Life Sciences Commons^™

Short-Term Removal Of Exercise Impairs Glycemic Control In Older Adults: A Randomized Trial, Leryn J. Reynolds, Troy M. Williams, Joel E. Harden, Hannah M. Twiddy, Monica L. Kearney

Human Movement Sciences Faculty Publications

Postprandial glycemia (PPG) predicts cardiovascular disease, and short-term physical inactivity increases PPG in young, active adults. Whether this occurs in older, active adults who may be more prone to bouts of inactivity is unknown. This study determined if postprandial interstitial glucose (PPIG) was impaired in active older adults following the removal of exercise for 3 days (NOEX) compared to active young adults. In this randomized, crossover study, 11 older (69.1 ± 1.9 years) and 9 young (32.8 ± 1.8 years) habitually active (≥90 min/week of exercise) adults completed 3-days of NOEX and 3-days of normal habitual exercise (EX), separated by …

The Intersection Between Toxicology And Aging Research: A Toxic Aging Coin Perspective., John P. Wise Jr.

Faculty Scholarship

We are imminently faced with the challenges of an increasingly aging population and longer lifespans due to improved health care. Concomitantly, we are faced with ubiquitous environmental pollution linked with various health effects and age-related diseases which contribute to increased morbidity with age. Geriatric populations are rarely considered in the development of environmental regulations or in toxicology research. Today, life expectancy is often into one’s 80s or beyond, which means multiple decades living as a geriatric individual. Hence, adverse health effects and late-onset diseases might be due to environmental exposures as a geriatric, and we currently have no way of …

Comparison Of Constant Load Exercise Intensity For Verification Of Maximal Oxygen Uptake Following A Graded Exercise Test In Older Adults, Ian R. Villanueva, John C. Campbell, Serena M. Medina, Theresa M. Jorgensen, Shannon L. Wilson, Siddhartha S. Angadi, Glenn A. Gaesser, Jared M. Dickinson

All Faculty Scholarship for the College of Education and Professional Studies

Maximal oxygen uptake (VO₂max) declines with advancing age and is a predictor of morbidity and mortality risk. The purpose here was to assess the utility of constant load tests performed either above or below peak work rate obtained from a graded exercise test for verification of VO₂max in older adults. Twenty-two healthy older adults (9M, 13F, 67 ± 6 years, BMI: 26.3 ± 5.1 kg·m⁻²) participated in the study. Participants were asked to complete two experimental trials in a randomized, counterbalanced cross-over design. Both trials (cycle ergometer) consisted of (1) an identical graded exercise …

The Impacts Of Aging, Sedentarism, And Exercise On Neurotrophic Factor Expression And Innervation In The Heart And The Effects Of Treatment With Α-Cgrp On Heart Function, Gabriel Almeida Alves

Dissertations

Neurotrophic factors (NFs) are important molecules responsible for development, differentiation, regeneration, and maintenance of new and mature neurons. Neurotrophic factors act as neurocytokines and may assist with the regulation of axonal and dendritic arrangements and synaptic plasticity between neurons themselves or with other non-neural target tissues. In this study, we analyze the levels of two NFs: glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). Cardiomyocytes produce these neurotrophic factors which assist with the innervation pattern of the heart. The heart is innervated by the two branches of the autonomic nervous system; namely the sympathetic nervous system and …

Multimodal Neuroimaging Of Hiv And Aging, Brandon Lew

Theses & Dissertations

HIV infection remains a significant contributor to disease burden, and with the success of antiretroviral therapies, the population of people with HIV is aging. A growing literature suggests a relationship between HIV-infection and a profile of age advancement, most notably in molecular studies of epigenetics. However, despite the widely-known high prevalence of HIV-related brain atrophy, functional deficits, and HIV-associated neurocognitive disorder (HAND), epigenetic age advancement has not been linked to HIV-related changes in neuroimaging metrics.

