551 research outputs found
Mechanisms of retroviral reverse transcription and assembly
The work described in these dissertation studies examines three aspects of retrovirus replication and dissects the uncovered phenomena to increase understanding of how retroviruses thrive in complex host environments. The first aspect of replication discussed is the mechanisms behind minus-strand DNA transfer, a crucial step of reverse transcription. We proved for the first time that non-viral sequences can be utilized to carry out this step of the replication process, and that the minus-strand DNA transfer step can be exploited to reconstitute a functional gene in the infected host cell. This finding serves as a proof-of-principle for a new class of self-activating gene therapy vectors. In the second study, mechanisms of trans-complementation were studied between two distantly related retroviruses, murine leukemia virus (MLV) and spleen necrosis virus. We showed that two different species of pol proteins can be incorporated into virions and cooperate to complete the reverse transcription and integration steps of replication. This finding highlights how different species of retroviruses could possibly interact and combine to form new and possibly more virulent or pathogenic species. Finally, in the third work, a previously uninvestigated region of MLV capsid protein was examined. Specifically, the contribution of the 33 carboxyl-terminal amino acids of MLV CA were found to consist of highly charged residues. The contribution of these residues to virus assembly was investigated via deletion analysis. A new phenotype of MLV CA assembly defect was demonstrated, and a structural model was proposed to explain the possible role of this region, termed the charged assembly helix, in MLV assembly. In summary, the work presented in this dissertation has revealed new properties of retroviral replication as well as further clarified previous knowledge of retroviral biology
Treatment of adult ADHD: Is current knowledge useful to clinicians?
Psychostimulant drugs have for decades been considered the cornerstone of ADHD treatment. Non-stimulant drugs have also been reported successful. However, many controlled studies exclude patients with comorbidities typical for patients seen in clinical setting. Many patients are also considered non-responders to medication. Current knowledge might not be directly useful to clinicians. The present article reviews the literature on pharmacological and psychotherapeutic treatment in adult ADHD emphasizing comorbidity and other clinically important factors, as well as ADHD specific outcomes. Thirty-three relevant studies of pharmacotherapy and three studies of psychotherapy were included. Most subjects had little current comorbidity, but some studies included subjects with substance use disorder. Significant effect of treatment on ADHD symptoms was found in most studies using pharmacotherapy and all studies of psychotherapy. Both positive and negative effects on comorbid anxiety and depression measures were reported. Pharmacotherapy did not seem to have effect on substance use disorder. Few pharmacotherapy studies conducted any long-term follow-up; two studies that did, found that most subjects had discontinued medication. A clear-cut dose-respons relationship was not substanciated. In conclusion, clinicians have good support for both pharmacological and psychotherapeutic treatment of ADHD in adults, but should take additional measures to deal with comorbidities as well as treatment adherence
PrƩcis-writing, Revision and Editing: Piloting the European Master in Translation
The paper reports on and discusses the authorsā development of and experience with PrĆ©cis-writing, revision and editing, a pilot module developed especially for the European Master in Translation (EMT). The background, aim and important characteristics of the EMT are briefly explained. Inspired by the IAMLADP report from 2001, the module development included an exploratory survey of the translation industry internationally and in Denmark, employing web-based questionnaires supplemented by a focus-group interview with translator-editors of the European Commission. Our findings generated knowledge about professional prĆ©cis-writing, revision and editing, including relevant norms and concepts. It also provided useful input on perceived training needs in this respect within the translation profession. The module development also comprised selecting a suitable theoretical foundation and designing a manageable course structure. Studentsā written evaluations of a course taught in the spring of 2005 are summarized, and the paper concludes with the authorsā recommendations for others involved in university-level translator training.Dans cet article, les auteurs rendent compte de leur expĆ©rience du module pilote PrĆ©cis-writing, revision and editing (Contraction, rĆ©vision et Ć©dition de textes), qui a Ć©tĆ© mis au point dans le cadre du European