Genetic Processes Commons^™

Relating The Metatranscriptome And Metagenome Of The Human Gut, Eric A. Franzosa, Xochitl C. Morgan, Nicola Segata, Levi Waldron, Joshua Reyes, Ashlee M. Earl, Georgia Giannoukos, Matthew R. Boylan, Dawn Ciulla, Dirk Gevers, Jacques Izard, Wendy S. Garrett, Andrew T. Chan, Curtis Huttenhower

Department of Food Science and Technology: Faculty Publications

Although the composition of the human microbiome is now well-studied, the microbiota’s > 8 million genes and their regulation remain largely uncharacterized. This knowledge gap is in part because of the difficulty of acquiring large numbers of samples amenable to functional studies of the microbiota. We conducted what is, to our knowledge, one of the first human microbiome studies in a well-phenotyped prospective cohort incorporating taxonomic, metagenomic, and metatranscriptomic profiling at multiple body sites using self-collected samples. Stool and saliva were provided by eight healthy subjects, with the former preserved by three different methods (freezing, ethanol, and RNAlater) to validate self-collection. …

Chmp1 Negatively Regulates Epidermal Growth Factor Signaling In The Drosophila Wing, Meagan Elisabeth Valentine

Theses, Dissertations and Capstones

A critical step in cellular signaling through transmembrane receptors is the down-regulation of activated receptors through the multivesicular body (MVB) pathway to the lysosome. MVB generation is mediated by the highly conserved ESCRT (0, I, II, and III) protein complexes. Though the ESCRT-III complex provides the core function of the ESCRT machinery, it is the least characterized of the ESCRT complexes. The Chmp1 protein is an ESCRT-III component and a putative tumor suppressor that has been linked to pancreatic and renal cancers in humans. However, published data on Chmp1 activity are conflicting and its role during tissue development is not …

Effect Of Heme Oxygenase-1 On Matrix Metalloproteinase-3 Expression In Human Fibroblasts, Theresa A. Stangl

PCOM Biomedical Studies Student Scholarship

Heme oxygenase-1(HO-1) is an enzyme that plays a very important role in the resolution of inflammation. HO-1-based therapies are effective in a number of disease conditions. However, HO-1 also increases tumor growth, angiogenesis, metastasis and chemoresistance. Matrix metalloproteinase-3 (MMP-3) is an enzyme involved in physiological and pathophysiological tissue remodeling. Unbalanced expression of MMPs is a key feature of connective tissue destruction in chronic inflammatory conditions. Previously shown in this laboratory, the HO-1 inducer, hemin, increased MMP-3 mRNA expression in some HGF cultures. To assess whether HO-1 and/or its products regulate expression of MMP-3 in human fibroblasts, the effect of HO-1 …

Expression Of The Chemokine Receptor, Cxcr4, And Its Ligand, Sdf-1, Are Increased In Purkinje Cells Of The Multiple System Atrophy Cerebellum, Megan Welter

Masters Theses

Multiple System Atrophy (MSA) is a sporadic, neurodegenerative disease that consists of three conditions: autonomic dysfunction, Parkinsonism and cerebellar ataxia. Our lab conducted an Affymetrix global gene expression analysis using pons tissue of MSA patients to determine genes that are differentially expressed when compared to non- MSA controls. This study identified upregulated genes, including the C-X-C chemokine receptor type 4, CXCR4, to which stromal cell-derived factor-I (SDF-1) is the natural ligand. The CXCR4/SDF-1 signaling pair has been sho.wn to play multiple roles in the brain, such as inducing neuronal apoptosis and promoting leukocyte recruitment during inflammation. The MSA cerebellum presents …

Generation And Characterization Of Peptide Fusion Proteins, Brianna L. Probasco

Graduate School of Biomedical Sciences Theses and Dissertations

Pathogenic Th17 cells drive progression of many autoimmune diseases. Th17 cells develop from naïve T cells in the immune system after antigen-driven stimulation in a specific cytokine environment. Normally, T cells act to fight off infection, but when not properly controlled, they can cause disease. The cytokine interleukin-23 (IL-23) plays an essential role in the expansion of pathogenic Th17 cells. IL-23 is a heterodimeric protein, composed of a p19 alpha chain and a p40 beta chain. The p40 is also part of IL-12 and binds to the IL-12 receptor beta 1 (IL-12Rβ1) subunit. Thus, it follows that the IL-23 receptor …

Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof

Dissertations and Theses (Open Access)

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …

Advancing Our Understanding Of The Inheritance And Transmission Of Pectus Excavatum, Lisa Horth, Michael W. Stacey, Virginia K. Proud, Kara Segna, Chelsea Rutherford, Donald Nuss, Robert E. Kelly

Bioelectrics Publications

Pectus excavatum is the most common congenital chest wall abnormality expressed in children, yet its inheritance is poorly understood. Here we present the first comprehensive assessment of the inheritance of this disorder. After evaluating 48 pedigrees and 56 clinical traits of probands and family members, we find strong evidence of autosomal recessive, genetic control for this disorder. Additionally there is likely more than one pectus disease-associated allele, as well as a relatively large number of disease allele carriers in the human population. Some clinical traits appear important and may serve as reliable indicators for predicting the likelihood of pectus excavatum …

Enforced Expression Of Tbx1 In Fetal Thymic Epithelial Cells Antagonizes Thymus Organogenesis, Kim T. Cardenas

Dissertations and Theses (Open Access)

Enforced expression of Tbx1 in fetal thymic epithelial cells antagonizes

thymus organogenesis

Kim T. Cardenas

The thymus and parathyroid glands originate from organ-specific domains of 3rd pharyngeal pouch (PP) endoderm. At embryonic day 11.5 (E11.5), the ventral thymus and dorsal parathyroid domains can be identified by Foxn1 and Gcm2 expression respectively. Neural crest cells, (NCCs) play a role in regulating patterning of 3rd PP endoderm. In addition, pharyngeal endoderm influences fate determination via secretion of Sonic hedgehog (Shh), a morphogen required for Gcm2 expression and generation of the parathyroid domain. Gcm2 is a downstream target of the transcription factor Tbx1, …

Altered Self-Assembly And Apatite Binding Of Amelogenin Induced By N-Terminal Proline Mutation, Li Zhu, Vuk Uskoković, Thuan Le, Pamela Denbesten, Yulei Huang, Stefan Habelitz, Wu Li

Pharmacy Faculty Articles and Research

Objective—A single Pro-70 to Thr (p.P70T) mutation of amelogenin is known to result in hypomineralized amelogenesis imperfecta (AI). This study aims to test the hypothesis that the given mutation affects the self-assembly of amelogenin molecules and impairs their ability to conduct the growth of apatite crystals.

Design—Recombinant human full-length wild-type (rh174) and p.P70T mutated amelogenins were analyzed using dynamic light scattering (DLS), protein quantification assay and atomic force microscopy (AFM) before and after the binding of amelogenins to hydroxyapatite crystals. The crystal growth modulated by both amelogenins in a dynamic titration system was observed using AFM.

Results—As …

Hydrolysis Of Amelogenin By Matrix Metalloprotease-20 Accelerates Mineralization In Vitro, Vuk Uskoković, Feroz Khan, Haichuan Liu, Halina Ewa Witkowska, Li Zhu, Wu Li, Stefan Habelitz

Pharmacy Faculty Articles and Research

In the following respects, tooth enamel is a unique tissue in the mammalian body: (a) it is the most mineralized and hardest tissue in it comprising up to 95 wt% of apatite; (b) its microstructure is dominated by parallel rods composed of bundles of 40 – 60 nm wide apatite crystals with aspect ratios reaching up to 1:10,000 and (c) not only does the protein matrix that gives rise to enamel guides the crystal growth, but it also conducts its own degradation and removal in parallel. Hence, when mimicking the process of amelogenesis in vitro, crystal growth has to …

Biomimetic Precipitation Of Uniaxially Grown Calcium Phosphate Crystals From Full-Length Human Amelogenin Sols, Vuk Uskoković, Wu Li, Stefan Habelitz

