P99Nrg1beta enhances glucose uptake in cardiomyocytes via mTOR, Src and Akt

Background: Neuregulin (Nrg)1β is a growth factor that activates PI3K/Akt and Src/FAK via the ErbB2/ErbB4receptors. Although it is currently in clinical trial to treat haert failure, itremains unclear which cellular mechanisms are responsible for its cardioprotective actions. Here we tested if Nrg1β regulates glucose uptake in cardiomyocytes and analyzed the underlying signaling mechanisms. Methods: Neonatal rat ventricular myocytes were treated with Nrg1β (10ng/ml) in combination with the mTOR inhibitors PP242 (2mM) and rapamycin (20ng/ml), the ErbB2 inhibitor lapatinib (1mM), the Src inhibitor PP2 (5mM), the Akt inhibitor VIII (20mM), or vehicle. Cells were pre-incubated for 30 min with the inhibitors and proteins extracted 30 min after the addition of Nrg1β for analysis by Western blot. Glucose uptake was assessed by measuring the incorporation of 3H-D-glucose for 30 min. ErbB2 or ErbB4 receptors were knocked down withsiRNAfor 48h before Nrg1β treatment. Results: Similar to IGF-I and Insulin, Nrg1β caused a 1.9 fold increase in 3H-D-glucose incorporation (P< 0.01).Nrg1β induced phosphorylation of mTOR (S2448), Akt (S308) and FAK (Y861), as well as of the mTORC1 targets 4E-BP1, p70-S6K1 and ULK and the mTORC2 target Akt (S473). Lapatinib, PP242 and Akt inhibitor VIII blocked the Nrg1β-induced Akt-, mTOR-, p70-S6K1-, ULK-, and 4E-BP1-phosphorylation, indicating that these effects require ErbB2 and are mediated by Akt and mTOR. However, only lapatinib and Akt inhibitor VIII fully blocked the Nrg1β-induced glucose uptake; PP242 partially blocked it and rapamycin did not block it at all. These results suggest that Akt is required for Nrg1β-induced glucose uptake, and that mTORC2-dependent Akt phosphorylation mediates, at least in part, this response. PP2 blocked phosphorylation of FAK as expected, and it also partially blocked phosphorylation of Akt (S473) and p70-S6K1. PP2 also decreased general glucose uptake (0.6-fold of Ctl, p<0.05) and Nrg1β-induced glucose uptake (1.06-fold of Ctl, p=ns). Knock-down of ErbB4 receptor alone was sufficient to decrease both mTORC1 and mTORC2 signaling, whereas knock-down of ErbB2 affected only the mTORC2 targets. Conclusions: Our results show that Nrg1β increases glucose uptake in cardiomyocytes via Akt. We also show that Nrg1β activates mTORC1 via ErbB4 and mTORC2 via the ErbB2/ErbB4 heterodimer. Our data also support the hypothesis that Src/FAK is upstream of mTORC2 and mediates the Nrg1β-induced phosphorylation of Akt and glucose uptak

Explicit and implicit own’s body and space perception in painful musculoskeletal disorders and rheumatic diseases: a systematic scoping review

Background: Pain and body perception are essentially two subjective mutually influencing experiences. However, in the field of musculoskeletal disorders and rheumatic diseases we lack of a comprehensive knowledge about the relationship between body perception dysfunctions and pain or disability. We systematically mapped the literature published about the topics of: a) somatoperception; b) body ownership; and c) perception of space, analysing the relationship with pain and disability. The results were organized around the two main topics of the assessment and treatment of perceptual dysfunctions. Methods: This scoping review followed the six-stage methodology suggested by Arksey and O’Malley. Ten electronic databases and grey literature were systematically searched. The PRISMA Extension for Scoping Reviews was used for reporting results. Two reviewers with different background, independently performed study screening and selection, and one author performed data extraction, that was checked by a second reviewer. Results: Thirty-seven studies fulfilled the eligibility criteria. The majority of studies (68%) concerned the assessment methodology, and the remaining 32% investigated the effects of therapeutic interventions. Research designs, methodologies adopted, and settings varied considerably across studies. Evidence of distorted body experience were found mainly for explicit somatoperception, especially in studies adopting self-administered questionnaire and subjective measures, highlighting in some cases the presence of sub-groups with different perceptual features. Almost half of the intervention studies (42%) provided therapeutic approaches combining more than one perceptual task, or sensory-motor tasks together with perceptual strategies, thus it was difficult to estimate the relative effectiveness of each single therapeutic component. Conclusions: To our knowledge, this is the first attempt to systematically map and summarize this research area in the field of musculoskeletal disorders and rheumatic diseases. Although methodological limitations limit the validity of the evidence obtained, some strategies of assessment tested and therapeutic strategies proposed represent useful starting points for future research. This review highlights preliminary evidence, strengths, and limitations of the literature published about the research questions, identifying key points that remain opened to be addressed, and make suggestions for future research studies. Body representation, as well as pain perception and treatment, can be better understood if an enlarged perspective including body and space perception is considered

