Extracellular signal-regulated kinase 5 (ERK5) is required for the Yes-associated protein (YAP) co-transcriptional activity

Yes-associated protein (YAP) is a transcriptional cofactor involved in the regulation of various physio-pathological cellular processes. YAP is the main downstream effector of the tumor-suppressive Hippo pathway. When Hippo signaling is activated, it induces YAP phosphorylation and cytoplasmic sequestration, thus inhibiting its co-transcriptional activity. On the contrary, when Hippo signaling is inhibited, YAP translocates into the nucleus where it drives several transcriptional programs in a cell- and context-dependent manner. However, recent observations indicate that YAP activity can be also modulated by Hippo independent/integrating pathways, still largely unexplored. In this study, we demonstrated the role of the extracellular signal-regulated kinase 5 (ERK5)/mitogen activated protein kinase in the regulation of YAP activity. By means of ERK5 inhibition/silencing and overexpression experiments, and by using as model liver stem cells, hepatocytes, and hepatocellular carcinoma (HCC) cell lines, we provided evidence that ERK5 is required for YAP transcriptional activity. Mechanistically, ERK5 is required for the recruitment of YAP on the promoters of target genes and for its physical interaction with the transcriptional partner TEAD4. Moreover, we observed that ERK5 modulates YAP activation in cell adhesion dynamics, TGFβ-induced EMT of liver cells and cell migration. Furthermore, we demonstrated that ERK5 modulates the activity also of a YAP mutant non-phosphorylatable by LATS1/2, thus providing evidence of its, at least in part, independence from the Hippo pathway. Finally, preliminary results obtained in mice overexpressing YAP in the liver confirmed the relevance of ERK5/YAP axis in vivo and suggested the ERK5 involvement in the YAP-induced liver fibrosis. Therefore, our observations identify ERK5 as a novel upstream regulator of YAP activity, thus unveiling a new target for therapeutic approaches aimed at interfering with its function

Power Tools for Talking: Custom Protocols Enrich Coaching Conversations

The article examines how the use of protocols increased professional learning among a group of reading specialists when Salem State University collaborated with a suburban school district. The objective was to support eight elementary and two middle school reading specialists as they acted as data coaches, helping classroom teachers investigate the implications of literacy data for teaching

Arbëreshë migration in the Sibaritide (Calabria, South Italy):Landscape archaeology, past mobility and present-day community identity

Since the early 1990s, the Groningen Institute of Archaeology has carried out surveys and excavations in the Sibaritide (Calabria, South Italy) with a strong interest in the study of mobility based on changes in material culture and settlement patterns related to Bronze Age Aegean, Greek and Roman presence. In a newly planned archaeological project, the authors aim to open a window on the multicultural interaction in the landscapes of the Sibaritide from the mediaeval to the modern period, particularly related to the arrival and enduring presence of Arbëreshë communities. The project will start out in the summer of 2023 with an archaeological survey of the landscapes surrounding the Arbëreshë villages of Civita/Çifti and Frascineto/Frasnita where the Groningen Institute of Archaeology already conducts excavations of Bronze Age sites. The local Arbëreshë communities will be involved in the project through participatory practices and ethnographic listening. This approach will help us to trace the history of migration and the strong sense of place of the contemporary Arbëreshë people within a shared process of knowledge production. With our new project we hope to support an inclusive long-term narrative of the cultural encounters in the Sibaritide in which the local landscape is valued as heritage conceptualised in archaeological and ethnographic terms, but also in the stories and memories of the local communities

Before the Iron Age:The oldest settlements in the hinterland of the Sibaritide (Calabria, Italy)

Deze dissertatie onderzoekt de bredere context van protohistorisch aardewerk gevonden tijdens onderzoek van het Groninger Instituut voor Archeologie in Noord-Calabrië in het kader van het Raganello Archaeological Project (RAP). Als onderdeel van een regionaal onderzoek naar de nederzettingsdynamiek in de Sibaritide en zijn achterland werd proto-historisch aardewerk gevonden tijdens veldkarteringen in het Raganello vallei en dit werd samen met het aardewerk uit opgravingen op de Timpone della Motta (Francavilla Marittima) onderzocht. Op basis van de gevonden sites en het aardewerk is een voorlopige reconstructie van de territoriale context gemaakt gebruikmakend van een landschapsarcheologische benadering. Het onderzoek begint met een samenvatting van de huidige kennis van pre- en proto-historische sites in de Sibaritide. Uit de literatuur blijkt dat er geringe aanwijzingen zijn voor sites uit de periode tussen het Neolithicum en het begin van de Bronstijd. Dit ondanks het feit dat vanaf Midden Bronstijd 2 een hoog aantal sites verspreid over de heuvelachtige strook rondom de vlakte van Sybaris is gedocumenteerd. Voornamelijk gebaseerd op het onderzoek van Renato Peroni en zijn team, lijkt de ontwikkeling van Midden Bronstijd sites te worden gekarakteriseerd door een lichte afname van sites die georienteerd waren op het heuvelachtige achterland; in de Finale Bronstijd stijgt het aantal sites in de voetheuvels met tegelijkertijd een aanzienlijke groei in de omvang van een aantal grotere sites die strategisch gelegen uitkijken over de vlakte. Peroni is van mening dat de politieke en economische veranderingen de consolidatie van een territoriale organisatie weerspiegelen, die zich verder zou ontwikkelen in de IJzertijd