Heterologous expression of equine CYP3A94 and investigation of a tunable system to regulate co-expressed NADPH P450 oxidoreductase levels.

The activity of cytochrome P450 enzymes depends on the enzyme NADPH P450 oxidoreductase (POR). The aim of this study was to investigate the activity of the equine CYP3A94 using a system that allows to regulate the POR protein levels in mammalian cells. CYP3A94 and the equine POR were heterologously expressed in V79 cells. In the system used, the POR protein regulation is based on a destabilizing domain (DD) that transfers its instability to a fused protein. The resulting fusion protein is therefore degraded by the ubiquitin-proteasome system (UPS). Addition of "Shield-1" prevents the DD fusion protein from degradation. The change of POR levels at different Shield-1 concentrations was demonstrated by cytochrome c reduction, Western immunoblot analysis, and immunocytochemistry. The alteration of CYP3A94 activity was investigated using a substrate (BFC) known to detect CYP3A4 activity. Equine CYP3A94 was demonstrated to be metabolically active and its activity could be significantly elevated by co-expression of POR. Cytochrome c reduction was significantly increased in V79-CYP3A94/DD-POR cells compared to V79-CYP3A94 cells. Surprisingly, incubation with different Shield-1 concentrations resulted in a decrease in POR protein shown by Western immunoblot analysis. Cytochrome c reduction did not change significantly, but the CYP3A94 activity decreased more than 4-fold after incubation with 500 nM and 1 µM Shield-1 for 24 hours. No differences were obtained when V79-CYP3A94 POR cells with and without Shield-1 were compared. The basal activity levels of V79-CYP3A94/DD-POR cells were unexpectedly high, indicating that DD/POR is not degraded without Shield-1. Shield-1 decreased POR protein levels and CYP3A94 activity suggesting that Shield-1 might impair POR activity by an unknown mechanism. Although regulation of POR with the pPTuner system could not be obtained, the cell line V79-CYP3A94/DD-POR system can be used for further experiments to characterize the equine CYP3A94 since the CYP activity was significantly enhanced with co-expressed POR.

On the Methyl-Transfer Reaction in Crystalline Methyl 2-(Methylthio)benzenesulfonate: a Thermally Induced Non-Topochemical Solid-State Reaction

The rearrangement of methyl 2-(methylthio)benzenesulfonate (1) to the zwitterionic 2-(dimethyl-sulfonium)benzenesulfonate (2) is known to proceed in solution by intermolecular Me transfers. The same rearrangement has been observed to occur in crystalline 1, but the crystal structure shows that the molecular packing is not conducive to intermolecular Me transfer. The reaction has been carried out with mixed crystals composed of 1 and deuteriomethylated (D6)-l. By fast-atom-bombardment mass spectroscopy, it has been shown that the product consists of a 1:2:1 mixture of the non-, tri-, and hexadeuterated species, the mixture expected, if the solid-state reaction proceeds by intermolecular Me transfers. From this result, together with the slower rates of conversion in the single crystal compared with the melt, it can be concluded that the reaction must occur not topochemically but rather at defects such as microcavities, surfaces, and other irregularities in the ordered crystal arrangement.

Demenzverdacht, aber normale neuropsychologische Screening-Untersuchung - wie weiter?

Die Demenz betrifft viele, belastet Angehörige und führt zu hohen Kosten, weshalb die Schweiz eine Sensibilisierungskampagne lancierte, um u.a. die Früherkennung der Demenz zu fördern. Dank der Früherkennung erleben Patienten und Angehörige Vorteile, wie weniger Notfallzuweisungen oder spätere Heimeintritte. Die Früherkennung ist aber schwierig, wenn Patienten zwar Gedächtnisprobleme beklagen, die Screening-Tests aber normal ausfallen. Möglicherweise helfen Geruchstests und weitere klinische Zeichen bei der Entscheidung, welche Patienten weiter abgeklärt werden. Die Zeit für funktionelle Bildgebungen und Biomarker ist noch nicht reif. Zentral bleibt bei kognitiven Beschwerden und normalem Screening das Gespräch mit Patient und Angehörigen, um nächste Schritte gemeinsam zu beschliessen. Der Hausarzt nimmt dabei eine zentrale, koordinierende und beratende Funktion ein, um Menschen mit Gedächtnisstörungen kompetent und effizient zu betreuen.

Die Schweiz anderswo - La Suisse ailleurs

Kurztext Gegenwärtig leben über 732 000 Schweizer Bürgerinnen und Bürger im Ausland, mehr als jede zehnte Person mit Schweizer Pass. Die Beiträge gehen den Fragen nach, inwiefern die erst seit dem 20. Jahrhundert so bezeichneten «Auslandschweizer» als wirtschaftliche «Brückenköpfe» dienten, inwiefern ihre kommunikativen Netzwerke kulturelle Transfers bewirkten und Formen des Wissensaustausches begünstigten oder welchen Beitrag umgekehrt die (ehemaligen) Auslandschweizerinnen und Auslandschweizer zu Wirtschaft, Wissenschaft, Sozialpolitik und Kultur in der Schweiz leisteten. Sie befassen sich aber auch mit der historischen Konstruktion der Bevölkerung als einer neuen politischen Kategorie. Nicht nur für die Neuzeit ist zu fragen, mit welchen Politiken und Massnahmen Obrigkeit, Behörden, Staat und Verwaltung die eigene Population konstituierten und festigten und sie je nachdem über die bestehenden (nationalstaatlichen) Grenzen hinweg ausdehnten. Plus de 732 000 citoyennes et citoyens suisses vivent actuellement à l’étranger, soit plus d’une personne sur dix titulaires du passeport helvétique. Les contributions rassemblées interrogent dans quelle mesure les «Suisses de l’étranger» – désignés ainsi à partir du 20e siècle seulement – ont servi de relais pour le commerce extérieur, ainsi que dans quelle mesure leurs réseaux de communication ont contribué aux transferts culturels et favorisé des formes d’échange du savoir ou, à l’inverse, quels sont les apports des (anciens) Suisses de l’étranger dans les domaines de l’économie, de la science, de la politique sociale et de la culture lors de leur retour en Suisse. Les contributions portent également sur la construction historique de la population en tant que nouvelle catégorie politique. La question de savoir à travers quelles politiques et mesures l’autorité, les pouvoirs publics, l’Etat et l’administration ont constitué et consolidé leur propre population et, suivant les cas, l’ont étendu au-delà des frontières (nationales) existantes concerne autant l’époque contemporaine que les périodes antérieures.

