Life Sciences Commons^™

Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang

Dartmouth College Ph.D Dissertations

DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …

Parent Perspectives On Barriers And Facilitators To Optimal Healthcare And Medical Screenings For Children With Down Syndrome In South Carolina, Vinita Oberoi Leedom

Theses and Dissertations

Children with Down syndrome (DS) often have co-occurring conditions affecting vision, hearing, sleeping, and more. Screenings, as recommended by the American Academy of Pediatrics (AAP), can help prevent secondary disability, and allow children to thrive. Studies have evaluated the receipt of recommended screenings, but barriers and facilitators surrounding access to screenings and care have not been described.

Parents of 24 children with DS in SC were recruited through schools and family support groups. One-hour long interviews were conducted in English and Spanish. Information was collected on health, healthcare quality, respiratory concerns, pandemic effects, access to care, and knowledge about AAP …

Local Translation And Focal Adhesions Are Dysregulated In Down Syndrome, Ashlyn Gotberg, Nikita Kirkise M.S., Kristy Welshhans Ph.D.

Senior Theses

During cellular migration, fibroblasts sense extracellular cues through membrane complexes at their leading edge and can respond to these cues via local translation. Local translation is the process in which mRNAs are transported to subcellular regions and translated in response to specific cues. There is evidence that local translation may be dysregulated in the neurodevelopmental disorder, Down syndrome, which is caused by the triplication of chromosome 21 and results in genome-wide dysregulation of protein expression. To determine if dysregulated local translation contributes to Down syndrome, we used three sets of primary fibroblasts from individuals with Down syndrome and apparently healthy …

Physical Activity In Individuals With Down Syndrome: A Qualitative Examination Of The Perspectives Of Guardians And Health Professionals, Emma Schultz

Theses and Dissertations

Identifying factors that influence physical activity (PA) among individuals with Down syndrome (DS) is essential for PA promotion. Insight can be gained from guardians and health professionals. The purpose was to compare guardians and health professional perspectives on facilitators and barriers of PA in individuals with DS. Interviews were conducted with 11 guardians (5 mothers, 4 fathers, 2 legal guardians) and 11 professionals (4 PA specialists, 3 physical therapists, 4 occupational therapists). Grounded Theory was applied to data analysis. Barriers and facilitators fit the levels of the Ecological Model of Health Behavior: (a) Intrapersonal (perceived rewards); (b) Interpersonal (interaction); (c) …

Effects Of A Remote Exercise Intervention On Aerobic Endurance In Individuals With Down Syndrome, Andrew Murata, Elena Wolf, Jonathan Crimm, Benjamin Lee

UNLV Theses, Dissertations, Professional Papers, and Capstones

Purpose: Down syndrome (Ds) or Trisomy 21 is a common genetic birth condition, and those with Ds typically display decreased cardiorespiratory fitness compared to those without Ds, potentially leading to an increased risk for cardiovascular conditions and mortality. Low cardiorespiratory fitness is partially caused by low physical activity levels in this population. The COVID-19 pandemic caused community-based activity programs to shut down, as individuals with Ds are at increased risk for COVID-19 hospitalization and death. Thus, it was vital to explore alternatives of in-person exercise during the pandemic. The purpose of this study was to investigate the effects of a …

The Effects Of A Telehealth Exercise Intervention On Balance In Adults With Down Syndrome, Mark Barton, Kristina Guerrero, Andrew Martinez, Alexandria Umagat

UNLV Theses, Dissertations, Professional Papers, and Capstones

Background: People with Down syndrome (Ds) often present with balance deficits, which compromise their safety during daily activity. While evidence shows that exercise can improve balance in the Ds population, it is unclear if a telehealth method will elicit similar benefits. We aimed to examine the effects of a virtual exercise program on balance in adults with Ds.

