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Articles 1 - 30 of 477

Full-Text Articles in Cell Biology

Role Of A 19s Proteasome Subunit- Psmd10(Gankyrin) In Neurogenesis Of Human Neuronal Progenitor Cells, Indrajit Sahu, Padma P. Nanaware, Minal Mane, Saim Wasi Mulla, Soumen Roy, Prasanna Venkatraman Aug 2019

Role Of A 19s Proteasome Subunit- Psmd10(Gankyrin) In Neurogenesis Of Human Neuronal Progenitor Cells, Indrajit Sahu, Padma P. Nanaware, Minal Mane, Saim Wasi Mulla, Soumen Roy, Prasanna Venkatraman

Open Access Articles

PSMD10(Gankyrin), a proteasome assembly chaperone, is a widely known oncoprotein which aspects many hall mark properties of cancer. However, except proteasome assembly chaperon function its role in normal cell function remains unknown. To address this issue, we induced PSMD10(Gankyrin) overexpression in HEK293 cells and the resultant large-scale changes in gene expression profile were analyzed. We constituted networks from microarray data of these differentially expressed genes and carried out extensive topological analyses. The overrecurring yet consistent theme that appeared throughout analysis using varied network metrics is that all genes and interactions identified as important would be involved in neurogenesis ...


Knocking Out A Negative Regulator Of Hedgehog Signaling Blocks Differentiation Of Cells Into Neurons, Danielle Margaret Spice, Gregory M. Kelly Ph.D. Jun 2019

Knocking Out A Negative Regulator Of Hedgehog Signaling Blocks Differentiation Of Cells Into Neurons, Danielle Margaret Spice, Gregory M. Kelly Ph.D.

Western Research Forum

Hedgehog (Hh) signaling, one of many different protein signaling pathways found in mammals, is vital in many stage of neural development. A major negative regulator of Hh signaling is a protein known as Suppressor of Fused (SUFU), which acts to sequester the full length Gli transcription factors, proteins that can turn genes on and off, in the cytoplasm or facilitates its conversion to a repressive form. The P19 embryonal carcinoma cell line is a model of hind-brain neuronal differentiation and the involvement of Hh signaling, in particular the role of SUFU in this process has yet to be explored. We ...


Smooth Muscle Cell-Specific Tmem16a Deletion Does Not Alter Ca2+ Signaling, Uterine Contraction, Gestation Length Or Litter Size In Micedagger, Mingzi Qu, Ping Lu, Karl D. Bellve, Kevin E. Fogarty, Lawrence M. Lifshitz, Fangxiong Shi, Ronghua Zhuge Jun 2019

Smooth Muscle Cell-Specific Tmem16a Deletion Does Not Alter Ca2+ Signaling, Uterine Contraction, Gestation Length Or Litter Size In Micedagger, Mingzi Qu, Ping Lu, Karl D. Bellve, Kevin E. Fogarty, Lawrence M. Lifshitz, Fangxiong Shi, Ronghua Zhuge

Program in Molecular Medicine Publications and Presentations

Ion channels in myometrial cells play critical roles in spontaneous and agonist-induced uterine contraction during the menstrual cycle, pregnancy maintenance and parturition; thus identifying the genes of ion channels in these cells and determining their roles are essential to understanding the biology of reproduction. Previous studies with in vitro functional and pharmacological approaches have produced controversial results regarding the presence and role of TMEM16A Ca2+-activated Cl- channels in myometrial cells. To unambiguously determine the function of this channel in these cells, we employed a genetic approach by using smooth muscle cell-specific TMEM16A deletion (i.e. TMEM16ASMKO) mice. We found ...


