Campaigning Against Europe? The Role of Euroskeptic Fringe and Mainstream Parties in the 2009 European Parliament Election

In this article, we analyze political parties' campaign communication during the 2009 European Parliamentary election in 11 countries (Austria, Bulgaria, Czech Republic, Germany, Hungary, The Netherlands, Poland, Portugal, Spain, Sweden, and the UK). We study which types of issues Euroskeptic fringe and Euroskeptic mainstream parties put on their campaign agendas and the kind and extent of EU opposition they voice. Further, we seek to understand whether Euroskeptic and non-Euroskeptic parties co-orient themselves toward each other within their national party systems with regard to their campaigns. To understand the role of Euroskeptic parties in the 2009 European Parliamentary elections, we draw on a systematic content analysis of parties' posters and televised campaign spots. Our results show that it is Euroskeptic parties at the edges of the political spectrum who discuss polity questions of EU integration and who most openly criticize the union. Principled opposition against the project of EU integration, however, can only be observed in the UK. Finally, we find indicators for co-orientation effects regarding the tone of EU mobilization: In national political environments where Euroskeptic parties strongly criticize the EU, pro-European parties at the same time publicly advance pro-EU positions.

MQN-Mapplet: Visualization of Chemical Space with Interactive Maps of DrugBank, ChEMBL, PubChem, GDB-11, and GDB-13

The MQN-mapplet is a Java application giving access to the structure of small molecules in large databases via color-coded maps of their chemical space. These maps are projections from a 42-dimensional property space defined by 42 integer value descriptors called molecular quantum numbers (MQN), which count different categories of atoms, bonds, polar groups, and topological features and categorize molecules by size, rigidity, and polarity. Despite its simplicity, MQN-space is relevant to biological activities. The MQN-mapplet allows localization of any molecule on the color-coded images, visualization of the molecules, and identification of analogs as neighbors on the MQN-map or in the original 42-dimensional MQN-space. No query molecule is necessary to start the exploration, which may be particularly attractive for nonchemists. To our knowledge, this type of interactive exploration tool is unprecedented for very large databases such as PubChem and GDB-13 (almost one billion molecules). The application is freely available for download at www.gdb.unibe.ch.

Social relationship correlates of major depressive disorder and depressive symptoms in Switzerland: nationally representative cross sectional study

BACKGROUND The quality and quantity of social relationships are associated with depression but there is less evidence regarding which aspects of social relationship are most predictive. We evaluated the relative magnitude and independence of the association of four social relationship domains with major depressive disorder and depressive symptoms. METHODS We analyzed a cross-sectional telephone interview and postal survey of a probability sample of adults living in Switzerland (N = 12,286). Twelve-month major depressive disorder was assessed via structured interview over the telephone using the Composite International Diagnostic Interview (CIDI). The postal survey assessed depressive symptoms as well as variables representing emotional support, tangible support, social integration, and loneliness. RESULTS Each individual social relationship domain was associated with both outcome measures, but in multivariate models being lonely and perceiving unmet emotional support had the largest and most consistent associations across depression outcomes (incidence rate ratios ranging from 1.55-9.97 for loneliness and from 1.23-1.40 for unmet support, p's < 0.05). All social relationship domains except marital status were independently associated with depressive symptoms whereas only loneliness and unmet support were associated with depressive disorder. CONCLUSIONS Perceived quality and frequency of social relationships are associated with clinical depression and depressive symptoms across a wide adult age spectrum. This study extends prior work linking loneliness to depression by showing that a broad range of social relationship domains are associated with psychological well-being.

Development of dendritic tonic GABAergic inhibition regulates excitability and plasticity in CA1 pyramidal neurons

Synaptic plasticity rules change during development: while hippocampal synapses can be potentiated by a single action potential pairing protocol in young neurons, mature neurons require burst firing to induce synaptic potentiation. An essential component for spike timing-dependent plasticity is the backpropagating action potential (BAP). BAP along the dendrites can be modulated by morphology and ion channel composition, both of which change during late postnatal development. However it is unclear whether these dendritic changes can explain the developmental changes in synaptic plasticity induction rules. Here, we show that tonic GABAergic inhibition regulates dendritic action potential backpropagation in adolescent but not pre-adolescent CA1 pyramidal neurons. These developmental changes in tonic inhibition also altered the induction threshold for spike timing-dependent plasticity in adolescent neurons. This GABAergic regulatory effect upon backpropagation is restricted to distal regions of apical dendrites (>200 μm) and mediated by α5-containing GABA(A) receptors. Direct dendritic recordings demonstrate α5-mediated tonic GABA(A) currents in adolescent neurons which can modulate backpropagating action potentials. These developmental modulations in dendritic excitability could not be explained by concurrent changes in dendritic morphology. To explain our data, model simulations propose a distally-increasing or localized distal expression of dendritic α5 tonic inhibition in mature neurons. Overall, our results demonstrate that dendritic integration and plasticity in more mature dendrites are significantly altered by tonic α5 inhibition in a dendritic region-specific and developmentally-regulated manner.

