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2014

Genetics and Genomics

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Articles 1 - 30 of 51

Full-Text Articles in Cell Biology

Higher-Order Unfolding Of Peri/Centric Satellite Heterochromatin Is An Early And Consistent Event In Cell Senescence: A Dissertation, Eric C. Swanson Dec 2014

Higher-Order Unfolding Of Peri/Centric Satellite Heterochromatin Is An Early And Consistent Event In Cell Senescence: A Dissertation, Eric C. Swanson

GSBS Dissertations and Theses

Cellular senescence is thought to play an essential role in many biological functions including tumor suppression and organismal aging. Senescent cells, which are permanently removed from the cell cycle, can be found both in vivo in many different tissue types and in vitro within cultures of non-immortalized cells. Despite their inability to proliferate, these cells persist and remain metabolically active for indefinite periods of time. This physiologic process occurs in response to a variety of cellular insults including oxidative stress, shortened telomeres, constitutive oncogene expression, and DNA damage, and can be initiated by upregulation of one of the two known ...


Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan Dec 2014

Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan

FIU Electronic Theses and Dissertations

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems.

In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq ...


Understanding The Meiotic Roles Of Sisters Unbound In Drosophila Melanogaster, Badri Krishnan Dec 2014

Understanding The Meiotic Roles Of Sisters Unbound In Drosophila Melanogaster, Badri Krishnan

Doctoral Dissertations

During meiosis, cohesin is required for sister chromatid cohesion and for formation of chromosome cores. Multiple processes including chromosome segregation, recombination and synaptonemal complex (SC) are dependent on cohesin. Cohesin complex consists of two SMC subunits- SMC1, SMC3 and two non-SMC subunits RAD21/REC8 in meiosis and SA. But in Drosophila, non-SMC subunits have not been shown to be required for cohesion. We have identified a gene sisters unbound, which along with previously identified ord and solo, form a group of three genes (sos) which do not have any sequence similarity to cohesins but performs functions demonstrated by cohesins.

Proper ...


Optimization Of Transcription Factor Binding Map Accuracy Utilizing Knockout-Mouse Models, Wolfgang Krebs, Susanne V. Schmidt, Alon Goren, Dominic De Nardo, Larisa Labzin, Anton Bovier, Thomas Ulas, Heidi Theis, Michael Kraut, Eicke Latz, Marc Beyer, Joachim L. Schultze Dec 2014

Optimization Of Transcription Factor Binding Map Accuracy Utilizing Knockout-Mouse Models, Wolfgang Krebs, Susanne V. Schmidt, Alon Goren, Dominic De Nardo, Larisa Labzin, Anton Bovier, Thomas Ulas, Heidi Theis, Michael Kraut, Eicke Latz, Marc Beyer, Joachim L. Schultze

Open Access Articles

Genome-wide assessment of protein-DNA interaction by chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) is a key technology for studying transcription factor (TF) localization and regulation of gene expression. Signal-to-noise-ratio and signal specificity in ChIP-seq studies depend on many variables, including antibody affinity and specificity. Thus far, efforts to improve antibody reagents for ChIP-seq experiments have focused mainly on generating higher quality antibodies. Here we introduce KOIN (knockout implemented normalization) as a novel strategy to increase signal specificity and reduce noise by using TF knockout mice as a critical control for ChIP-seq data experiments. Additionally, KOIN can identify 'hyper ChIPable ...


Autophagy In Plants And Algae, Diane C. Bassham, Jose L. Crespo Dec 2014

Autophagy In Plants And Algae, Diane C. Bassham, Jose L. Crespo

Genetics, Development and Cell Biology Publications

Autophagy is a major cellular degradation pathway in which materials are delivered to the vacuole in double-membrane vesicles known as autophagosomes, broken down, and recycled (Li and Vierstra, 2012; Liu and Bassham, 2012). In photosynthetic organisms, the pathway is strongly activated by biotic and abiotic stresses, including nutrient limitation, oxidative, salt and drought stress and pathogen infection, and during senescence (Perez-Perez et al., 2012; Lv et al., 2014). Mutation of genes required for autophagy causes hypersensitivity to stress, indicating that autophagy is important for tolerance of multiple stresses. While autophagy is often non-selective, a growing number of examples of selectivity ...


