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Choosing And Using Diversity Indices: Insights For Ecological Applications From The German Biodiversity Exploratories, Kathyrn Morris, T Caruso, F. Buscot 2014 Xavier University

Choosing And Using Diversity Indices: Insights For Ecological Applications From The German Biodiversity Exploratories, Kathyrn Morris, T Caruso, F. Buscot

Faculty Scholarship

Biodiversity, a multidimensional property of natural systems, is difficult to quantify partly because of the multitude of indices proposed for this purpose. Indices aim to describe general properties of communities that allow us to compare different regions, taxa, and trophic levels. Therefore, they are of fundamental importance for environmental monitoring and conservation, although there is no consensus about which indices are more appropriate and informative. We tested several common diversity indices in a range of simple to complex statistical analyses in order to determine whether some were better suited for certain analyses than others. We used data collected around the ...


Effect Of Heme Oxygenase-1 On Matrix Metalloproteinase-3 Expression In Human Fibroblasts, Theresa A. Stangl 2014 Philadelphia College of Osteopathic Medicine

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 ...


The Molecular Mechanisms Of Pitx2 In Tooth Development And Enamel Defects In Axenfeld-Rieger Syndrome, Xiao Li 2013 University of Iowa

The Molecular Mechanisms Of Pitx2 In Tooth Development And Enamel Defects In Axenfeld-Rieger Syndrome, Xiao Li

Theses and Dissertations

Patients with Axenfeld-Rieger Syndrome (ARS) present various dental abnormalities. ARS is genetically associated with mutations in the PITX2 gene, which encodes one of the earliest transcription factors to initiate tooth development. Thus, Pitx2 has long been considered as an upstream regulator of the transcriptional hierarchy in tooth development. However, it is unclear how its mutant forms cause ARS dental anomalies. In this report, we outline the transcriptional mechanism that is defective in ARS. We demonstrate that during normal tooth development Pitx2 activates Amelogenin (Amel) expression, whose product is required for enamel formation, and that this regulation is perturbed by missense ...


A Forward Genetics Approach To Identify Molecular Drivers Of Liver Cancer Using Sleeping Beauty Mouse Models, Jesse Daniel Riordan 2013 University of Iowa

A Forward Genetics Approach To Identify Molecular Drivers Of Liver Cancer Using Sleeping Beauty Mouse Models, Jesse Daniel Riordan

Theses and Dissertations

Each year liver cancer kills more than half a million people, making it the third

leading cause of cancer-related death worldwide. Annual incidence continues to rise steadily, both domestically and globally, increasing the burden of this disease. Advancements in the ability to obtain detailed molecular profiles of tumors have led to the successful development of targeted therapies for a number of different cancers. Unfortunately, however, the molecular pathogenesis of liver cancer is poorly understood relative to many other types of malignancies. Thus, the identification of factors contributing to the development and progression of liver tumors is a major goal of ...


Endothelial Agonists Stimulate Vwf Release In Vitro And Trigger Ttp In Vivo, Gilbert Van Schaeffer 2013 University of Iowa

Endothelial Agonists Stimulate Vwf Release In Vitro And Trigger Ttp In Vivo, Gilbert Van Schaeffer

Theses and Dissertations

Von Willebrand factor (VWF) is a plasma glycoprotein that can bind collagen at a wound site as well as circulating platelets. VWF forms high molecular weight multimers (>20,000 kDa). VWF can also form VWF strings that appear to be attached to the endothelial surface and are capable of binding platelets. These strings are only observed in vitro and in vivo in the absence of the VWF-cleaving protease ADAMTS13. Deficiency in ADAMTS13 results in thrombotic thrombocytopenic purpura (TTP), a clotting disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, renal dysfunction, neurological dysfunction and fever. Patients suffering from TTP demonstrate VWF-and platelet-rich ...


