Evolution of the epithelial sodium channel and the sodium pump as limiting factors of aldosterone action on sodium transport.

Despite large changes in salt intake, the mammalian kidney is able to maintain the extracellular sodium concentration and osmolarity within very narrow margins, thereby controlling blood volume and blood pressure. In the aldosterone-sensitive distal nephron (ASDN), aldosterone tightly controls the activities of epithelial sodium channel (ENaC) and Na,K-ATPase, the two limiting factors in establishing transepithelial sodium transport. It has been proposed that the ENaC/degenerin gene family is restricted to Metazoans, whereas the α- and β-subunits of Na,K-ATPase have homologous genes in prokaryotes. This raises the question of the emergence of osmolarity control. By exploring recent genomic data of diverse organisms, we found that: 1) ENaC/degenerin exists in all of the Metazoans screened, including nonbilaterians and, by extension, was already present in ancestors of Metazoa; 2) ENaC/degenerin is also present in Naegleria gruberi, an eukaryotic microbe, consistent with either a vertical inheritance from the last common ancestor of Eukaryotes or a lateral transfer between Naegleria and Metazoan ancestors; and 3) The Na,K-ATPase β-subunit is restricted to Holozoa, the taxon that includes animals and their closest single-cell relatives. Since the β-subunit of Na,K-ATPase plays a key role in targeting the α-subunit to the plasma membrane and has an additional function in the formation of cell junctions, we propose that the emergence of Na,K-ATPase, together with ENaC/degenerin, is linked to the development of multicellularity in the Metazoan kingdom. The establishment of multicellularity and the associated extracellular compartment ("internal milieu") precedes the emergence of other key elements of the aldosterone signaling pathway.

The embryonic blood-CSF barrier has molecular elements for specific glucose transport and for the general transport of molecules via transcellular routes.

In vertebrates, early brain development takes place at the expanded anterior end of the neural tube, which is filled with embryonic cerebrospinal fluid (E-CSF). We have recently identified a transient blood-CSF barrier that forms between embryonic days E3 and E4 in chick embryos and that is responsible for the transport of proteins and control of E-CSF homeostasis, including osmolarity. Here we examined the presence of glucose transporter GLUT-1 as well the presence of caveolae-structural protein Caveolin1 (CAV-1) in the embryonic blood-CSF barrier which may be involved in the transport of glucose and of proteins, water and ions respectively across the neuroectoderm. In this paper we demonstrate the presence of GLUT-1 and CAV-1 in endothelial cells of blood vessels as well as in adjacent neuroectodermal cells, located in the embryonic blood-CSF barrier. In blood vessels, these proteins were detected as early as E4 in chick embryos and E12.7 in rat embryos, i.e. the point at which the embryonic blood-CSF barrier acquires this function. In the neuroectoderm of the embryonic blood-CSF barrier, GLUT-1 was also detected at E4 and E12.7 respectively, and CAV-1 was detected shortly thereafter in both experimental models. These experiments contribute to delineating the extent to which the blood-CSF embryonic barrier controls E-CSF composition and homeostasis during early stages of brain development in avians and mammals. Our results suggest the regulation of glucose transport to the E-CSF by means of GLUT-1 and also suggest a mechanism by which proteins are transported via transcellular routes across the neuroectoderm, thus reinforcing the crucial role of E-CSF in brain development.

FDI from European Union to Western Balkan Countires: is the economic development being intensified in the region?

La inversió estrangera directa és important a causa dels seus avantatges per al país d'acollida, per exemple augmentarà la competitivitat i s’intensifica el desenvolupament. Els avantatges són significatives als països dels Balcans occidentals que s'enfronten a les dificultats de la competència i el creixement més baix de la UE-27. El treball analitza el tipus dominant de la IED de la UE-27 a la regió dels Balcans Occidentals a escala nacional i sectorial per formar les implicacions sobre el futur creixement de la competitivitat i la intensitat del desenvolupament econòmic. Es troba que la IED horitzontal domina als Balcans occidentals, per tant, el creixement de la competitivitat i el desenvolupament econòmic es va intensificar a la regió.

