Primary mechanism of apoptosis induction in a leukemia cell line by fraction FA-2-b-ß prepared from the mushroom Agaricus blazei Murill

Agaricus blazei Murill is a native Brazilian mushroom which functions primarily as an anticancer substance in transplanted mouse tumors. However, the mechanism underlying this function of A. blazei Murill remains obscure. The present study was carried out to investigate the effect of fraction FA-2-b-ß, an RNA-protein complex isolated from A. blazei Murill, on human leukemia HL-60 cells in vitro. Typical apoptotic characteristics were determined by morphological methods using DNA agarose gel electrophoresis and flow cytometry. The growth suppressive effect of fraction FA-2-b-ß on HL-60 cells in vitro occurred in a dose- (5-80 µg/mL) and time-dependent (24-96 h) manner. The proliferation of HL-60 cells (1 x 10(5) cells/mL) treated with 40 µg/mL of fraction FA-2-b-ß for 24-96 h and with 5-80 µg/mL for 96 h resulted in inhibitory rates ranging from 8 to 54.5%, and from 4.9 to 86.3%, respectively. Both telomerase activity determined by TRAP-ELISA and mRNA expression of the caspase-3 gene detected by RT-PCR were increased in HL-60 cells during fraction FA-2-b-ß treatment. The rate of apoptosis correlated negatively with the decrease of telomerase activity (r = 0.926, P < 0.05), but correlated positively with caspase-3 mRNA expression (r = 0.926, P < 0.05). These data show that fraction FA-2-b-ß can induce HL-60 cell apoptosis and that the combined effect of down-regulation of telomerase activity and up-regulation of mRNA expression of the caspase-3 gene could be the primary mechanism of induction of apoptosis. These findings provide strong evidence that fraction FA-2-b-ß could be of interest for the clinical treatment of acute leukemia.

Distribution of the human leukocyte antigen class II alleles in Brazilian patients with chronic hepatitis C virus infection

Hepatitis C virus (HCV) infection is a global medical problem. The current standard of treatment consists of the combination of peginterferon plus ribavirin. This regimen eradicates HCV in 55% of cases. The immune response to HCV is an important determinant of disease evolution and can be influenced by various host factors. HLA class II may play an important role in immune response against HCV. The objective of the present study was to determine the distribution of HLA class II (DRB1 and DQB1) alleles, their association with chronic HCV infection and their response to interferon therapy. One hundred and two unrelated white Brazilian patients with chronic HCV infection, 52 responders (45 males and 7 females) and 50 non-responders (43 males and 7 females) to antiviral treatment, were included in the study. Healthy Brazilian bone marrow donors of Caucasian origin from the same geographic area constituted the control group (HLA-DRB1, N = 99 and HLA-DQB1, N = 222 individuals). HLA class II genotyping was performed using a low-resolution DRB1, DQB1 sequence-specific primer amplification. There were higher frequencies of HLA-DRB1*13 (26.5 vs 14.1%) and HLA-DQB1*02 (52.9 vs 38.7%) in patients compared with controls; however, these were not significantly different after P correction (Pc = 0.39 and Pc = 0.082, respectively). There was no significant difference between the phenotypic frequencies of HLA-DRB1 (17.3 vs 14.0%) and HLA-DQB1 alleles in responder and non-responder HCV patients. The HLA-DRB1*07 allele was significantly more common in HCV patients (33.3 vs 12.1%) than in controls (Pc = 0.0039), suggesting that the HLA-DRB1*07 allele is associated with chronic HCV infection.

