Molecular Biology Commons^™

A Study On The Function Of 14-3-3sigma In Regulating Cancer Energy Metabolism, Liem M. Phan, Liem M. Phan

Dissertations and Theses (Open Access)

Metabolic reprogramming has been shown to be a major cancer hallmark providing tumor cells with significant advantages for survival, proliferation, growth, metastasis and resistance against anti-cancer therapies. Glycolysis, glutaminolysis and mitochondrial biogenesis are among the most essential cancer metabolic alterations because these pathways provide cancer cells with not only energy but also crucial metabolites to support large-scale biosynthesis, rapid proliferation and tumorigenesis. In this study, we find that 14-3-3σ suppresses all these three metabolic processes by promoting the degradation of their main driver, c-Myc. In fact, 14-3-3s significantly enhances c-Myc poly-ubiquitination and subsequent degradation, reduces c-Myc transcriptional activity, and down-regulates …

Mechanistic Studies Of A Novel Ppar-Gamma Mutant That Causes Lipodystrophy And Diabetes, Olga Astapova

Wayne State University Dissertations

PPAR-gamma is a nuclear receptor that plays a central role in metabolic regulation by regulating extensive gene expression networks in adipose, liver, skeletal muscle and many other tissues. Human PPAR-gamma mutations are rare and cause a monogenetic form of severe type II diabetes with metabolic syndrome, known as familiar partial lypodystrophy. The E157D PPAR-gamma mutant causes atypical lipodystrophy in a large Canadian kindred, presenting with multiple musculoskeletal, neurological and hematological abnormalities in addition to the classic lipodystrophy features of insulin-resistant diabetes, hypertension and dyslipidemia. This mutation is localized to the p-box of PPAR-gamma, a small region that interacts directly with …

A Proposal To Test The Effects Of Factor Ecat1 On Pluripotency, From Reprogramming To Differentiation Of Human Somatic Cells, Vritti R. Goel

CMC Senior Theses

The field of stem cell research has been growing more because of the interest in using stem cells to cure diseases and heal injuries. Human embryonic stem cells, because of the controversy surrounding them—and subsequently the difficulties in acquiring samples of the existing aging cell lines—can only be used in limited capacities. While the development of induced pluripotent stem cells in the last decade has allowed the field to progress closer to medical treatments, the low efficiency of reprogramming a somatic cell to a pluripotent state, and the vast molecular and genomic differences between human embryonic stem cells and human …

Gata-Family Transcription Factors In Magnaporthe Oryzae, Cristian F. Quispe

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

The filamentous fungus, Magnaporthe oryzae, responsible for blast rice disease, destroys around 10-30% of the rice crop annually. Infection begins when the specialized infection structure, the appressorium, generates enormous internal turgor pressure through the accumulation of glycerol. This turgor acts on a penetration peg emerging at the base of the cell, causing it to breach the leaf surface allowing its infection.

The enzyme trehalose-6- phosphate synthase (Tps1) is a central regulator of the transition from appressorium development to infectious hyphal growth. In the first chapter we show that initiation of rice blast disease requires a regulatory mechanism involving an …

Bilinear Programming And Protein Structure Alignment, J. Cain, D. Kamenetsky, N. Lavine

Mathematical Sciences Technical Reports (MSTR)

Proteins are a primary functional component of organic life, and understanding their function is integral to many areas of research in biochemistry. The three-dimensional structure of a protein largely determines this function. Protein structure alignment compares the structure of a protein with known function to that of a protein with unknown function. A protein’s three-dimensional structure can be transformed through a smooth piecewise-linear sigmoid function to a real symmetric contact matrix that represents the functional significance of certain parts of the protein. We address the protein alignment problem as a minimization of the 2-norm difference of two proteins’ contact matrices. …

An Entrepreneurial Approach To Librarianship, Flora Shrode, Jennifer Duncan, Wendy Holliday

Library Faculty & Staff Publications

Librarians from Utah State University explain recent efforts to encourage subject librarians to take a more holistic view of their roles. We are shifting from a traditional emphasis primarily on collection development and refocusing on natural connections between collections, instruction, liaison, and reference service. The poster provides background about Utah State University’s situation and explains our approach to analyzing local needs and culture to inform development of a new organizational structure. We describe our vision of subject librarianship, the process by which we assessed librarians’ ideas and goals for performing as subject librarians, and the actions we are taking to …