Two Ways To Fold The Genome During The Cell Cycle: Insights Obtained With Chromosome Conformation Capture, Job Dekker Nov 2014

Two Ways To Fold The Genome During The Cell Cycle: Insights Obtained With Chromosome Conformation Capture, Job Dekker

Open Access Articles

Genetic and epigenetic inheritance through mitosis is critical for dividing cells to maintain their state. This process occurs in the context of large-scale re-organization of chromosome conformation during prophase leading to the formation of mitotic chromosomes, and during the reformation of the interphase nucleus during telophase and early G1. This review highlights how recent studies over the last 5 years employing chromosome conformation capture combined with classical models of chromosome organization based on decades of microscopic observations, are providing new insights into the three-dimensional organization of chromatin inside the interphase nucleus and within mitotic chromosomes. One striking observation is that ...


Nuclear Pore Component Nup98 Is A Potential Tumor Suppressor And Regulates Posttranscriptional Expression Of Select P53 Target Genes, Stephan Singer, Ruiying Zhao, Anthony M. Barsotti, Anette Ouwehand, Mina Fazollahi, Elias Coutavas, Kai Breuhahn, Olaf Neumann, Thomas Longerich, Tobias Pusterla, Maureen A. Powers, Keith M. Giles, Peter J. Leedman, Jochen Hess, David Grunwald, Harmen J. Bussemaker, Robert H. Singer, Peter Schirmacher, Carol Prives Nov 2014

Nuclear Pore Component Nup98 Is A Potential Tumor Suppressor And Regulates Posttranscriptional Expression Of Select P53 Target Genes, Stephan Singer, Ruiying Zhao, Anthony M. Barsotti, Anette Ouwehand, Mina Fazollahi, Elias Coutavas, Kai Breuhahn, Olaf Neumann, Thomas Longerich, Tobias Pusterla, Maureen A. Powers, Keith M. Giles, Peter J. Leedman, Jochen Hess, David Grunwald, Harmen J. Bussemaker, Robert H. Singer, Peter Schirmacher, Carol Prives

David Grünwald

The p53 tumor suppressor utilizes multiple mechanisms to selectively regulate its myriad target genes, which in turn mediate diverse cellular processes. Here, using conventional and single-molecule mRNA analyses, we demonstrate that the nucleoporin Nup98 is required for full expression of p21, a key effector of the p53 pathway, but not several other p53 target genes. Nup98 regulates p21 mRNA levels by a posttranscriptional mechanism in which a complex containing Nup98 and the p21 mRNA 3'UTR protects p21 mRNA from degradation by the exosome. An in silico approach revealed another p53 target (14-3-3sigma) to be similarly regulated by Nup98. The ...


Exosome-Mediated Delivery Of Rna Interference And Mirna Mimic, Fatemeh Momen-Heravi, Shashi Bala, Terence N. Bukong, Gyongyi Szabo Nov 2014

Exosome-Mediated Delivery Of Rna Interference And Mirna Mimic, Fatemeh Momen-Heravi, Shashi Bala, Terence N. Bukong, Gyongyi Szabo

Gyongyi Szabo

Exosomes, membranous nanovesicles, naturally carry bio-macromolecules and play pivotal roles in both physiological intercellular crosstalk and disease pathogenesis. Here, we showed that B cell-derived exosomes can function as vehicles to deliver exogenous miRNA-155 mimic or inhibitor into hepatocytes or macrophages, respectively. Stimulation of B cells significantly increased exosome production. Unlike in parental cells, baseline level of miRNA-155 was very low in exosomes derived from stimulated B cells. Exosomes loaded with a miRNA-155 mimic significantly increased miRNA-155 levels in primary mouse hepatocytes and the liver of miRNA-155 knockout mice. Treatment of RAW macrophages with miRNA-155 inhibitor loaded exosomes resulted in statistically ...


