Open Access. Powered by Scholars. Published by Universities.®
- Institution
-
- The Texas Medical Center Library (10579)
- TÜBİTAK (1464)
- Thomas Jefferson University (1300)
- University of Nebraska - Lincoln (816)
- University of Kentucky (811)
-
- University of Alabama at Birmingham (789)
- Dartmouth College (448)
- University of Nebraska Medical Center (411)
- Touro College and University System (386)
- LSU Health New Orleans (366)
- Virginia Commonwealth University (329)
- Chulalongkorn University (303)
- Zucker School of Medicine at Hofstra/Northwell (290)
- Chapman University (285)
- Marshall University (273)
- Wright State University (263)
- University of South Carolina (256)
- University of Tennessee Health Science Center (229)
- Himmelfarb Health Sciences Library, The George Washington University (174)
- Loma Linda University (169)
- Rowan University (163)
- Edith Cowan University (162)
- Wayne State University (161)
- Old Dominion University (152)
- University of South Florida (128)
- City University of New York (CUNY) (119)
- University of Central Florida (118)
- Marquette University (113)
- Children's Mercy Kansas City (107)
- University of Texas Rio Grande Valley (107)
- Keyword
-
- Humans (7186)
- Animals (3428)
- Female (2693)
- Mice (2433)
- Male (2333)
-
- Adult (1091)
- Middle Aged (1010)
- Aged (855)
- Tumor (820)
- Doctor of Philosophy (PhD) Heersink School of Medicine (746)
- Cell Line (692)
- Mutation (673)
- Child (654)
- Neoplasms (651)
- Cell Line, Tumor (570)
- Biomarkers (566)
- Receptors (531)
- Carcinoma (497)
- Animal (480)
- Inbred C57BL (474)
- Inflammation (474)
- Signal Transduction (470)
- Mice, Inbred C57BL (465)
- Adolescent (460)
- Immunotherapy (460)
- Gene Expression Regulation (456)
- Tumor Microenvironment (421)
- RNA (416)
- Disease Models, Animal (414)
- Cancer (411)
- Publication Year
- Publication
-
- Faculty, Staff and Student Publications (5431)
- Faculty, Staff and Students Publications (4199)
- Turkish Journal of Medical Sciences (1464)
- All ETDs from UAB (785)
- Dartmouth Scholarship (439)
-
- School of Veterinary and Biomedical Sciences: Faculty Publications (329)
- Theses and Dissertations (300)
- Journal Articles (293)
- Chulalongkorn University Theses and Dissertations (Chula ETD) (288)
- Department of Pathology, Anatomy, and Cell Biology Faculty Papers (288)
- InTouch (277)
- Nebraska Center for Virology: Faculty Publications (265)
- Theses and Dissertations (ETD) (217)
- Department of Biochemistry and Molecular Biology Faculty Papers (209)
- Children’s Nutrition Research Center Staff Publications (208)
- School of Medicine Faculty Publications (202)
- Dissertations and Theses (Open Access) (201)
- Electronic Theses and Dissertations (189)
- Journal Articles: Biochemistry & Molecular Biology (187)
- Duncan NRI Faculty and Staff Publications (174)
- Pharmacy Faculty Articles and Research (163)
- Loma Linda University Electronic Theses, Dissertations & Projects (152)
- The Brown Foundation: Institute of Molecular Medicine (144)
- Biological Sciences Faculty Publications (131)
- Journal of the South Carolina Academy of Science (129)
- Center for Medical Ethics and Health Policy Staff Publications (118)
- Microbiology, Immunology, and Tropical Medicine Faculty Publications (107)
- Theses, Dissertations and Capstones (104)
- Manuscripts, Articles, Book Chapters and Other Papers (102)
- Microbiology, Immunology, and Molecular Genetics Faculty Publications (102)
- Publication Type
- File Type
Articles 22711 - 22740 of 24678
Full-Text Articles in Entire DC Network
Matrix Metalloproteinase Inhibitor, Cts-1027, Attenuates Liver Injury And Fibrosis In The Bile Duct-Ligated Mouse., Alisan Kahraman, Steven F. Bronk, Sophie Cazanave, Nathan W. Werneburg, Justin L. Mott, Patricia C. Contreras, Gregory J. Gores
Matrix Metalloproteinase Inhibitor, Cts-1027, Attenuates Liver Injury And Fibrosis In The Bile Duct-Ligated Mouse., Alisan Kahraman, Steven F. Bronk, Sophie Cazanave, Nathan W. Werneburg, Justin L. Mott, Patricia C. Contreras, Gregory J. Gores
Journal Articles: Biochemistry & Molecular Biology
Aim: Excessive matrix metalloproteinase (MMP) activity has been implicated in the pathogenesis of acute and chronic liver injury. CTS-1027 is an MMP inhibitor, which has previously been studied in humans as an anti-arthritic agent. Thus, our aim was to assess if CTS-1027 is hepato-protective and anti-fibrogenic during cholestatic liver injury. Methods: C57/BL6 mice were subjected to bile duct ligation (BDL) for 14 days. Either CTS-1027 or vehicle was administered by gavage. Results: BDL mice treated with CTS-1027 demonstrated a threefold reduction in hepatocyte apoptosis as assessed by the TUNEL assay or immunohistochemistry for caspase 3/7-positive cells as compared to vehicle-treated …
