195 research outputs found

    Faculty Publications and Creative Works 2002

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    Introduction One of the ways in which we recognize our faculty at the University of New Mexico is through Faculty Publications & Creative Works. An annual publication, it highlights our faculty\u27s scholarly and creative activities and achievements and serves as a compendium of UNM faculty efforts during the 2001 calendar year. Faculty Publications & Creative Works strives to illustrate the depth and breadth of research activities performed throughout our University\u27s laboratories, studios and classrooms. We believe that the communication of individual research is a significant method of sharing concepts and thoughts and ultimately inspiring the birth of new ideas. In support of this, UNM faculty during 2002 produced over 2,278 works, including 1,735 scholarly papers and articles, 64 books, 195 book chapters, 174 reviews, 84 creative works and 26 patented works. We are proud of the accomplishments of our faculty which are in part reflected in this book, which illustrates the diversity of intellectual pursuits in support of research and education at the University of New Mexico. Terry Yates Vice Provost for Researc

    Deciphering Effects of Idh1-R132H Mutations on the Regulation of Hematopoietic Differentiation

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    The hematopoietic system is a highly versatile regenerative tissue, in which hematopoietic stem cells drive the life-long production of multiple mature blood cell types. During hematopoietic differentiation, the regulation of genome-wide epigenetic patterns of histone modification or DNA methylation marks is an essential process orchestrating cell identities, lineage decisions and developmental cell fates. In acute myeloid leukemia, mutations frequently affect direct and indirect epigenetic regulators and modifiers such as isocitrate dehydrogenase 1 (IDH1) or DNA methyltransferase 3 alpha (DNMT3A), and result in disturbed epigenetic landscapes and differentiation patterns. Here, IDH1 mutations promote oncogenic transformation through the de novo production of the metabolite D2-hydroxyglutarate, which induces a genome and epigenome instability by inhibiting multiple histone and DNA demethylases. Yet, molecular details of how IDH1 mutations alter characteristics of individual hematopoietic cell types remain poorly understood. In the course of this thesis, combinatorial mouse models carrying specific Idh1-R132H and DNMT3A-R882H mutations, which frequently co-occur in acute myeloid leukemia patients, were extensively characterized. By integrating phenotypic readouts in combination with latest advances in high-throughput single-cell RNA-sequencing approaches, cooperativity and impact of these mutations on individual cell types of the hematopoietic system were delineated and gene regulatory networks which are altered upon the expression of an Idh1-R132H or a DNMT3A-R882H mutation were identified. At a phenotypic level, neither an Idh1-R132H mutation alone nor in combination with a DNMT3A-R882H mutation resulted in the development of myeloid malignancies, suggesting a restricted oncogenic potential of these mutations and additional intrinsic or extrinsic factors to be required for further malignant transformation. However, Idh1-R132H mutated hematopoietic stem cells displayed increased engraftment and reconstitution potential during serial transplantations and featured aberrant expression of genes associated with DNA damage and DNA repair. Furthermore, both Idh1-R132H single-mutant and Idh1-R132H DNMT3A-R882H double-mutant mice displayed aberrant differentiation patterns predominantly affecting the myelo-monocytic lineage, culminating in a favored monocytic cell fate and increased monocyte and monocyte progenitor counts in the bone marrow. By employing a multi-layered single-cell transcriptome analysis of nearly all cell types within the hematopoietic compartment, differentiation trajectories from hematopoietic stem cells towards mature differentiated cells were reconstructed and underlying molecular defects characterized. Pseudotime-inferred myeloid lineage trajectories revealed an aberrant lineage specification in particular for Idh1-R132H DNMT3A-R882H double-mutated myeloid progenitor cells, resembling a differentiation arrest at the stage of common myeloid progenitors and an ineffective hematopoietic differentiation as seen in myelodysplastic syndromes. At the molecular level, this aberrant population was characterized by an altered metabolic signature and elevated Myc signaling, which is involved in the regulation of terminal myeloid differentiation. Importantly, we could correlate this transcriptome-defined population to a surface marker-defined population, allowing the prospective isolation of these cells for further investigation. Independent of a DNMT3A-R882H mutation, the expression of an Idh1-R132H mutation resulted in the deregulation of several key regulatory factors which either orchestrate monocyte and macrophage development or their activation upon inflammatory stimuli. In line with this, monocyte progenitor cells displayed elevated interferon signaling levels, suggesting that a proinflammatory environment is a common characteristic of an Idh1-R132H mutated hematopoietic compartment and could contribute to leukemic transformation upon additional events. In summary, the experimental framework presented in this thesis enhanced our understanding of how IDH1-R132H mutations alone or in combination with a DNMT3A-R882H mutation in patients synergistically drive leukemia initiation and progression. The identified molecular characteristics will be of benefit in designing treatment strategies for patients carrying IDH1-R132H and DNMT3A-R882H mutations and can be used as a resource when studying these mutations in the context of altered physiological conditions and upon additional extrinsic stimuli

