Browsing by Subject "gene expression"

Now showing 1 - 5 of 5
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    Alpha synuclein functions as a sex-specific modulator of cognition and gene expression
    (2022-12) Brown, Jennifer
    Neurodegenerative diseases such as Alzheimer’s and Parkinson’s impact large portions of the population. Though such diseases have distinguishing features, they also often share pathology and symptomology. Alpha synuclein (αSyn; gene SNCA) is a protein commonly found in a range of neurodegenerative conditions. αSyn can interact with tau and amyloid-beta to modulate disease phenotypes, but its normal functions remain incompletely characterized. To explore the contribution of αSyn to Alzheimer’s disease, I first asked whether reducing αSyn in a mouse model of Alzheimer’s would improve cognition. Using a translationally relevant strategy, the reduction of αSyn reveled a sex-specific effect whereby male, but not female, mice showed improved spatial memory. Follow-up studies with constitutive SNCA knockout mice revealed a previously unreported female-specific deficit in spatial learning and memory. Next, we utilized electrophysiology, immunofluorescence imaging and transcriptomics to elucidate potential mechanisms underlying this effect. Results revealed a novel impairment in long-term potentiation, as well as differential expression of genes related to learning and immune function in female mice in response to SNCA ablation. These results not only describe a novel sex-specific function of αSyn, but provide translationally-relevant information regarding the potential effects of using αSyn reduction as a therapeutic strategy for neurodegenerative conditions.
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    Effects of milk yield genotype on immune, endocrine and metabolite interactions in dairy cows
    (2018-08) Cousillas, Georgina
    Studies were designed to assess the impact of milk yield genotype on the innate immune response and its interactions with endocrine and metabolic components when growing heifers and lactating cows are challenged with lipopolysaccharide (LPS). A novel aspect of these studies was the comparison of unique Holsteins that have not been subjected to selection since 1964 (unselected Holsteins; UH) with contemporary Holsteins (CH). In addition, our animal models included heifers from contemporary Red-Black Angus cows (CA) and our experimental designs included the use of repeated LPS administration to assess the impact of genotype on the acute immune response and on the development of a refractory (endotoxin tolerance) state. Pro-inflammatory cytokine and glucose concentrations were greater and cortisol concentrations increased more rapidly in Holsteins than in Angus heifers which is consistent with results from our collaborators that indicate Holsteins have a more robust immune response than Angus cattle. Differences in plasma concentrations of pro-inflammatory cytokines, glucose and cortisol, and in expression of adhesion molecules and phagocytic activity of polymorphonuclear leukocytes (PMNL) after LPS administration indicates UH heifers and cows have a more robust immune response than CH heifers and cows. This was further supported by hepatic gene expression data, which indicated greater expression of genes in the TLR4 signaling pathway and of genes involved in the production of pro and anti-inflammatory mediators (IL6, TNF, IL1RN, TGFB1) in UH than in CH cows during the acute immune response. In addition, results during the second challenge indicated greater development of tolerance to immunotoxin stimulation in UH than CH cows. Overall, our results demonstrate that TLR4 signaling pathways have been altered by five decades of selective breeding and these changes contribute to a less robust and less controlled innate immune response in CH cows. Thus, immune activation and the ability to minimize negative effects of prolonged inflammation are reduced in the CH cow. Although we did not assess the impact of selection, we assessed functionality of several anti-ADAM17 antibodies and inhibitors and for, the first time, characterized the presence and activity of ADAM17 (a disintegrin and metalloproteinase-17) protein in bovine PMNL.
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    Feeding high dietary zinc to gestating sows and implications on sow and piglet performance, their biological responses, and the environment
    (2023-10) Hammers, Kelsey
    High rates of pre-weaning mortality continue to trouble the swine industry. Feeding high dietary concentrations of zinc (Zn) to sows during late gestation may have utility as a fetal imprinting strategy to positively influence their offspring and mitigate these piglet losses. Supplemental zinc fed in previous experiments were fed in a topdress form that required additional labor. With an aim to determine a practical zinc supplementation approach, a commercial sow study was conducted to investigate the effects of two Zn supplementation methods on sow and piglet performance and piglet mortality. Research in chapter 3 revealed that feeding elevated Zn to sows throughout gestation increased the proportion of pigs born alive, suggesting that elevated gestational Zn intake makes piglets more robust to endure the stresses of farrowing and decreases intrapartum mortality. While supplemental Zn may positively impact piglet performance, the mode through which high Zn acts is unknown. This dissertation aims to investigate three possible modes of action that may explain the influence of zinc on fetal imprinting and ultimately piglet survival. Research presented in chapter 4 indicates that high dietary Zn concentration elicited minimal changes on mineral concentrations of various tissues and serum from sows and piglets. Additionally, elevated Zn fed to sows minimally influenced gene expression of their low birth weight offspring. Research in chapter 5 characterized the effect of high dietary zinc on the microbiome of sows and piglets. Elevated dietary zinc fed to pregnant sows increased prevalence of intestinal bacteria that can be pathogenic in their offspring and favored microbes active in carbohydrate fermentation. Public and governmental concern regarding potential negative impacts of high dietary Zn has increased. Chapter 6 demonstrates that feeding high Zn to gestating sows will increase the amount of Zn excreted. However, the observed performance benefits of feeding high dietary Zn levels may partially offset its negative environmental footprint. This dissertation investigates possible biological mechanisms that high dietary Zn may work through to improve piglet survival and the possible environmental impact of feeding high Zn to gestating sows.