The long run development of Chile and the Natural Resources curse. Linkages, policy and growth, 1850-1950

This chapter analyses the effects of Natural Resources on the Chilean economy in the long run -1850-1950-. Specifically, the authors focus their attention on the mining cycles -nitrates and copper- and their impact on the mining activity. We also compare it with the evolution of the industry and whole economy, and how this has affected the economic growth of the country. In that sense, the industrial performance in Chile at the end of the 19th century until the Great Depression is still under debate. The optimistic view of Kirsch -1977- forehead the pessimistic view of Lagos -1966- and Palma -1979-. The new data and its analyses shows a neutral effect of the Natural Resources in the industrial development.

eLab, a Personal Learning Environment for the Green Open Innovation Platform

Open Innovation is a relatively new concept which involves a change of paradigm in the R+D+i processes of companies whose aim is to create new technologies or new processes. If to this change, we add the need for innovation in the new green and sustainability economy, and we set out to create a collaborative platform with a learning space where this can happen, we will be facing an overwhelming challenge which requires the application of intelligent programming technologies and languages at the service of education.The aim of the Green IDI (Green Open Innovation) ¿ Economic development and job creation vector in SMEs, based on the environment and sustainability project is to create a platform where companies and individual researchers can perform open innovation processes in the field of sustainability and the environment.The Green IDI (Green Open Innovation) project is funded under the program INNPACTO by the Ministry of Science and Innovation of Spain and is being developed through a consortium formed by the following institutions: GRUPO ICA; COMPARTIA; GRUPO INTERCOM; CETAQUA and the Instituto de Investigación en Inteligencia Artificial (IIIA) from Consejo Superior de Investigaciones Científicas (CSIC). Also the consortium include FUNDACIÓ PRIVADA BARCELONA DIGITAL; PIMEC and UNIVERSITAT OBERTA DE CATALUNYA (UOC).Sustainability and positive action for the environment are considered the principle vector of economic development for companies. As Nicolás Scoli says (2007) ¿in short, preventing unnecessary consumption and the efficient consumption of resources means producing greater wealth with less. Both effects lead to reduced pollution linked to production and consumption¿.The Spanish Sustainable Development Strategy (EEDS) plan defends consumption and sustainable production linked to social and economic development by adhering to the commitment not to endanger ecosystems and abolishing the idea that economic growth is directly proportional to the deterioration of the environment.Uniting the Open Innovation and New Green Economy concepts leads to the "Green Open Innovation¿ Platform creation project.This article analyses the concept of open innovation and defines the importance of the new green and sustainable economy. Lastly, it proposes the creation of eLab. The eLab is defined as an Open Green Innovation Platform personal and collaborative education space which is fed by the interactions of users and which enables innovation processes based on new green economy concepts to be carried out.The creation of a personal learning environment such as eLab on the Green Open Innovation Platform meets the need to offer a collaborative space where platform users can improve their skills regarding the environment and sustainability based on collaborative synergies through Information and Communication Technologies.

Economic Geographical Analysis of The Finnish Paper Industry

The purpose of this academic economic geographical dissertation is to study and describe how competitiveness in the Finnish paper industry has developed during 2001–2008. During these years, the Finnish paper industry has faced economically challenging times. This dissertation attempts to fill the existing gap between theoretical and empirical discussions concerning economic geographical issues in the paper industry. The main research questions are: How have the supply chain costs and margins developed during 2001–2008? How do sales prices, transportation, and fixed and variable costs correlate with gross margins in a spatial context? The research object for this case study is a typical large Finnish paper mill that exports over 90 % of its production. The economic longitudinal research data were obtained from the case mill’s controlled economic system and, correlation (R2) analysis was used as the main research method. The time series data cover monthly economic and manufacturing observations from the mill from 2001 to 2008. The study reveals the development of prices, costs and transportation in the case mill, and it shows how economic variables correlate with the paper mills’ gross margins in various markets in Europe. The research methods of economic geography offer perspectives that pay attention to the spatial (market) heterogeneity. This type of research has been quite scarce in the research tradition of Finnish economic geography and supply chain management. This case study gives new insight into the research tradition of Finnish economic geography and supply chain management and its applications. As a concrete empirical result, this dissertation states that the competitive advantages of the Finnish paper industry were significantly weakened during 2001–2008 by low paper prices, costly manufacturing and expensive transportation. Statistical analysis expose that, in several important markets, transport costs lower gross margins as much as decreasing paper prices, which was a new finding. Paper companies should continuously pay attention to lowering manufacturing and transporting costs to achieve more profitable economic performance. The location of a mill being far from markets clearly has an economic impact on paper manufacturing, as paper demand is decreasing and oversupply is pressuring paper prices down. Therefore, market and economic forecasting in the paper industry is advantageous at the country and product levels while simultaneously taking into account the economic geographically specific dimensions.

