Protective Effect of Focal Adhesion Kinase against Skeletal Muscle Reperfusion Injury after Acute Limb Ischemia.

OBJECTIVES In cardiac muscle, ischemia reperfusion (IR) injury is attenuated by mitochondrial function, which may be upregulated by focal adhesion kinase (FAK). The aim of this study was to determine whether increased FAK levels reduced rhabdomyolysis in skeletal muscle too. MATERIAL AND METHODS In a translational in vivo experiment, rat lower limbs were subjected to 4 hours of ischemia followed by 24 or 72 hours of reperfusion. FAK expression was stimulated 7 days before (via somatic transfection with pCMV-driven FAK expression plasmid) and outcomes were measured against non-transfected and empty transfected controls. Slow oxidative (i.e., mitochondria-rich) and fast glycolytic (i.e., mitochondria-poor) type muscles were analyzed separately regarding rhabdomyolysis, apoptosis, and inflammation. Severity of IR injury was assessed using paired non-ischemic controls. RESULTS After 24 hours of reperfusion, marked rhabdomyolysis was found in non-transfected and empty plasmid-transfected fast-type glycolytic muscle, tibialis anterior. Prior transfection enhanced FAK concentration significantly (p = 0.01). Concomitantly, levels of BAX, promoting mitochondrial transition pores, were reduced sixfold (p = 0.02) together with a blunted inflammation (p = 0.01) and reduced rhabdomyolysis (p = 0.003). Slow oxidative muscle, m. soleus, reacted differently: although apoptosis was detectable after IR, rhabdomyolysis did not appear before 72 hours of reperfusion; and FAK levels were not enhanced in ischemic muscle despite transfection (p = 0.66). CONCLUSIONS IR-induced skeletal muscle rhabdomyolysis is a fiber type-specific phenomenon that appears to be modulated by mitochondria reserves. Stimulation of FAK may exploit these reserves constituting a potential therapeutic approach to reduce tissue loss following acute limb IR in fast-type muscle.

Europeanization in parliament and in the press

Europeanization challenges national democratic systems. As part and parcel of the broader internationalization of politics, Europeanization is associated with a shift from policymaking within majoritarian, elected representative bodies towards technocratic decisions among non-majoritarian and non-elected bodies (Kohler-Koch and Rittberger 2008, Lavenex 2013). It is thus said to weaken the influence of citizens and parliaments on the making of policies and to undermine democratic collective identity (Lavenex 2013, Schimmelfennig 2010). The weakening of national parliaments has been referred to as “de-parliamentarisation” (Goetz and Meyer-Sahling 2008) and has nurtured a broader debate regarding the democratic deficit in the EU. While not being a member of the EU, Switzerland has not remained unaffected by these changes. As discussed in the contribution by Fischer and Sciarini, state executive actors take the lead in Switzerland's European policy. They are responsible for the conduct of international negotiations, they own the treaty making power, and it is up to them to decide whether they wish to launch a negotiation with the EU. In addition, the strong take-it or leave-it character of Europeanized acts limits the room for manoeuver of the parliamentary body also in the ratification phase. Among the public, the rejection of the treaty on the European constitution has definitely closed the era of “permissive consensus” (Hooghe and Marks 2009). However, the process of European unification remains far remote from the European public. In Switzerland, the strongly administrative character of international legislation hinders public discussion (Vögeli 2007). In such a context, the media may serve as cue for the public: By delivering information about the extent and nature of Europeanized policymaking, the media enable citizens to form their own opinions and to hold their representatives accountable. In this sense media coverage may not only be considered an indicator of the information delivered to the public, but it may also enhance the democratic legitimacy of Europeanized policymaking (for a similar argument, see Tresch and Jochum 2005). While the previous contributions to this debate have examined the Europeanization of Swiss (primary and secondary) legislation, we take a closer look at two additional domestic arenas that are both supposed to be under pressure due to Europeanization: The parliament and the media. To that end, we rely on data gathered in a research project that two of us carried out in the context of the NCCR Democracy.1 While this project was primarily interested in the mediatization of decision-making processes in Switzerland, it also investigated the conditional role played by internationalization/Europeanization. For our present purposes, we shall exploit the two data-sets that were developed as part of a study of the political agenda-setting power of the media (Sciarini and Tresch 2012, 2013, Tresch et al. 2013): A data-set on issue attention in parliamentary interventions (initiatives, motions, postulates,2 interpellations and questions) and a data-set on issue attention in articles from the Neue Zürcher Zeitung (NZZ). The data covers the years 1995 to 2003 and the coding of issues followed the classification system developed in the “Policy Agendas Project” (Baumgartner and Jones 1993).

