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Articles 31 - 60 of 3435

Full-Text Articles in Cell Biology

Promotion Of Adipogenesis By Jmjd6 Requires The At Hook-Like Domain And Is Independent Of Its Catalytic Function, Pablo Reyes-Gutierrez, Jake W. Carrasquillo-Rodriguez, Anthony N. Imbalzano Aug 2019

Promotion Of Adipogenesis By Jmjd6 Requires The At Hook-Like Domain And Is Independent Of Its Catalytic Function, Pablo Reyes-Gutierrez, Jake W. Carrasquillo-Rodriguez, Anthony N. Imbalzano

Open Access Articles

JMJD6 is a member of the Jumonji C domain containing enzymes that demethylate and/or hydroxylate substrate proteins. It is a multi-functional protein that has been implicated in disparate aspects of transcriptional and post-transcriptional control of gene expression, including but not limited to enhancer and promoter binding, release of paused RNA polymerase II, control of splicing, and interaction with the translation machinery. JMJD6 contributes to multiple aspects of animal development, including adipogenesis modeled in culture. We mutated proposed or characterized domains in the JMJD6 protein to better understand the requirement for JMJD6 in adipogenic differentiation. Mutation of JMJD6 amino acids ...


Leptin Promotes Expression Of Emt-Related Transcription Factors And Invasion In A Src And Fak-Dependent Pathway In Mcf10a Mammary Epithelial Cells, Monserrat Olea-Flores, Miriam Zuñiga-Eulogio, Arvey Tacuba-Saavedra, Magdalena Bueno-Salgado, Andrea Sánchez-Carvajal, Yovani Vargas-Santiago, Miguel A. Mendoza-Catalán, Eduardo Pérez Salazar, Alejandra García-Hernández, Teresita Padilla-Benavides, Napoleón Navarro-Tito Aug 2019

Leptin Promotes Expression Of Emt-Related Transcription Factors And Invasion In A Src And Fak-Dependent Pathway In Mcf10a Mammary Epithelial Cells, Monserrat Olea-Flores, Miriam Zuñiga-Eulogio, Arvey Tacuba-Saavedra, Magdalena Bueno-Salgado, Andrea Sánchez-Carvajal, Yovani Vargas-Santiago, Miguel A. Mendoza-Catalán, Eduardo Pérez Salazar, Alejandra García-Hernández, Teresita Padilla-Benavides, Napoleón Navarro-Tito

University of Massachusetts Medical School Faculty Publications

Leptin is one of the main adipokines secreted in breast tissue, and has been associated with epithelial-mesenchymal transition (EMT) and tumor progression in breast cancer. Leptin promotes EMT, cell migration and invasion in epithelial breast cells, leading to tumor progression. However, the molecular mechanism that underlies these events is not fully understood; however, the activation of different signaling pathways appears to be essential. In this sense, the effect of leptin on the activation of kinases like Src and FAK, which regulate signaling pathways that activate the EMT program, has not been completely described. Therefore, we investigated the involvement of these ...


Ipsc Based Gene Correction And Disease Model Of A New Class Of Lgmd Due To Poglut1 Mutation, Jose Ortiz-Vitali Aug 2019

Ipsc Based Gene Correction And Disease Model Of A New Class Of Lgmd Due To Poglut1 Mutation, Jose Ortiz-Vitali

UT GSBS Dissertations and Theses (Open Access)

Recently, a novel class of muscular dystrophy has been discovered in a family due to autosomal recessive missense mutation in POGLUT1. Mutation of this enzyme leads to decreased O-glucosyltransferase activity and impaired Notch signaling, the pathways important for skeletal muscle stem cell (satellite cells) quiescence and activation. We hypothesize that reduced POGLUT1 activity and impaired Notch signaling is causative of this limb girdle muscular dystrophy through dysfunction of muscle stem cells and myogenic progenitors.

To test this, we have used iPSCs for disease modeling and rescue experiments. Using a CRISPR based gene targeting method, we aimed to correct the point ...


