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Neural Stem Cell Metabolic Changes In The Presence Of Interferon-Gamma, Dylan McKibben 2021 The University of Akron

Neural Stem Cell Metabolic Changes In The Presence Of Interferon-Gamma, Dylan Mckibben

Williams Honors College, Honors Research Projects

Spinal cord injury results in significant disability and health care costs due to an inability of the mature central nervous system to regenerate. One potential therapy would be implantation of neural stem cells to the injury site and stimulation of their differentiation to mature neurons. Previous work has shown that the cytokine interferon-gamma can promote this process; however, the signaling pathways induced in neural stem cells have not been well-defined. This proposal examines neural stem cell metabolic responses to signaling induced by interferon-gamma. Two questions will be answered: i) What specific metabolic pathway is activated to guide neural stem cell ...


Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish 2021 West Virginia University

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish

Graduate Theses, Dissertations, and Problem Reports

Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and ...


Altered Photoreceptor Metabolism In Mouse Causes Late Stage Age-Related Macular Degeneration-Like Pathologies, Shun-Yun Cheng, Joris Cipi, Shan Ma, Brian P. Hafler, Rahul N. Kanadia, Richard S. Brush, Martin-Paul Agbaga, Claudio Punzo 2020 University of Massachusetts Medical School

Altered Photoreceptor Metabolism In Mouse Causes Late Stage Age-Related Macular Degeneration-Like Pathologies, Shun-Yun Cheng, Joris Cipi, Shan Ma, Brian P. Hafler, Rahul N. Kanadia, Richard S. Brush, Martin-Paul Agbaga, Claudio Punzo

Open Access Articles

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. While the histopathology of the different disease stages is well characterized, the cause underlying the progression, from the early drusen stage to the advanced macular degeneration stage that leads to blindness, remains unknown. Here, we show that photoreceptors (PRs) of diseased individuals display increased expression of two key glycolytic genes, suggestive of a glucose shortage during disease. Mimicking aspects of this metabolic profile in PRs of wild-type mice by activation of the mammalian target of rapamycin complex 1 (mTORC1) caused early drusen-like pathologies, as well as advanced ...


Breast Cancer Sub-Clones That Metastasize To Lung And Bone Exhibit Different Metabolic Preferences, Mollie Merrell 2020 University of Mississippi

Breast Cancer Sub-Clones That Metastasize To Lung And Bone Exhibit Different Metabolic Preferences, Mollie Merrell

Honors Theses

Metastasis is responsible for the majority of cancer related deaths. In breast cancer the lungs and bones are the major sites for metastasis. Previous studies used the metastatic aggressive MDA-MB-231 breast cancer line to isolate sub-clones that preferentially invade the lungs (LM line) or bones (BoM line). While genes associated with the tissue specific metastasis have been identified, it is unknown if metabolic adaptations contribute to the growth of the LM and BoM lines in their respective organs. The goal of this study was to test the hypothesis that the LM and BoM lines exhibit differences in glucose and glutamine ...


Effects Of Nicotinamide Riboside And Beta-Hydroxybutyrate On C. Elegans Lifespan, Jeffery Peters 2020 East Tennessee State University

Effects Of Nicotinamide Riboside And Beta-Hydroxybutyrate On C. Elegans Lifespan, Jeffery Peters

Undergraduate Honors Theses

The nicotinamide riboside (NR) form of vitamin B3and the ketone body ß-hydroxybutyrate (BHB) are two of the most promising natural compounds yet identified for the treatment of aging and aging-related diseases. Forms of vitamin B3are precursors for the synthesis of the coenzymes nicotinamide adenine dinucleotide (NAD(H)) and nicotinamide adenine dinucleotide phosphate (NADP(H)). In aged cells levels of NAD+decline, decreasing metabolism and decreasing activity of protective sirtuin protein deacetylases. In aged cells NR, but not more common forms of vitamin B3, boost NAD+levels. BHB is naturally produced by the body when individuals fast ...


Plant-Based Diet: How It Affects Health, Sarah Marsland 2020 University of Rhode Island

Plant-Based Diet: How It Affects Health, Sarah Marsland

Senior Honors Projects

This research project aims to investigate the relationship between plant-based dieting and overall health, specifically the prevention and reversal of chronic disease. Two subjects committed to eating a plant-based diet comprised of primarily vegetables, fruits, whole grains and non-processed foods for six weeks. Before beginning, they were asked about their current health status, including a complete health history, and their knowledge of plant-based eating. Throughout the research period, the subjects shared what they were eating, challenges they faced, and any benefits they noticed. Upon completion of the diet, they answered questions about their experience. With this information, the researcher was ...