Intercellular Cooperation And Competition In Brain Cancers: Lessons From Drosophila And Human Studies, Indrayani Waghmare, Austin Roebke, Mutsuko Minata, Madhuri Kango-Singh, Ichiro Nakano Nov 2014

Intercellular Cooperation And Competition In Brain Cancers: Lessons From Drosophila And Human Studies, Indrayani Waghmare, Austin Roebke, Mutsuko Minata, Madhuri Kango-Singh, Ichiro Nakano

Biology Faculty Publications

Glioblastoma (GBM) is a primary brain cancer with an extremely poor prognosis. GBM tumors contain heterogeneous cellular components, including a small subpopulation of tumor cells termed glioma stem cells (GSCs). GSCs are characterized as chemotherapy- and radiotherapy-resistant cells with prominent tumorigenic ability. Studies in Drosophila cancer models demonstrated that interclonal cooperation and signaling from apoptotic clones provokes aggressive growth of neighboring tumorigenic clones, via compensatory proliferation or apoptosis induced proliferation. Mechanistically, these aggressive tumors depend on activation of Jun-N-terminal kinase (upstream of c-JUN), and Drosophila Wnt (Wg) in the apoptotic clones. Consistent with these nonmammalian studies, data from several mammalian ...


Genetic Analysis Of Ton2 Dependent Processes In Microtubule Organization In Arabidopsis Thaliana, Samantha Nicole Atkinson Oct 2014

Genetic Analysis Of Ton2 Dependent Processes In Microtubule Organization In Arabidopsis Thaliana, Samantha Nicole Atkinson

Theses and Dissertations

Microtubules carry out many functions within the cell. They're used during mitosis and meiosis to move chromosomes to opposite sides of the cell so that cell division can occur. They're also used as structural support for the cell and are involved in establishing the cell shape. Microtubules are also able to reorient from a longitudinal orientation to a transverse orientation in response to gibberellic acid and auxin (two hormones that are involved in cell elongation). The mechanism for how this reorientation occurs is unknown. The TONNEAU2 (TON2) protein is necessary for proper microtubule organization. We looked at how ...


Associated Behavioral, Genetic, And Gene Expression Variation With Alternative Life History Tactics In Salmonid Fishes, Ashley Chin-Baarstad Oct 2014

Associated Behavioral, Genetic, And Gene Expression Variation With Alternative Life History Tactics In Salmonid Fishes, Ashley Chin-Baarstad

Open Access Dissertations

Individual differences in behavior can have potential fitness consequences and often reflect underlying genetic variation. My research focuses on three objectives related to individual level variation: 1) evaluating the innate behavioral variation within and between individuals, families, and progeny of different life-history types across time; 2) testing for differences in gene expression within the brain associated with this behavioral variation; and 3) using genetic polymorphisms to test for associations with ecotype, as well as population structure, in polymorphic populations. First, we evaluated the variation in a suite of ecologically relevant behaviors across time in juvenile progeny produced from crosses within ...


Editorial Overview: Environmental Physiology: Insect Environmental Physiology, Brent J. Sinclair Oct 2014

Editorial Overview: Environmental Physiology: Insect Environmental Physiology, Brent J. Sinclair

Biology Publications

No abstract provided.


Modeling T Cell Receptor Recognition Of Cd1-Lipid And Mr1-Metabolite Complexes, Brian G. Pierce, Thom Vreven, Zhiping Weng Sep 2014

Modeling T Cell Receptor Recognition Of Cd1-Lipid And Mr1-Metabolite Complexes, Brian G. Pierce, Thom Vreven, Zhiping Weng

Open Access Articles

BACKGROUND: T cell receptors (TCRs) can recognize diverse lipid and metabolite antigens presented by MHC-like molecules CD1 and MR1, and the molecular basis of many of these interactions has not been determined. Here we applied our protein docking algorithm TCRFlexDock, previously developed to perform docking of TCRs to peptide-MHC (pMHC) molecules, to predict the binding of alphabeta and gammadelta TCRs to CD1 and MR1, starting with the structures of the unbound molecules.

RESULTS: Evaluating against TCR-CD1d complexes with crystal structures, we achieved near-native structures in the top 20 models for two out of four cases, and an acceptable-rated prediction for ...


Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo Sep 2014

Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo

Katherine A. Fitzgerald

Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis ...


Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo Sep 2014

Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo

Gyongyi Szabo

Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis ...


Small Rnas And Argonautes Provide A Paternal Epigenetic Memory Of Germline Gene Expression To Promote Thermotolerant Male Fertility: A Dissertation, Colin C. Conine Sep 2014

Small Rnas And Argonautes Provide A Paternal Epigenetic Memory Of Germline Gene Expression To Promote Thermotolerant Male Fertility: A Dissertation, Colin C. Conine

GSBS Dissertations and Theses

During each life cycle, gametes must preserve and pass on both genetic and epigenetic information, making the germline both immortal and totipotent. In the male germline the dramatic morphological transformation of a germ cell through meiosis, into a sperm competent for fertilization, while retaining this information is an incredible example of cellular differentiation. This process of spermatogenesis is inherently thermosensitive in numerous metazoa ranging from worms to man. Here, I describe the role of two redundant AGO-class paralogs, ALG-3/4, and their small RNA cofactors, in promoting thermotolerant male fertility in Caenorhabditis elegans. alg-3/4 double mutants exhibit temperature dependent ...


A Separable Domain Of The P150 Subunit Of Human Chromatin Assembly Factor-1 Promotes Protein And Chromosome Associations With Nucleoli, Corey L. Smith, Timothy D. Matheson, Daniel J. Trombly, Xiaoming Sun, Eric Campeau, Xuemei Han, John R. Yates Iii, Paul D. Kaufman Sep 2014

A Separable Domain Of The P150 Subunit Of Human Chromatin Assembly Factor-1 Promotes Protein And Chromosome Associations With Nucleoli, Corey L. Smith, Timothy D. Matheson, Daniel J. Trombly, Xiaoming Sun, Eric Campeau, Xuemei Han, John R. Yates Iii, Paul D. Kaufman

Program in Gene Function and Expression Publications and Presentations

Chromatin Assembly Factor-1 (CAF-1) is a three-subunit protein complex conserved throughout eukaryotes that deposits histones during DNA synthesis. Here, we present a novel role for the human p150 subunit in regulating nucleolar macromolecular interactions. Acute depletion of p150 causes redistribution of multiple nucleolar proteins and reduces nucleolar association with several repetitive element-containing loci. Notably, a point mutation in a SUMO-interacting motif (SIM) within p150 abolishes nucleolar associations, whereas PCNA or HP1 interaction sites within p150 are not required for these interactions. Additionally, acute depletion of SUMO-2 or the SUMO E2 ligase Ubc9 reduces alpha-satellite DNA association with nucleoli. The nucleolar ...


A System For Genome-Wide Histone Variant Dynamics In Es Cells Reveals Dynamic Macroh2a2 Replacement At Promoters, Ozlem Yildirim, Jui-Hung Hung, Ryan J. Cedeno, Zhiping Weng, Christopher J. Lengner, Oliver J. Rando Aug 2014

A System For Genome-Wide Histone Variant Dynamics In Es Cells Reveals Dynamic Macroh2a2 Replacement At Promoters, Ozlem Yildirim, Jui-Hung Hung, Ryan J. Cedeno, Zhiping Weng, Christopher J. Lengner, Oliver J. Rando

Open Access Articles

Dynamic exchange of a subset of nucleosomes in vivo plays important roles in epigenetic inheritance of chromatin states, chromatin insulator function, chromosome folding, and the maintenance of the pluripotent state of embryonic stem cells. Here, we extend a pulse-chase strategy for carrying out genome-wide measurements of histone dynamics to several histone variants in murine embryonic stem cells and somatic tissues, recapitulating expected characteristics of the well characterized H3.3 histone variant. We extended this system to the less-studied MacroH2A2 variant, commonly described as a "repressive" histone variant whose accumulation in chromatin is thought to fix the epigenetic state of differentiated ...