Methods: Twenty participants completed a 12-week telehealth exercise program based on the Mann Method. Balance testing took place before and after the intervention, which included: Timed Up and Go (TUG), Modified Clinical Test of Sensory Interaction in Balance (MCTSIB), Frailty and Injuries: …

Paternal Ages And Genetic Diseases And Congenital Anomalies, Neda Hamood

Honors Undergraduate Theses

The purpose of this thesis is to investigate the link between advanced paternal ages (APA) (i.e., APA ≥ 35 years and APA ≥ 50 years) and genetic diseases and congenital anomalies. Currently, the relationship between both advanced paternal ages and genetic diseases and congenital anomalies remains unclear. However, there is room for improvement to systematically investigate the relationship between specific congenital anomalies in newborns and advanced paternal ages. More recently, the link between advanced paternal age (as opposed to existing studies analyzing advanced maternal age alone) and genetic diseases has been recognized by researchers, epidemiologists, and various health experts. Thus, …

Distribution Of Microglial Phenotypes As A Function Of Age And Alzheimer's Disease Neuropathology In The Brains Of People With Down Syndrome, Alessandra C. Martini, Alex M. Helman, Katie L. Mccarty, Ira T. Lott, Eric Doran, Frederick A. Schmitt, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

Introduction: Microglial cells play an important role in the development of Alzheimer's disease (AD). People with Down syndrome (DS) inevitably develop AD neuropathology (DSAD) by 40 years of age. We characterized the distribution of different microglial phenotypes in the brains of people with DS and DSAD.

Methods: Autopsy tissue from the posterior cingulate cortex (PCC) from people with DS, DSAD, and neurotypical controls was immunostained with the microglial marker Iba1 to assess five microglia morphological types.

Results: Individuals with DS have more hypertrophic microglial cells in their white matter. In the gray matter, individuals with DSAD had significantly fewer ramified …

Revisiting The Essential Informational Needs Of Parents Receiving A Diagnosis Of Down Syndrome, Margaret Jean Wilkes

Theses and Dissertations

Down syndrome is a condition characterized by varying degrees of intellectual disability (ID), distinctive facial appearance, and congenital anomalies that results from the presence of a third 21st chromosome. Down syndrome is the most common chromosomal condition, affecting approximately 12.6 per 10,000 live births in the United States, making it imperative that we determine which information is most essential to impart to parents when first presenting the diagnosis. The aim of the present study is to reassess the informational needs of parents during the presentation of a Down syndrome diagnosis. In 2009, data were collected to define the essential information …

Restoration Of Aberrant Mtor Signaling By Intranasal Rapamycin Reduces Oxidative Damage: Focus On Hne-Modified Proteins In A Mouse Model Of Down Syndrome, Fabio Di Domenico, Antonella Tramutola, Eugenio Barone, Chiara Lanzillotta, Olivia Defever, Andrea Arena, Ilaria Zuliani, Cesira Foppoli, Federica Iavarone, Federica Vincenzoni, Massimo Castagnola, D. Allan Butterfield, Marzia Perluigi

Chemistry Faculty Publications

Increasing evidences support the notion that the impairment of intracellular degradative machinery is responsible for the accumulation of oxidized/misfolded proteins that ultimately results in the deposition of protein aggregates. These events are key pathological aspects of “protein misfolding diseases”, including Alzheimer disease (AD). Interestingly, Down syndrome (DS) neuropathology shares many features with AD, such as the deposition of both amyloid plaques and neurofibrillary tangles. Studies from our group and others demonstrated, in DS brain, the dysfunction of both proteasome and autophagy degradative systems, coupled with increased oxidative damage. Further, we observed the aberrant increase of mTOR signaling and of its …

Intranasal Rapamycin Ameliorates Alzheimer-Like Cognitive Decline In A Mouse Model Of Down Syndrome, Antonella Tramutola, Chiara Lanzillotta, Eugenio Barone, Andrea Arena, Ilaria Zuliani, Luciana Mosca, Carla Blarzino, D. Allan Butterfield, Marzia Perluigi, Fabio Di Domenico

Chemistry Faculty Publications

Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Within this context, the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena. By our work we aimed to rescue mTOR signalling …

Vascular Cognitive Impairment And Dementia: The Importance Of Mixed Pathologies From Mouse Models To Humans, Alex Marian Helman

