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Articles 10591 - 10620 of 11776
Full-Text Articles in Life Sciences
Role Of Msa In Immune Evasion, Persistence, And Protease Regulation In The Human Pathogenic Strains Of Staphylococcus Aureus, Maria Deepa Basco
Role Of Msa In Immune Evasion, Persistence, And Protease Regulation In The Human Pathogenic Strains Of Staphylococcus Aureus, Maria Deepa Basco
Dissertations
Opportunistic pathogens like Staphylococcus aureus on entering the host can stay colonized at the foci of infection or evade the immune system to disseminate to other sites. In this study we investigated the regulatory influence of the modulator of sarA (msa) on immune evasion and host persistence, employing the hospital-acquired strain S. aureus UAMS-1 and community-acquired strain S. aureus USA300 LAC. In the murine sepsis model, mutation of the msa gene in LAC showed no change in dissemination of infection; however, in UAMS-1 a decrease in microbial load was observed in the lungs. Differential regulation by the msa gene was …
Osmotic Stress, Not Aldose Reductase Activity, Directly Induces Growth Factors And Mapk Signaling Changes During Sugar Cataract Formation, Peng Zhang, Kuiyi Xing, James Randazzo, Karen Blessing, Marjorie F. Lou, Peter Kador
Osmotic Stress, Not Aldose Reductase Activity, Directly Induces Growth Factors And Mapk Signaling Changes During Sugar Cataract Formation, Peng Zhang, Kuiyi Xing, James Randazzo, Karen Blessing, Marjorie F. Lou, Peter Kador
School of Veterinary and Biomedical Sciences: Faculty Publications
In sugar cataract formation in rats, aldose reductase (AR) actitvity is not only linked to lenticular sorbitol (diabetic) or galactitol (galactosemic) formation but also to signal transduction changes, cytotoxic signals and activation of apoptosis. Using both in vitro and in vivo techniques, the interrelationship between AR activity, polyol (sorbitol and galactitol) formation, osmotic stress, growth factor induction, and cell signaling changes have been investigated. For in vitro studies, lenses from Sprague Dawley rats were cultured for up to 48 hrs in TC-199-bicarbonate media containing either 30 mM fructose (control), or 30 mM glucose or galctose with/without the aldose reductase inhibitors …
Alternations Of Nmda And Gabab Receptor Function In Development: A Potential Animal Model Of Schizophrenia, Monica Bolton
Alternations Of Nmda And Gabab Receptor Function In Development: A Potential Animal Model Of Schizophrenia, Monica Bolton
UNLV Theses, Dissertations, Professional Papers, and Capstones
Schizophrenia is a debilitating mental disorder that affects up to 3% of the world population. The behavioral symptoms are categorized into positive and negative symptoms, which appear during late adolescence/early adulthood. Unfortunately, the underlying cellular and molecular mechanisms of the disease are poorly understood. Several hypotheses exist to explain mechanisms contributing to these behavioral alterations. One model proposes that a reduced function of the NMDA glutamate receptor on specific GABAergic interneurons may be responsible for deficits in schizophrenia. Post-mortem investigations provide evidence of reductions in both glutamate and GABA-related proteins in patients with schizophrenia. Further, GABAergic interneurons that are activated …
Studies On Tracheorelaxant And Anti-Inflammatory Activities Of Rhizomes Of Polygonatum Verticillatum, Haroon Khan, Muhammad Saeed, Hassan Mehmood, Najeeb-Ur Rehman, Naveed Muhammad, Ikram-Ul Haq, Nadeem Ashraf, Kamal Eldin H El-Tahir, Anwar Gilani
Studies On Tracheorelaxant And Anti-Inflammatory Activities Of Rhizomes Of Polygonatum Verticillatum, Haroon Khan, Muhammad Saeed, Hassan Mehmood, Najeeb-Ur Rehman, Naveed Muhammad, Ikram-Ul Haq, Nadeem Ashraf, Kamal Eldin H El-Tahir, Anwar Gilani
Department of Biological & Biomedical Sciences
Background: The present study describes the tracheorelaxant and anti-inflammatory effects of Polygonatum verticillatum which may support its medicinal use in hyperactive airway complaints and inflammatory disorders.
