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Cardiac Effects Of Huntington’S Disease In Murine Models, Daniel David Child 2019 University of Pennsylvania

Cardiac Effects Of Huntington’S Disease In Murine Models, Daniel David Child

Publicly Accessible Penn Dissertations

Huntington’s disease (HD) is an autosomal dominant disease known for its severe neurologic phenotype. However, the causative protein in HD, mutant huntingtin (mHTT), is widely expressed across tissue types and may have profound consequences for peripheral organs. Notably, heart disease is the second leading cause of death in HD patients, but if or how cardiac mHTT expression causes pathology is still unknown. Here, I characterize the cardiac phenotype in two HD mouse models and show that dysregulated mTORC1 activity is a key underlying mechanism. I show that normal heart growth is limited in HD mouse models, with mass regulated ...


Unraveling The Beta Cell Translatome: Elucidation Of An Erk/Hnrnpk/Jund Axis, Austin Lewis Good 2019 University of Pennsylvania

Unraveling The Beta Cell Translatome: Elucidation Of An Erk/Hnrnpk/Jund Axis, Austin Lewis Good

Publicly Accessible Penn Dissertations

In type 2 diabetes, oxidative stress contributes to the dysfunction and loss of pancreatic β cells. A highly conserved feature of the cellular response to stress is the regulation of mRNA translation, however, the mechanisms underlying this process in β cells are not fully understood. Here we use TRAP-seq to examine changes in the ribosome occupancy of mRNAs during conditions associated with β cell dysfunction, leading us to identify a cohort of translationally regulated genes with 3’UTR enrichment of a cytosine-rich motif. Of particular interest was the gene encoding JUND, a transcription factor with anti-oxidant functions in other cell ...


The Role Of P120catenin In The Initiation And Dissemination Of Pancreatic Cancer, Basil Bakir 2019 University of Pennsylvania

The Role Of P120catenin In The Initiation And Dissemination Of Pancreatic Cancer, Basil Bakir

Publicly Accessible Penn Dissertations

Pancreatic cancer is the third leading cause of cancer mortality, the overwhelming majority of which is due to metastasis. The mechanisms of dissemination have been intensively studied, but questions remain as to how epithelial properties are regulated between the primary tumor site and destination as well as to how organotropic patterns of metastasis are determined. We demonstrate, using multiple complementary mouse models, that liver and lung metastatic organotropism in pancreatic cancer is dependent on p120catenin (p120ctn)-mediated epithelial identity. Monoallelic p120ctn loss accelerates KrasG12D-driven PanIN/PDAC formation and metastasis to the liver as well as being sufficient for E-CADHERIN-mediated cell ...


Roles Of Euchromatin And Heterochromatin In Hepatocyte Maturation And Liver Fibrosis, Jessica Mae Grindheim 2019 University of Pennsylvania

Roles Of Euchromatin And Heterochromatin In Hepatocyte Maturation And Liver Fibrosis, Jessica Mae Grindheim

Publicly Accessible Penn Dissertations

Liver transplantation is the main treatment for acute liver failure patients; however, there is an insufficient supply of donor livers. Since transplanting hepatocytes, the main liver cell type, provides therapeutic effect and can be a bridge to transplant or recovery, scientists are working on generating replacement hepatocytes from stem cells and other cell types through reprogramming protocols. Currently, replacement hepatocytes recapitulate a subset of natural hepatocyte features, yet are still in an immature state, as they have not silenced all immature hepatocyte genes and activated all mature hepatocyte genes. Consequently, replacement hepatocytes do not perform as well as natural hepatocytes ...


