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Articles 3751 - 3780 of 7026

Full-Text Articles in Medical Genetics

Unraveling The Intercellular Communication Disruption And Key Pathways In Alzheimer’S Disease: An Integrative Study Of Single-Nucleus Transcriptomes And Genetic Association, Andi Liu, Brisa S Fernandes, Citu Citu, Zhongming Zhao Jan 2024

Unraveling The Intercellular Communication Disruption And Key Pathways In Alzheimer’S Disease: An Integrative Study Of Single-Nucleus Transcriptomes And Genetic Association, Andi Liu, Brisa S Fernandes, Citu Citu, Zhongming Zhao

Faculty, Staff and Student Publications

BACKGROUND: Recently, single-nucleus RNA-seq (snRNA-seq) analyses have revealed important cellular and functional features of Alzheimer's disease (AD), a prevalent neurodegenerative disease. However, our knowledge regarding intercellular communication mediated by dysregulated ligand-receptor (LR) interactions remains very limited in AD brains.

METHODS: We systematically assessed the intercellular communication networks by using a discovery snRNA-seq dataset comprising 69,499 nuclei from 48 human postmortem prefrontal cortex (PFC) samples. We replicated the findings using an independent snRNA-seq dataset of 56,440 nuclei from 18 PFC samples. By integrating genetic signals from AD genome-wide association studies (GWAS) summary statistics and whole genome sequencing (WGS) data, we prioritized …


Investigation Into Cardiac Myhc-Α 334-352-Specific Tcr Transgenic Mice Reveals A Role For Cytotoxic Cd4 T Cells In The Development Of Cardiac Autoimmunity, Meghna Sur, Mahima T. Rasquinha, Kiruthiga Mone, Chandirasegaran Massilamany, Ninaad Lasrado, Channabasavaiah B. Gurumurthy, Raymond A Sobel, Jay Reddy Jan 2024

Investigation Into Cardiac Myhc-Α 334-352-Specific Tcr Transgenic Mice Reveals A Role For Cytotoxic Cd4 T Cells In The Development Of Cardiac Autoimmunity, Meghna Sur, Mahima T. Rasquinha, Kiruthiga Mone, Chandirasegaran Massilamany, Ninaad Lasrado, Channabasavaiah B. Gurumurthy, Raymond A Sobel, Jay Reddy

Journal Articles: Genetics, Cell Biology & Anatomy

Myocarditis is one of the major causes of heart failure in children and young adults and can lead to dilated cardiomyopathy. Lymphocytic myocarditis could result from autoreactive CD4+ and CD8+ T cells, but defining antigen specificity in disease pathogenesis is challenging. To address this issue, we generated T cell receptor (TCR) transgenic (Tg) C57BL/6J mice specific to cardiac myosin heavy chain (Myhc)-α 334-352 and found that Myhc-α-specific TCRs were expressed in both CD4+ and CD8+ T cells. To investigate if the phenotype is more pronounced in a myocarditis-susceptible genetic background, we backcrossed with A/J mice. At …


International Consensus On Sleep Problems In Pediatric Palliative Care: Paving The Way, Anna Mercante, Judith Owens, Oliviero Bruni, Magda L. Nunes, Paul Gringras, Shirley Xin Li, Simonetta Papa, Ulrika Kreicbergs, Joanne Wolfe, Boris Zernikow, Ana Lacerda, Franca Benini, Pediatric Sleep And Palliative Care Group Jan 2024

International Consensus On Sleep Problems In Pediatric Palliative Care: Paving The Way, Anna Mercante, Judith Owens, Oliviero Bruni, Magda L. Nunes, Paul Gringras, Shirley Xin Li, Simonetta Papa, Ulrika Kreicbergs, Joanne Wolfe, Boris Zernikow, Ana Lacerda, Franca Benini, Pediatric Sleep And Palliative Care Group

Journal Articles: Munroe-Meyer Institute

OBJECTIVE: Sleep problems constitute a common and heterogeneous complaint in pediatric palliative care (PPC), where they often contribute to disease morbidity and cause additional distress to children and adolescents and their families already facing the burden of life-threatening and life-limiting conditions. Despite the significant impact of sleep problems, clinical evidence is lacking. The application of general pediatric sleep recommendations appears insufficient to address the unique challenges of the PPC dimension in terms of disease variability, duration, comorbidities, complexity of needs, and particular features of sleep problems related to hospice care. Therefore, we initiated an international project aimed at establishing a …


Targeted Insertion Of Conditional Expression Cassettes Into The Mouse Genome Using The Modified I-Pitt, Hiromi Miura, Ayaka Nakamura, Aki Kurosaki, Ai Kotani, Masaru Motojima, Keiko Tanaka, Shigeru Kakuta, Sanae Ogiwara, Yuhsuke Ohmi, Hirotaka Komaba, Samantha L. P. Schilit, Cynthia C. Morton, Channabasavaiah B. Gurumurthy, Masato Ohtsuka Jan 2024