Synergistic antitumor effect of TRAIL and adriamycin on the human breast cancer cell line MCF-7

The aim of the present study was to determine the effect of the combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and adriamycin (ADM) on the human breast cancer cell line MCF-7 and to identify potential mechanisms of apoptosis. Cell viability was analyzed by the MTT assay and the synergistic effect was assessed by the Webb coefficient. Apoptosis was quantified using the annexin V-FITC and propidium iodide staining flow cytometry. The mRNA expression of TRAIL receptors was measured by RT-PCR. Changes in the quantities of Bax and caspase-9 proteins were determined by Western blot. MCF-7 cells were relatively resistant to TRAIL (IC50 >10 µg/mL), while MCF-7 cells were sensitive to ADM (IC50 <10 µg/mL). A subtoxic concentration of ADM (0.5 µg/mL) combined with 0.1, 1, or 10 µg/mL TRAIL had a synergistic cytotoxic effect on MCF-7 cells, which was more marked with the combination of TRAIL (0.1 µg/mL) and ADM (0.5 µg/mL). In addition, the combined treatment with TRAIL and ADM significantly increased cell apoptosis from 9.8% (TRAIL) or 17% (ADM) to 38.7%, resulting in a synergistic apoptotic effect, which is proposed to be mediated by up-regulation of DR4 and DR5 mRNA expression and increased expression of Bax and caspase-9 proteins. These results suggest that the combination of TRAIL and ADM might be a promising therapy for breast cancer.

Nichesourcing The Uralic Languages For The Benefit Of Linguistic Research And Lingual Societies

The emerging technologies have recently challenged the libraries to reconsider their role as a mere mediator between the collections, researchers, and wider audiences (Sula, 2013), and libraries, especially the nationwide institutions like national libraries, haven’t always managed to face the challenge (Nygren et al., 2014). In the Digitization Project of Kindred Languages, the National Library of Finland has become a node that connects the partners to interplay and work for shared goals and objectives. In this paper, I will be drawing a picture of the crowdsourcing methods that have been established during the project to support both linguistic research and lingual diversity. The National Library of Finland has been executing the Digitization Project of Kindred Languages since 2012. The project seeks to digitize and publish approximately 1,200 monograph titles and more than 100 newspapers titles in various, and in some cases endangered Uralic languages. Once the digitization has been completed in 2015, the Fenno-Ugrica online collection will consist of 110,000 monograph pages and around 90,000 newspaper pages to which all users will have open access regardless of their place of residence. The majority of the digitized literature was originally published in the 1920s and 1930s in the Soviet Union, and it was the genesis and consolidation period of literary languages. This was the era when many Uralic languages were converted into media of popular education, enlightenment, and dissemination of information pertinent to the developing political agenda of the Soviet state. The ‘deluge’ of popular literature in the 1920s to 1930s suddenly challenged the lexical orthographic norms of the limited ecclesiastical publications from the 1880s onward. Newspapers were now written in orthographies and in word forms that the locals would understand. Textbooks were written to address the separate needs of both adults and children. New concepts were introduced in the language. This was the beginning of a renaissance and period of enlightenment (Rueter, 2013). The linguistically oriented population can also find writings to their delight, especially lexical items specific to a given publication, and orthographically documented specifics of phonetics. The project is financially supported by the Kone Foundation in Helsinki and is part of the Foundation’s Language Programme. One of the key objectives of the Kone Foundation Language Programme is to support a culture of openness and interaction in linguistic research, but also to promote citizen science as a tool for the participation of the language community in research. In addition to sharing this aspiration, our objective within the Language Programme is to make sure that old and new corpora in Uralic languages are made available for the open and interactive use of the academic community as well as the language societies. Wordlists are available in 17 languages, but without tokenization, lemmatization, and so on. This approach was verified with the scholars, and we consider the wordlists as raw data for linguists. Our data is used for creating the morphological analyzers and online dictionaries at the Helsinki and Tromsø Universities, for instance. In order to reach the targets, we will produce not only the digitized materials but also their development tools for supporting linguistic research and citizen science. The Digitization Project