Aspects Of The Innate Immune System In The Caribbean Octocoral Swiftia Exserta, Lorenzo P. Menzel 2013 Florida International University

Aspects Of The Innate Immune System In The Caribbean Octocoral Swiftia Exserta, Lorenzo P. Menzel

FIU Electronic Theses and Dissertations

The immune systems of cnidaria are important to study for two reasons: to gain a better understanding of the evolution of immune responses, and to provide a basis to partially redress the precipitous world-wide die-offs of reef corals, some of which have been attributed to diseases and stress. Many immune responses share ancient evolutionary origins and are common across many taxa.

Using Swiftia exserta, an azooxanthellate ahermatypic local octocoral, as a proxy model organism to study aspects of innate immunity in corals and cnidaria allows us to address both of the reasons listed above while not using endangered species. Utilizing ...


Bax And Bak Function As The Outer Membrane Component Of The Mitochondrial Permeability Pore In Regulating Necrotic Cell Death In Mice, Jason Karch, Jennifer Q. Kwong, Adam R. Burr, Michelle A. Sargent, John W. Elrod, Pablo M. Peixoto, Sonia Martinez-Caballero, Hanna Osinskka, Emily H-Y Cheng, Jeffrey Robbins, Kathleen W. Kinnally, Jeffrey D. Molkentin 2013 Cincinnati Children's Hospital Medical Center

Bax And Bak Function As The Outer Membrane Component Of The Mitochondrial Permeability Pore In Regulating Necrotic Cell Death In Mice, Jason Karch, Jennifer Q. Kwong, Adam R. Burr, Michelle A. Sargent, John W. Elrod, Pablo M. Peixoto, Sonia Martinez-Caballero, Hanna Osinskka, Emily H-Y Cheng, Jeffrey Robbins, Kathleen W. Kinnally, Jeffrey D. Molkentin

Publications and Research

A critical event in ischemia-based cell death is the opening of the mitochondrial permeability transition pore (MPTP). However, the molecular identity of the components of the MPTP remains unknown. Here, we determined that the Bcl-2 family members Bax and Bak, which are central regulators of apoptotic cell death, are also required for mitochondrial pore-dependent necrotic cell death by facilitating outer membrane permeability of the MPTP. Loss of Bax/Bak reduced outer mitochondrial membrane permeability and conductance without altering inner membrane MPTP function, resulting in resistance to mitochondrial calcium overload and necrotic cell death. Reconstitution with mutants of Bax that cannot ...


The Mechanisms And Consequences Of Gene Suppression During The Unfolded Protein Response, Angela Marie Arensdorf 2013 University of Iowa

The Mechanisms And Consequences Of Gene Suppression During The Unfolded Protein Response, Angela Marie Arensdorf

Theses and Dissertations

The endoplasmic reticulum (ER) facilitates the synthesis, assembly and quality control of all secretory, transmembrane, and resident proteins of the endomembrane system. An accumulation of unfolded proteins or a disruption in the specialized folding environment within the organelle causes ER stress, thus impairing the folding capacity of the ER. In response to this stress, the ER initiates a signaling cascade called the unfolded protein response (UPR) in an attempt to restore ER homeostasis.

The vertebrate UPR is propagated by three ER-resident transmembrane proteins (i.e., PERK, IRE1α, and ATF6α), each initiating a signaling cascade that ultimately culminates in production of ...


Focal Adhesion Kinase Signaling Regulates Highly Productive Transduction Of Adeno-Associated Virus Through Integrin-Mediated Endocytosis, Paul Michael Kaminsky 2013 University of Iowa

Focal Adhesion Kinase Signaling Regulates Highly Productive Transduction Of Adeno-Associated Virus Through Integrin-Mediated Endocytosis, Paul Michael Kaminsky

Theses and Dissertations

Recombinant adeno-associated virus (rAAV) is a widely used gene therapy vector. Although a wide range of rAAV serotypes can effectively enter most cell types, their transduction efficiencies (i.e., transgene expression) can vary widely depending on the target cell type. Integrins play important roles as co-receptors for rAAV infection, however, it remains unclear how integrin-dependent and -independent mechanisms of rAAV endocytosis influence the efficiency of intracellular virus processing and ultimately transgene expression. In this thesis, I examined the contribution of integrin-mediated endocytosis to transduction of fibroblasts by rAAV2. I found that promoting AAV2/integrin binding with Mn++ greatly enhanced (~17-fold ...