Targeted Insertion Of Conditional Expression Cassettes Into The Mouse Genome Using The Modified I-Pitt, Hiromi Miura, Ayaka Nakamura, Aki Kurosaki, Ai Kotani, Masaru Motojima, Keiko Tanaka, Shigeru Kakuta, Sanae Ogiwara, Yuhsuke Ohmi, Hirotaka Komaba, Samantha L. P. Schilit, Cynthia C. Morton, Channabasavaiah B. Gurumurthy, Masato Ohtsuka

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Transgenic (Tg) mice are widely used in biomedical research, and they are typically generated by injecting transgenic DNA cassettes into pronuclei of one-cell stage zygotes. Such animals often show unreliable expression of the transgenic DNA, one of the major reasons for which is random insertion of the transgenes. We previously developed a method called "pronuclear injection-based targeted transgenesis" (PITT), in which DNA constructs are directed to insert at pre-designated genomic loci. PITT was achieved by pre-installing so called landing pad sequences (such as heterotypic LoxP sites or attP sites) to create seed mice and then injecting Cre recombinase or …


Identifying Factors That Reduce Substance Use Liability, Victoria Allen, Nick Blanch, Sunday Wright, Kelci Straka-Mai, Aarushi Patel, Caleb Bridgwater, Lubidia Menjivar, Cate Vaughn, Courtney Blondino Phd, The Mid-Atlantic Twin Registry, Michael M. Vanyukov Phd, Hermine H.M. Maes Phd, Elizabeth Prom-Wormley Phd Jan 2024

Identifying Factors That Reduce Substance Use Liability, Victoria Allen, Nick Blanch, Sunday Wright, Kelci Straka-Mai, Aarushi Patel, Caleb Bridgwater, Lubidia Menjivar, Cate Vaughn, Courtney Blondino Phd, The Mid-Atlantic Twin Registry, Michael M. Vanyukov Phd, Hermine H.M. Maes Phd, Elizabeth Prom-Wormley Phd

IRBEH/Spit for Science Publications and Presentations

No abstract provided.


The Role Of Liver-Specific Transcription Factor Hnf4 In Reprogramming Of Fibroblasts, Mary Odubote Jan 2024

The Role Of Liver-Specific Transcription Factor Hnf4 In Reprogramming Of Fibroblasts, Mary Odubote

Masters Theses

The mammalian liver, a vital organ with complex functions, relies on a network of transcription factors to regulate gene expression. Fusion of hepatoma cells with fibroblasts often leads to gene extinction, silencing approximately 400 liver-enriched genes, including critical transcription factors such as HNF4. Previous studies revealed that ectopic expression of HNF4 in fibroblasts failed to prevent the extinction of SERPINA1, a liver-specific gene, upon subsequent fusion with hepatoma cells. Here, we sought to investigate the extent to which ectopic expression of HNF4 can reprogram fibroblast cells and prevent gene extinction in hybrid cells.

Using whole-genome expression analysis, we compared RAT1 …


Actin Depolymerization Of Tenocytes Promotes A Tendinosis-Like Gene Expression, Kameron Inguito, Ba, Valerie West, Karl Matthew Ebron, Justin Parreno, Phd Jan 2024

Actin Depolymerization Of Tenocytes Promotes A Tendinosis-Like Gene Expression, Kameron Inguito, Ba, Valerie West, Karl Matthew Ebron, Justin Parreno, Phd

Alpha Omega Alpha Research Symposium Posters

Optimal cellular mechanotransduction is essential for tendon matrix homeostasis. We recently developed an in vivo rat model of tendinosis, where the plantaris tendon are overloaded through ablation of the synergistic Achilles tendon. Using this model we determined that tissue overload disrupts matrix-cell interactions, which results in under-stimulation of tendon cells (tenocytes) (Fig.1)

Using an ex vivo model of tendon stress deprivation by maintaining tail tendon fascicles in floating culture we showed that tenocyte under-stimulation results in destabilization of filamentous (F-)actin (Fig.2). F-actin destabilization coincides with tendinosis-like gene expression: downregulation of tenogenic genes (Col1, Tnc, asma, Scx), upregulation of chondrogenic (Acan, …


In Vivo Scanning Laser Fundus And High-Resolution Oct Imaging Of Retinal Ganglion Cell Injury In A Non-Human Primate Model With An Activatable Fluorescent-Labeled Tat Peptide Probe, Xudong Qiu, Seth T Gammon, Carol Rasmussen, Federica Pisaneschi, Charlene B Y Kim, James Ver Hoeve, Steven W Millward, Edward M Barnett, T Michael Nork, Paul L Kaufman, David Piwnica-Worms Jan 2024

