Live-cell p53 single-molecule binding is modulated by C-terminal acetylation and correlates with transcriptional activity

Live-cell microscopy has highlighted that transcription factors bind transiently to chromatin but it is not clear if the duration of these binding interactions can be modulated in response to an activation stimulus, and if such modulation can be controlled by post-translational modifications of the transcription factor. We address this question for the tumor suppressor p53 by combining live-cell single-molecule microscopy and single cell in situ measurements of transcription and we show that p53-binding kinetics are modulated following genotoxic stress. The modulation of p53 residence times on chromatin requires C-terminal acetylation - a classical mark for transcriptionally active p53 - and correlates with the induction of transcription of target genes such as CDKN1a. We propose a model in which the modification state of the transcription factor determines the coupling between transcription factor abundance and transcriptional activity by tuning the transcription factor residence time on target sites

Study of the Tissue Distribution of TLQP-21 in Mice Using [18F]JMV5763, a Radiolabeled Analog Prepared via [18F]Aluminum Fluoride Chelation Chemistry

TLQP-21 is a neuropeptide that is involved in the control of several physiological functions, including energy homeostasis. Since TLQP-21 could oppose the early phase of diet-induced obesity, it has raised a huge interest, but very little is known about its mechanisms of action on peripheral tissues. Our aim was to investigate TLQP-21 distribution in brain and peripheral tissues after systemic administration using positron emission tomography. We report here the radiolabeling of NODA-methyl phenylacetic acid (MPAA) functionalized JMV5763, a short analog of TLQP-21, with [18F]aluminum fluoride. Labeling of JMV5763 was initially performed manually, on a small scale, and then optimized and implemented on a fully automated radiosynthesis system. In the first experiment, mice were injected in the tail vein with [18F]JMV5763, and central and peripheral tissues were collected 13, 30, and 60 min after injection. Significant uptake of [18F]JMV5763 was found in stomach, intestine, kidney, liver, and adrenal gland. In the CNS, very low uptake values were measured in all tested areas, suggesting that the tracer does not efficiently cross the blood–brain barrier. Pretreatment with non-radioactive JMV5763 caused a significant reduction of tracer uptake only in stomach and intestine. In the second experiment, PET analysis was performed in vivo 10–120 min after i.v. [18F]JMV5763 administration. Results were consistent with those of the ex vivo determinations. PET images showed a progressive increase of [18F]JMV5763 uptake in intestine and stomach reaching a peak at 30 min, and decreasing at 120 min. Our results demonstrate that 18F-labeling of TLQP-21 analogs is a suitable method to study its distribution in the body

Academic inclusion: A debated and interdisciplinary concept

The first chapter—Academic inclusion: A debated and interdisciplinary concept (M.F. Freda, N. Rainone, M. Striano, and P. Valerio)—discusses the complex inclusion construct, currently under debate in many disciplines. The work addresses some theoretical issues regarding inclusion and highlights the opportunities and challenges created by the current international commitment to delivering social inclusion for all. This chapter takes into account the multiplicity of possible definitions for academic inclusion and examines the operationalization difficulties in terms of specific measurement indicators. Furthermore, it focuses on the measures and strategies adopted at the European level to promote inclusion in higher education to prevent student drop-out risks and underachievement. For this, this chapter argues for a link between resilience and inclusion, stressing the resilience competence to use resources in a functional manner. At the end, the chapter proposes a theoretical “resilient inclusion” model

REDUCING UNIVERSITY INEQUALITIES AND THE RISK OF ACADEMIC DROP-OUT: AN EXPLORATIVE RESEARCH WITH STUDENTS WITH VISUAL DISABILITY

The relationship with disabled peers which is based on a shared disability creates an amalgam of functions with mutual help: the peer is a figure you can help and from whom you can be helped, it becomes a mirror of themselves and the similarity is replaced with identity . Moreover, although They are conducive to emotional sharing, in experiences in which students belong to special schools for disabled students, the other is likely to hinder social inclusion. It seems clear, however, that the closure is detected when it is limited to experiences in relational contexts that are defined as primarily related to disability. In these contexts is apparent excessive protectionism against the disabled that would prevent the independence and choice. The relationship with non-disabled peers, however, even if it is more difficult to establish, is narrated as a place of choice for the student and autonomy "steered" in the social universe by the "normal" figure of a facilitator, a mentor able to activate His planning. The university, a "normal" context, is regulated by laws that don’t arise for the disabled person, there is a place that allows for more autonomy and opportunity to commit themselves to define their own life project. However, participation in such a social world is complicated and not always positive, if not adequately supported. In this regard, the presence of a mediator, a tutor can be a bridge in the relationship between disabled and "normal" students, is told as the key figure for the significant relationships with university colleagues who are not disabled. This is a spontaneous resource, if developed and nurtured, can make more flexible the process of inclusion. For this reason, this initial exploratory phase was useful to guide the larger project of research and intervention aimed at promoting social inclusion of disabled students, through tutor training activities, supporting this figure in his mediation function in the relation. The question that arises now is precisely the type of training for tutor. What are the skills of tutor to his function as mediator? Today, the psychology seems to be called to deal with the training of those tutors who accompany the disabled student in his formative career in order to better prepare the key role in the processes of inclusive educational contexts. What are the place for psychology in this training ? What should be the responsibilities to them are required? How psychology can help to promote this? In this context we believe that is useful to be able to answer these questions, make research projects in this regard. At the SINAPSI center, of the University of Naples Federico II, are starting a research project aimed at understanding the role of tutor in the process of inclusion of students with disability