Hsa-Mir-30c Promotes The Invasive Phenotype Of Metastatic Breast Cancer Cells By Targeting Nov/Ccn3, Jason R. Dobson, Hanna Taipaleenmaki, Yu-Jie Hu, Deli Hong, Andre J. Van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian, Jitesh Pratap Aug 2014

Hsa-Mir-30c Promotes The Invasive Phenotype Of Metastatic Breast Cancer Cells By Targeting Nov/Ccn3, Jason R. Dobson, Hanna Taipaleenmaki, Yu-Jie Hu, Deli Hong, Andre J. Van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian, Jitesh Pratap

Open Access Articles

BACKGROUND: For treatment and prevention of metastatic disease, one of the premier challenges is the identification of pathways and proteins to target for clinical intervention. Micro RNAs (miRNAs) are short, non-coding RNAs, which regulate cellular activities by either mRNA degradation or translational inhibition. Our studies focused on the invasive properties of hsa-mir30c based on its high expression in MDA-MB-231 metastatic cells and our bioinformatic analysis of the Cancer Genome Atlas that identified aberrant hsa-mir-30c to be associated with poor survival.

METHODS: Contributions of hsa-mir-30c to breast cancer cell invasion were examined by Matrigel invasion transwell assays following modulation of hsa-mir-30c ...


Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang Aug 2014

Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang

Theses and Dissertations

The potential of human embryonic stem cells (hESCs) to differentiate into insulin producing beta cells offers great hope for cell-based therapy for diabetes treatment. However, in vitro pancreatic differentiation of hESCs remains challenging. In the past decade, most protocols for differentiating pancreatic cells have been focused on the use of signaling molecule cocktails on 2D substrates. Studies on embryonic development biology strongly suggest that extracellular matrix (ECM) plays a critical role on hESCs behavior. In this work, we first established a 3D collagen scaffold culture system for hESCs differentiating into definitive endoderm (DE), which is the first and most important ...


Cellular Contractility And Extracellular Matrix Stiffness Regulate Matrix Metalloproteinase Activity In Pancreatic Cancer Cells, Amanda Haage, Ian C. Schneider Aug 2014

Cellular Contractility And Extracellular Matrix Stiffness Regulate Matrix Metalloproteinase Activity In Pancreatic Cancer Cells, Amanda Haage, Ian C. Schneider

Chemical and Biological Engineering Publications

The pathogenesis of cancer is often driven by local invasion and metastasis. Recently, mechanical properties of the tumor microenvironment have been identified as potent regulators of invasion and metastasis, while matrix metalloproteinases (MMPs) are classically known as significant enhancers of cancer cell migration and invasion. Here we have been able to sensitively measure MMP activity changes in response to specific extracellular matrix (ECM) environments and cell contractility states. A pancreatic cancer cell line, Panc-1 cells, up-regulate MMP activities between 3- and 10- fold with increased cell contractility. Conversely, they down-regulate MMP activities when contractility is blocked to levels seen with ...


Quantitative Proteomic Analysis Reveals Posttranslational Responses To Aneuploidy In Yeast, Noah Dephoure, Sunyoung Hwang, Ciara O'Sullivan, Stacie E. Dodgson, Steven P. Gygi, Angelika Amon, Eduardo M. Torres Jul 2014

Quantitative Proteomic Analysis Reveals Posttranslational Responses To Aneuploidy In Yeast, Noah Dephoure, Sunyoung Hwang, Ciara O'Sullivan, Stacie E. Dodgson, Steven P. Gygi, Angelika Amon, Eduardo M. Torres

Program in Gene Function and Expression Publications and Presentations

Aneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined the consequences of aneuploidy on the proteome of aneuploid budding yeast strains. We show that although protein levels largely scale with gene copy number, subunits of multi-protein complexes are notable exceptions. Posttranslational mechanisms attenuate their expression when their encoding genes are in excess. Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis. Indeed aneuploid cells harbor increased levels of reactive ...


