Matching Items (4)

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POTASSIUM EFFLUX DRIVES SYK-MEDIATED REGULATION OF INFLAMMASOME ACTIVITY IN MOUSE MACROPHAGES

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Inflammation is part of the body’s response to invading pathogens, injury, and a wide range of diseases. Although inflammation is paramount to maintain a healthy immune system, unregulated inflammation can

Inflammation is part of the body’s response to invading pathogens, injury, and a wide range of diseases. Although inflammation is paramount to maintain a healthy immune system, unregulated inflammation can aggravate chronic conditions or cause severe, acute pathologies. Pyroptosis, a caspase-1-dependent, pro-inflammatory cell death that results in the release of IL-1β and IL-18, has been implicated in propagating an inflammatory response in the body. Pyroptosis has been shown to result from the activation of the NLRP3 inflammasome. Furthermore, multiple reports have demonstrated that intracellular potassium efflux and spleen tyrosine kinase (Syk) activity are both essential for facilitating the assembly of the NLRP3 inflammasome and proper processing and release of IL-1β and IL-18. The focus of this thesis was to determine the relationship between intracellular potassium efflux and Syk during key regulatory events in the activation of the NLRP3 inflammasome by identifying their effect on pro-inflammatory cytokine release, inflammasome assembly, mitochondrial reactive oxygen species (mROS) generation, and cell death. Both inhibiting potassium efflux from occurring and deactivating Syk significantly reduced the amount of pro-inflammatory cytokine released (70-100% reduction), the number of inflammasomes assembled (60-80% reduction), the amount of mROS generation, and the quantity of cell death (50-90% reduction). Moreover, it was discovered that potassium efflux was required for Syk activation, but Syk activation had no effect on potassium efflux. Their relationship proved to be unidirectional. This study provides the first demonstration of ion flux-dependent regulation of kinase activation in the NLRP3 inflammasome pathway and provides support for targeting ion regulation mechanisms and Syk kinase activity to manipulate macrophage-mediate inflammatory processes.

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Date Created
  • 2015-05

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Solar wind sodium and potassium abundance analysis in Genesis diamond-on-silicon and silicon bulk solar wind collectors, and how hydration affects the microtexture of olivine phase transformation at 18 GPa

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The present work covers two distinct microanalytical studies that address issues in planetary materials: (1) Genesis Na and K solar wind (SW) measurements, and (2) the effect of water on

The present work covers two distinct microanalytical studies that address issues in planetary materials: (1) Genesis Na and K solar wind (SW) measurements, and (2) the effect of water on high-pressure olivine phase transformations.

NASA’s Genesis mission collected SW samples for terrestrial analysis to create a baseline of solar chemical abundances based on direct measurement of solar material. Traditionally, solar abundances are estimated using spectroscopic or meteoritic data. This study measured bulk SW Na and K in two different Genesis SW collector materials (diamond-like carbon (DlC) and silicon) for comparison with these other solar references. Novel techniques were developed for Genesis DlC analysis. Solar wind Na fluence measurements derived from backside depth profiling are generally lower in DlC than Si, despite the use of internal standards. Nevertheless, relative to Mg, the average SW Na and K abundances measured in Genesis wafers are in agreement with solar photospheric and CI chondrite abundances, and with other SW elements with low first ionization potential (within error). The average Genesis SW Na and K fluences are 1.01e11 (+9e09, -2e10) atoms/cm2 and 5.1e09 (+8e08, -8e08) atoms/cm2, respectively. The errors reflect average systematic errors. Results have implications for (1) SW formation models, (2) cosmochemistry based on solar material rather than photospheric measurements or meteorites, and (3) the accurate measurement of solar wind ion abundances in Genesis collectors, particularly DlC and Si.

Deep focus earthquakes have been attributed to rapid transformation of metastable olivine within the mantle transition zone (MTZ). However, the presence of H2O acts to overcome metastability, promoting phase transformation in olivine, so olivine must be relatively anhydrous (<75 ppmw) to remain metastable to depth. A microtextural analysis of olivine phase transformation products was conducted to test the feasibility for subducting olivine to persist metastably to the MTZ. Transformation (as intracrystalline or rim nucleation) shifts from ringwoodite to ringwoodite-wadsleyite nucleation with decreasing H2O content within olivine grains. To provide accurate predictions for olivine metastability at depth, olivine transformation models must reflect how changing H2O distributions lead to complex changes in strain and reaction rates within different parts of a transforming olivine grain.

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Date Created
  • 2015

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Hypotensive effects of potassium and magnesium

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Despite recent strides for awareness, treatment, and control of hypertension, prevalence remains high with estimates suggesting one third of Americans have hypertension. The hypotensive effects of potassium and magnesium have

Despite recent strides for awareness, treatment, and control of hypertension, prevalence remains high with estimates suggesting one third of Americans have hypertension. The hypotensive effects of potassium and magnesium have been known and administered in a clinical setting for nearly a century. The purpose of this study was to examine the effectiveness of taking a potassium/magnesium supplement to help reduce blood pressure in individuals with mildly-moderately elevated blood pressure. In this randomized, controlled crossover trial, potassium and magnesium supplementation was explored among healthy adults with mildly elevated blood pressure in Phoenix, Arizona. Subjects (n = 12) were randomly assigned to ingest either the treatment chewy bar (217 mg potassium/day; 70.8 mg magnesium/day) or a placebo chewy bar for four weeks. For the subsequent four weeks, subjects ingested the other corresponding chewy bar. Systolic (SBP), diastolic (DBP), and average blood pressure values were not significantly different between the two groups (p = 0.645, p = 0.464 and p = 0.939, respectively). Baseline mean blood pressure was 121.0/75.7 mm Hg. The 12 subjects (8 females, 4 males) had a mean age of 29.3 years old and a mean BMI of 26.2. After four weeks, the treatment group had a slightly higher SBP (118.3 ± 13.3 mm Hg) than the control group (116.5 ± 17.8 mm Hg); however, DBP was lower in the treatment group (71.7 ± 12.4 mm Hg) than the control group (73.0 ± 10.0 mm Hg). In conclusion, daily supplementation of potassium and magnesium (217.2 mg/day and 70.8 mg/day, respectively) did not significantly lower blood pressure in adults with mildly-moderately elevated blood pressure.

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Date Created
  • 2015

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Ammonium and potassium removal from real hydrolyzed urine using natural zeolites

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The goal of this research was to study the effect of dilution on ammonium and potassium removal from real hydrolyzed urine. The performance of two natural zeolites, clinoptilolite and chabazite,

The goal of this research was to study the effect of dilution on ammonium and potassium removal from real hydrolyzed urine. The performance of two natural zeolites, clinoptilolite and chabazite, was studied and compared with the help of batch equilibrium experiments at four dilution levels: 100%, 10%, 1% and 0.1% (urine volume/total solution volume). Further, the sorption behavior of other exchangeable ions (sodium, calcium and magnesium) in clinoptilolite and chabazite was studied to improve the understanding of ion exchange stoichiometry. Ammonium and potassium removal were highest at undiluted level in samples treated with clinoptilolite. This is a key finding as it illustrates the benefit of urine source separation. Chabazite treated samples showed highest ammonium and potassium removal at undiluted level at lower doses. At higher doses, potassium removal was similar in undiluted and 10% urine solutions whereas ammonium removal was the highest in 10% urine solutions. In general, chabazite showed higher ammonium and potassium removal than clinoptilolite. The result showed that ion exchange was stoichiometric in solutions with higher urine volumes.

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Date Created
  • 2019