In Vivo Scanning Laser Fundus And High-Resolution Oct Imaging Of Retinal Ganglion Cell Injury In A Non-Human Primate Model With An Activatable Fluorescent-Labeled Tat Peptide Probe, Xudong Qiu, Seth T Gammon, Carol Rasmussen, Federica Pisaneschi, Charlene B Y Kim, James Ver Hoeve, Steven W Millward, Edward M Barnett, T Michael Nork, Paul L Kaufman, David Piwnica-Worms

Faculty, Staff and Student Publications

The optical imaging agent TcapQ488 has enabled imaging of retinal ganglion cell (RGC) injury in vivo in rodents and has potential as an effective diagnostic probe for early detection and intervention monitoring in glaucoma patients. In the present study, we investigated TcapQ488 in non-human primates (NHPs) to identify labeling efficacy and early signals of injured RGC, to determine species-dependent changes in RGC probe uptake and clearance, and to determine dose-limiting toxicities. Doses of 3, 6, and 12 nmol of TcapQ488 were delivered intravitreally to normal healthy NHP eyes and eyes that had undergone hemiretinal endodiathermy axotomy (HEA) in the inferior …


The Influence Of Drd2 Polymorphism Exon 8 C/T (Rs6276) On Manifestations Of Delirium Tremens & Alcohol Withdrawal Seizures, Naomi Schneider Jan 2024

The Influence Of Drd2 Polymorphism Exon 8 C/T (Rs6276) On Manifestations Of Delirium Tremens & Alcohol Withdrawal Seizures, Naomi Schneider

Honors Theses and Capstones

This study explores the correlation between the DRD2 Polymorphism exon 8 C/T (rs6276) and manifestations of delirium tremens (DT). DT is a condition that is clinically diagnosed utilizing two characteristic symptom manifestations: the presence of delirium and severe alcohol withdrawal. It is not entirely understood why DT can occur in some patients, but evidence has suggested that genetic predisposition can play a role. Utilizing the National Institutes of Health (NIH) All of Us Research database and performing a secondary analysis of existing genomic data, this candidate gene association study aims to determine the genotype frequencies within three cohorts: a healthy …


Autochthonous Plasmodium Vivax Infections, Florida, Usa, 2023, Swamy Rakesh Adapa, Kami Kim, Liwang Cui Jan 2024

Autochthonous Plasmodium Vivax Infections, Florida, Usa, 2023, Swamy Rakesh Adapa, Kami Kim, Liwang Cui

College of Medicine & TGH Faculty Publications

During May–July 2023, a cluster of 7 patients at local hospitals in Florida, USA, received a diagnosis of Plasmodium vivax malaria. Whole-genome sequencing of the organism from 4 patients and phylogenetic analysis with worldwide representative P. vivax genomes indicated probable single parasite introduction from Central/South America.


Metabolink Is A Novel Algorithm For Unveiling Cell-Specific Metabolic Pathways In Longitudinal Datasets, Jared Lichtarge, Gerarda Cappuccio, Soumya Pati, Alfred Kwabena Dei-Ampeh, Senghong Sing, Lihua Ma, Zhandong Liu, Mirjana Maletic-Savatic Jan 2024

Metabolink Is A Novel Algorithm For Unveiling Cell-Specific Metabolic Pathways In Longitudinal Datasets, Jared Lichtarge, Gerarda Cappuccio, Soumya Pati, Alfred Kwabena Dei-Ampeh, Senghong Sing, Lihua Ma, Zhandong Liu, Mirjana Maletic-Savatic

Duncan NRI Faculty and Staff Publications

Introduction: In the rapidly advancing field of 'omics research, there is an increasing demand for sophisticated bioinformatic tools to enable efficient and consistent data analysis. As biological datasets, particularly metabolomics, become larger and more complex, innovative strategies are essential for deciphering the intricate molecular and cellular networks.

Methods: We introduce a pioneering analytical approach that combines Principal Component Analysis (PCA) with Graphical Lasso (GLASSO). This method is designed to reduce the dimensionality of large datasets while preserving significant variance. For the first time, we applied the PCA-GLASSO algorithm (i.e., MetaboLINK) to metabolomics data derived from Nuclear Magnetic Resonance (NMR) spectroscopy …


Facilitating Clinical Information Extraction With Synthetic Data And Ontology Using Large Language Models, Yan Hu, Huan He, Qingyu Chen, Xiaoqian Jiang, Kirk Roberts, Hua Xu Jan 2024

Facilitating Clinical Information Extraction With Synthetic Data And Ontology Using Large Language Models, Yan Hu, Huan He, Qingyu Chen, Xiaoqian Jiang, Kirk Roberts, Hua Xu

