Economic Survey of Latin America and the Caribbean 2009-2010: The distributive impact of public policies

Includes bibliography

Appraisal and conclusions from the 1994-2009 review of the implementation of the Cairo Programme of Action in the Caribbean

Incluye Bibliografía

The small economies of Latin America and the Caribbean

Includes bibliography

The employment situation in Latin America and the Caribbean: Recovery of employment: towards a sustainable model

The adverse effects on Latin America and the Caribbean of the global economic and financial crisis, the worst since the 1930s, have been considerably less than was once feared. Although a run of growth was cut short in 2009 and regional output shrank by 1.9%, the impact of the crisis was limited by the application of countercyclical fiscal and monetary policies by many of the region’s governments. The recovery in the economies, particularly in South America, has gone hand-in-hand with the rapid resurgence of the emerging economies of Asia, with all the favourable consequences this has had for global trade. A similar pattern may be observed regarding the impact of the crisis on labour markets in Latin America and the Caribbean. Although millions of people lost their jobs or had to trade down to lower-quality work, levels of employment (including formal employment) fell by less than originally foreseen. At the same time, real wages rose slightly in a context of falling inflation. The labour market thus stabilized domestic demand, and this contributed to the recovery that began in many countries in late 2009. Improved international trade and financing conditions, and the pick-up in domestic demand driven by macroeconomic policies, have led different commentators to estimate growth in the region’s economy at some 6% in 2010. As detailed in the first part of this edition of the Bulletin, the upturn has been manifested at the regional level by the creation of formal employment, a rise in the employment rate, a decline in joblessness and a moderate increase in real wages. Specifically, it is estimatedthat the regional unemployment rate will have dropped by 0.6 percentage points, from 8.1% in 2009 to 7.5% in 2010. The performance of different countries and subregions has been very uneven, however. On the one hand, there is Brazil, where high economic growth has been accompanied by vigorous creation of formal jobs and the unemployment rate has dropped to levels not seen in a long time. Other countries in South America have benefited from strong demand for natural resources from the Asian countries. Combined with higher domestic demand, this has raised their economic growth rates and had a positive impact on employment indicators. On the other hand, the recovery is still very weak in certain countries and subregions, particularly in the Caribbean, with employment indicators continuing to worsen.Thus, the recovery in the region’s economy in 2010 may be characterized as dynamic but uneven. Growth estimates for 2011 are less favourable. The risks associated with the imbalances in the world economy and the withdrawal of countercyclical fiscal packages are likely to cause the region to grow more slowly in 2011. Accordingly, a small further reduction of between 0.2 and 0.4 percentage points in the unemployment rate is projected for 2011. However, these indicators of recovery do not guarantee growth with decent work in the long term. To bolster the improvement in labour market indicators and generate more productive employment and decent work, the region’s countries need to strengthen their macroeconomic policies, improve regional and global policy coordination, identify and remove bottlenecks in the labour market itself and enhance instruments designed to promote greater equality. Like the rest of the world, the Latin American and Caribbean region is also confronted with the challenge of transforming the way it produces so that its economies can develop along tracks that are sustainable in the long term. Climate change and the consequent challenge of developing and strengthening low-carbon production and consumption patterns will also affect the way people work. A great challenge ahead is to create green jobs that combine decent work with environmentally sustainable production patterns. From this perspective, the second part of this Bulletin discusses the green jobs approach, offering some information on the challenges and opportunities involved in moving towards a sustainable economy in the region and presenting a set of options for addressing environmental issues and the repercussions of climate change in the world of work. Although the debate about the green jobs concept is fairly new in the region, examples already exist and a number of countries have moved ahead with the application of policies and programmes in this area. Costa Rica has formulated a National Climate Change Strategy, for example, whose foremost achievements include professional training in natural-resource management. In Brazil, fuel production from biomass has increased and social housing with solar panelling is being built. A number of other countries in the region are making progress in areas such as ecotourism, sustainable agriculture and infrastructure for climate change adaptation, and in formalizing the work of people who recycle household waste. The shift towards a more environmentally sustainable economy may cause jobs to be destroyed in some economic sectors and created in others. The working world will inevitably undergo major changes. If the issue is approached by way of social dialogue and appropriate public policies, there is a chance to use this shift to create more decent jobs, thereby contributing to growth in the economy, the construction of higher levels of equality and protection for the environment.

