I. Development of the In Situ Reductive Ozonolysis of Alkenes with Tertiary Amine N-Oxides. II. Progress toward the Asymmetric Synthesis of Peroxyplakoric Acid A3.

Ozone, first discovered in the mid 1800’s, is a triatomic allotrope of oxygen that is a powerful oxidant. For over a century, research has been conducted into the synthetic application and mechanism of reactions of ozone with organic compounds. One of the major areas of interest has been the ozonolysis of alkenes. The production of carbonyl compounds is the most common synthetic application of ozonolysis. The generally accepted mechanism developed by Rudolf Criegee for this reaction involves the 1,3-electrocyclic addition of ozone to the π bond of the alkene to form a 1,2,3-trioxolane or primary ozonide. The primary ozonide is unstable at temperatures above -100 °C and undergoes cycloreversion to produce the carbonyl oxide and carbonyl intermediates. These intermediates then recombine in another 1,3-electrocyclic addition step to form the 1,2,4-trioxolane or final ozonide. While the final ozonide is often isolable, most synthetic applications of ozonolysis require a subsequent reductive or oxidative step to form the desired carbonyl compound. During investigations into the nucleophilic trapping of the reactive carbonyl oxide, it was discovered that when amines were used as additives, an increased amount of reaction time was required in order to consume all of the starting material. Surprisingly, significant amounts of aldehydes and a suppression of ozonide formation also occurred which led to the discovery that amine N-oxides formed by the ozonation of the amine additives in the reaction were intercepting the carbonyl oxide. From the observed production of aldehydes, our proposed mechanism for the in situ reductive ozonolysis reaction with amine N-oxides involves the nucleophilic trapping of the carbonyl oxide intermediate to produce a zwitterionic adduct that fragments into 1O2, amine and the carbonyl thereby avoiding the formation of peroxidic intermediates. With the successful total syntheses of peroxyacarnoates A and D by Dr. Chunping Xu, the asymmetric total synthesis of peroxyplakorate A3 was investigated. The peroxyplakoric acids are cyclic peroxide natural products isolated from the Plakortis species of marine sponge that have been found to exhibit activity against malaria, cancer and fungi. Even though the peroxyplakorates differ from the peroxyacarnoates in the polyunsaturated tail and the head group, the lessons learned from the syntheses of the peroxyacarnoates have proven to be valuable in the asymmetric synthesis of peroxyplakorate A3. The challenges for the asymmetric synthesis of peroxyplakorate A3 include the stereospecific formation of the 3-methoxy-1,2-dioxane core with a propionate head group and the introduction of oxidation sensitive dienyl tail in the presence of a reduction sensitive 1,2-dioxane core. It was found that the stereochemistry of two of the chiral centers could be controlled by an anti-aldol reaction of a chiral propionate followed by the stereospecific intramolecular cyclization of a hydroperoxyacetal. The regioselective ozonolysis of a 1,2-disubstituted alkene in the presence of a terminal alkyne forms the required hydroperoxyacetal as a mixture of diastereomers. Finally, the dienyl tail is introduced by a hydrometallation/iodination of the alkyne to produce a vinyl iodide followed by a palladium catalyzed coupling reaction. While the coupling reaction was unsuccessful in these attempts, it is still believed that the intramolecular cyclization to introduce the 1,2-dioxane core could prove to be a general solution to many other cyclic peroxides natural products.

Description of <i>Paranoplocephala etholenii> n. sp. (Cestoda: Anoplocephalidae) in the Meadow Vole <i>Microtus pennsylvanicusi>, with a Synopsis of <i>Paranoplocehala s. l.i> in Holarctic Rodents

Paranoplocephala etholeni n. sp, parasitizing the meadow vole Microtus pennsylvanicus in Alaska and Wisconsin, USA. is described Paranaplocephala etholeni is morphologically most closely related to the Nearctic Paranoplocephala ondatrae (Rausch, 1948). Available data suggest that P. etholeni is a host-specific, locally rare species that may have a wide but sporadic geographical distribution in North America. The finding of P. ondatrae-like cestodes in Microtus spp. suggests that this poorly known species may actually be a parasite of voles rather than muskrat (type host). A tabular synopsis of all the known species of Paranoplocephala s. I. in the Holarctic region with their main morphological features is presented.

