Fire exclusion has defined 20th century forestry practices in North America and produced many unintended consequences. In the Canadian Rocky Mountains, the removal of fire from the landscape caused significant landscape changes over the past century. Mountain forests are now more uniform in stand composition and structure, and understorey diversity is reduced. These changes mean that forests are now more susceptible to high-intensity, difficult-to-control wildfires. Re-introducing Indigenous led historical burning patterns modeled on traditional burning techniques can be a restoration technique for these highly altered ecosystems. Indigenous fire regimes that emphasized regular, low-intensity burning created forests that had less fuel build up and were not as susceptible to dangerous wildfires. In order to effectively re-introduce historical fire regimes onto the Canadian mountain landscapes, it is essential to understand the history of human management of landscapes with fire. This project uses new methods of oblique image analysis that build on recent developments in oblique image analysis to examine the historical management of a portion of the traditional territory of the Stoney Nakoda Nation that overlaps present day Kananaskis Country in Alberta, Canada. While it is difficult to capture low-intensity Indigenous burns using traditional fire reconstruction methods, in-depth analysis of historical photos taken before the introduction of fire suppression laws may reveal new insights into historical fire regimes. Images were classified using machine learning software and compared to images classified by a human to verify the accuracy of the machine learning software. A case study of georeferencing images was also conducted, with the landcover estimates generated by georeferenced images compared to oblique estimates. Spatial signatures of Indigenous burning were identified and applied to repeat image sets to look for visual evidence of Indigenous burning on the landscape. The results from this study provide a useful starting point for further research into repeat photography and Indigenous burning. / Graduate

Akt plays a role in protecting macrophages from apoptosis induced by some oxysterols. Previously we observed enhanced degradation of Akt in P388D1 moncocyte/macrophages following treatment with 25-hydroxycholesterol (25-OH) or 7-ketocholesterol (7-KC). In the present report we examine the role of the ubiquitin proteasomal pathway in this process. We show that treatment with 25-OH or 7-KC results in the accumulation of poly-ubiquitinated Akt, an effect that is enhanced by co-treatment with the proteasome inhibitor MG-132. Modification of Akt by the addition of a Gly-Ala repeat (GAr), a domain known to block ubiquitin-dependent targeting of proteins to the proteasome, resulted in a chimeric protein that is resistant to turn-over induced by 25-OH or 7-KC and provides protection from apoptosis induced by these oxysterols. These results uncover a new aspect of oxysterol regulation of Akt in macrophages; oxysterol-stimulated poly-ubiquitination of Akt and degradation by the proteasomal pathway.

The purposes of this study are to examine migration disparities in primary, onward, and return migration by Hispanics, non-Hispanic black, and non-Hispanic white and to inspect the differences among the various types of migration. In addition, this study explores explanations of the migration disparities. These have been rarely studied because of a lack of proper migration data. This research employs the National Longitudinal Study of Youth (NLSY79) for a logistic regression of primary migration and for a hierarchical generalized linear model (HGLM) of the two types of repeat migration, namely onward and return. The results demonstrate that whites are more likely to make primary and onward migrations compared to blacks and Hispanics. But, with return migration, significant differences between whites and other minorities are not found. With respect to the contributors or explanations, this study indicates that the racial/ethnic migration disparities are not explained by socioeconomic status as opposed to explanations by human capital perspectives. The racial/ethnic disparities in migrations seem to be produced by discrimination and an unequal distribution of opportunities. Return migration presents several interesting different patterns compared with the other type migrations, including the effects of age and educational attainment. For return migration, old and less educated individuals have higher odds, showing reversed pattern of total, primary, and onward migration. The findings seem to indicate that different characteristics are involved in different types of migration.

