Genomic, Epigenomic and Transcriptomic Molecular Characterization of Splenic Marginal Zone Lymphoma Reveals Recurrent Abnormalities in miR-182

Splenic marginal zone lymphoma (SMZL) is a low grade B-cell non-Hodgkin's lymphoma. The molecular pathology of this entity remains poorly understood. To characterise this lymphoma at the molecular level, we performed an integrated analysis of 1) genome wide genetic copy number alterations 2) gene expression profiles and 3) epigenetic DNA methylation profiles.We have previously shown that SMZL is characterised by recurrent alterations of chromosomes 7q, 6q, 3q, 9q and 18; however, gene resolution oligonucleotide array comparative genomic hybridisation did not reveal evidence of cryptic amplification or deletion in these regions. The most frequently lost 7q32 region contains a cluster of miRNAs. qRT-PCR revealed that three of these (miR-182/96/183) show underexpression in SMZL, and miR-182 is somatically mutated in >20% of cases of SMZL, as well as in >20% of cases of follicular lymphoma, and between 5-15% of cases of chronic lymphocytic leukaemia, MALT-lymphoma and hairy cell leukaemia. We conclude that miR-182 is a strong candidate novel tumour suppressor miRNA in lymphoma.The overall gene expression signature of SMZL was found to be strongly distinct fromthose of other lymphomas. Functional analysis of gene expression data revealed SMZL to be characterised by abnormalities in B-cell receptor signalling (especially through the CD19/21-PI3K/AKT pathway) and apoptotic pathways. In addition, genes involved in the response to viral infection appeared upregulated. SMZL shows a unique epigenetic profile, but analysis of differentially methylated genes showed few with methylation related transcriptional deregulation, suggesting that DNA methylation abnormalities are not a critical component of the SMZL malignant phenotype.

BCR and TLR signalling pathways are recurrently targeted by genetic changes in splenic marginal zone lymphomas.

The genetics and pathogenesis of splenic marginal zone lymphoma are poorly understood. The lymphoma lacks chromosome translocation, and ~30% of cases are featured by 7q deletion, but the gene targeted by the deletion is unknown. A recent study showed inactivation of A20, a 'global' NF-kB negative regulator, in 1 of 12 splenic marginal zone lymphoma. To investigate further whether deregulation of the NF-kB pathway plays a role in the pathogenesis of splenic marginal zone lymphoma, we screened several NF-kB regulators for genetic changes by PCR and sequencing. Somatic mutations were found in A20 (6/46=13%), MYD88 (6/46=13%), CARD11 (3/34=8.8%), but not in CD79A, CD79B and ABIN1. Interestingly, these genetic changes are largely mutually exclusive from each other and MYD88 mutation was also mutually exclusive from 7q deletion. These results strongly suggest that deregulation of the TLR (toll like receptor) and BCR (B-cell receptor) signalling pathway may play an important role in the pathogenesis of splenic marginal zone lymphoma.

Programmes informatiques permettant l'adaptation des DRG aux statistiques médicales VESKA

Le présent cahier documente les différents programmes informatiques nécessaires à l'adaptation suisse des DRG.

PROX1 Promotes Metabolic Adaptation and Fuels Outgrowth of Wnt(high) Metastatic Colon Cancer Cells.

The Wnt pathway is abnormally activated in the majority of colorectal cancers, and significant knowledge has been gained in understanding its role in tumor initiation. However, the mechanisms of metastatic outgrowth in colorectal cancer remain a major challenge. We report that autophagy-dependent metabolic adaptation and survival of metastatic colorectal cancer cells is regulated by the target of oncogenic Wnt signaling, homeobox transcription factor PROX1, expressed by a subpopulation of colon cancer progenitor/stem cells. We identify direct PROX1 target genes and show that repression of a pro-apoptotic member of the BCL2 family, BCL2L15, is important for survival of PROX1(+) cells under metabolic stress. PROX1 inactivation after the establishment of metastases prevented further growth of lesions. Furthermore, autophagy inhibition efficiently targeted metastatic PROX1(+) cells, suggesting a potential therapeutic approach. These data identify PROX1 as a key regulator of the transcriptional network contributing to metastases outgrowth in colorectal cancer.