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    Misfits of wheat stem rust resistance-­‐ Unusual solutions to a consistent problem
    (2016-12) Briggs, Jordan
    Rust fungi include some of the most economically damaging pathogens of wheat. They are notorious for their ability to quickly spread in susceptible host populations and greatly reduce grain yield potential and quality when managed improperly. Puccinia graminis f. sp. tritici (Pgt), the causal agent of wheat stem rust, can cause yield losses exceeding 50%. Stem rust is controlled in the U.S.A. using several methods including the introduction of genetic resistance, selection for earlier maturing varieties, removal of the alternate host Berberis vulgaris, and the application of fungicides. Subsequently, epidemics of stem rust causing greater than 10% yield losses have not been observed in the U.S.A. since the mid 1950’s. Together, removal of B. vulgaris from wheat growing regions and the introduction of genetic resistance have accounted for much of the control of stem rust. Genetic resistance remains the dominant method of controlling stem rust in regions where removing B. vulgaris is not applicable. In more recent years, races of Pgt have been identified that overcome most widely deployed resistance genes. In 1999 race TTKSK was identified in Uganda that overcame stem rust resistance gene Sr31. Following deployment of Sr24 in Kenya, further selection for virulence resulted in the identification of race TTKST, then TTTSK (Sr36 virulence), and more recently TTKTT and TTKTK (SrTmp virulence). Major resistance genes have continually proven to not provide a durable form of resistance to wheat stem rust. Some resistance genes however have proven the test of time and remain effective to date. These resistance genes include Sr2, Lr34, Lr46, and Lr67. Each gene functions in an additive, minor-effect, and in some cases recessive manner, atypical of standard major genes, and provides and/or enhances resistance to multiple diseases including stem rust, leaf rust, stripe rust, and powdery mildew. Additionally Lr34 and Lr67 do not have the NB-LRR protein domains consistent with major genes. Durable genetic resistance to stem rust may require sources of resistance that deviate from standard mechanisms. This dissertation describes such sources of resistance. SrTm4 is a major gene identified in Triticum monococcum that functions in a recessive manner, is broadly effective, and elicits a mesothetic (intermediate-effect) infection type. The adult plant resistance observed in ‘Morocho Blanco’ was found to have two underlying QTL, Qsr.cdl.2BS.2 and Qsr.cdl.6AS.1. These two loci comprise much of the adult plant resistance in ‘Morocho Blanco’ and exhibit interactions with environment or pathogen race. The Sr12 mutants created in this dissertation were made to characterize the disease reducing capabilities of Sr12: a recessive, race specific major gene that co-locates with adult plant resistance to Sr12 virulent races. Lastly, this dissertation also describes the identification of putative susceptibility genes for rust pathogens in barley, maize, soybean, and Brachypodium distachyon. The putative susceptibility gene in B. distachyon was tested with a T-DNA insertion mutant and exhibits enhanced rust resistance, however, may be linked to changes in overall plant growth and development. Each source of rust resistance defies standard systems of characterization and includes some traits that are less desirable along with their resistance capabilities, for example: unstable expression due to environmental interactions, race specificity, or recessive gene action. However, the benefit of these sources of stem rust resistance may compensate for their less desirable traits.
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    Transcriptional Changes in the Breast Muscle of Thermally Challenged Turkey Poults
    (2018-05) Barnes, Natalie
    Thermal stress in poultry causes reduction in growth, impaired meat quality, and increased mortality. Growth selected and very young birds are especially susceptible. To investigate the transcriptional pathways involved in thermal stress we looked at the breast muscle (an economically important muscle group) of 1-day old turkey poults from a fast growth selected line and a related slow growing line. These young birds were brooded at one of 3 temperatures for 3 days: control (35°C), hot (39°C), or cold (31°C). RNA was isolated from the breast muscle after treatment and euthanasia. 28 libraries were sequenced for analysis (average 18 million reads per library). The reads were mapped to the current turkey genome assembly an analyzed for differential expression. As expected, the fast growing line responded differently to thermal stress than the slow growing line. It had a greater number of differentially expressed genes belonging to pathways that included: transcriptional control and ubiquitination. The slow growing line’s affected pathways were almost exclusively lipid metabolism There are no shared differentially expressed genes or pathways between the two lines. This divergence in response is highlighted by comparing the two lines at each temperature as well as there are more differentially expressed genes between the lines at the treatment temperatures than at the control temperature.