Identification of the Thyroid Transcription Factor-1 as a Target for Rat MST2 Kinase

Abstract Thyroid transcription factor-1 (TTF-1) is a homeodomain-containing transcription factor that is required for thyroid-specific expression of the thyroglobulin and thyroperoxidase genes as well as for lung-specific expression of the surfactant protein A, B, and C and the CC10 and the HNF-3α genes. TTF-1 is a phosphoprotein, and the phosphorylation of TTF-1 has been studied already. However, the kinase(s) that could be responsible for this phosphorylation have not been known. In this paper we report the identification by in-gel kinase assay of a 56-kDa serine/threonine kinase that is able to phosphorylate TTF-1 in thyroid cells. The cloning of this kinase revealed that we had identified the rat homolog of the human MST2 kinase. The pathway in which human MST2 functions is not known; however, it does not appear to involve either mitogen-activated protein kinases such as Erk1 and Erk2 nor the stress-activated protein kinases such as JNK and p38. We show that the activity responsible for TTF-1 phosphorylation is constitutive in thyroid cells. Furthermore, we demonstrate that TTF-1 is phosphorylatedin vivo by rMST2 at the same residues that had been identified previously as the major phosphorylation sites. Thus, TTF-1 represents the first identified target of this class of protein kinases

Transcriptional control of the forkhead thyroid transcription factor TTF-2 by thyrotropin, insulin, and insulin-like growth factor I

The hormonal regulation of both thyroglobulin and thyroperoxidase promoter activity in FRTL-5 thyroid cells takes place, at least in part, through a hormone-responsive element to which the thyroid transcription factor TTF-2 binds. The TTF-2 cDNA, encoded by the titf2 locus, has recently been cloned and classified as a member of the forkhead transcription factor family. Here, we demonstrate that TTF-2 mRNA levels become undetectable in FRTL-5 thyroid cells cultured for 4 days in 0.2% serum and in the absent of thyrotropin (TSH) and insulin. Addition of TSH, insulin or insulin-like growth factor I (IGF-I) to the culture medium increases the levels of this transcription factor in a dose- and time-dependent manner and requires ongoing protein synthesis. The TSH effect is greater than that produced by insulin or IGF-I and is similar to the effect produced by the cAMP analog forskolin. The TSH and insulin effects are additive. In all cases, the mRNA levels increase is accompanied by an increase in transcription rate, as demonstrated by run-off assays. These data demonstrate that the TTF-2 mRNA is under tight hormonal control. This is consistent with an important role for TTF-2 as a mediator of the transcriptional activation of thyroid-specific genes (thyroglobulin and thyroperoxidase) by TSH via cAMP and by insulin through the IGF-I receptor

I processi incorpati di costruzione della conoscenza nelle pratiche di cura

In ambito educativo, il corpo \ue8 stato tradizionalmente marginalizzato o rifiutato come fonte di conoscenza. Negli ultimi decenni, la letteratura pedagogica ha manifestato crescente interesse per il ruolo che ha il corpo dell\u2019insegnante, nel pianificare e realizzare l\u2019insegnamento, sfidando le ideologie e le epistemologie dominanti, secondo le quali la nostra mente \ue8 la fonte primaria di apprendimento. Al contrario, una pedagogia della conoscenza incorpata (embodiment) considera il corpo centrale nel nostro conoscere (le pratiche d\u2019insegnamento) e nel nostro essere (insegnanti). Analogamente, la letteratura delle professioni del caring si \ue8 rivelata molto attenta ai temi della conoscenza incorpata, ossia di quel sapere che \ue8 presente in un corpo, spesso in modo tacito. Le infermiere hanno da tempo esplorato il ruolo del loro corpo nei processi di costruzione della conoscenza, come anche il ruolo del corpo dello studente, e addirittura del paziente, nel conoscere la malattia. In questo paper riportiamo alcune riflessioni ed esperienze sulla conoscenza incorpata nelle pratiche assistenziali, mettendo in luce come questa, bench\ue9 spesso tacita, abbia un ruolo centrale nell\u2019aver cura delle persone malate.In educational contexts, the body has been traditionally marginalized or rejected as a source of knowledge. In the last decades, some pedagogical contributions have shown interest for the role that the teacher\u2019s body has in planning and implementing teaching, challenging dominant ideologies and epistemologies that tell us our minds are the primary sources of learning. Conversely, a pedagogy of embodiment makes the body central in our knowing (educational practices) and being (a teacher). Similarly, literature from the caring professions has revealed very receptive to-ward issues related to embodied knowledge, that is to say the knowledge that the body owns, which is frequently tacit. Since many years, nurses have explored the role of body in the processes of knowledge building, as well as the role of the student\u2019s body, and even the patient\u2019s body, in knowing the illness. In this paper we report some reflections and experiences concerning embodied knowledge in the nursing practice, highlighting that embodied knowledge, even if tacit, has a pivotal role when caring for sick people

The Interaction between the Forkhead Thyroid Transcription Factor TTF-2 and the Constitutive Factor CTF/NF-1 Is Required for Efficient Hormonal Regulation of the Thyroperoxidase Gene Transcription