of Kindred Languages is thus linked with the research of language technology. The mission is to improve the usage and usability of digitized content. During the project, we have advanced methods that will refine the raw data for further use, especially in the linguistic research. How does the library meet the objectives, which appears to be beyond its traditional playground? The written materials from this period are a gold mine, so how could we retrieve these hidden treasures of languages out of the stack that contains more than 200,000 pages of literature in various Uralic languages? The problem is that the machined-encoded text (OCR) contains often too many mistakes to be used as such in research. The mistakes in OCRed texts must be corrected. For enhancing the OCRed texts, the National Library of Finland developed an open-source code OCR editor that enabled the editing of machine-encoded text for the benefit of linguistic research. This tool was necessary to implement, since these rare and peripheral prints did often include already perished characters, which are sadly neglected by the modern OCR software developers, but belong to the historical context of kindred languages and thus are an essential part of the linguistic heritage (van Hemel, 2014). Our crowdsourcing tool application is essentially an editor of Alto XML format. It consists of a back-end for managing users, permissions, and files, communicating through a REST API with a front-end interface—that is, the actual editor for correcting the OCRed text. The enhanced XML files can be retrieved from the Fenno-Ugrica collection for further purposes. Could the crowd do this work to support the academic research? The challenge in crowdsourcing lies in its nature. The targets in the traditional crowdsourcing have often been split into several microtasks that do not require any special skills from the anonymous people, a faceless crowd. This way of crowdsourcing may produce quantitative results, but from the research’s point of view, there is a danger that the needs of linguists are not necessarily met. Also, the remarkable downside is the lack of shared goal or the social affinity. There is no reward in the traditional methods of crowdsourcing (de Boer et al., 2012). Also, there has been criticism that digital humanities makes the humanities too data-driven and oriented towards quantitative methods, losing the values of critical qualitative methods (Fish, 2012). And on top of that, the downsides of the traditional crowdsourcing become more imminent when you leave the Anglophone world. Our potential crowd is geographically scattered in Russia. This crowd is linguistically heterogeneous, speaking 17 different languages. In many cases languages are close to extinction or longing for language revitalization, and the native speakers do not always have Internet access, so an open call for crowdsourcing would not have produced appeasing results for linguists. Thus, one has to identify carefully the potential niches to complete the needed tasks. When using the help of a crowd in a project that is aiming to support both linguistic research and survival of endangered languages, the approach has to be a different one. In nichesourcing, the tasks are distributed amongst a small crowd of citizen scientists (communities). Although communities provide smaller pools to draw resources, their specific richness in skill is suited for complex tasks with high-quality product expectations found in nichesourcing. Communities have a purpose and identity, and their regular interaction engenders social trust and reputation. These communities can correspond to research more precisely (de Boer et al., 2012). Instead of repetitive and rather trivial tasks, we are trying to utilize the knowledge and skills of citizen scientists to provide qualitative results. In nichesourcing, we hand in such assignments that would precisely fill the gaps in linguistic research. A typical task would be editing and collecting the words in such fields of vocabularies where the researchers do require more information. For instance, there is lack of Hill Mari words and terminology in anatomy. We have digitized the books in medicine, and we could try to track the words related to human organs by assigning the citizen scientists to edit and collect words with the OCR editor. From the nichesourcing’s perspective, it is essential that altruism play a central role when the language communities are involved. In nichesourcing, our goal is to reach a certain level of interplay, where the language communities would benefit from the results. For instance, the corrected words in Ingrian will be added to an online dictionary, which is made freely available for the public, so the society can benefit, too. This objective of interplay can be understood as an aspiration to support the endangered languages and the maintenance of lingual diversity, but also as a servant of ‘two masters’: research and society.

