172 research outputs found
Characterization of hypertonic stress-induced protein damage and the cellular mechanisms for defense and repair in C. elegans
No full textProteostasis is maintained by a complex network of genes and processes which includes core synthesis and degradation machineries as well as chemical and protein chaperones. Much of what is known about the function and organization of the proteostasis network stems from analyzing how cells respond to genetic or environmental perturbation of proteomic integrity. Recent evidence points to a critical role for the proteostasis network in survival of hypertonic environments, but the proteotoxic effects of hypertonic stress remain largely undescribed. Employing the many experimental advantages of the nematode C. elegans, we provide the first detailed description of the nature and extent of protein damage caused by hypertonic stress. Misfolding and aggregation of diverse reporters and endogenous proteins are rapid and widespread in vivo. Additionally, we demonstrate that acclimation of C. elegans to a mild hypertonic environment activates unknown proteostasis activities capable of preventing aggregation during extreme hypertonic stress.
To define novel aspects of the hypertonic stress response and extend our understanding of cellular proteostasis strategies, we employ genetic and pharmacological approaches in determining the mechanism by which hypertonic acclimation enhances proteostasis. We hypothesize that chemical chaperones, protein chaperones, proteolysis machineries, and/or protein synthesis must be involved. Surprisingly, hypertonicity- or mutation-induced accumulation of glycerol, an organic osmolyte widely believed to act as a chemical chaperone in vivo, does not directly ameliorate protein damage during stress or aging. Protein chaperone expression is not transcriptionally upregulated. Further, hypertonic stress actually reduces protein degradation, an effect not reversed by acclimation. We demonstrate for the first time that suppression of protein translation during an environmental stress directly enhances proteostasis by preventing aggregation of extant proteins. Combined with recent observations that inhibition of translation extends lifespan and occurs naturally in response to other proteotoxic stressors, this finding suggests that translational reprogramming represents a conserved mechanism by which cells reduce the population of nascent, damage-prone proteins to enhance the availability and effectiveness of pre-existing chaperones
I Went to the End of Time, and This is What I Found: A Look into the Making of a Solo Performance
No full textabstract: I'll go to the end of time for you (and you don't even know my name) is an evening-length solo performance created and performed by Kristopher K.Q. Pourzal. It premiered November 8-10, 2013 in the Margaret Gisolo Dance Theatre of Arizona State University. The solo was the culmination (suspension, really) of a wild creative journey, the distillation of a process that initially involved several collaborators. Through a series of neurotically/erotically repetitive episodes of self-composed song, text, and dance, the work mines questions of the desire to be seen and the desire to feel alive. The conventions and constructs of the proscenium stage are both utilized and subverted in examining this platform as uniquely suited for revealing the nature of these experiences and their potential relationship. This document is primarily an account of the show's process--its before and after--and serves as a site of exploration, explanation, analysis, reflection, questioning, and ultimately furtherance of the practice-based research made manifest in the performances.Dissertation/ThesisM.F.A. Dance 201
AMPK at the Nexus of Energetics and Aging
No full textWhen energy supply is low, organisms respond by slowing aging and increasing resistance to diverse age-related pathologies. Targeting the mechanisms underpinning this response may therefore treat multiple disorders through a single intervention. Here, we discuss AMP-activated protein kinase (AMPK) as an integrator and mediator of several pathways and processes linking energetics to longevity. Activated by low energy, AMPK is both prolongevity and druggable, but its role in some pathologies may not be beneficial. As such, activating AMPK may modulate multiple longevity pathways to promote healthy aging, but unlocking its full potential may require selective targeting toward substrates involved in longevity assurance
Ultrafast extreme ultraviolet spectroscopy of transition metal dithiolate coordination complexes
No full textTransient tabletop M-edge x-ray absorption near edge structure (XANES) spectroscopy using extreme ultraviolet (XUV) light is used as a tool to interrogate the evolution of the metal center in a series of transition metal dithiolate complexes. The behavior of these molecules after absorption of light has implications for the development of catalysts and photosensitizers using earth-abundant transition metals. The cobalt dithiolene complex, [Co(bdt)2]- (bdt = 1,2-benzendithiolate), is primarily known for its ligand-noninnocence and participation in the catalytic production of hydrogen. After excitation of [Co(bdt)2]- with visible light, its relaxation dynamics are tracked with a combination of optical and transient M-edge XANES spectroscopic techniques that allow for the identification of a ligand-to-metal charge transfer (LMCT) excited state whose spin can be determined by comparison to semi-empirical ligand field multiplet calculations. The combination of optical and x-ray techniques is crucial to identifying relaxation processes that affect predominantly either the metal or the ligand. NEVPT2 calculations are used to understand its optical absorption spectrum and rationalize the timescale by which the molecule relaxes to the ground state. A set of three of cobalt tris(dithiolate) complexes with varying ligand field strength have been studied using optical transient absorption spectroscopy which shows a difference of a factor of at least ten in their excited state lifetimes. Understanding the origin of this change is important to further extending the lifetimes of photosensitizers. The sensitivity of M-edge XANES spectroscopy to the oxidation and spin state of a metal enabled the identification of the excited states involved in the relaxation of all three complexes. The contribution of a long-lived charge transfer state was ruled out and the final excited state was determined to be a 5T state. Finally, a nickel dithiocarbamate complex, Ni(dedtc)2 (dedtc = diethyldithiocarbamate, S2CNEt2) was studied as a simple analogue of a square planar nickel-centered hydrogen catalyst. Examination of this complex and the equivalent copper and zinc complexes reveal new phenomena in XUV spectroscopy, including dependence of the ligand absorbance on the metal center and observation of a ligand-based change in absorbance beneath the nickel M-edge after LMCT excitation.