Bioengineering Extracellular Matrix Scaffolds For Volumetric Muscle Loss, Kevin Roberts Aug 2019

Bioengineering Extracellular Matrix Scaffolds For Volumetric Muscle Loss, Kevin Roberts

Theses and Dissertations

Volumetric muscle loss overwhelms skeletal muscle’s ordinarily capable regenerative machinery, resulting in fibrosis and severe functional deficits which have defied clinical repair strategies. My work spans the design and preclinical evaluation of implants intended to drive the cell community of injured muscle toward a regenerative state, as well as the development of an understanding of the molecular responses of this cell community to biomaterial interventions. I demonstrate a new class of biomaterial by leveraging the productive capacity of sacrificial hollow fiber membrane cell culture; I show specifically that unique threads of whole extracellular matrix can be isolated by solvent ...


The Functional Conservation Of Frazzled In Insects, Benjamin Wadsworth Aug 2019

The Functional Conservation Of Frazzled In Insects, Benjamin Wadsworth

Theses and Dissertations

Axons in the developing embryo receive and react to signals that direct their growth to reach target tissues at specified locations. The signal pathways that direct midline crossing of axons during embryonic development have been comprehensively examined in the past years using the Drosophila ventral nerve cord or the spinal cord as a model system. A number of these signaling mechanisms are conserved, however disparities have been found between species in general strategy or the molecular signals controlling the response of axons to guidance cues.

The Netrin-Frazzled pathway has been shown to aid in midline crossing of axons in the ...


Multimodal Quantitative Imaging Of Brain Cancer In Cultured Cells, Xin Feng, Alona Muzikansky, Alonzo H. Ross, Michael R. Hamblin, Peter R. Jermain, Anna N. Yaroslavsky Jul 2019

Multimodal Quantitative Imaging Of Brain Cancer In Cultured Cells, Xin Feng, Alona Muzikansky, Alonzo H. Ross, Michael R. Hamblin, Peter R. Jermain, Anna N. Yaroslavsky

Open Access Articles

Fluorescence emission, polarization and subcellular localization of methylene blue (MB) were studied in four cancerous and two normal human brain cell lines. Fluorescence emission and polarization images were acquired and analyzed. The co-localization of MB with mitochondria, lysosomes and nuclei of the cells was evaluated. Glioblastoma cells exhibited significantly higher MB fluorescence polarization compared to normal astrocytes. Preferential accumulation of MB in mitochondria of glioblastoma cells may explain higher fluorescence polarization values in cancer cells as compared to normal. These findings may lead to the development of a quantitative method for the detection of brain cancer in single cells.


The ‘Law Of Environmental Dependence’ - Biology And Ethics In The Work Of Ernest Everett Just: + Found – Some 251 Mostly Typed Pages, Theodore Walker Jul 2019

The ‘Law Of Environmental Dependence’ - Biology And Ethics In The Work Of Ernest Everett Just: + Found – Some 251 Mostly Typed Pages, Theodore Walker

Perkins Faculty Research and Special Events

Abstract-

“The Origin of Man’s Ethical Behavior” (circa October 1941) by Ernest Everett Just and Hedwig A. Schnetzler Just - is an unpublished book manuscript about the biological origins and evolution of ethical behavior, and about “the law of environmental dependence.” Missing since Just’s death in October 1941, it was found and identified in May 2018 among the collected papers of Ernest Everett Just preserved at the Howard University Moorland-Spingarn Research Center in Washington, DC. In addition to the 1996 US postage with the caption “Ernest E. Just, Biologist,” we now have reason to add two new postage stamps ...