Theses and Dissertations--Molecular and Cellular Biochemistry

Age-related neurologic disease is a significant and growing burden on our society. Although the largest share of research effort has typically been devoted to the common neurodegenerative illnesses (such as Alzheimer’s disease, or AD), the reality is that nearly all cases of neurodegenerative disease possess elements of mixed pathology. Vascular contributions to cognitive impairment and dementia (VCID) is a complex form of dementia, combining aspects of vascular disease and other forms of dementia, such as Alzheimer’s disease. This pathology is heterogeneous and can include cerebral amyloid angiopathy (CAA), hemorrhages, white matter infarcts, and changes to the neurovascular unit. Given the …

Cerebral Amyloid Angiopathy In Down Syndrome And Sporadic And Autosomal-Dominant Alzheimer's Disease, María Carmona-Iragui, Mircea Balasa, Bessy Benejam, Daniel Alcolea, Susana Fernández, Laura Videla, Isabel Sala, María Belén Sánchez-Saudinós, Estrella Morenas-Rodriguez, Roser Ribosa-Nogué, Ignacio Illán-Gala, Sofía Gonzalez-Ortiz, Jordi Clarimón, Frederick A. Schmitt, David K. Powell, Beatriz Bosch, Albert Lladó, Michael S. Rafii, Elizabeth Head, José Luis Molinuevo, Rafael Blesa, Sebastián Videla, Alberto Lleó, Raquel Sánchez-Valle, Juan Fortea

Sanders-Brown Center on Aging Faculty Publications

Introduction—We aimed to investigate if cerebral amyloid angiopathy (CAA) is more frequent in genetically determined than in sporadic early-onset forms of Alzheimer's disease (AD) (early-onset AD [EOAD]).

Methods—Neuroimaging features of CAA, APOE, and cerebrospinal fluid-Aβ40 levels were studied in subjects with Down syndrome (DS, n = 117), autosomal-dominant AD (ADAD, n = 29), sporadic EOAD (n = 42), and healthy controls (n = 68).

Results—CAA was present in 31%, 38%, and 12% of cognitively impaired DS, symptomatic ADAD, and sporadic EOAD subjects and in 13% and 4% of cognitively unimpaired DS individuals and healthy controls, respectively. …

Down Syndrome, The Image Of God, And Personhood, Paris Webb

Dialogue & Nexus

People with Down syndrome help Christians understand what being made in the image of God truly means. After describing Down syndrome, we will examine the different views of the image of God and how these relate to people with Down syndrome. Another approach will be to define personhood in light of God’s image and relate it to Down syndrome. We will use the principles held by the L’Arche community as an exemplar in this discussion to demonstrate that those with Down syndrome encourage us to expand our understanding of the image of God. Consequently, Down’s persons allow us to apply …

Comparisons Of Isogenic Trisomic And Disomic Cells From People With Mosaicism For Down Syndrome Unmask Cellular Differences Related To Trisomy 21, Kelly A. Rafferty

Theses and Dissertations

It is known that age-related changes impacting multiple organ systems occur earlier in people with Down syndrome (Ds), but the biological basis underlying this trisomy 21-associated propensity for premature aging is poorly understood. Given that the trisomic/normal cells from people with mosaic Ds (mDs) are identical with regards to environmental exposures and genes (except for chromosome 21 copy number), comparisons of these isogenic trisomic/disomic cells allow one to “unmask” the cellular consequences of trisomy 21 by removing extraneous factors. The primary aim of this study was to determine if trisomy 21 results in an increase in the acquisition of age-related …

Investigating The Role Of Dna Polymerase Beta In The Aging Phenotype Of Down Syndrome, Aqila Ahmed Ahmed

Wayne State University Dissertations

Down syndrome (DS) is a chromosomal condition characterized by accelerated aging that has yet to be directly linked to a DNA repair defect. Reduced PolB and unrepaired damage from oxidative stress observed in DS, point toward defective base excision repair (BER). In this study, we report that low PolB transcript correlates with increased markers of senescence. The gene dosage effect of Trisomy 21 is likely the source for PolB downregulation. We show that the HSA21-localized miR-155 overexpression correlates with a decrease in Creb1 and PolB, thus establishing a putative regulatory pathway. Data from the DS mouse model, Ts65Dn, reveal low …