Tracking Profiles Of Genomic Instability In Spontaneous Transformation And Tumorigenesis, Lesley Lawrenson

Wayne State University Dissertations

The dominant paradigm for cancer research focuses on the identification of specific genes for cancer causation and for the discovery of therapeutic targets. Alternatively, the current data emphasize the significance of karyotype heterogeneity in cancer progression over specific gene-based causes of cancer. Variability of a magnitude significant to shift cell populations from homogeneous diploid cells to a mosaic of structural and numerical chromosome alterations reflects the characteristic low-fidelity genome transfer of cancer cell populations. This transition marks the departure from micro-evolutionary gene-level change to macro-evolutionary change that facilitates the generation of many unique karyotypes within a cell population. Considering cancer …

Applications Of Variable Number Tandem Repeat Genotyping In The Validation Of An Animal Medical Model And Gene Flow Studies In Threatened Populations Of Reptiles, Candace D. Smith

Graduate Theses and Dissertations

We used variable number tandem repeats (VNTR) to validate the chicken as a human medical model for Pulmonary Arterial Hypertension. We identified seven regions on four chromosomes and interrogated for VNTR markers that significantly associate with Pulmonary Hypertension Syndrome/ascites. In those regions, we identified 7 candidate genes; AGTR1, ACE, p38MAPK, SST, 5HT2B, NET1, and CALM3 for further analysis as significantly contributing QTL for ascites/PHS. We also used variable number tandem repeats to measure gene flow and gather evidence for multiple paternity in a population of Timber rattlesnakes, Crotalus horridus. We were able to verify 1 VNTR that can be used …

A Locus-Based Paradigm For Generating Systems Biological Inferences From Large Scale Functional Genomics Datasets, Ajish Dominic George

Legacy Theses & Dissertations (2009 - 2024)

Genomics data is growing at a exponential rate. The ability to integrate new results with existing knowledge about genomic biology is rapidly becoming the limiting factor as there no universal language with which to describe genomic functional elements. To integrate and compare new and existing genomic data, we define our basic functional unit of a genome to be a locus -- a set of positional coordinates along any genome with an arbitrary amount of functional annotations attached. The locus concept enables addressing genomic elements and annotations at any level of granularity from entire swaths of chromosomes to single base-positions. We …

Molecular Evolution Of Genes Underlying Phenotypic Differences Between Humans And Chimpanzees, Santhoshi Bandla

Legacy Theses & Dissertations (2009 - 2024)

Chimpanzees (Pan troglodytes) and bonobos (P. paniscus) are often used as models to study the genetic and morphological changes on the lineage leading to the modern humans (Homo sapiens). Results of this dissertation suggest that, in comparison to other hominoids, chimpanzees and bonobos are more derived in their relative testes sizes and promiscuous mating systems. Phylogenetic analysis of genes that might underlie increased testes size revealed that, in addition to being a sex-determining gene, SRY displays Pan-specific amino acid replacements that make it a compelling candidate as a testes-size determining gene. Strikingly, SRY and another candidate gene, DMRT3, display patterns …

Molecular Characterisation Of A Bovine-Like Rotavirus Detected From A Giraffe, Emily Mulherin, Jill Bryan, Marijke Beltman, Luke O'Grady, Eugene Pidgeon, Lucie Garon, Andrew Lloyd, John Bainbridge, Helen O'Shea, Paul Whyte, Séamus Fanning

Department of Biological Sciences Publications

Background

Rotavirus (RV), is a member of the Reoviridae family and an important etiological agent of acute viral gastroenteritis in the young. Rotaviruses have a wide host range infecting a broad range of animal species, however little is known about rotavirus infection in exotic animals. In this paper we report the first characterisation of a RV strain from a giraffe calf.