Faculty, Staff and Student Publications

The rapid growth of unstructured clinical text in electronic health records necessitates robust information extraction systems, yet their development is hindered by the scarcity of high-quality annotated data. This study explores the potential of large language models to generate synthetic data for clinical named entity recognition and examines its impact on model performance. We propose a novel framework that integrates self-verified synthetic data generation with domain-specific semantic mapping using SNOMED-CT. By leveraging GPT-4o-mini for synthetic data creation and refining its quality through iterative verification and anomaly detection, we systematically evaluate the influence of synthetic data quality and quantity on fine-tuning …


Design And Implementation Of Multicenter Pediatric And Congenital Studies With Cardiovascular Magnetic Resonance: Big Data In Smaller Bodies, Michael P Dilorenzo, Simon Lee, Rahul H Rathod, Francesca Raimondi, Kanwal M Farooqi, Supriya S Jain, Margaret M Samyn, Tiffanie R Johnson, Laura J Olivieri, Mark A Fogel, Wyman W Lai, Pierangelo Renella, Andrew J Powell, Sujatha Buddhe, Caitlin Stafford, Jason N Johnson, Willem A Helbing, Kuberan Pushparajah, Inga Voges, Vivek Muthurangu, Kimberley G Miles, Gerald Greil, Colin J Mcmahon, Timothy C Slesnick, Brian M Fonseca, Shaine A Morris, Jonathan H Soslow, Lars Grosse-Wortmann, Rebecca S Beroukhim, Heynric B Grotenhuis Jan 2024

Design And Implementation Of Multicenter Pediatric And Congenital Studies With Cardiovascular Magnetic Resonance: Big Data In Smaller Bodies, Michael P Dilorenzo, Simon Lee, Rahul H Rathod, Francesca Raimondi, Kanwal M Farooqi, Supriya S Jain, Margaret M Samyn, Tiffanie R Johnson, Laura J Olivieri, Mark A Fogel, Wyman W Lai, Pierangelo Renella, Andrew J Powell, Sujatha Buddhe, Caitlin Stafford, Jason N Johnson, Willem A Helbing, Kuberan Pushparajah, Inga Voges, Vivek Muthurangu, Kimberley G Miles, Gerald Greil, Colin J Mcmahon, Timothy C Slesnick, Brian M Fonseca, Shaine A Morris, Jonathan H Soslow, Lars Grosse-Wortmann, Rebecca S Beroukhim, Heynric B Grotenhuis

Faculty, Staff and Student Publications

Cardiovascular magnetic resonance (CMR) has become the reference standard for quantitative and qualitative assessment of ventricular function, blood flow, and myocardial tissue characterization. There is a preponderance of large CMR studies and registries in adults; However, similarly powered studies are lacking for the pediatric and congenital heart disease (PCHD) population. To date, most CMR studies in children are limited to small single or multicenter studies, thereby limiting the conclusions that can be drawn. Within the PCHD CMR community, a collaborative effort has been successfully employed to recognize knowledge gaps with the aim to embolden the development and initiation of high-quality, …


Emerging Unconventional Therapies For Glioblastoma Multiforme, Danielle Morang Jan 2024

Emerging Unconventional Therapies For Glioblastoma Multiforme, Danielle Morang

Capstone Showcase

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary malignant brain tumor occurring in adults with a median survival of less than two years. It is a highly invasive tumor characterized by genetic heterogeneity, angiogenesis, and rapid proliferation. Patients undergo a multimodal treatment regimen consisting of surgical resection and chemoradiation therapy, yet GBM tumors almost always recur with a worsening prognosis. The molecular and genetic complexities of GBM pose a significant challenge for developing effective therapeutics. Thus, it is imperative to identify new therapeutic targets and explore novel treatment strategies to improve patients’ overall survival time and quality of …


Statins Are Rarely Prescribed For Incidentally Discovered Covert Cerebrovascular Disease: A Retrospective Cohort In A Large Electronic Health Record (Ehr) Identified Using Natural Language Processing, Lester Y Leung, Eric Puttock, David F Kallmes, Patrick Luetmer, Sunyang Fu, Chengyi X Zheng, Hongfang Liu, Wansu Chen, David M Kent Jan 2024

Statins Are Rarely Prescribed For Incidentally Discovered Covert Cerebrovascular Disease: A Retrospective Cohort In A Large Electronic Health Record (Ehr) Identified Using Natural Language Processing, Lester Y Leung, Eric Puttock, David F Kallmes, Patrick Luetmer, Sunyang Fu, Chengyi X Zheng, Hongfang Liu, Wansu Chen, David M Kent

Faculty, Staff and Student Publications

Introduction: While incidentally discovered covert cerebrovascular diseases (id-CCD) are associated with future stroke, it is not known if patients with id-CCD are prescribed statins.