Nichesourcing for the benefit of linguistic research and native speakers

The National Library of Finland is implementing the Digitization Project of Kindred Languages in 2012–16. Within the project we will digitize materials in the Uralic languages as well as develop tools to support linguistic research and citizen science. Through this project, researchers will gain access to new corpora 329 and to which all users will have open access regardless of their place of residence. Our objective is to make sure that the new corpora are made available for the open and interactive use of both the academic community and the language societies as a whole. The project seeks to digitize and publish approximately 1200 monograph titles and more than 100 newspapers titles in various Uralic languages. The digitization will be completed by the early of 2015, when the Fenno-Ugrica collection would contain around 200 000 pages of editable text. The researchers cannot spend so much time with the material that they could retrieve a satisfactory amount of edited words, so the participation of a crowd in editing work is needed. Often the targets in crowdsourcing have been split into several microtasks that do not require any special skills from the anonymous people, a faceless crowd. This way of crowdsourcing may produce quantitative results, but from the research’s point of view, there is a danger that the needs of linguistic research are not necessarily met. Also, the number of pages is too high to deal with. The remarkable downside is the lack of shared goal or social affinity. There is no reward in traditional methods of crowdsourcing. Nichesourcing is a specific type of crowdsourcing where tasks are distributed amongst a small crowd of citizen scientists (communities). Although communities provide smaller pools to draw resources, their specific richness in skill is suited for the complex tasks with high-quality product expectations found in nichesourcing. Communities have purpose, identity and their regular interactions engenders social trust and reputation. These communities can correspond to research more precisely. Instead of repetitive and rather trivial tasks, we are trying to utilize the knowledge and skills of citizen scientists to provide qualitative results. Some selection must be made, since we are not aiming to correct all 200,000 pages which we have digitized, but give such assignments to citizen scientists that would precisely fill the gaps in linguistic research. A typical task would editing and collecting the words in such fields of vocabularies, where the researchers do require more information. For instance, there’s a lack of Hill Mari words in anatomy. We have digitized the books in medicine and we could try to track the words related to human organs by assigning the citizen scientists to edit and collect words with OCR editor. From the nichesourcing’s perspective, it is essential that the altruism plays a central role, when the language communities involve. Upon the nichesourcing, our goal is to reach a certain level of interplay, where the language communities would benefit on the results. For instance, the corrected words in Ingrian will be added onto the online dictionary, which is made freely available for the public and the society can benefit too. This objective of interplay can be understood as an aspiration to support the endangered languages and the maintenance of lingual diversity, but also as a servant of “two masters”, the research and the society.

Digital Exhaustion in relation to Video Games – The Consumer Perspective

This thesis regards exhaustion of copyright’s distribution right in intangible transfers of video games. It analyses whether, under the current law of the European Union, the phenomenon of digital exhaustion, especially in relation to games exists. The thesis analyses the consumers’ position in the market for copyright protected goods. It uses video games market as an example of the wider phenomenon of the effect of latest technological developments on consumers. The research conducted for the thesis is mostly legal dogmatic, although also comparative analysis, law and economics and law and technology methods are utilised. The thesis evaluates the effects of the most recent case law of the European Court of Justice to analyse the current state of digital exhaustion. In the analysis of effects that the existence of digital exhaustion has, the thesis uses the consumers’ point of view. The thesis introduces the current state of technology in the field of video games from a legal perspective. Furthermore the thesis analyses the effects on consumers of a scenario that no digital exhaustion exists in the future. Such scenario under the recent European case law at the moment seems realistic. The conclusion of my research is most importantly that the consumer position in the market for digital goods has deteriorated and that the probable exclusion of the exhaustion for digital goods is another piece of evidence of this development. Most importantly however, the state of affairs where no certainty prevails on whether digital exhaustion exists, creates injustice from the consumers’ point of view. Accordingly, acts by EU legislators of the Court of Justice of the European Union are required to clarify the issue.

Measuring software security from the design of software

The vast majority of our contemporary society owns a mobile phone, which has resulted in a dramatic rise in the amount of networked computers in recent years. Security issues in the computers have followed the same trend and nearly everyone is now affected by such issues. How could the situation be improved? For software engineers, an obvious answer is to build computer software with security in mind. A problem with building software with security is how to define secure software or how to measure security. This thesis divides the problem into three research questions. First, how can we measure the security of software? Second, what types of tools are available for measuring security? And finally, what do these tools reveal about the security of software? Measuring tools of these kind are commonly called metrics. This thesis is focused on the perspective of software engineers in the software design phase. Focus on the design phase means that code level semantics or programming language specifics are not discussed in this work. Organizational policy, management issues or software development process are also out of the scope. The first two research problems were studied using a literature review while the third was studied using a case study research. The target of the case study was a Java based email server called Apache James, which had details from its changelog and security issues available and the source code was accessible. The research revealed that there is a consensus in the terminology on software security. Security verification activities are commonly divided into evaluation and assurance. The focus of this work was in assurance, which means to verify one’s own work. There are 34 metrics available for security measurements, of which five are evaluation metrics and 29 are assurance metrics. We found, however, that the general quality of these metrics was not good. Only three metrics in the design category passed the inspection criteria and could be used in the case study. The metrics claim to give quantitative information on the security of the software, but in practice they were limited to evaluating different versions of the same software. Apart from being relative, the metrics were unable to detect security issues or point out problems in the design. Furthermore, interpreting the metrics’ results was difficult. In conclusion, the general state of the software security metrics leaves a lot to be desired. The metrics studied had both theoretical and practical issues, and are not suitable for daily engineering workflows. The metrics studied provided a basis for further research, since they pointed out areas where the security metrics were necessary to improve whether verification of security from the design was desired.

Investigation of the mechanism of transfer of a-tocopherol by the human a-tocopherol transfer protein (H-a-TTP) /

The human a-tocopherol transfer protein (h-a-TTP) is understood to be the entity responsible for the specific retention of a-tocopherol (a-toc) in human tissues over all other forms of vitamin E obtained from the diet. a-Tocopherol is the most biologically active form of vitamin E, and to date has been studied extensively with regard to its antioxidant properties and its role of terminating membrane lipid peroxidation chain reactions. However, information surrounding the distribution of a-tocopherol, specifically its delivery to intracellular membranes by a-TTP, is still unclear and the molecular factors influencing transfer remain elusive. To investigate the mechanism of ligand transfer by the h-a-TTP, a fluorescent analogue of a-toc has been used in the development of a fluorescence resonance energy transfer (FRET) assay. (/?)-2,5,7,8-tetramethyl-2-[9-(7-nitro-benzo[l,2,5]oxdiazol-4-ylamino)-nonyl]- chroman-6-ol (NBD-toc) has allowed for the development of the FRET-based ligand transfer assay. This ligand has been utilized in a series of experiments where changes were made to acceptor lipid membrane concentration and composition, as well as to the ionic strength and viscosity of the buffer medium. Such changes have yielded evidence supporting a collisional mechanism of ligand transfer by a-TTP, and have brought to light a new line of inquiry pertaining to the nature of the forces governing the collisional transfer interaction. Through elucidation of the transfer mechanism type, a deeper understanding of the transfer event and the in vivo fate of a-tocopherol have been obtained. Furthermore, the results presented here allow for a deeper investigation of the forces controlling the collisional protein-membrane interaction and their effect on the transfer of a-toc to membranes. Future investigation in this direction will raise the possibility of a complete understanding of the molecular events surrounding the distribution of a-toc within the cell and to the body's tissues.

Synthesis of fluorescent analogues of a-tocopherol as ligands for the human a-tocopherol transfer protein (a-TTP) /

To further understand in vivo localization and trafficking of a-tocopherol (a-Toe), the most biologically active form of vitamin E, between lipid environments, tocopherols are required that can be followed by teclu1iques such as confocal microscopy and fluorescence resonance energy transfer (FRET) assays. To this end, sixteen fluorescent analogues of a-tocopherol (la-d [(1)anthroy loxy -a-tocopherols, A O-a-Toes], 2a-d [w-nitro benzoxadiazole-a-tocopherols, NBD-aToes], 3a-d [w-dansyl-a-tocopherols, DAN-a-Toes], and 4a-d [w-N-methylanthranilamide-atocopherols, NMA-a-TocsD were prepared by substituting fluorescent labels at the terminus of w-functionalized alkyl chains extending from C-2 of the chroman ring while retaining key binding features of the natural ligand. These compounds were prepared starting from (S)-Trolox® acid VIa esterification, protection, and reduction producing the silyl-protected (S)-Trolox aldehyde that was coupled using Wittig chemistry to different w-hydroxyalkylphosphonium bromides. Reduction of the alkene generated the w-hydroxy functionalized 2-n-alkyl intermediates 9a-d having the necessary 2R stereochemistry. A series of functional group manipulations including mesylation, substitution with azide, and hydride reduction provided w-amino functionalized intermediates 12a-d as well. Coupling intermediates 9a-d and 12a-d with the selected fluorophores (9- anthracene carboxylic acid, 4-chloro-7-nitrobenz-2-oxa-l,3-diazole, 5- dimethylaminonapthalene-l-sulfonyl chloride, and I-methyl-2H-3,1-benzoxazine-2,4(1H)dione), followed by deprotection of the phenolic silyl group, gave the desired fluorescent ligands la-d, 2a-d, 3a-d and 4a-d in good yield. Assessment of their binding affinities with recombinant human a-tocopherol transfer protein (ha-TTP) utilizing fluorescent titration binding assays identified competent ligands for further use in protein studies. Compounds Id (C9-AO-a-Toc) and 2d (C9-NBD-a-Toc) both having nonyl alkyl chain extensions between the chromanol and fluorophore were shown to bind specifically to ha-TTP with dissociation constants (KdS) of approximately 280 nM and 55 nM respectively, as compared to 25 nM for the natural ligand 2R,4'R,^'R-a-tocophQxoL.

