Calcium Signalling during Primary Angiogenic Sprouting in Zebrafish

Angiogenesis, the formation of new blood vessels from pre-existing ones, is a critical step for the formation of a functional vascular system during embryonic development. Furthermore, dysregulation of the vascular patterning is associated with more than 70 different diseases, including cancer, myocardial infarction, stroke and ocular disorders, such as macular degeneration. Studies of endothelial cells (ECs) in vitro and in vivo, have revealed the importance of vascular endothelial growth factor (VEGF) signalling together with the activation of the Dll4/Notch pathway to regulate EC’s differentiation into tip vs stalk cells as well as EC migration and proliferation during angiogenesis. Similarities between the endothelial tip cell and the axonal growth cone are well established. The two cell types share not only a similar anatomical structure, but also common molecular pathways and respond to the same molecular cues. Ca2+ signalling especially through the L-type Ca2+ channel (LTCC) is crucial to regulate the axonal turning in order to promote attraction or repulsion in response to a molecular cue. In ECs, increase in cytosolic Ca2+ concentration (Ca2+i) is a key regulator of migration, proliferation, contraction, gene expression and other biological aspects. Despite the similarities between neuronal and vascular systems, the role of Ca2+ signalling through the LTCC during vascular formation and angiogenesis is still poorly understood. This study provides evidence that the LTCC regulates EC migration during the primary angiogenic sprouting of the intersegmental vessels (ISV) in zebrafish embryos. The stimulation of the LTCC strongly increased EC migration from the dorsal aorta (DA), resulting in an overbranching phenotype, while the downregulation of the channel reduced the EC migration and proliferation compromising the ISV formation. Additionally, I observed that LTCC synergistically interacts with the canonical transient receptor potential-1 (TRPC1) Ca2+ channel to promote ISV development, suggesting the importance of Ca2+ fluxes through the plasma membrane during angiogenesis. Furthermore, mRNA-expression analysis of VEGF signalling and Dll4/Notch-pathway components revealed the importance of the LTCC during angiogenesis: perturbation of LTCC conductance, but not TRPC1, increased the mRNA-expression level of the VEGF and Dll4/Notch pathway components, compromising the angiogenic behaviour of ECs. Taken together, this study demonstrates that Ca2+ fluxes through plasma membrane of endothelial cells represent an integral part of angiogenic process. Moreover, like axon growth cone, the endothelial migration requires a tight regulation of Ca2+ signaling.Die Angiogenese, die Entstehung neuer Blutgefäße aus vorbestehenden Blutgefäßen, stellt einen wichtigen Schritt bei der Formation eines funktionalen vaskulären Systems während der embryonalen Entwicklung dar. Fehlregulierungen bei der Entstehung des vaskulären Geflechts sind außerdem mit einer Vielzahl von Krankheiten, wie Krebs, Herzinfarkt und Schlaganfällen und Augenerkrankungen wie Makuladegeneration und mehr als 70 anderen Krankheiten assoziiert. Sowohl in vitro als auch in vivo Studien an Endothelzellen (EZ) zeigten einen wichtigen Einfluss des Vascular endothelial growth factor - (VEGF) Signalweges sowie der Aktivierung des Dll4/Notch-Signalweges auf die Regulierung der Differenzierung von EZ zu Spitzen- oder Stielzellen, auf die Migration von EZ sowie deren Proliferation während der Angiogenese. Gemeinsamkeiten zwischen der endothelialen Spitzenzelle und dem axonalen Wachstumskegel sind seit langem bekannt. Die beiden Zelltypen weisen nicht nur eine ähnliche anatomische Struktur, sondern auch gemeinsame molekulare Signalwege auf und reagieren auf dieselben Botenstoffe. Die Signaltransduktion durch Calciumionen, vorallem über den L-Typ Calciumkanal (LTCC), spielt eine wichtige Rolle bei der axonalen Wegfindung und beeinflusst entweder die Anziehung oder die Abstoßung der axonalen Zelle als Antwort auf Botenstoffe. In EZ ist ein Anstieg der zytosolischen Calcium-Konzentration (Ca2+i) unter anderem ein Schlüsselreiz für die Migration, Proliferation und Kontraktion der EZ sowie die Expression bestimmter Gene. Trotz der Gemeinsamkeiten zwischen dem neuronalen und vaskulären System, ist vor allem über die Rolle der Ca2+-Signaltransduktion über den LTCC bei der Formation des vaskulären Systems und der Angiogenese wenig bekannt. Die hier vorliegende Studie zeigt, dass der LTCC die Migration von EZ während der ersten angiogenetischen Aussprossung intersegmentaler Blutgefäße (ISV) in Zebrafisch-Embryonen reguliert. Eine Stimulation des LTCC führte zu einem starken Anstieg der Migration von EZ aus der dorsalen Aorta (DA) und resultierte in einer erhöhten Verzweigung entstehender Blutgefäße. Die Herunterregulation des Kanals reduzierte die Migration und Proliferation von EZ und führte zu einer Beeinträchtigung der Ausbildung von ISV. Des Weiteren konnte nachgewiesen werden, dass der LTCC bei der Entstehung von ISV synergistisch mit dem kanonischen transient receptor potential-1 (TRPC1) Ca2+-Kanal wechselwirkt, was die entscheidende Rolle des Ca2+-Fluxes durch die Plasmamembran während der Angiogenese beweist. Insgesamt zeigt die hier vorliegende Arbeit, dass Ca2+ - Ströme durch die Plasmamembran von Endothelzellen einen wichtigen Bestandteil des angiogenetischen Prozesses darstellen. Desweiteren ist für die Migration von Endothelzellen, wie beim axonalen Wachstumskegel, eine engmaschige Regulation von Calcium - Signalwegen vonnöten