A Big-Data Approach To Understanding Metabolic Rate And Response To Obesity In Laboratory Mice, June K. Corrigan, Deepti Ramachandran, Yuchen He, Colin J. Palmer, Michael J. Jurczak, Rui Chen, Bingshan Li, Randall H. Friedline, Jason K. Kim, Jon J. Ramsey, Louise Lantier, Owen P. McGuinness, Alexander S. Banks 2020 Harvard Medical School

A Big-Data Approach To Understanding Metabolic Rate And Response To Obesity In Laboratory Mice, June K. Corrigan, Deepti Ramachandran, Yuchen He, Colin J. Palmer, Michael J. Jurczak, Rui Chen, Bingshan Li, Randall H. Friedline, Jason K. Kim, Jon J. Ramsey, Louise Lantier, Owen P. Mcguinness, Alexander S. Banks

Open Access Articles

Maintaining a healthy body weight requires an exquisite balance between energy intake and energy expenditure. To understand the genetic and environmental factors that contribute to the regulation of body weight, an important first step is to establish the normal range of metabolic values and primary sources contributing to variability. Energy metabolism is measured by powerful and sensitive indirect calorimetry devices. Analysis of nearly 10,000 wild-type mice from two large-scale experiments revealed that the largest variation in energy expenditure is due to body composition, ambient temperature, and institutional site of experimentation. We also analyze variation in 2329 knockout strains and ...


The Role Of Nutrition In Promoting Gut Health And Treating Chronic Illness Through The Attenuation Of Inflammation, Allison Dalton 2020 HCA

The Role Of Nutrition In Promoting Gut Health And Treating Chronic Illness Through The Attenuation Of Inflammation, Allison Dalton

HCA Healthcare Journal of Medicine

Over the millennia, the human body and microorganisms such as bacteria, viruses, archaea, protozoa and parasites have coevolved together forming an intimate relationship. These microorganisms are found on the skin, in the mouth, genitourinary tract and most abundantly in the large intestine of the digestive tract. States of microbial dysbiosis contribute to chronic inflammation, which can lead to the pathogenesis and progression of numerous diseases. Micro- and macro-nutrients as well as dietary patterns like the Mediterranean diet can help improve health outcomes.


Developmental Regression And Mitochondrial Function In Children With Autism, Kanwaljit Singh, Indrapal N. Singh, Eileen Diggins, Susan Connors, Mohammad A. Karim, David Lee, Andrew W. Zimmerman, Richard E. Frye 2020 University of Massachusetts Medical School

Developmental Regression And Mitochondrial Function In Children With Autism, Kanwaljit Singh, Indrapal N. Singh, Eileen Diggins, Susan Connors, Mohammad A. Karim, David Lee, Andrew W. Zimmerman, Richard E. Frye

Open Access Articles

BACKGROUND: Developmental regression (DR) occurs in about one-third of children with Autism Spectrum Disorder (ASD) yet it is poorly understood. Current evidence suggests that mitochondrial function in not normal in many children with ASD. However, the relationship between mitochondrial function and DR has not been well-studied in ASD.

METHODS: This cross-sectional study of 32 children, 2 to 8 years old with ASD, with (n = 11) and without (n = 12) DR, and non-ASD controls (n = 9) compared mitochondrial respiration and mtDNA damage and copy number between groups and their relation to standardized measures of ASD severity.

RESULTS: Individuals with ASD demonstrated ...


The Coordinate Actions Of Calcineurin And Hog1 Mediate The Stress Response Through Multiple Nodes Of The Cell Cycle Network, Cassandra M. Leech, Mackenzie J. Flynn, Heather E. Arsenault, Jianhong Ou, Haibo Liu, Lihua Julie Zhu, Jennifer A. Benanti 2020 University of Massachusetts Medical School

The Coordinate Actions Of Calcineurin And Hog1 Mediate The Stress Response Through Multiple Nodes Of The Cell Cycle Network, Cassandra M. Leech, Mackenzie J. Flynn, Heather E. Arsenault, Jianhong Ou, Haibo Liu, Lihua Julie Zhu, Jennifer A. Benanti

Open Access Articles

Upon exposure to environmental stressors, cells transiently arrest the cell cycle while they adapt and restore homeostasis. A challenge for all cells is to distinguish between stress signals and coordinate the appropriate adaptive response with cell cycle arrest. Here we investigate the role of the phosphatase calcineurin (CN) in the stress response and demonstrate that CN activates the Hog1/p38 pathway in both yeast and human cells. In yeast, the MAPK Hog1 is transiently activated in response to several well-studied osmostressors. We show that when a stressor simultaneously activates CN and Hog1, CN disrupts Hog1-stimulated negative feedback to prolong Hog1 ...