The primary objective of this study is to examine U.S. repeat migration for blacks, Hispanics, and whites. It investi gates the relationships and patterns of these different racial/ethnic groups utilizing the National Longitudinal Survey of Youth 1979 (NLSY79). Repeat migration within and across categories of individual characteristics for blacks, Hispanics, and whites, is compared in order to determine if there are differences in the overall rates of repeat migration for these groups, once other factors are controlled. To do this several statistical procedures are utilized, and the results of selected descriptive and logistic analyses are presented. The descriptive statistics control for race/ethnicity and examine patterns within the groups; these findings display important relationships to onward and return migration. The inferential statistical method employed is logistic regression for the sample as a whole, which examines the effects across the groups, and the direction of migration. Where past research has not investigated the complexities of repeat migration in combination with race/ethnicity, there are several notable results from this study. Specifically, this research finds that in terms of onward migration, whites are significantly more likely to move onward than are blacks or Hispanics even after controlling for key socioeconomic factors. Changes in marital status are significantly related to migration, and to the direction of repeat migration; individuals who change from "single to married" are likely to be onward migrants, whereas those who change from "married to single" are likely to be return migrants. This study finds there are differences in rates of return migration by level of education for racial/ethnic groups. Moreover, the relationship between onward migration and employment status is different for Hispanics than blacks and whites.

Abstract: The purpose of this study was to determine if a correlation exists between suicide and CAG repeat length in Huntington’s disease. Methodology: A case-control study using the COHORT Study de-identified database was conducted. Responses were collected from 163 participants. Depression, substance abuse history and use of benzodiazepines were covariates. Responses to the UHDRS behavioral section pertaining to the frequency and severity of suicidal ideation (“feels life is not worth living”, “has suicidal thoughts”) were analyzed. Results: Despite taking depression, benzodiazepine use, and history of substance abuse into account, there was a predictive relationship between CAG repeat length and frequency of suicidal ideation (p = .010). When the effect of depression was taken into account, there was no significant relationship between CAG repeat length and the severity of suicidal ideation. Recommendations: The findings from this quantitative analysis supported using CAG length in a clinician’s risk factor assessment to determine the frequency of suicidality.

Indiana University-Purdue University Indianapolis (IUPUI) / Mutations in the gene encoding for leucine rich repeats kinase 2 (LRRK2) are commonly found in Parkinson’s disease. Recently, we found that the disease-associated point mutations at residue R1441 in the G domain (ROC) of LRRK2 resulted in perturbation of its GTPase activity. In this study, we compare the biochemical and biophysical properties of the ROC domain of LRRK2 carrying the PD-associated mutations at residue R1441 with those of the wild-type. We found that the disease-associated mutations (R1441C/G/H) showed marked quaternary structure compared to wild-type, in that the latter existed in solution in both monomeric and dimeric conformations dynamically regulated by GDP/GTP binding state, while we detected only monomeric conformation for three disease-associated mutants. To understand the structural basis for this plasticity and the activity reduction in the mutants, we solved a 1.6 Å crystal structure of the wild type ROC that shows a stable dimeric conformation in which the switch motifs and inter-switch regions mediate extensive interactions at the dimer interface. Residue R1441, where PD-associated mutations occur, forms exquisite interactions at the interface, thus suggesting a critical role of this residue in maintaining a dynamic dimer-monomer interconversion and conformational flexibility of the switch motifs. Consistently, substituting R1441 for other arbitrary mutations (R1441K/S/T) lead to similar perturbation of GTPase activity and dimerization defects as observed in the disease-associated mutants. Locking the ROC domain in either dimeric or monomeric conformations by engineered disulfide bond alters the binding affinity to GTP (but not GDP) and significantly reduce GTPase activity, thus suggesting that the dynamic dimer-monomer interconversion and conformational plasticity are essential for ROC function as a molecular switch modulating the kinase activity of LRRK2.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18161号 / 医博第3881号 / 新制||医||1003(附属図書館) / 31019 / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊達 洋至, 教授 杉田 昌彦, 教授 中山 健夫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20788号 / 医博第4288号 / 新制||医||1025(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙橋 良輔, 教授 高橋 淳, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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