Methods: The tracheorelaxant activity of crude extract of the rhizomes of P. verticillatum (PR) was assessed in isolated guinea-pig tracheal tissues immersed in tissue organ bath filled with Tyrode's solution and a continuous supply of carbogen gas (95% O2 and 5% CO2). The contractile and relaxant responses of the tissue were measured using isometric transducers coupled with Power-Lab data acquisition system. The anti-inflammatory effect was evaluated in carrageenan-induced rat paw edema model, while the …
Oncogenic Transformation Of Mammary Epithelial Cells By Transforming Growth Factor Beta Independent Of Mammary Stem Cell Regulation, Karen A. Dunphy, Jae-Hong Seo, Daniel J. Kim, Amy L. Roberts, James Direnzo, Amanda Balboni
Oncogenic Transformation Of Mammary Epithelial Cells By Transforming Growth Factor Beta Independent Of Mammary Stem Cell Regulation, Karen A. Dunphy, Jae-Hong Seo, Daniel J. Kim, Amy L. Roberts, James Direnzo, Amanda Balboni
Dartmouth Scholarship
BackgroundTransforming growth factor beta (TGFβ) is transiently increased in the mammary gland during involution and by radiation. While TGFβ normally has a tumour suppressor role, prolonged exposure to TGFβ can induce an oncogenic epithelial to mesenchymal transition (EMT) program in permissive cells and initiate the generation of cancer stem cells. Our objective is to mimic the transient exposure to TGFβ during involution to determine the persistent effects on premalignant mammary epithelium.
P2x4 Assembles With P2x7 And Pannexin-1 In Gingival Epithelial Cells And Modulates Reactive Oxygen Species Production And Inflammasome Activation, Shu-Chen Hung, Chul Hee Choi, Najwane Said-Sadier, Larry Johnson, Kalina Rosenova Atanasova, Hanen Sellami, Özlem Yilmaz, David M. Ojcius
P2x4 Assembles With P2x7 And Pannexin-1 In Gingival Epithelial Cells And Modulates Reactive Oxygen Species Production And Inflammasome Activation, Shu-Chen Hung, Chul Hee Choi, Najwane Said-Sadier, Larry Johnson, Kalina Rosenova Atanasova, Hanen Sellami, Özlem Yilmaz, David M. Ojcius
All Dugoni School of Dentistry Faculty Articles
We have previously reported that Porphyromonas gingivalis infection of gingival epithelial cells (GEC) requires an exogenous danger signal such as ATP to activate an inflammasome and caspase-1, thereby inducing secretion of interleukin (IL)-1β. Stimulation with extracellular ATP also stimulates production of reactive oxygen species (ROS) in GEC. However, the mechanism by which ROS is generated in response to ATP, and the role that different purinergic receptors may play in inflammasome activation, is still unclear. In this study, we revealed that the purinergic receptor P2X4 is assembled with the receptor P2X7 and its associated pore, pannexin-1. ATP induces ROS …
Ernest Everett Just, Phd: Pioneer In Ecological Developmental (Eco-Devo) Biology, Katelyn M. Williams, Bryan A. Wilson, Wendi G. O'Connor, Monte S. Willis
Ernest Everett Just, Phd: Pioneer In Ecological Developmental (Eco-Devo) Biology, Katelyn M. Williams, Bryan A. Wilson, Wendi G. O'Connor, Monte S. Willis
Journal of the South Carolina Academy of Science
Ernest Everett Just, a pioneering American biologist, discovered the fundamental role of the environment in the development of embryos. His work led to the creation of the area of biology known as ecological developmental (Eco-Devo) biology. However, both his work and the context of his scientific contributions are not widely known. His work covered a diversity of fields of biology, including marine biology, cytology, and parthogenesis (asexual reproduction where growth and development of embryos occur without fertilization). His findings provided important concepts in developmental biology that are used to this day. Specifically, he demonstrated the importance of the cellular cytoplasm …
Transcription Factor Binding Profiles Reveal Cyclic Expression Of Human Protein-Coding Genes And Non-Coding Rnas, Chao Cheng, Matthew Ung, Gavin D. Grant, Michael L. Whitfield
Transcription Factor Binding Profiles Reveal Cyclic Expression Of Human Protein-Coding Genes And Non-Coding Rnas, Chao Cheng, Matthew Ung, Gavin D. Grant, Michael L. Whitfield
Dartmouth Scholarship
Cell cycle is a complex and highly supervised process that must proceed with regulatory precision to achieve successful cellular division. Despite the wide application, microarray time course experiments have several limitations in identifying cell cycle genes. We thus propose a computational model to predict human cell cycle genes based on transcription factor (TF) binding and regulatory motif information in their promoters. We utilize ENCODE ChIP-seq data and motif information as predictors to discriminate cell cycle against non-cell cycle genes. Our results show that both the trans- TF features and the cis- motif features are predictive of cell cycle genes, and …