Drosophila Sirt2/Mammalian Sirt3 Deacetylates Atp Synthase Beta And Regulates Complex V Activity, Motiur Rahman, Niraj K. Nirala, Alka Singh, Lihua Julie Zhu, Kaori Taguchi, Takeshi Bamba, Eiichiro Fukusaki, Leslie M. Shaw, David G. Lambright, Jairaj K. Acharya, Usha R. Acharya Jul 2014

Drosophila Sirt2/Mammalian Sirt3 Deacetylates Atp Synthase Beta And Regulates Complex V Activity, Motiur Rahman, Niraj K. Nirala, Alka Singh, Lihua Julie Zhu, Kaori Taguchi, Takeshi Bamba, Eiichiro Fukusaki, Leslie M. Shaw, David G. Lambright, Jairaj K. Acharya, Usha R. Acharya

Program in Gene Function and Expression Publications and Presentations

Adenosine triphosphate (ATP) synthase beta, the catalytic subunit of mitochondrial complex V, synthesizes ATP. We show that ATP synthase beta is deacetylated by a human nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, sirtuin 3, and its Drosophila melanogaster homologue, dSirt2. dsirt2 mutant flies displayed increased acetylation of specific Lys residues in ATP synthase beta and decreased complex V activity. Overexpression of dSirt2 increased complex V activity. Substitution of Lys 259 and Lys 480 with Arg in human ATP synthase beta, mimicking deacetylation, increased complex V activity, whereas substitution with Gln, mimicking acetylation, decreased activity. Mass spectrometry and proteomic experiments from ...


Direct-To-Consumer Genetic Testing In The College Classroom: Knowledge, Attitudes, And Concerns Of Introductory Biology Students, Nicanor Austriaco Jul 2014

Direct-To-Consumer Genetic Testing In The College Classroom: Knowledge, Attitudes, And Concerns Of Introductory Biology Students, Nicanor Austriaco

Rev. Nicanor Austriaco, O.P.

Pioneered by companies like 23andMe.com, deCODEme.com, and Navigenics.com, direct-to-consumer genetic testing refers to genetic tests that are marketed directly to consumers via television, print media, or the Internet. This kind of testing provides access to a customer’s genetic information without necessarily involving either a medical health care professional or a genetic counselor in the process. In recent years, a course offered to medical and graduate students at Stanford University has included an option for students to undergo personal genotyping, raising the possibility that direct-to-consumer genetic testing could also be incorporated into undergraduate biology courses to enhance ...


Phosphatidic Acid Phospholipase A1 Mediates Er-Golgi Transit Of A Family Of G Protein-Coupled Receptors, Govind Kunduri, Changqing Yuan, Velayoudame Parthibane, Katherine M. Nyswaner, Ritu Kanwar, Kunio Nagashima, Steven G. Britt, Nickita Mehta, Varshika Kotu, Mindy Porterfield, Michael Tiemeyer, Patrick J. Dolph, Usha Acharya, Jairaj K. Acharya Jul 2014

Phosphatidic Acid Phospholipase A1 Mediates Er-Golgi Transit Of A Family Of G Protein-Coupled Receptors, Govind Kunduri, Changqing Yuan, Velayoudame Parthibane, Katherine M. Nyswaner, Ritu Kanwar, Kunio Nagashima, Steven G. Britt, Nickita Mehta, Varshika Kotu, Mindy Porterfield, Michael Tiemeyer, Patrick J. Dolph, Usha Acharya, Jairaj K. Acharya

Program in Gene Function and Expression Publications and Presentations

The coat protein II (COPII)-coated vesicular system transports newly synthesized secretory and membrane proteins from the endoplasmic reticulum (ER) to the Golgi complex. Recruitment of cargo into COPII vesicles requires an interaction of COPII proteins either with the cargo molecules directly or with cargo receptors for anterograde trafficking. We show that cytosolic phosphatidic acid phospholipase A1 (PAPLA1) interacts with COPII protein family members and is required for the transport of Rh1 (rhodopsin 1), an N-glycosylated G protein-coupled receptor (GPCR), from the ER to the Golgi complex. In papla1 mutants, in the absence of transport to the Golgi, Rh1 is ...


Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park Jul 2014

Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park

Open Access Theses

Reversible tyrosine phosphorylation plays an important role in signaling pathways that are essential for regulating cellular growth, differentiation and metabolism. Moreover, several human diseases such as diabetes, obesity and cancers are associated with the deregulation of protein tyrosine phosphatases (PTPs). Several studies provide evidence that PTPs not only contribute to cellular differentiation, but over-expression of these molecules also leads to transformation of non-transfomed cells as well. Based on these results, designing specific PTP inhibitors may ultimately function as potential therapeutic agents to treat various diseases including cancer, diabetes, and autoimmune diseases. EphA2 is a receptor tyrosine kinase which is hypo-phosphorylated ...


