Cyclin D1 Integrates G9a-Mediated Histone Methylation., 2019 Baruch S. Blumberg Institute
Cyclin D1 Integrates G9a-Mediated Histone Methylation., Zhiping Li, Xuanmao Jiao, Gabriele Di Sante, Adam Ertel, Mathew C. Casimiro, Min Wang, Sanjay Katiyar, Xiaoming Ju, D. V. Klopfenstein, Aydin Tozeren, William Dampier, Iouri Chepelev, Albert Jeltsch, Richard G. Pestell
Department of Cancer Biology Faculty Papers
Lysine methylation of histones and non-histone substrates by the SET domain containing protein lysine methyltransferase (KMT) G9a/EHMT2 governs transcription contributing to apoptosis, aberrant cell growth, and pluripotency. The positioning of chromosomes within the nuclear three-dimensional space involves interactions between nuclear lamina (NL) and the lamina-associated domains (LAD). Contact of individual LADs with the NL are dependent upon H3K9me2 introduced by G9a. The mechanisms governing the recruitment of G9a to distinct subcellular sites, into chromatin or to LAD, is not known. The cyclin D1 gene product encodes the regulatory subunit of the holoenzyme that phosphorylates pRB and NRF1 thereby governing ...
Characterization Of The Novel Interaction Between Neisseria Gonorrhoeae Tdfj And Its Human Ligand S100a7, 2019 Virginia Commonwealth University
Characterization Of The Novel Interaction Between Neisseria Gonorrhoeae Tdfj And Its Human Ligand S100a7, Stavros Maurakis
Theses and Dissertations
Neisseria gonorrhoeae is an obligate human pathogen that causes the common STI gonorrhea, which presents a growing threat to global health. The WHO estimated 78 million new cases of gonorrhea worldwide in 2017, with estimates of 820,000 new cases in the United States alone according to the CDC. High-frequency phase and antigenic variation inherent in N. gonorrhoeae, coupled with its natural ability to rapidly acquire and stably integrate antimicrobial resistance factors into its genome, have culminated in an infection against which there is no effective vaccine, and for which the list of viable therapeutic options is quickly shrinking. Moreover ...
A Poxvirus Pseudokinase Represses Viral Dna Replication Via A Pathway Antagonized By Its Paralog Kinase, 2019 University of Nebraska - Lincoln
A Poxvirus Pseudokinase Represses Viral Dna Replication Via A Pathway Antagonized By Its Paralog Kinase, Annabel T. Olson, Zhigang Wang, Amber B. Rico, Matthew S. Wiebe
Poxviruses employ sophisticated, but incompletely understood, signaling pathways that engage cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. For example, the vaccinia B1 protein kinase plays a vital role in inactivating the cellular antiviral factor BAF, and likely orchestrates other pathways as well. In this study, we utilized experimental evolution of a B1 deletion virus to perform an unbiased search for suppressor mutations and identify novel pathways involving B1. After several passages of the ΔB1 virus we observed a robust increase in viral titer of the adapted virus. Interestingly, our characterization of the adapted viruses reveals that ...
Persistent Viral Reservoirs In Lymphoid Tissues In Siv-Infected Rhesus Macaques Of Chinese-Origin On Suppressive Antiretroviral Therapy, 2019 Tulane National Primate Research Center
Persistent Viral Reservoirs In Lymphoid Tissues In Siv-Infected Rhesus Macaques Of Chinese-Origin On Suppressive Antiretroviral Therapy, Summer Siddiqui, Stefanie Perez, Yong Gao, Lara Doyle-Meyers, Brian T. Foley, Qingsheng Li, Binhua Ling
Understanding HIV latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. Here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of SIV-infected and fully suppressed rhesus macaques of Chinese-origin (cRMs). Eight cRMs were infected with SIVmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. Four of the eight animals reached sustained full viral suppression with undetectable viremia. The levels of cell-associated SIV DNA varied in peripheral blood mononuclear cells (PBMCs) and multiple lymphoid tissues, but with higher ...