    Faculty Publications and Creative Works 2004

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    Faculty Publications & Creative Works is an annual compendium of scholarly and creative activities of University of New Mexico faculty during the noted calendar year. Published by the Office of the Vice President for Research and Economic Development, it serves to illustrate the robust and active intellectual pursuits conducted by the faculty in support of teaching and research at UNM

    Faculty Publications and Creative Works 1999

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    One of the ways in which we recognize our faculty at the University of New Mexico is through Faculty Publications & Creative Works. An annual publication, it highlights our faculty\u27s scholarly and creative activities and achievements and serves as a compendium of UNM faculty efforts during the 1999 calendar year. Faculty Publications & Creative Works strives to illustrate the depth and breadth of research activities performed throughout our University\u27s laboratories, studios and classrooms. We believe that the communication of individual research is a significant method of sharing concepts and thoughts and ultimately inspiring the birth of new ideas. In support of this, UNM faculty during 1999 produced over 2,292 works, including 1,837 scholarly papers and articles, 78 books, 82 book chapters, 175 reviews, 113 creative works and 7 patented works. We are proud of the accomplishments of our faculty which are in part reflected in this book, which illustrates the diversity of intellectual pursuits in support of research and education at the University of New Mexico

    Transitions in teacher education and professional identities: proceedings

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    The University of Minho, Braga, Portugal, was the host for the 2014 Annual Conference of the Association for Teacher Education in Europe (ATEE), which took place in August, from the 25th to the 27th. The Conference focused on Transitions in Teacher Education and Professional Identities looked at the transitions in teacher education and analysed different experiences in professional identity of (student) teachers from an international perspective. Three keywords may be identified: challenges in teaching, dilemmas in teacher education and in teacher educators’ role and current trends that are shaping teacher education in different contexts. Similar dilemmas and even contradictions have been identified in different settings with different modes of government intervention in teacher education in which content, structure and duration are also diverse but with similar features. Another key theme discussed at the Conference was the complexity of the concept of identity and also the contested nature of the transitions: transitions for what? How? Why? These transitions and shifts in teacher education and professional identities need to be examined within the context of current policies but also in the light of the complexities and contradictions of teaching as a profession. Teacher educators are also facing transitions in teacher education curricula but also regarding their own identities. These are complex processes that may include resistance and turbulence because transitions may be troublesome for many reasons. In this regard context and language matter but also the kinds of policies and practices that exist within teacher education. There are questions that remain unanswered. However, despite the differences, the dilemmas, and even the contradictions, teacher education can make a difference in professional identity development as was the case of successful experiences that have been described in the Conference

    Gene-environment interactions in the causation and prevention of neural tube defects

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    The aim of the work described in this thesis is to investigate the mechanisms underlying neural tube defects (NTDs), birth defects of the developing central nervous system. The study makes use of mouse models of NTDs, and particularly focuses on the interaction between nutritional factors and genetic risk factors in determining susceptibility to NTDs. In humans some NTDs are preventable by folic acid supplementation, but this is not fully effective so investigation of alternative strategies was a key focus. The efficacy of oral nucleotide and/or inositol supplementation was evaluated for prevention of NTDs in the curly tail (Grhl3 hypomorph) mouse, a model for Folic acid-resistant NTDs. Metabolic effects were investigated by mass spectrometry methods for analysis of folate one-carbon metabolism (FOCM) and nucleotide, nucleoside and nucleobase pools. Genetic factors influencing FOCM in curly tail embryos were investigated, focussing on expression of Mthfd1L, which encodes an enzyme of mitochondrial FOCM. Effects on downstream metabolites and the potential for rescue by supplementation with one-carbon donors was evaluated, together with mass spectrometry based analysis of the treatment. The effect of caffeine on neural tube closure was investigated in several mouse strains to test the hypothesis that caffeine may be a risk factor for NTDs. Caffeine did not interfere with neurulation, and was in fact found to prevent spina bifida in curly tail mice. This prevention was accompanied by changes in embryonic FOCM, and cellular effects were analysed. The cellular basis for prevention of NTDs by folic acid was investigate in the Splotch (Pax3 mutant) mouse. Proliferation was investigated in the cranial neuroepithelium of Splotch mutant and wild-type embryos, under standard and folic acid supplemented conditions. The molecular basis of NTDs was investigated with a focus on abnormal Sonic Hedgehog signalling and disrupted dorso-ventral patterning as potentially contributing to NTDs in Splotch mutants

    Integrative Multi-Omics in Biomedical Research

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    Genomics technologies revolutionised biomedicine research, but the genome alone is not sufficient to capture biological complexity. Postgenomic methods, typically based on mass spectrometry, comprise the analysis of metabolites, lipids, and proteins and are an essential complement to genomics and transcriptomics. Multidimensional omics is becoming established to provide accurate and comprehensive state descriptions. This book covers the latest methodological developments for, and applications of integrative multi-omics in biomedical research

    Accountants\u27 index. Thirty-second supplement, January-December 1983, volume 2: M-Z

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    https://egrove.olemiss.edu/aicpa_accind/1042/thumbnail.jp

    Bowdoin College Catalogue (2003-2004)

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    https://digitalcommons.bowdoin.edu/course-catalogues/1284/thumbnail.jp
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