Characterization Of Pth Type-2 Receptor (Pth2rb) And Its Endogenous Ligand Pth2 In Zebrafish Development, Nicholas Seitz May 2019

Characterization Of Pth Type-2 Receptor (Pth2rb) And Its Endogenous Ligand Pth2 In Zebrafish Development, Nicholas Seitz

Theses and Dissertations

Members of the parathyroid hormone family of ligands, PTH (parathyroid hormone), PTH2, and PTHLH (parathyroid hormone-like hormone). These hormones interact with the class B GCPRs parathyroid hormone receptors PTH1R, PTH2R, and PTH3R to regulate a variety of biological processes. In mammals, PTH and PTHLH activate PTH1R and PTH3R to mediate serum calcium homeostasis, chondrogenesis, and bone maintenance. PTH2R activation by PTH2 has been studied primarily in regard to its neuroendocrine roles but is also found in the skin where it contributes to wound healing and keratinocyte differentiation. Still, little is known about the impacts of PTH2R signaling relative to PTH1R ...


Jnk(1/2) Represses Lkb(1)-Deficiency-Induced Lung Squamous Cell Carcinoma Progression, Jian Liu, Tianyuan Wang, Chad J. Creighton, San-Pin Wu, Madhumita Ray, Kyathanahalli S. Janardhan, Cynthia J. Willson, Sung-Nam Cho, Patricia D. Castro, Michael M. Ittmann, Jian-Liang Li, Roger J. Davis, Francesco J. Demayo May 2019

Jnk(1/2) Represses Lkb(1)-Deficiency-Induced Lung Squamous Cell Carcinoma Progression, Jian Liu, Tianyuan Wang, Chad J. Creighton, San-Pin Wu, Madhumita Ray, Kyathanahalli S. Janardhan, Cynthia J. Willson, Sung-Nam Cho, Patricia D. Castro, Michael M. Ittmann, Jian-Liang Li, Roger J. Davis, Francesco J. Demayo

Open Access Articles

Mechanisms of lung squamous cell carcinoma (LSCC) development are poorly understood. Here, we report that JNK1/2 activities attenuate Lkb1-deficiency-driven LSCC initiation and progression through repressing DeltaNp63 signaling. In vivo Lkb1 ablation alone is sufficient to induce LSCC development by reducing MKK7 levels and JNK1/2 activities, independent of the AMPKalpha and mTOR pathways. JNK1/2 activities is positively regulated by MKK7 during LSCC development. Pharmaceutically elevated JNK1/2 activities abates Lkb1 dependent LSCC formation while compound mutations of Jnk1/2 and Lkb1 further accelerate LSCC progression. JNK1/2 is inactivated in a substantial proportion of human LSCC and JNK1 ...


Muscle Degeneration In A Zebrafish Model Of Lysosomal Related Myopathy, Elizabeth Coffey May 2019

Muscle Degeneration In A Zebrafish Model Of Lysosomal Related Myopathy, Elizabeth Coffey

Electronic Theses and Dissertations

Muscle development and homeostasis are critical for normal muscle function. A key aspect of muscle physiology during development, growth and homeostasis is modulation of protein turnover. Protein turnover is the balance between synthesis and degradation of muscle proteins. The rate of protein degradation is the major factor underlying overall muscle growth during development. Protein degradation mainly takes place in the lysosome. The efficiency of lysosomal protein degradation depends upon lysosomal pH, which is generated and maintained by proton pumps. Despite the importance of protein degradation in muscle growth during development, the impact of dysregulated lysosomal pH on muscle development, growth ...


Molecular Mechanisms Mediating Morphogenesis Of The Basal Epithelial Tissue Fold During Midbrain-Hindbrain Boundary Formation In Zebrafish, Mike Roger Visetsouk May 2019

Molecular Mechanisms Mediating Morphogenesis Of The Basal Epithelial Tissue Fold During Midbrain-Hindbrain Boundary Formation In Zebrafish, Mike Roger Visetsouk

Theses and Dissertations

ABSTRACT

MOLECULAR MECHANISMS MEDIATING MORPHOGENESIS OF THE BASAL EPITHELIAL TISSUE FOLD DURING MIDBRAIN-HINDBRAIN BOUNDARY FORMATION IN ZEBRAFISH

by

Mike Roger Visetsouk

The University of Wisconsin-Milwaukee, 2019

Under the Supervision of Jennifer H. Gutzman, PhD

The formation of a fully functional organism requires the morphogenesis of cell and tissue structures during development. It is important to understand the mechanisms that mediate morphogenesis, since cell and tissue structures are crucial to physiological function. Here, we studied basal epithelial tissue folding as a model to determine the mechanisms of morphogenesis. We investigated a highly conserved basal tissue fold known as the midbrain-hindbrain boundary ...