Results

This report describes the identification and detailed molecular characterisation of a rotavirus strain detected from a 14-day-old Giraffe (Giraffa camelopardalis), presenting with acute diarrhea. The RV strain detected from the giraffe was characterized molecularly as G10P[11]. …

Computational Design Of Orthogonal Ribosomes, Lon Chubiz, Christopher Rao

Biology Department Faculty Works

Orthogonal ribosomes (o-ribosomes), also known as specialized ribosomes, are able to selectively translate mRNA not recognized by host ribosomes. As a result, they are powerful tools for investigating translational regulation and probing ribosome structure. To date, efforts directed towards engineering o-ribosomes have involved random mutagenesisbased approaches. As an alternative, we present here a computational method for rationally designing o-ribosomes in bacteria. Working under the assumption that base-pair interactions between the 16S rRNA and mRNA serve as the primary mode for ribosome binding and translational initiation, the algorithm enumerates all possible extended recognition sequences for 16S rRNA and then chooses those …

Improved Constrained Global Optimization For Estimating Molecular Structure From Atomic Distances, Terri Marie Grant

Mathematics & Statistics Theses & Dissertations

Determination of molecular structure is commonly posed as a nonlinear optimization problem. The objective functions rely on a vast amount of structural data. As a result, the objective functions are most often nonconvex, nonsmooth, and possess many local minima. Furthermore, introduction of additional structural data into the objective function creates barriers in finding the global minimum, causes additional computational issues associated with evaluating the function, and makes physical constraint enforcement intractable. To combat the computational problems associated with standard nonlinear optimization formulations, Williams et al. (2001) proposed an atom-based optimization, referred to as GNOMAD, which complements a simple interatomic distance …

Novel Functions Of Acyl-Coa Thioesterases And Acyltransferases As Auxiliary Enzymes In Peroxisomal Lipid Metabolism., Mary Hunt, Stefan Alexson

Articles

Peroxisomes are single membrane bound organelles present in almost all eukaryotic cells, and to date have been shown to contain approximately 60 identified enzymes involved in various metabolic pathways, including the oxidation of a variety of lipids. These lipids include very long-chain fatty acids, methyl branched fatty acids, prostaglandins, bile acid precursors, and xenobiotics that are either β-oxidized or α-oxidized in peroxisomes. The recent identification of several acyl-CoA thioesterases and acyltransferases in peroxisomes has revealed their various functions in acting as auxiliary enzymes in α- and β-oxidation in this organelle. To date, 9 functional acyl-CoA thioesterases and acyltransferases have been …

Analysis Of The Mouse And Human Acyl-Coa Thioesterase (Acot) Gene Clusters Shows That Convergent, Functional Evolution Results In A Reduced Number Of Human Peroxisomal Acots., Mary Hunt, Anna Rautanen, Maria Westin, Thomas Svensson, Stefan Alexson

Articles

The maintenance of cellular levels of free fatty acids and acyl-CoAs, the activated form of free fatty acids, is extremely important as imbalances in lipid metabolism have serious consequences for human health. Acyl-CoA thioesterases (ACOTs) hydrolyze acyl-CoAs to the free fatty acid and CoASH, and thereby have the potential to regulate intracellular levels of these compounds. We have previously identified and characterized a mouse ACOT gene cluster, comprised of six genes that apparently arose by gene duplications, encoding acyl- CoA thioesterases with localizations in cytosol (ACOT1), mitochondria (ACOT2) and peroxisomes (ACOT3-6). However, the corresponding human gene cluster contains only three …

Evaluation Of Multiple Models To Distinguish Closely Related Forms Of Disease Using Dna Microarray Data: An Application To Multiple Myeloma, Johanna S. Hardin, Michael Waddell, C. David Page, Fenghuang Zhan, Bart Barlogie, John Shaughnessy, John J. Crowley

Pomona Faculty Publications and Research

Motivation: Standard laboratory classification of the plasma cell dyscrasia monoclonal gammopathy of undetermined significance (MGUS) and the overt plasma cell neoplasm multiple myeloma (MM) is quite accurate, yet, for the most part, biologically uninformative. Most, if not all, cancers are caused by inherited or acquired genetic mutations that manifest themselves in altered gene expression patterns in the clonally related cancer cells. Microarray technology allows for qualitative and quantitative measurements of the expression levels of thousands of genes simultaneously, and it has now been used both to classify cancers that are morphologically indistinguishable and to predict response to therapy. It is …