Tristetraprolin Regulation of MyoD mRNA Stability Commits Quiescent Adult Muscle Stem Cells to Myogenesis

In animals, tissue maintenance, plasticity and repair rely on adult stem cells which have been identified in nearly all tissues. Many adult stem cells are typically quiescent and only activate when required for maintenance and repair of adult tissues. Within hours of activation skeletal muscle stem cells called satellite cells begin to express MyoD, a muscle-specific transcription factor that functions as a master regulator, committing satellite cells to myogenesis. The earliest detectable event in satellite cells following muscle injury is phosphorylation of p38α/β MAPKs, which is required for MyoD induction and cell-cycle entry. Loss of Syndecan-4, a component of the satellite cell niche disrupts p38α/β MAPK activation and severely delays MyoD induction. We performed a microarray gene chip experiment to identify genes expressed during satellite cell activation. We identified differentially expressed genes by subtracting genes changing in Sdc4-/- satellite cells from those changing in WT satellite cells following 12h of muscle injury. Unexpectedly, we observed that 70% of RNA-binding proteins (RNA-BPs) decreased in activated satellite cells. Expression levels of the Tristetraprolin (TTP) family of RNA-BPs declined dramatically as satellite cells activated. The TTP family is known to direct mRNA decay and we identified the 3‘UTR of MyoD as a direct TTP target. Furthermore, p38α/β MAPK signaling inhibits TTP-mediated mRNA decay in satellite cells. HuR, an RNA-BP that is induced during satellite cell activation is known to stabilize MyoD mRNA. The coordinate inhibition of TTP and induction of HuR may together function as a feed-forward loop to commit satellite cells to myogenesis by rapid induction of MyoD. A similar feed-forward circuit could operate in other stem cell systems, implicating that post-transcriptional regulation of mRNA could play a major role in regulating adult stem cells to maintain and repair adult tissues

Post-transcriptional regulation of satellite cell quiescence by TTP-mediated mRNA decay.

Skeletal muscle satellite cells in their niche are quiescent and upon muscle injury, exit quiescence, proliferate to repair muscle tissue, and self-renew to replenish the satellite cell population. To understand the mechanisms involved in maintaining satellite cell quiescence, we identified gene transcripts that were differentially expressed during satellite cell activation following muscle injury. Transcripts encoding RNA binding proteins were among the most significantly changed and included the mRNA decay factor Tristetraprolin. Tristetraprolin promotes the decay of MyoD mRNA, which encodes a transcriptional regulator of myogenic commitment, via binding to the MyoD mRNA 3' untranslated region. Upon satellite cell activation, p38α/β MAPK phosphorylates MAPKAP2 and inactivates Tristetraprolin, stabilizing MyoD mRNA. Satellite cell specific knockdown of Tristetraprolin precociously activates satellite cells in vivo, enabling MyoD accumulation, differentiation and cell fusion into myofibers. Regulation of mRNAs by Tristetraprolin appears to function as one of several critical post-transcriptional regulatory mechanisms controlling satellite cell homeostasis

Effects of environmental pollutants on the reproduction and welfare of ruminants

Anthropogenic pollutants comprise a wide range of synthetic organic compounds and heavy metals, which are dispersed throughout the environment, usually at low concentrations. Exposure of ruminants, as for all other animals, is unavoidable and while the levels of exposure to most chemicals are usually too low to induce any physiological effects, combinations of pollutants can act additively or synergistically to perturb multiple physiological systems at all ages but particularly in the developing foetus. In sheep, organs affected by pollutant exposure include the ovary, testis, hypothalamus and pituitary gland and bone. Reported effects of exposure include changes in organ weight and gross structure, histology and gene and protein expression but these changes are not reflected in changes in reproductive performance under the conditions tested. These results illustrate the complexity of the effects of endocrine disrupting compounds on the reproductive axis, which make it difficult to extrapolate between, or even within, species. Effects of pollutant exposure on the thyroid gland, immune, cardiovascular and obesogenic systems have not been shown explicitly, in ruminants, but work on other species suggests that these systems can also be perturbed. It is concluded that exposure to a mixture of anthropogenic pollutants has significant effects on a wide variety of physiological systems, including the reproductive system. Although this physiological insult has not yet been shown to lead to a reduction in ruminant gross performance, there are already reports indicating that anthropogenic pollutant exposure can compromise several physiological systems and may pose a significant threat to both reproductive performance and welfare in the longer term. At present, many potential mechanisms of action for individual chemicals have been identified but knowledge of factors affecting the rate of tissue exposure and of the effects of combinations of chemicals on physiological systems is poor. Nevertheless, both are vital for the identification of risks to animal productivity and welfare

Landwirthschaftliche Skizzen, auf einem Ausfluge nach Belgien, (England) und Holland gesammelt

von O. Hausbur

Die Familie Hausburg-Lütken und deren Seitenverwandte

Richard Hausbur

Teaching with Intention: Using WOOP to Support Social-Emotional Learning in the Classroom

American society and schools are increasingly recognizing the importance of tending to children’s social-emotional learning (SEL). According to social learning theory, one way children learn social-emotional skills, knowledge, and mindsets is by observing others—including their teachers. It is thus important that teachers model the same social-emotional practices that they hope to cultivate in students. This qualitative action research study explores how one psychological strategy—namely, intention-setting—can support teachers’ social-emotional development. As part of a multi-day, online professional development (PD) program, 28 teacher-participants used the WOOP (Wish-Outcome-Obstacle-Plan) framework to set intentions around their SEL goals, journaled about, and reflected on their experience. Three caselets tell the story of what this process looked like for three different teachers. Using a combination of inductive, deductive, and collaborative coding techniques, this study then zooms in on the intention-setting phase to take a close look at teachers’ SEL goals, and the reflection phase to see what teachers reported learning and feeling as they worked towards those goals. Finally, it looks across the entire intention-setting, enacting, and reflection process to illuminate the challenges and supports that participants encountered along the way. This analysis reveals that teachers face a wide range of social-emotional challenges in their classrooms and schools, and have an equally wide range of SEL goals; using WOOP to set and plan for these goals can lead to many (though not exclusively) positive learning and emotional outcomes; and the intention-setting process can be difficult, though doing it with others can help. These findings and their implications speak to education researchers and applied psychologists interested in if and how intentionality supports social-emotional learning and teaching; as well as teacher educators, PD providers, and perhaps most importantly, teachers looking for ways to support healthy SEL