People and the intertidal : human induced changes, biodiversity loss, livelihood implications and management in the Western Indian Ocean

Vad händer i tidvattenzonen? Var går gränsen mellan land och hav, vad händer i tidvattenzonen och vem ansvarar för detta? I västra Indiska oceanen (VIO) kan avståndet mellan den lägsta nivån för lågvattnet och den högsta nivån för högvattnet vara flera kilometer och nivåskillnaderna upp till 6 meter och detta skapar ett stort och föränderligt område. Syftet med min avhandling är att öka förståelsen för tidvattenzonen i tropiska och subtropiska västra Indiska oceanen. Sammanfattningsvis visar mina studier att det finns ett mycket stort värde i den komplexa tidvattenzonen, men också att det här området hotas från både land och hav, genom t.ex. överexploatering, erosion och föroreningar. Uttnyttjandet av tidvattenzonen är stort och min avhandling har visat att aktiviteter såsom fiske i form av plocking av musslor och andra ryggradslösa djur och hamnaktiviteter påverkar den biologiska mångfalden negativt, vilket leder till försämrad levnadsstandard för resursutnyttjande människor i regionen. För att förbättra situationen krävs det mer forskning, miljöövervakning och bättre förvaltning av tidvattenzonen. Experter i regionen har rangordnat förslag på förvaltningsstrategier som skulle kunna testas för att förbättra miljön och skapa ett mer hållbart nyttjande. Avhandlingen visar även att det är möjligt att använda fjärranalysteknik såsom satellitbildsanalys för att kvantifiera mängden sjögräsvegetation (i form av biomassa), vilket kan ha stor betydelse för att förbättra storskalig miljöövervakning av kustnära naturtyper (habitat). I avhandlingsarbetet har jag använt mig av ett multidisciplinärt tillvägagångssätt och använt metoder såsom ekologisk och biologisk provtagning, intervjuer, observationer, diskussionsgrupper, frågeformulär och fjärranalys. Resultaten presenterade i denna avhandling ger en ökad kunskap om tidvattenzonen i utvecklingsländerna inom VIO-regionen som kan användas för att initiera och fortsätta att utveckla hållbara förvaltningsstrategier av biologiska resurser.

Driver of Demand in Cargo and Passenger Traffic Between Penta Ports

Maritime transport moves around 6 billion tonnes of freight every year. The freight consists of liquid bulks (45%), dry bulks (23%) and general cargo (32%). Freight traffic and transports chains vary according to region, commodity and the origin and the destination of freight. In the European Union the ports sector handles over 90% of the trade with third countries. The share of intra-EU trade is approximately 30% of the total transportation and the number of passengers is over 200 million every year. The Baltic Sea has more than 50,000 vessels a year pass the Skaw at the northernmost tip of Denmark on their way into or out of the Baltic. Roughly 60% to 70% of these vessels are cargo vessels and 17% to 25% tankers. Ports and maritime transport play a crucial role in global commerce today. Today’s business environment is changing rapidly, and the constant changes create challenges for the transport industry and maritime traffic. Ports have to adapt to continuous changes in economic structures, logistics demands, and people’s travel and leisure patterns. In order to ensure the competitiveness of sea connections, the ports need to fully enhance multilateral cross-border understanding and cooperation. In this report the focus is on liner traffic between five ports in the Central Baltic Region: Stockholm, Tallinn, Helsinki Turku and Naantali. The report defines the drivers of the demand for cargo and passenger traffic and highlights the most important factors. The economic situation and foreign trade of each county are elaborated on with detailed information about the flows of traffic between the five ports. Based on expert interviews, the main characteristics of each port, including strengths and weaknesses, are presented. The report is based on primary and secondary data. Primary data was received through interviews and mail surveys. Secondary data was attained through a literature research, statistics, data given by the PENTA ports and webpages. The report is divided into two main parts: the drivers creating the demand for transport and the results of current cargo and passenger flows between PENTA ports.

