Ubiquitylation and SUMOylation of Cardiac Ion Channels

Cardiac ion channels play an essential role in the generation of the action potential of cardiomyocytes. Over the past 15 years, a new field of research called channelopathies has emerged; it regroups all diseases caused by ion channel dysfunction. Investigators have largely determined the physiological roles of cardiac ion channels, but little is known about the molecular determinants of their regulation. Two post-translational mechanisms that are crucial in determining the fate of proteins are ubiquitylation and the SUMOylation pathways, which lead to the degradation and/or regulation of modified proteins. Recently, several groups have investigated the physiological impacts of these mechanisms on the regulation of different classes of cardiac ion channels. The objective of this review is to summarize and briefly discuss these results.

Pens and Swords: Creative writing and poetry in post-conflict and displacement settings.

An overview of the use of poetry in creative writing and memoir writing in post-conflict contexts and for migrants illustrated with a number of proven activities, in the light of the (alleged) contrast between therapeutic and artistic writing.

Highlights in Analytical Chemistry in Switzerland: OMA & OPA - A Software Tool for Mass Spectrometric Sequencing of Nucleic Acids

Oligonucleotides comprising unnatural building blocks, which interfere with the translation machinery, have gained increased attention for the treatment of gene-related diseases (e.g. antisense, RNAi). Due to structural modifications, synthetic oligonucleotides exhibit increased biostability and bioavailability upon administration. Consequently, classical enzyme-based sequencing methods are not applicable to their sequence elucidation and verification. Tandem mass spectrometry is the method of choice for performing such tasks, since gas-phase dissociation is not restricted to natural nucleic acids. However, tandem mass spectrometric analysis can generate product ion spectra of tremendous complexity, as the number of possible fragments grows rapidly with increasing sequence length. The fact that structural modifications affect the dissociation pathways greatly increases the variety of analytically valuable fragment ions. The gas-phase dissociation of oligonucleotides is characterized by the cleavage of one of the four bonds along the phosphodiester chain, by the accompanying loss of nucleases, and by the generation of internal fragments due to secondary backbone cleavage. For example, an 18-mer oligonucleotide yields a total number of 272’920 theoretical fragment ions. In contrast to the processing of peptide product ion spectra, which nowadays is highly automated, there is a lack of tools assisting the interpretation of oligonucleotide data. The existing web-based and stand-alone software applications are primarily designed for the sequence analysis of natural nucleic acids, but do not account for chemical modifications and adducts. Consequently, we developed a software to support the interpretation of mass spectrometric data of natural and modified nucleic acids and their adducts with chemotherapeutic agents.

Temporal evolution of strut light intensity after implantation of bioresorbable polymeric intracoronary scaffolds in the ABSORB cohort B trial-an application of a new quantitative method based on optical coherence tomography.

BACKGROUND Quantitative light intensity analysis of the strut core by optical coherence tomography (OCT) may enable assessment of changes in the light reflectivity of the bioresorbable polymeric scaffold from polymer to provisional matrix and connective tissues, with full disappearance and integration of the scaffold into the vessel wall. The aim of this report was to describe the methodology and to apply it to serial human OCT images post procedure and at 6, 12, 24 and 36 months in the ABSORB cohort B trial. METHODS AND RESULTS In serial frequency-domain OCT pullbacks, corresponding struts at different time points were identified by 3-dimensional foldout view. The peak and median values of light intensity were measured in the strut core by dedicated software. A total of 303 corresponding struts were serially analyzed at 3 time points. In the sequential analysis, peak light intensity increased gradually in the first 24 months after implantation and reached a plateau (relative difference with respect to baseline [%Dif]: 61.4% at 12 months, 115.0% at 24 months, 110.7% at 36 months), while the median intensity kept increasing at 36 months (%Dif: 14.3% at 12 months, 75.0% at 24 months, 93.1% at 36 months). CONCLUSIONS Quantitative light intensity analysis by OCT was capable of detecting subtle changes in the bioresorbable strut appearance over time, and could be used to monitor the bioresorption and integration process of polylactide struts.