We applied three neuroimaging methods, structural MRI, resting state functional MRI, and resting state MEG, to study the brain structure and function of 121 virally-suppressed …

Cortical Iron Disrupts Functional Connectivity Networks Supporting Working Memory Performance In Older Adults, Valentinos Zachariou, Christopher E. Bauer, Elayna R. Seago, Flavius D. Raslau, David K. Powell, Brian T. Gold

Neuroscience Faculty Publications

Excessive brain iron negatively affects working memory and related processes but the impact of cortical iron on task-relevant, cortical brain networks is unknown. We hypothesized that high cortical iron concentration may disrupt functional circuitry within cortical networks supporting working memory performance. Fifty-five healthy older adults completed an N-Back working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Participants also underwent quantitative susceptibility mapping (QSM) imaging for assessment of non-heme brain iron concentration. Additionally, pseudo continuous arterial spin labeling scans were obtained to control for potential contributions of cerebral blood volume and structural brain images were used to control …

Microrna-Based Biomarkers In Alzheimer’S Disease (Ad), Yuhai Zhao, Vivian Jaber, Peter N. Alexandrov, Andrea Vergallo, Simone Lista, Harald Hampel, Walter J. Lukiw

School of Medicine Faculty Publications

Alzheimer’s disease (AD) is a multifactorial, age-related neurological disease characterized by complex pathophysiological dynamics taking place at multiple biological levels, including molecular, genetic, epigenetic, cellular and large-scale brain networks. These alterations account for multiple pathophysiological mechanisms such as brain protein accumulation, neuroinflammatory/neuro-immune processes, synaptic dysfunction, and neurodegeneration that eventually lead to cognitive and behavioral decline. Alterations in microRNA (miRNA) signaling have been implicated in the epigenetics and molecular genetics of all neurobiological processes associated with AD pathophysiology. These changes encompass altered miRNA abundance, speciation and complexity in anatomical regions of the CNS targeted by the disease, including modified miRNA expression …

Meta-Analysis Of The Alzheimer's Disease Human Brain Transcriptome And Functional Dissection In Mouse Models., Ying-Wooi Wan, Rami Al-Ouran, Carl G Mangleburg, Thanneer M Perumal, Tom V Lee, Katherine Allison, Vivek Swarup, Cory C Funk, Chris Gaiteri, Mariet Allen, Minghui Wang, Sarah M Neuner, Catherine C Kaczorowski, Vivek M Philip, Gareth R Howell, Heidi Martini-Stoica, Hui Zheng, Hongkang Mei, Xiaoyan Zhong, Jungwoo Wren Kim, Valina L Dawson, Ted M Dawson, Ping-Chieh Pao, Li-Huei Tsai, Jean-Vianney Haure-Mirande, Michelle E Ehrlich, Paramita Chakrabarty, Yona Levites, Xue Wang, Eric B Dammer, Gyan Srivastava, Sumit Mukherjee, Solveig K Sieberts, Larsson Omberg, Kristen D Dang, James A Eddy, Phil Snyder, Yooree Chae, Sandeep Amberkar, Wenbin Wei, Winston Hide, Christoph Preuss, Ayla Ergun, Phillip J Ebert, David C Airey, Sara Mostafavi, Lei Yu, Hans-Ulrich Klein, Accelerating Medicines Partnership, Alzheimer’S Disease Consortium, Gregory W Carter, David A Collier, Todd E Golde, Allan I Levey, David A Bennett, Karol Estrada, T Matthew Townsend, Bin Zhang, Eric Schadt, Philip L De Jager, Nathan D Price, Nilüfer Ertekin-Taner, Zhandong Liu, Joshua M Shulman, Lara M Mangravite, Benjamin A Logsdon

Articles, Abstracts, and Reports

We present a consensus atlas of the human brain transcriptome in Alzheimer's disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington's disease, amyotrophic …

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …

Metformin Blunts Muscle Hypertrophy In Response To Progressive Resistance Exercise Training In Older Adults: A Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial: The Masters Trial, R. Grace Walton, Cory M. Dungan, Douglas E. Long, S. Craig Tuggle, Kate Kosmac, Bailey D. Peck, Heather M. Bush, Alejandro G. Villasante Tezanos, Gerald Mcgwin, Samuel T. Windham, Fernando Ovalle, Marcas M. Bamman, Philip A. Kern, Charlotte A. Peterson

Center for Muscle Biology Faculty Publications

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double-blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body …

The Effects Of Aging On Sleep Parameters In A Healthy, Melatonin-Competent Mouse Model, Jiffin K. Paulose, Chanung Wang, Bruce F. O'Hara, Vincent M. Cassone

Biology Faculty Publications

Background: Sleep disturbances are common maladies associated with human age. Sleep duration is decreased, sleep fragmentation is increased, and the timing of sleep onset and sleep offset is earlier. These disturbances have been associated with several neurodegenerative diseases. Mouse models for human sleep disturbances can be powerful due to the accessibility to neuroscientific and genetic approaches, but these are hampered by the fact that most mouse models employed in sleep research have spontaneous mutations in the biosynthetic pathway(s) regulating the rhythmic production of the pineal hormone melatonin, which has been implicated in human sleep.