Le chef au bracelet d'or (3e édition) / par Mayne-Reid ; adaptation par André Laurie

Collection : Bibliothèque d'éducation et de récréation

Les Mille et une nuits : contes arabes choisis pour la jeunesse / adaptation nouvelle d'après la traduction de Galland par Paul de Maurelly... ; illustrations de H. Grobet

[Mille et une nuits (français). Adaptation. 1911]

Marginal/minority popular music : the concept of the "third space" and the case for "hybridities" of cultures/identities /

The topic of this thesis is marginaVminority popular music and the question of identity; the term "marginaVminority" specifically refers to members of racial and cultural minorities who are socially and politically marginalized. The thesis argument is that popular music produced by members of cultural and racial minorities establishes cultural identity and resists racist discourse. Three marginaVminority popular music artists and their songs have been chosen for analysis in support of the argument: Gil Scott-Heron's "Gun," Tracy Chapman's "Fast Car" and Robbie Robertson's "Sacrifice." The thesis will draw from two fields of study; popular music and postcolonialism. Within the area of popular music, Theodor Adorno's "Standardization" theory is the focus. Within the area of postcolonialism, this thesis concentrates on two specific topics; 1) Stuart Hall's and Homi Bhabha's overlapping perspectives that identity is a process of cultural signification, and 2) Homi Bhabha's concept of the "Third Space." For Bhabha (1995a), the Third Space defines cultures in the moment of their use, at the moment of their exchange. The idea of identities arising out of cultural struggle suggests that identity is a process as opposed to a fixed center, an enclosed totality. Cultures arise from historical memory and memory has no center. Historical memory is de-centered and thus cultures are also de-centered, they are not enclosed totalities. This is what Bhabha means by "hybridity" of culture - that cultures are not unitary totalities, they are ways of knowing and speaking about a reality that is in constant flux. In this regard, the language of "Otherness" depends on suppressing or marginalizing the productive capacity of culture in the act of enunciation. The Third Space represents a strategy of enunciation that disrupts, interrupts and dislocates the dominant discursive construction of US and THEM, (a construction explained by Hall's concept of binary oppositions, detailed in Chapter 2). Bhabha uses the term "enunciation" as a linguistic metaphor for how cultural differences are articulated through discourse and thus how differences are discursively produced. Like Hall, Bhabha views culture as a process of understanding and of signification because Bhabha sees traditional cultures' struggle against colonizing cultures as transforming them. Adorno's theory of Standardization will be understood as a theoretical position of Western authority. The thesis will argue that Adorno's theory rests on the assumption that there is an "essence" to music, an essence that Adorno rationalizes as structure/form. The thesis will demonstrate that constructing music as possessing an essence is connected to ideology and power and in this regard, Adorno's Standardization theory is a discourse of White Western power. It will be argued that "essentialism" is at the root of Western "rationalization" of music, and that the definition of what constitutes music is an extension of Western racist "discourses" of the Other. The methodological framework of the thesis entails a) applying semiotics to each of the three songs examined and b) also applying Bhabha's model of the Third Space to each of the songs. In this thesis, semiotics specifically refers to Stuart Hall's retheorized semiotics, which recognizes the dual function of semiotics in the analysis of marginal racial/cultural identities, i.e., simultaneously represent embedded racial/cultural stereotypes, and the marginal raciaVcultural first person voice that disavows and thus reinscribes stereotyped identities. (Here, and throughout this thesis, "first person voice" is used not to denote the voice of the songwriter, but rather the collective voice of a marginal racial/cultural group). This dual function fits with Hall's and Bhabha's idea that cultural identity emerges out of cultural antagonism, cultural struggle. Bhabha's Third Space is also applied to each of the songs to show that cultural "struggle" between colonizers and colonized produces cultural hybridities, musically expressed as fusions of styles/sounds. The purpose of combining semiotics and postcolonialism in the three songs to be analyzed is to show that marginal popular music, produced by members of cultural and racial minorities, establishes cultural identity and resists racist discourse by overwriting identities of racial/cultural stereotypes with identities shaped by the first person voice enunciated in the Third Space, to produce identities of cultural hybridities. Semiotic codes of embedded "Black" and "Indian" stereotypes in each song's musical and lyrical text will be read and shown to be overwritten by the semiotic codes of the first person voice, which are decoded with the aid of postcolonial concepts such as "ambivalence," "hybridity" and "enunciation."

