The biological activities of retinoic acid (RA) and its synthetic analogues are mediated through nuclear receptors, termed retinoic acid receptors (RARs) and retinoid X receptors (RXRs). The transcriptional activity of RAR on target gene expression is achieved by its AF-1 domain and AF-2 domain. The function of AF-2 is known to be mediated by a number of coregulatory proteins. However the mechanism of AF-1 function is not well studied. We have hypothesized that the AF-1 function of RAR is regulated by specific interacting proteins. HACE1 was identified as an AF-1 domain interacting protein in a yeast two-hybrid screen. HACE1 interacts with RAR&beta<sub>3 / Microbiology and Immunology

No description available.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Retinoic acid (RA) has been recognized as a chemotherapeutic agent for various malignances such as lung, skin as well as cervical cancers. It binds to retinoid receptors heterodimers and consequently activates several RA-responsive genes which are involved in many biological processes including vertebrate development, bone growth, vision, haematopoiesis, cell growth, differentiation and apoptosis. These genes are under the control of numerous regulators to ensure their timely ordered activities. Among these regulators, we focused here on the 26S proteasome and ubiquitination. It has been reported that the activity of the ubiquitin/proteasome system (UPS) plays a fundamental role in retinoic acid receptor (RAR)-regulated transactivation. The mechanisms underlying this role, however, remain to be established. Chromatin immunoprecipitation (ChIP) assays in our study demonstrated that the 26S proteasome activity is important for preserving the occupancy of a TATA box-containing RA-responsive promoters by liganded retinoid receptors and thus by their coactivators. Additionally, by using coimmunoprecipitation assays and by measuring the half-life of retinoid receptors, we found that the non-proteolytic function of the proteasome is required for ligand-dependent association between DNA-free RAR-α and both DNA-free RXR-α and coactivators. Moreover, using immunofluorescent staining and in vivo ubiquitination assays, a proteasome inhibition-dependent cytoplasmic localization of RAR-α as well as ligand-enhanced ubiquitination and stabilization of RAR-α were shown. Our findings therefore, define novel mechanisms by which the UPS controls RAR-regulated genes. Furthermore, we shed new light on the regulators of retinoid receptors ubiquitination and subcellular localization.

Retinoic acid (RA) has been recognized as a chemotherapeutic agent for various malignances such as lung, skin as well as cervical cancers. It binds to retinoid receptors heterodimers and consequently activates several RA-responsive genes which are involved in many biological processes including vertebrate development, bone growth, vision, haematopoiesis, cell growth, differentiation and apoptosis. These genes are under the control of numerous regulators to ensure their timely ordered activities. Among these regulators, we focused here on the 26S proteasome and ubiquitination. It has been reported that the activity of the ubiquitin/proteasome system (UPS) plays a fundamental role in retinoic acid receptor (RAR)-regulated transactivation. The mechanisms underlying this role, however, remain to be established. Chromatin immunoprecipitation (ChIP) assays in our study demonstrated that the 26S proteasome activity is important for preserving the occupancy of a TATA box-containing RA-responsive promoters by liganded retinoid receptors and thus by their coactivators. Additionally, by using coimmunoprecipitation assays and by measuring the half-life of retinoid receptors, we found that the non-proteolytic function of the proteasome is required for ligand-dependent association between DNA-free RAR-α and both DNA-free RXR-α and coactivators. Moreover, using immunofluorescent staining and in vivo ubiquitination assays, a proteasome inhibition-dependent cytoplasmic localization of RAR-α as well as ligand-enhanced ubiquitination and stabilization of RAR-α were shown. Our findings therefore, define novel mechanisms by which the UPS controls RAR-regulated genes. Furthermore, we shed new light on the regulators of retinoid receptors ubiquitination and subcellular localization.