Flash4 Dark Reference Images, George McNamara 2013 M.D. Anderson Cancer Center

Flash4 Dark Reference Images, George Mcnamara

George McNamara

Hamamatsu FLASH4.0 dark reference images, acquired with 10 second exposure times, no light to camera. Camera offset (set by Hamamatsu( is ~100 (the average intensity of the first image is always ~1 intensity level higher - an odd feature, but trivial in practice for a 16-bit camera).

George McNamara, Ph.D.

Single Cells Analyst at L.J.N. Cooper Lab

University of Texas M.D. Anderson Cancer Center


Identification Of Rtl1, A Retrotransposon-Derived Imprinted Gene, As A Novel Driver Of Hepatocarcinogenesis, Jesse D Riordan, Vincent W Keng, Barbara R Tschida, Todd E Scheetz, Jason B Bell, Kelly M Podetz-Pedersen, Catherine D Moser, Neal G Copeland, Nancy A Jenkins, Lewis R Roberts, David A Largaespada, Adam J Dupuy 2013 University of Iowa

Identification Of Rtl1, A Retrotransposon-Derived Imprinted Gene, As A Novel Driver Of Hepatocarcinogenesis, Jesse D Riordan, Vincent W Keng, Barbara R Tschida, Todd E Scheetz, Jason B Bell, Kelly M Podetz-Pedersen, Catherine D Moser, Neal G Copeland, Nancy A Jenkins, Lewis R Roberts, David A Largaespada, Adam J Dupuy

Department of Anatomy and Cell Biology Publications

We previously utilized a Sleeping Beauty (SB) transposon mutagenesis screen to discover novel drivers of HCC. This approach identified recurrent mutations within the Dlk1-Dio3 imprinted domain, indicating that alteration of one or more elements within the domain provides a selective advantage to cells during the process of hepatocarcinogenesis. For the current study, we performed transcriptome and small RNA sequencing to profile gene expression in SB–induced HCCs in an attempt to clarify the genetic element(s) contributing to tumorigenesis. We identified strong induction of Retrotransposon-like 1 (Rtl1) expression as the only consistent alteration detected in all SB–induced tumors with ...


Functional Analysis Of A Putative Membrane-Bound Endo-Β-1,4-Glucanase From Panicum Virgatum, Joshua N Grant, Jonathan D. Willis, Neal Stewart 2013 University of Tennessee - Knoxville

Functional Analysis Of A Putative Membrane-Bound Endo-Β-1,4-Glucanase From Panicum Virgatum, Joshua N Grant, Jonathan D. Willis, Neal Stewart

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Cellulose is the most abundant carbohydrate in the world and is degraded by the synergistic action of multiple enzymes. One large family of enzymes capable of hydrolyzing cellulose is glycoside hydrolase family 9 (GH9), which includes several endoglucanases. Recent research into the molecular biology of plants has revealed certain genes coding for endo-β-1,4-glucanases (EGases). The EGases in plants are primarily functional during cell elongation through wall stress relaxation. GH9 enzymes have been found in insects, bacteria, oomycetes, and fungi. In insects, EGases enable the organism to digest cellulose; in fungi, EGases are suspected to play an important role in ...


Video Codec Performance (Excel Spreadsheet), George McNamara 2013 M.D. Anderson Cancer Center

Video Codec Performance (Excel Spreadsheet), George Mcnamara

George McNamara

Video codec performance (Excel spreadsheet). Movie was made in 2005-2006 when I worked at City of Hope National Medical Center. VTLF refers to Video Timelapse Light Facility. Videos were outputted from MetaMorph as AVI files. Personally, I always recommend uncompressed video files fro scientific uses. I also encourage posting the original scientific data format (ex. .lsm, .zvi, .lif, .stk).