Transposable Elements Are a Significant Contributor to Tandem Repeats in the Human Genome

Sequence repeats are an important phenomenon in the human genome, playing important roles in genomic alteration often with phenotypic consequences. The two major types of repeat elements in the human genome are tandem repeats (TRs) including microsatellites, minisatellites, and satellites and transposable elements (TEs). So far, very little has been known about the relationship between these two types of repeats. In this study, we identified TRs that are derived from TEs either based on sequence similarity or overlapping genomic positions. We then analyzed the distribution of these TRs among TE families/subfamilies. Our study shows that at least 7,276 TRs or 23% of all minisatellites/satellites is derived from TEs, contributing ∼0.32% of the human genome. TRs seem to be generated more likely from younger/more active TEs, and once initiated they are expanded with time via local duplication of the repeat units. The currently postulated mechanisms for origin of TRs can explain only 6% of all TE-derived TRs, indicating the presence of one or more yet to be identified mechanisms for the initiation of such repeats. Our result suggests that TEs are contributing to genome expansion and alteration not only by transposition but also by generating tandem repeats.

Indigenous Language Reclamation: The Learners Perspective

ABSTRACT This study explored the link between learning an Indigenous language and the meanings second language learners attach to their language recovery experiences. The study delves into the factors that motivate, enhance and serve as barriers to individual language revitalization efforts. With the goal of reasserting an Indigenous world view, the traditional teachings of the Ojibwe medicine wheel were combined with the lessons of the seven Grandfathers to provide a methodological basis for conducting ethical research with and for the benefit of First Nations people. Within the context of our relationships with self, community, spirit and environment, the pairing of Indigenous theory with the practical community experiences of Indigenous second language learners, demonstrates how Indigenous systems of thought and ontology lend themselves well to the critical understanding necessary to enhance the recovery our own endangered languages. These research findings indicate that there is a definite link between ancestral language reclamation and increased levels of self-esteem, a sense of grounded cultural identity and resilience, an overall sense of healing and the social responsibility that comes with receiving the gift of language. The barriers associated with learning an ancestral language intersect on multiple and often simultaneous levels making it difficult for the language learners to discover their origin.This research found that it was important for language learners to identify that they often carry a collective sense of shame associated with an internalized attachment to the modality of Indigeneity. Once the origin of this shame was acknowledged – as resulting from settler/assimilation logics, it was often possible for people to move forward in their language recovery journeys, while at the same time considering more broadly the structural barriers that make individual learning so difficult.

Own the Podium Funding and Support: The Athletes' Perspective

The purpose of this study was to understand the experiences of Canada’s high performance athletes who have benefitted from Own the Podium (OTP)-recommended funding and support leading up to an Olympic or Paralympic Games. OTP, a nonprofit agency, is responsible for determining the overall investment strategy for high performance sport in Canada through recommendations to support national sport organizations (NSOs) with the aim to improve Canadian performances at the Olympic and Paralympic Games. For this study, data were collected through in-depth interviews with eleven Canadian high performance athletes (i.e., single-sport Summer/Winter Olympians and Paralympians and recently retired athletes). Analysis of the data resulted in twelve overarching themes; resources, pressure, missing gap, results, targeting, stress, expectations, boost in confidence, OTP relationship, OTP name, pre/post OTP, and lost funding. Overall, results from this exploratory research indicate that athletes generally had a favourable perception regarding OTP-recommended funding and support.