Transcriptomic Profiling Reveals Extraordinary Diversity Of Venom Peptides In Unexplored Predatory Gastropods Of The Genus Clavus, Aiping Lu, Maren Watkins, Qing Li, Samuel D. Robinson, Gisela P. Concepcion, Mark Yandell, Zhiping Weng, Baldomero M. Olivera, Helena Safavi-Hemami, Alexander E. Fedosov 2020 Tongji University

Transcriptomic Profiling Reveals Extraordinary Diversity Of Venom Peptides In Unexplored Predatory Gastropods Of The Genus Clavus, Aiping Lu, Maren Watkins, Qing Li, Samuel D. Robinson, Gisela P. Concepcion, Mark Yandell, Zhiping Weng, Baldomero M. Olivera, Helena Safavi-Hemami, Alexander E. Fedosov

Open Access Articles

Predatory gastropods of the superfamily Conoidea number over 12,000 living species. The evolutionary success of this lineage can be explained by the ability of conoideans to produce complex venoms for hunting, defense and competitive interactions. Whereas venoms of cone snails (family Conidae) have become increasingly well studied, the venoms of most other conoidean lineages remain largely uncharacterized. In the present study we present the venom gland transcriptomes of two species of the genus Clavus that belong to the family Drilliidae. Venom gland transcriptomes of two specimens of Clavus canalicularis, and two specimens of Cv. davidgilmouri were analyzed, leading to ...


Chemical Modifications Of Adenine Base Editor Mrna And Guide Rna Expand Its Application Scope, Tingting Jiang, Xiao-Ou Zhang, Yueying Cao, Zhiping Weng, Wen Xue 2020 University of Massachusetts Medical School

Chemical Modifications Of Adenine Base Editor Mrna And Guide Rna Expand Its Application Scope, Tingting Jiang, Xiao-Ou Zhang, Yueying Cao, Zhiping Weng, Wen Xue

Open Access Articles

CRISPR-Cas9-associated base editing is a promising tool to correct pathogenic single nucleotide mutations in research or therapeutic settings. Efficient base editing requires cellular exposure to levels of base editors that can be difficult to attain in hard-to-transfect cells or in vivo. Here we engineer a chemically modified mRNA-encoded adenine base editor that mediates robust editing at various cellular genomic sites together with moderately modified guide RNA, and show its therapeutic potential in correcting pathogenic single nucleotide mutations in cell and animal models of diseases. The optimized chemical modifications of adenine base editor mRNA and guide RNA expand the applicability of ...


How Immune T-Cell Augmentation Can Help Prevent Covid-19: A Possible Nutritional Solution Using Ketogenic Lifestyle, Ravi k. Kamepalli MD,FIDSA,CWSP 2020 Regional Infectious diseases and infusion ctr,Inc

How Immune T-Cell Augmentation Can Help Prevent Covid-19: A Possible Nutritional Solution Using Ketogenic Lifestyle, Ravi K. Kamepalli Md,Fidsa,Cwsp

The University of Louisville Journal of Respiratory Infections

No abstract provided.


Recapitulation Of The Accessible Interface Of Biopsy-Derived Canine Intestinal Organoids To Study Epithelial-Luminal Interactions, Yoko M. Ambrosini, Yejin Park, Albert E. Jergens, Woojung Shin, Soyoun Min, Todd Atherly, Dana C. Borcherding, Jinah Jang, Karin Allenspach, Jonathan P. Mochel, Hyun Jung Kim 2020 University of Texas at Austin and Iowa State University

Recapitulation Of The Accessible Interface Of Biopsy-Derived Canine Intestinal Organoids To Study Epithelial-Luminal Interactions, Yoko M. Ambrosini, Yejin Park, Albert E. Jergens, Woojung Shin, Soyoun Min, Todd Atherly, Dana C. Borcherding, Jinah Jang, Karin Allenspach, Jonathan P. Mochel, Hyun Jung Kim

Biomedical Sciences Publications

Recent advances in canine intestinal organoids have expanded the option for building a better in vitro model to investigate translational science of intestinal physiology and pathology between humans and animals. However, the three-dimensional geometry and the enclosed lumen of canine intestinal organoids considerably hinder the access to the apical side of epithelium for investigating the nutrient and drug absorption, host-microbiome crosstalk, and pharmaceutical toxicity testing. Thus, the creation of a polarized epithelial interface accessible from apical or basolateral side is critical. Here, we demonstrated the generation of an intestinal epithelial monolayer using canine biopsy-derived colonic organoids (colonoids). We optimized the ...