Examination of <i>Homalometron elongatumi> Manter, 1947 and Description of a New Congener from Eucinostomus currani Zahuranec, 1980 in the Pacific Ocean off Costa Rica

Homalometron elongatum is reexamined using heat-killed material that was not subjected to pressure during fixation from Gerres cinereus collected from San Juan Harbor, Puerto Rico, U.S.A. The new material is compared with some paratype specimens and differs by having a much less variable forebody length, and a median rather than submedian genital pore. Tegumental spines reportedly cover the anterior end of the body but we observed tegumental spines covering the entire body surface in both the paratype and new material. Homalometron lesliorum n. sp. is described from Eucinostomus currani from the Pacific coasts of Costa Rica and Nicaragua. The new species has three pairs of oral papillae surrounding the mouth and thus resembles three other congeners: H. elongatum, Homalometron carapevae, and Homalometron papilliferum. Homalometron lesliorum n. sp. is distinguished from the three species by having the anterior extent of the vitelline follicles at or above the base of the ventral sucker, compared with posterior to the ventral sucker at the level of the seminal vesicle (H. elongatum) or further posterior at the posterior margin of the ovary (H. carapevae and H. papilliferum). The four species are further differentiated from one another by sucker width ratio, tegumental spine size and distribution, egg size, host preference, and biogeography. Comparison of nuclear ribosomal DNA (3' end of 18S, internal transcribed spacer [ITS]1, ITS2, and 5' end of 28S) between H. elongatum and H. lesliorum n. sp. revealed one variable base (n = 162) at the 3' end of 18S, 12 variable bases (n = 476) at ITS1, 10 variable bases (n = 310) at ITS2, and 11 variable bases (n = 1,325) at the 5' end fragment of 28S. Nuclear ribosomal DNA from Homalometron pallidum and Homalometron armatum are included for further comparison with H. elongatum and H. lesliorum n. sp.

An Ardent Flame: Witness to Distant Suffering, Human Rights and Unworthy Victims in the Coverage by <i>The New York Timesi> and Two Journals of the Religious Left of the 1980s Civil Wars in El Salvador and Nicaragua

Scholars have investigated witness to distant suffering (WTDS) almost entirely in visual media. This study examines it in print. This form of reporting will be examined in two publications of the religious left as contrasted with the New York Times. The thesis is that, more than any technology, WTDS consists of the journalist’s moral commitment and narrative skills and the audience’s analytical resources and trust. In the religious journals, liberation theology provides the moral commitment, the writers and editors the narrative skills and trust and the special vision of the newly empowered poor the analytical foundation. In bearing witness to those who have suffered state or guerilla terrorism in El Salvador and Nicaragua during the 1980s, we will investigate a distinction between “worthy” and “unworthy victims.” This last issue has a special ethical and political significance. Media witnessing to the suffering of strangers can help them become known, and so “worthy.” It can help them, and their plight and cause, become better recognized. This is the power of the media.

The Specific Status of the Narrow-Skulled Vole (Subgenus <i>Stenocraniusi> Kashchenko) in North America