Apolipoprotein E Mediates Attachment Of Clinical Hepatitis C Virus To Hepatocytes By Binding To Cell Surface Heparan Sulfate Proteoglycan Receptors, Jieyun Jiang, Xianfang Wu, Hengli Tang, Guangxiang Luo
Apolipoprotein E Mediates Attachment Of Clinical Hepatitis C Virus To Hepatocytes By Binding To Cell Surface Heparan Sulfate Proteoglycan Receptors, Jieyun Jiang, Xianfang Wu, Hengli Tang, Guangxiang Luo
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Our previous studies demonstrated that the cell culture-grown hepatitis C virus of genotype 2a (HCVcc) uses apolipoprotein E (apoE) to mediate its attachment to the surface of human hepatoma Huh-7.5 cells. ApoE mediates HCV attachment by binding to the cell surface heparan sulfate (HS) which is covalently attached to the core proteins of proteoglycans (HSPGs). In the present study, we further determined the physiological importance of apoE and HSPGs in the HCV attachment using a clinical HCV of genotype 1b (HCV1b) obtained from hepatitis C patients and human embryonic stem cell-differentiated hepatocyte-like cells (DHHs). DHHs were found to resemble primary …
Spatially Explicit Modeling Of Schistosomiasis Risk In Eastern China Based On A Synthesis Of Epidemiological, Environmental, And Intermediate Host Genetic Data, Matthias Schrader, Torsten Hauffe, Zhijie Zhang, George M. Davis, Fred Jopp, Justin V. Remais, Thomas Wilke
Spatially Explicit Modeling Of Schistosomiasis Risk In Eastern China Based On A Synthesis Of Epidemiological, Environmental, And Intermediate Host Genetic Data, Matthias Schrader, Torsten Hauffe, Zhijie Zhang, George M. Davis, Fred Jopp, Justin V. Remais, Thomas Wilke
Microbiology, Immunology, and Tropical Medicine Faculty Publications
Schistosomiasis japonica is a major parasitic disease threatening millions of people in China. Though overall prevalence was greatly reduced during the second half of the past century, continued persistence in some areas and cases of re-emergence in others remain major concerns. As many regions in China are approaching disease elimination, obtaining quantitative data on Schistosoma japonicum parasites is increasingly difficult. This study examines the distribution of schistosomiasis in eastern China, taking advantage of the fact that the single intermediate host serves as a major transmission bottleneck. Epidemiological, population-genetic and high-resolution ecological data are combined to construct a predictive model capable …
Heterogeneous Nuclear Ribonucleoprotein K Supports Vesicular Stomatitis Virus Replication By Regulating Cell Survival And Cellular Gene Expression, Phat X. Dinh, Anshuman Das, Rodrigo Franco, Asit K. Pattnaik
Heterogeneous Nuclear Ribonucleoprotein K Supports Vesicular Stomatitis Virus Replication By Regulating Cell Survival And Cellular Gene Expression, Phat X. Dinh, Anshuman Das, Rodrigo Franco, Asit K. Pattnaik
School of Veterinary and Biomedical Sciences: Faculty Publications
The heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a member of the family of hnRNPs and was recently shown in a genome-wide small interfering RNA (siRNA) screen to support vesicular stomatitis virus (VSV) growth. To decipher the role of hnRNP K in VSV infection, we conducted studies which suggest that the protein is required for VSV spreading. Virus binding to cells, entry, and nucleocapsid uncoating steps were not adversely affected in the absence of hnRNP K, whereas viral genome transcription and replication were reduced slightly. These results indicate that hnRNP K is likely involved in virus assembly and/or release from …
Diabetes Mellitus And Hypercholesterolemia Are Risk Factors For Alzheimer’S Disease And Appear To Affect The Integrity Of The Blood Brain Barrier, Jacqueline Dash
Diabetes Mellitus And Hypercholesterolemia Are Risk Factors For Alzheimer’S Disease And Appear To Affect The Integrity Of The Blood Brain Barrier, Jacqueline Dash
Graduate School of Biomedical Sciences Theses and Dissertations
Studies have shown that the vascular risk factors common to diabetes mellitus and hypercholesterolemia are also risk factors for Alzheimer’s disease (AD). It is currently unknown how these diseases are associated with AD, but they may cause a leak in the blood brain barrier (BBB), which is one of the hallmarks of AD. In this preliminary study, over 150 pig brain slides were tested for the expression levels of tight junction proteins occludin and claudin V in the BBB microvasculature. There were three groups of pig brains used in this study namely, control pigs, pigs with diabetes mellitus and hypercholesterolemia …
Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu
Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu
Biochemistry and Microbiology
Pseudomonas aeruginosa is a Gram negative, opportunistic pathogen that uses the overproduction of alginate, a surface polysaccharide, to form biofilms in vivo. Overproduction of alginate, also known as mucoidy, affords the bacterium protection from the host's defenses and facilitates the establishment of chronic lung infections in individuals with cystic fibrosis. Expression of the alginate biosynthetic operon is primarily controlled by the alternative sigma factor AlgU (AlgT/σ22). In a nonmucoid strain, AlgU is sequestered by the transmembrane antisigma factor MucA to the cytoplasmic membrane. AlgU can be released from MucA via regulated intramembrane proteolysis by proteases AlgW and MucP …
Expression Of The Chemokine Receptor, Cxcr4, And Its Ligand, Sdf-1, Are Increased In Purkinje Cells Of The Multiple System Atrophy Cerebellum, Megan Welter
Masters Theses
Multiple System Atrophy (MSA) is a sporadic, neurodegenerative disease that consists of three conditions: autonomic dysfunction, Parkinsonism and cerebellar ataxia. Our lab conducted an Affymetrix global gene expression analysis using pons tissue of MSA patients to determine genes that are differentially expressed when compared to non- MSA controls. This study identified upregulated genes, including the C-X-C chemokine receptor type 4, CXCR4, to which stromal cell-derived factor-I (SDF-1) is the natural ligand. The CXCR4/SDF-1 signaling pair has been sho.wn to play multiple roles in the brain, such as inducing neuronal apoptosis and promoting leukocyte recruitment during inflammation. The MSA cerebellum presents …
The 23rd Annual Research Conference Abstract Booklet, Mulu Aderie Alemu, Nikki Lynn Rogers
The 23rd Annual Research Conference Abstract Booklet, Mulu Aderie Alemu, Nikki Lynn Rogers
University of Gondar Research Conferences
Staff members, postgraduate and senior undergraduate students of the University, invited guests and speakers participated in the conference. The annual conference of the University is meant to share experiences in research activities among juniors and seniors, staff and students, and invited guests. It is also meant to motivate students and young faculty to engage in research and also to initiate and strengthen interdisciplinary collaborations. The findings of the studies and the resulting recommendations are expected to be used in solving the diverse societal problems we have been facing.
Research activities at the University of Gondar are primarily aimed at solving …
Associations Between Alcohol Consumption And Fasting Blood Glucose In Young Adults, Julie Ann Lucca
Associations Between Alcohol Consumption And Fasting Blood Glucose In Young Adults, Julie Ann Lucca
Master's Theses
Current research shows moderate alcohol consumption is associated with decreased risk of diabetes and excessive consumption or binge drinking can cause insulin resistance and diabetes. In 2010, diabetes was the seventh leading cause of death in the United Statesand was responsible for significant health complications: blindness, kidney failure, and limb amputations, and is a large national economic burden. Fasting blood glucose (FBG) is a tool used to help diagnose diabetes. Abnormally high FBG, ≥100 mg/dl, is indicative of diabetes and pre-diabetes. Few studies have observed diabetic prevalence among young adults or college students. Studying young adults can help provide added …
Small Molecule Inhibitors Of Hpv16 E6, Chung-Hsiang Yuan
Small Molecule Inhibitors Of Hpv16 E6, Chung-Hsiang Yuan
Loma Linda University Electronic Theses, Dissertations & Projects
High-risk human papillomaviruses (HR-HPVs) cause nearly all cases of cervical cancer. HPV 16 E6, one of two viral oncogenes, protects cells from apoptosis by binding to and accelerating the degradation of several apoptotic proteins, including caspase 8 and p53. We proposed that blocking the interactions between HPV E6 and its partners using small molecules had the potential to re-sensitize HPV+ cells to apoptosis. To test this prediction, we screened libraries of small molecules for candidates that could block E6/caspase 8 binding, and identified several candidates from different chemical classes. Testing hits for dose-dependency and specificity in vitro and for toxicity …