The Role Of Ppal In The Moss Physcomitrella Patens., Noela M. Botaka May 2019

The Role Of Ppal In The Moss Physcomitrella Patens., Noela M. Botaka

College of Arts & Sciences Senior Honors Theses

Protein prenylation is a post-translational modification that involves the addition of lipid groups to the carboxy end of a target protein and is necessary for protein activity. Prenylation has important roles in the cell: targeting and localizing proteins to subcellular compartments and promoting protein-protein interactions. As a highly conserved process in eukaryotes, prenylation is especially important for plant development. In contrast to other eukaryotes, in which loss of prenylation components can be lethal, in the flowering plant Arabidopsis thaliana and the moss Physcomitrella patens, most are viable. Prior studies have shown that prenylation is involved in ABA hormone responses, polar ...


Platiscity Of C. Elegans Germline Stem Cells Under Nutritional And Metabolic Stress, Kenneth Trimmer May 2019

Platiscity Of C. Elegans Germline Stem Cells Under Nutritional And Metabolic Stress, Kenneth Trimmer

UT GSBS Dissertations and Theses (Open Access)

Stem cells are integral for tissue maintenance and fertility. Therefore, understanding how stem cells are regulated under stress is imperative. When confronted with acute starvation, stem cells must conserve energy and metabolites to cope with the lack of an external source. Caenorhabditis elegans germline stem cells (GSCs) are an excellent model for studying stem cell properties and regulation as they can divide throughout the life of the organism. While GSCs are an adult stem cell population, their cell cycle structure more closely mimics mouse and human embryonic stem cells with short G1 and long S phases. In this thesis, I ...


A Novel Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Synapse Development, Hao Wu May 2019

A Novel Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Synapse Development, Hao Wu

All Dissertations, Theses, and Capstone Projects

Cytoskeleton based active transport with motor proteins is essential for mRNA localization and local protein translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased screen for interaction between mRNA binding proteins (RBP) and motor proteins, we identified protein interacting with APP tail 1 (PAT1) as a potential direct adapter between the β-actin mRNA Zipcode-binding protein 1 (ZBP1) and Kinesin-1 motor complex.

Mouse PAT1 is similar to the Kinesin Light Chain (KLC) in amino acid sequence and binds directly to KLC. High-resolution images from structured illumination microscopy (SIM) indicates that synaptic stimulation ...


Characterization Of Microtubule Organizing Centers In The Genus Protostelium, Including Evolutionary Implications, Ethan Taylor Ozment May 2019

Characterization Of Microtubule Organizing Centers In The Genus Protostelium, Including Evolutionary Implications, Ethan Taylor Ozment

Theses and Dissertations

Microtubule organizing centers (MTOCs) are cellular regions of microtubule nucleation. The best known MTOCs are those associated with the centrosome, but several non-centrosomal MTOCs are known in eukaryotes, especially in land plants. MTOCs are poorly characterized across the breadth of amoebozoan diversity, but are well-known in certain amoebozoan lineages, including the genus of protosteloid slime molds Protostelium. The structure of the MTOC is known for two non-ciliated species, P. nocturnum and P. mycophaga, as well as P. aurantium, which can reversibly become ciliated under appropriate conditions. P. nocturnum and P. mycophaga have acentriolar centrosomal MTOCs while P. aurantium has a ...


The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin May 2019

The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin

All Dissertations, Theses, and Capstone Projects

Anxiety affects nearly twice as many women as it affects men across all cultures and economic groups. Importantly, girls have a higher chance of inheriting anxiety disorders than boys, and many anxiety disorders appear at a very young age. However, little is known about sex differences in brain and behavioral development and how they relate to anxiety in adulthood. Serotonin 1A receptor (5-HT1A-R) mediated signaling has been implicated in depression and anxiety, however most studies that focus on the involvement of the 5-HT1A-R have been conducted in adults. Little is known about how the 5-HT1A ...


Single-Cell Rna-Sequencing-Based Crispri Screening Resolves Molecular Drivers Of Early Human Endoderm Development, Ryan M. Genga, Eric M. Kernfeld, Krishna M. Parsi, Teagan J. Parsons, Michael J. Ziller, Rene Maehr Apr 2019

Single-Cell Rna-Sequencing-Based Crispri Screening Resolves Molecular Drivers Of Early Human Endoderm Development, Ryan M. Genga, Eric M. Kernfeld, Krishna M. Parsi, Teagan J. Parsons, Michael J. Ziller, Rene Maehr

Open Access Articles

Studies in vertebrates have outlined conserved molecular control of definitive endoderm (END) development. However, recent work also shows that key molecular aspects of human END regulation differ even from rodents. Differentiation of human embryonic stem cells (ESCs) to END offers a tractable system to study the molecular basis of normal and defective human-specific END development. Here, we interrogated dynamics in chromatin accessibility during differentiation of ESCs to END, predicting DNA-binding proteins that may drive this cell fate transition. We then combined single-cell RNA-seq with parallel CRISPR perturbations to comprehensively define the loss-of-function phenotype of those factors in END development. Following ...


Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey Apr 2019

Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey

Biology ETDs

Properly executed cell division is crucial to development, maintenance, and longevity of multicellular organisms. Defects in both symmetric and asymmetric divisions can lead to improper developmental patterning, as well as genomic instability, disruption of tissue homeostasis, and cancer. Our research focuses on how regulators orchestrate proper cell divisions. Mushroom Body Defect (Mud) is one such regulator, and here we describe how Mud is regulated via the Hippo signaling pathway kinase Warts (Wts), showing Wts phosphorylates Mud to enhance interaction with the polarity protein Partner of Inscuteable, promoting spindle orientation activity. We next focus on another regulator, Shortstop (Shot), describing a ...


The Erk Mapk Pathway Is Essential For Skeletal Development And Homeostasis, Jung-Min Kim, Yeon-Suk Yang, Kwang Hwan Park, Hwanhee Oh, Matthew B. Greenblatt, Jae-Hyuck Shim Apr 2019

The Erk Mapk Pathway Is Essential For Skeletal Development And Homeostasis, Jung-Min Kim, Yeon-Suk Yang, Kwang Hwan Park, Hwanhee Oh, Matthew B. Greenblatt, Jae-Hyuck Shim

Open Access Articles

Mitogen-activated protein kinases (MAPKs) are a family of protein kinases that function as key signal transducers of a wide spectrum of extracellular stimuli, including growth factors and pro-inflammatory cytokines. Dysregulation of the extracellular signal-regulated kinase (ERK) MAPK pathway is associated with human skeletal abnormalities including Noonan syndrome, neurofibromatosis type 1, and cardiofaciocutaneous syndrome. Here, we demonstrate that ERK activation in osteoprogenitors is required for bone formation during skeletal development and homeostasis. Deletion of Mek1 and Mek2, kinases upstream of ERK MAPK, in osteoprogenitors (Mek1(Osx)Mek2(-/-)), resulted in severe osteopenia and cleidocranial dysplasia (CCD), similar to that seen in humans ...


The Er-Localized Protein Dfcp1 Modulates Er-Lipid Droplet Contact Formation, Dongfang Li, Yan G. Zhao, Di Li, Hongyu Zhao, Jie Huang, Guangyan Miao, Du Feng, Pingsheng Liu, Dong Li, Hong Zhang Apr 2019

The Er-Localized Protein Dfcp1 Modulates Er-Lipid Droplet Contact Formation, Dongfang Li, Yan G. Zhao, Di Li, Hongyu Zhao, Jie Huang, Guangyan Miao, Du Feng, Pingsheng Liu, Dong Li, Hong Zhang