A Word. Palaver and Its Transferal Residues

The word 'palaver' is colloquially associated with useless verbiage and the nuisance of a tediously long, aimless and superfluous debate. At the same time, it insinuates an uncivilized culture of discourse beyond reason. Thus it appears to be of vaguely exotic origin but still firmly set in the European lexicon. Yet behind this contemporary meaning there lies a long history of linguistic and cultural transfers which is encased in a context of different usages of language and their intersections. By tracing the usage and semantics of 'palaver' in various encyclopaedias, glossaries and dictionaries of English, French, German, Portuguese and Spanish, the following article explores the rich history of this word. Moreover, it also regards the travelling semantics of the term 'palaver' as a process of cultural transfer that can be likened to the microcellular workings of a (retro)virus. Viral reproduction and evolution work through processes of transfer that enable the alteration of the host to adjust it to the replication and reproduction of the virus. In some cases, these processes also allow for the mutation or modification of the virus, making it suitable for transfer from one host to another. The virus is thus offered here as a vital model for cultural transfer: It not only encompasses the necessary adoption and adaption of contents or objects of cultural transfer in different contexts. It contributes to a conceptual understanding of the transferal residue that the transferred content is endowed with by its diversifying contexts. This model thereby surpasses an understanding of cultural transfer as literal translation or transmission: it conceptualizes cultural transfer as an agent of evolutionary processes, allowing for mutational effects of transfer as endowment.

Comparison of patients in three different rehabilitation settings after knee or hip arthroplasty: a natural observational, prospective study.

BACKGROUND Patients after primary hip or knee replacement surgery can benefit from postoperative treatment in terms of improvement of independence in ambulation, transfers, range of motion and muscle strength. After discharge from hospital, patients are referred to different treatment destination and modalities: intensive inpatient rehabilitation (IR), cure (medically prescribed stay at a convalescence center), or ambulatory treatment (AT) at home. The purpose of this study was to 1) measure functional health (primary outcome) and function relevant factors in patients with hip or knee arthroplasty and to compare them in relation to three postoperative management strategies: AT, Cure and IR and 2) compare the post-operative changes in patient's health status (between preoperative and the 6 month follow-up) for three rehabilitation settings. METHODS Natural observational, prospective two-center study with follow-up. Sociodemographic data and functional mobility tests, Timed Up and Go (TUG) and Iowa Level of Assistance Scale (ILOAS) of 201 patients were analysed before arthroplasty and at the end of acute hospital stay (mean duration of stay: 9.7 days +/- 3.9). Changes in health state were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) before and 6 months after arthroplasty. RESULTS Compared to patients referred for IR and Cure, patients referred for AT were significantly younger and less comorbid. Patients admitted to IR had the highest functional disability before arthroplasty. Before rehabilitation, mean TUG was 40.0 s in the IR group, 33.9 s in the Cure group, and 27.5 s in the AT group, and corresponding mean ILOAS was 16.0, 13.0 and 12.2 (50.0 = worst). At the 6 months follow-up, the corresponding effect sizes of the WOMAC global score were 1.32, 1.87, and 1.51 (>0 means improvement). CONCLUSIONS Age, comorbidity and functional disability are associated with referral for intensive inpatient rehabilitation after hip or knee arthroplasty and partly affect health changes after rehabilitation.

Potential for virus transfer between the honey bees Apis mellifera and A. cerana

Viruses seem to play a key role in European honey bee, Apis mellifera health, and have a much broader host spectrum than previously thought. Few studies have investigated interspecific virus transfer within the genus Apis. The introduction of A. mellifera into Asia exposed endemic Apis species to the risk of obtaining new viruses or viral strains and vice versa. To investigate the potential for host shifts, virus prevalence and sequences were monitored over three years in single and mixed-species apiaries hosting introduced A. mellifera and endemic Apis cerana. Deformed wing virus (DWV), Israeli acute paralysis virus (IAPV), black queen cell virus (BQCV), and sacbrood virus (SBV) were found, but not KBV, VDV-1, ABPV, or CBPV. Virus infections and prevalence were generally lower in A. cerana compared to A. mellifera, and varied over the years. The sequence data provided evidence for interspecific transfer of IAPV, BQCV, and DWV, but SBV strains seem to be species specific. Prevalence and sequence results taken together indicate that interspecific transfers of viruses are rare, even if honey bees are kept in close proximity. We discuss the pattern observed in the context host specificity and resistance. Our understanding of the extent of these exchanges is limited by a lack of knowledge on the mechanisms of adaptation of viruses to different hosts.