to cross-country and inter-firm knowledge and technology flows. We seek to address the internationalisation and networking of research and innovation activities, including the roles and strategies of enterprises, universities, research centres, governments in a cross-country and inter-sectoral way, to assess the impact and the implications for sustaining and enhancing the competitiveness of UK firms and other British knowledge producers and users.

Micro-based evidence of EU competitiveness: The CompNet Database. National Bank of Belgium Working Paper No. 253, March 2014

Drawing from confidential firm-level balance sheets in 11 European countries, the paper presents a novel sectoral database of comparable productivity indicators built by members of the Competitiveness Research Network (CompNet) using a newly developed research infrastructure. Beyond aggregate information available from industry statistics of Eurostat or EU KLEMS, the paper provides information on the distribution of firms across several dimensions related to competitiveness, e.g. productivity and size. The database comprises so far 11 countries, with information for 58 sectors over the period 1995-2011. The paper documents the development of the new research infrastructure, the construction of the database, and shows some preliminary results. Among them, it shows that there is large heterogeneity in terms of firm productivity or size within narrowly defined industries in all countries. Productivity, and above all, size distribution are very skewed across countries, with a thick left-tail of low productive firms. Moreover, firms at both ends of the distribution show very different dynamics in terms of productivity and unit labour costs. Within-sector heterogeneity and productivity dispersion are positively correlated to aggregate productivity given the possibility of reallocating resources from less to more productive firms. To this extent, we show how allocative efficiency varies across countries, and more interestingly, over different periods of time. Finally, we apply the new database to illustrate the importance of productivity dispersion to explain aggregate trade results.

The globalization of angel investments. Bruegel Working Paper 2015/09, 1 September 2015

The last decade has seen a rapid expansion and deepening of the types of vehicles that fund start-up firms in the U.S. and worldwide. In particular, we have seen a growing role of angel groups and other more “individualistic” funding options for start-ups, such as super angels or crowd sourcing platforms. Authors seek to understand the nature and consequences of angel investments across a variety of geographies with varying levels of venture capital markets and other forms of risk capital. They ask whether angel investors improve the outcomes and performance of the start-ups they invest in. Furthermore we want to understand whether and how the types of firms that seek angel funding vary with the overall entrepreneurial ecosystem in a country. Authors examine the records of 13 angel investment groups based in 12 nations and with applicants for financing transactions from 21 nations, examining both the applicants that were considered and rejected and those that were funded. Key findings from the analysis are two-fold. First, angel investors have a positive impact on the growth of the firms they fund, their performance, and survival. Second, they find that the selection of firms that apply for angel funding is different across countries.

Estrangement Day: The implications of Brexit for the EU. CEPS Commentary, 27 June 2016

In a post-imperial burst to define the boundaries of its sovereignty, Britannia is ruling the waves again, albeit in the form of air time devoted to the fallout from its referendum vote rather than in a show of force from its flotilla. It was with disbelief and sorrow that the UK’s partners in Europe and the rest of the world woke up to the news of the British Leave vote in the referendum on its EU membership. The prospect of a Brexit has sent shock waves throughout the international financial and political system and is set to occupy media debate for months to come.

Using multiple landscape genetic approaches to test the validity of genetic clusters in a species characterized by an isolation-by-distance pattern

Bayesian clustering methods are typically used to identify barriers to gene flow, but they are prone to deduce artificial subdivisions in a study population characterized by an isolation-by-distance pattern (IbD). Here we analysed the landscape genetic structure of a population of wild boars (Sus scrofa) from south-western Germany. Two clustering methods inferred the presence of the same genetic discontinuity. However, the population in question was characterized by a strong IbD pattern. While landscape-resistance modelling failed to identify landscape features that influenced wild boar movement, partial Mantel tests and multiple regression of distance matrices (MRDMs) suggested that the empirically inferred clusters were separated by a genuine barrier. When simulating random lines bisecting the study area, 60% of the unique barriers represented, according to partial Mantel tests and MRDMs, significant obstacles to gene flow. By contrast, the random-lines simulation showed that the boundaries of the inferred empirical clusters corresponded to the most important genetic discontinuity in the study area. Given the degree of habitat fragmentation separating the two empirical partitions, it is likely that the clustering programs correctly identified a barrier to gene flow. The differing results between the work published here and other studies suggest that it will be very difficult to draw general conclusions about habitat permeability in wild boar from individual studies.

Latin Americaʹs emergence in global services: a new driver of structural change in the region?

Studies of international production acknowledge that the ability of firms to learn, upgrade and innovate in global value chains (GVCs) is influenced by knowledge flows within these global networks and by the national institutional systems in which the firms are embedded. Little is known, however, about how differences in national innovation and business systems shape the way firms and national economies insert themselves in global value chains and how this influences their upgrading trajectories. Based on a review of the existing academic literature, the chapter examines the impact of national innovation and business systems from middle-income and developing countries on learning and innovation processes in services GVCs.

Legal shifts : shaping expectations of intellectual property protection in an open innovation industrial environment

Projet de recherche réalisé en 2014-2015 avec l'appui du Fonds de recherche du Québec – Société et culture.

Heat flow and heat conductivity coefficient measured in bottom sediments collected in Cruise 13 of R/V Akademik Sergey Vavilov in the Pechora Sea

In Cruise 13 of R/V Akademik Sergey Vavilov in the Pechora Sea, six heat flow varied from 50 to 75 mW/m**2. Deep heat flow in the Pechora Sea was calculated equal to 45 mW/m**2, which is confirmed by results of geological and geophysical studies and corresponds to Middle Baikal age of the basement. A model of structure of the lithosphere in the Pechora Sea is suggested. Total thickness of the lithosphere in the basin (190 km) determined from geothermal data agrees well with that in transition zones from the continent to the ocean. According to estimates of deep heat flow in the region obtained, thickness of the mantle (160 km), of the basaltic (15 km), and of the granitic (15 km) layers of the lithosphere were also evaluated. Temperature values at boundaries of the sedimentary layers were calculated over a geological and geophysical profile crossing the Pechora Sea basin. Temperatures obtained agree with the temperature interval of hydrocarbon generation and correspond to Permian-Triassic sedimentary sequences, which are the most productive ones in the Pechora Sea region from the point of view of oil and gas potential.