JNK, a versatile regulator of kinesin-1 transport and cytoskeleton dynamics

C-Jun N-terminal kinase (JNK) is traditionally recognized as a crucial factor in stress response and inducer of apoptosis upon various stimulations. Three isoforms build the JNK subfamily of MAPK; generally expressed JNK1 and JNK2 and brain specific JNK3. Degenerative potency placed JNK in the spotlight as potential pharmacological option for intervention. Unfortunately, adverse effects of potential drugs and observation that expression of only JNK2 and JNK3 are induced upon stress, restrained initial enthusiasm. Notably, JNK1 demonstrated atypical high constitutive activity in neurons that is not responsive to cellular stresses and indicated existence of physiological activity. This thesis aimed at revealing the physiological functions of JNK1 in actin homeostasis through novel effector MARCKS-Like 1 (MARCKSL1) protein, neuronal trafficking mediated by major kinesin-1 motor protein and microtubule (MT) dynamics via STMN2/SCG10. The screen for novel physiological JNK substrates revealed specific phosphorylation of C-terminal end of MARCKSL1 at S120, T148 and T183 both ex vivo and in vitro. By utilizing site-specific mutagenesis, various actin dynamics and migrations assays we were able to demonstrate that JNK1 phosphorylation specifically facilitates F-actin bundling and thus filament stabilisation. Consecutively, this molecular mechanism was proved to enhance formation of filopodia; cell surface projections that allow cell sensing surrounding environment and migrate efficiently. Our results visualize JNK dependent and MARCKSL1 executed induction of filopodia in neurons and fibroblast indicating general mechanism. Subsequently, inactivation of JNK action on MARCKSL1 shifts cellular actin machinery into lamellipodial dynamic arrangement. Tuning of actin cytoskeleton inevitably melds with cell migration. We observed that both active JNK and JNK pseudo-phosphorylated form of MARCKSL1 reduce actin turnover in intact cells leading to overall diminished cell motility. We demonstrate that tumour transformed cells from breast, prostate, lung and muscle-derived cancers upregulate MARCKSL1. We showed on the example of prostate cancer PC-3 cell line that JNK phosphorylation negatively controls MARCKSL1 ability to induce migration, which precedes cancer cell metastasis. The second round of identification of JNK physiological substrates resulted in detection of predominant motor protein kinesin-1 (Kif5). Mass spectrometry detailed analysis showed evident endogenous phosphorylation of kinesin-1 on S176 within motor domain that interacts with MT. In vitro phosphorylation of bacterially expressed kinesin heavy chain by JNK isoforms displayed higher specificity of JNK1 when compared to JNK3. Since, JNK1 is constitutively active in neurons it signified physiological aspect of kinesin-1 regulation. Subsequent biochemical examination revealed that kinesin-1, when not phosphorylated on JNK site, exhibits much higher affinity toward MTs. Expression of the JNK non-phosphorable kinesin-1 mutant in intact cells as well as in vitro single molecule imaging using total internal reflection fluorescence microscopy indicated that the mutant loses normal speed and is not able to move processively into proper cellular compartments. We identify novel kinesin-1 cargo protein STMN2/SCG10, which along with known kinesin-1 cargo BDNF is showing impaired trafficking when JNK activity is inhibited. Our data postulates that constitutive JNK activity in neurons is crucial for unperturbed physiologically relevant transport of kinesin-1 dependant cargo. Additionally, my work helps to validate another novel physiological JNK1 effector STMN2/SCG10 as determinant of axodendritic neurites dynamics in the developing brain through regulation of MT turnover. We show successively that this increased MT dynamics is crucial during developmental radial migration when brain layering occurs. Successively, we are able to show that introduction of JNK phosphorylation mimicking STMN2/SCG10 S62/73D mutant rescues completely JNK1 genetic deletion migration phenotype. We prove that STMN2/SCG10 is predominant JNK effector responsible for MT depolymerising activity and neurite length during brain development. Summarizing, this work describes identification of three novel JNK substrates MARCKSL1, kinesin-1 and STMN2/SCG10 and investigation of their roles in cytoskeleton dynamics and cargo transport. This data is of high importance to understand physiological meaning of JNK activity, which might have an adverse effect during pharmaceutical intervention aiming at blocking pathological JNK action.