Explicit and implicit own’s body and space perception in painful musculoskeletal disorders and rheumatic diseases: a systematic scoping review

Background: Pain and body perception are essentially two subjective mutually influencing experiences. However, in the field of musculoskeletal disorders and rheumatic diseases we lack of a comprehensive knowledge about the relationship between body perception dysfunctions and pain or disability. We systematically mapped the literature published about the topics of: a) somatoperception; b) body ownership; and c) perception of space, analysing the relationship with pain and disability. The results were organized around the two main topics of the assessment and treatment of perceptual dysfunctions. Methods: This scoping review followed the six-stage methodology suggested by Arksey and O’Malley. Ten electronic databases and grey literature were systematically searched. The PRISMA Extension for Scoping Reviews was used for reporting results. Two reviewers with different background, independently performed study screening and selection, and one author performed data extraction, that was checked by a second reviewer. Results: Thirty-seven studies fulfilled the eligibility criteria. The majority of studies (68%) concerned the assessment methodology, and the remaining 32% investigated the effects of therapeutic interventions. Research designs, methodologies adopted, and settings varied considerably across studies. Evidence of distorted body experience were found mainly for explicit somatoperception, especially in studies adopting self-administered questionnaire and subjective measures, highlighting in some cases the presence of sub-groups with different perceptual features. Almost half of the intervention studies (42%) provided therapeutic approaches combining more than one perceptual task, or sensory-motor tasks together with perceptual strategies, thus it was difficult to estimate the relative effectiveness of each single therapeutic component. Conclusions: To our knowledge, this is the first attempt to systematically map and summarize this research area in the field of musculoskeletal disorders and rheumatic diseases. Although methodological limitations limit the validity of the evidence obtained, some strategies of assessment tested and therapeutic strategies proposed represent useful starting points for future research. This review highlights preliminary evidence, strengths, and limitations of the literature published about the research questions, identifying key points that remain opened to be addressed, and make suggestions for future research studies. Body representation, as well as pain perception and treatment, can be better understood if an enlarged perspective including body and space perception is considered

Look Who’s Talking:Using creative, playful arts-based methods in research with young children

Young children are often ignored or marginalised in the drive to address children’s participation and their wider set of rights. This is the case generally in social research, as well as within the field of Arts-Based Education Research. This article contributes to the growing literature on young children’s involvement in arts-based research, by providing a reflective account of our learning and playful engagement with children using creative methods. This small pilot project forms part of a larger international project titled Look Who’s Talking: Eliciting the Voices of Children from Birth to Seven, led by Professor Kate Wall at the University of Strathclyde. Visiting one nursery in Scotland, we worked with approximately 30 children from 3 to 5 years old. Seeking to connect with their play-based nursery experiences, we invited children to participate in a range of arts-based activities including drawing, craft-making, sculpting, a themed ‘play basket’ with various props, puppetry and videography. In this article, we develop reflective, analytical stories of our successes and dilemmas in the project. We were keen to establish ways of working with children that centred their own creativity and play, shaped by the materials we provided but not directed by us. However, we struggled to balance our own agenda with the more open-ended methods we had used. We argue that an intergenerational approach to eliciting voice with young children – in which adults are not afraid to shape the agenda, but do so in responsive, gradual and sensitive ways – creates the potential for a more inclusive experience for children that also meets researcher needs