Filogeografía, Diversidad Genética Y Estructura Poblacional De La Raya Manta, Paratrygon Aiereba (Müller & Henle,1841) (Myliobatiformes: Potamotrygonidae) En Las Cuencas De Las Amazonas Y Orinoco, Maira Alejandra Rizo Fuentes 2019 Universidad de La Salle, Bogotá

Filogeografía, Diversidad Genética Y Estructura Poblacional De La Raya Manta, Paratrygon Aiereba (Müller & Henle,1841) (Myliobatiformes: Potamotrygonidae) En Las Cuencas De Las Amazonas Y Orinoco, Maira Alejandra Rizo Fuentes

Biología

La raya Manta de agua dulce Paratrygon aiereba (Müller & Henle,1841) es un pez de interés ornamental, tiene una amplia distribución en las cuencas del Amazonas y el Orinoco. Es la única especie descrita en el género Paratrygon, aunque algunos autores mencionan que dentro y entre las cuencas mencionadas, P. aiereba revela variaciones morfométricas, osteológicas y de coloración que podrían indicar la existencia de más de una especie. Con el fin de estimar la filogeografía, la diversidad genética y la estructura poblacional de P. aiereba en las cuencas del Amazonas y Orinoco en Colombia, se amplificó una porción del gen Citocromo oxidasa subunidad I (COXI) como marcador molecular de ADN mitocondrial (ADNmt), en 50 muestras de las dos cuencas principales (Amazonas y Orinoco) y ocho subcuencas diferentes, incluidos los cauces principales de ambos ríos. Se realizaron análisis de filogenia bayesiana con calibración fósil, análisis filogeográfico y red de haplotipos, seguido de un análisis de la varianza molecular. El análisis de agrupamiento (K) de los datos de secuencias de ADN para revelar la estructura genética de la población, se implementó mediante el uso de inferencia bayesiana. Los resultados sugieren tres Filogrupos, dos en la cuenca del Orinoco (A-B) y uno en la cuenca del Amazonas (C). Se reconoce un evento vicariante de hace 43 millones de años, que marcó la divergencia de Paratrygon. Se encontró una alta estructura poblacional con un valor significativo de (ST = 0.692; p <0.005), que sugiere una conectividad genética baja y un K = 3, en el cual el valor de probabilidad marginal logarítmica fue más alto, aunque se encontraron algunos haplotipos compartidos entre las cuencas del Amazonas y el Orinoco. Se determinaron 12 haplotipos y una diversidad genética relativamente alta (Filogrupo A) (h = 0.64; π = 2,48%), (Filogrupo B) (h = 0.552; π = 1,67%), y (Filogrupo C) (h = 0,49; π = 0,73%). Los resultados genéticos de este estudio deben ser considerados en los planes de manejo locales; programas de conservación y sugieren una reclasificación de esta especie por lo menos en estas dos cuencas (Amazonas y Orinoco). Se discute sobre la historia biogeográfica en América del Sur donde aparentemente, un evento vicariante después de la elevación de los Andes durante el Paleo Orinoco-Amazonas, fue crucial en la diversificación del género Paratrygon.


Molecular Homology & The Ancient Genetic Toolkit: How Evolutionary Development Could Shape Your Next Doctor's Appointment, Elizabeth G. Plender 2019 Regis University

Molecular Homology & The Ancient Genetic Toolkit: How Evolutionary Development Could Shape Your Next Doctor's Appointment, Elizabeth G. Plender

All Regis University Theses

Homology, i.e. the biological pattern of “sameness,” is a pervasive facet of evolution at both the organismic and molecular levels of organization. While traditionally interpreted at the anatomical scale, shared molecular phenotypes across vastly divergent species hint at the presence of a deeply conserved, ancient genetic “toolkit” characteristic of the animal kingdom. Through careful examination of the nuanced homologues implicated in comparative embryology, evolutionary developmental biologists provide a holistic approach to understanding how homologous patterns of gene regulation translate to anatomical similarities among animal species. My summer research project in the Division of Developmental Biology at Cincinnati Children’s ...