Master in Translation (EMT). Les origines, les objectifs et les caractĆ©ristiques du EMT sont briĆØvement passĆ©s en revue. La mise au point du module, inspirĆ© par le rapport IAMLADP de 2001, comprenait une Ć©tude exploratoire de lāindustrie de la traduction, tant sur le plan international que national. LāĆ©tude a Ć©tĆ© rĆ©alisĆ©e au moyen dāun questionnaire en ligne, et a Ć©tĆ© complĆ©tĆ©e par une entrevue focalisĆ©e de traducteurs-Ć©diteurs de la Commission europĆ©enne. Les rĆ©sultats obtenus ont fourni des informations dĆ©taillĆ©es sur la pratique de la contraction, la rĆ©vision et lāĆ©dition des textes professionnels, et ont permis de dĆ©gager un ensemble de normes et de concepts pertinents. LāĆ©tude a en outre contribuĆ© Ć identifier les besoins de formation professionnelle dans les mĆ©tiers de la traduction. La mise au point du module a impliquĆ© la constitution dāune base thĆ©orique appropriĆ©e et la mise en place dāun cadre didactique et pĆ©dagogique. Les Ć©valuations des Ć©tudiants sur un cours donnĆ© au printemps 2005 sont rĆ©sumĆ©es, et lāarticle se conclut sur des recommandations utiles pour lāĆ©volution de la formation universitaire des traducteurs
Does mental well-being protect against self-harm thoughts and behaviors during adolescence? A six-month prospective investigation
Mental well-being protects against the emergence of suicidal thoughts. However, it is not clear whether these findings extend to self-harm thoughts and behaviors irrespective of intent during adolescenceāor why this relationship exists. The current study aimed to test predictionsāinformed by the integrated motivationalāvolitional (IMV) model of suicideāconcerning the role of perceived defeat and entrapment within the link between mental well-being and self-harm risk. Young people (n = 573) from secondary schools across Scotland completed an anonymous self-report survey at two time points, six months apart, that assessed mental well-being, self-harm thoughts and behaviors, depressive symptomology and feelings of defeat and entrapment. Mental well-being was associated with reduced defeat and entrapment (internal and external) and a decrease in the likelihood that a young person would engage in self-harm thoughts and behaviors. The relationship between mental well-being and thoughts of self-harm was mediated by perceptions of defeat and entrapment (internal and external). Mental well-being was indirectly related to self-harm behaviors via decreased feelings of defeat and internal (but not external) entrapment. Taken together, these findings provide novel insights into the psychological processes linking mental well-being and self-harm risk and highlight the importance of incorporating the promotion of mental well-being within future prevention and early intervention efforts
An examination of hate motivated behavior among adults in Scotland: victimization, perpetration, and associations with risk factors for self-directed violence
Hate-motivated behavior (HMB) ranges from microaggressions to criminal acts and is a public health concern with consequences for the physical and mental wellbeing of individuals, families, and communities. The Hate Motivated Behavior Checklist (HMBC) was developed with the goal of advancing measurement of HMB perpetration. To provide insights into perpetration and victimization across the HMB continuum in Scotland, the present study sought to examine the factor-structure of both the original HMBC and our adapted victimization version (HMBC-V) in a sample of adults currently living in Scotland. It also aimed to test associations between HMB, and cognitions which are related to self-directed violence (defeat and entrapment). Participants (n=447) completed an online cross-sectional survey assessing demographic factors, HMB (perpetration and victimization), and perceptions of defeat and entrapment. Confirmatory factor analysis was used to examine the factor structure of the HMBC and HMBC-V and path analyses was implemented to provide insights into potential links between HMB, defeat, and entrapment. In line with previous work, results provided support for interpreting the HMBC as a single-factor total score. This was also true for the HMBC-V. Results indicated that HMB victimization (but not perpetration) was associated with increased perceptions of defeat and entrapment. These findings suggest that the HMBC and HMBC-V represent potentially useful tools for HMB research and supports their applicability outside of an American context. Furthermore, by examining HMB through the lens of a contemporary model of suicidal behavior, our findings also provide insights into potential psychological mechanisms linking interpersonal and self-directed violence. Future research should implement prospective research designs and integrate measures of self-directed violence outcomes alongside HMB, defeat, and entrapment, to further advance understanding of this association
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