Methods: Patients age ≥50 with id-CCD on neuroimaging from 2009 to 2019 with no prior ischaemic stroke, transient ischaemic attack or dementia were identified using natural language processing in a large real-world cohort. Robust Poisson multivariable regression was used to assess statin prescription among patients without prior statins.

Results: Among 2 41 050 patients, 74 975 patients (31.1%; 4.7% with covert brain infarcts (CBI); 29.0% with white matter disease (WMD)) had id-CCD. 53.5% (95% CI 53.2 …


Developing Medical Genetics In A Low-Income Country: Unveiling The Journey Of The Pakistani Society Of Medical Genetics And Genomics (Psmg), Aisha Furqan, Syed A Ahmed, Rizwan Naeem, Myla Ashfaq Jan 2024

Developing Medical Genetics In A Low-Income Country: Unveiling The Journey Of The Pakistani Society Of Medical Genetics And Genomics (Psmg), Aisha Furqan, Syed A Ahmed, Rizwan Naeem, Myla Ashfaq

Faculty, Staff and Student Publications

No abstract provided.


Siglec15, Negatively Correlated With Pd-L1 In Hcc, Could Induce Cd8+ T Cell Apoptosis To Promote Immune Evasion, Zheng Chen, Mincheng Yu, Bo Zhang, Lei Jin, Qiang Yu, Shuang Liu, Binghai Zhou, Jiuliang Yan, Wentao Zhang, Xiaoqiang Li, Yongfeng Xu, Yongsheng Xiao, Jian Zhou, Jia Fan, Mien-Chie Hung, Qinghai Ye, Hui Li, Lei Guo Jan 2024

Siglec15, Negatively Correlated With Pd-L1 In Hcc, Could Induce Cd8+ T Cell Apoptosis To Promote Immune Evasion, Zheng Chen, Mincheng Yu, Bo Zhang, Lei Jin, Qiang Yu, Shuang Liu, Binghai Zhou, Jiuliang Yan, Wentao Zhang, Xiaoqiang Li, Yongfeng Xu, Yongsheng Xiao, Jian Zhou, Jia Fan, Mien-Chie Hung, Qinghai Ye, Hui Li, Lei Guo

Faculty, Staff and Student Publications

Functional roles of SIGLEC15 in hepatocellular carcinoma (HCC) were not clear, which was recently found to be an immune inhibitor with similar structure of inhibitory B7 family members. SIGLEC15 expression in HCC was explored in public databases and further examined by PCR analysis. SIGLEC15 and PD-L1 expression patterns were examined in HCC samples through immunohistochemistry. SIGLEC15 expression was knocked-down or over-expressed in HCC cell lines, and CCK8 tests were used to examine cell proliferative ability in vitro. Influences of SIGLEC15 expression on tumor growth were examined in immune deficient and immunocompetent mice respectively. Co-culture system of HCC cell lines and …


G-Quadruplex Dna And Rna In Cellular Senescence, Rocio Diaz Escarcega, Paul Marshall, Andrey S Tsvetkov Jan 2024

G-Quadruplex Dna And Rna In Cellular Senescence, Rocio Diaz Escarcega, Paul Marshall, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Normal cells divide, are damaged, and are repaired across their lifetime. As cells age, they enter cellular senescence, characterized by a permanent state of cell-cycle arrest triggered by various stressors. The molecular mechanisms that regulate senescent phenotypes have been actively investigated over the last several decades; however, one area that has been neglected is how G-quadruplex (G4) DNA and RNA (G4-DNA and G4-RNA) mediate senescence. These non-canonical four-stranded DNA and RNA structures regulate most normative DNA and RNA-dependent processes, such as transcription, replication, and translation, as well as pathogenic mechanisms, including genomic instability and abnormal stress granule function. This review …


Harnessing Microrna-Enriched Extracellular Vesicles For Liquid Biopsy, Song Yi Ko, Wonjae Lee, Honami Naora Jan 2024

Harnessing Microrna-Enriched Extracellular Vesicles For Liquid Biopsy, Song Yi Ko, Wonjae Lee, Honami Naora

Faculty, Staff and Student Publications

Extracellular microRNAs (miRNAs) can be detected in body fluids and hold great potential as cancer biomarkers. Extracellular miRNAs are protected from degradation by binding various proteins and through their packaging into extracellular vesicles (EVs). There is evidence that the diagnostic performance of cancer-associated extracellular miRNAs can be improved by assaying EV-miRNA instead of total cell-free miRNA, but several challenges have hampered the advancement of EV-miRNA in liquid biopsy. Because almost all types of cells release EVs, cancer cell-derived EVs might constitute only a minor fraction of EVs in body fluids of cancer patients with low volume disease. Furthermore, a given …


