Kinetics of PKC epsilon Activating and Inhibiting Llama Single Chain Antibodies and Their Effect on PKC epsilon Translocation in HeLa Cells

Peer reviewe

Metabolic characterization of the natural progression of chronic hepatitis B

Background: Worldwide, over 350 million people are chronically infected with the hepatitis B virus (HBV) and are at increased risk of developing progressive liver diseases. The confinement of HBV replication to the liver, which also acts as the central hub for metabolic and nutritional regulation, emphasizes the interlinked nature of host metabolism and the disease. Still, the metabolic processes operational during the distinct clinical phases of a chronic HBV infection-immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis phases-remains unexplored. Methods: To investigate this, we conducted a targeted metabolomics approach on serum to determine the metabolic progression over the clinical phases of chronic HBV infection, using patient samples grouped based on their HBV DNA, alanine aminotransferase, and HBeAg serum levels. Results: Our data illustrate the strength of metabolomics to provide insight into the metabolic dysregulation experienced during chronic HBV. The immune tolerant phase is characterized by the speculated viral hijacking of the glycerol-3-phosphate-NADH shuttle, explaining the reduced glycerophospholipid and increased plasmalogen species, indicating a strong link to HBV replication. The persisting impairment of the choline glycerophospholipids, even during the inactive carrier phase with minimal HBV activity, alludes to possible metabolic imprinting effects. The progression of chronic HBV is associated with increased concentrations of very long chain triglycerides together with citrulline and ornithine, reflective of a dysregulated urea cycle peaking in the HBV envelope antigen-negative phase. Conclusions: The work presented here will aid in future studies to (i) validate and understand the implication of these metabolic changes using a thorough systems biology approach, (ii) monitor and predict disease severity, as well as (iii) determine the therapeutic value of the glycerol-3-phosphate-NADH shuttle

Ansätze für eine Neue Normalarbeitszeit: Ein Diskussionsbeitrag

Die aktuelle Regulierung von Arbeitszeiten schafft Anreize für belastende Zeiten und berücksichtigt nur unzureichend wissenschaftliche Erkenntnisse zu den Auswirkungen dieser Belastungen. Dieser Beitrag stellt einen neuen Ansatz vor: Ausgehend von einer einerseits weit verbreiteten und andererseits auch sozial- und gesundheitspolitisch wünschenswerten ‚Neuen Normalarbeitszeit‘, nämlich der Gleitzeit von Montag bis Freitag tagsüber, sollen abweichende Ar-beitszeiten hinsichtlich ihrer Belastung bewertet werden. Eine angemessene Kompensation in zusätzlicher Freizeit statt finanzieller Zulagen soll dann diese Belastung ausgleichen statt sie finanziell abzugelten. Damit würden auch bestehende Anreize für ein freiwilliges Verbleiben in belastenden Arbeitszeiten reduziert

Ansätze für eine "neue Normalarbeitszeit": ein Diskussionsbeitrag

Auf Basis von vorhandenen empirischen Untersuchungen, einschlägigen Dokumenten und Interviews mit Expertinnen und Experten werden die Beschäftigungs- und Arbeitsbedingungen in der Pflege und Betreuung mit Fokus auf Langzeitpflege beschrieben. Dabei geht es insbesondere um die Beschäftigungs- und Branchenbedingungen in der stationären sowie mobilen Pflege und Betreuung, die Einkommenssituation, die Arbeitsbedingungen und Belastungen sowie um Ausweichstrategien der Beschäftigten (Arbeitsplatzwechsel und Unterbrechungen, Berufsausstieg und Pensionszugang). Die wesentlichsten Ergebnisse sind: Schwere körperliche Arbeit, hohe emotionale Belastungen und geringe Entlohnung sind wesentliche Kennzeichen, wobei die Anforderungen kontinuierlich zunehmen. Teilzeitarbeit und Berufsunterbrechungen - auch in Form von Arbeitslosigkeit - sind Teil der Erwerbsbiografie, um den enormen Belastungen über Jahre standzuhalten. Diese individuellen Ausweichstrategien gehen aber zulasten der Erwerbseinkommen und Transferleistungen der vornehmlich weiblichen Pflege- und Betreuungskräfte.We discuss why current working hour regulations incentivize strenuous working times, not sufficiently recognizing scientific results regarding the effects of these stress factors. We introduce a new concept: To assess the stress and strain due to working hours by comparing it to a reference "new normal working time", which is flexitime from Monday to Friday during daytime. We present suggestions on how to assess working hours this way and how to compensate for strenuous working hours by giving additional work-free time instead of financial compensation. The most important results are: Development of the concept of "new normal working time"; Suggestion on the assessment of working hours based on the stress and strain they produce; Discussion of upper stress and strain limits, and practical implications

Attachment of HeLa cells during early G1 phase

Both growth factor directed and integrin dependent signal transduction were shown to take place directly after completion of mitosis. The local activation of these signal transduction cascades was investigated in early G1 cells. Interestingly, various key signal transduction proteins were found in blebs at the cell membrane within 30 min after mitosis. These membrane blebs appeared in round, mitotic-like cells and disappeared rapidly during spreading of the cells in G1 phase. In addition to tyrosine-phosphorylated proteins, the blebs contained also phosphorylated FAK and phosphorylated MAP kinase. The formation of membrane blebs in round, mitotic cells before cell spreading is not specific for mitotic cells, because similar features were observed in trypsinized cells. Just before cell spreading also these cells exhibited membrane blebs containing active signal transduction proteins. Inhibition of signal transduction did not affect membrane bleb formation, suggesting that the membrane blebs were formed independent of signal transduction

Novel role of cPLA2α in membrane and actin dynamics

Actin-directed processes such as membrane ruffling and cell migration are regulated by specific signal transduction pathways that become activated by growth factor receptors. The same signaling pathways that lead to modifications in actin dynamics also activate cPLA2α. Moreover, arachidonic acid, the product of cPLA2α activity, is involved in regulation of actin dynamics. Therefore, it was investigated whether cPLA2α plays a role in actin dynamics, more specifically during growth factor-induced membrane ruffling and cell migration. Upon stimulation of ruffling and cell migration by growth factors, endogenous cPLA2α and its active phosphorylated form were shown to relocate at protrusions of the cell membrane involved in actin and membrane dynamics. Inhibition of cPLA2α activity with specific inhibitors blocked growth factor-induced membrane and actin dynamics, suggesting an important role for cPLA2α in these processes