Genome Sequences Of Three Cruciviruses Found In The Willamette Valley (Oregon), Ignacio de la Higuera, Ellis L. Torrance, Alyssa A. Pratt, George Kasun, Amberlee Maluenda, Kenneth M. Stedman 2019 Portland State University

Genome Sequences Of Three Cruciviruses Found In The Willamette Valley (Oregon), Ignacio De La Higuera, Ellis L. Torrance, Alyssa A. Pratt, George Kasun, Amberlee Maluenda, Kenneth M. Stedman

Biology Faculty Publications and Presentations

Cruciviruses are single-stranded DNA (ssDNA) viruses whose genomes suggest the possibility of gene transfer between DNA and RNA viruses. Many crucivirus genome sequences have been found in metagenomic data sets, although no crucivirus has been isolated. Here, we present the complete genome sequences of three cruciviruses recovered from environmental samples from Oregon.


Vitamin D Receptor Gene Polymorphisms Knowledge And Breast Cancer In Texas, Ejike Roland Egwuekwe 2019 Walden University

Vitamin D Receptor Gene Polymorphisms Knowledge And Breast Cancer In Texas, Ejike Roland Egwuekwe

Walden Dissertations and Doctoral Studies

Breast cancer is a world health problem and is a leading cause of cancer-related death among women in the United States. However, breast cancer risks were reported to be reduced through exposure to Vitamin D through its Receptors identified as the p53 target gene. The purpose of this study was to assess the associations between VDR gene polymorphisms knowledge/awareness and decisions to reduce breast cancer risks and likelihood of mammogram screening among women in Texas. Data from survey were used. Roy adaptation model was the theoretical framework that guided this quasi- experimental, quantitative research. The dependent variables were decisions ...


Effects Of Pag1 On Src-Family Kinase Trafficking In Neuroblastoma Cells, Makenzie E. Mayfield 2019 University of Montana, Missoula

Effects Of Pag1 On Src-Family Kinase Trafficking In Neuroblastoma Cells, Makenzie E. Mayfield

Undergraduate Theses and Professional Papers

The receptor tyrosine kinases (RTKs) are known to help regulate cell behaviors including differentiation, proliferation and migration during embryonic development of the neural crest. RTKs are believed to initiate signaling cascades in response to extracellular cues in part by controlling localization of Src-family kinases (SFKs). The scaffolding protein PAG1 binds SFKs and is believed to influence SFK activity and location within the cell by promoting interaction of SFKs with regulatory proteins and by drawing SFKs into different components of the endocytic pathway. By targeting the PAG1 gene in SH-SY5Y neuroblastoma cells with CRISPR/Cas9 plasmids, we created PAG1-mutant cell-lines in ...


Exosomes Mediate Zika Virus Transmission Through Smpd3 Neutral Sphingomyelinase In Cortical Neurons, Wenshuo Zhou, Michael Woodson, Michael B. Sherman, Girish Neelakanta, Hameeda Sultana 2019 Old Dominion University

Exosomes Mediate Zika Virus Transmission Through Smpd3 Neutral Sphingomyelinase In Cortical Neurons, Wenshuo Zhou, Michael Woodson, Michael B. Sherman, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

The harmful effects of ZIKA virus (ZIKV) infection are reflected by severe neurological manifestations such as microcephaly in neonates and other complications associated with Guillain-Barre syndrome in adults. The transmission dynamics of ZIKV in or between neurons, or within the developing brains of the foetuses are not fully understood. Using primary cultures of murine cortical neurons, we show that ZIKV uses exosomes as mediators of viral transmission between neurons. Cryo-electron microscopy showed heterogeneous population of neuronal exosomes with a size range of 30-200 nm. Increased production of exosomes from neuronal cells was noted upon ZIKV infection. Neuronal exosomes contained both ...


Expression Of Alternative Oxidase In The Copepod T. Californicus When Exposed To Environmental Stressors, Carly Tward 2019 Wilfrid Laurier University

Expression Of Alternative Oxidase In The Copepod T. Californicus When Exposed To Environmental Stressors, Carly Tward

Theses and Dissertations (Comprehensive)

In addition to the typical electron transport system in animal mitochondria responsible for oxidative phosphorylation, some species possess an alternative oxidase (AOX) pathway, which causes electrons to bypass proton pumping complexes. Although AOX appears to be energetically wasteful, studies have revealed its wide taxonomic distribution, and indicate it plays a role in environmental stress tolerance. AOX discovery in animals is recent, and further research into its expression, regulation, and physiological role has been impeded by the lack of an experimental model organism. DNA database searches using bioinformatics revealed an AOX sequence present in the arthropod Tigriopus californicus. Multiple sequence alignments ...