Dysregulation Of Epigenetic Modifications In Inborn Errors Of Immunity, Zhongyao Xiao, Rongjing He, Zihan Zhao, Taiping Chen, Zhengzhou Ying Jan 2024

Dysregulation Of Epigenetic Modifications In Inborn Errors Of Immunity, Zhongyao Xiao, Rongjing He, Zihan Zhao, Taiping Chen, Zhengzhou Ying

Faculty, Staff and Student Publications

Inborn errors of immunity (IEIs) are a group of typically monogenic disorders characterized by dysfunction in the immune system. Individuals with these disorders experience increased susceptibility to infections, autoimmunity and malignancies due to abnormal immune responses. Epigenetic modifications, including DNA methylation, histone modifications and chromatin remodeling, have been well explored in the regulation of immune cell development and effector function. Aberrant epigenetic modifications can disrupt gene expression profiles crucial for immune responses, resulting in impaired immune cell differentiation and function. Dysregulation of these processes caused by mutations in genes involving in epigenetic modifications has been associated with various IEIs. In …


The Role Of Micrornas In Cellular Senescence, Inflammation, And Cancer Induced By Childhood Obesity, Sarah S. Siddiqi Jan 2024

The Role Of Micrornas In Cellular Senescence, Inflammation, And Cancer Induced By Childhood Obesity, Sarah S. Siddiqi

Honors Undergraduate Theses

Childhood obesity has escalated into a major public health crisis with serious implications for long-term health. As obesity rates among children continue to rise globally, it is crucial to understand its effects on cellular aging and inflammation—key processes that underpin many metabolic diseases. Obesity not only directly contributes to various metabolic disorders but also disrupts fundamental cellular mechanisms, accelerating aging and fostering systemic inflammation. By examining the impact of obesity on cellular aging and chronic inflammation, as well as the regulatory role of microRNAs (miRNAs) in these pathways, we have been able to identify critical biomarkers and molecular mechanisms involved …


Factors Leading To Osteoporosis In Turner Syndrome, Daniella O. Aleshinloye Jan 2024

Factors Leading To Osteoporosis In Turner Syndrome, Daniella O. Aleshinloye

Honors Undergraduate Theses

Turner Syndrome (TS) is a chromosomal disorder from conception characterized by the partial or complete absence of the second X chromosome in females. Chromosomal abnormalities, both numerical and structural, contribute to a significantly higher prevalence of fractures (30.5-32.2%) compared to non-TS postmenopausal women (14.9%). This highlights the intrinsic bone abnormalities associated with TS and increased fracture risk. Peripheral quantitative computed tomography (pQCT) is commonly used to assess bone mineral density (BMD). However, its accuracy in individuals with TS is limited due to the partial volume effect, highlighting the need for further clinical research to understand bone density changes compared to …


Genotypes Of Snps Of Key Genes Regulate Susceptibility And Drug Sensitivity To Neovascular Amd, Jinglin Cui Jan 2024

Genotypes Of Snps Of Key Genes Regulate Susceptibility And Drug Sensitivity To Neovascular Amd, Jinglin Cui

Theses and Dissertations (ETD)

Age-related macular degeneration (AMD), particularly its neovascular form, stands as a leading cause of blindness globally, with its prevalence in our country on a steady rise. This underscores the critical impact of neovascular AMD (nAMD) management on patient quality of life and societal burden. Current optimal treatments hinge on anti-vascular endothelial growth factor (anti-VEGF) therapies, though their efficacy varies across different drugs and individuals, highlighting the importance of precise drug selection in clinical outcomes. Research suggests that factors such as baseline vision, age, disease duration, lesion size, central retina thickness, neovascularization type, and demographic differences influence nAMD prognosis. In addition, …


Pdgfra And B Copositive Fibroblasts Drive Fibrosis In Mouse Salivary Glands Through Tgfβ Signaling, Renae Williams Atkinson Jan 2024

Pdgfra And B Copositive Fibroblasts Drive Fibrosis In Mouse Salivary Glands Through Tgfβ Signaling, Renae Williams Atkinson

Electronic Theses & Dissertations (2024 - present)

Fibrosis is of significant concern to the medical community as numerous disease processes are characterized by progressive fibrosis leading to organ damage. We begin the process of examining the mechanism of fibrosis to salivary gland hypofunction and briefly consider Sjögren’s Disease (SjD). Method: We employed single-cell RNA sequencing data from a reversible mouse salivary gland injury model and from NOD/ShiLtJ mice, a model of secondary SjD. We performed treatment comparisons with the help of Seurat dotplots and UMAPS. Using differential gene expression analysis and the publicly available R packages: clusterProfiler, WikiPathways and Cytoscape, we identified the processes and pathways …