Determinants of farm size expansion among eu farmers

This paper aims to identify the determinants of the intention to expand farm size under two different policy scenarios 1) baseline, that implies the current Health Check policy, and 2) a NO-CAP scenario, providing a full removing of all CAP payments. Results highlight that farm/farmer and household characteristics such as age, amount of SFP and land size are determinants of farm size expansion under baseline scenario. Otherwise, under NO-CAP scenario, farm specialisation and organisational variables became significant in explaining the farm size expansion.farm expansion; multinomial logit; stated intentions

The role of the Common Agricultural Policy in the spatial location of agricultural activities

The objective of this paper is to analyse and quantify the spatial dimension of the CAP effects in an area of Northern Italy. The analysis is based on survey information about stated intentions of farm-household in two CAP scenarios, treated through statistical analysis intended to identify the potential determinants of different farm reactions, focusing on explicit spatial variables (altitude, LFA, agrarian regions) among explanatory variables. Altogether, the study shows the relevance of explicitly addressing the spatial effects of policies and also the differentiated spatial effect of policy on different dimensions of agricultural activities. However, the work also highlights the limitation of the location-based representation of the spatial dimension compared with both non-spatial variables and more functional variables underlying the spatial dimension.Common Agricultural Policy, Spatial effects, Emilia-Romagna., Agribusiness, Agricultural and Food Policy, Community/Rural/Urban Development, Food Consumption/Nutrition/Food Safety, Labor and Human Capital,

Country report : Italy

ITHACA - Integration, Transnational Mobility and Human, Social and Economic Capital Transfer

India : economic indicators and trade with EU

At the beginning of the century, the EU and India were growing exactly at the same path: how about today? Who is the main trade partner of India: China or the EU? And would you ever think that the EU exports to India pearls and precious stones more than electronic equipment? And how much is it easy to do business in New Delhi? Find the answers to these and many more questions in our EPRS publication on ‘India: Economic indicators and trade with EU’, part of a series of infographics produced in collaboration with the European University Institute's GlobalStat on the world's main economies

A new Volcanic managEment Risk Database desIgn (VERDI): Application to El Hierro Island (Canary Islands)

