224 research outputs found
Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus
No full textThe Hey protein family, comprising Hey1, Hey2 and HeyL in mammals, conveys Notch signals in many cell types. The helix-loop-helix (HLH) domain as well as the Orange domain, mediate homo- and heterodimerization of these transcription factors. Although distinct interaction partners have been identified so far, their physiological relevance for Hey functions is still largely unclear. Using a tandem affinity purification approach and mass spectrometry analysis we identified members of an ubiquitin E3-ligase complex consisting of FBXO45, PAM and SKP1 as novel Hey1 associated proteins. There is a direct interaction between Hey1 and FBXO45, whereas FBXO45 is needed to mediate indirect Hey1 binding to SKP1. Expression of Hey1 induces translocation of FBXO45 and PAM into the nucleus. Hey1 is a short-lived protein that is degraded by the proteasome, but there is no evidence for FBXO45-dependent ubiquitination of Hey1. On the contrary, Hey1 mediated nuclear translocation of FBXO45 and its associated ubiquitin ligase complex may extend its spectrum to additional nuclear targets triggering their ubiquitination. This suggests a novel mechanism of action for Hey bHLH factors
Didactics in vocational education & training : A case of diversity and intercepts
No full textIn an earlier contribution (Gesler & Moreno Herrera, 2016) we argued that depending on differences in perspectives and even on language´s differences we are facing a remarkable conceptual diversity of what didactics is about. Furthermore, the debate about conceptualization, in particular in relation to the equivalence in English of what in other languages, specifically Germanic and Latin languages, is termed ‘didactics’, is well documented in the research literature. I do claim that there was, and still there is, a need to transcend the language discussion to focus on content related aspects to advance knowledge and research in this area within the field of Vocational Education & training (VET).This article draws substantially on an earlier contribution by the author (Gessler & Moreno Herrera, 2016) and revisits shortly earlier research on didactics with the intention to highlight transitions and diversity in various approaches. Particular highlighted are the challenges in designing vocational which the authors first presented in an earlier study (Gessler & Moreno Herrera, 2016). Furthermore, it looks into selected contributions from scholars in the VET field with the intention to illustrate and propose discussion about the diversity and intercepts that are visible today. To accomplish these aims the focus is on a few selected cases considered to be illustrative enough. A thorough comparative study of didactics for vocational training in the Nordic countries still remains as a necessary project ahead.</p
Survival in patients with high-risk prostate cancer is predicted by miR-221, which regulates proliferation, apoptosis, and invasion of prostate cancer cells by inhibiting IRF2 and SOCS3
No full textA lack of reliably informative biomarkers to distinguish indolent and lethal prostate cancer is one reason this disease is overtreated. miR-221 has been suggested as a biomarker in high-risk prostate cancer, but there is insufficient evidence of its potential utility. Here we report that miR-221 is an independent predictor for cancer-related death, extending and validating earlier findings. By mechanistic investigations we showed that miR-221 regulates cell growth, invasiveness, and apoptosis in prostate cancer at least partially via STAT1/STAT3-mediated activation of the JAK/STAT signaling pathway. miR-221 directly inhibits the expression of SOCS3 and IRF2, two oncogenes that negatively regulate this signaling pathway. miR-221 expression sensitized prostate cancer cells for IFN-γ-mediated growth inhibition. Our findings suggest that miR-221 offers a novel prognostic biomarker and therapeutic target in high-risk prostate cancer
Downstream Application of Persuasive Design and Usability Engineering Methods to Health Information Platforms
No full textAntibiotic resistance is a global health crisis but careful usage of medicine might reduce the problem. One way to achieve this is to spread resistance and guideline information using eHealth platforms. In this work, downstream application of usability engineering and persuasive design methods were combined to create the Antibiotic Treatment Recommender (ATR), an enhanced version of the eHealth website INFECT. Different design processes were analyzed and combined to ensure both usability and persuasion. A qualitative study was conducted to compare the results. This led to an understanding of the different needs of the target groups. While some users still preferred INFECT, the new ATR website was able to fulfill the requirements, satisfy most users, and offer promising opportunities for additional functionality
Defective autophagy through [i]epg[/i]5 mutation results in failure to reduce germ plasm and mitochondria
No full textAutophagy is an evolutionarily conservedcatabolic process that transports cytoplasmic componentsto lysosomes for degradation. In addition to the canonicalview of strict stress-response–induced autophagy, selectivelyprogrammed autophagy was recently reported in thecontext of gonad development of flies and worms, whereautophagy seems to be necessary for clearance of germplasm components. Similar functions have not been describedin vertebrates. We used the medaka fish to studythe role of autophagy in gonad formation and gametogenesisfor the first time in a vertebrate organism for whichthegermline is specifiedby germplasm.Using a transgenicline deficient in the Ol-epg5 gene—a new critical componentof the autophagy pathway—we show that such deficiencyleads to an impaired autophagic flux, possiblyattributed to compromised maturation or processing ofthe autophagosomes. Ol-epg5 deficiency correlates withselectively impaired spermatogenesis and low allele transmissionrates of the mutant allele caused by failure of germplasm and mitochondria clearance during the process ofgerm cell specification and in the adult gonads. The mouseepg-5 homolog is similarly expressed in the maturating andadult testes, suggesting an at least partially conserved functionof this process during spermatogenesis in vertebrates.—Herpin, A., Englberger, E., Zehner, M.,Wacker, R., Gessler,M., Schartl, M. Defective autophagy through epg5 mutationresults in failure to reduce germ plasm and mitochondria
- …