Micrornas Involved In Tumor Suppressor And Oncogene Pathways: Implications For Hepatobiliary Neoplasia., Justin L. Mott
Micrornas Involved In Tumor Suppressor And Oncogene Pathways: Implications For Hepatobiliary Neoplasia., Justin L. Mott
Journal Articles: Biochemistry & Molecular Biology
MicroRNAs are a class of small regulatory RNAs that function to modulate protein expression. This control allows for fine-tuning of the cellular phenotype, including regulation of proliferation, cell signaling, and apoptosis; not surprisingly, microRNAs contribute to liver cancer biology. Recent investigations in human liver cancers and tumor-derived cell lines have demonstrated decreased or increased expression of particular microRNAs in hepatobiliary cancer cells. Based on predicted and validated protein targets as well as functional consequences of altered expression, microRNAs with decreased expression in liver tumor cells may normally aid in limiting neoplastic transformation. Conversely, selected microRNAs that are up-regulated in liver …
An Iterative Strategy Combining Biophysical Criteria And Duration Hidden Markov) Models For Structural Predictions Of Chlamydia Trachomatis S66 Promoters, Ronna R. Mallios, David M. Ojcius, David H. Ardell
An Iterative Strategy Combining Biophysical Criteria And Duration Hidden Markov) Models For Structural Predictions Of Chlamydia Trachomatis S66 Promoters, Ronna R. Mallios, David M. Ojcius, David H. Ardell
All Dugoni School of Dentistry Faculty Articles
Background: Promoter identification is a first step in the quest to explain gene regulation in bacteria. It has been demonstrated that the initiation of bacterial transcription depends upon the stability and topology of DNA in the promoter region as well as the binding affinity between the RNA polymerase σ-factor and promoter. However, promoter prediction algorithms to date have not explicitly used an ensemble of these factors as predictors. In addition, most promoter models have been trained on data from Escherichia coli. Although it has been shown that transcriptional mechanisms are similar among various bacteria, it is quite possible that the …
Didox Modulates Reactive Oxygen Species Production And Inflammatory Events Induced By Lipopolysaccharide (Lps) And Aryl Hydrocarbon Receptor (Ahr) Ligands In Raw 264.7 Murine Macrophages., Thabe Matsebatlela
All Dissertations
Aberrant activation of macrophages during inflammation results in oxidative burst release of reactive oxygen and reactive nitrogen species (ROS/RNS) which are widely accepted to participate in pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing. It is demonstrated here that Didox (3,4-Dihydroxybenzohydroxamic acid) possesses antioxidative and anti-inflammatory properties that can protect against inflammation and oxidative stress induced by lipopolysaccharide (LPS) and aryl hydrocarbon receptor (AHR) ligands (PCB126, E804, and IO) in Raw 264.7 murine macrophages. In brief, it is demonstrated here that Didox inhibits LPS-induced oxidative stress, …
Intra-Tumor Heterogeneity Of Mlh1 Promoter Methylation Revealed By Deep Single Molecule Bisulfite Sequencing., Katherine E Varley, David G Mutch, Tina B Edmonston, Paul J Goodfellow, Robi D Mitra
Intra-Tumor Heterogeneity Of Mlh1 Promoter Methylation Revealed By Deep Single Molecule Bisulfite Sequencing., Katherine E Varley, David G Mutch, Tina B Edmonston, Paul J Goodfellow, Robi D Mitra
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
A single tumor may contain cells with different somatic mutations. By characterizing this genetic heterogeneity within tumors, advances have been made in the prognosis, treatment and understanding of tumorigenesis. In contrast, the extent of epigenetic intra-tumor heterogeneity and how it influences tumor biology is under-explored. We have characterized epigenetic heterogeneity within individual tumors using next-generation sequencing. We used deep single molecule bisulfite sequencing and sample-specific DNA barcodes to determine the spectrum of MLH1 promoter methylation across an average of 1000 molecules in each of 33 individual samples in parallel, including endometrial cancer, matched blood and normal endometrium. This first glimpse, …