Retinoic acid (RA) has been recognized as a chemotherapeutic agent for various malignances such as lung, skin as well as cervical cancers. It binds to retinoid receptors heterodimers and consequently activates several RA-responsive genes which are involved in many biological processes including vertebrate development, bone growth, vision, haematopoiesis, cell growth, differentiation and apoptosis. These genes are under the control of numerous regulators to ensure their timely ordered activities. Among these regulators, we focused here on the 26S proteasome and ubiquitination. It has been reported that the activity of the ubiquitin/proteasome system (UPS) plays a fundamental role in retinoic acid receptor (RAR)-regulated transactivation. The mechanisms underlying this role, however, remain to be established. Chromatin immunoprecipitation (ChIP) assays in our study demonstrated that the 26S proteasome activity is important for preserving the occupancy of a TATA box-containing RA-responsive promoters by liganded retinoid receptors and thus by their coactivators. Additionally, by using coimmunoprecipitation assays and by measuring the half-life of retinoid receptors, we found that the non-proteolytic function of the proteasome is required for ligand-dependent association between DNA-free RAR-α and both DNA-free RXR-α and coactivators. Moreover, using immunofluorescent staining and in vivo ubiquitination assays, a proteasome inhibition-dependent cytoplasmic localization of RAR-α as well as ligand-enhanced ubiquitination and stabilization of RAR-α were shown. Our findings therefore, define novel mechanisms by which the UPS controls RAR-regulated genes. Furthermore, we shed new light on the regulators of retinoid receptors ubiquitination and subcellular localization.

Retinoic acid (RA) has been recognized as a chemotherapeutic agent for various malignances such as lung, skin as well as cervical cancers. It binds to retinoid receptors heterodimers and consequently activates several RA-responsive genes which are involved in many biological processes including vertebrate development, bone growth, vision, haematopoiesis, cell growth, differentiation and apoptosis. These genes are under the control of numerous regulators to ensure their timely ordered activities. Among these regulators, we focused here on the 26S proteasome and ubiquitination. It has been reported that the activity of the ubiquitin/proteasome system (UPS) plays a fundamental role in retinoic acid receptor (RAR)-regulated transactivation. The mechanisms underlying this role, however, remain to be established. Chromatin immunoprecipitation (ChIP) assays in our study demonstrated that the 26S proteasome activity is important for preserving the occupancy of a TATA box-containing RA-responsive promoters by liganded retinoid receptors and thus by their coactivators. Additionally, by using coimmunoprecipitation assays and by measuring the half-life of retinoid receptors, we found that the non-proteolytic function of the proteasome is required for ligand-dependent association between DNA-free RAR-α and both DNA-free RXR-α and coactivators. Moreover, using immunofluorescent staining and in vivo ubiquitination assays, a proteasome inhibition-dependent cytoplasmic localization of RAR-α as well as ligand-enhanced ubiquitination and stabilization of RAR-α were shown. Our findings therefore, define novel mechanisms by which the UPS controls RAR-regulated genes. Furthermore, we shed new light on the regulators of retinoid receptors ubiquitination and subcellular localization.

No description available.