Dbf4-Dependent Kinase (Ddk)-Mediated Proteolysis Of Cenp-A Prevents Mislocalization Of Cenp-A In Saccharomyces Cerevisiae, Jessica R. Eisenstatt, Lars Boeckmann, Wei-Chun Au, Valerie Garcia, Levi Bursch, Josefina Ocampo, Michael Costanzo, Michael Weinreich, Robert A. Sclafani, Anastasia Baryshnikova, Chad L. Myers, Charles Boone, David J. Clark, Richard E. Baker, Munira A. Basrai 2020 National Cancer Institute

Dbf4-Dependent Kinase (Ddk)-Mediated Proteolysis Of Cenp-A Prevents Mislocalization Of Cenp-A In Saccharomyces Cerevisiae, Jessica R. Eisenstatt, Lars Boeckmann, Wei-Chun Au, Valerie Garcia, Levi Bursch, Josefina Ocampo, Michael Costanzo, Michael Weinreich, Robert A. Sclafani, Anastasia Baryshnikova, Chad L. Myers, Charles Boone, David J. Clark, Richard E. Baker, Munira A. Basrai

Open Access Articles

The evolutionarily conserved centromeric histone H3 variant (Cse4 in budding yeast, CENP-A in humans) is essential for faithful chromosome segregation. Mislocalization of CENP-A to non-centromeric chromatin contributes to chromosomal instability (CIN) in yeast, fly, and human cells and CENP-A is highly expressed and mislocalized in cancers. Defining mechanisms that prevent mislocalization of CENP-A is an area of active investigation. Ubiquitin-mediated proteolysis of overexpressed Cse4 (GALCSE4) by E3 ubiquitin ligases such as Psh1 prevents mislocalization of Cse4, and psh1Delta strains display synthetic dosage lethality (SDL) with GALCSE4. We previously performed a genome-wide screen and identified five alleles of CDC7 and DBF4 ...


Identification And Characterization Of The Lactating Mouse Mammary Gland Citrullinome, Guangyuan Li, Coleman H. Young, Bryce Snow, Amanda O. Christensen, M. Kristen Demoruelle, Venkatesh V. Nemmara, Paul R. Thompson, Heather M. Rothfuss, Brian D. Cherrington 2020 University of Wyoming

Identification And Characterization Of The Lactating Mouse Mammary Gland Citrullinome, Guangyuan Li, Coleman H. Young, Bryce Snow, Amanda O. Christensen, M. Kristen Demoruelle, Venkatesh V. Nemmara, Paul R. Thompson, Heather M. Rothfuss, Brian D. Cherrington

Open Access Articles

Citrullination is a post-translational modification (PTM) in which positively charged peptidyl-arginine is converted into neutral peptidyl-citrulline by peptidylarginine deiminase (PAD or PADI) enzymes. The full protein citrullinome in many tissues is unknown. Herein, we used mass spectrometry and identified 107 citrullinated proteins in the lactation day 9 (L9) mouse mammary gland including histone H2A, alpha-tubulin, and beta-casein. Given the importance of prolactin to lactation, we next tested if it stimulates PAD-catalyzed citrullination using mouse mammary epithelial CID-9 cells. Stimulation of CID-9 cells with 5 microg/mL prolactin for 10 min induced a 2-fold increase in histone H2A citrullination and a ...


Histone Deacetylases 1 And 2 Silence Cryptic Transcription To Promote Mitochondrial Function During Cardiogenesis, Zachary J. Milstone, Sherin Saheera, Lauren Bourke, Tomer Shpilka, Cole M. Haynes, Chinmay M. Trivedi 2020 University of Massachusetts Medical School

Histone Deacetylases 1 And 2 Silence Cryptic Transcription To Promote Mitochondrial Function During Cardiogenesis, Zachary J. Milstone, Sherin Saheera, Lauren Bourke, Tomer Shpilka, Cole M. Haynes, Chinmay M. Trivedi

Open Access Articles

Cryptic transcription occurs widely across the eukaryotic genome; however, its regulation during vertebrate development is not understood. Here, we show that two class I histone deacetylases, Hdac1 and Hdac2, silence cryptic transcription to promote mitochondrial function in developing murine hearts. Mice lacking Hdac1 and Hdac2 in heart exhibit defective developmental switch from anaerobic to mitochondrial oxidative phosphorylation (OXPHOS), severe defects in mitochondrial mass, mitochondrial function, and complete embryonic lethality. Hdac1/Hdac2 promotes the transition to OXPHOS by enforcing transcriptional fidelity of metabolic gene programs. Mechanistically, Hdac1/Hdac2 deacetylates histone residues including H3K23, H3K14, and H4K16 to suppress cryptic transcriptional initiation ...


