Laboratory and Basic Science Research Commons^™

Modeling Sporadic Tumor Formation Driven By Telomere Dysfunction In The Gastrointestinal Tract, Suzanne S. Chan

Dissertations and Theses (Open Access)

Colorectal cancer is a complex disease that is thought to arise when cells accumulate mutations that allow for uncontrolled growth. There are several recognized mechanisms for generating such mutations in sporadic colon cancer; one of which is chromosomal instability (CIN). One hypothesized driver of CIN in cancer is the improper repair of dysfunctional telomeres. Telomeres comprise the linear ends of chromosomes and play a dual role in cancer. Its length is maintained by the ribonucleoprotein, telomerase, which is not a normally expressed in somatic cells and as cells divide, telomeres continuously shorten. Critically shortened telomeres are considered dysfunctional as they …

Genetic Connections Between Neurological Disorders And Cholesterol Metabolism, Ingemar Bjorkhem, Valerio Leoni, Steve Meaney

Articles

Cholesterol is an essential component of both the peripheral and central nervous systems of mammals. Over the last decade, evidence has accumulated that disturbances in cholesterol metabolism are associated with the development of various neurological conditions. In addition to genetically defined defects in cholesterol synthesis, which will be covered in another review in this Thematic Series, defects in cholesterol metabolism (cerebrotendinous xanthomatosis) and intracellular transport (Niemann Pick Syndrome) lead to neurological disease. A subform of hereditary spastic paresis (type SPG5) and Huntington's disease are neurological diseases with mutations in genes that are of importance for cholesterol metabolism. Neurodegeneration is generally …

High-Density Screening Reveals A Different Spectrum Of Genomic Aberrations In Chronic Lymphocytic Leukemia Patients With ‘Stereotyped’ Ighv3-21 And Ighv4-34 B-Cell Receptors, Millaray Marincevic, Nicola Cahill, Rebeqa Gunnarsson, Anders Isaksson, Mahmoud Mansouri, Hanna Göransson, Markus Rasmussen, Mattias Jansson, Fergus Ryan, Karin Karlsson, Hans-Olov Adami, Fred Davi, Jesper Jurlander, Gunnar Juliusson, Kostas Stamatopoulos, Richard Rosenquist

Articles

Background The existence of multiple subsets of chronic lymphocytic leukemia expressing ‘stereotyped’ Bcell receptors implies the involvement of antigen(s) in leukemogenesis. Studies also indicate that ‘stereotypy’ may influence the clinical course of patients with chronic lymphocytic leukemia, for example, in subsets with stereotyped IGHV3-21 and IGHV4-34 B-cell receptors; however, little is known regarding the genomic profile of patients in these subsets. Design and Methods We applied 250K single nucleotide polymorphism-arrays to study copy-number aberrations and copy-number neutral loss-of-heterozygosity in patients with stereotyped IGHV3-21 (subset #2, n=29), stereotyped IGHV4-34 (subset #4, n=17; subset #16, n=8) and non-subset #2 IGHV3-21 (n=13) and …

Identification Of Eurycea Using Cytochrome B, Karis A. Myers

Senior Honors Theses

Genomic sequencing is a powerful tool that has many applications for research, one of which is in the field of taxonomy and the identification of species. This thesis discusses the mitochondrial gene cytochrome b and its utility in population genetics and identification of larval amphibians. The development of the Polymerase Chain Reaction and primers are an integral part of the modern DNA sequencing process. The Polymerase Chain Reaction is used to amplify a target DNA sequence, and the protocol for this procedure must be optimized for the specific sequence of target DNA. Primers must also be designed and modified for …

Towards An Action Spectrum For Photoentrainment Of The Chlamydomonas Reinhardtii Circadian Clock, Christa Gaskill

Masters Theses & Specialist Projects

No abstract provided.

The Effect Of Radiation And Repeated Sub-Culturing On Tgf-Β1 Signaling In Frtl-5 Cells, Cheryl G. Burrell

Loma Linda University Electronic Theses, Dissertations & Projects

From our ongoing in vitro studies using the Fisher Rat Thyroid cell line-5 (FRTL-5) we recorded accelerated growth, reduced follicularization and reduction in thyroxin release that occurred as the cells were repeatedly sub-cultured. We also recorded that these changes occurred earlier and more rapidly following radiation exposure. We determined that TGF-β1 production increased under both conditions. We hypothesized that alteration in the TGF-β1 signaling pathway contributed to the changes observed in the cellular properties of FRTL-5 cells. Our objective was to examine some of the players in the TGF-β1 signaling pathway to determine whether radiation and/or repeated subculturing promoted changes …

Radiation-Induced Increases In Pkc Modulate Integrin Expression And Contribute To Fibrotic Changes, Pinal Rushikesh Pandya

