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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

A symmetry breaking process proposes non-coding functions for olfactory receptor mRNAs.

Pourmorady, Ariel David January 2024 (has links)
Some of life’s most important behaviors are guided by the sense of smell. Detecting and interpreting odor information influences food-seeking, predator avoidance, sociality, competition, mating rituals, and more, shaping how organisms interact with their environment. In vertebrates, odors are detected by olfactory sensory neurons (OSNs) of the main olfactory epithelium (MOE). OSNs rely on olfactory receptors (ORs) to recognize odorants and trigger neural activation. The OR gene pool is typically vast, containing between 200-4000 olfactory receptor genes across mammals, yet mature OSNs stably express only one gene from one allele. Data from mice show that ORs are anatomically restricted to designated sections of the MOE, but within these zones, OR expression appears mosaic and random. Since the discovery of the OR gene pool 30 years ago, deciphering how OSNs choose which OR they are going to express remains a central question. While multiple differentiation-dependent alterations to the OSN nucleus are required for OR expression, the most notable contribution comes from the organization of OR-gene specific enhancers, called Greek Islands (GIs), around the chosen allele. GIs use the transcription factors Lhx2 and Ebf1, as well as the coactivator Ldb1, to form a nucleoprotein complex known as the Greek Island Hub (GIH) to associate with the active OR gene and support its transcription. Bulk Hi-C data show that GIs form strong, specific, and singular associations with the active OR gene, suggesting a possible role for the GIH in singular OR choice. However, single-cell Hi-C analysis shows that multiple GIHs exist in every OSN with no clear differences between them, complicating the contribution of the GIH. Furthermore, ectopic OR gene activation is sufficient to drive association of an OR locus with a GIH and bias choice, suggesting a role for OR transcription itself in supporting its own stable expression. To clarify the genomic transformations that result in the formation of multiple GIHs, I performed combined scRNA-seq and scATAC-seq in the MOE. I determined that a selective inactivation event was taking place during the INP3-to-iOSN transition, where OSNs would silence a large fraction of the GI pool. GI inactivation takes place during a phase preceding OR choice, where OR expression is polygenic but skewed towards one OR. My single-cell Hi-C analysis verifies the presence of multiple GIHs per cell, with similar GI-GI interaction properties, but I also observe that the single active GIH contains much more specific GI-OR gene interactions than those in inactive GIHs. These architectural differences are supported by Liquid Hi-C and H3K27ac HiChIP analysis where I observe that the active GIH is more highly acetylated than inactive GIHs and possesses more euchromatic physical properties. Taken together these data show that while most GIs were initially euchromatic during the polygenic phase of OR expression, once choice has taken place, GIHs possess distinct OR interaction properties, chromatin marks, and physical features that are determined by their association with the active OR gene. I believe that these data are best explained by a winner-takes-all event, where GIHs containing transcribed OR genes during the polygenic phase are in competition for choice. Once one OR begins to win, it recruits resources to maintain its expression which consequently results in the silencing of other GIHs. Ectopic induction of OR gene transcription is sufficient to bias choice and silence other ORs by impeding their specific association with a GIH. I find that this does not depend on the coding properties of OR protein, as the transcription of non-coding OR mRNAs still results in OR gene silencing. I describe this competition as a symmetry breaking process, where asymmetrical reorganization of transcriptional resources to a single GIH is mediated by non-coding properties of a single highly expressed OR mRNA, culminating in the stable expression of that allele alone for the remainder of a cell’s lifetime.
12