Pubspectra Tattletales, George McNamara 2013 M.D. Anderson Cancer Center

Pubspectra Tattletales, George Mcnamara

George McNamara

Tattletales for Multiplex Fluorescent Reporters in Single Cells for Metabolomics

George McNamara

As of April 2013: L.J.N. Cooper & D.A. Lee Cellular Immunotherapy Lab, University of Texas M.D. Anderson Cancer Center, Houston, TX

Email: gtmcnamara@mdanderson.org, geomcnamara@earthlink.net

Tattletales is my concept for spatial multiplexing many fluorescent protein (FP) biosensors in the same live cell. For example, there are excellent FP biosensors to Ca++ ions, pH, glucose, ribose, glutamine, glutamate, ATP, redox, ROS, pyruvate, cAMP, cGMP, IP3, PI(3,4,5)P3, cell cycle indicators (Fucci2), PKA, PKC, photsphatases, caspase(s) [1, 2]. However, these are typically used one biosensor per experiment, due in part to flooding the cell with soluble biosensor. That is, conventionally, either a metabolite (glucose) reporter or a signal transduction (Ca++) reporter can be imaged. By flooding the cell with the reporter, signal to noise ratio is compromized by autofluorescence.

Tattletales takes advantage of spatial multiplexing to both increase the number of different reporters, and improve signal to noise ratio by localizing each biosensor to a small volume. I started with the observation by Robinett et al [3] who localized 512 GFP-nls-LacI to a 256 LacO array as a 200 nm diameter diffraction limited spot (nuclear background due to overexpression). Many thousands of DNA binding proteins, of known sequence specifities, exist (LacI, TetR, GalR, etc for cell line studies; ZF-FPs, TALE-FPs to STRs, telomere repeat binding factors-FPs, etc for primary cells) and can be fused (as cDNAs) to different fluorescent proteins and FP biosensors.

Many biosensors are available as affinity series [1, 4], now enabling extended dynamic range. I realized that spatial multiplexing of many DNA binding protein-reporters by localizing to different spots in the cell nucleus and distinguished by combinatorial addressing, where N address colors provide 2^N addresses (example, 3 colors is 2^3 = 8 combinations). Multiplexing ...


Abnormal Trafficking Of Endogenously Expressed Bmpr2 Mutant Allelic Products In Patients With Heritable Pulmonary Arterial Hypertension, Andrea L Frump, Jonathan W. Lowery Ph.D., Rizwan Hamid, Eric D Austin, Mark de Caestecker 2013 Vanderbilt University

Abnormal Trafficking Of Endogenously Expressed Bmpr2 Mutant Allelic Products In Patients With Heritable Pulmonary Arterial Hypertension, Andrea L Frump, Jonathan W. Lowery Ph.D., Rizwan Hamid, Eric D Austin, Mark De Caestecker

Faculty Publications and Research

More than 200 heterozygous mutations in the type 2 BMP receptor gene, BMPR2, have been identified in patients with Heritable Pulmonary Arterial Hypertension (HPAH). More severe clinical outcomes occur in patients with BMPR2 mutations by-passing nonsense-mediated mRNA decay (NMD negative mutations). These comprise 40% of HPAH mutations and are predicted to express BMPR2 mutant products. However expression of endogenous NMD negative BMPR2 mutant products and their effect on protein trafficking and signaling function have never been described. Here, we characterize the expression and trafficking of an HPAH-associated NMD negative BMPR2 mutation that results in an in-frame deletion of BMPR2 EXON2 ...


