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Elevated Cochlear Adenosine Causes Hearing Loss Via Adora2b Signaling, Jeanne Manalo 2020 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Elevated Cochlear Adenosine Causes Hearing Loss Via Adora2b Signaling, Jeanne Manalo

Dissertations and Theses (Open Access)

Over 538 million people in the world have been diagnosed with hearing loss (HL). Current treatments for the most common type of HL, sensorineural HL, are limited to hearing aids and cochlear implants with no FDA-drugs available. The hearing process demands an abundance of ATP and HL is often attributed to a disruption in this metabolic energy currency. Patients who lack adenosine deaminase (ADA), the enzyme that irreversibly metabolizes adenosine, have high levels of adenosine that yield severe health problems, including HL; however, the pathogenic mechanisms behind HL and adenosine remain elusive. Our lab has found a HL phenotype in …


Silencing Innovation: The Patent Eligibility Of Sirna Therapeutics, Alexander M. Walker 2020 University of Minnesota Law School

Silencing Innovation: The Patent Eligibility Of Sirna Therapeutics, Alexander M. Walker

Minnesota Journal of Law, Science & Technology

No abstract provided.


Using Novel Mouse Knockout Models To Study The Roles Of Asm (Acid Sphingomyelinase) In The Regulation Of Multiple Stem Cell Compartments In Vivo, Amro Abdalla 2020 University of Nevada, Las Vegas

Using Novel Mouse Knockout Models To Study The Roles Of Asm (Acid Sphingomyelinase) In The Regulation Of Multiple Stem Cell Compartments In Vivo, Amro Abdalla

UNLV Theses, Dissertations, Professional Papers, and Capstones

Acid Sphingomyelinase (ASM) is a lipid-modifying enzyme that breaks down sphingomyelin lipids into ceramide and phosphorylcholine. Genetic mutations in the human ASM gene leads to Niemann pick diseases (NPD) type A & B. In NPD type A, patients die between 1-2 years old due to severe neurological complications, while NPD type B patients live to adulthood but suffer from severe visceral organ complications. Type A is usually associated with complete inactivation of the ASM gene. The hallmark of NPD is Purkinje neuron (PN) death. PNs, the major neurons in the cerebellum part of the brain, regulate the balance and fine …


Protease Oma1 Modulates Mitochondrial Bioenergetics And Ultrastructure Through Dynamic Association With Micos Complex, Martonio P. Viana 2020 University of Nebraska-Lincoln

Protease Oma1 Modulates Mitochondrial Bioenergetics And Ultrastructure Through Dynamic Association With Micos Complex, Martonio P. Viana

Department of Biochemistry: Dissertations, Theses, and Student Research

Remodeling of mitochondrial ultrastructure is a complex dynamic process that is critical for a variety of mitochondrial functions and apoptosis. Although the key regulators of this process - mitochondrial contact site and cristae junction organizing system (MICOS) and GTPase Optic Atrophy 1 (OPA1) have been characterized, the mechanisms behind this regulation remain incompletely defined. Here, we found that in addition to its role in mitochondrial division, metallopeptidase OMA1 is required for maintenance of contacts between the inner and outer membranes through a dynamic association with MICOS. This association is independent of OPA1, appears to be mediated via the MIC60 MICOS …


A Novel Serpinb1 Single-Nucleotide Polymorphism Associated With Glycemic Control And Β-Cell Function In Egyptian Type 2 Diabetic Patients, Dina H. Kassem, Aya Adel, Ghada H. Sayed, Mohamed M. Kamal 2020 Ain Shams University

A Novel Serpinb1 Single-Nucleotide Polymorphism Associated With Glycemic Control And Β-Cell Function In Egyptian Type 2 Diabetic Patients, Dina H. Kassem, Aya Adel, Ghada H. Sayed, Mohamed M. Kamal

Pharmacy

Aims: Serine protease inhibitor B1 (SerpinB1) is a neutrophil elastase inhibitor that has been proved to be associated with type 2 diabetes mellitus and pancreatic β-cell proliferation. In this study, we investigated 2 SERPINB1 SNPs, rs114597282 and rs15286, regarding their association with diabetes risk and various anthropometric and biochemical parameters in Egyptian type 2 diabetic patients.