On morphological and zoogeographical grounds, discussed in the present paper, it is concluded that the narrow-skulled vole in North America, previously designated Microtus (Stenocranius) miurus Osgood, is conspecific with the Eurasian M. (Stenocranius) gregalis Pallas. Fourteen subspecies in Eurasia and 5 in North America are now recognized, but it is probable that the number in Eurasia will be reduced through future investigation. The Eurasian subspecies of this vole comprise two major groups, of which one occupies the tundra zone and the other occurs across central Asia below latitude 60° N; their geographic ranges are largely separate but evidently become confluent in northeastern Siberia. The members of the northern group of Eurasian subspecies and the North American forms are closely related; the present distribution of the latter indicates post-glacial dispersal from the Amphiberingian Refugium. It is believed that the tundra-inhabiting voles in Eurasia likewise survived the Pleistocene glaciations in northern refugia, while the members of the southern group of subspecies probably represent populations that survived south of the limits of the continental glaciers. The ranges of the two Eurasian groups probably have become confluent during post-glacial time in northeastern Siberia as a result of the southward spread of the northern forms. At least, the subspecies having the intervening range closely resembles members of the northern group. Some of the ecological and ethological characteristics of these voles are briefly discussed. The chromosome number of one of the North American subspecies of narrow-skulled vole was determined to be 54; this is the first time that the chromosomes of a member of the subgenus Stenocranius have been investigated. A karyogram has been included. German abstract: Auf morphologischen und tiergeographischen Grundlagen, die in dieser Arbeit besprochen wurden, ist festgestellt worden, daß die schmalschädlige Wiihlmaus in Nordamerika, friiher Microtus (Stenocranius) miurus Osgood bezeichnet, mit der palaearktischen Art M. (Stenocranius) gregalis Pallas identisch ist. Zur Zeit gelten 14 Unterarten in Eurasien und 5 in Nordamerika als unterscheidbar; vermutlich aber wird die Zahl der palaearktischen Unterarten durch eingehendere Untersuchungen künftig vermindert werden. Auf Grund ihrer Verbreitung bilden die palaearktischen Unterarten zwei beinahe vollständig getrennte Gruppen. Die Wühlmäuse der nördlichen Gruppe bewohnen die Tundrazone, während die Vertreter der zweiten Gruppe über Mittelasien südlicher als 60° N.B. verbreitet sind. Die Verbreitungsgebiete der zwei Gruppen verbinden sich anscheinend. Die nordamerikanischen schmalschädligen Wühlmäuse sind mit den in der Tundrazone vorkommenden palaearktischen Formen nahe verwandt; sie haben sich wahrscheinlich während der Postglazialzeit aus dem Amphiberingschen Refugium verbreitet. Möglicherweise überlebten die tundrabewohnenden Wühlmäuse Eurasiens die Eiszeit ebenfalls in vereinzelten Refugien in Nordostsibirien, während die Formen der südlichen Gruppe sie jenseits der Grenzen des Festlandsgletschers überlebten. Wahrscheinlich wurden die zwei Verbreitungsgebiete dieser Art in Eurasien erst während der Postglazialzeit durch das Vordringen der nordischen Formen verbunden, da eine nähere Verwandtschaft zwischen den nördlichen und der dazwischenliegenden Unterart besteht. Einige ökologische und ethologische Eigentümlichkeiten dieser Wühlmäuse werden kurz besprochen. Es wurde festgestellt, daß eine der nordamerikanischen Unterarten der schmalschädligen Wühlmaus 54 Chromosomen hat; sie ist der einzige Vertreter der Untergattung Stenocranius, dessen Chromosomen untersucht worden sind.

Detection of DENV-4 genotype I from mosquitoes collected in the city of Manaus, Brazil

Background Dengue epidemics have been reported in Brazil since 1981. In Manaus, a large city in the Amazon region, dengue is endemic with all four-virus serotypes (DENV-1, -2, -3, and -4) simultaneously causing human disease. In 2008, during a surveillance of dengue virus in mosquitoes in the district of Tancredo Neves in Manaus, 260 mosquitoes of Aedes genus were captured, identified and grouped into pools of 10 mosquitoes. Findings RNA extracts of mosquito pools were tested by a RT-Hemi-Nested-PCR for detection of flaviviruses. One amplicon of 222 bp, compatible with dengue virus serotype 4, was obtained from a pool of Aedes aegypti. The nucleotide sequence of the amplicon indicated that the mosquitoes were infected with DENV-4 of genotype I. This virus of Asian origin has been described in Manaus in 2008 infecting acute febrile illness patients. Conclusion This is the first report of dengue virus serotype 4 genotype I infecting Aedes aegypti in the Americas.

Identification of SL addition trans-splicing acceptor sites in the internal transcribed spacer I region of pre-rRNA in Leishmania (Leishmania) amazonensis

Trypanosomatidae is a family of early branching eukaryotes harbouring a distinctive repertoire of gene expression strategies. Functional mature messenger RNA is generated via the trans-splicing and polyadenylation processing of constitutively transcribed polycistronic units. Recently, trans-splicing of pre-small subunit ribosomal RNA in the 5' external transcribed spacer region and of precursor tRNAsec have been described. Here, we used a previously validated semi-nested reverse transcription-polymerase chain reaction strategy to investigate internal transcribed spacer (ITS) I acceptor sites in total RNA from Leishmania (Leishmania) amazonensis. Two distinct spliced leader-containing RNAs were detected indicating that trans-splicing reactions occur at two AG acceptor sites mapped in this ITS region. These data provide further evidence of the wide spectrum of RNA molecules that act as trans-splicing acceptors in trypanosomatids.