Calcineurin Broadly Regulates The Initiation Of Skeletal Muscle-Specific Gene Expression By Binding Target Promoters And Facilitating The Interaction Of The Swi/Snf Chromatin Remodeling Enzyme, Hanna Witwicka, Jumpei Nogami, Sabriya A. Syed, Kazumitsu Maehara, Teresita Padilla-Benavides, Yasuyuki Ohkawa, Anthony N. Imbalzano Jul 2019

Calcineurin Broadly Regulates The Initiation Of Skeletal Muscle-Specific Gene Expression By Binding Target Promoters And Facilitating The Interaction Of The Swi/Snf Chromatin Remodeling Enzyme, Hanna Witwicka, Jumpei Nogami, Sabriya A. Syed, Kazumitsu Maehara, Teresita Padilla-Benavides, Yasuyuki Ohkawa, Anthony N. Imbalzano

Open Access Articles

Calcineurin (Cn) is a calcium-activated serine/threonine protein phosphatase that is broadly implicated in diverse cellular processes, including the regulation of gene expression. During skeletal muscle differentiation, Cn activates the NFAT transcription factor but also promotes differentiation by counteracting the negative influences of protein kinase C beta (PKCbeta) via dephosphorylation and activation of BRG1, an enzymatic subunit of the mammalian SWI/SNF ATP-dependent chromatin remodeling enzyme. Here we identified four major temporal patterns of Cn-dependent gene expression in differentiating myoblasts and determined that Cn is broadly required for the activation of the myogenic gene expression program. Mechanistically, Cn promotes gene ...


Development Of A Prolyl Endopeptidase Expression System In Lactobacillus Reuteri To Reduce The Clinical Manifestation Of Celiac Disease, Kara Lynn Jew Jul 2019

Development Of A Prolyl Endopeptidase Expression System In Lactobacillus Reuteri To Reduce The Clinical Manifestation Of Celiac Disease, Kara Lynn Jew

Master's Theses and Project Reports

Celiac Disease (CD) is an autoimmune disorder that emerges due to the ingestion of gluten, a protein found in a variety of common grains such as wheat, rye, and barley. Approximately 1 in 100 individuals in the US suffer from CD, making it the most commonly diagnosed gastrointestinal disorder (Ciclitira et. al., 2005). These proline-rich gluten peptides are resistant to proteolysis and accumulate in the duodenum of the small intestine. Once in the duodenum, these peptides illicit an autoimmune response resulting in villous atrophy. Current treatment for CD requires a rigorous adherence to a gluten-free diet. Nevertheless, gluten-containing grains are ...


F-Box Protein Fbxo16 Functions As A Tumor Suppressor By Attenuating Nuclear Beta-Catenin Function, Debasish Paul, Sehbanul Islam, Rajesh Kumar. Manne, U. S. Dinesh, Sunil K. Malonia, Biswanath Maity, Ramanamurthy Boppana, Srikanth Rapole, Praveen Kumar Shetty, Manas Kumar Santra Jul 2019

F-Box Protein Fbxo16 Functions As A Tumor Suppressor By Attenuating Nuclear Beta-Catenin Function, Debasish Paul, Sehbanul Islam, Rajesh Kumar. Manne, U. S. Dinesh, Sunil K. Malonia, Biswanath Maity, Ramanamurthy Boppana, Srikanth Rapole, Praveen Kumar Shetty, Manas Kumar Santra

Open Access Articles

Aberrant activation of beta-catenin has been implicated in a variety of human diseases, including cancer. In spite of significant progress, the regulation of active Wnt/beta-catenin-signaling pathways is still poorly understood. In this study, we show that F-box protein 16 (FBXO16) is a putative tumor suppressor. It is a component of the SCF (SKP1-Cullin1-F-box protein) complex, which targets the nuclear beta-catenin protein to facilitate proteasomal degradation through the 26S proteasome. FBXO16 interacts physically with the C-terminal domain of beta-catenin and promotes its lysine 48-linked polyubiquitination. In addition, it inhibits epithelial-to-mesenchymal transition (EMT) by attenuating the level of beta-catenin. Therefore, depletion ...