Genetic Mechanisms of Regulated Stochastic Gene Expression

Horta, Adan January 2019 (has links)
The adaptability and robustness of the central nervous system is partially explained by the vast diversity of neuronal identities. Molecular mechanisms generating such heterogeneity have evolved through multiple independent pathways. The olfactory sensory system provides a unique and tractable platform for investigating at least two orthogonal gene expression systems that generate neuronal diversity through stochastic promoter choice: olfactory receptor genes and clustered protocadherins. Olfactory sensory neuron identity is defined by the specific olfactory receptor (OR) gene chosen. Greater than 1300 OR genes are scattered throughout the mouse genome, and expression of an OR defines a unique sensory neuron class that responds to a selective set of odorants. This work further delineated an unprecedented network interchromosomal (trans) interactions indispensable for singular OR choice. In a largely orthogonal gene expression system, I sought to understand the molecular mechanisms governing stochastic protocadherin choice. Clustered protocadherins are an evolutionary- conserved system that is involved in cell-cell identification through a series of homo- and heterophilic interactions. This work uncovered a methylation-dependent mechanism for generating stochastic gene expression in the context of cis-regulatory elements. Overall, this work highlighted divergent cis and trans transcriptional regulatory mechanisms for generating stochastic gene expression and neuronal diversity.
13

Olfactory sensitivity in CD-1 mice for six L- and D amino acids

Wallén, Helena January 2010 (has links)
No description available.
14

Olfactory sensitivity in CD-1 mice for six L- and D amino acids

Wallén, Helena January 2010 (has links)
The olfactory sensitivity of five male CD-1 mice (Mus musculus) for six amino acids was determined using an operant conditioning paradigm. All animals significantly distinguished dilutions as low as 0.01 mM L-cysteine, 3.3 mM L-methionine, 10 mM L-proline, 0.03 mM D-cysteine, 0.3 mM D-methionine and 10 mM D-proline from the odorless solvent, with individual animals displaying even lower detection thresholds. Among the three different L-forms of the amino acids the mice were most sensitive for cysteine and least sensitive for proline, and among the three D-forms the animals displayed a lower sensitivity for D-proline compared to D-cysteine and D-methionine. A comparison between the present data and results obtained with other species showed that the CD-1 mice displayed a higher sensitivity than human subjects and spider monkeys with three (L-Cysteine, D-cysteine and L-proline) of the six amino acids. Results from this report support the idea that the number of functional olfactory receptor genes is not suitable to predict a species’ olfactory sensitivity.
15

Patterns of natural selection and demography in coastal Oregon coho salmon (Oncorhynchus kisutch) populations : evidence from neutral and olfactory receptor gene-linked markers /

Johnson, Marc Aaron. January 1900 (has links)
Thesis (Ph. D.)--Oregon State University, 2009. / Printout. Includes bibliographical references (leaves 93-102). Also available on the World Wide Web.
16

Development of improved T cell receptor beta variable gene identification technology and its application post hematopoietic stem cell transplantation

Brewer, Jamie Leigh. January 1900 (has links)
Thesis (Ph. D.)--West Virginia University, 2005. / Title from document title page. Document formatted into pages; contains vi, 139 p. : ill. Vita. Includes abstract. Includes bibliographical references.
17

Genetic patterns of demography and diversity in eastern North Pacific rockfishes (genus Sebastes) /

Johansson, Mattias Lars. January 1900 (has links)
Thesis (Ph. D.)--Oregon State University, 2011. / Printout. Includes bibliographical references (leaves 92-102). Also available on the World Wide Web.
18

Atf5 Links Olfactory Receptor Induced Stress Response to Proper Neuronal Function

Kahiapo, Jerome Keoki January 2020 (has links)
Mammalian olfaction requires the enduring expression of a single olfactory receptor (OR) gene for the life of each sensory neuron. This is due to the fact that OR proteins play multiple roles in the coherent perception of odors, first by sensing molecular cues from the external environment, and by directing the wiring of neuronal projections faithfully from the peripheral sensory neurons to the brain. Both of these processes require singular and stable OR expression in olfactory sensory neurons (OSNs. The transcription factor Atf5 has previously been shown to enforce these modes of expression, through a process that requires the unfolded protein response (UPR). The work presented in this thesis deciphers how Atf5 enables proper OR expression and neuronal function in the olfactory system. We identify the developmental window in which UPR is activated, and provide evidence that Atf5 protein expression coincides with the assembly of a multi-chromosomal enhancer hub that drives singular and robust OR transcription, opposing a model in which precocious polygenic OR transcription initiates UPR. Further, we show that Atf5 directly regulates a collection of genes that facilitate proper OR trafficking, axonogenesis, as well as transcription factors and chromatin modifiers, which we propose to be involved in stable OR expression and neuronal maturation. Finally, we find that Atf5 has a special role in the olfactory system that cannot be replaced by its ubiquitously expressed homologue, Atf4, and that this is due to a requisite interaction between Atf5 and the bZIP transcription factor Cebpγ, and potentially other transcription factors known to be critical for olfactory function.
19

Estudo do polimorfismo dos genes KIR na esclerose sistêmica

Salim, Patrícia Hartstein January 2009 (has links)
As células Natural Killer (NK) fazem parte da resposta imune inata, sendo a primeira linha de defesa do organismo contra vírus, bactérias, tumores e microorganismos. Estas células induzem a morte da célula-alvo quando não há o reconhecimento das moléculas de antígenos leucocitários humanos (HLA) de classe I, através de seus receptores, chamados Killer cell Immunoglobulin-like Receptor (KIR). Vários estudos demonstram o envolvimento dos genes KIR na patogênese das doenças auto-imunes. Acredita-se que combinações desses genes possam ser favoráveis para o desenvolvimento da esclerose sistêmica (ES). Portanto, o conhecimento destes genes relacionados às células NK poderiam ser úteis para o entendimento da patogênese da ES. O objetivo deste estudo é investigar o polimorfismo dos genes KIR em um grupo de pacientes com ES, incluindo a forma difusa e limitada da doença. A freqüência do receptor inibidor KIR2DL2 foi significantemente menor nos pacientes comparada com a do grupo controle (28,7% versus 65,2%; P<0,001; OR=0,21; IC95% 0,11–0,38). Quando analisamos a combinação do receptor inibidor 2DL2, com a presença do ativador 2DS2 (KI2DS2+/KIR2DL2-), encontramos uma maior freqüência nos pacientes (26,1% versus 1,7%; P<0,001; OR=19,94; IC95% 4,7–175,1). Por outro lado, a presença de ambos KIR2DL2 e KIR2DS2 foi mais freqüente no grupo controle (26,9% versus 57,3%; P<0,001; OR=0,27; 95%CI 0,1–0,4). Nenhuma diferença estatística no polimorfismo dos genes KIR foi encontrada entre a forma difusa e a forma limitada. A combinação KIR2DS2+/KIR2DL2– parece ser um fator de risco para o desenvolvimento da ES enquanto a alta freqüência do gene inibidor KIR2DL2 no grupo controle parece ter uma função protetora. Estes resultados indicam um potencial papel dos genes KIR na patogênese da ES. / Natural killer (NK) cells have an important role in the early responses to viral infections. They kill diverse target cells with decreased or absent expression of major histocompatibility complex (MHC) class I molecules through the Killer Cell Immunoglobulin-Like Receptors (KIR). Many studies have reported association of KIR genes with autoimmune diseases. The objective of this study is to investigate possible associations of KIR polymorphisms with systemic sclerosis (SSc), including the limited (lSSc) and diffuse (dSSc) forms of the disease. The frequency of inhibitory KIR2DL2 was significantly decreased among patients with SSc compared with healthy controls (28.7% versus 65.2; P<0.001, odds ratio [OR] 0.21, 95% confidence interval [95% CI] 0.11–0.38). When activatory and inhibitory KIR genes were analyzed in combination, the concomitant presence of KIR2DS2 and absence of KIR2DL2 (KI2DS2+/KIR2DL2-) phenotype was more frequent in SSc patients than in the control group (26.08% versus 1.75%; P<0.001, OR=19.94, 95%CI [4.78–175.10]). On the other hand, the presence of both KIR2DS2 and KIR2DL2 was more frequent in the control group (26.96% versus 57.39%; P=0.000005, OR=0.27, 95%CI [0.15–0.49]). No significant difference in KIR genes polymorphisms was found between lSSc and dSSc disease subsets. The combination of KIR2DS2+/KIR2DL2– may be a risk factor for development of SSc while the higher frequency of the inhibitory KIR2DL2 gene in the control group suggest to a protective effect. These results indicate a potential role of KIR genes in the SSc pathogenesis.
20

Estudo do polimorfismo dos genes KIR na esclerose sistêmica

Salim, Patrícia Hartstein January 2009 (has links)
As células Natural Killer (NK) fazem parte da resposta imune inata, sendo a primeira linha de defesa do organismo contra vírus, bactérias, tumores e microorganismos. Estas células induzem a morte da célula-alvo quando não há o reconhecimento das moléculas de antígenos leucocitários humanos (HLA) de classe I, através de seus receptores, chamados Killer cell Immunoglobulin-like Receptor (KIR). Vários estudos demonstram o envolvimento dos genes KIR na patogênese das doenças auto-imunes. Acredita-se que combinações desses genes possam ser favoráveis para o desenvolvimento da esclerose sistêmica (ES). Portanto, o conhecimento destes genes relacionados às células NK poderiam ser úteis para o entendimento da patogênese da ES. O objetivo deste estudo é investigar o polimorfismo dos genes KIR em um grupo de pacientes com ES, incluindo a forma difusa e limitada da doença. A freqüência do receptor inibidor KIR2DL2 foi significantemente menor nos pacientes comparada com a do grupo controle (28,7% versus 65,2%; P<0,001; OR=0,21; IC95% 0,11–0,38). Quando analisamos a combinação do receptor inibidor 2DL2, com a presença do ativador 2DS2 (KI2DS2+/KIR2DL2-), encontramos uma maior freqüência nos pacientes (26,1% versus 1,7%; P<0,001; OR=19,94; IC95% 4,7–175,1). Por outro lado, a presença de ambos KIR2DL2 e KIR2DS2 foi mais freqüente no grupo controle (26,9% versus 57,3%; P<0,001; OR=0,27; 95%CI 0,1–0,4). Nenhuma diferença estatística no polimorfismo dos genes KIR foi encontrada entre a forma difusa e a forma limitada. A combinação KIR2DS2+/KIR2DL2– parece ser um fator de risco para o desenvolvimento da ES enquanto a alta freqüência do gene inibidor KIR2DL2 no grupo controle parece ter uma função protetora. Estes resultados indicam um potencial papel dos genes KIR na patogênese da ES. / Natural killer (NK) cells have an important role in the early responses to viral infections. They kill diverse target cells with decreased or absent expression of major histocompatibility complex (MHC) class I molecules through the Killer Cell Immunoglobulin-Like Receptors (KIR). Many studies have reported association of KIR genes with autoimmune diseases. The objective of this study is to investigate possible associations of KIR polymorphisms with systemic sclerosis (SSc), including the limited (lSSc) and diffuse (dSSc) forms of the disease. The frequency of inhibitory KIR2DL2 was significantly decreased among patients with SSc compared with healthy controls (28.7% versus 65.2; P<0.001, odds ratio [OR] 0.21, 95% confidence interval [95% CI] 0.11–0.38). When activatory and inhibitory KIR genes were analyzed in combination, the concomitant presence of KIR2DS2 and absence of KIR2DL2 (KI2DS2+/KIR2DL2-) phenotype was more frequent in SSc patients than in the control group (26.08% versus 1.75%; P<0.001, OR=19.94, 95%CI [4.78–175.10]). On the other hand, the presence of both KIR2DS2 and KIR2DL2 was more frequent in the control group (26.96% versus 57.39%; P=0.000005, OR=0.27, 95%CI [0.15–0.49]). No significant difference in KIR genes polymorphisms was found between lSSc and dSSc disease subsets. The combination of KIR2DS2+/KIR2DL2– may be a risk factor for development of SSc while the higher frequency of the inhibitory KIR2DL2 gene in the control group suggest to a protective effect. These results indicate a potential role of KIR genes in the SSc pathogenesis.

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