Chaperone Expression And Effects Of Its Inhibition On Breast Cancer Sensitization, Malissa Diehl
Chaperone Expression And Effects Of Its Inhibition On Breast Cancer Sensitization, Malissa Diehl
Theses and Dissertations
Breast cancer is one of the most prevalent and deadly forms of cancer in women and is not restricted by race or ethnicity. Although a wealth of knowledge has been amassed on the biology of breast cancer, including its risk factors, diagnosis, prognosis, prevention, and treatment, it remains a serious health concern and active area of research. Initial response to standard chemotherapeutic and radiotherapeutic regimens is generally strong for many patients, yet breast tumors often recur, leading to more aggressive and resistant tumors. Because recurrence is such a clinical issue, more effective therapeutic approaches are needed to eliminate partial clinical …
Chaperone Association With Telomere Binding Proteins, Amy Depcrynski
Chaperone Association With Telomere Binding Proteins, Amy Depcrynski
Theses and Dissertations
The Hsp90 chaperone complex associates with the telomerase enzyme, facilitating the assembly of the ribonucleoprotein complex. While previous data from our laboratory indicate that Hsp90 and p23 remain stably associated with (functionally active) telomerase, more recent experiments suggest that these chaperones associate with telomeres independent of telomerase, presumably through a specific interaction with telomere binding proteins. The current study examines the novel interactions between TRF2, TRF1, TIN2 and TPP1 and molecular chaperones (Hsp90, Hsp70, p23). In vitro and in cell experiments have shown an interaction between TRF1 and TRF2 and the molecular chaperones Hsp90 and Hsp70. Inhibition of Hsp90 using …
Exploring The Methylation Status Of Rai1 And The Rai1 Consensus Binding Sequence, Eri Kamura
Exploring The Methylation Status Of Rai1 And The Rai1 Consensus Binding Sequence, Eri Kamura
Theses and Dissertations
Smith Magenis Syndrome (SMS) is a multiple congenital anomalies/ mental retardation disorder caused by deletion or mutation of the RAI1 gene on chromosome 17p11.2. The majority of patients with SMS phenotypes have a deletion or mutation of RAI1. However, some patients have been observed with SMS-like phenotypes and yet have no deletions or mutations in the RAI1 gene. One possible explanation could be aberrant methylation of RAI1 since RAI1 is present and yet may be silenced. In order to study this possibility, patient cell lines were treated with 5-Aza-2’-deoxycytidine. RNA was extracted and real-time PCR was used to check the …
Retinoic Acid Induced 1 Gene Analysis In Humans And Zebrafish, Bijal Vyas
Retinoic Acid Induced 1 Gene Analysis In Humans And Zebrafish, Bijal Vyas
Theses and Dissertations
Smith-Magenis syndrome (SMS) is a complex mental retardation syndrome caused by deletion of 17p11.2 region or mutation of the RAI1 gene (retinoic acid induced 1). Individuals with SMS typically exhibit speech and motor delays, mental retardation, characteristic craniofacial and skeletal anomalies, and a distinct neurobehavioral phenotype that includes sleep disturbances, stereotypes, and maladaptive and self-injurious behaviors. RAI1 is thought to be a transcription factor modulating the expression of genes involved in a variety of cellular functions. Previous studies have shown the RAI1 gene being induced by retinoic acid (RA), a derivative of vitamin A. RA plays a significant role in …
Lipid Nanoparticles With Accessible Nickel As A Vaccine Delivery System For Single And Multiple His-Tagged Hiv Antigens, Weili Yan, Anekant Jain, Ronan O'Carra, Jerold Woodward, Wenxue Li, Guanhan Li, Avindra Nath, Russell J. Mumper
Lipid Nanoparticles With Accessible Nickel As A Vaccine Delivery System For Single And Multiple His-Tagged Hiv Antigens, Weili Yan, Anekant Jain, Ronan O'Carra, Jerold Woodward, Wenxue Li, Guanhan Li, Avindra Nath, Russell J. Mumper
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Lipid-based nanoparticles (NPs) with a small amount of surface-chelated nickel (Ni-NPs) were developed to easily formulate the HIV his-tagged Tat protein, as well as to formulate and co-deliver two HIV antigens (his-p24 and his-Nef) on one particle. Female BALB/c mice were immunized by s.c. injection with his-Tat/Ni-NP formulation (1.5 μg Tat-his/mouse) and control formulations on day 0 and 14. The day 28 anti-Tat specific IgG titer with his-Tat/Ni-NP was significantly greater than that with Alum/his-Tat. Furthermore, splenocytes from his-Tat/Ni-NP immunized mice secreted significantly higher IFN-γ than those from mice immunized with Alum/his-Tat. Although Ni-NPs did not show better adjuvant activity …
Dna-Binding By Haemophilus Influenzae And Escherichia Coli Ybab, Members Of A Widely-Distributed Bacterial Protein Family, Anne E. Cooley, Sean P. Riley, Keith Kral, M. Clarke Miller, Edward Demoll, Michael G. Fried, Brian Stevenson
Dna-Binding By Haemophilus Influenzae And Escherichia Coli Ybab, Members Of A Widely-Distributed Bacterial Protein Family, Anne E. Cooley, Sean P. Riley, Keith Kral, M. Clarke Miller, Edward Demoll, Michael G. Fried, Brian Stevenson
Microbiology, Immunology, and Molecular Genetics Faculty Publications
BACKGROUND: Genes orthologous to the ybaB loci of Escherichia coli and Haemophilus influenzae are widely distributed among eubacteria. Several years ago, the three-dimensional structures of the YbaB orthologs of both E. coli and H. influenzae were determined, revealing a novel "tweezer"-like structure. However, a function for YbaB had remained elusive, with an early study of the H. influenzae ortholog failing to detect DNA-binding activity. Our group recently determined that the Borrelia burgdorferi YbaB ortholog, EbfC, is a DNA-binding protein. To reconcile those results, we assessed the abilities of both the H. influenzae and E. coli YbaB proteins to bind DNA …
Enzymatic Regulation Of Opioid Antinociception And Tolerance, Lynn Hull
Enzymatic Regulation Of Opioid Antinociception And Tolerance, Lynn Hull
Theses and Dissertations
ENZYMATIC REGULATION OF OPIOID ANTINOCICEPTION AND TOLERANCE By Lynn C. Hull, Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2009 Director: William L. Dewey, Ph.D. Department of Pharmacology and Toxicology The involvement of kinases in opioid actions has long been established. The acute actions of opioids, through the Gi/Go G-proteins, cause the inhibition of adenylyl cyclase and therefore a decrease in protein kinase A (PKA) activation. Additionally, acute opioid administration may cause the G-protein to activate the phospholipase C (PLC)-mediated cascade leading to the …
R992c (P.R1192c) Substitution In Collagen Ii Alters The Structure Of Mutant Molecules And Induces The Unfolded Protein Response., Hye Jin Chung, Deborah A. Jensen, Katarzyna Gawron, Andrzej Steplewski, Andrzej Fertala
R992c (P.R1192c) Substitution In Collagen Ii Alters The Structure Of Mutant Molecules And Induces The Unfolded Protein Response., Hye Jin Chung, Deborah A. Jensen, Katarzyna Gawron, Andrzej Steplewski, Andrzej Fertala
Department of Dermatology and Cutaneous Biology Faculty Papers
We investigated the molecular bases of spondyloepiphyseal dysplasia (SED) associated with the R992C (p.R1192C) substitution in collagen II. At the protein level, we analyzed the structure and integrity of mutant molecules, and at the cellular level, we specifically studied the effects of the presence of the R992C collagen II on the biological processes taking place in host cells. Our studies demonstrated that mutant collagen II molecules were characterized by altered electrophoretic mobility, relatively low thermostability, the presence of atypical disulfide bonds, and slow rates of secretion into the extracellular space. Analyses of cellular responses to the presence of the mutant …
Nanofiber Scaffolds With Gradations In Mineral Content For Mimicking The Tendon-To-Bone Insertion Site, Xiaoran Li, Jingwei Xie, Justin Lipner, Xiaoyan Yuan, Stavros Thomopoulos, Younan Xia
Nanofiber Scaffolds With Gradations In Mineral Content For Mimicking The Tendon-To-Bone Insertion Site, Xiaoran Li, Jingwei Xie, Justin Lipner, Xiaoyan Yuan, Stavros Thomopoulos, Younan Xia
MIIR Faculty Research
We have demonstrated a simple and versatile method for generating a continuously graded, bonelike calcium phosphate coating on a nonwoven mat of electrospun nanofibers. A linear gradient in calcium phosphate content could be achieved across the surface of the nanofiber mat. The gradient had functional consequences with regard to stiffness and biological activity. Specifically, the gradient in mineral content resulted in a gradient in the stiffness of the scaffold and further influenced the activity of mouse preosteoblast MC3T3 cells. This new class of nanofiberbased scaffolds can potentially be employed for repairing the tendon-to-bone insertion site via a tissue engineering approach.
Use Of Phage Display To Isolate Specifi C Human Monoclonal Antibody Fragments Against A Potential Target For Multiple Myeloma, Pei Xiong Liew, Feng Ge, Charles A. Gullo, Gerrard Kh Teoh, William Yk Hwang
Use Of Phage Display To Isolate Specifi C Human Monoclonal Antibody Fragments Against A Potential Target For Multiple Myeloma, Pei Xiong Liew, Feng Ge, Charles A. Gullo, Gerrard Kh Teoh, William Yk Hwang
Biochemistry and Microbiology
Introduction: Multiple myeloma (MM), a malignancy of plasma cells, accounts for 10% of all haematological malignancies and is currently incurable. Although it can be treated, the disease tends to relapse after several years and becomes increasingly resistant to conventional therapy. Investigations into using humoral therapy for MM are now underway with a view that novel therapeutic agents may provide a more targeted therapy for MM.
Materials and Methods: Here, phage display, a faster and more efficient method compared to classical hybridoma fusion technology, was used as a proof-of-concept to isolate several single-chain Fragment variables (scFv) against Ku86.
Results …
Aging-Associated Dysfunction Of Akt/Protein Kinase B: S-Nitrosylation And Acetaminophen Intervention, Miaozong Wu, Anjaiah Katta, Murali K. Gadde, Hua Liu, Sunil K. Kakarla, Jacqueline Fannin, Satyanarayana Paturi, Ravi K. Arvapalli, Kevin M. Rice, Yeling Wang, Eric R. Blough
Aging-Associated Dysfunction Of Akt/Protein Kinase B: S-Nitrosylation And Acetaminophen Intervention, Miaozong Wu, Anjaiah Katta, Murali K. Gadde, Hua Liu, Sunil K. Kakarla, Jacqueline Fannin, Satyanarayana Paturi, Ravi K. Arvapalli, Kevin M. Rice, Yeling Wang, Eric R. Blough
MIIR Faculty Research
Background: Aged skeletal muscle is characterized by an increased incidence of metabolic and functional disorders, which if allowed to proceed unchecked can lead to increased morbidity and mortality. The mechanism(s) underlying the development of these disorders in aging skeletal muscle are not well understood. Protein kinase B (Akt/PKB) is an important regulator of cellular metabolism and survival, but it is unclear if aged muscle exhibits alterations in Akt function. Here we report a novel dysfunction of Akt in aging muscle, which may relate to S-nitrosylation and can be prevented by acetaminophen intervention.
Principal Findings: Compared to 6- and 27-month rats, …
The Effect Of Endothelin-1 On The Expression Of Cdk Inhibitors P21 & P27 In Bovine Corneal Endothelial Cells, Lakshmi Reddy Bollu
The Effect Of Endothelin-1 On The Expression Of Cdk Inhibitors P21 & P27 In Bovine Corneal Endothelial Cells, Lakshmi Reddy Bollu
Masters Theses & Specialist Projects
Mammalian corneal endothelial cells are considered to be non-proliferative due to the arrest of cells at the G1 phase of the cell cycle. The purpose of this study was to determine whether the down regulation of cyclin dependant kinase inhibitors (p21cip1 and p27kip1) levels by Endothelin-1 (ET-1), would overcome the G1 phase arrest and promote cell cycle progression and proliferation in cultured BCECs (Bovine corneal endothelial cells). BCECs were isolated from bovine corneas and cultured in DMEM supplemented with 10% serum. 5-Bromo 2-deoxy Uridine (BrdU) incorporation was determined in serum starved cultures in 24-well plates as a measure of cell …
Triptolide Is A Potential Therapeutic Agent For Alzheimer’S Disease, Matthew Allsbrook
Triptolide Is A Potential Therapeutic Agent For Alzheimer’S Disease, Matthew Allsbrook
Theses and Dissertations
Mounting evidence indicates an involvement of inflammation in the pathogenesis of Alzheimer’s disease. While there are other mechanisms involved, it is this role of inflammatory processes that we wish to investigate. Triptolide is the major constituent in the Chinese herb, Tripterygium wilfordii Hook F, and has been used for centuries as part of Chinese herbal medicine. The four ringed structure has close homology to drugs of the steroid class and it has been shown to be beneficial as an anti-inflammatory for rheumatoid arthritis and for treatment of certain cancers. The aim of this study was to evaluate the potential therapeutic …
Section Abstracts: Medical Sciences
Section Abstracts: Medical Sciences
Virginia Journal of Science
Abstracts of the Medical Science Section for the 87th Annual Meeting of the Virginia Academy of Science, May 27-29, 2009, Virginia Commonwealth University, Richmond, Virginia.
Native Cellular Architecture Of Treponema Denticola Revealed By Cryo-Electron Tomography, Jacques Izard, Chyong-Ere Hsieh, Ronald J. Limberger, Carmen A. Mannella, Michael Marko
Native Cellular Architecture Of Treponema Denticola Revealed By Cryo-Electron Tomography, Jacques Izard, Chyong-Ere Hsieh, Ronald J. Limberger, Carmen A. Mannella, Michael Marko
Department of Food Science and Technology: Faculty Publications
Using cryo-electron tomography, we are developing a refined description of native cellular structures in the pathogenic spirochete Treponema denticola. Tightly organized bundles of periplasmic flagella were readily observed in intact plunge-frozen cells. The periplasmic space was measured in both wild-type and aflagellate strains, and found to widen by less than the diameter of flagella when the latter are present. This suggests that a structural change occurs in the peptidoglycan layer to accommodate the presence of the flagella. In dividing cells, the flagellar filaments were found to bridge the cytoplasmic cylinder constriction site. Cytoplasmic filaments, adjacent to the inner membrane, …
Nerve Injection Of Viral Vectors Efficiently Transfers Transgenes Into Motor Neurons And Delivers Rnai Therapy Against Als., Rui Wu, Hongyan Wang, Xugang Xia, Hongxia Zhou, Chunyan Liu, Maria Castro, Zuoshang Xu
Nerve Injection Of Viral Vectors Efficiently Transfers Transgenes Into Motor Neurons And Delivers Rnai Therapy Against Als., Rui Wu, Hongyan Wang, Xugang Xia, Hongxia Zhou, Chunyan Liu, Maria Castro, Zuoshang Xu
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
RNA interference (RNAi) mediates sequence-specific gene silencing, which can be harnessed to silencing disease-causing genes for therapy. Particularly suitable diseases are those caused by dominant, gain-of-function type of gene mutations. In these diseases, the mutant gene generates a mutant protein or RNA product, which possesses toxic properties that harm cells. By silencing the mutant gene, the toxicity can be lessened because the amount of the toxic product is lowered in cells. In this report, we tested RNAi therapy in a mouse model for amyotrophic lateral sclerosis (ALS), which causes motor neuron degeneration, paralysis, and death. We used a transgenic model …
Transcriptional, Epigenetic, And Signal Events In Antifolate Therapeutics, Alexandra Racanelli
Transcriptional, Epigenetic, And Signal Events In Antifolate Therapeutics, Alexandra Racanelli
Theses and Dissertations
A targeted approach to the development of antifolate therapies has been sought for many years. Central to the success of such development is an understanding of the molecular mechanisms dictating the sensitivity of cells to antifolates and the fundamental differences of these processes between normal and neoplastic phenotypes. This dissertation addressed transcriptional mechanisms and cell-signaling events responsible for the efficacy of antifolate therapies. Transcriptional processes and cell signaling pathways are often aberrant in neoplastic tissues, providing a potential point of distinction between a normal and neoplastic cellular state. Folylpolyglutamate synthetase (FPGS) catalyzes the formation of poly-γ-glutamate derivatives of folates and …
Kinetics And Phenotype Of Vaccine-Induced Cd8+ T-Cell Responses To Toxoplasma Gondii, Kimberly A. Jordan, Emma H. Wilson, Elia D. Tait, Barbara A. Fox, David S. Roos, David J. Bzik
Kinetics And Phenotype Of Vaccine-Induced Cd8+ T-Cell Responses To Toxoplasma Gondii, Kimberly A. Jordan, Emma H. Wilson, Elia D. Tait, Barbara A. Fox, David S. Roos, David J. Bzik
Dartmouth Scholarship
Multiple studies have established that the ability of CD8+ T cells to act as cytolytic effectors and produce gamma interferon is important in mediating resistance to the intracellular parasite Toxoplasma gondii. To better understand the generation of the antigen-specific CD8+ T-cell responses induced by T. gondii, mice were immunized with replication-deficient parasites that express the model antigen ovalbumin (OVA). Class I tetramers specific for SIINFEKL were used to track the OVA-specific endogenous CD8+ T cells. The peak CD8+ T-cell response was found at day 10 postimmunization, after which the frequency and numbers of antigen-specific cells …
Roles Of Krüppel Like Factors Klf1, Klf2, And Klf4 In Embryonic Beta-Globin Gene Expression, Yousef Alhashem
Roles Of Krüppel Like Factors Klf1, Klf2, And Klf4 In Embryonic Beta-Globin Gene Expression, Yousef Alhashem
Theses and Dissertations
Krüppel like factors (KLFs) are a family of 17 proteins whose main function is gene regulation by binding to DNA elements in the promoters of various genes. KLF transcription factors recognize CACCC-elements and act as activators or repressors of the gene expression. Among the 17 family members, KLF1, KLF2, and KLF4 share high homology to each other. KLF1 is the founding member of the family and is an erythroid-specific protein. KLF2 is expressed in erythroid, endothelial, and other cells. KLF4 is expressed in endothelial, smooth muscle, and other cells. In this thesis, the functions of these KLFs were reviewed in …
A Truncation Mutation In Tbc1d4 In A Family With Acanthosis Nigricans And Postprandial Hyperinsulinemia, Satya Dash, Hiroyuki Sano, Justin J. Rochford, Robert K. Semple
A Truncation Mutation In Tbc1d4 In A Family With Acanthosis Nigricans And Postprandial Hyperinsulinemia, Satya Dash, Hiroyuki Sano, Justin J. Rochford, Robert K. Semple
Dartmouth Scholarship
Tre-2, BUB2, CDC16, 1 domain family member 4 (TBC1D4) (AS160) is a Rab-GTPase activating protein implicated in insulin-stimulated glucose transporter 4 (GLUT4) translocation in adipocytes and myotubes. To determine whether loss-of-function mutations in TBC1D4 might impair GLUT4 translocation and cause insulin resistance in humans, we screened the coding regions of this gene in 156 severely insulin-resistant patients. A female presenting at age 11 years with acanthosis nigricans and extreme postprandial hyperinsulinemia was heterozygous for a premature stop mutation (R363X) in TBC1D4. After demonstrating reduced expression of wild-type TBC1D4 protein and expression of the truncated protein in lymphocytes from the proband, …
A Dominant Loss-Of-Function Gja1 (Cx43) Mutant Impairs Parturition In The Mouse, Dan Tong, Xuerong Lu, Hong-Xing Wang, Isabelle Plante, Ed Lui, Dale W. Laird, Donglin Bai, Gerald M. Kidder
A Dominant Loss-Of-Function Gja1 (Cx43) Mutant Impairs Parturition In The Mouse, Dan Tong, Xuerong Lu, Hong-Xing Wang, Isabelle Plante, Ed Lui, Dale W. Laird, Donglin Bai, Gerald M. Kidder
Physiology and Pharmacology Publications
Expression of GJA1 (commonly known as connexin43 or Cx43), a major myometrial gap junction protein, is upregulated before the onset of delivery, suggesting an essential role for Cx43-mediated gap junctional intercellular communication (GJIC) in normal uterine contraction during parturition. To determine how a disease-linked Cx43 mutation affects myometrial function, we studied a mutant mouse model carrying an autosomal dominant mutation (Gja1Jrt) in the gene encoding Cx43 that displays features of the human genetic disease oculodentodigital dysplasia. We found that Cx43 level, specifically the phosphorylated species of the protein, is significantly reduced in the myometrium of the mutant mice (Gja1Jrt/+), as …
Death Receptor 5 Internalization Is Required For Lysosomal Permeabilization By Trail In Malignant Liver Cell Lines., Yuko Akazawa, Justin L. Mott, Steven F. Bronk, Nathan W. Werneburg, Alisan Kahraman, Maria Eugenia Guicciardi, Xue Wei Meng, Shigeru Kohno, Vijay H. Shah, Scott H. Kaufmann, Mark A. Mcniven, Gregory J. Gores
Death Receptor 5 Internalization Is Required For Lysosomal Permeabilization By Trail In Malignant Liver Cell Lines., Yuko Akazawa, Justin L. Mott, Steven F. Bronk, Nathan W. Werneburg, Alisan Kahraman, Maria Eugenia Guicciardi, Xue Wei Meng, Shigeru Kohno, Vijay H. Shah, Scott H. Kaufmann, Mark A. Mcniven, Gregory J. Gores
Journal Articles: Biochemistry & Molecular Biology
BACKGROUND & AIMS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) cytotoxicity in hepatocellular carcinoma cells is mediated by lysosomal permeabilization. Our aims were to determine which TRAIL receptor, death receptor (DR) 4 or DR5, mediates lysosomal permeabilization and assess whether receptor endocytosis followed by trafficking to lysosomes contributes in this process.
METHODS: TRAIL ligand internalization in Huh-7 cells was examined by confocal microscopy using Flag-tagged TRAIL, whereas DR4- and DR5-enhanced green fluorescent protein internalization was assessed by total internal reflection microscopy. Clathrin-dependent endocytosis was inhibited by expressing dominant negative dynamin.
RESULTS: Although Huh-7 cells express both TRAIL receptors, short hairpin RNA …
Revisiting Histidine-Dependent Acid Phosphatases: A Distinct Group Of Tyrosine Phosphatases., Suresh Veeramani, Ming-Shyue Lee, Ming-Fong Lin
Revisiting Histidine-Dependent Acid Phosphatases: A Distinct Group Of Tyrosine Phosphatases., Suresh Veeramani, Ming-Shyue Lee, Ming-Fong Lin
Journal Articles: Biochemistry & Molecular Biology
Although classical protein tyrosine phosphatase (PTP) superfamily members are cysteine-dependent, emerging evidence shows that many acid phosphatases (AcPs) function as histidine-dependent PTPs in vivo. These AcPs dephosphorylate phospho-tyrosine substrates intracellularly and could have roles in development and disease. In contrast to cysteine-dependent PTPs, they utilize histidine, rather than cysteine, for substrate dephosphorylation. Structural analyses reveal that active site histidine, but not cysteine, faces towards the substrate and functions as the phosphate acceptor. Nonetheless, during dephosphorylation, both histidine-dependent and cysteine-dependent PTPs use their active site arginine and aspartate for substrate binding and proton donation, respectively. Thus, we propose that they should …
Field Testing Adolescent Females For Cardiovascular Disease Risk, C. Jayne Brahler, Wesley R. Stephens, Betsy Donahoe Fillmore
Field Testing Adolescent Females For Cardiovascular Disease Risk, C. Jayne Brahler, Wesley R. Stephens, Betsy Donahoe Fillmore
Physical Therapy Faculty Publications
Over-fatness and poor cardiovascular (CV) fitness are well-documented risk factors for cardiovascular disease (CVD) in adults, but less is known about their association with disease risk in adolescents. This study aimed to determine the relationship between anthropometrics, fitness, and CVD risk.
Six anthropometric indicators of body fatness, seven measures of fitness, and seven metabolic and hemodynamic CVD risk factors were measured in a convenience sample of 28 female high school students (15-18 years of age). A tally was made of the number of factors for which each subject was outside the normal reference range (CVD risk).
Correlation analyses were completed …
Postprandial Effects Of Pecans Ingestion On Plasma Level Of Nutrients, Polyphenolic Compounds And Biomarkers Of Antioxidant Status In Human Volunteers, Chatrapa Hudthagosol
Postprandial Effects Of Pecans Ingestion On Plasma Level Of Nutrients, Polyphenolic Compounds And Biomarkers Of Antioxidant Status In Human Volunteers, Chatrapa Hudthagosol
Loma Linda University Electronic Theses, Dissertations & Projects
Pecans (Carya illinoinensis) are rich sources of polyphenolic compounds and nutrients, which have antioxidant capacity results in favorable reductions in plasma lipids and lipoproteins. However, the health benefits of pecans may not be limited to blood lipid changes. There has been very little investigation into the contribution of bioactive components found in nuts to antioxidant protection. The purposes of the study were 1) to determine the impact of pecan consumption on concentration of total plasma polyphenols and their peak concentration over time. 2) to measure the effect of a pecan diet on postprandial levels of plasma lipid peroxidation …