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-05-01The student, Kristopher Benke, accepted the attached license on 2021-04-12 at 10:11.The student, Kristopher Benke, submitted this Dissertation for approval on 2021-04-12 at 10:46.This Dissertation was approved for publication on 2021-04-14 at 11:42.DSpace SAF Submission Ingestion Package generated from Vireo submission #16283 on 2021-09-16 at 17:02:51Made available in DSpace on 2021-09-17T02:34:23Z (GMT). No. of bitstreams: 3
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Previous issue date: 2021-04-14Embargo set by: Seth Robbins for item 118497
Lift date: 2023-09-17T02:34:57Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemAuthor requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Onl
Nutritional Justice Action Plan
No full textYou are a part of a collegewide effort to increase access to education and empower students through "open pedagogy." Open pedagogy is a "free access" educational practice that places you - the student - at the center of your own learning process in a more engaging, collaborative learning environment. The ultimate purpose of this effort is to achieve greater social justice in our community in which the work can be freely shared with the broader community. This is a renewable assignment that is designed to enable you to become an agent of change in your community through the framework of the United Nations Sustainable Development Goals (SDGs). For this work, you will integrate the disciplines of Sociology and Nutrition to achieve SDG #2: Zero Hunger with a focus on Target 2.1
Nutritional Injustice Public Service Announcement
No full textYou are a part of a collegewide effort to increase access to education and empower students through "open pedagogy." Open pedagogy is a "free access" educational practice that places you - the student - at the center of your own learning process in a more engaging, collaborative learning environment. The ultimate purpose of this effort is to achieve greater social justice in our community in which the work can be freely shared with the broader community. This is a renewable assignment that is designed to enable you to become an agent of change in your community through the framework of the United Nations Sustainable Development Goals (SDGs). For this work, you will integrate the disciplines of Sociology and Nutrition to achieve SDG #2: Zero Hunger with a focus on Target 2.1.Assignment Guideline
Nutritional Justice stakeholder analysis/ power analysis/ systems analysis/ infographic
No full textYou are a part of a collegewide effort to increase access to education and empower students through "open pedagogy." Open pedagogy is a "free access" educational practice that places you - the student - at the center of your own learning process in a more engaging, collaborative learning environment. The ultimate purpose of this effort is to achieve greater social justice in our community in which the work can be freely shared with the broader community. This is a renewable assignment that is designed to enable you to become an agent of change in your community through the framework of the United Nations Sustainable Development Goals (SDGs). For this work, you will integrate the disciplines of Sociology and Nutrition to achieve SDG #2: Zero Hunger with a focus on Target 2.1.Assignment Guideline
Characterization of the proteostasis roles of glycerol accumulation, protein degradation and protein synthesis during osmotic stress in C. elegans.
No full textExposure of C. elegans to hypertonic stress-induced water loss causes rapid and widespread cellular protein damage. Survival in hypertonic environments depends critically on the ability of worm cells to detect and degrade misfolded and aggregated proteins. Acclimation of C. elegans to mild hypertonic stress suppresses protein damage and increases survival under more extreme hypertonic conditions. Suppression of protein damage in acclimated worms could be due to 1) accumulation of the chemical chaperone glycerol, 2) upregulation of protein degradation activity, and/or 3) increases in molecular chaperoning capacity of the cell. Glycerol and other chemical chaperones are widely thought to protect proteins from hypertonicity-induced damage. However, protein damage is unaffected by gene mutations that inhibit glycerol accumulation or that cause dramatic constitutive elevation of glycerol levels. Pharmacological or RNAi inhibition of proteasome and lyosome function and measurements of cellular protein degradation activity demonstrated that upregulation of protein degradation mechanisms plays no role in acclimation. Thus, changes in molecular chaperone capacity must be responsible for suppressing protein damage in acclimated worms. Transcriptional changes in chaperone expression have not been detected in C. elegans exposed to hypertonic stress. However, acclimation to mild hypertonicity inhibits protein synthesis 50-70%, which is expected to increase chaperone availability for coping with damage to existing proteins. Consistent with this idea, we found that RNAi silencing of essential translational components or acute exposure to cycloheximide results in a 50-80% suppression of hypertonicity-induced aggregation of polyglutamine-YFP (Q35::YFP). Dietary changes that increase protein production also increase Q35::YFP aggregation 70-180%. Our results demonstrate directly for the first time that inhibition of protein translation protects extant proteins from damage brought about by an environmental stressor, demonstrate important differences in aging- versus stress-induced protein damage, and challenge the widely held view that chemical chaperones are accumulated during hypertonic stress to protect protein structure/function
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