Raman Spectroscopic Analysis Of Human Skin Tissue Sections Ex-Vivo: Evaluation Of The Effects Of Tissue Processing And Dewaxing, Syed Mehmood Ali, Franck Bonnier, Ali Tfayli, Helen Lambkin, Kathleen Flynn, Vincent Mcdonagh, Claragh Healy, Thomas Lee, Fiona Lyng, Hugh Byrne
Raman Spectroscopic Analysis Of Human Skin Tissue Sections Ex-Vivo: Evaluation Of The Effects Of Tissue Processing And Dewaxing, Syed Mehmood Ali, Franck Bonnier, Ali Tfayli, Helen Lambkin, Kathleen Flynn, Vincent Mcdonagh, Claragh Healy, Thomas Lee, Fiona Lyng, Hugh Byrne
Articles
Raman spectroscopy coupled with K-means clustering analysis (KMCA) is employed to elucidate the biochemical structure of human skin tissue sections, and the effects of tissue processing. Both hand and thigh sections of human cadavers were analysed in their unprocessed and formalin fixed paraffin processed (FFPP) and subsequently dewaxed forms. In unprocessed sections, KMCA reveals clear differentiation of the stratum corneum, intermediate underlying epithelium and dermal layers for sections from both anatomical sites. The stratum corneum is seen to be relatively rich in lipidic content; the spectrum of the subjacent layers is strongly influenced by the presence of melanin, while that …
Microproteinuria During Opisthorchis Viverrini Infection: A Biomarker For Advanced Renal And Hepatobiliary Pathologies From Chronic Opisthorchiasis, Prasert Saichua, Paiboon Sithithaworn, Amar R. Jariwala, David J. Diemert, Jiraporn Sithithaworn, Banchob Sripa, Thewarach Laha, Eimorn Mairiang, Chawalit Pairojkul, Maria V. Periago, Narong Khuntikeo, Jason Mulvenna, Jeffrey M. Bethony
Microproteinuria During Opisthorchis Viverrini Infection: A Biomarker For Advanced Renal And Hepatobiliary Pathologies From Chronic Opisthorchiasis, Prasert Saichua, Paiboon Sithithaworn, Amar R. Jariwala, David J. Diemert, Jiraporn Sithithaworn, Banchob Sripa, Thewarach Laha, Eimorn Mairiang, Chawalit Pairojkul, Maria V. Periago, Narong Khuntikeo, Jason Mulvenna, Jeffrey M. Bethony
Microbiology, Immunology, and Tropical Medicine Faculty Publications
Approximately 680 million people are at risk of infection with Opisthorchis viverrini (OV) andClonorchis sinensis, with an estimated 10 million infected with OV in Southeast Asia alone. While opisthorchiasis is associated with hepatobiliary pathologies, such as advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA), animal models of OV infection show that immune-complex glomerulonephritis is an important renal pathology that develops simultaneously with hepatobiliary pathologies. A cardinal sign of immune-complex glomerulonephritis is the urinary excretion of immunoglobulin G (IgG) (microproteinuria). In community-based studies in OV endemic areas along the Chi River in northeastern Thailand, we observed that over half of …
The Role Of Indoleamine 2,3-Dioxygenase In Lp-Bpm5 Murine Retroviral Disease Progression, Megan A. O'Connor, William R. Green
The Role Of Indoleamine 2,3-Dioxygenase In Lp-Bpm5 Murine Retroviral Disease Progression, Megan A. O'Connor, William R. Green
Dartmouth Scholarship
Indoleamine 2,3-dioxygenase (IDO) is an immunomodulatory intracellular enzyme involved in tryptophan degradation. IDO is induced during cancer and microbial infections by cytokines, ligation of co-stimulatory molecules and/or activation of pattern recognition receptors, ultimately leading to modulation of the immune response. LP-BM5 murine retroviral infection induces murine AIDS (MAIDS), which is characterized by profound and broad immunosuppression of T- and B-cell responses. Our lab has previously described multiple mechanisms regulating the development of immunodeficiency of LP-BM5-induced disease, including Programmed Death 1 (PD-1), IL-10, and T-regulatory (Treg) cells. Immunosuppressive roles of IDO have been demonstrated in other retroviral models, suggesting a possible …
Polyethylenimine-Enhanced Alumina Nanoscale Adjuvant For Cancer Vaccine, Naoko Uno, Haiyan Li, Hong-Ming Hu, Jun Jiao
Polyethylenimine-Enhanced Alumina Nanoscale Adjuvant For Cancer Vaccine, Naoko Uno, Haiyan Li, Hong-Ming Hu, Jun Jiao
Student Research Symposium
Aluminum oxide nanoparticles (Al2O3 NPs) have been shown to increase the efficiency of cell-mediated immune response. Specifically, CD8 and CD4 immune response is required for T cell activation by dendritic cells. These nanoparticles, when functionalized with peptides and other molecules, can be used as vaccine in cancer treatment. In this study, Al2O3 NPs were attached to E6/E7 proteins. HPV-induced cervical cancer expresses E6/E7 antigens. E6/E7 proteins were attached using surface modification of the Al2O3 NPs; different types of molecules were tested to see which adhered the highest amount of protein and produced the strongest cell response. Protein measurements were done …