Near-Atomic Structure Of A Giant Virus, 2019 Purdue University
Near-Atomic Structure Of A Giant Virus, Qianglin Fang, Dongjie Zhu, Irina Agarkova, Jagat Adhikari, Thomas Klose, Yue Liu, Zhenguo Chen, Yingyuan Sun, Michael L. Gross, James L. Van Etten, Xinzheng Zhang, Michael G. Rossmann
Although the nucleocytoplasmic large DNA viruses (NCLDVs) are one of the largest group of viruses that infect many eukaryotic hosts, the near-atomic resolution structures of these viruses have remained unknown. Here we describe a 3.5 Å resolution icosahedrally averaged capsid structure of Paramecium bursaria chlorella virus 1 (PBCV-1). This structure consists of 5040 copies of the major capsid protein, 60 copies of the penton protein and 1800 minor capsid proteins of which there are 13 different types. The minor capsid proteins form a hexagonal network below the outer capsid shell, stabilizing the capsid by binding neighboring capsomers together. The ...
Relationship Between The Cervical Microbiome, Hiv Status, And Precancerous Lesions, 2019 University of Nebraska - Lincoln
Relationship Between The Cervical Microbiome, Hiv Status, And Precancerous Lesions, Cameron Klein, Daniela Gonzalez, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Nirosh Aluthge, Samodha Fernando, John T. West, Charles Wood, Peter C. Angeletti
Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with high-grade ...
21 - Cigarette Smoke Exposure Upregulation Of Pge₂ Expression In The Bladder, 2018 University of North Georgia
21 - Cigarette Smoke Exposure Upregulation Of Pge₂ Expression In The Bladder, Jessica Nix
Georgia Undergraduate Research Conference (GURC)
CIGARETTE SMOKE EXPOSURE UPREGULATION OF PGE₂ EXPRESSION IN THE BLADDER
Jessica Nix, Jane McHowat, Shannon Kispert
Cigarette smoking remains the leading cause of preventable death and disease in the United States. Despite known risks, 42.1 million Americans continue to smoke, making research into tobacco-related pathologies relevant and necessary. We previously discovered that cigarette smoke exposure leads to tumor progression in the breast via platelet activating factor (PAF) and other phospholipase A₂ (PLA₂) metabolic pathways. These results led us to examine the PLA2 metabolite, prostaglandin E₂ (PGE₂). We observed the expression of PGE₂ in mouse bladder and human heart ...
Potential Role Of Csf Cytokine Profiles In Discriminating Infectious From Non-Infectious Cns Disorders., 2018 Hospital of the University of Pennsylvania
Potential Role Of Csf Cytokine Profiles In Discriminating Infectious From Non-Infectious Cns Disorders., Danielle Fortuna, D. Craig Hooper, Amity L. Roberts, Larry A. Harshyne, Michelle Nagurney, Mark T. Curtis
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Current laboratory testing of cerebrospinal fluid (CSF) does not consistently discriminate between different central nervous system (CNS) disease states. Rapidly distinguishing CNS infections from other brain and spinal cord disorders that share a similar clinical presentation is critical. New approaches focusing on aspects of disease biology, such as immune response profiles that can have stimulus-specific attributes, may be helpful. We undertook this preliminary proof-of-concept study using multiplex ELISA to measure CSF cytokine levels in various CNS disorders (infections, autoimmune/demyelinating diseases, lymphomas, and gliomas) to determine the potential utility of cytokine patterns in differentiating CNS infections from other CNS diseases ...
Reduced Gut Microbiome Protects From Alcohol-Induced Neuroinflammation And Alters Intestinal And Brain Inflammasome Expression, 2018 University of Massachusetts Medical School
Reduced Gut Microbiome Protects From Alcohol-Induced Neuroinflammation And Alters Intestinal And Brain Inflammasome Expression, Patrick P. Lowe, Benedek Gyongyosi, Abhishek Satishchandran, Arvin Iracheta-Vellve, Yeonhee Cho, Aditya Ambade, Gyongyi Szabo
Open Access Articles
BACKGROUND: The end-organ effects of alcohol span throughout the entire body, from the gastrointestinal tract to the central nervous system (CNS). In the intestine, alcohol use changes the microbiome composition and increases gut permeability allowing translocation of microbial components into the circulation. Gut-derived pathogen-associated signals initiate inflammatory responses in the liver and possibly elsewhere in the body. Because previous studies showed that the gut microbiome contributes to alcohol-induced liver disease, we hypothesized that antibiotic administration to reduce the gut microbiome would attenuate alcohol-induced inflammation in the brain and small intestine (SI).
