Community perceptions of a Cree immersion program at Cumberland House

This thesis contributes to the literature on language revitalization, a hopeful branch of research that counters the foreboding conclusions of language shift studies. It is based on data collected in May, 1998, at Cumberland House, an Aboriginal community in northeastern Saskatchewan. Fifty-five community members participated in six focus groups organized by the following criteria: administrators, school board trustees, elders, parents, students and teachers. These research participants expressed their vision, expectations, and needs related to an Aboriginal Language Immersion Pilot Program proposed by the Northern Lights School Division. Community members envisioned an education that contributes to their children's Cree and Anglo-Canadian bicultural competence. They expected the Cree immersion program in the provincial school would develop their children's Cree and English bilingual fluency. They needed training, administrative support, materials and ongoing communication between school and community. Factors that instill a sense of optimism about this language revitalization effort, include the role and status of the school, and the strong bonds of kinship and friendship in this community context. The process and content of the research project records the development and product of a research relationship between Aboriginal people. It attests to the value of community involvement in language planning and illustrates the beneficial attributes of community-based participatory action research. Overall, the thesis informs the topic of decolonization at the personal, community, and institutional level

Overcoming Resistance: Motivating Students to Join the Information Age

The suggestions gathered from the Talk Table can assist both the public library patron and the academic library student in gaining confidence in using the library. In the discussion, patron resistance was generally seen as anxiety created by inexperience withusing libraries. The experience of the participants reflected that when students and patrons become oriented to the library, resistance and hesitation greatly diminish. Ideas offered by the group fell mainly into the categories of library resources and library instruction

FINDING INDIGENOUS DISCOURSE SURVIVANCE AND SENDING IT FORWARD

This research is an interdisciplinary study of rhetorical analyses of three textual forms made by Indigenous women local to the Saskatchewan parkland. My purpose was to identify the survivance of a tribally specific cultural rhetoric (meaning-making practices) in contemporary local Indigenous works. The rhetorical analyses were grounded in Cree, Métis and Saulteaux intellectual traditions accessible to me through observation, experience, and published literature. The Indigenous research methodology was guided by the principles inherent in the concepts of bimaadiziwin, (an Anishinaabe philosophy of being alive well), and wahkohtowin, (a Cree overarching law of respect and belonging), and n’kiinigaanaa, (an Anishinaabe principle of relating to all of creation in equality, and harmony). The data that emerged from my rhetorical analyses were consistent elements of meaning-making practices. I considered the question, “How do I translate this information to knowledge transfer to be useful in preparing pre-service teachers to teach Indigenous content and perspectives?” I sought an answer by referencing the data to the academic literature in literary criticism, literacy, sociolinguistics, narrative, and rhetoric. From the aggregate I adapted the rhetorical situation to represent a model of a local Indigenous rhetorical discourse to explain the elements of an Indigenous rhetorical situation. This model describes the creative expression and critical interpretation of meaning-making practices that are grounded in the principles, protocols, values, and beliefs of a northern plains Algonquian (Cree, Métis and Saulteaux) world view. The implications of the research are presented as potential benefit to teachers and students of Indigenous literatures and rhetorics

RUNX-mediated growth arrest and senescence are attenuated by diverse mechanisms in cells expressing RUNX1 fusion oncoproteins

RUNX gene over-expression inhibits growth of primary cells but transforms cells with tumor suppressor defects, consistent with reported associations with tumor progression. In contrast, chromosomal translocations involving RUNX1 are detectable in utero, suggesting an initiating role in leukemias. How do cells expressing RUNX1 fusion oncoproteins evade RUNX-mediated growth suppression? Previous studies showed that the TEL-RUNX1 fusion from t(12;21) B-ALLs is unable to induce senescence-like growth arrest (SLGA) in primary fibroblasts while potent activity is displayed by the RUNX1-ETO fusion found in t(8;21) AMLs. We now show that SLGA potential is suppressed in TEL-RUNX1 but reactivated by deletion of the TEL HLH domain or mutation of a key residue (K99R). Attenuation of SLGA activity is also a feature of RUNX1-ETO9a, a minor product of t(8;21) translocations with increased leukemogenicity. Finally, while RUNX1-ETO induces SLGA it also drives a potent senescence-associated secretory phenotype (SASP), and promotes the immortalisation of rare cells that escape SLGA. Moreover, the RUNX1-ETO SASP is not strictly linked to growth arrest as it is largely suppressed by RUNX1 and partially activated by RUNX1-ETO9a. These findings underline the heterogeneous nature of premature senescence and the multiple mechanisms by which this failsafe process is subverted in cells expressing RUNX1 oncoproteins

Alzheimer disease genetic risk factor APOE e4, and cognitive abilities in 111,739 UK Biobank participants