Oral Transmission Of Listeria Monocytogenes In Mice Via Ingestion Of Contaminated Food, Elsa N. Bou Ghanem, Tanya Myers-Morales, Grant S. Jones, Sarah E. F. D'Orazio
Oral Transmission Of Listeria Monocytogenes In Mice Via Ingestion Of Contaminated Food, Elsa N. Bou Ghanem, Tanya Myers-Morales, Grant S. Jones, Sarah E. F. D'Orazio
Microbiology, Immunology, and Molecular Genetics Faculty Publications
L. monocytogenes are facultative intracellular bacterial pathogens that cause food borne infections in humans. Very little is known about the gastrointestinal phase of listeriosis due to the lack of a small animal model that closely mimics human disease. This paper describes a novel mouse model for oral transmission of L. monocytogenes. Using this model, mice fed L. monocytogenes-contaminated bread have a discrete phase of gastrointestinal infection, followed by varying degrees of systemic spread in susceptible (BALB/c/By/J) or resistant (C57BL/6) mouse strains. During the later stages of the infection, dissemination to the gall bladder and brain is observed. The …
Effect Of Coconut Oil On Ulcerative Colitis In The Mouse Model, Pranav Chandra Alok
Effect Of Coconut Oil On Ulcerative Colitis In The Mouse Model, Pranav Chandra Alok
Masters Theses & Specialist Projects
Ulcerative colitis (UC) is a chronic disease of the colon or large intestine that causes inflammation and ulceration of the inner lining of the colon and rectum. In patients with ulcerative colitis, the body’s immune system overreacts and the body mistakes food, bacteria or other internal materials in the colon for an invading substance. The immune system attacks the material, thus irritating the colon. Limited knowledge of inflammatory conditions coupled with a narrow range of therapeutic options necessitates investigating the role of natural products. This study describes the effect of natural coconut oil on chemically-induced acute and chronic disease in …
Influence Of Genetic Variation On Birth Defects In Caenorhabditis Elegans, Daniel Robert Kepple
Influence Of Genetic Variation On Birth Defects In Caenorhabditis Elegans, Daniel Robert Kepple
Renée Crown University Honors Thesis Projects - All
In my Renee Crown Honors Capstone project, I studied how genetic variation influences birth defects that cause death in C. elegans embryos. I performed high-throughput hatching assay experiments of recombinant inbred advance intercross lines of C. elegans. These lines are genetically distinct from each other. I found significant variation in birth defects causing embryo death in these recombinant inbred advanced intercross lines. My results give evidence that gene interaction may play a significant role in causing birth defects resulting in death. My data also provides a starting point for studies making statistical arguments linking these birth defects to specific …
Proteomic Studies Of The Influenza Virus-Human Cell Interactions: The Responses Of Host Cell Protein Expression To Viral Infection And The Novel Host Proteins That Interact With Virus Protein Ns1, Yimeng Wang
Graduate Theses and Dissertations
Influenza A viruses (IAVs) continue to be a threat to human health. Despite extensive studies, the mechanisms underlying the IAVs-host interactions during IAV infection remain elusive. We employed quantitative proteomic methods to systematically explore the host cell protein expression responses to IAV infection and examine the function of a critical IAV protein called NS1 by identifying its host binding partners. Specifically, we used a 2-dimentional gel electrophoresis (2-DE) based proteomic method to screen host proteins whose expression was substantially altered by IAV. One critical protein named IκB kinase-gamma (IKKγ) was found to be significantly down-regulated during IAV infection. Functional studies …
Mismatch Repair Deficient Tumors Lacking Known Sporadic Causes: Are They All Due To Lynch Syndrome?, Katherine M. Dempsey
Mismatch Repair Deficient Tumors Lacking Known Sporadic Causes: Are They All Due To Lynch Syndrome?, Katherine M. Dempsey
Dissertations and Theses (Open Access)
BACKGROUND: Mismatch repair deficient (MMRD) colorectal (CRC) or endometrial (EC) cancers in the absence of MLH1 promoter hypermethylation and BRAF mutations are suggestive of Lynch syndrome (LS). Positive germline genetic test results confirm LS. It is unclear if individuals with MMRD tumors but no identified germline mutation or sporadic cause (MMRD+/germline-) have LS.