Molecular epidemiology of animal rabies in the semiarid region of Paraíba, Northeastern Brazil

In the semiarid of the state of Paraíba, the anti-rabies vaccination is not common, most of the local inhabitants who deal with the animals do not know the incidence of the disease in the region. In this study, samples of foxes (Pseudalopex vetulus), insectivorous bats (Molossus molossus), raccoons (Procyon cancrivorous) and domestic animals brains were submitted to the diagnosis of rabies, by using the direct fluorescent antibody technique (d-FAT) and mouse inoculation test (MIT). Of the 581 examined materials, 50 (8.60 %) were positive for d-FAT and 47 (8.09 %) for MIT. From the positive samples for rabies, RNAs were extracted and transformed to cDNA, at the Laboratory of Rabies/Faculdade de Medicina Veterinária e Zootecnia/USP, SP. The phylogenetic characterization of the N gene was performed at the Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia, Departamento de Medicina Veterinária Preventiva e Saúde Animal, Universidade Nihon, Faculdade de Ciências Bioresource, Fujisawa, Kanagawa, Japão. Based on the results of genotyping and phylogenetic analyzes, it is concluded that the epidemiology of rabies is complex in the semiarid of Paraíba, with different viral variants being maintained in domestic dogs, foxes, insectivorous bats and vampire bats. All the isolates examined belong to the genotype I of the genus Lyssavirus and it is possible to state that in the region, foxes are important sylvatic reservoirs of the rabies virus.

Dynamics of cell and tissue genesis in the male reproductive system of ticks (Acari: Ixodidae) Amblyomma cajennense (Fabricius, 1787) and Amblyomma aureolatum (Pallas, 1772): a comparative analysis

Ticks are classified into three families: Argasidae, Ixodidae, and Nutalliellidae. The taxonomy and phylogeny within Ixodidae are still discussed by the specialists, thus requiring further studies. Amblyomma cajennese and Amblyomma aureolatum (Brazil) belong to two species complexes known as “cajennese” and “ovale”, respectively, and are directly related to the transmission of the Brazilian spotted fever. This confirms the medical and veterinary significance of these species, as well as the need for further morphological studies that will bring a better understanding of their taxonomy, phylogeny, and control. In this context, the present study aimed to characterize the morphology of the male reproductive system of A. cajennese and A. aureolatum when unfed and after 4 days of feeding, thereby seeking to: (a) distinguish the two species or “complexes”, and (b) study an internal system which has the potential to be targeted by acaricides. Therefore, males from both species (unfed and after 4 days of feeding) were cold-anesthetized, dissected, and had their reproductive systems removed for histological analysis. The results showed that the morphology of the male reproductive system is generally similar between both species, like in other Ixodidae ticks, exhibiting a multilobed accessory gland complex related to seminal fluid secretion, a pair of vasa deferentia and a pair of testes housing germ cells (spermatocytes) in different stages. The main differences were found in the development of the accessory gland complex cells and germ cells, showing that the maturation of the male reproductive system starts later in A. aureolatum, when compared to A. cajennese. However, during the blood meal, A. aureolatum development is increased, thus making germ cell maturation and gland complex activity higher than in A. cajennese. This study shows the differences in the development of the male reproductive systems of both species, while providing information that can assist in the establishment of new control methods.

Genetic characterization and molecular identification of the bloodmeal sources of the potential bluetongue vector Culicoides obsoletus in the Canary Islands, Spain

[EN] Background: Culicoides (Diptera: Ceratopogonidae) biting midges are vectors for a diversity of pathogens including bluetongue virus (BTV) that generate important economic losses. BTV has expanded its range in recent decades, probably due to the expansion of its main vector and the presence of other autochthonous competent vectors. Although the Canary Islands are still free of bluetongue disease (BTD), Spain and Europe have had to face up to a spread of bluetongue with disastrous consequences. Therefore, it is essential to identify the distribution of biting midges and understand their feeding patterns in areas susceptible to BTD. To that end, we captured biting midges on two farms in the Canary Islands (i) to identify the midge species in question and characterize their COI barcoding region and (ii) to ascertain the source of their bloodmeals using molecular tools.Methods: Biting midges were captured using CDC traps baited with a 4-W blacklight (UV) bulb on Gran Canaria and on Tenerife. Biting midges were quantified and identified according to their wing patterns. A 688 bp segment of the mitochondrial COI gene of 20 biting midges (11 from Gran Canaria and 9 from Tenerife) were PCR amplified using the primers LCO1490 and HCO2198. Moreover, after selected all available females showing any rest of blood in their abdomen, a nested-PCR approach was used to amplify a fragment of the COI gene from vertebrate DNA contained in bloodmeals. The origin of bloodmeals was identified by comparison with the nucleotide-nucleotide basic alignment search tool (BLAST). Results: The morphological identification of 491 female biting midges revealed the presence of a single morphospecies belonging to the Obsoletus group. When sequencing the barcoding region of the 20 females used to check genetic variability, we identified two haplotypes differing in a single base. Comparison analysis using the nucleotide-nucleotide basic alignment search tool (BLAST) showed that both haplotypes belong to Culicoides obsoletus, a potential BTV vector. As well, using molecular tools we identified the feeding sources of 136 biting midges and were able to confirm that C. obsoletus females feed on goats and sheep on both islands.Conclusions: These results confirm that the feeding pattern of C. obsoletus is a potentially important factor in BTV transmission to susceptible hosts in case of introduction into the archipelago. Consequently, in the Canary Islands it is essential to maintain vigilance of Culicoides-transmitted viruses such as BTV and the novel Schmallenberg virus.

