70 research outputs found

    Ein Jahr GUdig! Von digitaler Lernwerkstattarbeit, Teamarbeit und interaktiven Gamebooks

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    Linda Hammann und Christiane van Hoof legen in ihrer Hochschullernwerkstatt „Geschichtsunterricht digital“ (GUdig) den Fokus auf Digitalität in Geschichtsvermittlung und Geschichtsdidaktik. In ihrem Beitrag stellen sie das Konzept und Angebot der Hochschullernwerkstatt vor, geben einen Erfahrungsbericht aus dem ersten Jahr von GUdig und fokussieren dabei vor allem die Entwicklung digitalisierungsbezogener Kompetenzen bei den Lehramtsstudierenden. Ein besonderer Schwerpunkt liegt dabei auf der „digitalen Lernwerkstattarbeit“ und der Beschreibung der Kommunikations- und Interaktionsprozesse im digitalen Angebot von GUdig. (DIPF/Orig.

    The role of deadenylation in the degradation of unstable mRNAs in trypanosomes

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    Removal of the poly(A) tail is the first step in the degradation of many eukaryotic mRNAs. In metazoans and yeast, the Ccr4/Caf1/Not complex has the predominant deadenylase activity, while the Pan2/Pan3 complex may trim poly(A) tails to the correct size, or initiate deadenylation. In trypanosomes, turnover of several constitutively-expressed or long-lived mRNAs is not affected by depletion of the 5′–3′ exoribonuclease XRNA, but is almost completely inhibited by depletion of the deadenylase CAF1. In contrast, two highly unstable mRNAs, encoding EP procyclin and a phosphoglycerate kinase, PGKB, accumulate when XRNA levels are reduced. We here show that degradation of EP mRNA was partially inhibited after CAF1 depletion. RNAi-targeting trypanosome PAN2 had a mild effect on global deadenylation, and on degradation of a few mRNAs including EP. By amplifying and sequencing degradation intermediates, we demonstrated that a reduction in XRNA had no effect on degradation of a stable mRNA encoding a ribosomal protein, but caused accumulation of EP mRNA fragments that had lost substantial portions of the 5′ and 3′ ends. The results support a model in which trypanosome mRNAs can be degraded by at least two different, partially independent, cytoplasmic degradation pathways attacking both ends of the mRNA

    A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia

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    The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

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    X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

    PP2A: the expected tumor suppressor

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    PP2A is one of the few serine/threonine-specific phosphatases in the cell, and its complex structure and regulation guarantees its many different functions. Some viruses have chosen to target this enzyme system in order to manage the host cell machinery for their own profit and to program cells into a malignant state. Suppression of PR61/B'gamma, a specific third regulatory subunit of PP2A, can substitute for the viral SV40 protein small t antigen in causing tumorigenic transformation of several human cell lines -- provided that telomerase, SV40 large T antigen and oncogenic Ras are also present. Accumulation of c-Myc seems to be the common denominator.status: publishe

    PTPA regulating PP2A as a dual specificity phosphatase

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    Governing Risks of Multi-Use: Seaweed Aquaculture at Offshore Wind Farms

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    Spatial claims concerning the rapidly growing European offshore wind sector give rise to various ideas for the multi-use application of wind farms. Seaweed is considered a promising feedstock for food and feed that could be produced at offshore wind farms. Concerns about risks resulting in liability claims and insurance premiums are often seen as show-stoppers to multi-use at offshore wind farms. In this study, key environmental risks of seaweed cultivation at offshore wind farms, identified through literature review, are characterized based on stakeholder consultation. The current approach to risk governance is evaluated to assess how it can handle the uncertain, complex, and/or ambiguous risks of multi-use. It is concluded that current risk governance for multi-use is poorly equipped to deal with the systemic nature of risks. Risk governance should be a joint effort of governments and private regulators. It can improve if it is based on an adaptive framework for risk assessment that can deal with complex, systemic risks. Furthermore, it should be flexible and inclusive, i.e., open to new incoming information and stakeholder input, and taking into account and communicate about the different stakes and values of the various parties involved. The importance of communication and inclusion must be recognized, which promotes participation of concerned stakeholders.</p
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