Mellan september 2010 till augusti 2011 påbörjade Polisen ett införande av ett nytt utredningsstöd, PUST (Polisens UtredningsStöd). Syftet med detta var att det skulle effektivisera avrapporteringen och att fler poliser skulle bli mer synliga ute i samhället. Systemet PUST med plattformen Java ansågs vara framgångsrikt men efter endast ett par månaders användning togs ett beslut av polisledningen att plattformen skulle bytas ut och ersättas med ett standardsystem, PUST Siebel. Till skillnad från Java fick Siebel en enorm kritik då det upplevdes svårhanterligt och komplicerat att arbeta i. I februari 2014 togs beslutet att PUST Siebel skulle avvecklas.Detta ledde till att vi formulerade frågeställningen; Vilka faktorer bidrog till att PUST Siebel lades ned?För att kunna besvara vår forskningsfråga genomförde vi en kvalitativ studie där utgångspunkten var att undersöka den problematik som kan uppstå vid implementeringen av ett större IT-system i offentlig sektor. Vi har genomfört intervjuer med sex representanter från Polismyndigheten i Göteborg, Borås och Jönköping. Samtliga respondenter har arbetat i PUST Siebel, vilka var relevanta för vår undersökning. Huvudinriktningen i vår studie är hur användbarhet och handlingsbarhet påverkar införandet av ett större IT-system.Tidigare forskning som har gjorts om införande av IT-system har visat att användbarhet och handlingsbarhet ofta prioriteras bort. En orsak till det är att det saknas kunskap om dessa begrepp, vilket medför att det inte går att förstå användarnas behov. Enligt författarna Lind m.fl. (2011) kan konsekvensen bli att det skapas ett ologiskt system som inte blir hållbart i längden.Resultatet i vår studie visar att användbarhet och handlingsbarhet är viktiga komponenter att ta hänsyn till vid införandet av ett IT-system. När ett IT-system skall införas skall det utvecklas på ett sådant sätt att det främst gynnar användarna. De bidragande faktorerna till att PUST Siebel avvecklades var bland annat att systemet inte var komplett när det infördes i verksamheten, vilket bidrog till att användarna uppfattade systemet som ologiskt och komplicerat att arbeta i. En annan bidragande orsak till nedläggningen var att det fattades ett felaktigt beslut om att byta till ett standardsystem då det senare skulle visa sig att det saknades teknisk kompetens om hur ett sådant system fungerar och är uppbyggt. / Between September 2010 and August 2011, the Swedish Police force began to implement a new investigation support system, PUST (Polisens UtredningsStöd). The purpose of this was to make debriefing more efficient and thereby enable more police officers to be visible out on the streets. The system was considered successful when using the platform Java, however, after only a few months the decision was taken by the Police management to replace the platform by a standard system, PUST Siebel. Unlike Java, Siebel was harshly criticised as it was perceived to be cumbersome and complicated to use. Then, in February 2014, the decision was taken to shut down PUST Siebel.This led to us formulating the question; Which factors led to PUST Siebel being discontinued?To be able to answer our research question we carried out a qualitative study where the starting point was to look into the problems that can arise when implementing a larger IT- system in the public sector. We interviewed six representatives from the Police Department in Gothenburg, Borås and Jönköping. All of the respondents had direct experience of working with PUST Siebel. The main focus of our study is how usability and actability affect the implementation of a larger IT- system.Previous research has shown that usability and actability are often deprioritised when an IT- system is developed. One reason is that there is a lack of knowledge regarding these aspects, which means that the needs of the users are not fully understood. The authors Lind et (2011) says that one consequence of this could be that the system created is illogical and not sustainable long term. The result of our study shows that usability and actability are important aspects to consider when implementing an IT- system. When an IT-system is due to be implemented it should be developed in such a way so that it benefits the users.One contributing factor that led to PUST Siebel being discontinued was that the system not was complete when it was introduced into the business, which led to the users perceived the system as illogical and difficult to work in. Another contributing factor to the demise was that it was made a wrong decision about switching to a standard system where it subsequently turns out that there was no technical skills on how such a system works and is structured. This study is written in swedish.

As part of the current fast growing development of digital technologies, collaborations between professions such as neurosciences, robotics, big data processing and artificial intelligence offer new possibilities for healthcare. For these new technologies to reach clinical practice, there is an increasing need for interdisciplinary organizational work to support decision-making over their introduction. In the field of neurorehabilitation, exoskeletons are an example of a robotic tool that can be used to regain locomotion abilities after a neurological injury. They are part of an umbrella term, Robot-Assisted-Rehabilitation (RAR), that stands for neurological recovery techniques assisted with robotic tools. For these tools, the introduction, evaluation and implementation in clinical practice have not been evaluated. In many cases it is also not taken into account that tools such as rehabilitation robotics are context-dependent. In other words, the needs, opportunities and challenges that come together with working efficiently with this new technology can widely vary between clinics, regions and countries. Lastly, it appears that smaller hospitals consider themselves in need of tools to support their decision-making in the RAR introduction phase. In collaboration with Hälsostaden and Region Skåne, we set out to develop a tool to support Ängelholm Hospital (ÄH) in their decision-making over a test-bed trial of RAR in their clinical setting. A tool that we coined the Co-Strategy Process (CSP), was developed based on identified needs related to this stage of the process, using a blend of interdisciplinary scientific methods. It integrates internal and external interdisciplinary expertise and includes four steps: Preparation, Knowledge Empowerment, Exchange & Development and Synthesis & Report. The current Master thesis presents the development and assessment of the CSP at ÄH. In the present context, it results in a new tool for supporting organizations implementing new technologies, optimized based on its application in a Swedish clinical setting. This tool aims at serving this introductory process, so that new technologies can be implemented meeting the needs of both the clinic and patients. / e Rehab-robotic project in collaboration with Uppsala University, Basel University and ETH Zurich