Purpose and method: The present study …

Distinct Patterns Of Default Mode And Executive Control Network Circuitry Contribute To Present And Future Executive Function In Older Adults, Christopher A. Brown, Frederick A. Schmitt, Charles D. Smith, Brian T. Gold

Neuroscience Faculty Publications

Executive function (EF) performance in older adults has been linked with functional and structural profiles within the executive control network (ECN) and default mode network (DMN), white matter hyperintensities (WMH) burden and levels of Alzheimer's disease (AD) pathology. Here, we simultaneously explored the unique contributions of these factors to baseline and longitudinal EF performance in older adults. Thirty-two cognitively normal (CN) older adults underwent neuropsychological testing at baseline and annually for three years. Neuroimaging and AD pathology measures were collected at baseline. Separate linear regression models were used to determine which of these variables predicted composite EF scores at baseline …

The Influence Of Stressful Life Events On The Development Of Type 2 Diabetes, Joshua Minks

Dissertations

This study examined the relationship between distress and the development of Type 2 diabetes mellitus (T2DM) in the presence of established risk factors. Distress secondary to mental health disparities, stressful life events, and work conditions has been shown to promote insulin resistance and the development of T2DM.

Subjects (N=79) diagnosed with T2DM within the previous six months were recruited from SSM Health Centers and VA Medical Centers in the greater St. Louis area. They completed the Recent Life Changes Questionnaire, ENRICHD Social Support Instrument, and a demographic survey and analyses were conducted to determine differences between the veteran …

Neuroimaging Biomarkers Of Mtor Inhibition On Vascular And Metabolic Functions In Aging Brain And Alzheimer’S Disease, Jennifer Lee, Lucille M. Yanckello, David Ma, Jared D. Hoffman, Ishita Parikh, Scott Thalman, Bjoern Bauer, Anika M. S. Hartz, Fahmeed Hyder, Ai-Ling Lin

Pharmacology and Nutritional Sciences Faculty Publications

The mechanistic target of rapamycin (mTOR) is a nutrient sensor of eukaryotic cells. Inhibition of mechanistic mTOR signaling can increase life and health span in various species via interventions that include rapamycin and caloric restriction (CR). In the central nervous system, mTOR inhibition demonstrates neuroprotective patterns in aging and Alzheimer’s disease (AD) by preserving mitochondrial function and reducing amyloid beta retention. However, the effects of mTOR inhibition for in vivo brain physiology remain largely unknown. Here, we review recent findings of in vivo metabolic and vascular measures using non-invasive, multimodal neuroimaging methods in rodent models for brain aging and AD. …

Human Body Composition And Immunity: Visceral Adipose Tissue Produces Il-15 And Muscle Strength Inversely Correlates With Nk Cell Function In Elderly Humans, Ahmad Al-Attar, Steven R. Presnell, Jody L. Clasey, Douglas E. Long, R. Grace Walton, Morgan Sexton, Marlene E. Starr, Philip A. Kern, Charlotte A. Peterson, Charles T. Lutz

Pathology and Laboratory Medicine Faculty Publications

Natural killer (NK) lymphocyte-mediated cytotoxicity and cytokine secretion control infections and cancers, but these crucial activities decline with age. NK cell development, homeostasis, and function require IL-15 and its chaperone, IL-15 receptor alpha (IL-15Rα). Macrophages and dendritic cells (DC) are major sources of these proteins. We had previously postulated that additional IL-15 and IL-15Rα is made by skeletal muscle and adipose tissue. These sources may be important in aging, when IL-15-producing immune cells decline. NK cells circulate through adipose tissue, where they may be exposed to local IL-15. The objectives of this work were to determine (1) if human muscle, …

Serum Tumor Necrosis Factor-Alpha Associates With Myocardial Oxygen Demand And Exercise Tolerance In Postmenopausal Women, Stephen J. Carter, David R. Bryan, William H. Neumeier, Stephen P. Glasser, Gary R. Hunter