Electoral and Financial Bookkeeping: A Comparison of Pre-Electoral Pledges on Public Spending and the Outcome of Post-Electoral Budget Debates

In the wake of the financial crisis, budgetary discipline has taken centre stage in politics. More than ever a country's budget mirrors the true policy preferences of the legislative majority beyond all political discourse and cheap talk. The paper sheds light on mandate fulfilment in the field of public spending and fiscal policy in general. Based on previous work on pledge fulfilment in Switzerland the paper compares publicised pre-electoral statements of MPs on public spending and the development of the public finances with their post-electoral legislative behaviour during budget debates and votes. The findings of the paper confirm the results of the aforementioned earlier studies and point to the potential of budgetary statements for future mandate fulfilment research.

Rainer Werner Fassbinder’s "Garbage, The City, and Death". A Four Act Scandal in Post-war Germany

Rainer Werner Fassbinder’s Garbage, The City, and Death. A Four Act Scandal in Post-war Germany The paper explores the dramaturgy of the scandals around the play Garbage, The City and Death (Der Müll, die Stadt und der Tod) by German playwright, theatre and film maker Rainer Werner Fassbinder. Published in 1976, the play immediately caused a scandal in West Germany, because it was accused of reproducing anti-Semitic stereotypes. The presentation sheds light on the different phases of the scandal and their historical and cultural contexts in post-war Germany – starting as a literary scandal in 1976, being transformed into a theatre scandal in the 1980ies and finally being dissolved by the German premiere in 2009. The paper is structured as follows: Act One: The Literary Scandal. Destroying Fassbinder’s Garbage, Act Two: Preventing the Staging of the Play, Act Three: Blocking the Opening Night, Act Four: Performing the Play in Germany. By analysing the dramaturgical structure of this specific scandal, the paper discusses the following hypotheses: 1. Scandals arise through the circulation of decontextualised information in public. This is due to either a lack of information about the actual object or incident being scandalised or a lack of information about the context of the object or incident. This lack is caused by the logic of the scandal itself: Because the play or the performance is prohibited, it has been withdrawn from the public, making it impossible to form a well-founded opinion on the controversy. 2. The scandal is driven forward by an emotionalising rhetoric built around the decontextualised information. 3. Once the gap of information is filled, the scandalising rhetoric turns into a rhetoric of irrelevance: Reviews of the first performance of Garbage, The City and Death in Germany considered the play hardly a matter of public concern.

SALSA: a tool to estimate the stray light contamination for low-Earth orbit observatories

Stray light contamination reduces considerably the precision of photometric of faint stars for low altitude spaceborne observatories. When measuring faint objects, the necessity of coping with stray light contamination arises in order to avoid systematic impacts on low signal-to-noise images. Stray light contamination can be represented by a flat offset in CCD data. Mitigation techniques begin by a comprehensive study during the design phase, followed by the use of target pointing optimisation and post-processing methods. We present a code that aims at simulating the stray-light contamination in low-Earth orbit coming from reflexion of solar light by the Earth. StrAy Light SimulAtor (SALSA) is a tool intended to be used at an early stage as a tool to evaluate the effective visible region in the sky and, therefore to optimise the observation sequence. SALSA can compute Earth stray light contamination for significant periods of time allowing missionwide parameters to be optimised (e.g. impose constraints on the point source transmission function (PST) and/or on the altitude of the satellite). It can also be used to study the behaviour of the stray light at different seasons or latitudes. Given the position of the satellite with respect to the Earth and the Sun, SALSA computes the stray light at the entrance of the telescope following a geometrical technique. After characterising the illuminated region of the Earth, the portion of illuminated Earth that affects the satellite is calculated. Then, the flux of reflected solar photons is evaluated at the entrance of the telescope. Using the PST of the instrument, the final stray light contamination at the detector is calculated. The analysis tools include time series analysis of the contamination, evaluation of the sky coverage and an objects visibility predictor. Effects of the South Atlantic Anomaly and of any shutdown periods of the instrument can be added. Several designs or mission concepts can be easily tested and compared. The code is not thought as a stand-alone mission designer. Its mandatory inputs are a time series describing the trajectory of the satellite and the characteristics of the instrument. This software suite has been applied to the design and analysis of CHEOPS (CHaracterizing ExOPlanet Satellite). This mission requires very high precision photometry to detect very shallow transits of exoplanets. Different altitudes and characteristics of the detector have been studied in order to find the best parameters, that reduce the effect of contamination. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Genome and transcriptome sequencing identifies breeding targets in the orphan crop tef (Eragrostis tef)