Requirements for the selective degradation of CD4 receptor molecules by the human immunodeficiency virus type 1 Vpu protein in the endoplasmic reticulum.

BACKGROUND: HIV-1 Vpu targets newly synthesized CD4 receptor for rapid degradation by a process reminiscent of endoplasmic reticulum (ER)-associated protein degradation (ERAD). Vpu is thought to act as an adaptor protein, connecting CD4 to the ubiquitin (Ub)-proteasome degradative system through an interaction with beta-TrCP, a component of the SCFbeta-TrCP E3 Ub ligase complex. RESULTS: Here, we provide direct evidence indicating that Vpu promotes trans-ubiquitination of CD4 through recruitment of SCFbeta-TrCP in human cells. To examine whether Ub conjugation occurs on the cytosolic tail of CD4, we substituted all four Ub acceptor lysine residues for arginines. Replacement of cytosolic lysine residues reduced but did not prevent Vpu-mediated CD4 degradation and ubiquitination, suggesting that Vpu-mediated CD4 degradation is not entirely dependent on the ubiquitination of cytosolic lysines and as such might also involve ubiquitination of other sites. Cell fractionation studies revealed that Vpu enhanced the levels of ubiquitinated forms of CD4 detected in association with not only the ER membrane but also the cytosol. Interestingly, significant amounts of membrane-associated ubiquitinated CD4 appeared to be fully dislocated since they could be recovered following sodium carbonate salt treatment. Finally, expression of a transdominant negative mutant of the AAA ATPase Cdc48/p97 involved in the extraction of ERAD substrates from the ER membrane inhibited Vpu-mediated CD4 degradation. CONCLUSION: Taken together, these results are consistent with a model whereby HIV-1 Vpu targets CD4 for degradation by an ERAD-like process involving most likely poly-ubiquitination of the CD4 cytosolic tail by SCFbeta-TrCP prior to dislocation of receptor molecules across the ER membrane by a process that depends on the AAA ATPase Cdc48/p97.

The uses of the outline for cultural formulation of the DSM-IV : from case conceptualization to treatment plan