Endogenous Force Transmission Between Epithelial Cells And A Role For Α-Catenin, Sandeep Dumbali Jul 2019

Endogenous Force Transmission Between Epithelial Cells And A Role For Α-Catenin, Sandeep Dumbali

Mechanical & Aerospace Engineering Theses & Dissertations

In epithelial tissues, epithelial cells adhere to each other as well as to the underlying extra-cellular matrix (ECM). E-cadherin-based intercellular junctions play an important role in tissue integrity. These junctions experience cell-generated mechanical forces via apparent adaptor proteins such as beta (β) catenin, alpha (α) catenin and vinculin. Abnormalities in these junctions may result in skin related diseases and cancers. Here, I devised methods to determine the endogenous intercellular force within cell pairs as well as in large epithelial islands. I further ascertained the factors that affect the level of inter-cellular tension.

Experiments with pairs of epithelial cells exogenously expressing ...


The Expression Of Connexin-43 By Cd11c+ Dendritic Cells Is Required To Maintain Cd4+ Foxp3+ Regulatory T Cell Population In Peripheral Lymphoid Organs, Caroline Titus Miller Jul 2019

The Expression Of Connexin-43 By Cd11c+ Dendritic Cells Is Required To Maintain Cd4+ Foxp3+ Regulatory T Cell Population In Peripheral Lymphoid Organs, Caroline Titus Miller

Biological Sciences Theses & Dissertations

Foxp3+ regulatory T cells (TR) are an immunosuppressive subset of CD4+ T cells that maintain homeostasis of the immune system. They are sustained by the interaction between the Major Histocompatibility Complex (MHC) molecules present on antigen presenting dendritic cells and the T Cell Receptor (TCR) expressed on TR cells that is specific for the MHC loaded with an antigenic peptide. Here, we show that in addition to MHC/TCR interaction, Connexin-43 (Cx43) expression by dendritic cells is required to maintain the TR cell population. CD11c+ dendritic cells represent a major subset of antigen presenting cells. Using flow cytometry ...


Regulation Of Endoplasmic Reticulum Stress Sensitivity By Torc1 Signalling In Yeast, Khadija Ahmed, Patrick Lajoie Jun 2019

Regulation Of Endoplasmic Reticulum Stress Sensitivity By Torc1 Signalling In Yeast, Khadija Ahmed, Patrick Lajoie

Western Research Forum

Incorrect folding of secretory proteins in the endoplasmic reticulum (ER) results in an aberrant accumulation of misfolded proteins (ER stress) and activates a coping mechanism known as the unfolded protein response (UPR). While the mechanisms of UPR activation have been well established, how it integrates with other stress responses remains unclear.

Given that TORC1 is an important regulator of cell growth during protein misfolding stress, we sought to investigate how TORC1 signalling acts in parallel with the UPR to regulate ER stress sensitivity. Our studies employ the budding yeast, Saccharomyces cerevisiae, a biochemically traceable model organism that allows for extensive ...


Uncovering The Role Of Ovol1 In Placental Stem Cell Differentiation Using Saccharomyces Cerevisiae, Maram Albakri, Patrick Lajoie, Stephen Renaud, Gargi Jaju, Hazel Dhaliwal Jun 2019

Uncovering The Role Of Ovol1 In Placental Stem Cell Differentiation Using Saccharomyces Cerevisiae, Maram Albakri, Patrick Lajoie, Stephen Renaud, Gargi Jaju, Hazel Dhaliwal

Western Research Forum

OVOL1 is a conserved transcription factor involved in regulating cytrophoblast differentiation in the placenta. Our objective for this study is to use Saccharomyces cerevisiae to uncover the role of OVOL1 in placental stem cell differentiation and proliferation. Previous research suggests that OVOL1 regulates cytotrophoblast progenitor state by regulating genome acetylation. Therefore, our study aims to determine how OVOL1 effect yeast growth and the yeast acetylome, and to use the yeast model to determine downstream targets of OVOL1. In order to understand the role of OVOL1, we will develop a yeast model and employ growth assays to assess growth defects and ...


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 ...