The forkhead thyroid-specific transcription factor TTF-2 is the main mediator of thyrotropin and insulin regulation of thyroperoxidase (TPO) gene expression. This function depends on multimerization and specific orientation of its DNA-binding site, suggesting that TTF-2 is part of a complex interaction network within the TPO promoter. This was confirmed by transfection experiments and by protein-DNA interaction studies, which demonstrated that CTF/NF1 proteins bind 10 base pairs upstream of the TTF-2- binding site to enhance its action in hormone-induced expression of the TPO gene. GST pull-down assays showed that TTF-2 physically interacts with CTF/NF1 proteins. In addition, we demonstrate that increasing the distance between both transcription factors binding sites by base pair insertion results in loss of promoter activity and in a drastic decrease on the ability of the promoter to respond to the hormones. CTF/NF1 is a family of transcription factors that contributes to constitutive and cell-type specific gene expression. Originally identified as factors implicated in the replication of adenovirus, this group of proteins (CTF/NF1-A, -B, -C, and - X) is now known to be involved in the regulation of several genes. In contrast to other reports regarding the involvement of these proteins in inducible gene expression, we show here that members of this family of transcription factors are regulated by hormones. With the use of specific CTF/NF1 DNA probes and antibodies we demonstrate that CTF/NF1-C is a thyrotropin-, cAMP-, and insulin-inducible protein. Thus CTF/NF1 proteins do not only mediate hormone-induced gene expression cooperating with TTF-2, but are themselves hormonally regulated. All these findings are clearly of important value in understanding the mechanisms governing the transcription regulation of RNA polymerase II promoters, which often contain binding sites for multiple transcription factors

Le storie di vita dei malati di Leucemia Mieloide Cronica: “dare un posto” all’esperienza di malattia nella propria esistenza 
e contribuire all’implementazione della qualità delle cure

Il presente progetto ha raccolto le storie di vita di alcuni membri dell\u2019Associazione Italiana Pazienti di Leucemia Mieloide Cronica (AIP-LMC), in modo da poter esplorare quanto da essi vissuto, anche in relazione all\u2019esperienza di malattia incontrata. La proposta di ripensare, attraverso il racconto, il proprio percorso esistenziale, pu\uf2 costituire un\u2019occasione per ri-significare, ri-pensare e rielaborare l\u2019esperienza di malattia esperita dai partecipanti. Una tale rielaborazione, oltre a favorire una ricostruzione di s\ue9 e della propria storia , utile in primo luogo a chi narra, pu\uf2 consentire di nominare e mettere in luce vissuti, sentimenti, emozioni attraversati nell\u2019esperienza di malattia che potrebbero aiutare lo staff medico e sanitario a riconoscere dimensioni a cui prestare attenzione nel percorso diagnostico e terapeutico

La formazione medica alle cure palliative come ΠΆΘΕΙ ΜΆΘΟΣ : guadagnare saggezza dall'incontro con la finitudine

In this paper we reflect on medical knowledge and professional identity change that may occur when physicians start train-ing in palliative care (PC). Our reflections are based on a secondary analysis of data collected in a qualitative study on the development of competence in PC, which involved all the profession-als (n=30) who in 2014-2015 attended a master program in PC offered by the University of Milan (Italy). They were involved in three focus group (FG), at the beginning, in the middle and at the end of the training. We focus on FGs conducted with physicians (N=10) to reflect on the impact of PC training on their knowledge and identity. Physicians claimed to have a therapeutic role in the CP, even though they realized from the beginning of the Master that their role had to move from caring dimension \u2013 in biomedical sense \u2013 into taking care one referring to patients / family members. The participants affirmed that they had to \u201cun-dress\u201d languages and philosophies that characterized their previ-ous education, in order to acquire the skill to confront suffering. Even if, at the beginning of the Master, the encounter with death and suffering seems to put. Even if encountering death and grief, at the beginning of the Master, seems to intensely challenge med-ical knowledge and role, later, physicians seem to enlarge their idea of competence and wisdom arises from coming to terms with human finitude. Entering in the context of PC makes the doctors confront not only with patients\u2019 finitude, but also with their own sense of finitude. Therefore, the process of \u3c0\u3ac\u3b8\u3b5\u3b9 \u3bc\u3ac\u3b8\u3bf\u3c3 seems put in place here, which allows the construction of a new idea of medical knowledge that we called \u201csapience\u201d. The latter can not be intended as a simple transmission/acquisition of knowledge, but has been described as a process of "becoming". In conclusion, we reflect on the importance of making medical stu-dents confront with finitude, and therefore on the value of intro-ducing PC also in undergraduate training, in order to enlarge medical students\u2019 knowledge and identity

Финансово-экономический механизм функционирования кредитных союзов в Украине

Цель статьи - исследование финансово-экономического механизма функционирования кредитных союзов как альтернативного финансирования населения, что позволяет максимально приблизить финансовые услуги к потребителям, создать надлежащие условия для долгосрочного кредитования с применением современной рыночной инфраструктуры и финансовых инструментов

Becoming competent in palliative care as perceived by nurses attending a Master programme : A qualitative study

This study analysed the perceived process of developing competence in a group of nurses attending a University Master programme in Palliative Care (PC). To evaluate and monitor PC competences, validated questionnaires are available in the literature. Nevertheless, nursing competence in PC is not always evident and measurable. Qualitative instruments as interviews, focus groups could be useful to explore that aspect of nurses\u2019 expertise and to better evaluate the development of competence in PC during and after training experiences Since we focused on a process, we opted to follow the Grounded Theory method. Data were collected through three focus groups, carried out at the beginning, in the middle and at the end of the training. All the nurses participating in the programme were involved. The development of nurses\u2019 competence in PC turned out to be characterised by: 1) transforming clients\u2019 representation from a fixed and uniformed image of the patient to a multi-faceted idea of him/her; 2) transforming the idea of the family from an obstacle to a system integrated with patients; 3) proceeding from an idealized representation of the team to its perception as a real working group; 4) experiencing the accompanying to death as a feasible team work and no more as a solitary endeavour; 5) shifting from a focus just on relational needs to competence in a global patient\u2019s management. Nurses who apply for post-graduate PC training appear to have high predisposition towards considering communicative/relational competences as crucial in that field. Nevertheless, they should be oriented to critically reflect on these core competences to transform their often idealised, and therefore self-protective, image of patients