Becoming deafblind: Negotiating a place in a hostile world

Doctor of PhilosophyThis study addresses the situation of adults who become deafblind. To date, their everday lives have received little attention in the research literature. Of the few studies conducted many involve surveys, the findings of which present the characteristics of people who are deafblind such as their rates of employment, need for support, or use of equipment. There are also a small number of qualitative studies that have explored the effects of having dual sensory impairment, and particularly in relation to communication and psycho-social wellbeing. Important as these research efforts have been, there is little empirical information available about the everyday lives of people who become deafblind and their concerns, nor any systematic attempt to theorise their experiences. There are however many personal anecdotes typically presented at conferences or through community publications and newsletters. This project aimed to redress the gap in the literature by developing a theoretical framework to explain the everyday experiences of adult who become deafblind. In doing so, it built upon the research and anecdotal literature with an overall purpose of presenting, through rigorous research, the experiences of adults who become deafblind and to do so within the broader discourse on disability and disablism. The study was informed by the social relational understanding of disability developed within the Nordic countries. Grounded theory was the method of choice to examine the lives of adults who become deafblind from their own perspective.Participant observation was employed through direct engagement in shared experiences with adults who have become deafblind both at a social group and via an e-mail list group. Mulitple in-depth interviews were undertaken both face to face and by e-mail with a smaller group of eight participants.The core finding from this study is that people who become deafblind are rendered interactionally powerless in a society predicated on seeing and hearing. The powerlessness that they experience comes from having this dual impairment in a world in which being able to see and hear are expected both in the physical and social environment. The inability of people who become deafblind to 'know and be' in the world in the same way as others results in them feeling, and experienceing, interactional powerlessness. In response, people who become deafblind actively engage in trying to minimise or remove their powerlessness. They do so by working to negotiate a place in this hostile world. They adopt four interrelated strategies, namely, doing things differently, managing support relationships, survivings others' perceptions and presenting sides of self.This study, with its central tenet that interactional powerlessness drives ongoing attempts to negotiate a place makes a theoretical contribution to understanding the experience of becoming deafblind. The findings support the concept of disbaility as social relational. Disability is not the same as the sensory impairment, rather it is expressed in the organisation of personal relations in society which render some more powerful than others and in this case, some less powerful due to their inability to use the natural means of communication of hearing and sight. Moreover, the study findings propose that professionals working with people with this dual sensory impairment must endeavour to reduce their part in the hostile world by providing information about options and support available; recognising the complexity of these adults support requirements; and considering the link between psycho-emotional issues and disablism. Further research is needed to understand empirically and theoretically the relative contribution of personal relationships vis a vis organisational or structural relationships in disabling people who become deafblind

High DNA-methyltransferase 3B expression predicts poor outcome in acute myeloid leukemia, especially among patients with co-occurring NPM1 and FLT3 mutations

Contains fulltext : 138167.pdf (publisher's version ) (Open Access

Nuove terapie delle malattie allergiche

Negli ultimi anni la prevalenzadelle malattie allergicheè aumentata considerevolmente,soprattutto nelle nazioni altamente industrializzate(> 20%) e, attualmente, l'asmaè una delle patologie più diffuse nel mondo (prevalenzastimata circa 300 milioni di individui affetti). Purtroppo la maggior parte dei farmaci è in grado di controllare i sintomi ma non di modulare la disregolazioneimmunologica che è alla base delle malattie allergiche.Negli ultimi trent'anni sono stati introdotti sul mercato solo pochi nuovi farmaci (gli anti-Ieucotrienici e l'omalizumab,anticorpo monoclonale anti-lgE),che intervengono sulla risposta di tipo Th2, ritenuta finora la maggioreresponsabiledell'infiammazioneallergicaRecentemente la ricerca ha aperto un nuovo scenarioche coinvolge le citochine di tipo Th I eTh 17 ed il sistemadell'immunità innatacome attori del processo infiammatorio asmatico e allergico.Queste nuove conoscenze suggeriscono un promettente ruolo terapeutico di molecole che hanno come target specifichecitochine. Scopo di tale articolo è quello di presentare un aggiornamento sulle nuove terapie delle malattie allergichecon particolare riferimento all'asma,patologia estremamente complessama con rilevante impatto nella nostra società

Identification of the ubiquitin ligase Triad1 as a regulator of endosomal transport

Contains fulltext : 108211.pdf (publisher's version ) (Open Access)The ubiquitin system plays an important role in trafficking of signaling receptors from the plasma membrane to lysosomes. Triad1 is a ubiquitin ligase that catalyzes the formation of poly-ubiquitin chains linked via lysine-48 as well as lysine-63 residues. We show that depletion of Triad1 affects the sorting of both growth hormone and epidermal growth factor. Triad1-depleted cells accumulate both ligands in endosomes. While fluid phase transport to the lysosomes is reduced in the absence of Triad1, growth hormone receptor can recycle back to the plasma membrane together with transferrin. Using immune electron microscopy we show that Triad1 depletion results in enlarged endosomes with enlarged and irregular shaped intraluminal vesicles. The endosomes display prominent clathrin coats and show increased levels of growth hormone label. We conclude that Triad1 is required for the proper function of multivesicular bodies

The E3 ligase HOIP specifies linear ubiquitin chain assembly through its RING-IBR-RING domain and the unique LDD extension

Item does not contain fulltextActivation of the NF-kappaB pathway requires the formation of Met1-linked 'linear' ubiquitin chains on NEMO, which is catalysed by the Linear Ubiquitin Chain Assembly Complex (LUBAC) E3 consisting of HOIP, HOIL-1L and Sharpin. Here, we show that both LUBAC catalytic activity and LUBAC specificity for linear ubiquitin chain formation are embedded within the RING-IBR-RING (RBR) ubiquitin ligase subunit HOIP. Linear ubiquitin chain formation by HOIP proceeds via a two-step mechanism involving both RING and HECT E3-type activities. RING1-IBR catalyses the transfer of ubiquitin from the E2 onto RING2, to transiently form a HECT-like covalent thioester intermediate. Next, the ubiquitin is transferred from HOIP onto the N-terminus of a target ubiquitin. This transfer is facilitated by a unique region in the C-terminus of HOIP that we termed 'Linear ubiquitin chain Determining Domain' (LDD), which may coordinate the acceptor ubiquitin. Consistent with this mechanism, the RING2-LDD region was found to be important for NF-kappaB activation in cellular assays. These data show how HOIP combines a general RBR ubiquitin ligase mechanism with unique, LDD-dependent specificity for producing linear ubiquitin chains