HYPOTHESIS: Since LS is hereditary, individuals with LS should have a stronger family history of LS-related cancers than individuals with sporadic tumors. We hypothesized that MMRD+/germline- CRC and/or EC patients would have less suggestive family histories than LS CRC and/or EC patients.
METHODS: 253 individuals with an …
Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu
Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu
Dissertations and Theses (Open Access)
CD8+ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8+ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8+ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8+ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8+CD57+ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …
Inflammatory Breast Cancer: The Immune Perspective, Evan N. Cohen
Inflammatory Breast Cancer: The Immune Perspective, Evan N. Cohen
Dissertations and Theses (Open Access)
Inflammatory breast cancer (IBC) is the most insidious form of locally advanced disease. Although rare and less than 2% of all breast cancer, IBC is responsible for up to 10% of all breast cancer deaths. Despite the name, very little is known about the role of inflammation or immune mediators in IBC. Therefore, we analyzed blood samples from IBC patients and non-IBC patients, as well as healthy donor controls to establish an IBC-specific profile of peripheral blood leukocyte phenotype and function of T cells and dendritic cells and serum inflammatory cytokines.
Emerging evidence suggests that host factors in the microenviromement …
Delayed Thrombus Resolution And Fibroproliferative Vascular Wound Healing From Deficiency Of Type Iii Collagen: A Paradoxical Mechanism For Tissue Fragility, Amy J. Reid
Dissertations and Theses (Open Access)
Vascular Ehlers-Danlos syndrome is a heritable disease of connective tissue caused by mutations in COL3A1, conferring a tissue deficiency of type III collagen. Cutaneous wounds heal poorly in these patients, and they are susceptible to spontaneous and catastrophic rupture of expansible hollow organs like the gut, uterus, and medium-sized to large arteries, which leads to premature death. Although the predisposition for organ rupture is often attributed to inherent tissue fragility, investigation of arteries from a haploinsufficient Col3a1 mouse model (Col3a1+/-) demonstrates that mutant arteries withstand even supraphysiologic pressures comparably to wild-type vessels. We hypothesize that injury …
The Fungal Pathogen Aspergillus Fumigatus Regulates Growth, Metabolism, And Stress Resistance In Response To Light, Kevin K. Fuller, Carol S. Ringelberg, Jennifer J. Loros, Jay C. Dunlap
The Fungal Pathogen Aspergillus Fumigatus Regulates Growth, Metabolism, And Stress Resistance In Response To Light, Kevin K. Fuller, Carol S. Ringelberg, Jennifer J. Loros, Jay C. Dunlap
Dartmouth Scholarship
Light is a pervasive environmental factor that regulates development, stress resistance, and even virulence in numerous fungal species. Though much research has focused on signaling pathways in Aspergillus fumigatus, an understanding of how this pathogen responds to light is lacking. In this report, we demonstrate that the fungus does indeed respond to both blue and red portions of the visible spectrum. Included in the A. fumigatus light response is a reduction in conidial germination rates, increased hyphal pigmentation, enhanced resistance to acute ultraviolet and oxidative stresses, and an increased susceptibility to cell wall perturbation. By performing gene deletion analyses, we …