Interdisciplinary assessment of complex regional water systems and their future evolution: how socioeconomic drivers can matter more than climate

Modeling of future water systems at the regional scale is a difficult task due to the complexity of current structures (multiple competing water uses, multiple actors, formal and informal rules) both temporally and spatially. Representing this complexity in the modeling process is a challenge that can be addressed by an interdisciplinary and holistic approach. The assessment of the water system of the Crans-Montana-Sierre area (Switzerland) and its evolution until 2050 were tackled by combining glaciological, hydrogeological, and hydrological measurements and modeling with the evaluation of water use through documentary, statistical and interview-based analyses. Four visions of future regional development were co-produced with a group of stakeholders and were then used as a basis for estimating future water demand. The comparison of the available water resource and the water demand at monthly time scale allowed us to conclude that for the four scenarios socioeconomic factors will impact on the future water systems more than climatic factors. An analysis of the sustainability of the current and future water systems based on four visions of regional development allowed us to identify those scenarios that will be more sustainable and that should be adopted by the decision-makers. The results were then presented to the stakeholders through five key messages. The challenges of communicating the results in such a way with stakeholders are discussed at the end of the article.

Vascular Plants and Biocrusts Modulate How Abiotic Factors Affect Wetting and Drying Events in Drylands

Understanding how organisms control soil water dynamics is a major research goal in dryland ecology. Although previous studies have mostly focused on the role of vascular plants on the hydrological cycle of drylands, recent studies highlight the importance of biological soil crusts formed by lichens, mosses, and cyanobacteria (biocrusts) as a major player in this cycle. We used data from a 6.5-year study to evaluate how multiple abiotic (rainfall characteristics, temperature, and initial soil moisture) and biotic (vascular plants and biocrusts) factors interact to determine wetting and drying processes in a semi-arid grassland from Central Spain. We found that the shrub Retama sphaerocarpa and biocrusts with medium cover (25–75%) enhanced water gain and slowed drying compared with bare ground areas (BSCl). Well-developed biocrusts (>75% cover) gained more water, but lost it faster than BSCl microsites. The grass Stipa tenacissima reduced water gain due to rainfall interception, but increased soil moisture retention compared to BSCl microsites. Biotic modulation of water dynamics was the result of different mechanisms acting in tandem and often in opposite directions. For instance, biocrusts promoted an exponential behavior during the first stage of the drying curve, but reduced the importance of soil characteristics that accentuate drying rates. Biocrust-dominated microsites gained a similar amount of water than vascular plants, although they lost it faster than vascular plants during dry periods. Our results emphasize the importance of biocrusts for water dynamics in drylands, and illustrate the potential mechanisms behind their effects. They will help to further advance theoretical and modeling efforts on the hydrology of drylands and their response to ongoing climate change.

Dysfunction of Cortical Dendritic Integration in Neuropathic Pain Reversed by Serotoninergic Neuromodulation

Neuropathic pain is caused by long-term modifications of neuronal function in the peripheral nervous system, the spinal cord, and supraspinal areas. Although functional changes in the forebrain are thought to contribute to the development of persistent pain, their significance and precise subcellular nature remain unexplored. Using somatic and dendritic whole-cell patch-clamp recordings from neurons in the anterior cingulate cortex, we discovered that sciatic nerve injury caused an activity-dependent dysfunction of hyperpolarization-activated cyclic nucleotide-regulated (HCN) channels in the dendrites of layer 5 pyramidal neurons resulting in enhanced integration of excitatory postsynaptic inputs and increased neuronal firing. Specific activation of the serotonin receptor type 7 (5-HT7R) alleviated the lesion-induced pathology by increasing HCN channel function, restoring normal dendritic integration, and reducing mechanical pain hypersensitivity in nerve-injured animals in vivo. Thus, serotoninergic neuromodulation at the forebrain level can reverse the dendritic dysfunction induced by neuropathic pain and may represent a potential therapeutical target.

In-situ, satellite measurement and model evidence on the dominant regional contribution to fine particulate matter levels in the Paris Megacity

A detailed characterization of air quality in the megacity of Paris (France) during two 1-month intensive campaigns and from additional 1-year observations revealed that about 70% of the urban background fine particulate matter (PM) is transported on average into the megacity from upwind regions. This dominant influence of regional sources was confirmed by in situ measurements during short intensive and longer-term campaigns, aerosol optical depth (AOD) measurements from ENVISAT, and modeling results from PMCAMx and CHIMERE chemistry transport models. While advection of sulfate is well documented for other megacities, there was surprisingly high contribution from long-range transport for both nitrate and organic aerosol. The origin of organic PM was investigated by comprehensive analysis of aerosol mass spectrometer (AMS), radiocarbon and tracer measurements during two intensive campaigns. Primary fossil fuel combustion emissions constituted less than 20%in winter and 40%in summer of carbonaceous fine PM, unexpectedly small for a megacity. Cooking activities and, during winter, residential wood burning are the major primary organic PM sources. This analysis suggests that the major part of secondary organic aerosol is of modern origin, i.e., from biogenic precursors and from wood burning. Black carbon concentrations are on the lower end of values encountered in megacities worldwide, but still represent an issue for air quality. These comparatively low air pollution levels are due to a combination of low emissions per inhabitant, flat terrain, and a meteorology that is in general not conducive to local pollution build-up. This revised picture of a megacity only being partially responsible for its own average and peak PM levels has important implications for air pollution regulation policies.