Exosome-Mediated Delivery Of Rna Interference And Mirna Mimic, Fatemeh Momen-Heravi, Shashi Bala, Terence N. Bukong, Gyongyi Szabo May 2014

Exosome-Mediated Delivery Of Rna Interference And Mirna Mimic, Fatemeh Momen-Heravi, Shashi Bala, Terence N. Bukong, Gyongyi Szabo

UMass Center for Clinical and Translational Science Research Retreat

Exosomes, membranous nanovesicles, naturally carry bio-macromolecules and play pivotal roles in both physiological intercellular crosstalk and disease pathogenesis. Here, we showed that B cell-derived exosomes can function as vehicles to deliver exogenous miRNA-155 mimic or inhibitor into hepatocytes or macrophages, respectively. Stimulation of B cells significantly increased exosome production. Unlike in parental cells, baseline level of miRNA-155 was very low in exosomes derived from stimulated B cells. Exosomes loaded with a miRNA-155 mimic significantly increased miRNA-155 levels in primary mouse hepatocytes and the liver of miRNA-155 knockout mice. Treatment of RAW macrophages with miRNA-155 inhibitor loaded exosomes resulted in statistically ...


Functional Study Of The Suppressor Of Hairy-­Wing Insulator Protein In Drosophila Melanogaster, Shih-Jui Hsu May 2014

Functional Study Of The Suppressor Of Hairy-­Wing Insulator Protein In Drosophila Melanogaster, Shih-Jui Hsu

Doctoral Dissertations

Eukaryotic chromatin insulators play an essential role in regulating gene expression and modifying nuclear architecture by organizing the higher-order chromatin structure in response to cellular and developmental cues. The details on how insulators function in this capacity are not completely understood.

Five different types of insulators have been identified in Drosophila. Each functional insulator consists of an insulator DNA response element bound by an insulator protein, which recognizes specific DNA sequences. Each type of insulator functions individually as well as collaboratively. Except for the Su(Hw) insulator protein, the other insulator proteins are necessary for viability considering loss of Su ...


Natural And Exogenous Genome Editing In Wiskott-Aldrich Syndrome Patient Cells, Tamara J. Laskowski May 2014

Natural And Exogenous Genome Editing In Wiskott-Aldrich Syndrome Patient Cells, Tamara J. Laskowski

UT GSBS Dissertations and Theses (Open Access)

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease characterized by thrombocytopenia, recurrent infections and increased autoimmunity. This disease is caused by mutations in the WAS gene (WAS) which encodes for the WAS protein (WASp), exclusively expressed in hematopoietic cells and required for proper platelet production and lymphoid cell function. Approximately 11% of patients with WAS exhibit a phenomenon called Somatic Revertant Mosaicism which is characterized by the presence of lymphocytes which naturally revert back to normal phenotype by restoring WASp expression. To date, the mechanisms of this naturally-occurring gene therapy remains poorly understood, and the full extent of the ...


Characterization Of Ftsa-Ftsn Interaction During Escherichia Coli Cell Division, Kimberly.Busiek@Gmail.Com K. Busiek May 2014

Characterization Of Ftsa-Ftsn Interaction During Escherichia Coli Cell Division, Kimberly.Busiek@Gmail.Com K. Busiek

UT GSBS Dissertations and Theses (Open Access)

Division of a bacterial cell into two equal daughter cells requires precise assembly and constriction of the division machinery, or divisome. The Escherichia coli divisome includes nearly a dozen essential cell division proteins that assemble at midcell between segregating sister chromosomes. FtsZ, a homolog of eukaryotic tubulin, is the first essential cell division protein to localize at midcell where it polymerizes into a ring-shaped scaffold (Z ring). Establishment of the Z ring is required for recruitment of downstream cell division proteins including FtsA, a cytoplasmic protein that tethers the Z ring to the inner membrane. Following localization of FtsA and ...