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Full-Text Articles in Biochemistry
Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw
Dissertations & Theses (Open Access)
Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …
Ngly1 Deficiency Affects Glycosaminoglycan Biosynthesis And Wnt Signaling Pathway In Mice, Amy Batten
Ngly1 Deficiency Affects Glycosaminoglycan Biosynthesis And Wnt Signaling Pathway In Mice, Amy Batten
PANDION: The Osprey Journal of Research and Ideas
Individuals affected by NGLY1 Deficiency cannot properly deglycosylate and recycle certain proteins. Even though less than 100 people worldwide have been diagnosed with this rare autosomal recessive condition, thousands are affected by similar glycosylation disorders. Common phenotypic manifestations of NGLY1 Deficiency include severe neural and intellectual delay, impaired muscle and liver function, and seizures that may become intractable. Very little is currently known about the various mechanisms through which NGLY1 deficiency affects the body and this has led to a lack of viable treatment options for those afflicted. This experiment uses a loss-of-function (LOF) mouse model of NGLY1 Deficiency homologous …
Assembly Of The Peripheral Arm Subunits Of Escherichia Coli Complex I And Analysis Of Clinical Mutations, Hind Alkhaldi
Assembly Of The Peripheral Arm Subunits Of Escherichia Coli Complex I And Analysis Of Clinical Mutations, Hind Alkhaldi
Biological Sciences Theses and Dissertations
Respiratory Complex I from E. coli is a proto-type of the mitochondrial enzyme, consisting of a 6-subunit peripheral arm (B-CD-E-F-G-I) and a 7-subunit membrane arm. When subunits E-F-G (N-module), were expressed alone they formed an active complex as determined by co-immunoprecipitation and native gel electrophoresis. When co-expressed with subunits B and CD, only a complex of E-F-G was found. When these five subunits were co-expressed with subunit I and two membrane subunits, A and H, a complex of B-CD-E-F-G-I was membrane-bound, constituting the N- and Q-modules. Assembly of Complex I was also followed by splitting the genes between two plasmids, …
Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro
Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro
Senior Honors Projects
In recent years, advancements in genetic testing methods have revolutionized the medical field by enhancing the ability to identify persons with an inherited predisposition to cancer. According to the American Society for Clinical Oncology, individuals should undergo genetic testing when he or she meets the following criteria: the individual demonstrates familial history that indicates a predisposition to certain cancers, the test can be adequately interpreted, and the results will aid in the diagnosis, treatment, or management of the patient or additional family members at risk. Genetic testing can be done on samples of hair, skin, blood, amniotic fluid, or other …
Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek
Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek
Dissertations, Theses, and Capstone Projects
Escherichia coli is a well-known pathogen, and importantly, a widely used model organism in all fields of biological sciences for cloning, protein purification, and as a model for Gram-negative bacterial species. And yet, researchers do not fully understand how this bacterium replicates and divides. Every year additional division proteins are discovered, which adds complexity to how we understand E. coli undergoes cell division. Due to their specific roles in cytokinesis, some of these proteins may be potential targets for development of antibacterials or bacteriostatics, which are much needed for fighting the current global antibacterial deficit. My thesis work focuses on …
Identification Of Set1 Target Genes, William Beyer, Scott D. Briggs
Identification Of Set1 Target Genes, William Beyer, Scott D. Briggs
The Summer Undergraduate Research Fellowship (SURF) Symposium
The Set1 complex, a histone methyltransferase complex found in S. cerevisiae (budding yeast), is the only histone methyltransferase responsible for catalyzing methylation of histone H3 at Lysine 4. It possesses homologues in other species, humans included. While yeast only have the Set1 complex, the human homologues of the yeast Set1 complex include mixed-lineage leukemia family (MLL1-4), Set1 A, Set1 B, among others. MLL1-4 has been shown to play a role in transcription, cell type specification, and the development of leukemia. One application of characterizing the role of a protein is that the information gained can provide insight into the function …
Integral Membrane Proteins Brr6 And Apq12 Link Assembly Of The Nuclear Pore Complex To Lipid Homeostasis In The Endoplasmic Reticulum, Christine A. Hodge, Vineet Choudhary, Michael J. Wolyniak, John J. Scarcelli, Roger Schneiter, Charles N. Cole