Internal Medicine Faculty Publications

The functional implications of serum tumor necrosis factor-alpha (TNF-α), a marker of oxidative stress, on hemodynamic parameters at rest and during physical exertion are unclear. The aims of this investigation were to examine the independent associations of TNF-α on myocardial oxygen demand at rest and during submaximal exercise, while also evaluating the association of TNF-α on exercise tolerance. Forty, postmenopausal women, provided blood samples and completed a modified-Balke protocol to measure maximal oxygen uptake (VO_2max). Large artery compliance was measured by pulse contour analyses while rate-pressure product (RPP), an index of myocardial oxygen demand, was measured at rest …

Aging, Inflammation, And Gut Microbiota In Mice, Jody Demeo

Honors Projects

Inflammation and gut microbiota are two areas of study that can be linked to aging in the body. As a person ages, systemic inflammation tends to increase, and changes in microbiota in the gastrointestinal system occur as well.

Clinically Silent Alzheimer's And Vascular Pathologies Influence Brain Networks Supporting Executive Function In Healthy Older Adults, Brian T. Gold, Christopher A. Brown, Jonathan G. Hakun, Leslie M. Shaw, John Q. Trojanowski, Charles D. Smith

Neuroscience Faculty Publications

Aging is associated with declines in executive function. We examined how executive functional brain systems are influenced by clinically silent Alzheimer’s disease (AD) pathology and cerebral white matter hyperintensities (WMHs). Twenty-nine younger adults and thirty-four cognitively normal older adults completed a working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Older adults further underwent lumbar cerebrospinal fluid (CSF) draw for assessment of AD pathology and FLAIR imaging for assessment of WMHs. Accurate working memory performance in both age groups was associated with high fronto-visual functional connectivity (fC). However, in older adults, higher expression of fronto-visual fC was linked …

Pro-Angiogenesis Therapy And Aging: A Mini-Review, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Apart from major illnesses and chronic afflictions, the elderly experience lesser ailments, such as muscle weakness, cold intolerance, and transient memory lapses. Physical signs in the aged include wrinkled skin and the slow healing of skin abrasions. These ailments and signs are grouped together because they may be due in part to an age-linked, waning microcirculation. A reduced capillary density (CD) throughout the body of aged people and animals has been reported in over 40 papers. The reduced CD is due in turn to declining levels of angiogenic growth factors (AGFs) throughout the body during old age, as documented in …

Influence Of Expectations Of Aging On Older Women’S Use Of Dietary Supplements Using The Health Promotion Theory, Barbara Emily Hekel

Theses and Dissertations

The use of vitamins, minerals and herbal supplements by older adults is increasing and changing. There are concerns about supplement quality, safety, and vitamin D overuse. Little is known about supplement use by nursing home residents and about factors that influence older women to use supplements. The current study describes the supplement use of 247 nursing home residents and 110 independent living women 65 years or older in the Midwestern United States. A secondary analysis of 247 medication administration records describes the prevalence of vitamin, mineral, and herbal supplement use of nursing home residents. Using the health promotion theory, the …

Progressive Age-Dependence And Frequency Difference In The Effect Of Gap Junctions On Active Cochlear Amplification And Hearing, Liang Zong, Jin Chen, Yan Zhu, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Mutations of Connexin 26 (Cx26, GJB2), which is a predominant gap junction isoform in the cochlea, can induce high incidence of nonsyndromic hearing loss. We previously found that targeted-deletion of Cx26 in supporting Deiters cells and outer pillar cells in the cochlea can influence outer hair cell (OHC) electromotility and reduce active cochlear amplification leading to hearing loss, even though there are no gap junction connexin expressions in the auditory sensory hair cells. Here, we further report that hearing loss and the reduction of active amplification in the Cx26 targeted-deletion mice are progressive and different at high and low …

Csf Protein Changes Associated With Hippocampal Sclerosis Risk Gene Variants Highlight Impact Of Grn/Pgrn, David W. Fardo, Yuriko Katsumata, John S. K. Kauwe, Yuetiva Deming, Oscar Harari, Carlos Cruchaga, Alzheimer’S Disease Neuroimaging Initiative, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Objective—Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).

Methods—Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.