Open Access Articles

Very little is known about the spatiotemporal generation of lipid droplets (LDs) from the endoplasmic reticulum (ER) and the factors that mediate ER-LD contacts for LD growth. Using super-resolution grazing incidence structured illumination microscopy (GI-SIM) live-cell imaging, we reveal that upon LD induction, the ER-localized protein DFCP1 redistributes to nascent puncta on the ER, whose formation depends on triglyceride synthesis. These structures move along the ER and fuse to form expanding LDs. Fusion and expansion of DFCP1-labeled nascent structures is controlled by BSCL2. BSCL2 depletion causes accumulation of nascent DFCP1 structures. DFCP1 overexpression increases LD size and enhances ER-LD contacts ...


Genome-Scale Crispr Screens Identify Human Pluripotency-Specific Genes, Robert J. Ihry, Zinger Yang, Ajamete Kaykas Apr 2019

Genome-Scale Crispr Screens Identify Human Pluripotency-Specific Genes, Robert J. Ihry, Zinger Yang, Ajamete Kaykas

Open Access Articles

Human pluripotent stem cells (hPSCs) generate a variety of disease-relevant cells that can be used to improve the translation of preclinical research. Despite the potential of hPSCs, their use for genetic screening has been limited by technical challenges. We developed a scalable and renewable Cas9 and sgRNA-hPSC library in which loss-of-function mutations can be induced at will. Our inducible mutant hPSC library can be used for multiple genome-wide CRISPR screens in a variety of hPSC-induced cell types. As proof of concept, we performed three screens for regulators of properties fundamental to hPSCs: their ability to self-renew and/or survive (fitness ...


A Screen For Genetic Modifiers Of Protein Phosphatase 1 Function In Drosophila Collective Cell Cohesion And Migration, Carmen F. Del Real, Yujun Chen, Marissa Komp, Jocelyn A. Mcdonald Apr 2019

A Screen For Genetic Modifiers Of Protein Phosphatase 1 Function In Drosophila Collective Cell Cohesion And Migration, Carmen F. Del Real, Yujun Chen, Marissa Komp, Jocelyn A. Mcdonald

Kansas State University Undergraduate Research Conference

Cells can migrate collectively in tightly or loosely-associated groups during tissue and organ formation, during embryonic development, in tumor metastases, and in wound healing. Drosophilaborder cellsserve as an excellent genetic model of collective cell migration inside a developing tissue. During ovarian development, 6-8 cells form the border cell cluster and migrate together as a cohesive group to reach the large oocyte. Previous experiments have shown that Nuclear inhibitor of Protein Serine Threonine Phosphatase 1 (NiPP1) causes border cells to separate into single cells, rather than stay in a group, and limits their ability to migrate. NiPP1 inhibits the ...


A Functional Unfolded Protein Response Is Required For Normal Vegetative Development, Yan Bao, Diane C. Bassham, Stephen H. Howell Apr 2019

A Functional Unfolded Protein Response Is Required For Normal Vegetative Development, Yan Bao, Diane C. Bassham, Stephen H. Howell

Genetics, Development and Cell Biology Publications

The unfolded protein response (UPR) is activated in plants in response to endoplasmic reticulum stress and plays an important role in mitigating stress damage. Multiple factors act in the UPR, including the membrane-associated transcription factor, BASIC LEUCINE ZIPPER 17 (bZIP17), and the membrane-associated RNA splicing factor, INOSITOL REQUIRING ENZYME1 (IRE1). We have analyzed an Arabidopsis (Arabidopsis thaliana) ire1a ire1b bzip17 triple mutant, with defects in stress signaling, and found that the mutant is also impaired in vegetative plant growth under conditions without externally applied stress. This raised the possibility that the UPR functions in plant development in the same manner ...