Metabolomics Of Mammalian And Cellular Models Of Aging, Nathan Gonzales Duval

Electronic Theses and Dissertations

Aging is often associated with impaired cognition and a progressive loss of organ function over time accompanied by an increased susceptibility for many disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), heart disease, osteoporosis, type II diabetes, and many forms of cancer. With a rapidly aging population, the negative impacts of aging and age-related disorders is a major cause of increased human suffering both for affected individuals and for families and caregivers. Metabolic changes are also apparent in normal aging, but may increase in magnitude or nature with accompanying disease states or with accelerated aging. Thus, studying aging in a …

Exploring Birthparent’S Experiences Of Creating An Adoption Plan For Their Children With Special Needs, Sanjukta Tawde

Theses and Dissertations

Very little information is available regarding the experience and needs of families who create an adoption plan for their child with disability. The purpose of this study was to learn more about the experiences of birthparents who created an adoption plan after the diagnosis of Down syndrome so as to understand their needs during the process. Birthparents were invited to participate in the study through National Down Syndrome Adoption Network (NDSAN) by membership emails. Information about the study was made available on the organization’s website and social media pages. Potential participants also learned about the study from one of the …

The Experience Of Having Primary Caregiving Responsibilities For An Adult Sibling With Down Syndrome, Patricia Sciscione

Seton Hall University Dissertations and Theses (ETDs)

Abstract

Background: The current generation of adults with Down syndrome is living longer and is likely to outlive their parents. Siblings have been identified as the likely future caregivers for adults with Down syndrome, yet little is known about what the experience is like for those who are currently caring for their siblings. It is necessary to gain an understanding of what the service needs are for this population in order to assist sibling caregivers.

Objectives: To explore and describe the experience of being an adult who is partially or fully involved with primary caregiving responsibilities for a sibling with …

Parents' Dreams For Their Young Adults With Down Syndrome: What Resources Are Needed To Achieve Them?, Julianna Elise Hudnall

Theses and Dissertations

This study sought to identify the goals parents have for their young adult sons and daughters with Down syndrome, the factors that help to achieve those goals, and parents' perceived barriers to successful attainment of those objectives. While many supports are readily available to youths with Down syndrome in primary and secondary school, many of these supports disappear as these individuals transition into adulthood. When combined with the inherent challenges of emerging adulthood, significant gaps in resources become evident for this population. In order to identify areas in need of improvement, this study surveyed parents of post- and peri-transitional young …

The Cellular Nucleic Acid Binding Protein In Aging And Disease, Robin Webb

Theses and Dissertations--Molecular and Cellular Biochemistry

The ZNF9 gene on chromosome 3 encodes the cellular nucleic acid binding protein (CNBP), a ubiquitously expressed, 177 amino acid (≈19.5kDa) protein that is highly conserved among vertebrates. The function of the protein is largely unknown, however an expansion in the first intron of the protein results in myotonic dystrophy type 2 (DM2), a multisystemic disease featuring cardiac arrhythmia, muscle wasting, cataracts, and a range of neuropathologies. Remarkably, we recently discovered that CNBP is involved in regulating the activity of β-secretase, the enzyme that produces the first cleavage event in the generation of the amyloid-β peptide (Aβ). The progressive fibrillization …

Use Of Social Media As A Support Network In Families With A Child Diagnosed With Trisomy 13, 18, Or 21, Ginger Elizabeth Edwardsen

Theses and Dissertations

Social media is a web based technology that allows individuals to communicate with other individuals, organizations, and communities about common interests and experiences. Recently, social media use has expanded into the healthcare field and many individuals are using social media to connect with others in similar situations and find support. Family members of children or pregnancies with trisomy 13, 18, or 21 were invited to participate in an online survey that explored the use of social media as a support network including their purposes for using social media as a support network, how often the use social media, and what …

Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit

Dartmouth Scholarship

There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.