ROSINA/DFMS and IES observations of 67P: Ion-neutral chemistry in the coma of a weakly outgassing comet

Context. The Rosetta encounter with comet 67P/Churyumov-Gerasimenko provides a unique opportunity for an in situ, up-close investigation of ion-neutral chemistry in the coma of a weakly outgassing comet far from the Sun. Aims. Observations of primary and secondary ions and modeling are used to investigate the role of ion-neutral chemistry within the thin coma. Methods. Observations from late October through mid-December 2014 show the continuous presence of the solar wind 30 km from the comet nucleus. These and other observations indicate that there is no contact surface and the solar wind has direct access to the nucleus. On several occasions during this time period, the Rosetta/ROSINA/Double Focusing Mass Spectrometer measured the low-energy ion composition in the coma. Organic volatiles and water group ions and their breakup products (masses 14 through 19), CO2+ (masses 28 and 44) and other mass peaks (at masses 26, 27, and possibly 30) were observed. Secondary ions include H3O+ and HCO+ (masses 19 and 29). These secondary ions indicate ion-neutral chemistry in the thin coma of the comet. A relatively simple model is constructed to account for the low H3O+/H2O+ and HCO+/CO+ ratios observed in a water dominated coma. Results from this simple model are compared with results from models that include a more detailed chemical reaction network. Results. At low outgassing rates, predictions from the simple model agree with observations and with results from more complex models that include much more chemistry. At higher outgassing rates, the ion-neutral chemistry is still limited and high HCO+/CO+ ratios are predicted and observed. However, at higher outgassing rates, the model predicts high H3O+/H2O+ ratios and the observed ratios are often low. These low ratios may be the result of the highly heterogeneous nature of the coma, where CO and CO2 number densities can exceed that of water.

Functional Characterization and Comparison of Intercellular Communication in Stem Cell-Derived Cardiomyocytes

One novel treatment strategy for the diseased heart focuses on the use of pluripotent stem cell-derived cardiomyocytes (SC-CMs) to overcome the heart's innate deficiency for self-repair. However, targeted application of SC-CMs requires in-depth characterization of their true cardiogenic potential in terms of excitability and intercellular coupling at cellular level and in multicellular preparations. In this study, we elucidated the electrical characteristics of single SC-CMs and intercellular coupling quality of cell pairs, and concomitantly compared them with well-characterized murine native neonatal and immortalized HL-1 cardiomyocytes. Firstly, we investigated the electrical properties and Ca2+ signaling mechanisms specific to cardiac contraction in single SC-CMs. Despite heterogeneity of the new cardiac cell population, their electrophysiological activity and Ca2+ handling were similar to native cells. Secondly, we investigated the capability of paired SC-CMs to form an adequate subunit of a functional syncytium and analyzed gap junctions and signal transmission by dye transfer in cell pairs. We discovered significantly diminished coupling in SC-CMs compared with native cells, which could not be enhanced by a coculture approach combining SC-CMs and primary CMs. Moreover, quantitative and structural analysis of gap junctions presented significantly reduced connexin expression levels compared with native CMs. Strong dependence of intercellular coupling on gap junction density was further confirmed by computational simulations. These novel findings demonstrate that despite the cardiogenic electrophysiological profile, SC-CMs present significant limitations in intercellular communication. Inadequate coupling may severely impair functional integration and signal transmission, which needs to be carefully considered for the prospective use of SC-CMs in cardiac repair.

Similarity Mapplet: Interactive Visualization of the Directory of Useful Decoys and ChEMBL in High Dimensional Chemical Spaces

An Internet portal accessible at www.gdb.unibe.ch has been set up to automatically generate color-coded similarity maps of the ChEMBL database in relation to up to two sets of active compounds taken from the enhanced Directory of Useful Decoys (eDUD), a random set of molecules, or up to two sets of user-defined reference molecules. These maps visualize the relationships between the selected compounds and ChEMBL in six different high dimensional chemical spaces, namely MQN (42-D molecular quantum numbers), SMIfp (34-D SMILES fingerprint), APfp (20-D shape fingerprint), Xfp (55-D pharmacophore fingerprint), Sfp (1024-bit substructure fingerprint), and ECfp4 (1024-bit extended connectivity fingerprint). The maps are supplied in form of Java based desktop applications called “similarity mapplets” allowing interactive content browsing and linked to a “Multifingerprint Browser for ChEMBL” (also accessible directly at www.gdb.unibe.ch) to perform nearest neighbor searches. One can obtain six similarity mapplets of ChEMBL relative to random reference compounds, 606 similarity mapplets relative to single eDUD active sets, 30 300 similarity mapplets relative to pairs of eDUD active sets, and any number of similarity mapplets relative to user-defined reference sets to help visualize the structural diversity of compound series in drug optimization projects and their relationship to other known bioactive compounds.