Entosis Controls A Developmental Cell Clearance In C. Elegans, Yongchan Lee, Jens C. Hamann, Mark Pellegrino, Joanne Durgan, Marie-Charlotte Domart, Lucy M. Collinson, Cole M. Haynes, Oliver Florey, Michael Overholtzer Mar 2019

Entosis Controls A Developmental Cell Clearance In C. Elegans, Yongchan Lee, Jens C. Hamann, Mark Pellegrino, Joanne Durgan, Marie-Charlotte Domart, Lucy M. Collinson, Cole M. Haynes, Oliver Florey, Michael Overholtzer

Open Access Articles

Metazoan cell death mechanisms are diverse and include numerous non-apoptotic programs. One program called entosis involves the invasion of live cells into their neighbors and is known to occur in cancers. Here, we identify a developmental function for entosis: to clear the male-specific linker cell in C. elegans. The linker cell leads migration to shape the gonad and is removed to facilitate fusion of the gonad to the cloaca. We find that the linker cell is cleared in a manner involving cell-cell adhesions and cell-autonomous control of uptake through linker cell actin. Linker cell entosis generates a lobe structure that ...


Receptor Interacting Protein Kinase 3 (Rip3) Regulates Ipscs Generation Through Modulating Cell Cycle Progression Genes, Ahmad Al-Moujahed, Bo Tian, Nikolaos E. Efstathiou, Eleni K. Konstantinou, Mien Hoang, Haijiang Lin, Joan W. Miller, Demetrios G. Vavvas Mar 2019

Receptor Interacting Protein Kinase 3 (Rip3) Regulates Ipscs Generation Through Modulating Cell Cycle Progression Genes, Ahmad Al-Moujahed, Bo Tian, Nikolaos E. Efstathiou, Eleni K. Konstantinou, Mien Hoang, Haijiang Lin, Joan W. Miller, Demetrios G. Vavvas

Open Access Articles

The molecular mechanisms involved in induced pluripotent stem cells (iPSCs) generation are poorly understood. The cell death machinery of apoptosis-inducing caspases have been shown to facilitate the process of iPSCs reprogramming. However, the effect of other cell death processes, such as programmed necrosis (necroptosis), on iPSCs induction has not been studied. In this study, we investigated the role of receptor-interacting protein kinase 3 (RIP3), an essential regulator of necroptosis, in reprogramming mouse embryonic fibroblast cells (MEFs) into iPSCs. RIP3 was found to be upregulated in iPSCs compared to MEFs. Deletion of RIP3 dramatically suppressed the reprogramming of iPSCs (~82%). RNA-seq ...


Hypomorphic Mutations Of Trip11 Cause Odontochondrodysplasia, Anika Wehrle, John A. Follit, Gregory J. Pazour, Andrea Superti-Furga, Martin Lowe, Ekkehart Lausch Feb 2019

Hypomorphic Mutations Of Trip11 Cause Odontochondrodysplasia, Anika Wehrle, John A. Follit, Gregory J. Pazour, Andrea Superti-Furga, Martin Lowe, Ekkehart Lausch

Open Access Articles

Odontochondrodysplasia (ODCD) is an unresolved genetic disorder of skeletal and dental development. Here, we show that ODCD is caused by hypomorphic TRIP11 mutations, and we identify ODCD as the nonlethal counterpart to achondrogenesis 1A (ACG1A), the known null phenotype in humans. TRIP11 encodes Golgi-associated microtubule-binding protein 210 (GMAP-210), an essential tether protein of the Golgi apparatus that physically interacts with intraflagellar transport 20 (IFT20), a component of the ciliary intraflagellar transport complex B. This association and extraskeletal disease manifestations in ODCD point to a cilium-dependent pathogenesis. However, our functional studies in patient-derived primary cells clearly support a Golgi-based disease mechanism ...