Quantification of Toxin Biosynthesis Genes In Cyanobacteria and Dinoflagellates - Genetic Factors as Predictors of Toxin Production in the Environment

Harmful algal blooms (HABs) are events caused by the massive proliferation of microscopic, often photosynthetic organisms that inhabit both fresh and marine waters. Although HABs are essentially a natural phenomenon, they now cause worldwide concern. Recent anthropogenic effects, such as climate change and eutrophication via nutrient runoff, can be seen in their increased prevalence and severity. Cyanobacteria and dinoflagellates are often the causative organisms of HABs. In addition to adverse effects caused by the sheer biomass, certain species produce highly potent toxic compounds: hepatotoxic microcystins are produced exclusively by cyanobacteria and neurotoxic saxitoxins, also known as paralytic shellfish toxins (PSTs), by both cyanobacteria and dinoflagellates. Specific biosynthetic genes in the cyanobacterial genomes direct the production of microcystin and paralytic shellfish toxins. Recently also the first paralytic shellfish toxin gene sequences from dinoflagellate genomes have been elucidated. The public health risks presented by HABs are evident, but the monitoring and prediction of toxic events is challenging. Characterization of the genetic background of toxin biosynthesis, including that of microcystins and paralytic shellfish toxins, has made it possible to develop highly sensitive molecular tools which have shown promise in the monitoring and study of potentially toxic microalgae. In this doctoral work, toxin-specific genes were targeted in the developed PCR and qPCR assays for the detection and quantification of potentially toxic cyanobacteria and dinoflagellates in the environment. The correlation between the copy numbers of the toxin biosynthesis genes and toxin production were investigated to assess whether the developed methods could be used to predict toxin concentrations. The nature of the correlation between gene copy numbers and amount of toxin produced varied depending on the targeted gene and the producing organism. The combined mcyB copy numbers of three potentially microcystin-producing cyanobacterial genera showed significant positive correlation to the observed total toxin production. However, the presence of PST-specific sxtA, sxtG, and sxtB genes of cyanobacterial origin was found to be a poor predictor of toxin production in the studied area. Conversely, the dinoflagellate sxtA4 was a good qualitative indicator of a neurotoxic bloom both in the laboratory and in the field, and population densities reflected well the observed toxin concentrations. In conclusion, although the specificity of each potential targeted toxin biosynthesis gene must be assessed individually during method development, the results obtained in this doctoral study support the use of quantitative PCR -based approaches in the monitoring of toxic cyanobacteria and dinoflagellates.

Innovation, competition and financial vulnerability in economic development

The financial sector has been viewed traditionally as either providing the "oil" for the "wheels of commerce" or as a parasite on the real sector of the economy where real productivity gains provide for increasing real wages and per capita incomes. The present paper takes a different route and attempts to an analysis of financial institutions on a par with the production sector of the economy. It also develops a link which amalgamates "the knowledge-based" perspective on firms' operations with Schumpeterian financial leverage to exploit productivity enhancing innovations, and Minsky's tendency towards financial fragility. The analysis also leads to some policy recommendations concerning financial regulation, risk management and financial institution's building.

States and Economic Development

Today the Washington Consensus on development lies in tatters. The recent history of the developing world has been unkind to the core claim that a nation that opens its economy and keeps government's role to a minimum invariably experiences rapid economic growth. The evidence against this claim is strong: the developing world as a whole grew faster during the era of state intervention and import substitution (1950-1980) than in the more recent era of structural adjustment (1990-2005); and the recent economic performance of both Latin America and Sub-Saharan Africaregions that truly embraced neoliberalismhas lagged well behind that of many Asian economies, which have instead pursued judicial and unorthodox combinations of state intervention and economic openness. As scholars and policy makers reconstruct alternatives to the Washington Consensus on development, it is important to underline that prudent and effective state intervention and selective integration with the global economy have been responsible for development success in the past; they are also likely to remain the recipes for upward mobility in the global economy in the future."

