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Full-Text Articles in Cell Biology

Systematic Dissection Of Roles For Chromatin Regulators In Dynamics Of Transcriptional Response To Stress In Yeast: A Dissertation, Hsiuyi V. Chen Dec 2015

Systematic Dissection Of Roles For Chromatin Regulators In Dynamics Of Transcriptional Response To Stress In Yeast: A Dissertation, Hsiuyi V. Chen

GSBS Dissertations and Theses

The following work demonstrates that chromatin regulators play far more pronounced roles in dynamic gene expression than they do in steady-state. Histone modifications have been associated with transcription activity. However, previous analyses of gene expression in mutants affecting histone modifications show limited alteration. I systematically dissected the effects of 83 histone mutants and 119 gene deletion mutants on gene induction/repression in response to diamide stress in yeast. Importantly, I observed far more changes in gene induction/repression than changes in steady-state gene expression. The extensive dynamic gene expression profile of histone mutants and gene deletion mutants also allowed me ...


Roles Of Protein Arginine Methyltransferase 7 And Jumonji Domain-Containing Protein 6 In Adipocyte Differentiation: A Dissertation, Yu-Jie Hu Oct 2015

Roles Of Protein Arginine Methyltransferase 7 And Jumonji Domain-Containing Protein 6 In Adipocyte Differentiation: A Dissertation, Yu-Jie Hu

GSBS Dissertations and Theses

Regulation of gene expression comprises a wide range of mechanisms that control the abundance of gene products in response to environmental and developmental changes. These biological processes can be modulated by posttranslational modifications including arginine methylation. Among the enzymes that catalyze the methylation, protein arginine methyltransferase 7 (PRMT7) is known to modify histones to repress gene expression. Jumonji domain-containing protein 6 (JMJD6) is a putative arginine demethylase that potentially antagonize PRMT7. However, the biological significance of these enzymes is not well understood. This thesis summarizes the investigation of both PRMT7 and JMJD6 in cell culture models for adipocyte differentiation. The ...


Exploring The Role Of Fus Mutants From Stress Granule Incorporation To Nucleopathy In Amyotrophic Lateral Sclerosis: A Dissertation, Hae Kyung Ko Sep 2015

Exploring The Role Of Fus Mutants From Stress Granule Incorporation To Nucleopathy In Amyotrophic Lateral Sclerosis: A Dissertation, Hae Kyung Ko

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by preferential motor neuron death in the brain and spinal cord. The rapid disease progression results in death due to respiratory failure, typically within 3-5 years after disease onset. While ~90% of cases occur sporadically, remaining 10% of ALS cases show familial inheritance, and the number of genes linked to ALS has increased dramatically over the past decade.

FUS/TLS (Fused in Sarcoma/ Translocated to liposarcoma) is a nucleic acid binding protein that may regulate several cellular functions, including RNA splicing, transcription, DNA damage repair and microRNA biogenesis. More than ...


Investigating The Effects Of Mutant Fus On Stress Response In Amyotrophic Lateral Sclerosis: A Thesis, Laura J. Kaushansky Aug 2015

Investigating The Effects Of Mutant Fus On Stress Response In Amyotrophic Lateral Sclerosis: A Thesis, Laura J. Kaushansky

GSBS Dissertations and Theses

During stress, eukaryotes regulate protein synthesis in part through formation of cytoplasmic, non-membrane-bound complexes called stress granules (SGs). SGs transiently store signaling proteins and stalled translational complexes in response to stress stimuli (e.g. oxidative insult, DNA damage, temperature shifts and ER dysfunction). The functional outcome of SGs is proper translational regulation and signaling, allowing cells to overcome stress.

The fatal motor neuron disease Amyotrophic Lateral Sclerosis (ALS) develops in an age-related manner and is marked by progressive neuronal death, with cytoplasmic protein aggregation, excitotoxicity and increased oxidative stress as major hallmarks. Fused in Sarcoma/Translocated in Liposarcoma (FUS) is ...


Jun Kinases In Hematopoiesis, And Vascular Development And Function: A Dissertation, Kasmir Ramo Jul 2015

Jun Kinases In Hematopoiesis, And Vascular Development And Function: A Dissertation, Kasmir Ramo

GSBS Dissertations and Theses

Arterial occlusive diseases are major causes of morbidity and mortality in industrialized countries and represent a huge economic burden. The extent of the native collateral circulation is an important determinant of blood perfusion restoration and therefore the severity of tissue damage and functional impairment that ensues following arterial occlusion. Understanding the mechanisms responsible for collateral artery development may provide avenues for therapeutic intervention. Here, we identify a critical requirement for mixed lineage kinase (MLK) – cJun-NH2-terminal kinase (JNK) signaling in vascular morphogenesis and native collateral artery development. We demonstrate that Mlk2-/-Mlk3-/- mice or mice with compound JNK-deficiency in the vascular ...


Cell Size Control In The Fission Yeast Schizosaccharomyces Pombe: A Dissertation, Daniel L. Keifenheim Jun 2015

Cell Size Control In The Fission Yeast Schizosaccharomyces Pombe: A Dissertation, Daniel L. Keifenheim

GSBS Dissertations and Theses

The coordination between cell growth and division is a highly regulated process that is intimately linked to the cell cycle. Efforts to identify an independent mechanism that measures cell size have been unsuccessful. Instead, we propose that size control is an intrinsic function of the basic cell cycle machinery.