Tethering Of Vesicles To The Golgi By Gmap210 Controls Lat Delivery To The Immune Synapse, Andres Ernesto Zucchetti, Laurence Bataille, Jean-Marie Carpier, Stephanie Dogniaux, Mabel San Roman-Jouve, Mathieu Maurin, Michael W. Stuck, Rosa M. Rios, Cosima T. Baldari, Gregory J. Pazour, Claire Hivroz Jun 2019

Tethering Of Vesicles To The Golgi By Gmap210 Controls Lat Delivery To The Immune Synapse, Andres Ernesto Zucchetti, Laurence Bataille, Jean-Marie Carpier, Stephanie Dogniaux, Mabel San Roman-Jouve, Mathieu Maurin, Michael W. Stuck, Rosa M. Rios, Cosima T. Baldari, Gregory J. Pazour, Claire Hivroz

Open Access Articles

The T cell immune synapse is a site of intense vesicular trafficking. Here we show that the golgin GMAP210, known to capture vesicles and organize membrane traffic at the Golgi, is involved in the vesicular transport of LAT to the immune synapse. Upon activation, more GMAP210 interact with LAT-containing vesicles and go together with LAT to the immune synapse. Regulating LAT recruitment and LAT-dependent signaling, GMAP210 controls T cell activation. Using a rerouting and capture assay, we show that GMAP210 captures VAMP7-decorated vesicles. Overexpressing different domains of GMAP210, we also show that GMAP210 allows their specific delivery to the immune ...


Somatic Molecular Analysis Augments Cytologic Evaluation Of Pancreatic Cyst Fluids As A Diagnostic Tool, Ali Sakhdari, Parnian Ahmadi Moghaddam, Chi Young Ok, Otto Walter, Keith Tomaszewicz, Mandi-Lee Caporelli, Xiuling Meng, Jennifer Lafemina, Giles F. Whalen, Edward Belkin, Jaroslav Zivny, Wahid Y. Wassef, Bruce A. Woda, Lloyd Hutchinson, Ediz F. Cosar Jun 2019

Somatic Molecular Analysis Augments Cytologic Evaluation Of Pancreatic Cyst Fluids As A Diagnostic Tool, Ali Sakhdari, Parnian Ahmadi Moghaddam, Chi Young Ok, Otto Walter, Keith Tomaszewicz, Mandi-Lee Caporelli, Xiuling Meng, Jennifer Lafemina, Giles F. Whalen, Edward Belkin, Jaroslav Zivny, Wahid Y. Wassef, Bruce A. Woda, Lloyd Hutchinson, Ediz F. Cosar

Open Access Articles

Objective: Better tools are needed for early diagnosis and classification of pancreatic cystic lesions (PCL) to trigger intervention before neoplastic precursor lesions progress to adenocarcinoma. We evaluated the capacity of molecular analysis to improve the accuracy of cytologic diagnosis for PCL with an emphasis on non-diagnostic/negative specimens.

Design: In a span of 7 years, at a tertiary care hospital, 318 PCL endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) were evaluated by cytologic examination and molecular analysis. Mucinous PCL were identified based on a clinical algorithm and 46 surgical resections were used to verify this approach. The mutation allele frequency (MAF ...


Ste5 Membrane Localization Allows Mapk Pathway Signaling In Trans Between Kinases On Separate Scaffold Molecules, Rachel E. Lamson, Matthew J. Winters, Peter M. Pryciak Jun 2019

Ste5 Membrane Localization Allows Mapk Pathway Signaling In Trans Between Kinases On Separate Scaffold Molecules, Rachel E. Lamson, Matthew J. Winters, Peter M. Pryciak

University of Massachusetts Medical School Faculty Publications

The MAP kinase cascade is a ubiquitous eukaryotic signaling module that can be controlled by a diverse group of scaffold proteins. In budding yeast, activation of the mating MAP kinase cascade involves regulated membrane recruitment of the archetypal scaffold protein Ste5. This event promotes activation of the first kinase, but it also enhances subsequent signal propagation through the remainder of the cascade. By studying this latter effect, we find that membrane recruitment promotes signaling in trans between kinases on separate Ste5 molecules. First, trans signaling requires all Ste5 domains that mediate membrane recruitment, including both protein-binding and membrane-binding domains. Second ...