Background: Tef (Eragrostis tef), an indigenous cereal critical to food security in the Horn of Africa, is rich in minerals and protein, resistant to many biotic and abiotic stresses and safe for diabetics as well as sufferers of immune reactions to wheat gluten. We present the genome of tef, the first species in the grass subfamily Chloridoideae and the first allotetraploid assembled de novo. We sequenced the tef genome for marker-assisted breeding, to shed light on the molecular mechanisms conferring tef's desirable nutritional and agronomic properties, and to make its genome publicly available as a community resource. Results: The draft genome contains 672 Mbp representing 87% of the genome size estimated from flow cytometry. We also sequenced two transcriptomes, one from a normalized RNA library and another from unnormalized RNASeq data. The normalized RNA library revealed around 38000 transcripts that were then annotated by the SwissProt group. The CoGe comparative genomics platform was used to compare the tef genome to other genomes, notably sorghum. Scaffolds comprising approximately half of the genome size were ordered by syntenic alignment to sorghum producing tef pseudo-chromosomes, which were sorted into A and B genomes as well as compared to the genetic map of tef. The draft genome was used to identify novel SSR markers, investigate target genes for abiotic stress resistance studies, and understand the evolution of the prolamin family of proteins that are responsible for the immune response to gluten. Conclusions: It is highly plausible that breeding targets previously identified in other cereal crops will also be valuable breeding targets in tef. The draft genome and transcriptome will be of great use for identifying these targets for genetic improvement of this orphan crop that is vital for feeding 50 million people in the Horn of Africa.

Post-colonial (American?) English Presence on the North-Western Pacific Island of Kosrae: A cross-linguistic analysis of the overlaps and divergences of Kosraean English compared to standard American English

Kosrae is the most remote island of the Federated States of Micronesia (FSM), with a population of less than 7,000 inhabitants, located in the Pacific Ocean between Hawaii and Guam. FSM is an independent sovereign nation consisting of four states in total: Pohnpei, Chuuk, Yap, and Kosrae. Having passed through the hands of Spain, Germany and Japan, the United States gained administrative control of FSM after WWII, as commissioned by the UN. The FSM became an independent nation in 1986 while still retaining affiliation with the US under a ‘Compact of Free Association’. Now both Kosraean and English are considered to be the two official languages and the variety of Kosraean English which has arisen proves for an interesting comparative study. In order to obtain the relevant data, I spent three months on the island of Kosrae, interviewing 90 local speakers, ranging in age (16-70), occupation, sex and time spent off island. The 45 minute long interviews were informal but supported by participant information to capture relevant data and conversations were guided in a way that aimed to reveal language and cultural attitudes. With reference to these samples, I examine the effects of American English on the language use in Kosrae. This paper aims to present a broad analysis of phonological, morphosyntactic and pragmatic features, such as pro-dropping, discourse markers and other practices in order to demonstrate the similarities and differences between the two varieties, which are coming to shape the variety developing on Kosrae. Having transcribed conversations using the tool Elan, I will put particular focus on [h] deletion and insertion, a rare occurrence found in a variety of post-colonial American English which I believe is of particular interest. I assess the presence of English in Kosrae with reference to sociological influences, past and present. First, I discuss the extralinguistic factors which have shaped the English that is currently used on Kosrae, including migration between US and FSM, and English as a language of administration, social media usage and visual media presence. Secondly, I assess the use of English in this community in light of Schneider’s (2007) ‘Dynamic Model’, with reference to America’s contribution as an ‘exploitation colony’ as defined by Mufwene (2001). Finally, an overview of the salient linguistic characteristics of Kosraean English, based on the data collected will be presented and compared to features associated with standard American English in view of examining overlap and divergence. The overall objective is to present a cross-linguistic description of a hitherto unexamined English emerging in a postcolonial environment with a juxtaposed contact variety. Mufwene, Salikoko S. 2001. The ecology of language evolution. Cambridge: Cambridge University Press. Schneider, E. (2007). Postcolonial Englishes. Cambridge: Cambridge University Press. Segal, H.G. (1989) Kosrae, The Sleeping Lady Awakens. Kosrae: Kosrae Tourist Division, Dept. Of Conservation and Development. Keywords: American English, Global English, Pacific English, Morphosyntactic, Phonological, Variation, Discourse