Integral Membrane Proteins Brr6 And Apq12 Link Assembly Of The Nuclear Pore Complex To Lipid Homeostasis In The Endoplasmic Reticulum, Christine A. Hodge, Vineet Choudhary, Michael J. Wolyniak, John J. Scarcelli, Roger Schneiter, Charles N. Cole
Dartmouth Scholarship
Cells of Saccharomyces cerevisiae lacking Apq12, a nuclear envelope (NE)-endoplasmic reticulum (ER) integral membrane protein, are defective in assembly of nuclear pore complexes (NPCs), possibly because of defects in regulating membrane fluidity. We identified BRR6, which encodes an essential integral membrane protein of the NE-ER, as a dosage suppressor of apq12 Delta. Cells carrying the temperature-sensitive brr6-1 allele have been shown to have defects in nucleoporin localization, mRNA metabolism and nuclear transport. Electron microscopy revealed that brr6-1 cells have gross NE abnormalities and proliferation of the ER. brr6-1 cells were hypersensitive to compounds that affect membrane biophysical properties and to …
The Yeast Integral Membrane Protein Apq12 Potentially Links Membrane Dynamics To Assembly Of Nuclear Pore Complexes, John J. Scarcelli, Christin A. Hodge, Charles N. Cole
The Yeast Integral Membrane Protein Apq12 Potentially Links Membrane Dynamics To Assembly Of Nuclear Pore Complexes, John J. Scarcelli, Christin A. Hodge, Charles N. Cole
Dartmouth Scholarship
Although the structure and function of components of the nuclear pore complex (NPC) have been the focus of many studies, relatively little is known about NPC biogenesis. In this study, we report that Apq12 is required for efficient NPC biogenesis in Saccharomyces cerevisiae. Apq12 is an integral membrane protein of the nuclear envelope (NE) and endoplasmic reticulum. Cells lacking Apq12 are cold sensitive for growth, and a subset of their nucleoporins (Nups), those that are primarily components of the cytoplasmic fibrils of the NPC, mislocalize to the cytoplasm. APQ12 deletion also causes defects in NE morphology. In the absence of …
The Yeast Orthologue Of Grasp65 Forms A Complex With A Coiled-Coil Protein That Contributes To Er To Golgi Traffic, Rudy Behnia, Francis A. Barr, John J. Flanagan, Charles Barlowe, Sean Munro
The Yeast Orthologue Of Grasp65 Forms A Complex With A Coiled-Coil Protein That Contributes To Er To Golgi Traffic, Rudy Behnia, Francis A. Barr, John J. Flanagan, Charles Barlowe, Sean Munro
Dartmouth Scholarship
The mammalian Golgi protein GRASP65 is required in assays that reconstitute cisternal stacking and vesicle tethering. Attached to membranes by an N-terminal myristoyl group, it recruits the coiled-coil protein GM130. The relevance of this system to budding yeasts has been unclear, as they lack an obvious orthologue of GM130, and their only GRASP65 relative (Grh1) lacks a myristoylation site and has even been suggested to act in a mitotic checkpoint. In this study, we show that Grh1 has an N-terminal amphipathic helix that is N-terminally acetylated and mediates association with the cis-Golgi. We find that Grh1 forms a complex with …
The Allantois And Chorion, When Isolated Before Circulation Or Chorio-Allantoic Fusion, Have Hematopoietic Potential, Brandon M. Zeigler, Daisuke Sugiyama, Michael Chen, Yalin Guo, K. M. Downs, N. A. Speck
The Allantois And Chorion, When Isolated Before Circulation Or Chorio-Allantoic Fusion, Have Hematopoietic Potential, Brandon M. Zeigler, Daisuke Sugiyama, Michael Chen, Yalin Guo, K. M. Downs, N. A. Speck
Dartmouth Scholarship
The chorio-allantoic placenta forms through the fusion of the allantois (progenitor tissue of the umbilical cord), with the chorionic plate. The murine placenta contains high levels of hematopoietic stem cells, and is therefore a stem cell niche. However, it is not known whether the placenta is a site of hematopoietic cell emergence, or whether hematopoietic cells originate from other sites in the conceptus and then colonize the placenta. Here, we show that the allantois and chorion, isolated prior to the establishment of circulation, have the potential to give rise to myeloid and definitive erythroid cells following explant culture. We further …
Dictyostelium Myosin-Ie Is A Fast Molecular Motor Involved In Phagocytosis, Ulrike Durrwang, Setsuko Fujita-Becker, Muriel Erent, F. Jon Kull
Dictyostelium Myosin-Ie Is A Fast Molecular Motor Involved In Phagocytosis, Ulrike Durrwang, Setsuko Fujita-Becker, Muriel Erent, F. Jon Kull
Dartmouth Scholarship
Class I myosins are single-headed motor proteins, implicated in various motile processes including organelle translocation, ion-channel gating, and cytoskeleton reorganization. Here we describe the cellular localization of myosin-IE and its role in the phagocytic uptake of solid particles and cells. A complete analysis of the kinetic and motor properties of Dictyostelium discoideum myosin-IE was achieved by the use of motor domain constructs with artificial lever arms. Class I myosins belonging to subclass IC like myosin-IE are thought to be tuned for tension maintenance or stress sensing. In contrast to this prediction, our results show myosin-IE to be a fast motor. …