Análise energética em refino de petróleo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Antinociceptive effects of the essential oil of Mentha x villosa leaf and its major constituent piperitenone oxide in mice

Mentha x villosa Huds (Labiatae) is an aromatic herb widely used in folk medicine. Since the essential oil of the herb has many pharmacological activities, including antispasmodic effects, we determined whether the oil and its major constituent, piperitenone oxide (PO), have antinociceptive activity. The essential oil of M. x villosa (EOMV) and PO administered orally at 200 mg/kg (vehicle: 0.1% Tween 80 in water) significantly reduced the writhings induced by acetic acid from control values of 59.5 ± 3.1 s (N = 10) to 31.9 ± 2.8 s (N = 10) and 23.8 ± 3.4 s (N = 10), respectively. When administered at 100 and 200 mg/kg, EOMV reduced the paw licking time for the second phase of the formalin test from the control value of 20.6 ± 2.1 s (N = 13) to 5.3 ± 2.2 s (N = 12) and 2.7 ± 1.2 s (N = 18), respectively. At 100 and 200 mg/kg, PO reduced this second phase to 8.3 ± 2.7 s (N = 12) and 3.0 ± 1.2 s (N = 10), respectively. This effect of EOMV and PO was not reversed by naloxone. EOMV and PO had no significant effect on the first phase of the formalin test. As evaluated by the hot-plate and tail immersion test, EOMV and PO, at doses up to 200 mg/kg, showed no analgesic activity. These results show that EOMV and PO have antinociceptive activity and suggest that this effect is probably an indirect anti-inflammatory effect, which does not involve the central nervous system.

Essays on the political economy of European integration

Recently, a rising interest in political and economic integration/disintegration issues has been developed in the political economy field. This growing strand of literature partly draws on traditional issues of fiscal federalism and optimum public good provision and focuses on a trade-off between the benefits of centralization, arising from economies of scale or externalities, and the costs of harmonizing policies as a consequence of the increased heterogeneity of individual preferences in an international union or in a country composed of at least two regions. This thesis stems from this strand of literature and aims to shed some light on two highly relevant aspects of the political economy of European integration. The first concerns the role of public opinion in the integration process; more precisely, how economic benefits and costs of integration shape citizens' support for European Union (EU) membership. The second is the allocation of policy competences among different levels of government: European, national and regional. Chapter 1 introduces the topics developed in this thesis by reviewing the main recent theoretical developments in the political economy analysis of integration processes. It is structured as follows. First, it briefly surveys a few relevant articles on economic theories of integration and disintegration processes (Alesina and Spolaore 1997, Bolton and Roland 1997, Alesina et al. 2000, Casella and Feinstein 2002) and discusses their relevance for the study of the impact of economic benefits and costs on public opinion attitude towards the EU. Subsequently, it explores the links existing between such political economy literature and theories of fiscal federalism, especially with regard to normative considerations concerning the optimal allocation of competences in a union. Chapter 2 firstly proposes a model of citizens’ support for membership of international unions, with explicit reference to the EU; subsequently it tests the model on a panel of EU countries. What are the factors that influence public opinion support for the European Union (EU)? In international relations theory, the idea that citizens' support for the EU depends on material benefits deriving from integration, i.e. whether European integration makes individuals economically better off (utilitarian support), has been common since the 1970s, but has never been the subject of a formal treatment (Hix 2005). A small number of studies in the 1990s have investigated econometrically the link between national economic performance and mass support for European integration (Eichenberg and Dalton 1993; Anderson and Kalthenthaler 1996), but only making informal assumptions. The main aim of Chapter 2 is thus to propose and test our model with a view to providing a more complete and theoretically grounded picture of public support for the EU. Following theories of utilitarian support, we assume that citizens are in favour of membership if they receive economic benefits from it. To develop this idea, we propose a simple political economic model drawing on the recent economic literature on integration and disintegration processes. The basic element is the existence of a trade-off between the benefits of centralisation and the costs of harmonising policies in presence of heterogeneous preferences among countries. The approach we follow is that of the recent literature on the political economy of international unions and the unification or break-up of nations (Bolton and Roland 1997, Alesina and Wacziarg 1999, Alesina et al. 2001, 2005a, to mention only the relevant). The general perspective is that unification provides returns to scale in the provision of public goods, but reduces each member state’s ability to determine its most favoured bundle of public goods. In the simple model presented in Chapter 2, support for membership of the union is increasing in the union’s average income and in the loss of efficiency stemming from being outside the union, and decreasing in a country’s average income, while increasing heterogeneity of preferences among countries points to a reduced scope of the union. Afterwards we empirically test the model with data on the EU; more precisely, we perform an econometric analysis employing a panel of member countries over time. The second part of Chapter 2 thus tries to answer the following question: does public opinion support for the EU really depend on economic factors? The findings are broadly consistent with our theoretical expectations: the conditions of the national economy, differences in income among member states and heterogeneity of preferences shape citizens’ attitude towards their country’s membership of the EU. Consequently, this analysis offers some interesting policy implications for the present debate about ratification of the European Constitution and, more generally, about how the EU could act in order to gain more support from the European public. Citizens in many member states are called to express their opinion in national referenda, which may well end up in rejection of the Constitution, as recently happened in France and the Netherlands, triggering a European-wide political crisis. These events show that nowadays understanding public attitude towards the EU is not only of academic interest, but has a strong relevance for policy-making too. Chapter 3 empirically investigates the link between European integration and regional autonomy in Italy. Over the last few decades, the double tendency towards supranationalism and regional autonomy, which has characterised some European States, has taken a very interesting form in this country, because Italy, besides being one of the founding members of the EU, also implemented a process of decentralisation during the 1970s, further strengthened by a constitutional reform in 2001. Moreover, the issue of the allocation of competences among the EU, the Member States and the regions is now especially topical. The process leading to the drafting of European Constitution (even if then it has not come into force) has attracted much attention from a constitutional political economy perspective both on a normative and positive point of view (Breuss and Eller 2004, Mueller 2005). The Italian parliament has recently passed a new thorough constitutional reform, still to be approved by citizens in a referendum, which includes, among other things, the so called “devolution”, i.e. granting the regions exclusive competence in public health care, education and local police. Following and extending the methodology proposed in a recent influential article by Alesina et al. (2005b), which only concentrated on the EU activity (treaties, legislation, and European Court of Justice’s rulings), we develop a set of quantitative indicators measuring the intensity of the legislative activity of the Italian State, the EU and the Italian regions from 1973 to 2005 in a large number of policy categories. By doing so, we seek to answer the following broad questions. Are European and regional legislations substitutes for state laws? To what extent are the competences attributed by the European treaties or the Italian Constitution actually exerted in the various policy areas? Is their exertion consistent with the normative recommendations from the economic literature about their optimum allocation among different levels of government? The main results show that, first, there seems to be a certain substitutability between EU and national legislations (even if not a very strong one), but not between regional and national ones. Second, the EU concentrates its legislative activity mainly in international trade and agriculture, whilst social policy is where the regions and the State (which is also the main actor in foreign policy) are more active. Third, at least two levels of government (in some cases all of them) are significantly involved in the legislative activity in many sectors, even where the rationale for that is, at best, very questionable, indicating that they actually share a larger number of policy tasks than that suggested by the economic theory. It appears therefore that an excessive number of competences are actually shared among different levels of government. From an economic perspective, it may well be recommended that some competences be shared, but only when the balance between scale or spillover effects and heterogeneity of preferences suggests so. When, on the contrary, too many levels of government are involved in a certain policy area, the distinction between their different responsibilities easily becomes unnecessarily blurred. This may not only leads to a slower and inefficient policy-making process, but also risks to make it too complicate to understand for citizens, who, on the contrary, should be able to know who is really responsible for a certain policy when they vote in national,local or European elections or in referenda on national or European constitutional issues.

The Role of Multiple Social Categorisation in Promoting the Inclusion in the Human Group of Outgroup Members

Stimulus-induced gamma activity in the electrocorticogram of freely moving telemetric implanted rats: the neuronal signature of novelty detection

During this thesis a new telemetric recording system has been developed allowing ECoG/EEG recordings in freely behaving rodents (Lapray et al., 2008; Lapray et al., in press). This unit has been shown to not generate any discomfort in the implanted animals and to allow recordings in a wide range of environments. In the second part of this work the developed technique has been used to investigate what cortical activity was related to the process of novelty detection in rats’ barrel cortex. We showed that the detection of a novel object is accompanied in the barrel cortex by a transient burst of activity in the γ frequency range (40-47 Hz) around 200 ms after the whiskers contact with the object (Lapray et al., accepted). This activity was associated to a decrease in the lower range of γ frequencies (30-37 Hz). This network activity may represent the optimal oscillatory pattern for the propagation and storage of new information in memory related structures. The frequency as well as the timing of appearance correspond well with other studies concerning novelty detection related burst of activity in other sensory systems (Barcelo et al., 2006; Haenschel et al., 2000; Ranganath & Rainer, 2003). Here, the burst of activity is well suited to induce plastic and long-lasting modifications in neuronal circuits (Harris et al., 2003). The debate is still open whether synchronised activity in the brain is a part of information processing or an epiphenomenon (Shadlen & Movshon, 1999; Singer, 1999). The present work provides further evidence that neuronal network activity in the γ frequency range plays an important role in the neocortical processing of sensory stimuli and in higher cognitive functions.

Biochemical analysis of the phosphatase domain of the human soluble epoxide hydrolase (sEH)

Die lösliche Epoxidhydrolase (sEH) gehört zur Familie der Epoxidhydrolase-Enzyme. Die Rolle der sEH besteht klassischerweise in der Detoxifikation, durch Umwandlung potenziell schädlicher Epoxide in deren unschädliche Diol-Form. Hauptsächlich setzt die sEH endogene, der Arachidonsäure verwandte Signalmoleküle, wie beispielsweise die Epoxyeicosatrienoic acid, zu den entsprechenden Diolen um. Daher könnte die sEH als ein Zielenzym in der Therapie von Bluthochdruck und Entzündungen sowie diverser anderer Erkrankungen eingesetzt werden. rnDie sEH ist ein Homodimer, in dem jede Untereinheit aus zwei Domänen aufgebaut ist. Das katalytische Zentrum der Epoxidhydrolaseaktivität befindet sich in der 35 kD großen C-terminalen Domäne. Dieser Bereich der sEH s wurde bereits im Detail untersucht und nahezu alle katalytischen Eigenschaften des Enzyms sowie deren dazugehörige Funktionen sind in Zusammenhang mit dieser Domäne bekannt. Im Gegensatz dazu ist über die 25 kD große N-terminale Domäne wenig bekannt. Die N-terminale Domäne der sEH wird zur Haloacid Dehalogenase (HAD) Superfamilie von Hydrolasen gezählt, jedoch war die Funktion dieses N-terminal Domäne lange ungeklärt. Wir haben in unserer Arbeitsgruppe zum ersten Mal zeigen können, dass die sEH in Säugern ein bifunktionelles Enzym ist, welches zusätzlich zur allgemein bekannten Enzymaktivität im C-terminalen Bereich eine weitere enzymatische Funktion mit Mg2+-abhängiger Phosphataseaktivität in der N-terminalen Domäne aufweist. Aufgrund der Homologie der N-terminalen Domäne mit anderen Enzymen der HAD Familie wird für die Ausübung der Phosphatasefunktion (Dephosphorylierung) eine Reaktion in zwei Schritten angenommen.rnUm den katalytischen Mechanismus der Dephosphorylierung weiter aufzuklären, wurden biochemische Analysen der humanen sEH Phosphatase durch Generierung von Mutationen im aktiven Zentrum mittels ortsspezifischer Mutagenese durchgeführt. Hiermit sollten die an der katalytischen Aktivität beteiligten Aminosäurereste im aktiven Zentrum identifiziert und deren Rolle bei der Dephosphorylierung spezifiziert werden. rnrnAuf Basis der strukturellen und möglichen funktionellen Ähnlichkeiten der sEH und anderen Mitgliedern der HAD Superfamilie wurden Aminosäuren (konservierte und teilweise konservierte Aminosäuren) im aktiven Zentrum der sEH Phosphatase-Domäne als Kandidaten ausgewählt.rnVon den Phosphatase-Domäne bildenden Aminosäuren wurden acht ausgewählt (Asp9 (D9), Asp11 (D11), Thr123 (T123), Asn124 (N124), Lys160 (K160), Asp184 (D184), Asp185 (D185), Asn189 (N189)), die mittels ortsspezifischer Mutagenese durch nicht funktionelle Aminosäuren ausgetauscht werden sollten. Dazu wurde jede der ausgewählten Aminosäuren durch mindestens zwei alternative Aminosäuren ersetzt: entweder durch Alanin oder durch eine Aminosäure ähnlich der im Wildtyp-Enzym. Insgesamt wurden 18 verschiedene rekombinante Klone generiert, die für eine mutante sEH Phosphatase Domäne kodieren, in dem lediglich eine Aminosäure gegenüber dem Wildtyp-Enzym ersetzt wurde. Die 18 Mutanten sowie das Wildtyp (Sequenz der N-terminalen Domäne ohne Mutation) wurden in einem Expressionsvektor in E.coli kloniert und die Nukleotidsequenz durch Restriktionsverdau sowie Sequenzierung bestätigt. Die so generierte N-terminale Domäne der sEH (25kD Untereinheit) wurde dann mittels Metallaffinitätschromatographie erfolgreich aufgereinigt und auf Phosphataseaktivität gegenüber des allgemeinen Substrats 4-Nitophenylphosphat getestet. Diejenigen Mutanten, die Phosphataseaktivität zeigten, wurden anschließend kinetischen Tests unterzogen. Basiered auf den Ergebnissen dieser Untersuchungen wurden kinetische Parameter mittels vier gut etablierter Methoden berechnet und die Ergebnisse mit der „direct linear blot“ Methode interpretiert. rnDie Ergebnisse zeigten, dass die meisten der 18 generierten Mutanten inaktiv waren oder einen Großteil der Enzymaktivität (Vmax) gegenüber dem Wildtyp verloren (WT: Vmax=77.34 nmol-1 mg-1 min). Dieser Verlust an Enzymaktivität ließ sich nicht durch einen Verlust an struktureller Integrität erklären, da der Wildtyp und die mutanten Proteine in der Chromatographie das gleiche Verhalten zeigten. Alle Aminosäureaustausche Asp9 (D9), Lys160 (K160), Asp184 (D184) und Asn189 (N189) führten zum kompletten Verlust der Phosphataseaktivität, was auf deren katalytische Funktion im N-terminalen Bereich der sEH hindeutet. Bei einem Teil der Aminosäureaustausche die für Asp11 (D11), Thr123 (T123), Asn124 (N124) und Asn185 (D185) durchgeführt wurden, kam es, verglichen mit dem Wildtyp, zu einer starken Reduktion der Phosphataseaktivität, die aber dennoch für die einzelnen Proteinmutanten in unterschiedlichem Ausmaß zu messen war (2 -10% and 40% of the WT enzyme activity). Zudem zeigten die Mutanten dieser Gruppe veränderte kinetische Eigenschaften (Vmax allein oder Vmax und Km). Dabei war die kinetische Analyse des Mutanten Asp11  Asn aufgrund der nur bei dieser Mutanten detektierbaren starken Vmax Reduktion (8.1 nmol-1 mg-1 min) und einer signifikanten Reduktion der Km (Asp11: Km=0.54 mM, WT: Km=1.3 mM), von besonderem Interesse und impliziert eine Rolle von Asp11 (D11) im zweiten Schritt der Hydrolyse des katalytischen Zyklus.rnZusammenfassend zeigen die Ergebnisse, dass alle in dieser Arbeit untersuchten Aminosäuren für die Phosphataseaktivität der sEH nötig sind und das aktive Zentrum der sEH Phosphatase im N-terminalen Bereich des Enzyms bilden. Weiterhin tragen diese Ergebnisse zur Aufklärung der potenziellen Rolle der untersuchten Aminosäuren bei und unterstützen die Hypothese, dass die Dephosphorylierungsreaktion in zwei Schritten abläuft. Somit ist ein kombinierter Reaktionsmechanismus, ähnlich denen anderer Enzyme der HAD Familie, für die Ausübung der Dephosphorylierungsfunktion denkbar. Diese Annahme wird gestützt durch die 3D-Struktur der N-terminalen Domäne, den Ergebnissen dieser Arbeit sowie Resultaten weiterer biochemischer Analysen. Der zweistufige Mechanismus der Dephosphorylierung beinhaltet einen nukleophilen Angriff des Substratphosphors durch das Nukleophil Asp9 (D9) des aktiven Zentrums unter Bildung eines Acylphosphat-Enzym-Zwischenprodukts, gefolgt von der anschließenden Freisetzung des dephosphorylierten Substrats. Im zweiten Schritt erfolgt die Hydrolyse des Enzym-Phosphat-Zwischenprodukts unterstützt durch Asp11 (D11), und die Freisetzung der Phosphatgruppe findet statt. Die anderen untersuchten Aminosäuren sind an der Bindung von Mg 2+ und/oder Substrat beteiligt. rnMit Hilfe dieser Arbeit konnte der katalytischen Mechanismus der sEH Phosphatase weiter aufgeklärt werden und wichtige noch zu untersuchende Fragestellungen, wie die physiologische Rolle der sEH Phosphatase, deren endogene physiologische Substrate und der genaue Funktionsmechanismus als bifunktionelles Enzym (die Kommunikation der zwei katalytischen Einheiten des Enzyms) wurden aufgezeigt und diskutiert.rn

The constitutive activation of the DNA damage response pathway is a novel therapeutic target in aggressive B-cell lymphoma

The recent finding that MYC-driven cancers are sensitive to inhibition of the DNA damage response (DDR) pathway, prompted us to investigate the role of DDR pathway as therapeutic target in diffuse large B-cell lymphoma (DLBCL), which frequently overexpresses the MYC oncogene. In a preliminary immunohistochemical study conducted on 99 consecutive DLBCL patients, we found that about half of DLBCLs showed constitutive expression of the phosphorylated forms of checkpoint kinases (CHK) and CDC25c, markers of DDR activation, and of phosphorylated histone H2AX (γH2AX), marker of DNA damage and genomic instability. Constitutive γH2AX expression correlated with c-MYC levels and DDR activation, and defined a subset of tumors characterised by poor outcome. Next, we used the CHK inhibitor PF-0477736 as a tool to investigate whether the inhibition of the DDR pathway might represent a novel therapeutic approach in DLBCL. Submicromolar concentrations of PF-0477736 hindered proliferation in DLBCL cell lines with activated DDR pathway. These results were fully recapitulated with a different CHK inhibitor (AZD-7762). Inhibition of checkpoint kinases induced rapid DNA damage accumulation and apoptosis in DLBCL cell lines and primary cells. These data suggest that pharmacologic inhibition of DDR through targeting of CHK kinases may represent a novel therapeutic strategy in DLBCL. The second part of this work is the clinical, molecular and functional description of a paradigmatic case of primary refractory Burkitt lymphoma characterized by spatial intratumor heterogeneity for the TP53 mutational status, high expression levels of genomic instability and DDR activation markers, primary resistance to chemotherapy and exquisite sensitivity to DDR inhibitors.

Extracting evolutionary information from the spectral decomposition of early-type galaxies.

Holding the major share of stellar mass in galaxies and being also old and passively evolving, early-type galaxies (ETGs) are the primary probes in investigating these various evolution scenarios, as well as being useful means to provide insights on cosmological parameters. In this thesis work I focused specifically on ETGs and on their capability in constraining galaxy formation and evolution; in particular, the principal aims were to derive some of the ETGs evolutionary parameters, such as age, metallicity and star formation history (SFH) and to study their age-redshift and mass-age relations. In order to infer galaxy physical parameters, I used the public code STARLIGHT: this program provides a best fit to the observed spectrum from a combination of many theoretical models defined in user-made libraries. the comparison between the output and input light-weighted ages shows a good agreement starting from SNRs of ∼ 10, with a bias of ∼ 2.2% and a dispersion 3%. Furthermore, also metallicities and SFHs are well reproduced. In the second part of the thesis I performed an analysis on real data, starting from Sloan Digital Sky Survey (SDSS) spectra. I found that galaxies get older with cosmic time and with increasing mass (for a fixed redshift bin); absolute light-weighted ages, instead, result independent from the fitting parameters or the synthetic models used. Metallicities, instead, are very similar from each other and clearly consistent with the ones derived from the Lick indices. The predicted SFH indicates the presence of a double burst of star formation. Velocity dispersions and extinctiona are also well constrained, following the expected behaviours. As a further step, I also fitted single SDSS spectra (with SNR∼ 20), to verify that stacked spectra gave the same results without introducing any bias: this is an important check, if one wants to apply the method at higher z, where stacked spectra are necessary to increase the SNR. Our upcoming aim is to adopt this approach also on galaxy spectra obtained from higher redshift Surveys, such as BOSS (z ∼ 0.5), zCOSMOS (z 1), K20 (z ∼ 1), GMASS (z ∼ 1.5) and, eventually, Euclid (z 2). Indeed, I am currently carrying on a preliminary study to estabilish the applicability of the method to lower resolution, as well as higher redshift (z 2) spectra, just like the Euclid ones.

In vitro modulation of epileptiform activity in the hippocampal formation of immature rodents by GABAergic antagonists, dopamine and methylxanthines

Während des frühen Lebens stellen epileptische Anfälle schwere neurologische Zustände dar, weil sie ein großer Risikofaktor für die Manifestation der Epilepsie sind und eine hohe pharmakologische Resistenz zeigen. In meiner Doktorarbeit konzentrierte ich mich auf die Frage, wie verschiedene Neurotransmitter-Systeme und klinisch verwendete Medikamente epileptiforme Entladungen im perinatalen Hippocampus beeinflussen. rnIm ersten Teil meines Projektes untersuchte ich die Wirkung von GABA-Antagonisten und Modulatoren, die zwischen phasischen und tonischen GABAergen Strömen differenzieren, auf Feldpotentialaktivität in Hippocampusschnitten. Diese Experimente zeigten, dass im unreifen Hippocampus synaptische GABAerge Aktivität benötigt wird, um die Erregbarkeit zu begrenzen, während tonische GABAerge Ströme die Erregbarkeit verstärken können. Dies könnte darauf hinweisen, dass Antiepileptika mit einer höheren Spezifität für synaptische GABAA-Rezeptoren wirksamer zur Behandlung von epileptischen Anfällen bei Neugeborenen sein können. rnUm den Einfluss von Dopamin auf die Erregbarkeit des unreifen Hippocampus herauszufinden, untersuchte ich im zweiten Teil meiner Arbeit die Wirkung von verschiedenen Dopaminkonzentrationen und spezifische Agonisten und Antagonisten der Dopamin-Rezeptor-Subtypen auf epileptiforme Entladungen. Diese Experimente zeigten, dass niedrige Dopamin Konzentrationen eine antikonvulsive Wirkung haben, welche vom D2-ähnliche-Rezeptor-Agonisten Quinpirol nachgeahmt werden kann, während höhere Dopamin-Konzentrationen eine prokonvulsive Wirkung über Aktivierung von D1-ähnlichen Rezeptoren hervorrufen. Obwohl unsere Untersuchungen eine mögliche Verwendung von D2-ähnlichen Rezeptor-Agonisten zur Kontrolle epileptischer Anfälle in Neugeborenen nahelegen, müssen mögliche negative Auswirkungen von DAergen Agonisten und Antagonisten auf die neuronale Entwicklung berücksichtigt werden.rnIm dritten Teil meiner Arbeit untersuchte ich welche Konzentrationen von Methylxanthinen epileptische Anfälle in Hippocampuspreparationen auslösen die synaptische Übertragungen verändern können. Diese Experimente zeigten, dass sowohl Theophyllin als auch Koffein in höheren Konzentrationen die basale synaptische Übertragungen in der CA1-Region des Hippocampus modifizieren und epileptiforme Entladungen provozieren. Die Auswirkungen auf die postsynaptischen Antworten und spontanen epileptiformen Entladungen durch Koffein waren weniger ausgeprägt, was darauf hindeutet, dass diese Substanz potentiell vorteilhafter für therapeutische Anwendungen bei Frühgeborenen sein kann. rnZusammenfassend bereichern die Ergebnisse meiner Studie erheblich unser Wissen über die zugrunde liegenden Mechanismen epileptiformer Aktivität im unreifen Hippocampus und den therapeutischen Einsatz von Methylxanthinen und Pharmaka, die auf das GABAerge und DArge System einwirken.rnrn

Interplay between BDNF,TrkB signalling and GABAergic inhibition in the visual cortex of mice

Der visuelle Kortex ist eine der attraktivsten Modellsysteme zur Untersuchung der molekularen Mechanismen der synaptischen Plastizität im Gehirn. Es hat sich gezeigt, dass der Wachstumsfaktor brain-derived-neurotrophic-factor (BDNF) und die GABAerge Hemmung während der Entwicklung eine essentielle Funktion in der Regulierung der synaptischen Plastizität im visuellen Kortex besitzen. BDNF bindet u.a. an TrkB Rezeptoren, die das Signal intrazellular an unterschiedliche Effektormoleküle weiter vermitteln. Außer BDNF sind auch andere TrkB-Rezeptor Agonisten in der Literatur beschrieben. Einer davon ist das kürzlich identifizierte Flavonoid 7,8-Dihydroxyflavone (7,8-DHF), welchem eine neurotrophe Wirkung zugeschrieben wird. Im ersten Abschnitt der vorliegenden Doktorarbeit wurde der Effekt dieses Agonisten auf die synaptische Übertragung und intrinsischen Zelleigenschaften im visuellen Kortex der Maus untersucht. Dies wurde mit Hilfe der whole-cell patch clamp Methode durchgeführt, wobei die synaptischen Eingänge der Pyramidalzellen der kortikalen Schicht 2/3 von besonderem Interesse waren.rnEine 30 minütige Inkubationszeit der kortikalen Schnitte mit 7,8 DHF (20µM) erzielte eine signifikante Reduktion der GABAergen Hemmung, während die glutamaterge synaptische Übertragung unverändert blieb. Des weiteren konnte in Gegenwart von 7,8 DHF eine Veränderung der intrinsischen neuronalen Zellmembraneigenschaften beobachtet werden. Dies wurde deutlich in der Erhöhung des Eingangwiderstandes und der Frequenz der induzierten Aktionspotentiale. Die chronische Applikation von 7,8 DHF in vivo bestätigte die selektive Wirkung von 7,8 DHF auf das GABAerge System. rnDie Rolle des BDNF-TrkB-Signalweges in der GABAergen Hemmung nach kortikalen Verletzungen ist bisher wenig verstanden. Eine häufig beschriebene elektrophysiologische Veränderung nach kortikaler Verletzung ist eine Reduktion in der GABAergen Hemmung. Im zweiten Abschnitt dieser Doktorarbeit wurde hierzu die Funktion des BDNF-TrkB-Signalweges auf die GABAerge Hemmung nach kortikaler Verletzung untersucht. Es wurde ein "ex-vivo/in-vitro“ Laser-Läsions Modell verwendet, wobei mittels eines Lasers im visuellen Kortex von WT und heterozygoten BDNF (+/−) Mäusen eine definierte, reproduzierbare Läsion induziert wurde. Nachfolgende elektrophysiologische Messungen ergaben, dass die Auswirkung einer Verletzung des visuellen Kortex auf die GABAerge Funktion signifikant von der basalen BDNF Konzentration im Kortex abhängt. Des weiteren konnte beobachtet werden, dass nach kortikaler Verletzung in WT Mäusen sowohl die Frequenz der basalen inhibitorischen, postsynaptischen Potentiale (mIPSCs) reduziert war, als auch ein erhöhtes Paired-Pulse Verhältnis vorlag. Diese Ergebnisse deuten auf Veränderungen der präsynaptischen Funktion inhibitorischer Synapsen auf Pyramidalneurone hin. Im Gegensatz dazu konnte in BDNF (+/−) mice Mäusen eine erhöhte und gleichzeitig verlängerte mIPSC-Amplitude beobachtet werden, induziert durch Reizung afferenter Nervenfasern. Hieraus lässt sich schließen, dass kortikale Verletzungen in BDNF (+/−) mice Mäusen Auswirkungen auf die Eigenschaften von postsynaptischen GABAA-Rezeptoren haben. Die nachfolgende Gabe eines TrkB-Rezeptor Antagonisten bestätigte diese Ergebnisse für das GABAerge System post-Läsion. Dies zeigt auch, dass die Änderungen der synaptischen Hemmung nicht auf eine Reduktion der BDNF-Konzentration zurückzuführen sind. Zusammengefasst zeigen die Ergebnisse der vorliegenden Arbeit, dass der BDNF-TrkB Signalweg eine wichtige Rolle in der Reorganisation der GABAergen Hemmung nach kortikalen Verletzungen spielt. So könnte ein TrkB-Rezeptor Agonist, wie das kürzlich entdeckte 7,8-DHF, über eine Modulation der BDNF-TrB Signalkaskade pharmakologisch die funktionelle Reorganisation des Kortex nach einer fokalen Gehirnverletzung fördern. rnrn