Diagnostic performance of a new red light LED device for approximal caries detection

The aim of this study was to test a newly developed LED-based fluorescence device for approximal caries detection in vitro. We assembled 120 extracted molars without frank cavitations or fillings pairwise in order to create contact areas. The teeth were independently assessed by two examiners using visual caries detection (International Caries Detection and Assessment System, ICDAS), bitewing radiography (BW), laser fluorescence (LFpen), and LED fluorescence (Midwest Caries I.D., MW). The measurements were repeated at least 1 week later. The diagnostic performance was calculated with Bayesian analyses. Post-test probabilities were calculated in order to judge the diagnostic performance of combined methods. Reliability analyses were performed using kappa statistics for nominal data and intraclass correlation (ICC) for absolute data. Histology served as the gold standard. Sensitivities/specificities at the enamel threshold were 0.33/0.84 for ICDAS, 0.23/0.86 for BW, 0.47/0.78 for LFpen, and 0.32/0.87 for MW. Sensitivities/specificities at the dentine threshold were 0.04/0.89 for ICDAS, 0.27/0.94 for BW, 0.39/0.84 for LFpen, and 0.07/0.96 for MW. Reliability data were fair to moderate for MW and good for BW and LFpen. The combination of ICDAS and radiography yielded the best diagnostic performance (post-test probability of 0.73 at the dentine threshold). The newly developed LED device is not able to be recommended for approximal caries detection. There might be too much signal loss during signal transduction from the occlusal aspect to the proximal lesion site and the reverse.

Ion channel macromolecular complexes in cardiomyocytes: roles in sudden cardiac death.

The movement of ions across specific channels embedded on the membrane of individual cardiomyocytes is crucial for the generation and propagation of the cardiac electric impulse. Emerging evidence over the past 20 years strongly suggests that the normal electric function of the heart is the result of dynamic interactions of membrane ion channels working in an orchestrated fashion as part of complex molecular networks. Such networks work together with exquisite temporal precision to generate each action potential and contraction. Macromolecular complexes play crucial roles in transcription, translation, oligomerization, trafficking, membrane retention, glycosylation, post-translational modification, turnover, function, and degradation of all cardiac ion channels known to date. In addition, the accurate timing of each cardiac beat and contraction demands, a comparable precision on the assembly and organizations of sodium, calcium, and potassium channel complexes within specific subcellular microdomains, where physical proximity allows for prompt and efficient interaction. This review article, part of the Compendium on Sudden Cardiac Death, discusses the major issues related to the role of ion channel macromolecular assemblies in normal cardiac electric function and the mechanisms of arrhythmias leading to sudden cardiac death. It provides an idea of how these issues are being addressed in the laboratory and in the clinic, which important questions remain unanswered, and what future research will be needed to improve knowledge and advance therapy.

A detector based on silica fibers for ion beam monitoring in a wide current range

A detector based on doped silica and optical fibers was developed to monitor the profile of particle accelerator beams of intensity ranging from 1 pA to tens of µA. Scintillation light produced in a fiber moving across the beam is measured, giving information on its position, shape and intensity. The detector was tested with a continuous proton beam at the 18 MeV Bern medical cyclotron used for radioisotope production and multi-disciplinary research. For currents from 1 pA to 20 µA, Ce3+ and Sb3+ doped silica fibers were used as sensors. Read out systems based on photodiodes, photomultipliers and solid state photomultipliers were employed. Profiles down to the pA range were measured with this method for the first time. For currents ranging from 1 pA to 3 µA, the integral of the profile was found to be linear with respect to the beam current, which can be measured by this detector with an accuracy of ∼1%. The profile was determined with a spatial resolution of 0.25 mm. For currents ranging from 5 µA to 20 µA, thermal effects affect light yield and transmission, causing distortions of the profile and limitations in monitoring capabilities. For currents higher than ∼1 µA, non doped optical fibers for both producing and transporting scintillation light were also successfully employed.