Striatal pre- and postsynaptic profile of adenosine A2A receptor antagonists

Striatal adenosine A2A receptors (A2ARs) are highly expressed in medium spiny neurons (MSNs) of the indirect efferent pathway, where they heteromerize with dopamine D2 receptors (D2Rs). A2ARs are also localized presynaptically in cortico-striatal glutamatergic terminals contacting MSNs of the direct efferent pathway, where they heteromerize with adenosine A1 receptors (A1Rs). It has been hypothesized that postsynaptic A2AR antagonists should be useful in Parkinson's disease, while presynaptic A2AR antagonists could be beneficial in dyskinetic disorders, such as Huntington's disease, obsessive-compulsive disorders and drug addiction. The aim or this work was to determine whether selective A2AR antagonists may be subdivided according to a preferential pre- versus postsynaptic mechanism of action. The potency at blocking the motor output and striatal glutamate release induced by cortical electrical stimulation and the potency at inducing locomotor activation were used as in vivo measures of pre- and postsynaptic activities, respectively. SCH-442416 and KW-6002 showed a significant preferential pre- and postsynaptic profile, respectively, while the other tested compounds (MSX-2, SCH-420814, ZM-241385 and SCH-58261) showed no clear preference. Radioligand-binding experiments were performed in cells expressing A2AR-D2R and A1R-A2AR heteromers to determine possible differences in the affinity of these compounds for different A2AR heteromers. Heteromerization played a key role in the presynaptic profile of SCH-442416, since it bound with much less affinity to A2AR when co-expressed with D2R than with A1R. KW-6002 showed the best relative affinity for A2AR co-expressed with D2R than co-expressed with A1R, which can at least partially explain the postsynaptic profile of this compound. Also, the in vitro pharmacological profile of MSX-2, SCH-420814, ZM-241385 and SCH-58261 was is in accordance with their mixed pre- and postsynaptic profile. On the basis of their preferential pre- versus postsynaptic actions, SCH-442416 and KW-6002 may be used as lead compounds to obtain more effective antidyskinetic and antiparkinsonian compounds, respectively.

Is response to fire influenced by dietary specialization and mobility? A comparative study with multiple animal assemblages

Fire is a major agent involved in landscape transformation and an indirect cause of changes in species composition. Responses to fire may vary greatly depending on life histories and functional traits of species. We have examined the taxonomic and functional responses to fire of eight taxonomic animal groups displaying a gradient of dietary and mobility patterns: Gastropoda, Heteroptera, Formicidae, Coleoptera, Araneae, Orthoptera, Reptilia and Aves. The fieldwork was conducted in a Mediterranean protected area on 3 sites (one unburnt and two burnt with different postfire management practices) with five replicates per site. We collected information from 4606 specimens from 274 animal species. Similarity in species composition and abundance between areas was measured by the Bray-Curtis index and ANOSIM, and comparisons between animal and plant responses by Mantel tests. We analyze whether groups with the highest percentage of omnivorous species, these species being more generalist in their dietary habits, show weak responses to fire (i.e. more similarity between burnt and unburnt areas), and independent responses to changes in vegetation. We also explore how mobility, i.e. dispersal ability, influences responses to fire. Our results demonstrate that differences in species composition and abundance between burnt and unburnt areas differed among groups. We found a tendency towards presenting lower differences between areas for groups with higher percentages of omnivorous species. Moreover, taxa with a higher percentage of omnivorous species had significantly more independent responses of changes in vegetation. High- (e.g. Aves) and low-mobility (e.g. Gastropoda) groups had the strongest responses to fire (higher R scores of the ANOSIM); however, we failed to find a significant general pattern with all the groups according to their mobility. Our results partially support the idea that functional traits underlie the response of organisms to environmental changes caused by fire.