Materials and Methods: A total of 160 subjects (62 control and 98 type 2 diabetic patients) participated in this study. Various anthropometric and biochemical parameters were assessed. Genotyping assay for the two SNPs was done using TaqMan genotyping assays. The association of rs15286 variants …


Influence Of Edge Effects On Laser-Induced Surface Displacement Of Opaque Materials By Photothermal Interferometry, G. A. S. Flizikowski, B. Anghinoni, J. H. Rohling, M. P. Belançon, R. S. Mendes, M. L. Baesso, L. C. Malacarne, T. Požar, Stephen E. Bialkowski, N. G. C. Astrath 2020 Universidade Estadual de Maringá

Influence Of Edge Effects On Laser-Induced Surface Displacement Of Opaque Materials By Photothermal Interferometry, G. A. S. Flizikowski, B. Anghinoni, J. H. Rohling, M. P. Belançon, R. S. Mendes, M. L. Baesso, L. C. Malacarne, T. Požar, Stephen E. Bialkowski, N. G. C. Astrath

Chemistry and Biochemistry Faculty Publications

We demonstrate the influence of edge effects on the photothermal-induced phase shift measured by a homodyne quadrature laser interferometer and compare the experiments with rigorous theoretical descriptions of thermoelastic surface displacement of metals. The finite geometry of the samples is crucial in determining how the temperature is distributed across the material and how this affects the interferometer phase shift measurements. The optical path change due to the surface thermoelastic deformation and thermal lens in the surrounding air is decoded from the interferometric signal using analytical and numerical tools. The boundary/edge effects are found to be relevant to properly describe the …


The Shape Of Metabolism: Mitochondrial Dynamics, Remodeling, And Bioenergetic Reprogramming In Disease, Carl Decker 2020 Claremont Colleges

The Shape Of Metabolism: Mitochondrial Dynamics, Remodeling, And Bioenergetic Reprogramming In Disease, Carl Decker

KGI Theses and Dissertations

Mitochondria are dynamic, double-membrane bound hubs of bioenergetics, cell signaling, and redox balance that exist as an oscillating network of fused superstructures and smaller, single organelles. Importantly, their position at the junction of catabolic and anabolic metabolism connects these morphological fluctuations to larger cellular metabolic programs, which in turn have implicated mitochondrial dynamics in a number of disease states and a varied set of cell phenomena. For example, differentiation of memory t-cells is dependent on mitochondrial network morphology, and in particular on remodeling dynamics that yield fused mitochondrial assemblies favoring oxidative phosphorylation-driven metabolism. In contrast, many cancers have been shown …


The Nitrogen Budget Of Laboratory-Simulated Western Us Wildfires During The Firex 2016 Fire Lab Study, James M. Roberts, Chelsea E. Stockwell, Robert J. Yokelson, Joost De Gouw, Yong Liu, Vanessa Selimovic, Abigail R. Koss, Kanako Sekimoto, Matthew M. Coggon, Bin Yuan, Kyle J. Zarzana, Steven S. Brown, Cristina Santin, Stefan H. Doerr, Carsten Warneke 2020 National Oceanic and Atmospheric Administration

The Nitrogen Budget Of Laboratory-Simulated Western Us Wildfires During The Firex 2016 Fire Lab Study, James M. Roberts, Chelsea E. Stockwell, Robert J. Yokelson, Joost De Gouw, Yong Liu, Vanessa Selimovic, Abigail R. Koss, Kanako Sekimoto, Matthew M. Coggon, Bin Yuan, Kyle J. Zarzana, Steven S. Brown, Cristina Santin, Stefan H. Doerr, Carsten Warneke

Chemistry and Biochemistry Faculty Publications

Reactive nitrogen (Nr, defined as all nitrogencontaining compounds except for N2 and N2O) is one of the most important classes of compounds emitted from wildfire, as Nr impacts both atmospheric oxidation processes and particle formation chemistry. In addition, several Nr compounds can contribute to health impacts from wildfires. Understanding the impacts of wildfire on the atmosphere requires a thorough description of Nr emissions. Total reactive nitrogen was measured by catalytic conversion to NO and detection by NO-O3 chemiluminescence together with individual Nr species during a series of laboratory fires of fuels characteristic of western US wildfires, conducted as part of …


The Gcn5 Complexes In Drosophila As A Model For Metazoa, Eliana F. Torres-Zelada, Vikki M. Weake 2020 Purdue University

The Gcn5 Complexes In Drosophila As A Model For Metazoa, Eliana F. Torres-Zelada, Vikki M. Weake

Department of Biochemistry Faculty Publications

The histone acetyltransferase Gcn5 is conserved throughout eukaryotes where it functions as part of large multi-subunit transcriptional coactivator complexes that stimulate gene expression. Here, we describe how studies in the model insect Drosophila melanogaster have provided insight into the essential roles played by Gcn5 in the development of multicellular organisms. We outline the composition and activity of the four different Gcn5 complexes in Drosophila: the Spt-Ada-Gcn5 Acetyltransferase (SAGA), Ada2a-containing (ATAC), Ada2/Gcn5/Ada3 transcription activator (ADA), and Chiffon Histone Acetyltransferase (CHAT) complexes. Whereas the SAGA and ADA complexes are also present in the yeast Saccharomyces cerevisiae, ATAC has only been …


The Drosophila Dbf4 Ortholog Chiffon Forms A Complex With Gcn5 That Is Necessary For Histone Acetylation And Viability, Eliana F. Torres-Zelada, Robert E. Stephenson, Aktan Aksoy, Benjamin D. Anderson, Selene K. Swanson, Laurence Laurence Florens, Emily C. Dykhuizen, Michael P. Washburn, Vikki M. Weake 2020 Purdue University

The Drosophila Dbf4 Ortholog Chiffon Forms A Complex With Gcn5 That Is Necessary For Histone Acetylation And Viability, Eliana F. Torres-Zelada, Robert E. Stephenson, Aktan Aksoy, Benjamin D. Anderson, Selene K. Swanson, Laurence Laurence Florens, Emily C. Dykhuizen, Michael P. Washburn, Vikki M. Weake

Department of Biochemistry Faculty Publications

Metazoans contain two homologs of the Gcn5-binding protein Ada2, Ada2a and Ada2b, which nucleate formation of the ATAC and SAGA complexes respectively. In Drosophila melanogaster, there are two splice isoforms of Ada2b: Ada2b-PA and Ada2b-PB. Here we show only the Ada2b-PB isoform is in SAGA; in contrast, Ada2b-PA associates with Gcn5, Ada3, Sgf29 and Chiffon forming the Chiffon Histone Acetyltransferase (CHAT) complex. Chiffon is theDrosophila ortholog of Dbf4, which binds and activates the cell cycle kinase Cdc7 to initiate DNA replication. In flies, Chiffon and Cdc7 are required in ovary follicle cells for gene amplification, a specialized form of DNA …


Comparison Of Accelerated Solvent Extraction (Ase) And Energized Dispersive Guided Extraction (Edge) For The Analysis Of Pesticides In Leaves, Ashlie D. Kinross, Kimberly J. Hageman, William J. Doucette, Alexandria L. Foster 2020 Utah State University

Comparison Of Accelerated Solvent Extraction (Ase) And Energized Dispersive Guided Extraction (Edge) For The Analysis Of Pesticides In Leaves, Ashlie D. Kinross, Kimberly J. Hageman, William J. Doucette, Alexandria L. Foster

Chemistry and Biochemistry Faculty Publications

Various techniques have been evaluated for the extraction and cleanup of pesticides from environmental samples. In this work, a Selective Pressurized Liquid Extraction (SPLE) method for pesticides was developed using a Thermo Fisher Scientific Accelerated Solvent Extraction (ASE) system. This instrument was compared to the newly introduced (2017) extraction instrument, the Energized Dispersive Guided Extraction (EDGE) system, which combines Pressurized Liquid Extraction (PLE) and dispersive Solid Phase Extraction (dSPE). We first optimized the SPLE method using the ASE instrument for pesticide extraction from alfalfa leaves using layers of Florisil and graphitized carbon black (GCB) downstream of the leaf homogenate in …


Characterization Of The Overexpression Of The Native H+-Pumping Pyrophosphatase In The Microalga Picochlorum Soloecismus, Kimberly T. Wright 2020 University of New Mexico

Characterization Of The Overexpression Of The Native H+-Pumping Pyrophosphatase In The Microalga Picochlorum Soloecismus, Kimberly T. Wright

Biology ETDs

Microalgae are of interest for the creation of sustainable and cost competitive alternatives to petroleum-based fuels and chemicals. However, cultivation, extraction and processing of algal biomass requires improved yields to achieve economic feasibility. The advancement of microalgal biotechnology and various genetic engineering techniques allow the improvement of microalgae biomass for this purpose. Here, the characterization of the overexpression of the native vacuolar H+ pumping pyrophosphate (AVP1) in Picochlorum soloecismus was examined. AVP1 overexpression causes biomass increase in relevant plant crops. When overexpressed in this microalga it increases carbon storage in the form of starch in a closed laboratory photobioreactor. However, …


Nobiletin Affects Circadian Rhythms And Oncogenic Characteristics In A Cell-Dependent Manner, Sujeewa S. Lellupitiyage Don, Kelly L. Robertson, Hui-Hsien Lin, Caroline Labriola, Mary E. Harrington, Stephanie R. Taylor, Michelle E. Farkas 2020 University of Massachusetts Amherst

Nobiletin Affects Circadian Rhythms And Oncogenic Characteristics In A Cell-Dependent Manner, Sujeewa S. Lellupitiyage Don, Kelly L. Robertson, Hui-Hsien Lin, Caroline Labriola, Mary E. Harrington, Stephanie R. Taylor, Michelle E. Farkas

Psychology: Faculty Publications

The natural product nobiletin is a small molecule, widely studied with regard to its therapeutic effects, including in cancer cell lines and tumors. Recently, nobiletin has also been shown to affect circadian rhythms via their enhancement, resulting in protection against metabolic syndrome. We hypothesized that nobiletin’s anti-oncogenic effects, such as prevention of cell migration and formation of anchorage independent colonies, are correspondingly accompanied by modulation of circadian rhythms. Concurrently, we wished to determine whether the circadian and anti-oncogenic effects of nobiletin differed across cancer cell lines. In this study, we assessed nobiletin’s circadian and therapeutic characteristics to ascertain whether these …


Collaborative, Multidisciplinary Evaluation Of Cancer Variants Through Virtual Molecular Tumor Boards Informs Local Clinical Practices., Shruti Rao, Beth Pitel, Alex H Wagner, Simina M Boca, Matthew McCoy, Ian King, Samir Gupta, Ben Ho Park, Jeremy L Warner, James Chen, Peter Rogan, Debyani Chakravarty, Malachi Griffith, Obi L Griffith, Subha Madhavan 2020 The University of Western Ontario

Collaborative, Multidisciplinary Evaluation Of Cancer Variants Through Virtual Molecular Tumor Boards Informs Local Clinical Practices., Shruti Rao, Beth Pitel, Alex H Wagner, Simina M Boca, Matthew Mccoy, Ian King, Samir Gupta, Ben Ho Park, Jeremy L Warner, James Chen, Peter Rogan, Debyani Chakravarty, Malachi Griffith, Obi L Griffith, Subha Madhavan

Biochemistry Publications

PURPOSE: The cancer research community is constantly evolving to better understand tumor biology, disease etiology, risk stratification, and pathways to novel treatments. Yet the clinical cancer genomics field has been hindered by redundant efforts to meaningfully collect and interpret disparate data types from multiple high-throughput modalities and integrate into clinical care processes. Bespoke data models, knowledgebases, and one-off customized resources for data analysis often lack adequate governance and quality control needed for these resources to be clinical grade. Many informatics efforts focused on genomic interpretation resources for neoplasms are underway to support data collection, deposition, curation, harmonization, integration, and analytics …


Investigation Of The Role Of Heparin-Binding Pocket In Amyloid Fibrils Formation Of Fgf-1, I Gusti Ayu Agung Septiari 2020 University of Arkansas, Fayetteville

Investigation Of The Role Of Heparin-Binding Pocket In Amyloid Fibrils Formation Of Fgf-1, I Gusti Ayu Agung Septiari

Graduate Theses and Dissertations

Human acidic fibroblast growth factor (aFGF/hFGF-1) is one of the promising molecules to be investigated to generate an in-depth understanding of the pathological mechanism of Alzheimer's disease (AD) neurodegenerative disorder characterized by the presence of amyloid fibrils. Some in vivo and human brain tissue studies proved the correlation of high-level expression of FGF-1-induced neuroinflammation and the occurrence of AD. The presence of amyloid fibrils as a hallmark of AD can be related to the generic property of the proteins to form amyloid fibrils; High level of FGF-1, in this case, may contribute to the formation of amyloid fibrils. As a …


Acute Toxicity, Antidiarrhoeal And Antioxidant Activities Of Methanolic Leaf Extract Of Baphia Macrocalyx In Mice, Regina Malekela, Jacob Mwakalinga, Rosta Antony, Flora Stephano 2020 College of Natural and Applied Sciences University of Dar es Salaam

Acute Toxicity, Antidiarrhoeal And Antioxidant Activities Of Methanolic Leaf Extract Of Baphia Macrocalyx In Mice, Regina Malekela, Jacob Mwakalinga, Rosta Antony, Flora Stephano

Tanzania Journal of Science

The aim of the current study was to assess the acute toxicity, antidiarrhoeal and antioxidant potentials of methanolic leaf extract of Baphia macrocalyx (BM) in mice. Acute toxicity test of BM extract was performed based on OECD guideline 423. Results revealed that the extract did not produce any changes in general behaviour, body weight or mortality of the tested mice even at the highest oral administered dose (2000 mg/kg body weight). The antidiarrhoeal effect was examined using castor oil induced diarrhoea test. Results showed that BM extract delayed the onset of diarrhoea, decreased frequency of defaecation and reduced the severity …


Comparative In Vitro Antioxidant Activities Of Aqueous Extracts Of Garcinia Kola And Buchholzia Coriacea Seeds, Abdulkadir Abubakar, Moshood Olorunkemi, Musa Busari, Rabiat Hamzah, Tawakaltu Abdulrasheed-Adeleke 2020 University of Dar es Salaam

Comparative In Vitro Antioxidant Activities Of Aqueous Extracts Of Garcinia Kola And Buchholzia Coriacea Seeds, Abdulkadir Abubakar, Moshood Olorunkemi, Musa Busari, Rabiat Hamzah, Tawakaltu Abdulrasheed-Adeleke

Tanzania Journal of Science

Comparative in vitro antioxidant activities of aqueous extracts of Garcinia kola and Buchholzia coriacea seeds were carried out using 2, 2-diphenyl 1-picrylhydrazyl (DPPH) free radical scavenging activities, ferric reducing antioxidant power (FRAP) and inhibition of lipid peroxidation assays. Total phenolics, alkaloids, tannins, saponins and flavonoids constituents of the samples were also determined. G. kola seeds contained higher concentrations of secondary metabolites compared to B. coriacea seeds except flavonoids. Both G. kola and B. coriacea exhibited minimum percentage inhibition when compared with the gallic acid. However, B. coriacea exhibited significantly (p < 0.05) higher percentage DPPH scarvenging activities (44.66%) when compared with G. kola (43.62%) at maximum concentration of 100 µg/mL. G. kola on the other hand, showed higher percentage inhibition of lipid peroxidation when compared with B. coriacea at all tested concentrations. Percentage FRAP by B. coriacea was significantly (p < 0.05) higher than G. kola at 100 µg/mL (46.65%, and 38.35%, respectively) and 50 µg/mL (38.75%, and 46.05%, respectively), while lower percentage FRAP of the G. kola than B. coriacea were recorded at 25 µg/mL (24.26% and 38.24%, respectively) and 12.5 µg/mL (34.41% and 37.41%, respectively). Therefore, Garcinia kola and B. coriacea showed appreciable antioxidant activities at varying concentrations and this may be due to the presence of various phenolic compounds in both samples Keywords:    Buchholzia coriacea; Garcinia kola; Antioxidant; DPPH free radicals; Secondary metabolites.


Leaf Traits Can Be Used To Predict Rates Of Litter Decomposition, Marc Rosenfield, Jennifer L. Funk, Jason K. Keller, Catrina Clausen, Kimberlee Cyphers 2020 Chapman University

Leaf Traits Can Be Used To Predict Rates Of Litter Decomposition, Marc Rosenfield, Jennifer L. Funk, Jason K. Keller, Catrina Clausen, Kimberlee Cyphers

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Strong relationships exist between litter chemistry traits and rates of litter decomposition. However, leaf traits are more commonly found in online trait databases than litter traits and fewer studies have examined how well leaf traits predict litter decomposition rates. Furthermore, while bulk leaf nitrogen (N) content is known to regulate litter decomposition, few studies have explored the importance of N biochemistry fractions, such as protein and amino acid concentration. Here, we decomposed green leaves and naturally senesced leaf litter of nine species representing a wide range of leaf functional traits. We evaluated the ability of traits associated with leaf and …


Adsorption Behavior Of Chemically / Charged Modified Antibodies On Gold Nanoparticles, Samuel Okyem 2020 Illinois State University

Adsorption Behavior Of Chemically / Charged Modified Antibodies On Gold Nanoparticles, Samuel Okyem

Theses and Dissertations

Gold nanoparticles (AuNPs) have been exploited in the various domains of science such as drug delivery, bio-sensing, immunoassays and environmental sensors, due to their optical properties and intriguing surface chemistry. Different scientific procedures have been used to effectively immobilize antibodies onto AuNPs. Although acceptable outcomes have been achieved in the immobilization of antibodies onto AuNPs, the sensitivity of these immobilized antibodies to target antigen or binding sites is limited due to improper orientation of the antibodies. Also, the possibility of nanoparticle aggregation when exposed to proteins limits its biomedical applicability.

There is some evidence that the surface charge of antibodies …


Heterometallic Multinuclear Nodes Directing Mof Electronic Behavior, Otega A. Ejegbavwo, Anna A. Berseneva, Corey R. Martin, Gabrielle A. Leith, Shubham Pandey, Amy J. Brandt, Kyoung Chul Park, Abhijai Mathur, Sharfa Farzandh, Vladislav V. Klepov, Brittany J. Heiser, Mvs Chandrashekhar, Stavros G. Karakalos, Mark D. Smith, Simon R. Phillpot, Sophya Garashchuk, Donna A. Chen, Natalia B. Shustova Prof. Dr. 2020 University of South Carolina

Heterometallic Multinuclear Nodes Directing Mof Electronic Behavior, Otega A. Ejegbavwo, Anna A. Berseneva, Corey R. Martin, Gabrielle A. Leith, Shubham Pandey, Amy J. Brandt, Kyoung Chul Park, Abhijai Mathur, Sharfa Farzandh, Vladislav V. Klepov, Brittany J. Heiser, Mvs Chandrashekhar, Stavros G. Karakalos, Mark D. Smith, Simon R. Phillpot, Sophya Garashchuk, Donna A. Chen, Natalia B. Shustova Prof. Dr.

Faculty Publications

Metal node engineering in combination with modularity, topological diversity, and porosity of metal–organic frameworks (MOFs) could advance energy and optoelectronic sectors. In this study, we focus on MOFs with multinuclear heterometallic nodes for establishing metal−property trends, i.e., connecting atomic scale changes with macroscopic material properties by utilization of inductively coupled plasma mass spectrometry, conductivity measurements, X-ray photoelectron and diffuse reflectance spectroscopies, and density functional theory calculations. The results of Bader charge analysis and studies employing the Voronoi–Dirichlet partition of crystal structures are also presented. As an example of frameworks with different nodal arrangements, we have chosen MOFs with mononuclear, …


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