Disruption of a GATA4/Ankrd1 Signaling Axis in Cardiomyocytes Leads to Sarcomere Disarray: Implications for Anthracycline Cardiomyopathy

Doxorubicin (Adriamycin) is an effective anti-cancer drug, but its clinical usage is limited by a dose-dependent cardiotoxicity characterized by widespread sarcomere disarray and loss of myofilaments. Cardiac ankyrin repeat protein (CARP, ANKRD1) is a transcriptional regulatory protein that is extremely susceptible to doxorubicin; however, the mechanism(s) of doxorubicin-induced CARP depletion and its specific role in cardiomyocytes have not been completely defined. We report that doxorubicin treatment in cardiomyocytes resulted in inhibition of CARP transcription, depletion of CARP protein levels, inhibition of myofilament gene transcription, and marked sarcomere disarray. Knockdown of CARP with small interfering RNA (siRNA) similarly inhibited myofilament gene transcription and disrupted cardiomyocyte sarcomere structure. Adenoviral overexpression of CARP, however, was unable to rescue the doxorubicin-induced sarcomere disarray phenotype. Doxorubicin also induced depletion of the cardiac transcription factor GATA4 in cardiomyocytes. CARP expression is regulated in part by GATA4, prompting us to examine the relationship between GATA4 and CARP in cardiomyocytes. We show in co-transfection experiments that GATA4 operates upstream of CARP by activating the proximal CARP promoter. GATA4-siRNA knockdown in cardiomyocytes inhibited CARP expression and myofilament gene transcription, and induced extensive sarcomere disarray. Adenoviral overexpression of GATA4 (AdV-GATA4) in cardiomyocytes prior to doxorubicin exposure maintained GATA4 levels, modestly restored CARP levels, and attenuated sarcomere disarray. Interestingly, siRNA-mediated depletion of CARP completely abolished the Adv-GATA4 rescue of the doxorubicin-induced sarcomere phenotype. These data demonstrate co-dependent roles for GATA4 and CARP in regulating sarcomere gene expression and maintaining sarcomeric organization in cardiomyocytes in culture. The data further suggests that concurrent depletion of GATA4 and CARP in cardiomyocytes by doxorubicin contributes in large part to myofibrillar disarray and the overall pathophysiology of anthracycline cardiomyopathy

Tre sassolini, ovvero il peso dell’esperienza: La valutazione sommativa, formativa e l’autovalutazione all’interno della pratica didattica

The didactic formula of formation tries to contain methods, perspectives, places, tools and concepts of and for formation which, although sometimes traditionally, disciplinarily and historically disjointed, are united by a strong and virtuous attention to the person. Or rather, it is a formula that contains the various meanings within which an innate intentionality is allocated to enhance and support the flowering of the individual through training. The volume tries to collect all this by proposing an articulation of the various declinations of the didactic formula of training and drawing on the testimony of a figure who has been able to demonstrate the value of teaching, Prof. Giuseppe Tacconi. In fact, to animate the volume, it is precisely the testimony of a human, critical and reflective approach, that is, what can be read in the words of the authors of the contributions in their advancement of scientific proposals, drawing on the memory of Tacconi, trainer, researcher, friend, colleague and teacher. Per una didattica della formazione is a single volume that collects scientific contributions from different disciplinary backgrounds (e.g. pedagogy, sociology, psychology, philosophy) and that is used by students, professionals, practitioners, scholars and scholars, with the aim of intellectually stimulating a true human, critical and reflective approach to training and having concrete tools to support this approach

Teaching as Dance. An Ethnographic Pathway for studies on Teaching

Contextualise, identify, and describe the characteristics of the teacher’s professional practice is not easy. Recent researches on work and the influence of the concept of practice have contributed to the budding of studies aimed at explaining aspects of the work and at clarifying its features compared to the knowledge and know-how. In the Practice Theory perspective, and considering the work as a performance, this article reports the results of a field study. The present paper draws attention to a particular category of analysis, the dance that not only emphasizes the role of the body and of movement, instead proposes a reading of the work as a practical and situated activity