Distinct roles of transcription factors EGL-46 and DAF-19 in specifying the functionality of a polycystin-expressing sensory neuron necessary for C. elegans male vulva location behavior

Caenorhabditis elegans polycystins LOV-1 and PKD-2 are expressed in the male-specific HOB neuron, and are necessary for sensation of the hermaphrodite vulva during mating. We demonstrate that male vulva location behavior and expression of lov-1 and pkd-2 in the ciliated sensory neuron HOB require the activities of transcription factor EGL-46 and to some extent also EGL-44. This EGL-46- regulated program is specific to HOB and is distinct from a general ciliogenic pathway functioning in all ciliated neurons. The ciliogenic pathway regulator DAF-19 affects downstream components of the HOB-specific program indirectly and is independent of EGL-46 activity. The sensory function of HOB requires the combined action of these two distinct regulatory pathways

Relevanz ist alles: Algorithmen im Intranet

oai:hup2.journals.sub.uni-hamburg.de:article/578Durch den Einzug elektronischer Verbreitungsmedien in den Alltag spielen einerseits der Ort und die Zeit in der Kommunikation eine kontinuierlich geringere Bedeutung. Mitarbeiter leiden deshalb nicht mehr an Informationsdefiziten, sondern an Informationsüberflutungen. In diesem Beitrag soll dargestellt werden, wie in der Praxis in Intranets durch Algorithmen versucht wird, die Informationsüberflutung einzudämmen. Hierzu wird eine soziologische Herangehensweise gewählt, wobei nicht der Aushandlungsprozess von Algorithmen in den Fokus gerückt wird, sondern die Ideen hinter Algorithmen,und wie diese sich auf organisatorische Strukturen und alltägliche Praktiken auswirken. Die folgenden Bemerkungen basieren auf 27 Experteninterviews, die mit der dokumentarischen Methode ausgewertet wurden. Angereichert werden diese durch eigene Projekterfahrungen der vergangenen 2,5 Jahre, die ich in Unternehmen und öffentlichen Diensteinrichtungen gesammelt habe

Relevanz ist alles: Algorithmen im Intranet

oai:hup2.journals.sub.uni-hamburg.de:article/578Durch den Einzug elektronischer Verbreitungsmedien in den Alltag spielen einerseits der Ort und die Zeit in der Kommunikation eine kontinuierlich geringere Bedeutung. Mitarbeiter leiden deshalb nicht mehr an Informationsdefiziten, sondern an Informationsüberflutungen. In diesem Beitrag soll dargestellt werden, wie in der Praxis in Intranets durch Algorithmen versucht wird, die Informationsüberflutung einzudämmen. Hierzu wird eine soziologische Herangehensweise gewählt, wobei nicht der Aushandlungsprozess von Algorithmen in den Fokus gerückt wird, sondern die Ideen hinter Algorithmen,und wie diese sich auf organisatorische Strukturen und alltägliche Praktiken auswirken. Die folgenden Bemerkungen basieren auf 27 Experteninterviews, die mit der dokumentarischen Methode ausgewertet wurden. Angereichert werden diese durch eigene Projekterfahrungen der vergangenen 2,5 Jahre, die ich in Unternehmen und öffentlichen Diensteinrichtungen gesammelt habe

Targeting class I histone deacetylases by the novel small molecule inhibitor 4SC-202 blocks oncogenic hedgehog-GLI signaling and overcomes smoothened inhibitor resistance

Aberrant activation of Hedgehog (HH)/GLI signaling is causally involved in numerous human malignancies, including basal cell carcinoma (BCC) and medulloblastoma. HH pathway antagonists targeting smoothened (SMO), an essential effector of canonical HH/GLI signaling, show significant clinical success in BCC patients and have recently been approved for the treatment of advanced and metastatic BCC. However, rapid and frequent development of drug resistance to SMO inhibitors (SMOi) together with severe side effects caused by prolonged SMOi treatment call for alternative treatment strategies targeting HH/GLI signaling downstream of SMO. In this study, we report that 4SC-202, a novel clinically validated inhibitor of class I histone deacetylases (HDACs), efficiently blocks HH/GLI signaling. Notably, 4SC-202 treatment abrogates GLI activation and HH target gene expression in both SMOi-sensitive and -resistant cells. Mechanistically, we propose that the inhibition of HDACs 1/2/3 is crucial for targeting oncogenic HH/GLI signaling, and that class I HDAC inhibitors either in combination with SMOi or as second-line therapy may improve the treatment options for HH-associated malignancies with SMOi resistance

Targeting class I histone deacetylases by the novel small molecule inhibitor 4SC-202 blocks oncogenic hedgehog-GLI signaling and overcomes smoothened inhibitor resistance

Aberrant activation of Hedgehog (HH)/GLI signaling is causally involved in numerous human malignancies, including basal cell carcinoma (BCC) and medulloblastoma. HH pathway antagonists targeting smoothened (SMO), an essential effector of canonical HH/GLI signaling, show significant clinical success in BCC patients and have recently been approved for the treatment of advanced and metastatic BCC. However, rapid and frequent development of drug resistance to SMO inhibitors (SMOi) together with severe side effects caused by prolonged SMOi treatment call for alternative treatment strategies targeting HH/GLI signaling downstream of SMO. In this study, we report that 4SC-202, a novel clinically validated inhibitor of class I histone deacetylases (HDACs), efficiently blocks HH/GLI signaling. Notably, 4SC-202 treatment abrogates GLI activation and HH target gene expression in both SMOi-sensitive and -resistant cells. Mechanistically, we propose that the inhibition of HDACs 1/2/3 is crucial for targeting oncogenic HH/GLI signaling, and that class I HDAC inhibitors either in combination with SMOi or as second-line therapy may improve the treatment options for HH-associated malignancies with SMOi resistance

Sea level rise and South Florida coastal forests

Coastal ecosystems lie at the forefront of sea level rise. We posit that before the onset of actual inundation, sea level rise will influence the species composition of coastal hardwood hammocks and buttonwood (Conocarpus erectus L.) forests of the Everglades National Park based on tolerance to drought and salinity. Precipitation is the major water source in coastal hammocks and is stored in the soil vadose zone, but vadose water will diminish with the rising water table as a consequence of sea level rise, thereby subjecting plants to salt water stress. A model is used to demonstrate that the constraining effect of salinity on transpiration limits the distribution of freshwater-dependent communities. Field data collected in hardwood hammocks and coastal buttonwood forests over 11 years show that halophytes have replaced glycophytes. We establish that sea level rise threatens 21 rare coastal species in Everglades National Park and estimate the relative risk to each species using basic life history and population traits. We review salinity conditions in the estuarine region over 1999–2009 and associate wide variability in the extent of the annual seawater intrusion to variation in freshwater inflows and precipitation. We also examine species composition in coastal and inland hammocks in connection with distance from the coast, depth to water table, and groundwater salinity. Though this study focuses on coastal forests and rare species of South Florida, it has implications for coastal forests threatened by saltwater intrusion across the globe