Using Bayes' rule to define the value of evidence from syndromic surveillance

In this work we propose the adoption of a statistical framework used in the evaluation of forensic evidence as a tool for evaluating and presenting circumstantial "evidence" of a disease outbreak from syndromic surveillance. The basic idea is to exploit the predicted distributions of reported cases to calculate the ratio of the likelihood of observing n cases given an ongoing outbreak over the likelihood of observing n cases given no outbreak. The likelihood ratio defines the Value of Evidence (V). Using Bayes' rule, the prior odds for an ongoing outbreak are multiplied by V to obtain the posterior odds. This approach was applied to time series on the number of horses showing clinical respiratory symptoms or neurological symptoms. The separation between prior beliefs about the probability of an outbreak and the strength of evidence from syndromic surveillance offers a transparent reasoning process suitable for supporting decision makers. The value of evidence can be translated into a verbal statement, as often done in forensics or used for the production of risk maps. Furthermore, a Bayesian approach offers seamless integration of data from syndromic surveillance with results from predictive modeling and with information from other sources such as disease introduction risk assessments.

An in situ surface electrochemistry approach towards whole-cell studies: the structure and reactivity of a Geobacter sulfurreducens submonolayer on electrified metal/electrolyte interfaces

A direct electron transfer process between bacterial cells of electrogenic species Geobacter sulfurreducens (Gs) and electrified electrode surfaces was studied to exploit the reactivity of Gs submonolayers on gold and silver surfaces. A submonolayer of Gs was prepared and studied to explore specifically the heterogeneous electron transfer properties at the bacteria/electrode interface. In situ microscopic techniques characterised the morphology of the Gs submonolayers under the operating conditions. In addition, complementary in situ spectroscopic techniques that allowed us to access in situ molecular information of the Gs with high surface selectivity and sensitivity were employed. The results provided clear evidence that the outermost cytochrome C in Gs is responsible for the heterogeneous electron transfer, which is in direct contact with the metal electrode. Feasibility of single cell in situ studies under operating conditions was demonstrated where the combination of surface-electrochemical tools at the nano- and micro-scale with microbiological approaches can offer unique opportunities for the emerging field of electro-microbiology to explore processes and interactions between microorganisms and electrical devices.

To sense or not to sense viral RNA--essentials of coronavirus innate immune evasion.

An essential function of innate immunity is to distinguish self from non-self and receptors have evolved to specifically recognize viral components and initiate the expression of antiviral proteins to restrict viral replication. Coronaviruses are RNA viruses that replicate in the host cytoplasm and evade innate immune sensing in most cell types, either passively by hiding their viral signatures and limiting exposure to sensors or actively, by encoding viral antagonists to counteract the effects of interferons. Since many cytoplasmic viruses exploit similar mechanisms of innate immune evasion, mechanistic insight into the direct interplay between viral RNA, viral RNA-processing enzymes, cellular sensors and antiviral proteins will be highly relevant to develop novel antiviral targets and to restrict important animal and human infections.

Comparison of GOCE-GPS gravity fields derived by different approaches

Several techniques have been proposed to exploit GNSS-derived kinematic orbit information for the determination of long-wavelength gravity field features. These methods include the (i) celestial mechanics approach, (ii) short-arc approach, (iii) point-wise acceleration approach, (iv) averaged acceleration approach, and (v) energy balance approach. Although there is a general consensus that—except for energy balance—these methods theoretically provide equivalent results, real data gravity field solutions from kinematic orbit analysis have never been evaluated against each other within a consistent data processing environment. This contribution strives to close this gap. Target consistency criteria for our study are the input data sets, period of investigation, spherical harmonic resolution, a priori gravity field information, etc. We compare GOCE gravity field estimates based on the aforementioned approaches as computed at the Graz University of Technology, the University of Bern, the University of Stuttgart/Austrian Academy of Sciences, and by RHEA Systems for the European Space Agency. The involved research groups complied with most of the consistency criterions. Deviations only occur where technical unfeasibility exists. Performance measures include formal errors, differences with respect to a state-of-the-art GRACE gravity field, (cumulative) geoid height differences, and SLR residuals from precise orbit determination of geodetic satellites. We found that for the approaches (i) to (iv), the cumulative geoid height differences at spherical harmonic degree 100 differ by only ≈10 % ; in the absence of the polar data gap, SLR residuals agree by ≈96 % . From our investigations, we conclude that real data analysis results are in agreement with the theoretical considerations concerning the (relative) performance of the different approaches.