One of the most important issues in modem volcanology is the assessment of volcanic risk, which will depend - among other factors - on both the quantity and quality of the available data and an optimum storage mechanism. This will require the design of purpose-built databases that take into account data format and availability and afford easy data storage and sharing, and will provide for a more complete risk assessment that combines different analyses but avoids any duplication of information. Data contained in any such database should facilitate spatial and temporal analysis that will (1) produce probabilistic hazard models for future vent opening, (2) simulate volcanic hazards and (3) assess their socio-economic impact. We describe the design of a new spatial database structure, VERDI (Volcanic managEment Risk Database design), which allows different types of data, including geological, volcanological, meteorological, monitoring and socio-economic information, to be manipulated, organized and managed. The root of the question is to ensure that VERDI will serve as a tool for connecting different kinds of data sources, GIS platforms and modeling applications. We present an overview of the database design, its components and the attributes that play an important role in the database model. The potential of the VERDI structure and the possibilities it offers in regard to data organization are here shown through its application on El Hierro (Canary Islands). The VERDI database will provide scientists and decision makers with a useful tool that will assist to conduct volcanic risk assessment and management. (C) 2014 Elsevier B.V. All rights reservedThis research has been partially funded by the European Commission (FP7 Theme: ENV.2011.1.3.3-1; Grant 282759: VUELCO) and the MINECO grant CGL2011-16144-E.Peer Reviewe

Understanding the participation in agri-environmental schemes: evidence from Tuscany Region

Agri-Environmental Schemes (AESs) represent one of the main agricultural policy instruments which address environmental objectives in Common Agricultural Policy. In spite of twenty years of application and its high share of RDP budget, several evaluation reports and scientific literature have measured a low environmental impacts compared with expectations. Economic literature has identified in low target level of schemes, low participation rates, spatial heterogeneity and asymmetric information between farmers and public administration the main reasons for low impact. The objective of the paper is to provide a comprehensive analysis of determinants of agrienvironmental adoption. The objective is pursued combining results of farm level adoption analysis with spatial analysis of participation rate. Results show that both micro and meso-characteristics strongly affect participation to AESs. In fact, farm and household structure, quality of advice services and territory endogeneity, significantly affect AESs adoption

Stress controls of monogenetic volcanism: A review

The factors controlling the preparation of volcanic eruptions in monogenetic fields are still poorly understood. The fact that in monogenetic volcanism each eruption has a different vent suggests that volcanic susceptibility has a high degree of randomness, so that accurate forecasting is subjected to a very high uncertainty. Recent studies on monogenetic volcanism reveal how sensitive magma migration is to the existence of changes in the stress field caused by regional and/or local tectonics or rheological contrasts (stratigraphic discontinuities). These stress variations may induce changes in the pattern of further movements of magma, thus conditioning the location of future eruptions. This implies that a precise knowledge of the stress configuration and distribution of rheological and structural discontinuities at crustal level of such volcanic systems would aid in forecasting monogenetic volcanism. This contribution reviews several basic concepts relative to the stress controls of magma transport into the brittle lithosphere, and uses this information to explain how magma migrates inside monogenetic volcanic systems and how it prepares to trigger a new eruption. © 2016 Martí, López, Bartolini, Becerril and Geyer.This research was funded by the European Commission (FP7 Theme: NV.2011.1.3.3-1; Grant 282759: VUELCO and EC ECHO Grant SI2.695524: VeTOOLS). AG thanks the support provided by the Ramón y Cajal research program (RYC-2012-11024). We thank Gregg Valentine and Alessandro Tibaldi for their useful and constructive reviews.Peer reviewe

Post-traumatic infection of the lower limb caused by rare Enterobacteriaceae and mucorales in a young healthy male.

Summary Enterobacter amnigenus and Leclercia adecarboxylata are Gram-negative aerobic bacilli of the family Enterobacteriaceae that have been isolated from water and, rarely, from various clinical specimens. Absidia is a filamentous fungus of the class Zygomycetes that is ubiquitous in nature and can cause infection, primarily in immunocompromised hosts. Here, we describe an infection of the left lower limb caused by E. amnigenus and L. adecarboxylata with subsequent isolation of Absidia spp. in a patient with multiple traumatic injuries after a major motor vehicle accident. The severity of the clinical picture made amputation necessary, despite aggressive anti-infective therapy with both antibacterial and antifungal agents. Prompt diagnosis and management are mandatory in order to minimize morbidity and even mortality, and reduce the social and economic cost

Determinants of farm size expansion among eu farmers

This paper aims to identify the determinants of the intention to expand farm size under two different policy scenarios 1) baseline, that implies the current Health Check policy, and 2) a NO-CAP scenario, providing a full removing of all CAP payments. Results highlight that farm/farmer and household characteristics such as age, amount of SFP and land size are determinants of farm size expansion under baseline scenario. Otherwise, under NO-CAP scenario, farm specialisation and organisational variables became significant in explaining the farm size expansion