Ninjurin1 Positively Regulates Osteoclast Development By Enhancing The Survival Of Prefusion Osteoclasts, Sung-Jin Bae, Min Wook Shin, Taekwon Son, Hye Shin. Lee, Ji Soo Chae, Sejin Jeon, Goo Taeg Oh, Kyu-Won Kim Jan 2019

Ninjurin1 Positively Regulates Osteoclast Development By Enhancing The Survival Of Prefusion Osteoclasts, Sung-Jin Bae, Min Wook Shin, Taekwon Son, Hye Shin. Lee, Ji Soo Chae, Sejin Jeon, Goo Taeg Oh, Kyu-Won Kim

Open Access Articles

Osteoclasts (OCs) are bone-resorbing cells that originate from hematopoietic stem cells and develop through the fusion of mononuclear myeloid precursors. Dysregulation of OC development causes bone disorders such as osteopetrosis, osteoporosis, and rheumatoid arthritis. Although the molecular mechanisms underlying osteoclastogenesis have been well established, the means by which OCs maintain their survival during OC development remain unknown. We found that Ninjurin1 (Ninj1) expression is dynamically regulated during osteoclastogenesis and that Ninj1(-/-) mice exhibit increased trabecular bone volume owing to impaired OC development. Ninj1 deficiency did not alter OC differentiation, transmigration, fusion, or actin ring formation but increased Caspase-9-dependent intrinsic apoptosis ...


Roles Of Euchromatin And Heterochromatin In Hepatocyte Maturation And Liver Fibrosis, Jessica Mae Grindheim Jan 2019

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 ...


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

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 ...


Effects Of Pag1 On Src-Family Kinase Trafficking In Neuroblastoma Cells, Makenzie E. Mayfield Jan 2019

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 ...


Development And Characterization Of An Immunologically Humanized And Cancer Xenograft Model In Pigs With Severe Combined Immunodeficiency (Scid), Adeline Nicole Boettcher Jan 2019

Development And Characterization Of An Immunologically Humanized And Cancer Xenograft Model In Pigs With Severe Combined Immunodeficiency (Scid), Adeline Nicole Boettcher

Graduate Theses and Dissertations

Swine with severe combined immunodeficiency (SCID) are an emerging large animal model for biomedical research. There have been several SCID pig models described since our first discovery of naturally occurring SCID with mutations in Artemis (DCLRE1C) in 2012. SCID animals are particularly useful in biomedical research due to their lack of T, B, and sometimes NK cells. Absence of the adaptive immune system allows for human cell and tissue xenotransplantation into these SCID animals. The works described within this thesis are categorized under four main goals: (1) further characterization of the immune system of Art-/- SCID pigs, (2) development of ...


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 Dec 2018

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 ...


Using Arabidopsis Mesophyll Protoplasts To Study Unfolded Protein Response Signaling, Yan Bao, Diane C. Bassham Dec 2018

Using Arabidopsis Mesophyll Protoplasts To Study Unfolded Protein Response Signaling, Yan Bao, Diane C. Bassham

Genetics, Development and Cell Biology Publications

Various environmental stresses or artificial reagents can trigger unfolded protein accumulation in the endoplasmic reticulum (ER) due to the folding capacity of the ER being exceeded. This is termed ER stress, and triggers the unfolded protein response (UPR). Assays for activation of the UPR in plants include Tunicamycin (Tm)- or dithiothreitol (DTT)-mediated root growth inhibition, analysis of splicing of the UPR-responsive transcription factor bZIP60 (basic Leucine Zipper Domain 60), and upregulation of relevant UPR genes. We provide here a quick and robust method to detect UPR signaling in Arabidopsis thaliana protoplasts. This assay can also be applied to other ...


Autophagy In Crop Plants: What's New Beyond Arabidopsis?, Jie Tang, Diane C. Bassham Dec 2018

Autophagy In Crop Plants: What's New Beyond Arabidopsis?, Jie Tang, Diane C. Bassham

Genetics, Development and Cell Biology Publications

Autophagy is a major degradation and recycling pathway in plants. It functions to maintain cellular homeostasis and is induced by environmental cues and developmental stimuli. Over the past decade, the study of autophagy has expanded from model plants to crop species. Many features of the core machinery and physiological functions of autophagy are conserved among diverse organisms. However, several novel functions and regulators of autophagy have been characterized in individual plant species. In light of its critical role in development and stress responses, a better understanding of autophagy in crop plants may eventually lead to beneficial agricultural applications. Here, we ...