METHODS: Six- to 8-week-old C57BL/6J female mice were ...
Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, 2018 Stanford University
Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, Sunhee Hwang, Karen Mruk, Simin Rahighi, Andrew G. Raub, Che-Hong Chen, Lisa E. Dorn, Naoki Horikoshi, Soichi Wakatsuki, James K. Chen, Daria Mochly-Rosen
Pharmacy Faculty Articles and Research
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the ...
Experimental Evaluation Of The Importance Of Colonization History In Early-Life Gut Microbiota Assembly, 2018 University of Nebraska-Lincoln
Experimental Evaluation Of The Importance Of Colonization History In Early-Life Gut Microbiota Assembly, Inés Martínez, Maria X. Maldonado-Gomez, João Carlos Gomes-Neto, Hatem Kittana, Hua Ding, Robert J. Schmaltz, Payal Joglekar, Roberto Jiménez Cardona, Nathan L Marsteller, Steven W. Kembel, Andrew K. Benson, Daniel A. Peterson, Amanda Ramer-Tait, Jens C. Walther
Faculty Publications in Food Science and Technology
The factors that govern assembly of the gut microbiota are insufficiently understood. Here, we test the hypothesis that inter-individual microbiota variation can arise solely from differences in the order and timing by which the gut is colonized early in life. Experiments in which mice were inoculated in sequence either with two complex seed communities or a cocktail of four bacterial strains and a seed community revealed that colonization order influenced both the outcome of community assembly and the ecological success of individual colonizers. Historical contingency and priority effects also occurred in Rag1-/- mice, suggesting that the adaptive immune system is ...
The Epidemiology Of Infective Endocarditis Among People Who Inject Drugs In London, Ontario., 2018 The University of Western Ontario
The Epidemiology Of Infective Endocarditis Among People Who Inject Drugs In London, Ontario., Brian Hallam
Electronic Thesis and Dissertation Repository
Infective endocarditis is an infectious disease that affects the valves of the heart. Injection drug use is currently a leading risk factor among patients with endocarditis. We conducted a prospective study using data from hospital chart records among patients with endocarditis in London, Ontario, which has a relatively high prevalence of people who inject drugs to assess the severity of the issue and the major risk factors of mortality pertaining to this population. This study had a sample size of 353 and included a review of the incidence of admissions of endocarditis, as well as a survival analysis, using both ...
Evaluation Of Endothelial Cell Responses To Elevated Glucose, 2018 Cal Poly, San Luis Obispo
Evaluation Of Endothelial Cell Responses To Elevated Glucose, Gabriella Sugerman
Master's Theses and Project Reports
Developing a tissue-engineered Blood Vessel Mimic (BVM) to represent diabetic macrovascular disease could expedite design of new vascular devices specifically tailored to diabetic patients. In contribution toward this model, this thesis assessed Human Umbilical Vein Endothelial Cell (HUVEC) responses to high glucose conditions. Interleukin 6 (IL-6) and Cluster of Differentiation 36 (CD36) were selected to signify oxidative stress activity, a hallmark of diabetic macrovascular disease. Next, activity of potential reference genes B2M, HPRT1, and ACTB was assessed. All genes were found to exceed acceptable variability, so the E-ΔC T method of data analysis was selected. Next, cellular responses to high ...
Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle
Electronic Theses and Dissertations
Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences ...
Defining The Radioresponse Of Mossy Cells, 2018 California State University, San Bernardino
Defining The Radioresponse Of Mossy Cells, Devon Ivy
Electronic Theses, Projects, and Dissertations
Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in ...