Spatiotemporal Modeling And Model Restructuration Approaches In Studies Of Intracellular Signalling Pathways, Md Shahinuzzaman 2019 Missouri University of Science and Technology

Spatiotemporal Modeling And Model Restructuration Approaches In Studies Of Intracellular Signalling Pathways, Md Shahinuzzaman

Doctoral Dissertations

"The main focus of the research is to understand the complex phenomena of cell transduction pathways and cell biology in a single cell. Mathematical modeling and experimental evaluation are widely used approaches for this kind of research. Firstly, A multiscale framework for protein-protein interaction has been established using Brownian dynamics algorithm. Sit specific feature, steric collision, diffusion, co-localization and complex formation with time and space has been included in this spatial modeling framework. By implementation of the time adaptive feature in this framework, the computation time reduces in an order of magnitude compared with traditional modeling framework. This multiscale Brownian ...


The Phytoremediative Effects Of Cilantro (Coriandrum Sativum) In Lead Contaminated Soil, Sierra D. Garrett, Timothy D. Trott 2019 Southern Adventist University

The Phytoremediative Effects Of Cilantro (Coriandrum Sativum) In Lead Contaminated Soil, Sierra D. Garrett, Timothy D. Trott

Research in Biology

Environmental exposure to heavy metals such as lead pose a significant health threat. The goal of this project was to evaluate the effectiveness of Coriandrum sativum (Cilantro) as a potential lead (II), Pb2+, phytoremediator. C. sativumplants were allowed to grow for 43 days while exposed to with different amounts of lead nitrate, Pb(NO3)2. Lead exposure was accomplished by regular watering with a concentration series of lead nitrate solutions. The roots and shoots of these plants were separated and dried. Ground plant material was liquefied by nitric acid digestion. The amount of lead absorbed by each ...


Relación Entre La Grasa Subcutánea Y Desempeño Maternal En Vacas Angus Primerizas, Esteban Mendoza de la Pava, Adel David Kalil Rey 2019 Universidad de La Salle, Bogotá

Relación Entre La Grasa Subcutánea Y Desempeño Maternal En Vacas Angus Primerizas, Esteban Mendoza De La Pava, Adel David Kalil Rey

Zootecnia

El objetivo del presente estudio, tuvo como finalidad lograr identificar el porcentaje de grasa dorsal que se moviliza en vacas Angus primerizas posterior al parto y cómo este podría verse relacionado con el desempeño maternal y el peso al destete del ternero. Para poder lograr este objetivo, se evaluaron doce vacas primerizas de la raza Angus del CIC (centro de investigación y capacitación) San Miguel en Facatativa, Cundinamarca, con diversos parámetros productivos como: peso corporal, puntaje de condición corporal del preparto y al destete, espesor de grasa dorsal (preparto y destete), espesor de grasa en el anca (preparto y destete ...


Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks 2019 Missouri State University

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

MSU Graduate Theses

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine ...


Hla-Do Modulates The Diversity Of The Mhc-Ii Self-Peptidome, Padma P. Nanaware, Mollie M. Jurewicz, John D. Leszyk, Scott A. Shaffer, Lawrence J. Stern 2018 University of Massachusetts Medical School

Hla-Do Modulates The Diversity Of The Mhc-Ii Self-Peptidome, Padma P. Nanaware, Mollie M. Jurewicz, John D. Leszyk, Scott A. Shaffer, Lawrence J. Stern

Open Access Articles

Presentation of antigenic peptides on MHC-II molecules is essential for tolerance to self and for initiation of immune responses against foreign antigens. DO (HLA-DO in humans, H2-O in mice) is a non-classical MHC-II protein that has been implicated in control of autoimmunity and regulation of neutralizing antibody responses to viruses. These effects likely are related to a role of DO in selecting MHC-II epitopes, but previous studies examining the effect of DO on presentation of selected CD4 T cell epitopes have been contradictory. To understand how DO modulates MHC-II antigen presentation, we characterized the full spectrum of peptides presented by ...