Pharmacy Faculty Articles and Research

Human dental enamel forms over a period of 2 – 4 years by substituting the enamel matrix, a protein gel mostly composed of a single protein, amelogenin with fibrous apatite nanocrystals. Self-assembly of a dense amelogenin matrix is presumed to direct the growth of apatite fibers and their organization into bundles that eventually comprise the mature enamel, the hardest tissue in the mammalian body. This work aims to establish the physicochemical and biochemical conditions for the synthesis of fibrous apatite crystals under the control of a recombinant fulllength human amelogenin matrix in combination with a programmable titration system. The growth …

Enzymatic Processing Of Amelogenin During Continuous Crystallization Of Apatite, Vuk Uskoković, M.-K. Kim, W. Li, S. Habelitz

Pharmacy Faculty Articles and Research

Dental enamel forms through a protein-controlled mineralization and enzymatic degradation with a nanoscale precision that new engineering technologies may be able to mimic. Recombinant fulllength human amelogenin (rH174) and a matrix-metalloprotease (MMP-20) were employed in a pHstat titration system that enabled a continuous supply of calcium and phosphate ions over several days, mimicking the initial stages of matrix processing and crystallization in enamel in-vitro. Effects on the self-assembly and crystal growth from a saturated aqueous solution containing 0.4 mg/ml rH174 and MMP-20 with the weight ratio of 1:1000 with respect to rH174 were investigated. A transition from nanospheres to fibrous …

Direct Inhibition Of Cdk9 Blocks Hiv-1 Replication Without Preventing T Cell Activation In Primary Human Peripheral Blood Lymphocytes, Dominic Salerno, Muneer G Hasham, Renee Marshall Demarest, Judit Garriga, Alexander Y Tsygankov, Xavier Graña

Rowan-Virtua School of Osteopathic Medicine Departmental Research

HIV-1 transcription is essential for the virus replication cycle. HIV-1 Tat is a viral transactivator that strongly stimulates the processivity of RNA polymerase II (RNAPII) via recruitment of the cyclin T1/CDK9 positive transcription elongation factor, which phosphorylates the C-terminal domain (CTD) of RNAPII. Consistently, HIV-1 replication in transformed cells is very sensitive to direct CDK9 inhibition. Thus, CDK9 could be a potential target for anti-HIV-1 therapy. A clearer understanding of the requirements for CDK9 activity in primary human T cells is needed to assess whether the CDK9-dependent step in HIV-1 transcription can be targeted clinically. We have investigated the effects …

Gene Expression In The Mouse Placenta: Developmental And Stress Responses, Ciprian P. Gheorghe

Loma Linda University Electronic Theses, Dissertations & Projects

Successful placental development is crucial for optimal growth, maturation, and survival of the embryo/fetus. Placental failure and placental pathology contributes to both morbidity and mortality of the fetus. We sought to understand normal placental development and also placental responses to stress using oligonucleotide microarray technology. To examine genetic aspects of normal placental development, we investigated gene expression patterns in the murine placenta at embryonic day 10.5 (E10.5), E12.5, E15.5, and E17.5. Hypoxia has been identified as a major stressor in placental and fetal development. In order to comprehend more completely hypoxic stress responses we sought to measure gene expression changes …

Potential Associations Among Genetic Markers In The Serotonergic System And The Antisocial Alcoholism Subtype, E. M. Hill, S. F. Stoltenberg, M. Burmeister, M. Closser, R. A. Zucker

Department of Psychology: Faculty Publications

Alcoholism is transmitted in families. The complexity and heterogeneity of this disorder has made it difficult to identify specific genetic correlates. One design with the potential to do so is the family-based association study, in which the frequencies of genetic polymorphisms are compared between affected and nonaffected members. Reduced central serotonin neurotransmission is associated with features of an antisocial subtype of alcoholism, although a primary deficit has not been traced to a particular component. Genetic markers related to the serotonergic system have been identified, located, and cloned. If associations can be discovered, the development process for pharmacotherapy could be facilitated. …