ARTICLE 1 : RÉSUMÉ Amputation traumatique: Une étude de cas laotien sur l’indignation et l’injustice. La culture est un contexte essentiel à considérer pour produire un diagnostic et un plan d’intervention psychiatrique. Une perspective culturelle met en relief le contexte social dans lequel les symptômes émergent, et comment ils sont interprétés et gérés par la personne atteinte. Des études ethnoculturelles sur les maladies nous suggèrent que la plupart des gens nous donnent des explications pour leurs symptômes qui ont un fondement culturel. Bien que ces explications contredisent la théorie biomédicale, elles soulagent la souffrance des patients et leur permettent de donner une signification à cette dernière. L’exploration des caractéristiques, contextes et antécédents des symptômes permet au patient de les communiquer au clinicien qui pourrait avoir une explication différente de sa maladie. Cette étude de cas permet de montrer comment le Guide pour Formulation Culturelle du DSM-IV (The DSM-IV Outline for Cultural Formulation) permet aux cliniciens de solliciter un récit du patient en lien avec son expérience de la maladie. Notre étude examine l’utilisation par un patient laotien de « l’indignation sociale » (« Khuâm khum khang ») comme le modèle explicatif culturel de son problème malgré le diagnostic de trouble de stress post-traumatique qui lui fut attribué après une amputation traumatique. L’explication culturelle de son problème a permis au patient d’exprimer la signification personnelle et collective à sa colère et sa frustration, émotions qu’il avait réprimées. Cet idiome culturel lui a permis d’exprimer sa détresse et de réfléchir sur le système de soins de santé et, plus précisément, le contexte dans lequel les symptômes et leurs origines sont racontés et évalués. Cette représentation laotienne a aussi permis aux cliniciens de comprendre des expériences et les explications du client, autrement difficiles à situer dans un contexte biomédical et psychiatrique Euro-américain. Cette étude démontre comment il est possible d’améliorer les interactions entre cliniciens et patients et dès lors la qualité des soins par la compréhension de la perspective du patient et l’utilisation d’une approche culturelle. Mots clés: Culture, signification, idiome culturel, modèle explicatif, Guide pour Formulation culturelle du DSM-IV, indignation sociale, interaction entre patient et intervenant. ARTICLE 2 : RÉSUMÉ Impact de l’utilisation du Guide pour la formulation culturelle du DSM-IV sur la dynamique de conférences multidisciplinaires en santé mentale. La croissance du pluralisme culturel en Amérique du nord a obligé la communauté oeuvrant en santé mentale d’adopter une sensibilité culturelle accrue dans l’exercice de leur métier. Les professionnels en santé mentale doivent prendre conscience du contexte historique et social non seulement de leur clientèle mais également de leur propre profession. Les renseignements exigés pour les soins professionnels proviennent d’ évaluations cliniques. Il faut examiner ces informations dans un cadre culturellement sensible pour pouvoir formuler une évaluation des cas qui permet aux cliniciens de poser un diagnostic juste et précis, et ce, à travers les frontières culturelles du patient aussi bien que celles du professionnel en santé mentale. Cette situation a suscité le développement du Guide pour la formulation culturelle dans la 4ième édition du Manuel diagnostique et statistique des troubles mentaux américain (Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV) de l’Association psychiatrique américaine. Ce guide est un outil pour aider les cliniciens à obtenir des informations de nature culturelle auprès du client et de sa famille afin de guider la production des soins en santé mentale. L’étude vise l’analyse conversationnelle de la conférence multidisciplinaire comme contexte d’utilisation du Guide pour la formulation culturelle qui sert de cadre dans lequel les pratiques discursives des professionnels de la santé mentale évoluent. Utilisant la perspective théorique de l’interactionnisme symbolique, l’étude examine comment les diverses disciplines de la santé mentale interprètent et conceptualisent les éléments culturels et les implications de ce cadre pour la collaboration interdisciplinaire dans l’évaluation, l’élaboration de plans de traitement et des soins. Mots clé: Guide pour Formulation culturelle – Santé mentale – Psychiatrie transculturelle – Analyse conversationnelle – Interactionnisme symbolique

Family members' perceptions of nurse caring behaviours in the intensive care unit

La présence de membres de la famille dans les milieux de soins critiques a augmentée graduellement au cours des dernières années. La présente recherche visait à décrire la perception que les membres de la famille avait eu à l’égard des comportements de caring des infirmières lors de leur visite aux soins intensifs. Plus spécifiquement, ce projet avait pour but d’explorer les différences entre les perceptions de membres de la famille dont le proche était hospitalisé pour une blessure traumatique versus une maladie grave non-traumatique. Les différences ont aussi été examinées selon certaines caractéristiques personnelles d’un membre de la famille soit leur genre, leur expérience antérieure de visites aux soins intensifs, leur âge et leur perception de la gravité du problème de santé de leur proche. Le cadre de référence de cette étude était basé sur les facteurs caratifs proposés par Watson (1985). L’importance et la satisfaction des membres de la famille à l’égard des comportements de caring de la part des infirmières ont été mesurées par les versions française et anglaise adaptées du Caring Behaviors Assessment (CBA) (Cronin & Harrison, 1988). Les données ont été analysées en utilisant les techniques d’analyse MANOVA et des tests de corrélation de Pearson. En général, les résultats indiquent que les membres de la famille rapportent des degrés d’importance et de satisfaction similaires selon que leur proche était hospitalisé pour une blessure traumatique ou une maladie grave non-traumatique. Peu de différences émergent selon les caractéristiques personnelles des membres de la famille. Un coefficient de corrélation significatif (0.36, p = 0.012) existe entre la perception des membres de la famille de la gravité du problème de santé, et l’importance de la dimension ‘réponses aux besoins’. Par ailleurs, les comportements de caring regroupés dans la dimension ‘réponses aux besoins’ ont été perçus comme étant les plus importants et les membres de familles étaient très satisfaits des comportements de caring des infirmières. Cette étude fournit des pistes pour l’enseignement, la clinique et la recherche et met en lumière la perception des membres de la famille des soins infirmiers humains chez des proches hospitalisés dans une unité de soins intensifs.