Chemically Modified Monolayer Surfaces Influence Valvular Interstitial Cell Attachment And Differentiation For Heart Valve Tissue Engineering, Matthew N. Rush 2018 University of New Mexico - Main Campus

Chemically Modified Monolayer Surfaces Influence Valvular Interstitial Cell Attachment And Differentiation For Heart Valve Tissue Engineering, Matthew N. Rush

Nanoscience and Microsystems ETDs

As a cell mediated-process, valvular heart disease (VHD) results in significant morbidity and mortality world-wide. In the US alone, valvular heart disease VHD is estimated to affect 2.5% of the population with a disproportionate impact on an increasing elderly populous. It is well understood that the primary driver for valvular calcification is the differentiation of valvular interstitial cells (VICs) into an osteoblastic-like phenotype. However, the factors leading to the onset of osteoblastic-like VICs (obVICs) and resulting calcification are not fully understood and a more complete characterization of VIC differentiation and phenotypic change is required before treatment of valve disease ...


Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer 2018 University of Nebraska Medical Center

Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer

Theses & Dissertations

The Hippo pathway is conserved regulator of organ size through control of proliferation, apoptosis, and stem-cell self-renewal. In addition to this important function, many of the canonical signaling members have also been shown to be regulated during mitosis. Importantly, Hippo pathway components are frequently dysregulated in cancers and have attracted attention as possible targets for improved cancer therapeutics. Further exploration of Hippo-YAP (yes-associated protein) signaling has revealed new regulators and effectors outside the canonical signaling network and has revealed a larger non-canonical network of signaling proteins in which canonical Hippo pathway components crosstalk with important cellular homeostasis and apoptosis signaling ...


Manganese Influx And Expression Of Zip8 Is Essential In Primary Myoblasts And Contributes To Activation Of Sod2, Shellaina J. V. Gordon, Daniel E. Fenker, Katherine E. Vest, Teresita Padilla-Benavides 2018 University of Massachusetts Medical School

Manganese Influx And Expression Of Zip8 Is Essential In Primary Myoblasts And Contributes To Activation Of Sod2, Shellaina J. V. Gordon, Daniel E. Fenker, Katherine E. Vest, Teresita Padilla-Benavides

University of Massachusetts Medical School Faculty Publications

Trace elements such as copper (Cu), zinc (Zn), iron (Fe), and manganese (Mn) are enzyme cofactors and second messengers in cell signaling. Trace elements are emerging as key regulators of differentiation and development of mammalian tissues including blood, brain, and skeletal muscle. We previously reported an influx of Cu and dynamic expression of various metal transporters during differentiation of skeletal muscle cells. Here, we demonstrate that during differentiation of skeletal myoblasts an increase of additional trace elements such as Mn, Fe and Zn occurs. Interestingly the Mn increase is concomitant with increased Mn-dependent SOD2 levels. To better understand the Mn ...


The Effects Of Sugars On Lactobacillus Casei Growth, Alexis Felty, Sidney Gerkin, Taylor Kowalski, Parker Williams 2018 Marian University - Indianapolis

The Effects Of Sugars On Lactobacillus Casei Growth, Alexis Felty, Sidney Gerkin, Taylor Kowalski, Parker Williams

Undergraduate Research Symposium (URS)

The Western culture tends to deem the Eastern culture as obese and unhealthy due to the large amounts of saturated fats and abundance of sugars that it consumes. Some studies argue that Lactobacillus casei can alter health and researchers are attempting to prove that different sugars, natural or artificial, have different effects on the growth of L. casei [1]. L. casei was chosen as the experimental model due to easily replicable growing conditions and the importance of the bacteria in the gut microbiome.

Sugar-bacteria solutions were created and their turbidities were taken to quantify the amount of bacteria growth after ...


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