Mtf1, A Classic Metal Sensing Transcription Factor, Promotes Myogenesis In Response To Copper, Cristina Tavera-Montañez, Sarah J. Hainer, Daniella Cangussu, Shellaina J. V. Gordon, Yao Xiao, Pablo Reyes-Gutierrez, Anthony N. Imbalzano, Juan G. Navea, Thomas G. Fazzio, Teresita Padilla-Benavides Jun 2019

Mtf1, A Classic Metal Sensing Transcription Factor, Promotes Myogenesis In Response To Copper, Cristina Tavera-Montañez, Sarah J. Hainer, Daniella Cangussu, Shellaina J. V. Gordon, Yao Xiao, Pablo Reyes-Gutierrez, Anthony N. Imbalzano, Juan G. Navea, Thomas G. Fazzio, Teresita Padilla-Benavides

University of Massachusetts Medical School Faculty Publications

MTF1 is a conserved metal-binding transcription factor in eukaryotes that binds to conserved DNA sequence motifs, termed metal response elements (MREs). MTF1 responds to metal excess and deprivation, protects cells from oxidative and hypoxic stresses, and is required for embryonic development in vertebrates. We used multiple strategies to identify an unappreciated role for MTF1 and copper (Cu) in cell differentiation. Upon initiation of myogenesis from primary myoblasts, MTF1 expression increased, as did nuclear localization. Mtf1 knockdown impaired differentiation, while addition of non-toxic concentrations of Cu+ enhanced MTF1 expression and promoted myogenesis. Cu+ bound stoichiometrically to a C-terminus tetra-cysteine of MTF1 ...


Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito Jun 2019

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito

Open Access Articles

Epithelial-mesenchymal transition (EMT) is a reversible cellular process, characterized by changes in gene expression and activation of proteins, favoring the trans-differentiation of the epithelial phenotype to a mesenchymal phenotype. This process increases cell migration and invasion of tumor cells, progression of the cell cycle, and resistance to apoptosis and chemotherapy, all of which support tumor progression. One of the signaling pathways involved in tumor progression is the MAPK pathway. Within this family, the ERK subfamily of proteins is known for its contributions to EMT. The ERK subfamily is divided into typical (ERK 1/2/5), and atypical (ERK 3/4 ...


Insulin Signal Transduction Mediates Ethanol-Induced Feeding Dysfunction In A Fly Model Of Fetal Alcohol Spectrum Disorder, Manae Matsubara Jun 2019

Insulin Signal Transduction Mediates Ethanol-Induced Feeding Dysfunction In A Fly Model Of Fetal Alcohol Spectrum Disorder, Manae Matsubara

McNair Research Journal SJSU

Fetal alcohol spectrum disorder (FASD) is the leading cause of congenital intellectual disabilities in the Western World, with a worldwide prevalence of 2-11% of all births. FASD is preventable but recent epidemiological studies suggest that public awareness campaigns have reached the limits of their effectiveness. Therefore, research is shifting from prevention to treatment and mitigation of symptoms. No biological treatments for FASD exist, due in part to the fact the cellular mechanisms of alcohol toxicity are not well-understood. Developmental alcohol exposure (DAE) causes a variety of deleterious effects in both vertebrates and invertebrates, including increased mortality, slow growth, learning and ...


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 ...