Results—The GRN risk …

The Default Mode Network And Executive Function: Influence Of Age, White Matter Connectivity, And Alzheimer’S Pathology, Christopher A. Brown

Theses and Dissertations--Neuroscience

The default mode network (DMN) consists of a set of interconnected brain regions supporting autobiographical memory, our concept of the self, and the internal monologue. These processes must be maintained at all times and consume the highest amount of the brain’s energy during its baseline state. However, when faced with an active, externally-directed cognitive task, the DMN shows a small, but significant, decrease in activity. The reduction in DMN activity during the performance of an active, externally-directed task compared to a baseline state is termed task-induced deactivation (TID), which is thought to ‘free-up’ resources required to respond to external demands. …

Narrative Review Of Vitamin D And Its Specific Impact On Balance Capacity In Older Adults, Ray Marks

Publications and Research

Introduction and Aims: Falls injuries among older adults, a widespread well-established contributor to high disability levels, excess morbidity and mortality rates, have many causes. This review examines the association between vitamin D levels and postural stability or balance control—a fairly consistent predictor of falls among older adults.

Materials and Method: All relevant English language peer reviewed research publications detailing the relationship between vitamin D levels and balance control among the elderly were sought. Key words included “Vitamin D and Balance or Postural Control.” Databases used were Academic Search Complete, PubMed, Scopus, and Web of Science.

Results: Analysis showed no consistent …

Age- And Sex-Related Changes In Fasting Plasma Glucose And Lipoprotein In Cynomolgus Monkeys, Feng Yue, Guodong Zhang, Rongping Tang, Zhouquan Zhang, Liqiong Teng, Zhiming Zhang

Neuroscience Faculty Publications

Background: The age-related dysfunction of glucose and lipid metabolism has a long-standing relationship with cardiovascular and neurodegenerative disease. However, the effects of metabolic dysfunction on men and women are different. Reasons for these sex differences remains unclear. Cynomolgus monkeys have been used, in the past, for the study of human metabolic diseases due to their biologically proximity to humans. Nevertheless, few studies to date have focused on both age- and sex-related differences in glucose and lipid metabolism. The present study was designed to specifically address these questions by using a large cohort of cynomolgus monkeys (N = 1,399) including …

The Role Of Capillaries In The Lesser Ailments Of Old Age And In Alzheimer's Disease And Vascular Dementia: The Potential Of Pro-Therapeutic Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Apart from chronic diseases (arthritis, diabetes, etc.), old age is generally characterized by three lesser ailments: muscle weakness, minor memory lapses, and cold intolerance. This trio of complaints may have a common, underlying cause, namely, the age-associated reduced microcirculation in muscles, brain, skin, and elsewhere in the body. The Angiogenesis Hypothesis proposes that old age is in part a deficiency disease due to the decline in angiogenic (AG) factors, resulting in a reduced capillary density (CD) throughout the body. Over fifty published papers document waning levels of AG factors and/or decreased CD in various organ systems of aged animals and …

Muscle Weakness During Aging: A Deficiency State Involving Declining Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

This essay begins by proposing that muscle weakness of old age from sarcopenia is due in large part to reduced capillary density in the muscles, as documented in 9 reports of aged persons and animals. Capillary density (CD) is determined by local levels of various angiogenic factors, which also decline in muscles with aging, as reported in 7 studies of old persons and animals. There are also numerous reports of reduced CD in the aged brain and other studies showing reduced CD in the kidney and heart of aged animals. Thus a waning angiogenesis throughout the body may be …

Impaired Skeletal Muscle Blood Flow Control With Advancing Age In Humans: Attenuated Atp Release And Local Vasodilation During Erythrocyte Deoxygenation, Brett S. Kirby, Anne R. Crecelius, Wyatt F. Voyles, Frank A. Dinenno

Anne R. Crecelius

Rationale: Skeletal muscle blood flow is coupled with the oxygenation state of hemoglobin in young adults, whereby the erythrocyte functions as an oxygen sensor and releases ATP during deoxygenation to evoke vasodilation. Whether this function is impaired in humans of advanced age is unknown. Objective: To test the hypothesis that older adults demonstrate impaired muscle blood flow and lower intravascular ATP during conditions of erythrocyte deoxygenation. Methods and Results: We showed impaired forearm blood flow responses during 2 conditions of erythrocyte deoxygenation (systemic hypoxia and graded handgrip exercise) with age, which was caused by reduced local vasodilation. In young adults, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …