Biochemistry, Biophysics, and Structural Biology Commons^™

Ptpro Represses Erbb2-Driven Breast Oncogenesis By Dephosphorylation And Endosomal Internalization Of Erbb2., H Dong, L Ma, J Gan, W Lin, Rakesh Kumar, +9 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

The plasma membrane-associated tyrosine phosphatase PTPRO is frequently transcriptionally repressed in cancers and signifies poor prognosis of breast cancer patients. In this study, deletion of Ptpro inMMTV-Erbb2 transgenic mice dramatically shortened the mammary tumor latency and accelerated tumor growth due to loss of Ptpro within the breast cancer cells but not in surrounding tissue as confirmed by hetero-transplantation studies. Both in vitro and in vivo data demonstrated that the phosphatase activity was required for the inactivation of ERBB2 and its downstream signaling. PTPRO regulated the phosphorylation status of ERBB2 at Y1248. Co-immunoprecipitation and proximity ligation assay (Duolink) indicated that …

Myeloperoxidase-Mediated Protein Lysine Oxidation Generates 2- Aminoadipic Acid And Lysine Nitrile In Vivo, Hongqiao Lin, Bruce S. Levison, Jennifer A. Buffa, Ying Huang, Xiaoming Fu, Zeneng Wang, Valentin Gogonea, Joseph A. Didonato, Stanley L. Hazen

Chemistry Faculty Publications

Recent studies reveal 2-aminoadipic acid (2-AAA) is both elevated in subjects at risk for diabetes and mechanistically linked to glucose homeostasis. Prior studies also suggest enrichment of protein-bound 2-AAA as an oxidative post-translational modification of lysyl residues in tissues associated with degenerative diseases of aging. While in vitro studies suggest redox active transition metals or myeloperoxidase (MPO) generated hypochlorous acid (HOCl) may produce protein-bound 2-AAA, the mechanism(s) responsible for generation of 2- AAA during inflammatory diseases are unknown. In initial studies we observed that traditional acid- or basecatalyzed protein hydrolysis methods previously employed to measure tissue 2-AAA can artificially generate …

Isolation And Spectroscopic Characterization Of Zn(Ii), Cu(Ii), And Pd(Ii) Complexes Of 1,3,4-Thiadiazole-Derived Ligand, Dariusz Karcz, Arkadiusz Matwijczuk, Bozena Boron, Bernadette Creaven, Leszek Fiedor, Andrzej Niewiadomy, Mariusz Gagos

Articles

A series of complexes incorporating Zn(II), Cu(II), and Pd(II) ions, and 4-(5-heptyl-1,3,4-thiadiazol-2-yl)benzene-1,3-diol (L1) as model ligand, was synthesized in order to examine the nature of potential interactions between biologically active ligands, 1,3,4-thiadiazoles and metal ions with proven biological relevance. The structures of the compounds isolated were characterized using a number of spectroscopic methods including IR, Uv–vis, AAS, steady state and time-resolved fluorescence (TRF). The results obtained suggest that the L1-Zn(II) and L1-Pd(II) complexes consist of one molecule of L1 and one acetate ion acting as ligands, while the L1-Cu(II) complex adapts a 2:1 (L1: metal) stoichiometry. The coordination of L1 …

Identification Of Expression And Function Of The Glucagon-Like Peptide-1 Receptor In Gastrointestinal Smooth Muscle, Alexander T. May

Theses and Dissertations

In response to ingestion of nutrients, enteroendocrine L cells secrete the incretin hormone, glucagon-like peptide-1 (GLP-1), to enhance glucose-dependent insulin release. Therapies related to GLP-1 are approved for type 2 diabetes. The GLP-1 receptor (GLP-1R) is expressed in cells of the gastrointestinal tract and elsewhere. In pancreatic beta cells, GLP-1R are coupled to the Gs/cAMP/PKA pathway. The expression and function of GLP-1R in gastrointestinal smooth muscle are not known. Aim. To test the hypothesis that GLP-1 regulates smooth muscle function by acting on GLP-1R expressed on smooth muscle. Methods. Smooth muscle cells (SMC) were isolated and cultured. Expression of GLP-1R …

Determining The Effects Of Methanol, Ethanol, Isopropanol, And Glycerol On Both Thermal Stability And Catalytic Activity Of Rv0045c, An Enzyme From M. Tuberculosis, Katelyn Baumer

Undergraduate Honors Thesis Collection

Tuberculosis (TB) is a highly infectious respiratory disease contracted through the inhalation of Mycobacterium tuberculosis. Serine hydrolases are abundant in M. tuberculosis and serve as a model for studying the inhibition of TB. Rv0045c is an example of such with little known regarding its biological function. Rv0045c was exposed to methanol, ethanol, isopropanol, or glycerol and the effects of varying concentration of these alcohols on the catalytic efficiency and thermal stability of the enzyme was determined. The thermal stability of Rv0045c was found to decrease with concentration of methanol, ethanol, or isopropanol. The opposite was true of the thermal stability …

Nitrosative Stress Sensing In Porphyromonas Gingivalis: Structure And Function Of The Heme Binding Transcriptional Regulator Hcpr, Benjamin R. Belvin

Theses and Dissertations

Porphyromonas gingivalis, a Gram negative anaerobe implicated in the progression of periodontal disease, is capable of surviving and causing infection despite high levels of reactive nitrogen species found in the oral cavity due to its efficient nitrosative stress response. HcpR is an important sensor-regulator that plays a vital step in the initiation of the nitrosative stress response in many Gram negative anaerobic bacteria. We employ a combination of X-ray crystallography, SAXS, resonance Raman spectroscopy, UV-Vis spectroscopy, and molecular biology techniques to better understand this key regulator. Knockout of the hcpR gene in W83 P. gingivalis results in the inability of …

Development And Characterization Of Novel Anti-Bat Monoclonal Antibodies For Studying Bat Immunity, Cailyn Cowan

Legacy Theses & Dissertations (2009 - 2024)

Abstract

Discovering Small Molecule Inhibitors Targeted To Ligand-Stimulated Rage-Diaph1 Signaling Transduction, Jinhong Pan

Legacy Theses & Dissertations (2009 - 2024)

The receptor of advanced glycation end product (RAGE) is a multiligand receptor of the immunoglobulin superfamily of cell surface molecules, which plays an important role in immune responses. Full-length RAGE includes three extracellular immunoglobulin domains, a transmembrane domain and an intracellular domain. It is a pattern recognition receptor that can bind diverse ligands. NMR spectroscopy and x-ray crystallization studies of the extracellular domains of RAGE indicate that RAGE ligands bind by distinct charge- and hydrophobicity-dependent mechanisms. It is found that calgranulin binding to the C1C2 domain or AGEs binding to the V domain activates extracellular signaling, which triggers interactions of …

The Role Of N-Myc Downstream Regulated Gene 1 In Breast Cancer Lipid Metabolism, Christopher James Sevinsky

Legacy Theses & Dissertations (2009 - 2024)

Altered carbohydrate and lipid metabolism are increasingly well characterized hallmarks of aggressive breast cancers. While aerobic glycolysis, or “the Warburg effect”, is a well-established metabolic adaptation exploited by tumor cells, the understanding of unique aspects of cancer lipid metabolism lags behind. This is especially true regarding the coordination of complex lipid synthesis and trafficking pathways, which remains poorly understood. N-Myc Downstream Regulated Gene1 (NDRG1) is overexpressed in many solid tumors, but its function is unclear. The importance of NDRG1 is best exemplified by the effect of null mutations on human physiology: inactivating mutations give rise to the severe autosomal recessive …

Benzylideneoxymorphone: A New Lead For Development Of Bifunctional Mu/Delta Opioid Receptor Ligands, Jason R. Healy, Padmavani Bezawada, Nicholas W. Griggs, Andrea L. Devereaux, Rae Reiko Matsumoto, John R. Traynor, Christopher W. Cunningham

Faculty Publications & Research of the TUC College of Pharmacy

Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR) antagonists attenuates the development of tolerance to mu opioid receptor (MOR) agonists has led to interest in producing bifunctional MOR agonist/DOR antagonist ligands. Herein, we present 7-benzylideneoxymorphone (6, UMB 246) displaying MOR partial agonist/DOR antagonist activity, representing a new lead for designing bifunctional MOR/DOR ligands.

Detoxification Of Mitochondrial Oxidants And Apoptotic Signaling Are Facilitated By Thioredoxin-2 And Peroxiredoxin-3 During Hyperoxic Injury, Benjamin J. Forred, Darwin R. Daugaard, Brianna K. Titus, Ryan R. Wood, Miranda J. Floen, Michelle L. Booze, Peter F. Vitiello

School of Veterinary and Biomedical Sciences: Faculty Publications

Mitochondria play a fundamental role in the regulation of cell death during accumulation of oxidants. High concentrations of atmospheric oxygen (hyperoxia), used clinically to treat tissue hypoxia in premature newborns, is known to elicit oxidative stress and mitochondrial injury to pulmonary epithelial cells. A consequence of oxidative stress in mitochondria is the accumulation of peroxides which are detoxified by the dedicated mitochondrial thioredoxin system. This system is comprised of the oxidoreductase activities of peroxiredoxin-3 (Prx3), thioredoxin-2 (Trx2), and thioredoxin reductase-2 (TrxR2). The goal of this study was to understand the role of the mitochondrial thioredoxin system and mitochondrial injuries during …

Maternal Inflammation At Mid-Gestation In Pregnant Rats Impairs Fetal Muscle Growth And Development At Term, C. N. Cadaret, K. A. Beede, E. M. Merrick, T. L. Barnes, J. D. Loy, D. T. Yates

School of Veterinary and Biomedical Sciences: Faculty Publications

Intrauterine growth restriction (IUGR) is a leading cause of perinatal morbidity and mortality. Low birth weight resulting from preterm birth and/or IUGR is an underlying factor in 60–80% of perinatal death worldwide, and is particularly common in developing countries (UNICEF, 2008). Furthermore, studies have linked IUGR and the associated fetal malnutrition to increased incidence of metabolic syndrome in adult life (Barker et al., 1993; Godfrey and Barker, 2000). The “thrifty phenotype hypothesis” developed by David Barker (Hales et al., 1991) states that IUGR-associated fetal malnutrition forces the fetus to spare nutrients by altering tissue-specific metabolism in order to survive. In …

A Parapoxviral Virion Protein Targets The Retinoblastoma Protein To Inhibit Nf-Κb Signaling, Ponnuraj Nagendraprabhu, Sushil Khatiwada, Sabal Chaulagain, Gustavo A. Delhon, Daniel L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

Poxviruses have evolved multiple strategies to subvert signaling by Nuclear Factor κB (NF-κB), a crucial regulator of host innate immune responses. Here, we describe an orf virus (ORFV) virion-associated protein, ORFV119, which inhibits NF-κB signaling very early in infection (≤30 min post infection). ORFV119 NF-κB inhibitory activity was found unimpaired upon translation inhibition, suggesting that virion ORFV119 alone is responsible for early interference in signaling. A C-terminal LxCxE motif in ORFV119 enabled the protein to interact with the retinoblastoma protein (pRb) a multifunctional protein best known for its tumor suppressor activity. Notably, experiments using a recombinant virus containing an ORFV119 …

Micro-Spectroscopy Of Bio-Assemblies At The Single Cell Level, Jeslin Kera

Honors Undergraduate Theses

In this thesis, we investigate biological molecules on a micron scale in the ultraviolet spectral region through the non-destructive confocal absorption microscopy. The setup involves a combination of confocal microscope with a UV light excitation beam to measure the optical absorption spectra with spatial resolution of 1.4 μm in the lateral and 3.6 μm in the axial direction. Confocal absorption microscopy has the benefits of requiring no labels and only low light intensity for excitation while providing a strong signal from the contrast generated by the attenuation of propagating light due to absorption. This enables spatially resolved measurements of single …

Steroidogenesis In The Green Anole Lizard Brain And Gonad, Christine Peek

All Graduate Theses, Dissertations, and Other Capstone Projects

Seasonally breeding animals reproduce during certain times of the year and, subsequently, behaviors, steroid hormone levels, and brain morphology change. The green anole lizard (Anolis carolinensis) is an excellent model to study the regulation of steroid hormone production because they have distinct hormonal and behavioral differences between sexes and seasons. As in other vertebrates, steroidogenesis in anoles is under the control of the hypothalamus-pituitary-gonadal (HPG) axis. We tested the hypothesis that natural variations in steroid hormone levels between sexes and seasons are mediated within the brain and gonad by examining four genes involved in steroidogenesis: StAR, Cyp17α1, HSD17β3, and Cyp19α1. …

Exosomes Serve As Novel Modes Of Tick-Borne Flavivirus Transmission From Arthropod To Human Cells And Facilitates Dissemination Of Viral Rna And Proteins To The Vertebrate Neuronal Cells, Wenshuo Zhou, Michael Woodson, Biswas Neupane, Fengwei Bai, Michael B. Sherman, Kyung H. Choi, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Molecular determinants and mechanisms of arthropod-borne flavivirus transmission to the vertebrate host are poorly understood. In this study, we show for the first time that a cell line from medically important arthropods, such as ticks, secretes extracellular vesicles (EVs) including exosomes that mediate transmission of flavivirus RNA and proteins to the human cells. Our study shows that tick-borne Langat virus (LGTV), a model pathogen closely related to tick-borne encephalitis virus (TBEV), profusely uses arthropod exosomes for transmission of viral RNA and proteins to the human- skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed the presence of purified arthropod/neuronal exosomes …

Cytolytic Toxin Production By Staphylococcus Aureus Is Dependent Upon The Activity Of The Protoheme Ix Farnesyltransferase, Emily Stevens, Maisem Laabei, Stewart Gardner, Greg A. Somerville, Ruth C. Massey

School of Veterinary and Biomedical Sciences: Faculty Publications

Staphylococcus aureus is a medically important pathogen with an abundance of virulence factors that are necessary for survival within a host, including the production of cytolytic toxins. The regulation of toxin production is mediated by the Agr quorum sensing system, and a poorly defined post-exponential growth phase signal independent of Agr. As part of a recent genome wide association study (GWAS) to identify novel loci that alter the expression of cytolytic toxins, a polymorphism in the cyoE gene, which encodes a protoheme IX farnesyltransferase, was identified. This enzyme is essential for processing heme into the electron transport chain for use …

Portulaca Oleracea Extract Can Inhibit Nodule Formation Of Colon Cancer Stem Cells By Regulating Gene Expression Of Notch Signal Transduction Pathway, Li Chen

Dissertations, Master's Theses and Master's Reports

The main aim of this study was to investigate the effects of Portulaca oleracea extract on tumor formation in colon cancer stem cells and chemotherapy sensitivity. In addition, this study analyzed the genetic changes within the Notch signal transduction pathway associated with the effects of the extracts. Serum-free cultures of colon cancer cells (HT-29) and HT-29 stem cells were treated with the chemotherapeutic drug 5-FU to assess sensitivity. Injections of the stem cells were also given to BALB/c mice to confirm tumor growth and characteristics. In addition, the effect of different concentrations of P. oleracea extract was tested on the …

Toward Biochemical Conversion Of Lignocellulose On-Farm: Pretreatment And Hydrolysis Of Corn Stover In Situ, Alicia A. Modenbach, Sue E. Nokes, Michael D. Montross, Barbara L. Knutson

Biosystems and Agricultural Engineering Faculty Publications

High-solids lignocellulosic pretreatment using NaOH followed by high-solids enzymatic hydrolysis was evaluated for an on-farm biochemical conversion process. Increasing the solids loadings for these processes has the potential for increasing glucose concentrations and downstream ethanol production; however, sequential processing at high-solids loading similar to an on-farm cellulose conversion system has not been studied. This research quantified the effects of high-solids pretreatment with NaOH and subsequent high-solids enzymatic hydrolysis on cellulose conversion. As expected, conversion efficiency was reduced; however, the highest glucose concentration (40.2 g L^-1), and therefore the highest potential ethanol concentration, resulted from the high-solids combined pretreatment …

Sex Differences In The Subjective Effects Of Oral Δ9-Thc In Cannabis Users, Jessica S. Fogel, Thomas H. Kelly, Philip M. Westgate, Joshua A. Lile

Behavioral Science Faculty Publications

Previous studies suggest that there are sex differences in endocannabinoid function and the response to exogenous cannabinoids, though data from clinical studies comparing acute cannabinoid effects in men and women under controlled laboratory conditions are limited. To further explore these potential differences, data from 30 cannabis users (N=18 M, 12 F) who completed previous Δ⁹-tetrahydrocannabinol (Δ⁹-THC) discrimination studies were combined for this retrospective analysis. In each study, subjects learned to discriminate between oral Δ⁹-THC and placebo and then received a range of Δ⁹-THC doses (0, 5, 15 and a “high” dose of …

Micrornas Modulate Pathogenesis Resulting From Chlamydial Infection In Mice, Laxmi Yeruva, S. Pouncey, Michael R. Eledge, Sudeepa Bhattacharya, Chunqiao Luo, Erin W. Weatherford, David M. Ojcius, Roger G. Rank

All Dugoni School of Dentistry Faculty Articles

Not all women infected with chlamydiae develop upper genital tract disease, but the reason(s) for this remains undefined. Host genetics and hormonal changes associated with the menstrual cycle are possible explanations for variable infection outcomes. It is also possible that disease severity depends on the virulence of the chlamydial inoculum. It is likely that the inoculum contains multiple genetic variants, differing in virulence. If the virulent variants dominate, then the individual is more likely to develop severe disease. Based on our previous studies, we hypothesized that the relative degree of virulence of a chlamydial population dictates the microRNA (miRNA) expression …

Characterization Of Staphylococcal Nuclease And Tudor Domain Containing Protein 1 (Snd1) As A Molecular Target In Hepatocellular Carcinoma And Non-Alcoholic Steatohepatitis, Nidhi H. Jariwala

Theses and Dissertations

CHARACTERIZATION OF STAPHYLOCOCCAL NUCLEASE AND TUDOR DOMAIN CONTAINING PROTEIN 1 (SND1) AS A MOLECULAR TARGET IN HEPATOCELLULAR CARCINOMA AND NON-ALCOHOLIC STEATOHEPATITIS

Nidhi Jariwala, PhD

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Integrative Life Sciences

Virginia Commonwealth University, 2017

Devanand Sarkar, M.B.B.S., PhD.

Associate Professor, Department of Human and Molecular Genetics

Virginia Commonwealth University

Richmond, Virginia

SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). Oncoprotein SND1 regulates gene expression at a post-transcriptional level in multiple cancers including hepatocellular carcinoma (HCC). …

Study Of Molecular Interactions Of Glycosaminoglycans And Glycosaminoglycan Mimetics With Their Protein Targets, Daniel K. Afosah

Theses and Dissertations

Glycosaminoglycans (GAGs) are complex linear chain carbohydrate molecules found on virtually all animal cell surfaces. Owing to their negatively charged nature, GAGs interact with a number of different proteins. Thus, although they have great potential as therapeutic agents, their apparent promiscuous interactions increase their side effect risk. GAG mimetics, including GAG oligosaccharides and non-saccharide GAG mimetics (NSGMs) are viable approaches to address this. This work discusses sulfated benzofuran thrombin inhibitors with submaximal protease inhibition, sulfated diflavonoid inhibitors of plasmin and GAG oligosaccharides with selectivity for human neutrophil elastase (HNE).

Anticoagulants are very important for the treatment of thrombotic diseases. The …

Rapid Typing Of Mannheimia Haemolytica Major Genotypes 1 And 2 Using Maldi-Tof Mass Spectrometry, John Dustin Loy, Michael L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

Genotype 2 M. haemolytica predominantly associate over genotype 1 with the lungs of cattle with respiratory disease and ICEs containing antimicrobial resistance genes. Distinct protein masses were detected by MALDI-TOF MS between genotype 1 and 2 strains. MALDI-TOF MS could rapidly differentiate genotype 2 strains in veterinary diagnostic laboratories.

Efficacy Of Urtoxazumab (Tma-15 Humanized Monoclonal Antibody Specific For Shiga Toxin 2) Against Post-Diarrheal Neurological Sequelae Caused By Escherichia Coli O157:H7 Infection In The Neonatal Gnotobiotic Piglet Model, Rodney A. Moxley, David H. Francis, Mizuho Tamura, David B. Marx, Kristina Santiago-Mateo, Mojun Zhao

School of Veterinary and Biomedical Sciences: Faculty Publications

Enterohemorrhagic Escherichia coli (EHEC) is the most common cause of hemorrhagic colitis and hemolytic uremic syndrome in human patients, with brain damage and dysfunction the main cause of acute death. We evaluated the efficacy of urtoxazumab (TMA-15, Teijin Pharma Limited), a humanized monoclonal antibody against Shiga toxin (Stx) 2 for the prevention of brain damage, dysfunction, and death in a piglet EHEC infection model. Forty-five neonatal gnotobiotic piglets were inoculated orally with 3 x 10⁹ colony-forming units of EHEC O157:H7 strain EDL933 (Stx1⁺, Stx2⁺) when 22–24 h old. At 24 h post-inoculation, piglets were intraperitoneally …

Branched Chain Α-Ketoacid Dehydrogenase Kinase 111–130, A T Cell Epitope That Induces Both Autoimmune Myocarditis And Hepatitis In A/J Mice, Bharathi Krishnan, Chandirasegara Massilamany, Rakesh H. Basavalingappa, Arunakumar Gangaplara, Guobin Kang, Qingsheng Li, Francisco A. Uzal, Jennifer L. Strande, Gustavo A. Delhon, Jean-Jack Riethoven, David J. Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Introduction: Organ-specific autoimmune diseases are believed to result from immune responses generated against self-antigens specific to each organ. However, when such responses target antigens expressed promiscuously in multiple tissues, then the immune-mediated damage may be wide spread.

Methods: In this report, we describe a mitochondrial protein, branched chain α-ketoacid dehydrogenase kinase (BCKD_k) that can act as a target autoantigen in the development of autoimmune inflammatory reactions in both heart and liver.

Results: We demonstrate that BCKD_k protein contains at least nine immunodominant epitopes, three of which, BCKD_k 71–90, BCKD_k 111–130 and BCKD_k 141–160, …

Β1-Adrenergic Receptor Contains Multiple IaK And IeK Binding Epitopes That Induce T Cell Responses With Varying Degrees Of Autoimmune Myocarditis In A/J Mice, Rakesh H. Basavalingappa, Chandirasegaran Massilamany, Bharathi Krishnan, Arunakumar Gangaplara, Rajkumar A. Rajasekaran, Muhammad Z. Afzal, Jean-Jack Riethoven, Jennifer L. Strande, David J. Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Myocarditis/dilated cardiomyopathy (DCM) patients can develop autoantibodies to various cardiac antigens and one major antigen is β1-adrenergic receptor (β₁AR). Previous reports indicate that animals immunized with a β₁AR fragment encompassing, 197–222 amino acids for a prolonged period can develop DCM by producing autoantibodies, but existence of T cell epitopes, if any, were unknown. Using A/J mice that are highly susceptible to lymphocytic myocarditis, we have identified β₁AR 171–190, β₁AR 181–200, and β₁AR 211–230 as the major T cell epitopes that bind major histocompatibility complex class II/IA^k or IE^{k …}

The Effect Of Feed Form On Diet Digestibility And Cecal Parameters In Rabbits, Isabella Corsato Alvarenga, Charles Gregory Aldrich, Micah Kohles

School of Veterinary and Biomedical Sciences: Faculty Publications

Fifteen New Zealand rabbits were randomly assigned to one of 3 dietary treatment groups of 5 animals each and fed pelleted, extruded, or muesli diets in a completely randomized design experiment. Rabbits were placed in individual cages with ad libitum access to water and food for 45 days acclimation followed by 30 days experimental period. Feed intake of rabbits fed pelleted and extruded diets was greater (p < 0.05) than rabbits fed the muesli diet (125.6 and 130.4 vs. 91.9 g/d), but weight change and feed efficiency were not affected by treatment. Diet digestibility among the treatments was inconsistent when comparing results obtained from total fecal collection and AIA (please define) as an internal marker. Rabbits fed extruded and pelleted diets had lower (p < 0.05) cecal pH (6.42 and 6.38 vs. 7.02, respectively), and higher (p < 0.05) production of SCFA (18.5 and 19.0 vs. 11.7 mM, respectively) than those fed muesli. The fermentation products from rabbits fed pelleted and extruded diets had a greater proportion of butyrate and less propionate than rabbits fed muesli. The results of this study indicate that the basal dietary composition had a greater impact on diet utilization and cecal fermentation than food form.

Mechanistic Understanding Of N-Glycosylation In Ebola Virus Glycoprotein Maturation And Function, Bin Wang, Yujie Wang, Dylan A. Frabutt, Xihe Zhang, Xiaoyu Yao, Dan Hu, Zhuo Zhang, Chaonan Liu, Shimin Zheng, Shi-Hua Xiang, Yong-Hui Zheng

School of Veterinary and Biomedical Sciences: Faculty Publications

The Ebola virus (EBOV) trimeric envelope glycoprotein (GP) precursors are cleaved into the receptor-binding GP₁ and the fusion-mediating GP₂ subunits and incorporated into virions to initiate infection. GP₁ and GP₂ form heterodimers that have 15 or two N-glycosylation sites (NGSs), respectively. Here we investigated the mechanism of how N-glycosylation contributes to GP expression, maturation, and function. As reported before, we found that, although GP₁ NGSs are not critical, the two GP₂ NGSs, Asn⁵⁶³ and Asn⁶¹⁸, are essential for GP function. Further analysis uncovered that Asn⁵⁶³ and Asn^{618 …}

A Novel Role Of Silibinin As A Putative Epigenetic Modulator In Human Prostate Carcinoma, Ioannis Anestopoulos, Aristeidis P. Sfakianos, Rodrigo Franco, Katerina Chlichlia, Mihalis I. Panayiotidis, David J. Kroll, Aglaia Pappa

School of Veterinary and Biomedical Sciences: Faculty Publications

Silibinin, extracted from milk thistle (Silybum marianum L.), has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin’s pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2) members Enhancer of Zeste Homolog 2 (EZH2), Suppressor of Zeste Homolog 12 (SUZ12), and Embryonic Ectoderm Development (EED) in DU145 and PC3 human prostate cancer cells, …