Isotope geochemical and geochronologic studies of basement units in the Central Western Carpathians (Slovakia)

In dieser Arbeit werden geochronologische und isotopen-geochemische Daten zur Entwicklung der Zentralen Westlichen Karpathen präsentiert. Die Karpathen bilden die östliche Fortsetzung der Alpen und können in drei Alpine Grundgebirgsdecken unterteilt werden, von denen zwei, die Veporische und die Gemerische, bearbeitet wurden. In der Veporischen Einheit wurden polymetamorphe Grundgebirgseinheiten untersucht, um deren genaue Altersstellung zu definieren und sie isotopengeochemisch zu klassifizieren. Dagegen wurde in der der Gemerischen Einheit, welche die Veporische Einheit überlagert, ein spezialisierter S-Typ Granit im Detail untersucht, um die petrogenetischen Prozesse, die zur magmatischen Entwicklung dieses Granits geführt haben, zu identifizieren. U-Pb Datierungen an Zirkonen der Veporischen Grundgebirgseinheiten zeigen für die gesamte Veporische Einheit ordovizische Entsehungsalter an (440-470 Ma). Diese Datierungen revidieren publizierte kambrische Entstehungsalter dieses Grundgebirges. Die Isotopensignatur (epsilon Nd und 87Sr/86Sr) der ordovizischen Grundgebirgseinheiten, bestehend aus stark überprägten Amphiboliten und Gneissen, ist von der Signatur der sich im Norden anschliessenden Tatrischen Einheit gut unterscheidbar. Die Bleiisotopenzusammensetzung dieser Gesteine ist stark krustal geprägt und überschneidet sich mit der der Tatrischen Einheit. Zusammen mit den T-DM Altern sind diese Einheiten vergleichbar mit prävariskischen Einheiten der Alpen. Somit kann das ordovizische Grundgebirge zu den peri-Gondwana Terranen gezählt werden, die an einem aktiven Kontinentalrand im Norden von Gondwana gebildet wurden. In den Gesteinen der Veporischen Einheit wurde im Weiteren eine starke metamorphe überprägung und intensiver felsischer Magmatismus karbonischen Alters erkannt (320-350 Ma). Dieses Ereignis ist zeitgleich mit dem Magmatismus, welcher hauptsächlich in der sich im Norden anschliessenden Tatrischen Einheit beobachtet wird. Dieser gehört der variskischen Orogenese an. Intensive alpine Deformation und Metamorphose konnte in der südlichen Veporischen Einheit anhand der Einzelzirkondatierungen und der Isotopendaten der ordovizischen Einheiten nachgewiesen werden. Am Dlha Dolina Granit in der Gemerischen Einheit können starke Fraktionierungs- und Auto-Metasomatose-Effekte beobachtet werden. Durch die magmatische Fraktionierung wird eine Anreicherung der SEE erzeugt, wogegen die Metasomatose die SEE stark verarmt. Es kommt sogar zur Ausbildung eines Tetraden Effektes im SEE Muster, welche den starken Einfluss von Fluiden während der spät-magmatischen Phase belegt. Gesamtgesteins Pb-Pb Daten beschränken das minimale Intrusionsalter dieses Granites auf 240 Ma. Dieses Alter ist in guter übereinstimmung mit den Sr-Isotopendaten der magmatisch dominierten Gesteine, wohingegen die stark metasomatisch geprägten Gesteine ein zu radiogenes 87Sr/86Sri aufweisen. Während dieser Arbeit wurde intensiv mit der Blei-Isotopenzusammensetzung von Gesamtgesteinsproben gearbeitet. Um die Auswertung dieser Daten optimieren zu können wurde ein Computerscript für das GPL Programm Octave erstellt. Die Hauptaufgabe dieses Scripts besteht darin, Regressionen für geochronologische Anwendungen gemäss York (1969) zu berechnen. Ausserdem können mu und kappa-Werte für diese Regressionen berechnet und eine Hauptkomponentenanalyse, welche hilfreich für den Vergleich von zwei Datensätzen ist, durchgeführt werden. Am Ende der vorliegenden Arbeit wird die analytische Methode für einen Mikrowellen beschleunigten Säureaufschluss von granitoidem Material zur Bestimmung der Sr- und Nd-Isotopenzusammensetzung und der Elementkonzentrationen vorgestellt. Diese kombinierte Methode nutzt ein TIMS für die Sr und Nd Isotopenmessungen und eine Einzelkollektor-ICPMS zur Bestimmung der SEE, Rb und Sr Konzentrationen, welche mithilfe von relativen Sensitivitätsfaktoren gegenüber einem internen Standard quantifiziert werden. Diese Methode wird durch Messungen von internationalen Referenzmaterialien bewertet. Die Ergebnisse zeigen eine Reproduzierbarkeit von <10% für die Elementkonzentrationen und von <5% für Elementverhältnisse.