Evaluation Of Antibiotic Resistance Emerging From Use Of Antibiotics In Cafos, J. R. Robbins, D. Hellman, N. Pease, M. Costello 2013 Xavier University

Evaluation Of Antibiotic Resistance Emerging From Use Of Antibiotics In Cafos, J. R. Robbins, D. Hellman, N. Pease, M. Costello

Faculty Scholarship

No abstract provided.


Embryonic Stem Cells Are Redirected To Non-Tumorigenic Epithelial Cell Fate By Interaction With The Mammary Microenvironment, Corinne A. Boulanger, Robert D. Bruno, David L. Mack, Monica Gonzales, Nadia P. Castro, David S. Salomon, Gilbert H. Smith 2013 Old Dominion University

Embryonic Stem Cells Are Redirected To Non-Tumorigenic Epithelial Cell Fate By Interaction With The Mammary Microenvironment, Corinne A. Boulanger, Robert D. Bruno, David L. Mack, Monica Gonzales, Nadia P. Castro, David S. Salomon, Gilbert H. Smith

Medical Diagnostics & Translational Sciences Faculty Publications

Experiments were conducted to redirect mouse Embryonic Stem (ES) cells from a tumorigenic phenotype to a normal mammary epithelial phenotype in vivo. Mixing LacZ-labeled ES cells with normal mouse mammary epithelial cells at ratios of 1:5 and 1:50 in phosphate buffered saline and immediately inoculating them into epithelium-divested mammary fat pads of immune-compromised mice accomplished this. Our results indicate that tumorigenesis occurs only when normal mammary ductal growth is not achieved in the inoculated fat pads. When normal mammary gland growth occurs, we find ES cells (LacZ+) progeny interspersed with normal mammary cell progeny in the mammary epithelial ...


Cancer Gene Discovery And Immunosurveillance Studies Using Sleeping Beauty Mouse Models, Laura Marie Rogers 2012 University of Iowa

Cancer Gene Discovery And Immunosurveillance Studies Using Sleeping Beauty Mouse Models, Laura Marie Rogers

Theses and Dissertations

Cancer is the second leading cause of death in the United States. The majority of cases are caused by sporadic somatic mutation, which leads to cellular transformation over time. Therefore, cancer gene identification is a major focus of current research efforts. Understanding how key driver mutations result in cancer could lead to the design of better targeted therapies.

The Sleeping Beauty (SB) transposon system can be used to identify driver mutations in a variety of tumor types. SB mutagenesis mimics the sporadic accumulation of somatic mutations found in spontaneous human cancers. This system also has an additional benefit over chemical ...


Ferret Cftr Processing And Function, John T. Fisher 2012 University of Iowa

Ferret Cftr Processing And Function, John T. Fisher

Theses and Dissertations

The most common cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation is δF508 and this causes cystic fibrosis (CF). Animal models that recapitulate the human disease phenotype are critical to understanding pathophysiologic mechanisms in CF and developing therapies. New CF models in the pig and ferret have been generated that develop lung, pancreatic, liver, and intestinal pathologies that reflect disease in CF patients. Species-specific biology in the processing of CFTR has demonstrated that pig and mouse δF508-CFTR proteins are more effectively processed to the apical membrane of airway epithelia than human δF508-CFTR. The processing behavior of ferret wild-type (WT) and ...


Halloween 2012 Jack O'Lanterns Trick Or Treat, George McNamara 2012 M.D. Anderson Cancer Center

Halloween 2012 Jack O'Lanterns Trick Or Treat, George Mcnamara

George McNamara

Halloween 2012 makes trick or treating more visual and interactive than in past years.

the download is a ZIP file containing three files.

Print out the (unnumbered) image on as large and nice printer paper as possible - I used glossy 44" wide here in Miami (University of Miami, MillerSchool of Medicine, Calder Library, Biomedical Communications dept - I also made another print on "fabric", also 44" wide to take with me to an HHMI Janelia Farm conference on 'turning images into knowledge' that ends on Oct 31 - might stay up for a second conference, "GFP..." that start Nov 4).

The other ...


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