Trichostatin A Enhances Gap Junctional Intercellular Communication in Primary Cultures of Adult Rat Hepatocytes

The effects of histone deacetylase inhibitor Trichostatin A (TSA) on connexin (Cx) expression and gap junctional intercellular communication (GJIC) were investigated in primary cultures of adult rat hepatocytes. GJIC was monitored by using the scrape-loading/dye transfer method. Immunoblotting and immunocytochemistry were used to investigate Cx protein levels and localization. Cx gene expression was studied by means of quantitative reverse transcriptase-polymerase chain reaction. TSA increased Cx32 protein levels and affected negatively the Cx26 protein levels. The latter was preferentially located in the cytosol of cultured cells. TSA also promoted the appearance of Cx43 in the nuclear compartment of primary cultured hepatocytes. Overall, this resulted in enhanced GJIC activity. It is important to note that the time of onset of TSA treatment was crucial for the extent of its outcome and that the effects of TSA on Cx protein levels occurred independently of transcriptional changes. TSA differentially affects Cx proteins in primary rat hepatocyte cultures, suggesting distinct regulation and/or distinct roles of the different Cx species in the control of hepatic homeostasis. TSA enhances GJIC between primary cultured rat hepatocytes, an interesting finding supporting its use to further optimize liver-based in vitro models for pharmacotoxicological purpose

Memento Mori. Aktuelle Forschungen zu Bestattungssitten im Rheinland

Getreu nach dem Motto „Memento mori“ wurden in den letzten Semestern zahlreiche Abschlussarbeiten zum Bestattungswesen im römischen Rheinland und den angrenzenden Nachbarregionen am Archäologischen Institut der Universität zu Köln unter Betreuung von E. Deschler-Erb vergeben und erfolgreich abgeschlossen. Um die Studierenden und Doktorand*innen zu unterstützen und einen wissenschaftlichen Austausch zu ermöglichen, konnten wir im November 2019 ein Kolloquium zu diesem Thema organisieren. Im Rahmen der Veranstaltung sollte ein Überblick über aktuelle Forschungen zu römischen Bestattungen und Bestattungssitten im Rheinland gegeben werden. Der Fokus lag vor allem auf den verschiedenen Arbeitsweisen, Methoden und Auswertungsmöglichkeiten in der provinzialrömischen Gräberfeldforschung. Der Aufruf für das Kolloquium war erfolgreich und so gelang es im Rahmen der insgesamt 17 Vorträge (darunter Beiträge von fünf Absolvent*innen des Archäologischen Instituts) einen geographischen Bogen von den Niederlanden nach Deutschland und über die Schweiz bis nach Österreich zu schlagen. Neben archäologischen Beiträgen konnten auch interdisziplinäre Forschungen vorgestellt und deren großes Potential für die Erforschung von provinzialrömischen Bestattungssitten verdeutlicht werden. Das Fazit zum Kolloquium: Die Erforschung von Bestattungen und Bestattungssitten der römischen Kaiserzeit ist noch lange nicht zu einem Ende gekommen. Der beständige Austausch sowie der offene und vor allem interdisziplinäre Dialog stellen eine notwendige Grundlage für weitere, zukünftige Forschungen dar. Insgesamt konnten 10 der Referent*innen für einen Beitrag in den Kolloquiums-Akten gewonnen werden, deren Edition als erster Band der neu etablierten Reihe „Kölner Studien zur Archäologie der Römischen Provinzen – digital (KSARP-digi 1)“ jetzt vorliegt. Clarissa Agricola & Eckhard Deschler-Er

Pathogenic characteristics of persistent feline enteric coronavirus infection in cats

Feline coronaviruses (FCoV) comprise two biotypes: feline enteric coronaviruses (FECV) and feline infectious peritonitis viruses (FIPV). FECV is associated with asymptomatic persistent enteric infections, while FIPV causes feline infectious peritonitis (FIP), a usually fatal systemic disease in domestic cats and some wild Felidae. FIPV arises from FECV by mutation. FCoV also occur in two serotypes, I and II, of which the serotype I viruses are by far the most prevalent in the field. Yet, most of our knowledge about FCoV infections relates to serotype II viruses, particularly about the FIPV, mainly because type I viruses grow poorly in cell culture. Hence, the aim of the present work was the detailed study of the epidemiologically most relevant viruses, the avirulent serotype I viruses. Kittens were inoculated oronasally with different doses of two independent FECV field strains, UCD and RM. Persistent infection could be reproducibly established. The patterns of clinical symptoms, faecal virus shedding and seroconversion were monitored for up to 10 weeks revealing subtle but reproducible differences between the two viruses. Faecal virus, i.e. genomic RNA, was detected during persistent FECV infection only in the large intestine, downstream of the appendix, and could occasionally be observed also in the blood. The implications of our results, particularly our insights into the persistently infected state, are discussed

Testing for Trends in Dose-Response Microarray Experiments: A Comparison of Several Testing Procedures, Multiplicity and Resampling-Based Inference

Dose-response studies are commonly used in experiments in pharmaceutical research in order to investigate the dependence of the response on dose, i.e., a trend of the response level toxicity with respect to dose. In this paper we focus on dose-response experiments within a microarray setting in which several microarrays are available for a sequence of increasing dose levels. A gene is called differentially expressed if there is a monotonic trend (with respect to dose) in the gene expression. We review several testing procedures which can be used in order to test equality among the gene expression means against ordered alternatives with respect to dose, namely Williams' (Williams 1971 and 1972), Marcus' (Marcus 1976), global likelihood ratio test (Bartholomew 1961, Barlow et al. 1972, and Robertson et al. 1988), and M (Hu et al. 2005) statistics. Additionally we introduce a modification to the standard error of the M statistic. We compare the performance of these five test statistics. Moreover, we discuss the issue of one-sided versus two-sided testing procedures. False Discovery Rate (Benjamni and Hochberg 1995, Ge et al. 2003), and resampling-based Familywise Error Rate (Westfall and Young 1993) are used to handle the multiple testing issue. The methods above are applied to a data set with 4 doses (3 arrays per dose) and 16,998 genes. Results on the number of significant genes from each statistic are discussed. A simulation study is conducted to investigate the power of each statistic. A R library IsoGene implementing the methods is available from the first author.

Search for Scalar Diphoton Resonances in the Mass Range 65−60065-600 GeV with the ATLAS Detector in pppp Collision Data at s\sqrt{s} = 8 TeVTeV

A search for scalar particles decaying via narrow resonances into two photons in the mass range 65–600 GeV is performed using $20.3\text{}\text{}{\mathrm{fb}}^{-1}$ of $\sqrt{s}=8\text{}\text{}\mathrm{TeV}$ $pp$ collision data collected with the ATLAS detector at the Large Hadron Collider. The recently discovered Higgs boson is treated as a background. No significant evidence for an additional signal is observed. The results are presented as limits at the 95% confidence level on the production cross section of a scalar boson times branching ratio into two photons, in a fiducial volume where the reconstruction efficiency is approximately independent of the event topology. The upper limits set extend over a considerably wider mass range than previous searches