Loma Linda University Electronic Theses, Dissertations & Projects

The sequences of events in fibrosis are similar to those in wound healing; however, the normal termination and resolution stages do not take place. The initial cellular response following ionizing radiation involves accumulation of the ECM (extracellular matrix) including collagen, fibronectin and the interaction of many growth factors (cytokines) with their receptors. There are a number of unanswered questions regarding many aspects of radiation-induced fibrosis, including the initial triggers and physical changes that initiate the process. We have confirmed that elevated pKC and other cellular changes following radiation are similar to those found at sites of inflammation. This information leads …

An In Vitro Model Of Ovarian Cancer: Studying The Effects Of Talc And Pycnogenol®, Amber Renée Buz'zard

Loma Linda University Electronic Theses, Dissertations & Projects

Ovarian cancer is the sixth most common cancer and accounts for more deaths than any other cancer of the female reproductive system. The American Cancer Society has suggested that poor diet, talc and industrial pollutants may increase the risk of developing ovarian cancer. Talc is ubiquitous and concern is raised about its safety, role as a possible carcinogen and known ability to cause irritation and inflammation. Due to the silent nature of ovarian cancer, chemoprevention is a high priority. The most useful chemopreventive compounds will inhibit, delay or reverse carcinogenesis, and can be taken for long periods of time with …

Semiparametric Regression Of Multi-Dimensional Genetic Pathway Data: Least Squares Kernel Machines And Linear Mixed Models, Dawei Liu, Xihong Lin, Debashis Ghosh

Harvard University Biostatistics Working Paper Series

No abstract provided.

Multiple Tests Of Association With Biological Annotation Metadata, Sandrine Dudoit, Sunduz Keles, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We propose a general and formal statistical framework for the multiple tests of associations between known fixed features of a genome and unknown parameters of the distribution of variable features of this genome in a population of interest. The known fixed gene-annotation profiles, corresponding to the fixed features of the genome, may concern Gene Ontology (GO) annotation, pathway membership, regulation by particular transcription factors, nucleotide sequences, or protein sequences. The unknown gene-parameter profiles, corresponding to the variable features of the genome, may be, for example, regression coefficients relating genome-wide transcript levels or DNA copy numbers to possibly censored biological and …

A Pseudolikelihood Approach For Simultaneous Analysis Of Array Comparative Genomic Hybridizations (Acgh), David A. Engler, Gayatry Mohapatra, David N. Louis, Rebecca Betensky

Harvard University Biostatistics Working Paper Series

DNA sequence copy number has been shown to be associated with cancer development and progression. Array-based Comparative Genomic Hybridization (aCGH) is a recent development that seeks to identify the copy number ratio at large numbers of markers across the genome. Due to experimental and biological variations across chromosomes and across hybridizations, current methods are limited to analyses of single chromosomes. We propose a more powerful approach that borrows strength across chromosomes and across hybridizations. We assume a Gaussian mixture model, with a hidden Markov dependence structure, and with random effects to allow for intertumoral variation, as well as intratumoral clonal …

Application Of A Multiple Testing Procedure Controlling The Proportion Of False Positives To Protein And Bacterial Data, Merrill D. Birkner, Alan E. Hubbard, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Simultaneously testing multiple hypotheses is important in high-dimensional biological studies. In these situations, one is often interested in controlling the Type-I error rate, such as the proportion of false positives to total rejections (TPPFP) at a specific level, alpha. This article will present an application of the E-Bayes/Bootstrap TPPFP procedure, presented in van der Laan et al. (2005), which controls the tail probability of the proportion of false positives (TPPFP), on two biological datasets. The two data applications include firstly, the application to a mass-spectrometry dataset of two leukemia subtypes, AML and ALL. The protein data measurements include intensity and …

The Potential Role Of Ledgf/P75 In Prostate Cancer, Tracy Ruth Daniels

Loma Linda University Electronic Theses, Dissertations & Projects

The serum autoantibody repertoire from cancer patients is currently being exploited for the identification of tumor associated antigens (TAA) and the design of TAA arrays. Such arrays would facilitate autoantibody profiling and potentially aid in the serological diagnosis and prognosis of tumors. The goal of this study was to identify and characterize prostate-specific TAA. We observed that while the general frequency and titers of autoantibodies in PCa patients were relatively similar to those in matched controls, significant differences could be detected between the two groups in the autoantibody response to the lens epithelial-derived growth factor p75 (LEDGF/p75). LEDGF/p75 is a …

Construction Of Rhas And Rhar Overexpression Plasmids And The Effects Of Crp Mutants On E.Coli L-Rhamnose Gene Expression, Amber Bromenshenkel, Susan Egan

Honors Capstones

Capstone submitted as a graduation requirement for the BSU Honors Program.