Organization Of The Centromeric Satellite I Cluster And D21z1 Short Arm Junction Region Of Human Chromosome 21, Riddhi V. Patel

Master's Theses

To study chromosomal segregation errors causing Down syndrome one needs a chromosome 21 (HC21) specific centromeric marker, which presently does not exist. Alphoid DNA is the only repetitive sequence at all human centromeres. The current map of HC21 has a gap in the p-arm alphoid (D21Z1) junction region and the centromeric satellite I (satI) sequence. This satellite I cluster was shown not to be a specific centromeric marker since it is also on HC13. There are actually multiple satI families on both HC13 and HC21. This project also filled the gap in the HC21map and characterized the D21Z1 p- arm …

Aging And Down Syndrome, Elizabeth Head, Wayne Silverman, David Patterson, Ira T. Lott

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Genome-Wide Expression Analysis In Down Syndrome: Insight Into Immunodeficiency, Chong Li, Lei Jin, Yun Bai, Qimin Chen, Lijun Fu, Minjun Yang, Huasheng Xiao, Guoping Zhao, Shengyue Wang

PCOM Scholarly Papers

Down syndrome (DS) is caused by triplication of Human chromosome 21 (Hsa21) and associated with an array of deleterious phenotypes, including mental retardation, heart defects and immunodeficiency. Genome-wide expression patterns of uncultured peripheral blood cells are useful to understanding of DS-associated immune dysfunction. We used a Human Exon microarray to characterize gene expression in uncultured peripheral blood cells derived from DS individuals and age-matched controls from two age groups: neonate (N) and child (C). A total of 174 transcript clusters (gene-level) with eight located on Hsa21 in N group and 383 transcript clusters including 56 on Hsa21 in C group …

Skeletal Muscle Function, Morphology, And Biochemistry In Ts65dn Mice: A Model Of Down Syndrome, Patrick Michael Cowley

Exercise Science - Dissertations

A common clinical observation of persons with Down syndrome at all developmental stages is hypotonia and generalized muscle weakness. The cause of muscle weakness in Down syndrome is not known and there is an immediate need to establish an acceptable animal model to explore the muscle dysfunction that is widely reported in the human population. Using a combination of functional, histological, and biochemical analyses this dissertation provides the initial characterization of skeletal muscle from the Ts65Dn mouse, a model of Down syndrome. The experiments revealed that Ts65Dn muscle over-expresses SOD1 protein but this did not lead to oxidative stress. Ts65Dn …

Quantitative Proteomics Analysis Of Differentially Expressed Proteins In Aβ(17-42) Treated Synaptosomes, Jaffer Mohammed

Online Theses and Dissertations

Oxidative stress has been associated in the pathogenesis of numerous diseases such as neurodegenerative disorders, ischemia, and cancer. The brain is susceptible to oxidative stress due to its high content of peroxidizable unsaturated fatty acids, high consumption of oxygen per unit weight, high levels of free radicals, and comparatively low levels of antioxidant defense systems. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can react with biomolecules such as proteins, lipids, carbohydrates, DNA, and RNA, which can lead to oxidative damage, cellular dysfunction, and can ultimately cause cell death. Down syndrome (DS) is the most common form of chromosomal …

Reliability Of Sixteen Balance Tests In Individuals With Down Syndrome, Romina Villamonte

Theses and Dissertations

The purpose of this study was to determine the reliability of sixteen balance tests in individuals with Down syndrome (DS). The following tests were performed on 21 participants with DS, aged 5-31 years of age; standing test on firm and soft surfaces with the eyes opened and closed, a balance subset of the Bruininks-Oseretsky test, full turn, timed-up-and-go test, forward reach, and sit-to-stand. Each participant completed all 16 assessments twice on one day and then again on a subsequent day for a total of four trials. Seven tests had reliability coefficients greater than 0.55; one-leg stand on floor (0.76), on …

Neuromotor And Cognitive Development In Children With Cerebral Palsy In Relation To Neural Plasticity, Vaniecea Pollard

McCabe Thesis Collection

Infants with neurological disabilities, such as cerebral palsy (CP) and Down syndrome (DS), show severe delays in motor and cognitive development relative to chronological age. Involvement of neural plasticity as a treatment of such neurological disorders is increasingly being seen. Previous studies have found that interventions involving sensory linked motor performance have been critical in facilitating motor improvement. The purpose of this study was to compare self-initiated mobility in children with CP and DS. Three infants, ages 8, 9, and 22 months, with diagnoses of no CP, DS, and CP respectively, participated in the study. The infants were videotaped in …