The stratigraphic record of the quaternary sea level fluctuations and the impact of the post-glacial sea level rise (Termination I) in the Adriatic basin (Mediterranean sea)

The modern stratigraphy of clastic continental margins is the result of the interaction between several geological processes acting on different time scales, among which sea level oscillations, sediment supply fluctuations and local tectonics are the main mechanisms. During the past three years my PhD was focused on understanding the impact of each of these process in the deposition of the central and northern Adriatic sedimentary successions, with the aim of reconstructing and quantifying the Late Quaternary eustatic fluctuations. In the last few decades, several Authors tried to quantify past eustatic fluctuations through the analysis of direct sea level indicators, among which drowned barrier-island deposits or coral reefs, or indirect methods, such as Oxygen isotope ratios (δ18O) or modeling simulations. Sea level curves, obtained from direct sea level indicators, record a composite signal, formed by the contribution of the global eustatic change and regional factors, as tectonic processes or glacial-isostatic rebound effects: the eustatic signal has to be obtained by removing the contribution of these other mechanisms. To obtain the most realistic sea level reconstructions it is important to quantify the tectonic regime of the central Adriatic margin. This result has been achieved integrating a numerical approach with the analysis of high-resolution seismic profiles. In detail, the subsidence trend obtained from the geohistory analysis and the backstripping of the borehole PRAD1.2 (the borehole PRAD1.2 is a 71 m continuous borehole drilled in -185 m of water depth, south of the Mid Adriatic Deep - MAD - during the European Project PROMESS 1, Profile Across Mediterranean Sedimentary Systems, Part 1), has been confirmed by the analysis of lowstand paleoshorelines and by benthic foraminifera associations investigated through the borehole. This work showed an evolution from inner-shelf environment, during Marine Isotopic Stage (MIS) 10, to upper-slope conditions, during MIS 2. Once the tectonic regime of the central Adriatic margin has been constrained, it is possible to investigate the impact of sea level and sediment supply fluctuations on the deposition of the Late Pleistocene-Holocene transgressive deposits. The Adriatic transgressive record (TST - Transgressive Systems Tract) is formed by three correlative sedimentary bodies, deposited in less then 14 kyr since the Last Glacial Maximum (LGM); in particular: along the central Adriatic shelf and in the adjacent slope basin the TST is formed by marine units, while along the northern Adriatic shelf the TST is represented by costal deposits in a backstepping configuration. The central Adriatic margin, characterized by a thick transgressive sedimentary succession, is the ideal site to investigate the impact of late Pleistocene climatic and eustatic fluctuations, among which Meltwater Pulses 1A and 1B and the Younger Dryas cold event. The central Adriatic TST is formed by a tripartite deposit bounded by two regional unconformities. In particular, the middle TST unit includes two prograding wedges, deposited in the interval between the two Meltwater Pulse events, as highlighted by several 14C age estimates, and likely recorded the Younger Dryas cold interval. Modeling simulations, obtained with the two coupled models HydroTrend 3.0 and 2D-Sedflux 1.0C (developed by the Community Surface Dynamics Modeling System - CSDMS), integrated by the analysis of high resolution seismic profiles and core samples, indicate that: 1 - the prograding middle TST unit, deposited during the Younger Dryas, was formed as a consequence of an increase in sediment flux, likely connected to a decline in vegetation cover in the catchment area due to the establishment of sub glacial arid conditions; 2 - the two-stage prograding geometry was the consequence of a sea level still-stand (or possibly a fall) during the Younger Dryas event. The northern Adriatic margin, characterized by a broad and gentle shelf (350 km wide with a low angle plunge of 0.02° to the SE), is the ideal site to quantify the timing of each steps of the post LGM sea level rise. The modern shelf is characterized by sandy deposits of barrier-island systems in a backstepping configuration, showing younger ages at progressively shallower depths, which recorded the step-wise nature of the last sea level rise. The age-depth model, obtained by dated samples of basal peat layers, is in good agreement with previous published sea level curves, and highlights the post-glacial eustatic trend. The interval corresponding to the Younger Dyas cold reversal, instead, is more complex: two coeval coastal deposits characterize the northern Adriatic shelf at very different water depths. Several explanations and different models can be attempted to explain this conundrum, but the problem remains still unsolved.

Geochemistry, petrogenesis and tectonic setting of ophiolites and mafic-ultramafic complexes in the Northeastern Aegean Region

In this study two ophiolites and a mafic-ultramafic complexes of the northeastern Aegean Sea, Greece, have been investigated to re-evaluate their petrogenetic evolution and tectonic setting. These complexes are: the mafic-ultramafic complex of Lesvos Island and the ophiolites of Samothraki Island and the Evros area. In order to examine these complexes in detail whole-rock major- and trace-elements as well as Sr and Nd isotopes, and minerals were analysed and U-Pb SHRIMP ages on zircons were determined. The mafic-ultramafic complex of Lesvos Island consists of mantle peridotite thrusted over a tectonic mélange containing metasediments, metabasalts and a few metagabbros. This succession had previously been interpreted as an ophiolite of Late Jurassic age. The new field and geochemical data allow a reinterpretation of this complex as representing an incipient continental rift setting that led to the subsequent formation of the Meliata-Maliac-Vardar branches of Neotethys in Upper Permian times (253 ± 6 Ma) and the term “Lesvos ophiolite” should be abandoned. With proceeding subduction and closure of the Maliac Ocean in Late Jurassic times (155 Ma) the Lesvos mafic-ultramafic complex was obducted. Zircon ages of 777, 539 and 338 Ma from a gabbro strongly suggest inheritance from the intruded basement and correspond to ages of distinct terranes recently recognized in the Hellenides (e.g. Florina terrane). Geochemical similar complexes which contain rift associations with Permo-Triassic ages can be found elsewhere in Greece and Turkey, namely the Teke Dere Thrust Sheet below the Lycian Nappes (SW Turkey), the Pindos subophiolitic mélange (W Greece), the Volcanosedimentary Complex on Central Evia Island (Greece) and the Karakaya Complex (NW Turkey). This infers that the rift-related rocks from Lesvos belong to an important Permo-Triassic rifting episode in the eastern Mediterranean. The ‘in-situ’ ophiolite of Samothraki Island comprises gabbros, sparse dykes and basalt flows as well as pillows cut by late dolerite dykes and had conventionally been interpreted as having formed in an ensialic back-arc basin. The results of this study revealed that none of the basalts and dolerites resemble mid-ocean ridge or back-arc basin basalts thus suggesting that the Samothraki ophiolite cannot represent mature back-arc basin crust. The age of the complex is regarded to be 160 ± 5 Ma (i.e. Oxfordian; early Upper Jurassic), which precludes any correlation with the Lesvos mafic-ultramafic complex further south (253 ± 6 Ma; Upper Permian). Restoration of the block configuration in NE Greece, before extensional collapse of the Hellenic hinterland and exhumation of the Rhodope Metamorphic Core Complex (mid-Eocene to mid-Miocene), results in a continuous ophiolite belt from Guevgueli in the NW to Samothraki in the SE, thus assigning the latter to the Innermost Hellenic Ophiolite Belt. In view of the data of this study, the Samothraki ophiolite represents a rift propagation of the Sithonia ophiolite spreading ridge into the Chortiatis calc-alkaline arc. The ophiolite of the Evros area consists of a plutonic sequence comprising cumulate and non-cumulate gabbros with plagiogranite veins, and an extrusive sequence of basalt dykes, massive and pillow lavas as well as pyroclastic rocks. Furthermore, in the Rhodope Massif tectonic lenses of harzburgites and dunites can be found. All rocks are spatially separated. The analytical results of this study revealed an intra-oceanic island arc setting for the Evros ophiolitic rocks. During late Middle Jurassic times (169 ± 2 Ma) an intra-oceanic arc has developed above a northwards directed intra-oceanic subduction zone of the Vardar Ocean in front of the Rhodope Massif. The boninitic, island arc tholeiitic and calc-alkaline rocks reflect the evolution of the Evros island arc. The obduction of the ophiolitic rocks onto the Rhodope basement margin took place during closure of the Vardar ocean basins. The harzburgites and dunites of the Rhodope Massif are strongly depleted and resemble harzburgites from recent oceanic island arcs. After melt extraction they underwent enrichment processes by percolating melts and fluids from the subducted slab. The relationship of the peridotites and the Evros ophiolite is still ambiguous, but the stratigraphic positions of the peridotites and the ophiolitic rocks indicate separated origin. The harzburgites and dunites most probably represent remnants of the mantle wedge of the island arc of the Rhodope terrane formed above subducted slab of the Nestos Ocean in late Middle Jurassic times. During collision of the Thracia terrane with the Rhodope terrane thrusting of the Rhodope terrane onto the Thracia terrane took place, whereas the harzburgites and dunites were pushed between the two terranes now cropping out on top of the Thracia terrane of the Rhodope Massif.