The Impact of Foreign Direct Investment Inflows on the Economic Growth of Bangladesh. The Roles of Infrastructural Facilities

Foreign direct investment (FDI) inflow has been a key concern for Bangladesh to obtain additional support for the economic development. The Government of Bangladesh continuously competing with other South Asian countries and putting more effort to increase the number of FDI inflows in the country. From the country’s perspective, the constant increasing rate of economic growth shows a positive outcome of FDI inflow. However, the country still not performing up to the mark to pull enough FDI inflows to its potential. Thus, this study discusses about the major determinants and factors affecting FDI inflows in Bangladesh. Among those determinants and factors, infrastructural facility is considered as the most important to affect FDI inflows. FDI inflow is fundamentally depending upon infrastructural facilities to achieve its desire success. Foreign investors take this issue very seriously because based on this they can measure their ease of doing business in the host country. Despite of providing a large market size, due to having weak and lack of infrastructural facilities, Bangladesh is facing trouble in drawing attention of the foreign investors. In order to make the infrastructural facilities happen, it is highly required to organize each of the systems under of it. The body of this study discussed about the weak infrastructures in Bangladesh such as transport and communication, power and energy, education system, and governance services. Improvement in one of these systems cannot provide valuable positive changes on FDI inflows. It requires improvement in all the weak systems to grasp multinational companies and attract foreign investors. On the basis of this research problem, research questions are established. Both qualitative and quantitative methods are used to answer the research questions. Furthermore, several theories have been applied to justify possible scenarios from the research problem. In addition, the history in between Bangladesh, trade liberalization, and FDI inflows is presented briefly.

The Impact of Foreign Direct Investment Inflows on the Economic Growth of Bangladesh. The Roles of Infrastructural Facilities

Foreign direct investment (FDI) inflow has been a key concern for Bangladesh to obtain additional support for the economic development. The Government of Bangladesh continuously competing with other South Asian countries and putting more effort to increase the number of FDI inflows in the country. From the country’s perspective, the constant increasing rate of economic growth shows a positive outcome of FDI inflow. However, the country still not performing up to the mark to pull enough FDI inflows to its potential. Thus, this study discusses about the major determinants and factors affecting FDI inflows in Bangladesh. Among those determinants and factors, infrastructural facility is considered as the most important to affect FDI inflows. FDI inflow is fundamentally depending upon infrastructural facilities to achieve its desire success. Foreign investors take this issue very seriously because based on this they can measure their ease of doing business in the host country. Despite of providing a large market size, due to having weak and lack of infrastructural facilities, Bangladesh is facing trouble in drawing attention of the foreign investors. In order to make the infrastructural facilities happen, it is highly required to organize each of the systems under of it. The body of this study discussed about the weak infrastructures in Bangladesh such as transport and communication, power and energy, education system, and governance services. Improvement in one of these systems cannot provide valuable positive changes on FDI inflows. It requires improvement in all the weak systems to grasp multinational companies and attract foreign investors. On the basis of this research problem, research questions are established. Both qualitative and quantitative methods are used to answer the research questions. Furthermore, several theories have been applied to justify possible scenarios from the research problem. In addition, the history in between Bangladesh, trade liberalization, and FDI inflows is presented briefly

Trade with China and strategy in South American recent economic development

Trade between South America and China has been an important source of the high growth shown by those economies in the 2000s. During the globalization of the 1990s, trade between the region and China had not developed so much. A rather sharp growth in China's presence in world trade since the beginning of the 2000s changed the world trade trends for MERCOSUR countries, or, at least, for many of them. The impact of the increasing trade of agrifood has been very relevant, and different per country. Strategy is another important issue, referring to bilateral relations with China. This country should be seen as a partner in the global trade, and not as a new foreign investor for the region, but this may be different in the context of different national strategies of South American countries.