Effects Of Liposome-Encapsulated Tnf-Alpha And Radiation Against Colon Cancer, Dong Won Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies have shown that tumor necrosis factor-α (TNF-α) can augment the antitumor effects of radiation, inhibiting tumor progression to a greater extent than either modality alone. However, nonspecific toxicities associated with TNF-α have limited its use as an adjuvant. This limitation is potentially resolved with the encapsulation of TNF-α in sterically stabilized, PEGylated liposomes (STEALTH®). Thus, the overall hypothesis of the research was that the combination of radiation with STEALTH® liposome encapsulated TNF-α (SL-TNF-α) will have greater efficacy and fewer dose-limiting side effects in the LS174T human colorectal tumor xenograft model compared to the combination of free TNF-α and …

Vaccinia Virus-Mediated Glioma Gene Therapy Using P53, Il-2 And Il-12, Bing Chen

Loma Linda University Electronic Theses, Dissertations & Projects

Malignant brain tumors are generally lethal soon after their diagnosis, and the five-year survival rate for the patient is low in spite of neurosurgery, radiation therapy, and/or chemotherapy. Gene therapy has the potential to improve patient survival and quality of life by delivering specific combinations of therapeutic genes directly to the tumor for localized treatment.

We have based our cancer gene therapy for glioma on a highly attenuated variant of the Lister strain of vaccinia virus (VV) which has been proven to be a safe and effective vaccine vector. Other advantages include a wide host range, a strong promoter system, …

Connexin-32 Contributes To Radiation Resistance In Thyroid Follicles, Da-Thao Dinh Tran

Loma Linda University Electronic Theses, Dissertations & Projects

The objective of this study was to examine the role of gap junctions in the radiation resistance of thyroid follicles. The question of whether gap junctional intercellular communication plays an important role in the “contact effect”, wherein cells in direct apposition are more resistant to the damaging effects of radiation, has been debated for years. We used the Fischer rat thyroid cell line (FRTL-5) to carry out our experiments. This thesis is divided into two parts: 1) characterization of gap junctional properties in FRTL-5 cells and, 2) exposure of these cells to radiation.

We found that, unlike primary thyroid cells, …

The Role Of Brn-3.2 In Retinal Ganglion Cell Differentiation, Jerin Marie Wright

Loma Linda University Electronic Theses, Dissertations & Projects

Within the retina, the POU domain of transcription factors brn-3.0, brn-3.1, and brn-3.2 are present only in retinal ganglion cells. These genes are believed to be involved in establishing neural cell lineages in mammals. In this study brn-3.2 was examined by comparing the number of ganglion cells present during postnatal development in normal mice (+/+), in mice homozygous (-/-) for the brn-3.2 gene, and in adult mice with a heterozygous gene deletion (+/-) for brn-3.2. Optic nerve cross sections were imaged by electron microscopy, and axon profiles counted systematically by hand. These counts were then related to the nerve cross …

Study Of The Hiv-1 Gene Regulatory Proteins Tat And Rev By The Two-Hybrid System In Yeast, David Allen Elkins

Loma Linda University Electronic Theses, Dissertations & Projects

Tat and Rev, small proteins encoded by the Human Immunodeficiency Virus type 1 (HIV-1), regulate its pattern of gene expression within infected cells. Tat increases transcription from the integrated pro virus by approximately a thousand-fold; Rev effects a shift in the pattern of splicing of the viral mRNA. Both are likely to interact with cellular proteins in executing their respective functions. Tat has additional activities (including neurotoxicity and inhibition of lymphocyte activation) which may be extraneous to its viral functions.

In order to identify cellular proteins interacting with Tat and Rev, the genes for both were cloned into plasmid vectors …

Connexin32 Is A Myelin-Related Protein In The Pns And Cns, Steven S. Scherer, Suzanne M. Deschênes, Yi-Tian Xu, Judith B. Grinspan, Kenneth H. Fischbeck, David L. Paul

Biology Faculty Publications

We have examined the expression of a gap junction protein, connexin32 (Cx32), in Schwann cells and oligodendrocytes. In peripheral nerve, Cx32 is found in the paranodal myelin loops and Schmidt-Lanterman incisures of myelinating Schwann cells, and the levels of Cx32 protein and mRNA change in parallel with those of other myelin-related genes during development, Wallerian degeneration, and axonal regeneration. In the central nervous system, Cx32 is found in oligodendrocytes and their processes, but not in compact myelin, and the levels of Cx32 protein and mRNA increase during development in parallel with those of the other myelin genes. Thus, Cx32 is …

Molecular Weight Determinations Of Some Salmonella Potsdam Bacteriophage Dna's, Winston H. Richards

Loma Linda University Electronic Theses, Dissertations & Projects

Two group A phages, P9c/2 and P4/2, were studied. Their density, sedimentation velocity, and biochemical properties were compared. Their densities were determined by density gradient centrifugation in 38.3% cesium chloride. Sedimentation velocity was used to determine their molecular weights. To accomplish this, the DNA of P9c/2 and P4/2 was labeled with tritium and T₂ DNA, labeled with ³²P, was used as a standard. The DNA of P9c/2 and P4/2 was separately mixed with T₂ DNA and centrifuged in a 0-15% sucrose gradient. The molecular weights were calculated using the formula D₂/D₁= (M_{2 …}