Interpretation Of The Epigenetic Signature Of Facioscapulohumeral Muscular Dystrophy In Light Of Genotype-Phenotype Studies, Ana Nikolic, Louise Maranda, Rossella Ginevra Tupler 2020 University of Modena and Reggio Emilia

Interpretation Of The Epigenetic Signature Of Facioscapulohumeral Muscular Dystrophy In Light Of Genotype-Phenotype Studies, Ana Nikolic, Louise Maranda, Rossella Ginevra Tupler

Open Access Articles

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by incomplete penetrance and intra-familial clinical variability. The disease has been associated with the genetic and epigenetic features of the D4Z4 repetitive elements at 4q35. Recently, D4Z4 hypomethylation has been proposed as a reliable marker in the FSHD diagnosis. We exploited the Italian Registry for FSHD, in which FSHD families are classified using the Clinical Comprehensive Evaluation Form (CCEF). A total of 122 index cases showing a classical FSHD phenotype (CCEF, category A) and 110 relatives were selected to test with the receiver operating characteristic (ROC) curve, the diagnostic and predictive value of D4Z4 ...


Visualizing Metabolic Network Dynamics Through Time-Series Metabolomic Data., Lea F Buchweitz, James T Yurkovich, Christoph Blessing, Veronika Kohler, Fabian Schwarzkopf, Zachary A King, Laurence Yang, Freyr Jóhannsson, Ólafur E Sigurjónsson, Óttar Rolfsson, Julian Heinrich, Andreas Dräger 2020 Institute for Systems Biology, 401 Terry Ave. N., Seattle, 98109, WA, United States

Visualizing Metabolic Network Dynamics Through Time-Series Metabolomic Data., Lea F Buchweitz, James T Yurkovich, Christoph Blessing, Veronika Kohler, Fabian Schwarzkopf, Zachary A King, Laurence Yang, Freyr Jóhannsson, Ólafur E Sigurjónsson, Óttar Rolfsson, Julian Heinrich, Andreas Dräger

Articles, Abstracts, and Reports

BACKGROUND: New technologies have given rise to an abundance of -omics data, particularly metabolomic data. The scale of these data introduces new challenges for the interpretation and extraction of knowledge, requiring the development of innovative computational visualization methodologies. Here, we present GEM-Vis, an original method for the visualization of time-course metabolomic data within the context of metabolic network maps. We demonstrate the utility of the GEM-Vis method by examining previously published data for two cellular systems-the human platelet and erythrocyte under cold storage for use in transfusion medicine.

RESULTS: The results comprise two animated videos that allow for new insights ...


Biomarker Exploration In Human Peripheral Blood Mononuclear Cells For Monitoring Sulforaphane Treatment Responses In Autism Spectrum Disorder, Hua Liu, Andrew W. Zimmerman, Kanwaljit Singh, Susan Connors, Eileen Diggins, Katherine K. Stephenson, Albena T. Dinkova-Kostova, Jed W. Fahey 2020 Johns Hopkins University

Biomarker Exploration In Human Peripheral Blood Mononuclear Cells For Monitoring Sulforaphane Treatment Responses In Autism Spectrum Disorder, Hua Liu, Andrew W. Zimmerman, Kanwaljit Singh, Susan Connors, Eileen Diggins, Katherine K. Stephenson, Albena T. Dinkova-Kostova, Jed W. Fahey

Open Access Articles

Autism Spectrum Disorder (ASD) is one of the most common neurodevelopmental disorders with no drugs treating the core symptoms and no validated biomarkers for clinical use. The multi-functional phytochemical sulforaphane affects many of the biochemical abnormalities associated with ASD. We investigated potential molecular markers from three ASD-associated physiological pathways that can be affected by sulforaphane: redox metabolism/oxidative stress; heat shock response; and immune dysregulation/inflammation, in peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with ASD. We first analyzed the mRNA levels of selected molecular markers in response to sulforaphane ex vivo treatment in PBMCs from healthy ...


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