La selecció del fons documental a la biblioteca escolar: com, qui i per què triar els llibres per a infants

L’infant ha de tenir l’oportunitat d’estar envoltat per una col·lecció de llibres que el permeti escollir les lectures que necessita a cada moment. L’escola, concretament la biblioteca escolar, ha de possibilitar aquesta trobada mitjançant un fons documental seleccionat a partir de les necessitats i els interessos d’infants i mestres. El present treball pretén recollir algunes recomanacions bàsiques per a la selecció de documents a la biblioteca escolar en un marc teòric inicial. En la segona part del projecte, s’intenta analitzar com es porta a la pràctica aquest procés en el nostre territori a partir de l’anàlisi de tres realitats concretes: la biblioteca escolar, la biblioteca pública i el Seminari de Bibliografia Infantil i Juvenil de l’Associació de Mestres Rosa Sensat.

Geographic patterns of genetic variation in a broadly distributed marine vertebrate: new insights into loggerhead turtle stock structure from expanded mitochondrial DNA sequences

Previous genetic studies have demonstrated that natal homing shapes the stock structure of marine turtle nesting populations. However, widespread sharing of common haplotypes based on short segments of the mitochondrial control region often limits resolution of the demographic connectivity of populations. Recent studies employing longer control region sequences to resolve haplotype sharing have focused on regional assessments of genetic structure and phylogeography. Here we synthesize available control region sequences for loggerhead turtles from the Mediterranean Sea, Atlantic, and western Indian Ocean basins. These data represent six of the nine globally significant regional management units (RMUs) for the species and include novel sequence data from Brazil, Cape Verde, South Africa and Oman. Genetic tests of differentiation among 42 rookeries represented by short sequences (380 bp haplotypes from 3,486 samples) and 40 rookeries represented by long sequences (~800 bp haplotypes from 3,434 samples) supported the distinction of the six RMUs analyzed as well as recognition of at least 18 demographically independent management units (MUs) with respect to female natal homing. A total of 59 haplotypes were resolved. These haplotypes belonged to two highly divergent global lineages, with haplogroup I represented primarily by CC-A1, CC-A4, and CC-A11 variants and haplogroup II represented by CC-A2 and derived variants. Geographic distribution patterns of haplogroup II haplotypes and the nested position of CC-A11.6 from Oman among the Atlantic haplotypes invoke recent colonization of the Indian Ocean from the Atlantic for both global lineages. The haplotypes we confirmed for western Indian Ocean RMUs allow reinterpretation of previous mixed stock analysis and further suggest that contemporary migratory connectivity between the Indian and Atlantic Oceans occurs on a broader scale than previously hypothesized. This study represents a valuable model for conducting comprehensive international cooperative data management and research in marine ecology.

Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS: Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS: In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS: Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS: Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Legend I

Soitinnus: orkesteri.

Melody I, Op. 17 N:o 1

Ei vapaa, vapautuu 2027. Kosti Vehanen (1887-1957).

Formaterade nyheter : studier i hur tv-nyheter formatmässigt editeras, gestaltas och tas emot