Background: the apolipoprotein (APOE) e4 locus is a genetic risk factor for dementia. Carriers of the e4 allele may be more vulnerable to conditions that are independent risk factors for cognitive decline, such as cardiometabolic diseases. Objective: we tested whether any association with APOE e4 status on cognitive ability was larger in older ages or in those with cardiometabolic diseases. Subjects: UK Biobank includes over 500,000 middle- and older aged adults who have undergone detailed medical and cognitive phenotypic assessment. Around 150,000 currently have genetic data. We examined 111,739 participants with complete genetic and cognitive data. Methods: baseline cognitive data relating to information processing speed, memory and reasoning were used. We tested for interactions with age and with the presence versus absence of type 2 diabetes (T2D), coronary artery disease (CAD) and hypertension. Results: in several instances, APOE e4 dosage interacted with older age and disease presence to affect cognitive scores. When adjusted for potentially confounding variables, there was no APOE e4 effect on the outcome variables. Conclusions: future research in large independent cohorts should continue to investigate this important question, which has potential implications for aetiology related to dementia and cognitive impairment

On the Biological Importance of the 3-hydroxyanthranilic Acid: Anthranilic Acid Ratio

Of the major components of the kynurenine pathway for the oxidative metabolism of tryptophan, most attention has focussed on the N-methyl-D-aspartate (NMDA) receptor agonist quinolinic acid, and the glutamate receptor blocker kynurenic acid. However, there is increasing evidence that the redox-active compound 3-hydroxyanthranilic acid may also have potent actions on cell function in the nervous and immune systems, and recent clinical data show marked changes in the levels of this compound, associated with changes in anthranilic acid levels, in patients with a range of neurological and other disorders including osteoporosis, chronic brain injury, Huntington’s disease, coronary heart disease, thoracic disease, stroke and depression. In most cases, there is a decrease in 3-hydroxyanthranilic acid levels and an increase in anthranilic acid levels. In this paper, we summarise the range of data obtained to date, and hypothesise that the levels of 3-hydroxyanthranilic acid or the ratio of 3-hydroxyanthranilic acid to anthranilic acid levels, may contribute to disorders with an inflammatory component, and may represent a novel marker for the assessment of inflammation and its progression. Data are presented which suggest that the ratio between these two compounds is not a simple determinant of neuronal viability. Finally, a hypothesis is presented to account for the development of the observed changes in 3-hydroxyanthranilic acid and anthranilate levels in inflammation and it is suggested that the change of the 3HAA:AA ratio, particularly in the brain, could possibly be a protective response to limit primary and secondary damage

AluY-mediated germline deletion, duplication and somatic stem cell reversion in <i>UBE2T</i> defines a new subtype of Fanconi anemia

Fanconi anemia (FA) is a rare inherited disorder clinically characterized by congenital malformations, progressive bone marrow failure and cancer susceptibility. At the cellular level, FA is associated with hypersensitivity to DNA-crosslinking genotoxins. Eight of 17 known FA genes assemble the FA E3 ligase complex, which catalyzes monoubiquitination of FANCD2 and is essential for replicative DNA crosslink repair. Here, we identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T. Both mutations were aluY-mediated: a paternal deletion and maternal duplication of exons 2-6. These loss-of-function mutations in UBE2T induced a cellular phenotype similar to biallelic defects in early FA genes with the absence of FANCD2 monoubiquitination. The maternal duplication produced a mutant mRNA that could encode a functional protein but was degraded by nonsense-mediated mRNA decay. In the patient's hematopoietic stem cells, the maternal allele with the duplication of exons 2-6 spontaneously reverted to a wild-type allele by monoallelic recombination at the duplicated aluY repeat, thereby preventing bone marrow failure. Analysis of germline DNA of 814 normal individuals and 850 breast cancer patients for deletion or duplication of UBE2T exons 2-6 identified the deletion in only two controls, suggesting aluY-mediated recombinations within the UBE2T locus are rare and not associated with an increased breast cancer risk. Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk breast cancer patient with wild-type BRCA1/2. Cumulatively, we identified UBE2T as a bona fide FA gene (FANCT) that also may be a rare cancer susceptibility gene.</p

Genome-Wide Survey and Expression Profiling of CCCH-Zinc Finger Family Reveals a Functional Module in Macrophage Activation

Previously, we have identified a novel CCCH zinc finger protein family as negative regulators of macrophage activation. To gain an overall insight into the entire CCCH zinc finger gene family and to evaluate their potential role in macrophage activation, here we performed a genome-wide survey of CCCH zinc finger genes in mouse and human. Totally 58 CCCH zinc finger genes in mouse and 55 in human were identified and most of them have not been reported previously. Phylogenetic analysis revealed that the mouse CCCH family was divided into 6 groups. Meanwhile, we employed quantitative real-time PCR to profile their tissue expression patterns in adult mice. Clustering analysis showed that most of CCCH genes were broadly expressed in all of tissues examined with various levels. Interestingly, several CCCH genes Mbnl3, Zfp36l2, Zfp36, Zc3h12a, Zc3h12d, Zc3h7a and Leng9 were enriched in macrophage-related organs such as thymus, spleen, lung, intestine and adipose. Consistently, a comprehensive assessment of changes in expression of the 58 members of the mouse CCCH family during macrophage activation also revealed that these CCCH zinc finger genes were associated with the activation of bone marrow-derived macrophages by lipopolysaccharide. Taken together, this study not only identified a functional module of CCCH zinc finger genes in the regulation of macrophage activation but also provided the framework for future studies to dissect the function of this emerging gene family