De Novo Missense Variants In Zbtb47 Are Associated With Developmental Delays, Hypotonia, Seizures, Gait Abnormalities, And Variable Movement Abnormalities, Scott K Ward, Alexandrea Wadley, Chun-Hui Anne Tsai, Paul J Benke, Lisa Emrick, Kristen Fisher, Kimberly M Houck, Hongzheng Dai, Undiagnosed Diseases Network, Maria J Guillen Sacoto, William Craigen, Kimberly Glaser, David R Murdock, Luis Rohena, Karin E M Diderich, Hennie T Bruggenwirth, Brendan Lee, Carlos Bacino, Lindsay C Burrage, Jill A Rosenfeld Jan 2024

De Novo Missense Variants In Zbtb47 Are Associated With Developmental Delays, Hypotonia, Seizures, Gait Abnormalities, And Variable Movement Abnormalities, Scott K Ward, Alexandrea Wadley, Chun-Hui Anne Tsai, Paul J Benke, Lisa Emrick, Kristen Fisher, Kimberly M Houck, Hongzheng Dai, Undiagnosed Diseases Network, Maria J Guillen Sacoto, William Craigen, Kimberly Glaser, David R Murdock, Luis Rohena, Karin E M Diderich, Hennie T Bruggenwirth, Brendan Lee, Carlos Bacino, Lindsay C Burrage, Jill A Rosenfeld

Faculty, Staff and Students Publications

The collection of known genetic etiologies of neurodevelopmental disorders continues to increase, including several syndromes associated with defects in zinc finger protein transcription factors (ZNFs) that vary in clinical severity from mild learning disabilities and developmental delay to refractory seizures and severe autism spectrum disorder. Here we describe a new neurodevelopmental disorder associated with variants in ZBTB47 (also known as ZNF651), which encodes zinc finger and BTB domain-containing protein 47. Exome sequencing (ES) was performed for five unrelated patients with neurodevelopmental disorders. All five patients are heterozygous for a de novo missense variant in ZBTB47, with p.(Glu680Gly) (c.2039A>G) detected …


Case Report: P40phox Deficiency Underlying Pediatric-Onset Systemic Lupus Erythematosus, Alejandro Nieto-Patlán, Natalia S Fernández Dávila, Yuqing Wang, Michelle Zelnick, Eyal Muscal, Martha Curry, James R Lupski, Steven M Holland, Bo Yuan, Douglas B Kuhns, Tiphanie P Vogel, Ivan K Chinn Jan 2024

Case Report: P40phox Deficiency Underlying Pediatric-Onset Systemic Lupus Erythematosus, Alejandro Nieto-Patlán, Natalia S Fernández Dávila, Yuqing Wang, Michelle Zelnick, Eyal Muscal, Martha Curry, James R Lupski, Steven M Holland, Bo Yuan, Douglas B Kuhns, Tiphanie P Vogel, Ivan K Chinn

Faculty, Staff and Students Publications

Introduction

Systemic lupus erythematosus is a multi-faceted autoimmune disorder of complex etiology. Pre-pubertal onset of pediatric systemic lupus erythematosus (pSLE) is uncommon and should raise suspicion for a genetic driver of disease. Autosomal recessive p40phox deficiency is a rare immunologic disorder characterized by defective but not abolished NADPH oxidase activity with residual production of reactive oxygen species (ROS) by phagocytic cells.

Case presentation

We report the case of a now 18-year-old female with pSLE onset at 7 years of age. She presented with recurrent fever and malar rash. Aspects of her immune dysregulation over time have included typical pSLE …


International Society For Extracellular Vesicles Workshop Quantitatevs: Multiscale Analyses, From Bulk To Single Extracellular Vesicle, Manuela Basso, Alessandro Gori, Caterina Nardella, Mari Palviainen, Marija Holcar, Ioannis Sotiropoulos, Sylwia Bobis-Wozowicz, Vito G D'Agostino, Elena Casarotto, Yari Ciani, Shiro Suetsugu, Alice Gualerzi, Lorena Martin-Jaular, Daniela Boselli, Anna Kashkanova, Pietro Parisse, Lien Lippens, Martina Pagliuca, Martin Blessing, Roberto Frigerio, Thibaut Fourniols, Ana Meliciano, Anna Fietta, Paolo Vincenzo Fioretti, Karolina Soroczyńska, Silvia Picciolini, Amanda Salviano-Silva, Paolo Bergese, Davide Zocco, Marcella Chiari, Guido Jenster, Levi Waldron, Aleksandar Milosavljevic, John Nolan, Marco P Monopoli, Kenneth W Witwer, Benedetta Bussolati, Dolores Di Vizio, Juan Falcon Perez, Metka Lenassi, Marina Cretich, Francesca Demichelis Jan 2024