Under de trettio senaste åren har tv-nyhetsjournalistiken som genre, d.v.s. som en egen särpräglad läsart och form av journalistik, på olika sätt förändrats. Hur denna formatförändring ser ut och om tv-nyheter i takt med samhällets och massmediernas allmänna kommersialisering har blivit mer tabloida är två centrala frågeställningar i avhandlingen. Nyhetsprogrammet TV-nytt i public service-företaget Yle:s svenskspråkiga kanal FST5, har långt en monopolställning. På svenska har TV-nytt inga konkurrenter i tv-etern i Finland och som ett sorts flaggskepp för hela FST5, har nyhetsredaktionen länge haft en stark ställning och uppbackning på svenska Yle. Så om t.o.m. TV-nytts nyhetsformat har förändrats och t.ex. blivit mer tabloida, torde åtminstone public service-nyheter i tv överlag ha förändrats minst lika mycket. Detta granskas empiriskt i avhandlingen. Utan att i frågeställningarna även ta med hur mottagarna, det vill säga hur tv-tittarna reagerar på tv-nyheter, är det svårt att mer ingående och trovärdigt förklara tv-nyheters roll i samhället. Därför är det viktigt att även fråga hur tittarnas intresse och uppmärksamhet påverkas av olika sorts tv-nyheter och hur deras ihågkomst samt nyhetsförståelse påverkas av olika slags tv-nyhetsformat såsom ett mer tabloidiserat dylikt? Avhandling har följaktligen fyra syften: att undersöka vad tv-nyhetsformatet för public service-tv består av, hur detta format ur olika synvinklar har förändrats, om det har tabloidiserats och hur tittarna reagerar på olika tv-nyhetsformat. Avhandlingen består av tre innehållsanalyser och ett laboratorietest. Resultaten visar i korthet att tv-nyhetsformatet både på inslags- och sändningsnivå kan sägas ha två olika formatdimensioner; det audiovisuellt editerade och det journalistiskt innehållsgestaltande formatet. Det senare formatet har för TV-nytts del sedan 1980-talet förändrats mycket mindre än det förra och i synnerhet det audiovisuellt editerade formatet har tydligt utvecklats i en tabloid riktning. Resultaten från de laborativa publiktesterna visar igen att tittarnas uppmärksamhet och intresse i första hand har med audiovisuell editering och allmän visualitet att göra. Mer tabloida nyhetsinslag får därför generellt mer uppmärksamhet än övriga inslag. I synnerhet bildtempo, bildsättning och inslagslängd är här utslagsgivande. Det att tabloidisering ger förbättrad uppmärksamhet betyder ändå inte att tittarna mycket bättre kommer ihåg eller bättre förstår tabloida nyhetsinslag än icke-tabloida. Testerna visar samtidigt att även längre, icke-tabloida nyhetsinslag väl kan fånga tittarens uppmärksamhet och fasta i minnet om inslaget är i en sorts ideologisk resonans med tittaren.

Social media and public libraries : exploring information activities of library professionals and users

Social media has become a part of many people’s everyday lives. In the library field the adoption of social media has been widespread and discussions of the development of “Library 2.0” began at an early stage. The aim with this thesis is to study the interface between public libraries, social media, and users, focusing on information activities. The main research question is: How is the interface between public libraries and social media perceived and acted upon by its main stakeholders (library professionals and users)? The background of Library 2.0 is strongly associated with the development of the Web and social media, as well as with the public libraries and their user-centered and information technological development. The theoretical framework builds on the research within the area of Library and Information Science concerning information behavior, information practice, and information activities. Earlier research on social media and public libraries is also highlighted in this thesis. The methods survey and content analysis were applied to map the interface between social media and public libraries. A questionnaire was handed out to the users and another questionnaire was sent out to the library professionals. The results were statistically analyzed. In the content analysis public library Facebook pages were studied. All the empirical investigations were conducted in the area of Finland Proper. An integrated analysis of the results deepens the understanding of the key elements of the social media and public library context. These elements are interactivity, information activities, perceptions, and stakeholders. In this context seven information activities were distinguished: reading, seeking, creating, communicating, informing, mediating, and contributing. This thesis contributes to develop the research concerning information activities and draws a realistic picture of the challenges and opportunities in the social media and public library context. It also contributes with knowledge on library professionals and library users, and the existing differences in their perceptions of the interface between libraries and social media.

Project Resource Management in R&D Public Sector Organization

In R&D organizations multiple projects are executed concurrently. Problems arises in managing shared resources since they are needed by multiple projects simultaneously. The objective of this thesis was to study how the project and resource management could be developed in a public sector R&D organization. The qualitative research was carried out in the Magnetic Measurements section at CERN where the section measures magnets for particle accelerators and builds state of the art measurement devices for various needs. Hence, the R&D and measurement projects are very time consuming and very complex. Based on the previous research and the requirements from the organization the best alter- native for resource management was to build a project management information system. A centralized database was constructed and on top of it was built an application for interacting and visualizing the project data. The application allows handling project data, which works as a basis for resource planning before and during the projects are executed. It is one way to standardize the work-flow of projects, which strengthens the project process. Additionally, it was noted that the inner customer’s database, the measurement system and the new application needed to be integrated. Further integration ensures that the project data is received efficiently from customers and available not only within the application but also during the concrete work. The research results introduced a new integrated application, which centralizes the project information flow with better visibility.