Proteome Of The Central Apparatus Of A Ciliary Axoneme, Lei Zhao, Yuqing Hou, Tyler Picariello, Branch Craige, George B. Witman Jun 2019

Proteome Of The Central Apparatus Of A Ciliary Axoneme, Lei Zhao, Yuqing Hou, Tyler Picariello, Branch Craige, George B. Witman

Radiology Publications and Presentations

Nearly all motile cilia have a "9+2" axoneme containing a central apparatus (CA), consisting of two central microtubules with projections, that is essential for motility. To date, only 22 proteins are known to be CA components. To identify new candidate CA proteins, we used mass spectrometry to compare axonemes of wild-type Chlamydomonas and a CA-less mutant. We identified 44 novel candidate CA proteins, of which 13 are conserved in humans. Five of the latter were studied more closely, and all five localized to the CA; therefore, most of the other candidates are likely to also be CA components. Our ...


Adipocyte Acly Facilitates Dietary Carbohydrate Handling To Maintain Metabolic Homeostasis In Females, Sully Fernandez, John M. Viola, Annmarie Torres, Martina Wallace, Sophie Trefely, Steven Zhao, Hayley C. Affronti, Jivani M. Gengatharan, David A. Guertin, Nathaniel W. Snyder, Christian M. Metallo, Kathryn E. Wellen May 2019

Adipocyte Acly Facilitates Dietary Carbohydrate Handling To Maintain Metabolic Homeostasis In Females, Sully Fernandez, John M. Viola, Annmarie Torres, Martina Wallace, Sophie Trefely, Steven Zhao, Hayley C. Affronti, Jivani M. Gengatharan, David A. Guertin, Nathaniel W. Snyder, Christian M. Metallo, Kathryn E. Wellen

Open Access Articles

Sugars and refined carbohydrates are major components of the modern diet. ATP-citrate lyase (ACLY) is upregulated in adipocytes in response to carbohydrate consumption and generates acetyl-coenzyme A (CoA) for both lipid synthesis and acetylation reactions. Here, we investigate the role of ACLY in the metabolic and transcriptional responses to carbohydrates in adipocytes and unexpectedly uncover a sexually dimorphic function in maintaining systemic metabolic homeostasis. When fed a high-sucrose diet, Acly(FAT-/-) females exhibit a lipodystrophy-like phenotype, with minimal fat accumulation, insulin resistance, and hepatic lipid accumulation, whereas Acly(FAT-/-) males have only mild metabolic phenotypes. We find that ACLY is ...


Serum Deprivation Of Mesenchymal Stem Cells Improves Exosome Activity And Alters Lipid And Protein Composition, Reka A. Haraszti, Rachael Miller, Michelle L. Dubuke, Andrew H. Coles, Marie C. Didiot, Dimas Echeverria, Matteo Stoppato, Yves Y. Sere, John D. Leszyk, Julia F. Alterman, Bruno M. D. C. Godinho, Matthew R. Hassler, Rachel Wollacott, Yan Wang, Scott A. Shaffer, Neil Aronin, Anastasia Khvorova May 2019

Serum Deprivation Of Mesenchymal Stem Cells Improves Exosome Activity And Alters Lipid And Protein Composition, Reka A. Haraszti, Rachael Miller, Michelle L. Dubuke, Andrew H. Coles, Marie C. Didiot, Dimas Echeverria, Matteo Stoppato, Yves Y. Sere, John D. Leszyk, Julia F. Alterman, Bruno M. D. C. Godinho, Matthew R. Hassler, Rachel Wollacott, Yan Wang, Scott A. Shaffer, Neil Aronin, Anastasia Khvorova

Open Access Articles

Exosomes can serve as delivery vehicles for advanced therapeutics. The components necessary and sufficient to support exosomal delivery have not been established. Here we connect biochemical composition and activity of exosomes to optimize exosome-mediated delivery of small interfering RNAs (siRNAs). This information is used to create effective artificial exosomes. We show that serum-deprived mesenchymal stem cells produce exosomes up to 22-fold more effective at delivering siRNAs to neurons than exosomes derived from control cells. Proteinase treatment of exosomes stops siRNA transfer, indicating that surface proteins on exosomes are involved in trafficking. Proteomic and lipidomic analyses show that exosomes derived in ...