International Society For Extracellular Vesicles Workshop Quantitatevs: Multiscale Analyses, From Bulk To Single Extracellular Vesicle, Manuela Basso, Alessandro Gori, Caterina Nardella, Mari Palviainen, Marija Holcar, Ioannis Sotiropoulos, Sylwia Bobis-Wozowicz, Vito G D'Agostino, Elena Casarotto, Yari Ciani, Shiro Suetsugu, Alice Gualerzi, Lorena Martin-Jaular, Daniela Boselli, Anna Kashkanova, Pietro Parisse, Lien Lippens, Martina Pagliuca, Martin Blessing, Roberto Frigerio, Thibaut Fourniols, Ana Meliciano, Anna Fietta, Paolo Vincenzo Fioretti, Karolina Soroczyńska, Silvia Picciolini, Amanda Salviano-Silva, Paolo Bergese, Davide Zocco, Marcella Chiari, Guido Jenster, Levi Waldron, Aleksandar Milosavljevic, John Nolan, Marco P Monopoli, Kenneth W Witwer, Benedetta Bussolati, Dolores Di Vizio, Juan Falcon Perez, Metka Lenassi, Marina Cretich, Francesca Demichelis

Faculty, Staff and Students Publications

The “QuantitatEVs: multiscale analyses, from bulk to single vesicle” workshop aimed to discuss quantitative strategies and harmonized wet and computational approaches toward the comprehensive analysis of extracellular vesicles (EVs) from bulk to single vesicle analyses with a special focus on emerging technologies. The workshop covered the key issues in the quantitative analysis of different EV‐associated molecular components and EV biophysical features, which are considered the core of EV‐associated biomarker discovery and validation for their clinical translation. The in‐person‐only workshop was held in Trento, Italy, from January 31st to February 2nd, 2023, and continued in Milan on February 3rd with “Next …


Pretreatment Characteristics Associated With Symptom Reduction During Group Cognitive Processing Therapy Versus Exposure Therapy For Ptsd: An Exploratory Study Of Veterans, Christopher Hunt, Brooks Casas, Pearl H Chiu, Lia J Smith, Laura Priorello, Kelly Lee, Matthew Estey, Mary R Newsome, M Wright Williams Jan 2024

Pretreatment Characteristics Associated With Symptom Reduction During Group Cognitive Processing Therapy Versus Exposure Therapy For Ptsd: An Exploratory Study Of Veterans, Christopher Hunt, Brooks Casas, Pearl H Chiu, Lia J Smith, Laura Priorello, Kelly Lee, Matthew Estey, Mary R Newsome, M Wright Williams

Faculty, Staff and Students Publications

Exposure and cognitive-based therapies are both effective for PTSD, but knowledge of which intervention is best for which patient is lacking. This lack of knowledge is particularly noticeable for group treatments, as no study has examined whether responses to different group therapies are associated with different pretreatment characteristics. Here, we explored whether pretreatment levels of three types of psychological characteristics-PTSD symptom clusters, posttraumatic cognitions, and emotion regulation difficulties-were associated with symptom reduction during group-delivered cognitive versus exposure-based PTSD treatment. Participants were Veterans with PTSD drawn from two previous clinical trials: one of group CPT (GCPT;


Continuing Education And Professional Development: Unifying Opportunities For Genetic Counselors Globally, Kathleen D Valverde, Tiffiney R Hartman, Sara L Reichert, Robin L Bennett, Martha Dudek, Debra Duquette, Daniel Riconda, Nancy J Cox, Gail P Jarvik, Sarah H Elsea, Elizabeth M Mcnally, Kim C Worley, Daniel J Rader Jan 2024

Continuing Education And Professional Development: Unifying Opportunities For Genetic Counselors Globally, Kathleen D Valverde, Tiffiney R Hartman, Sara L Reichert, Robin L Bennett, Martha Dudek, Debra Duquette, Daniel Riconda, Nancy J Cox, Gail P Jarvik, Sarah H Elsea, Elizabeth M Mcnally, Kim C Worley, Daniel J Rader

Faculty, Staff and Students Publications

No abstract provided.


Cutting Edge Of Genetically Modified Pigs Targeting Complement Activation For Xenotransplantation, Qin Sun, Si-Yuan Song, Jiabao Ma, Danni Li, Yiping Wang, Zhengteng Yang, Yi Wang Jan 2024

Cutting Edge Of Genetically Modified Pigs Targeting Complement Activation For Xenotransplantation, Qin Sun, Si-Yuan Song, Jiabao Ma, Danni Li, Yiping Wang, Zhengteng Yang, Yi Wang

Faculty, Staff and Students Publications

In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of …