My work shows that in the fission yeast Schizosaccharomyces pombe Cdc25 accumulates in a size dependent manner. This accumulation of Cdc25 occurs over a large range of cell sizes. Additionally, experiments with short pulses of cycloheximide have shown that Cdc25 is an inherently unstable protein that quickly returns to a size ...


Cathosis: Cathepsins In Particle-Induced Inflammatory Cell Death: A Dissertation, Gregory M. Orlowski May 2015

Cathosis: Cathepsins In Particle-Induced Inflammatory Cell Death: A Dissertation, Gregory M. Orlowski

GSBS Dissertations and Theses

Sterile particles underlie the pathogenesis of numerous inflammatory diseases. These diseases can often become chronic and debilitating. Moreover, they are common, and include silicosis (silica), asbestosis (asbestos), gout (monosodium urate), atherosclerosis (cholesterol crystals), and Alzeihmer’s disease (amyloid Aβ). Central to the pathology of these diseases is a repeating cycle of particle-induced cell death and inflammation. Macrophages are the key cellular mediators thought to drive this process, as they are especially sensitive to particle-induced cell death and they are also the dominant producers of the cytokine responsible for much of this inflammation, IL-1β. In response to cytokines or microbial cues ...


Role And Regulation Of Autophagy During Developmental Cell Death In Drosophila Melanogaster: A Dissertation, Kirsten M. Tracy Apr 2015

Role And Regulation Of Autophagy During Developmental Cell Death In Drosophila Melanogaster: A Dissertation, Kirsten M. Tracy

GSBS Dissertations and Theses

Autophagy is a conserved catabolic process that traffics cellular components to the lysosome for degradation. Autophagy is required for cell survival during nutrient restriction, but it has also been implicated in programmed cell death. It is associated with several diseases, including cancer. Cancer is a disease characterized by aberrant cell growth and proliferation. To support this growth, the tumor cell often deregulates several metabolic processes, including autophagy. Interestingly, autophagy plays paradoxical roles in tumorigenesis. It has been shown to be both tumor suppressive through cell death mechanisms and tumor promoting through its cytoprotective properties. However, the mechanisms regulating the balance ...


A Tale Of Two Projects: Basis For Centrosome Amplification After Dna Damage And Practical Assessment Of Photodamage In Live-Cell Imaging: A Dissertation, Stephen Douthwright Apr 2015

A Tale Of Two Projects: Basis For Centrosome Amplification After Dna Damage And Practical Assessment Of Photodamage In Live-Cell Imaging: A Dissertation, Stephen Douthwright

GSBS Dissertations and Theses

This thesis comprises two separate studies that focus on the consequences of cellular damage. The first investigates the effects of DNA damage on centriole behavior and the second characterizes phototoxicity during live-cell imaging.

Cancer treatments such as ionizing radiation and/or chemotherapeutic DNA damaging agents are intended to kill tumor cells, but they also damage normal proliferating cells. Although centrosome amplification after DNA damage is a well-established phenomenon for transformed cells, it is not fully understood in untransformed cells. The presence of extra centrosomes in normal cell populations raises the chances of genomic instability, thus posing additional threats to patients ...


Microrna Regulation Of Autophagy During Programmed Cell Death: A Dissertation, Charles J. Nelson Mar 2015

Microrna Regulation Of Autophagy During Programmed Cell Death: A Dissertation, Charles J. Nelson

GSBS Dissertations and Theses

Autophagy delivers cytoplasmic material to the lysosome for degradation, and has been implicated in many cellular processes, including stress, infection, survival, and death. Although the regulation and role that autophagy plays in stress, infection, and survival is apparent, its involvement during cell death remains relatively unclear. In this thesis I summarize what is known about the roles autophagy can play in cell death, and the differences between the utilization of autophagy during nutrient deprivation and cell death. Utilizing Drosophila melanogaster as a model system, the roles autophagy plays in both of these contexts can be studied. The goal of this ...


Function And Regulation Of The Α6 Integrins In Mammary Epithelial Biology And Breast Cancer: A Dissertation, Cheng Chang Feb 2015

Function And Regulation Of The Α6 Integrins In Mammary Epithelial Biology And Breast Cancer: A Dissertation, Cheng Chang

GSBS Dissertations and Theses

Integrins have the ability to impact major aspects of epithelial biology including adhesion, migration, invasion, signaling and differentiation, as well as the formation and progression of cancer (Hynes 2002; Srichai and Zent 2010; Anderson et al. 2014). This thesis focuses on how integrins are regulated and function in the context of mammary epithelial biology and breast cancer with a specific focus on the α6 integrin heterodimers (α6β1 and α6β4). These integrins function primarily as receptors for the laminin family of extracellular matrix (ECM) proteins and they have been implicated in mammary gland biology and breast cancer (Friedrichs et al. 1995 ...


Calcium Dependent Regulatory Mechanism In Wolfram Syndrome: A Dissertation, Simin Lu Feb 2015

Calcium Dependent Regulatory Mechanism In Wolfram Syndrome: A Dissertation, Simin Lu

GSBS Dissertations and Theses

Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration. Two causative genes have been identified so far, WFS1 and WFS2, both encoding endoplasmic reticulum (ER) localized transmembrane proteins. Since WFS1 is involved in the ER stress pathway, Wolfram syndrome is considered an ER disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome, the molecular mechanism linking ER to the death of β cells and neurons has not been elucidated.

The endoplasmic reticulum (ER) is an organelle that forms a network of enclosed sacs and tubes that connect the nuclear membrane and other organelles including Golgi and ...