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 ...


Differential Roles Of Mammalian Target Of Rapamycin Complexes 1 And 2 In Migration Of Prostate Cancer Cells, Smrruthi Vaidegi Venugopal May 2019

Differential Roles Of Mammalian Target Of Rapamycin Complexes 1 And 2 In Migration Of Prostate Cancer Cells, Smrruthi Vaidegi Venugopal

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

In this study, we investigated differential activation and the role of two mTOR complexes in cell migration of prostate cancer cells. Specific knock-down of endogenous RAPTOR and RICTOR by siRNA resulted in decreased cell migration in LNCaP, DU145, and PC3 cells indicating that both mTORC1 and mTORC2 are required for cell migration. EGF treatment induced the activation of both mTORC1 and mTORC2 as determined by complex-specific phosphorylation of mTOR protein. Specific knock-down or inhibition of Rac1 activity in PC3 cells blocked EGF-induced activation of mTORC2, but had no effect on mTORC1 activation. Furthermore, the over-expression of constitutively active Rac1 (Rac1Q61L ...


Extraction, Purification And Evaluation Of Prmt5-Inhibitory Phytochemical Compounds For The Treatment Of Prostate Adenocarcinoma, Oliver H. Richmond Iii May 2019

Extraction, Purification And Evaluation Of Prmt5-Inhibitory Phytochemical Compounds For The Treatment Of Prostate Adenocarcinoma, Oliver H. Richmond Iii

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The development and advancement of prostate cancer is supported by a plethora of genetic and proteomic abnormalities, including events of post-translational modifications. The protein arginine methyltransferase 5 (PRMT5) enzyme regulates epigenetic events of histone modifications and protein post-translational modifications within protein signaling pathways. PRMT5 functions by catalyzing the symmetric dimethylation of terminal arginine residues on target protein substrates. Under abnormal conditions of overexpression and upregulation, PRMT5 methyltransferase activity constitutively drives the growth and proliferation of dysregulated cells. Overexpression or upregulation of PRMT5 correlates with disease progression as observed among numerous cancer types, including breast, colorectal, leukemia, lung, melanoma and prostate ...


Role Of High Mobility Group A2 (Hmga2) In Prostate Cancer, Ohuod Hawsawi May 2019

Role Of High Mobility Group A2 (Hmga2) In Prostate Cancer, Ohuod Hawsawi

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

High mobility group A2 (HMGA2) is a non-histone protein highly expressed during the development but is low or absent in most adult tissues. Epithelial-mesenchymal transition (EMT) plays a critical role in prostate cancer progression and metastasis. HMGA2 has been shown to promote EMT in separate studies. Interestingly, wild-type HMGA2 and truncated (lacking the 3’UTR) HMGA2 isoforms are overexpressed in many cancers. However, there are no studies on the role of each isoform in prostate cancer progression. We hypothesized that wild-type and truncated HMGA2 promotes prostate cancer progression by different mechanisms. We analyzed the expression of HMGA2 in the prostate ...


Establishment Of Crispr/Cas-9 Aided Knockout Of The Zic2 Gene In The African-American Prostate Cancer Cell Line E006aa-Pr, Janelle Moore May 2019

Establishment Of Crispr/Cas-9 Aided Knockout Of The Zic2 Gene In The African-American Prostate Cancer Cell Line E006aa-Pr, Janelle Moore

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The largest U.S. cancer health disparity exists in prostate cancer, with African American men having the highest incidence and mortality rates. The present study evaluated the effects of ZIC2 and the underlying mechanisms in the E006 parental African-American cell line that produces tumors at accelerated growth rates because of the increase of ZIC2 genes in African-American males. We analyzed the experimental research that the overexpression of ZIC2 contributes to progression of prostate cancer. E006AA cells with overexpressed or suppressed ZIC2 were analyzed to determine phenotypic differences, PCR, cell proliferation and immunoblot assays. The expression levels of ZIC2 were analyzed ...