Studying MHC I-dependent CD8 + T cell responses in the model of murine cutaneous leishmaniasis

Der Ausheilung von Infektionen mit Leishmania major liegt die Sekretion von IFN- von sowohl CD4+ als auch CD8+ T Zellen zugrunde.rnAktuell konnte in der Literatur nur ein Epitop aus dem parasitären LACK Protein für eine effektive CD4+ T Zell-vermittelte Immunantwort beschrieben werden. Das Ziel der vorliegenden Arbeit bestand daher darin, mögliche MHC I abhängige CD8+ T Zell Antworten zu untersuchen. rnFür diesen Ansatz wurde als erstes der Effekt einer Vakzinierung mit LACK Protein fusioniert an die Protein-Transduktionsdomäne des HIV-1 (TAT) analysiert. Die Effektivität von TAT-LACK gegenüber CD8+ T Zellen wurde mittels in vivo Protein-Vakzinierung von resistenten C57BL/6 Mäusen in Depletions-Experimenten gezeigt.rnDie Prozessierung von Proteinen vor der Präsentation immunogener Peptide gegenüber T Zellen ist unbedingt erforderlich. Daher wurde in dieser Arbeit die Rolle des IFN--induzierbaren Immunoproteasoms bei der Prozessierung von parasitären Proteinen und Präsentation von Peptiden gebunden an MHC I Moleküle durch in vivo und in vitro Experimente untersucht. Es konnte in dieser Arbeit eine Immunoproteasom-unabhängige Prozessierung aufgezeigt werden.rnWeiterhin wurde Parasitenlysat (SLA) von sowohl Promastigoten als auch Amastigoten fraktioniert. In weiterführenden Experimenten können diese Fraktionen auf immunodominante Proteine/Peptide hin untersucht werden. rnLetztlich wurden Epitop-Vorhersagen für CD8+ T Zellen mittels computergestützer Software von beiden parasitären Lebensformen durchgeführt. 300 dieser Epitope wurden synthetisiert und werden in weiterführenden Experimenten zur Charakterisierung immunogener Eigenschaften weiter verwendet. rnIn ihrer Gesamtheit trägt die vorliegende Arbeit wesentlich zum Verständnis über die komplexen Mechanismen der Prozessierung und letztendlich zur Identifikation von möglichen CD8+ T Zell Epitopen bei. Ein detailiertes Verständnis der Prozessierung von CD8+ T Zell Epitopen von Leishmania major über den MHC Klasse I Weg ist von höchster Bedeutung. Die Charakterisierung sowie die Identifikation dieser Peptide wird einen maßgeblichen Einfluss auf die weiteren Entwicklungen von Vakzinen gegen diesen bedeutenden human-pathogenen Parasiten mit sich bringen. rn