The Estimation of the Ecological Condition of the City Environment by Methods of Phytoindication (as Applied to the Vasileostrovsky District of St. Petersburg)

The project aimed to use results of contamination of city vegetation with heavy metals and sulphur compounds as the basis for analysing the integral response of trees and shrubs to contamination, through a complex method of phytoindication. The results were used to draw up recommendations on pollution reduction in the city and to develop the method of phytoindication as a means of monitoring environmental pollution in St. Petersburg and other large cities. Field investigations were carried out in August 1996, and 66 descriptions of green areas were made in order to estimate the functional state of plants in the Vasileostrovsky district. Investigations of the spectrum reflecting properties of plants showed considerable variation of albedo meanings of leaves under the influence of various internal and external factors. The results indicated that lime trees most closely reflect the condition of the environment. Practically all the green areas studied were in poor condition, the only exceptions being areas of ash trees, which are more resistant to environmental pollution, and one lime-tree alley in a comparatively unpolluted street. The study identified those types of trees which are more or less resistant to complex environmental pollution and Ms. Terekhina recommends that the species in the present green areas be changed to include a higher number of the more resistant species. The turbidimetric analysis of tree barks for sulphates gave an indication of the level and spatial distribution of each pollutant, and the results also confirmed other findings that electric conductivity is a significant feature in determining the extent of sulphate pollution. In testing for various metals, the lime tree showed the highest contents for all elements except magnesium, copper, zinc, cadmium and strontium, again confirming the species' vulnerability to pollution. Medium rates of concentration in the city and environs showed that city plants concentrate 3 times as many different elements and 10 times more chromium, copper and lead than do those in the suburbs. The second stage of the study was based on the concept of phytoindication, which presupposes that changes in the relation of chemical elements in regional biological circulation under the influence of technogenesis provide a criterion for predicting displacements in people's health. There are certain basic factors in this concept. The first is that all living beings are related ecologically as well as by their evolutionary origin, and that the lower an organism is on the evolutionary scale, the less adaptational reserve it has. The second is that smaller concentrations of chemical elements are needed for toxicological influence on plants than on people and so the former's reactions to geochemical factors are easier to characterise. Visual indicational features of urban plants are well defined and can form the basis of a complex "environment - public health" analysis. Specific plant reactions reflecting atmospheric pollution and other components of urbogeosystems make it possible to determine indication criteria for predicting possible disturbances in the general state of health of the population. Thirdly the results of phytoindication investigations must be taken together with information about public health in the area. It only proved possibly to analyse general indexes of public health based on statistical data from the late 1980s and early 1990s as the data of later years were greatly influenced by social factors. These data show that the rates of illness in St. Petersburg (especially for children) are higher than in Russia as a whole, for most classes of diseases, indicating that the population there is more sensitive to the ecological state of the urban environment. The Vasileostrovsky district had the second highest sick rate for adullts, while the rate of infant mortality in the first year of life was highest there. Ms. Terekhina recommends further studies to more precisely assess the effectiveness of the methods she tested, but has drawn up a proposed map of environmental hazard for the population, taking into account prevailing wind directions.