Nova et accurata delineatio Ingriae et Careliae

Julkaisuvuosi arvioitu. Mittakaavaa ei määritelty.

Ninon I

Soitinnus: lauluääni, piano.

Lumbar estrecho: experiencia de 10 años en la fundación santa fé de Bogotá

El canal lumbar estrecho de tipo degenerativo, es una enfermedad que se presenta en pacientes entre la quinta y la sexta década de vida; es la causa más común de cirugía lumbar después de los 65 años. Este trabajo busca determinar cuáles son los factores asociados a la presentación de eventos adversos o re-intervención en cirugía de canal lumbar estrecho en la Fundación Santa Fe de Bogotá en los años comprendidos entre 2003 y 2013. Métodos: se realizó un estudio de prevalencia de tipo analítico, en donde se analizaron 249 pacientes sometidos a intervención quirúrgica por cirugía de canal lumbar estrecho.

Tracing the Origin and Spread of Agriculture in Europe

The origins of early farming and its spread to Europe have been the subject of major interest for some time. The main controversy today is over the nature of the Neolithic transition in Europe: the extent to which the spread was, for the most part, indigenous and animated by imitatio (cultural diffusion) or else was driven by an influx of dispersing populations (demic diffusion). We analyze the spatiotemporal dynamics of the transition using radiocarbon dates from 735 early Neolithic sites in Europe, the Near East, and Anatolia. We compute great-circle and shortest-path distances from each site to 35 possible agricultural centers of origin—ten are based on early sites in the Middle East and 25 are hypothetical locations set at 58 latitude/longitude intervals. We perform a linear fit of distance versus age (and vice versa) for each center. For certain centers, high correlation coefficients (R . 0.8) are obtained. This implies that a steady rate or speed is a good overall approximation for this historical development. The average rate of the Neolithic spread over Europe is 0.6–1.3 km/y (95% confidence interval). This is consistent with the prediction of demic diffusion(0.6–1.1 km/y). An interpolative map of correlation coefficients, obtained by using shortest-path distances, shows that the origins of agriculture were most likely to have occurred in the northern Levantine/Mesopotamian area

Mutations in H5N1 influenza virus hemagglutinin that confer binding to human tracheal airway epithelium

The emergence in 2009 of a swine-origin H1N1 influenza virus as the first pandemic of the 21st Century is a timely reminder of the international public health impact of influenza viruses, even those associated with mild disease. The widespread distribution of highly pathogenic H5N1 influenza virus in the avian population has spawned concern that it may give rise to a human influenza pandemic. The mortality rate associated with occasional human infection by H5N1 virus approximates 60%, suggesting that an H5N1 pandemic would be devastating to global health and economy. To date, the H5N1 virus has not acquired the propensity to transmit efficiently between humans. The reasons behind this are unclear, especially given the high mutation rate associated with influenza virus replication. Here we used a panel of recombinant H5 hemagglutinin (HA) variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for influenza virus infection and spread. While parental H5 HA exhibited limited binding to human tracheal epithelium, introduction of selected mutations converted the binding profile to that of a current human influenza strain HA. Strikingly, these amino-acid changes required multiple simultaneous mutations in the genomes of naturally occurring H5 isolates. Moreover, H5 HAs bearing intermediate sequences failed to bind airway tissues and likely represent mutations that are an evolutionary "dead end." We conclude that, although genetic changes that adapt H5 to human airways can be demonstrated, they may not readily arise during natural virus replication. This genetic barrier limits the likelihood that current H5 viruses will originate a human pandemic.