Improving the oral health status of functionally independent and dependent seniors residing in long-term care facilities through dental hygiene education /

The purpose of this study was to evaluate the oral health status of residents residing in 2 long-term care facilities and determine if dental hygiene education was required in order to improve their current oral health. The oral health status of 6 independent and 4 dependent individuals residing in 2 long-term care facilities was evaluated. In addition, the current oral health and disease prevention practices employed by 4 caregivers who were responsible for providing oral care to dependent residents in the long-term care facilities were evaluated. Furthermore, an evaluation of the oral care practices of independent residents who were responsible for providing their own care was conducted. Finally, the challenges that caregivers and independent residents faced when performing oral care were determined, and methodological changes were proposed. Using a generic qualitative research methodology, data collection was comprised of semi structured interviews, field observations, and documentation. The oral health status of the residents was reevaluated 3 months later. The findings of this study demonstrated an increase in plaque accumulation, gingival inflammation, and unhealthy gingival tissue colour changes among the residents over the 3-month period. The study revealed that poor oral health among the residents was a result of inadequate oral hygiene care techniques, difficulties accessing oral health care, financial limitations, insufficient care staff, insufficient time for personal care duties, lack of professional development, minimal interprofessional collaboration of health disciplines, and lack of perseverance on the part of the caregivers and residents. Overall, oral health is essential, and maintaining optimal oral health requires increased collaboration and communication between health care providers.

A method of evaluating psychomotor tooth preparation skills in preclinical dental programs

Preclinical and clinical tooth important and significant aspect of preparation is an a dental student's education. The associated procedures rely heavily on the development of particular psychomotor skills. The most common format of instruction and evaluation in tooth preparation at many Dental Faculties, emphasizes the product (tooth preparation) and associates performance with characteristics of this product. This integrated study examines which skills should be developed and how a course of instruction can best be structured to develop the necessary skills. The skills which are identified are those necessary for tooth preparation are selected from a psychomotor taxonomy. The purpose of evaluating these skills is identified. Behavioral objectives are set for student performance and the advisability of establishing standards of performance is examined. After reviewing studies related to learning strategy for dental psychomotor the most suitable tasks as well as articles on instructor effectiveness a model is proposed. A pilot project at the University of Toronto, based on this proposed model is described. The paper concludes wi th a discussion of the implications of this proposed model.

A possible role for intrinsic calcium buffers in the long- term adaptation of crayfish neurons

Increasing the impulse activity of neurons in vivo over 3 or more days causes a reduction in transmitter release that persists for days or weeks (eg. Mercier and Atwood, 1989). This effect is usually accompanied by decreased synaptic fatigue. These two changes involve presynaptic mechanisms and indicate "long-term adaptation" (LTA) of nerve terminals. Previous experiments have shown that LTA requires extracellular calcium and protein synthesis (eg. Hong and Lnenicka, Soc. Neurosci. Abstr. 17:1322) and appears to involve communication between the cell body and the nerve terminals. The present study examines the possibility that the reduction in transmitter release is caused by an -increase in the calcium buffering ability within the nerve terminals. It examines the responses of adapted and control nerve terminals to exogenously applied calcium buffer, BAPTA-AM, which decreases transmitter release (Robitialle and Charlton, 1992). If LTA increases intrinsic Ca2+-buffering, the membrane permeant form of BAPTA should have less effect on adapted nerve terminals than on controls. Experiments are performed on the phasic abdominal extensor motor neurons of the crayfish, Procambarns clarkii. BAPTA-AM decreases excitatory postsynaptic potentials (EPSP's) of the phasic extensor muscles in a dosedependent manner between 5 and 50 JLM. LTA is elicited by in vivo stimulation at 2.5 Hz for 2-4 h per day over 3 days, which reduces EPSP's by over 50%. Experiments indicate that BAPTA-AM produces no significant change in EPSP reduction in adapted neurons when compared to controls. These results do not support the hypothesis that increased daily activity alters rapid intrinsic calcium buffers, that are able to reduce transmitter output in the same manner as BAPTA.

