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Surviving death: emerging concepts of RIPK3 and MLKL ubiquitination in the regulation of necroptosis
(2021)
Lytic forms of programmed cell death, like necroptosis, are characterised by cell rupture and the release of cellular contents, often provoking inflammatory responses. In the recent years, necroptosis has been shown to play important roles in human diseases like cancer, infections and ischaemia/reperfusion injury. Coordinated interactions between RIPK1, RIPK3 and MLKL lead to the formation of a dedicated death complex called the necrosome that triggers MLKL-mediated membrane rupture and necroptotic cell death. Necroptotic cell death is tightly controlled by post-translational modifications, among which especially phosphorylation has been characterised in great detail. Although selective ubiquitination is relatively well-explored in the early initiation stages of necroptosis, the mechanisms and functional consequences of RIPK3 and MLKL ubiquitination for necrosome function and necroptosis are only starting to emerge. This review provides an overview on how site-specific ubiquitination of RIPK3 and MLKL regulates, fine-tunes and reverses the execution of necroptotic cell death.
Unmotivated and unprepared, an Austrian young man leaves his home town Vienna, only to dive into the unknown Romania. He already has images of this country in his mind. He is on his way towards the magical, dark, sparkling Transdanubien, about which he only knows clichés: that Romanians barely have anything to eat, that it is a country of gypsies, that the official language is Russian, that it is an anachronistic country par excellence. With this perspective, his relationship with local Ilina can only fail. This article follows along the lines of a complicated inter-cultural communication.
Looking back, my memories seem like distant, made-up stories. These words of the main character are to be found all over Jan Koneffkes novel. A foreigner on the run, Felix Kannmacher is forced to tell stories in order to survive. He is at the mercy of a teenager who is avid for constantly new and different bedtime stories. Felix gives in, as he has no other choice but to be a slaveto this child. The following article analyses the fine line between the stories Felix invents for Virginia and two narratological aspects: the actual plot of the novel on the one hand, and the actual course of history, on the other. The entire novel is built on stories-within-stories that twist and turn the course of Story and History alike. Because each one of us writes their own (hi)story.
For intercultural language teaching, coaching students on how to perceive the cultural “other” is of crucial importance in order to avoid culturally based misunderstandings. This paper explores how perceiving the other can offer conclusions for perceiving and becoming aware of the self. Through that, a process of giving and taking ensues in which perceptions of the self and of the other are constantly fluctuating depending on the context in which the communication is taking place. At the crossroads between members of two different cultures, a dialogue emerges in which the points of view of both parties are changed. The paper outlines how perception is a construct in which one’s own origin, education, and emotions are blended in. Intercultural learning is the way to deal with this constructs in a flexible manner so as to create new interpretation patterns. It teaches how to sympathize with the other and how to better understand oneself.
Film is a wonderful means of reflecting upon the identity of the self and the other. A movie like Didi Danquart’s Offset (2006), which deals with intercultural conflicts, even more so. The clash of the Romanian and German cultures depicted in this movie illustrates how the construction of identity – of the self and the other – works.
Using literature in culture and civilization classes enables the contact to foreign culture. Literature does not merely copy reality, but has its own rules of story telling, its own way of changing the perspective on reality, of correcting cliches, in omitting something, so as for the reader to become curious and fill in these „gaps”. In this paper, a fragment from a novel shows how a german businessman arriving in interbellic Romania finds that time is measured differently in those two countries.
Prämissen für die Vermittlung interkultureller Kompetenzen im studienbegleitenden DaF-Unterricht
(2014)
Language teaching alone is not sufficient in order to communicate successfully in the foreign language. Even with the acquisition of one’s native language, one does not learn just vocabulary, grammar, reading, writing, speaking and listening. Apart from all that one learns how to identify and to practice cultural patterns. Here, the learning and teaching process is accompanied by another component: intercultural communication and the acquisition of intercultural competences. These teach the lerner to understand first and foremost their own cultural background in order for them to be able to change perspective and look at and understand the cultural background of the target language. Teaching must be centered on the learner, and the foreign language is not taught „in general“, but with regard to the learners’ culture of origin.
Language teaching through the medium of film may prove very rewarding in that it moves the focus away from language and its general markers (grammar, vocabulary) alone and casts it onto culture, cultural boundaries and rules. Among them, space plays a very important role. It defines who we are, where we come from. Especially the fine line between what is considered public or private space is worth being analyzed. With examples from two movies, students of German as a Foreign Language are meant to discover this fine line, look beyond it and restore an equilibrium between the public and the private in order to be prepared for intercultural experiences.
Cosmin, a twelve-year-old Roma boy from Transylvania, only goes to school for a short while. For his mother, it is more important, that he, the only male of a household with many mouths to feed, help her with work. But Cosmin’s teacher does not give up and proposes a bargain: If Cosmin’s mother lets her children go to school, she will get electricity from the school to be able to watch TV. Due to this arrangement, Cosmin returns to school for a few days, becomes a little thief and embarks on a journey that can become an opportunity for him. A kind of a bildungsroman, a coming of age novel focused on the ups and downs between two worlds on Romanian soil, that could not be more different from one another: the Romanian majority and the Roma minority. This article sets out to document life at the brink of society, with all of its facets.
Background: Current prognostic gene signatures for breast cancer mainly reflect proliferation status and have limited value in triple-negative (TNBC) cancers. The identification of prognostic signatures from TNBC cohorts was limited in the past due to small sample sizes.
Methodology/Principal Findings: We assembled all currently publically available TNBC gene expression datasets generated on Affymetrix gene chips. Inter-laboratory variation was minimized by filtering methods for both samples and genes. Supervised analysis was performed to identify prognostic signatures from 394 cases which were subsequently tested on an independent validation cohort (n = 261 cases).
Conclusions/Significance: Using two distinct false discovery rate thresholds, 25% and <3.5%, a larger (n = 264 probesets) and a smaller (n = 26 probesets) prognostic gene sets were identified and used as prognostic predictors. Most of these genes were positively associated with poor prognosis and correlated to metagenes for inflammation and angiogenesis. No correlation to other previously published prognostic signatures (recurrence score, genomic grade index, 70-gene signature, wound response signature, 7-gene immune response module, stroma derived prognostic predictor, and a medullary like signature) was observed. In multivariate analyses in the validation cohort the two signatures showed hazard ratios of 4.03 (95% confidence interval [CI] 1.71–9.48; P = 0.001) and 4.08 (95% CI 1.79–9.28; P = 0.001), respectively. The 10-year event-free survival was 70% for the good risk and 20% for the high risk group. The 26-gene signatures had modest predictive value (AUC = 0.588) to predict response to neoadjuvant chemotherapy, however, the combination of a B-cell metagene with the prognostic signatures increased its response predictive value. We identified a 264-gene prognostic signature for TNBC which is unrelated to previously known prognostic signatures.