Alcohol Drives Oxidation-Dependent Desensitization Of Airway Cilia Motility Responsiveness, 2018 University of Nebraska Medical Center
Alcohol Drives Oxidation-Dependent Desensitization Of Airway Cilia Motility Responsiveness, Michael Price
Theses & Dissertations
Alcohol abuse, which can impair clearance of pathogens and debris from the airway, is associated with an increase in complications and a higher mortality rate during the progression of pneumonia. With prolonged alcohol exposure, mucociliary clearance (MCC), which depends on the coordinated beating of cilia, is dysfunctional. Effective MCC relies on cAMP-dependent protein kinase (PKA) activation of ciliary beat frequency (CBF). PKA activation and stimulation of CBF are blunted with chronic exposure to alcohol. This phenomenon is known as alcohol-induced ciliary dysfunction (AICD). Previous studies have shown that concomitant feeding of mice with alcohol and antioxidants prevents AICD, suggesting a ...
Factors Involved In Suppression Of Human Vγ9vδ2 T-Lymphocytes And Impact Of Checkpoint Blockades On The Effector Functions Of Vγ9vδ2 T-Lymphocytes, Minji Choi, Andrew Wiemer, Andrea Hubbard, Brian Aneskievich
University Scholar Projects
Chronic antigenic stimulation leads to T cell exhaustion, which drastically dampens T cell effector functions. Upon exhaustion, T cells progressively lose their proliferative capacity, cytokine production, and cytotoxic effector functions against tumors. T cell exhaustion involves programmed cell death-1 (PD-1), which is an inhibitory co-stimulation receptor. Limited scope of studies has been done regarding impact of PD-1 expression on the effector functions of γδ T cells. In this study, we investigated expression of PD-1 and its impact on effector functions of human γδ T cells. When γδ T cells were stimulated with phosphoantigens (HMBPP and POM2-C-HMBP) and analyzed ...
Determining The Effects Of Cancer Mutations On The Coactivator Function Of The P300 Core Domain In Human Cells, Katlyn Myers, Erin Shanle, Meagan St. John
In human cells, DNA is packed into chromosomes by wrapping around proteins called histones. Histone proteins contain chains of amino acids called histone tails and can be modified by acetylation. Acetylating histone proteins is important to the cell because it opens up the chromatin and allows for gene expression. Proteins can recognize and bind histone acetylation with a region called a bromodomain. p300 is a bromodomain-containing protein with histone acetyltransferase activity (HAT) which also aids with gene expression and is a coactivator protein of transcription. The bromodomain and HAT domain of this protein is considered the p300 core. Previous research ...
The Effect Of Cx43 On The Motility Of Prostate Cancer Cells, 2018 Kent State University
The Effect Of Cx43 On The Motility Of Prostate Cancer Cells, Suzanne Hales, Abdulaziz Aloliqi, Gail Fraizer
Undergraduate Research Symposium
Prostate cancer (PC) is a very common type of cancer in males and metastatic growth often leads to death. Connexins (Cx) are important to intercellular communication and may also play a role in metastasis. Cultured PC3 metastatic prostate cancer cells have high levels of Cx43 and readily migrate in Boyden chambers, a model for metastasis. We previously silenced Cx43 in PC3 cells and tested their migration in Boyden chamber assays. Silencing Cx34 reduced the motility of the migratory PC3 cells. Conversely, LNCaP prostate cancer cells are not migratory and express very little Cx43. We hypothesized that over-expressing Cx43 in LNCaP ...
Autism And Vaccines: Exploring Misperceptions In Science, 2018 Germanna Community College
Autism And Vaccines: Exploring Misperceptions In Science, Arsenio Menendez
This paper will be exploring the supposed link between vaccines and autism which is a hot button topic as of late. Starting at the roots of where this myth began with the infamous and long since disproved initial paper penned by Andrew Wakefield. As of late with the ever-rising numbers of parents deciding to forego the vaccination of their children there is an increasing risk of herd immunity failing leading to old diseases that had been wiped out making a massive resurgence. Detailed in my research findings will be data driven explorations of psychology and human nature changing perception of ...