Living between two cultures : personality and adaptation in Chinese immigrant youth /

The aim of the present study was to examine the relationship between shyness and acculturation modes of Chinese immigrant youth in Canada and whether shyness moderates the relationship between acculturation and adaptation. In addition, I examined whether shyness, in conjunction with sociability, moderates the relationship between acculturation and adaptation. Ninety-nine young Chinese immigrants (42 men), ranging in age from 16 to 26 years old, completed a questionnaire that assessed their demographic information, acculturation modes, shyness, sociability, psychological adaptation Oife satisfaction, self-esteem, and depression), and socio-cultural adaptation. Results showed that Chinese orientation was significantly and negatively correlated with age, generation status, English proficiency, and length of residence in Canada. In contrast, Canadian orientation was significantly and positively correlated with generation status, English proficiency, and length of residence in Canada. Canadian orientation was also significantly and negatively correlated with shyness and positively correlated with sociability and psychological and socio-cultural adaptation. Participants who were shyer were more likely to have poorer psychological and socio-cultural adaptation, and to report lower life satisfaction and self-esteem and higher depression. Results from hierarchical multiple regression analyses indicated that Chinese immigrant youth who were separated had higher scores on shyness than those who were integrated and assimilated. There were no significant differences in shyness between youth who were separated and youth who were marginalized, nor were there differences between youth who were integrated and those who were assimilated. Furthermore, integrated Chinese youth reported significantly higher scores in sociability than those who were separated and marginalized but not significantly higher than those who were assimilated.' Shyness did not moderate the relationship between acculturation modes and psychological and socio-cultural adaptation. Unfortunately, the hypothesis to examine if shyness, in combination with sociability, moderated the relationship between acculturation and psychological adaptation could not be tested in the present study because of limitations in cell sizes. The findings suggested that how Chinese immigrant youth acculturate in the receiving country might not be the crucial factor in determining their adaptation. Instead, other factors, such as personality characteristics and nature of the acculturating group, may playa more crucial role. Shyness may have important ramifications for the acculturation and adaptation of young Chinese immigrants to a new society.

Innovation and adaptation in the Ontario grape and wine industry: An integrated, transdisciplinary response to climate change

With scientific consensus supporting a 4oC increase in global mean temperature over the next century and increased frequency of severe weather events, adaptation to climate change is critical. Given the dynamic and complex nature of climate change, a transdisciplinary approach toward adaptation can create an environment that supports knowledge sharing and innovation, improving existing strategies and creating new ones. The Ontario wine industry provides a case study to illustrate the benefits of this approach. We describe the formation and work of the Ontario Grape and Wine Research Network within this context, and present some preliminary results to highlight the opportunities for innovation that will drive the successful adaption of the Ontario grape and wine industry.

Plant rhizosphere specificity and variability in the insect and plant adhesins, Madl and Mad2, within the genus Metarhizium suggest plant adaptation as an evolutionary force

Metarhizium is a soil-inhabiting fungus currently used as a biological control agent against various insect species, and research efforts are typically focused on its ability to kill insects. In section 1, we tested the hypothesis that species of Metarhizium are not randomly distributed in soils but show plant rhizosphere-specific associations. Results indicated an association of three Metarhizium species (Metarhizium robertsii, M. brunneum and M. guizhouense) with the rhizosphere of certain types of plant species. M. robertsii was the only species that was found associated with grass roots, suggesting a possible exclusion of M. brunneum and M. guizhouense, which was supported by in vitro experiments with grass root exudate. M. guizhouense and M. brunneum only associated with wildflower rhizosphere when co-occurring with M. robertsii. With the exception of these co-occurrences, M. guizhouense was found to associate exclusively with the rhizosphere of tree species, while M. brunneum was found to associate exclusively with the rhizosphere of shrubs and trees. These associations demonstrate that different species of Metarhizium associate with specific plant types. In section 2, we explored the variation in the insect adhesin, Madl, and the plant adhesin, Mad2, in fourteen isolates of Metarhizium representing seven different species. Analysis of the transcriptional elements within the Mad2 promoter region revealed variable STRE, PDS, degenerative TATA box, and TATA box-like regions. Phylogenetic analysis of 5' EF-Ia, which is used for species identification, as well as Madl and Mad2 sequences demonstrated that the Mad2 phylogeny is more congruent with 5' EF-1a than Madl. This suggests Mad2 has diverged among Metarhizium lineages, contributing to clade- and species-specific variation. While other abiotic and biotic factors cannot be excluded in contributing to divergence, it appears that plant associations have been the driving factor causing divergence among Metarhizium species.