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Articles 91 - 120 of 838
Full-Text Articles in Biology
Aging, Fast And Slow: Gene Expression Signatures Of Physiological Age Vs. Future Lifespan In Caenorhabditis Elegans, Matthew Mosley
Aging, Fast And Slow: Gene Expression Signatures Of Physiological Age Vs. Future Lifespan In Caenorhabditis Elegans, Matthew Mosley
Arts & Sciences Graduate Student Theses and Dissertations
An outstanding question in the field of aging biology is the origin of variability in lifespans among members of the same species. Traditional wisdom dictates that differences in one individual’s genes or environment, “nature” and “nurture,” could predispose that individual to a long or short life. However, these explanations are radically incomplete. Even in a model system as homogenous as C. elegans, using an isogenic population in a lab-controlled environment, we observe a distribution in lifespans comparable to that seen in outbred human populations. The first part of this dissertation focuses on characterizing this non-genetic, non-environmental variability in the aging …
Gene Expression Regulation By Au-Rich Elements And Au-Rich Element Binding Proteins, Courtney Fay Jungers
Gene Expression Regulation By Au-Rich Elements And Au-Rich Element Binding Proteins, Courtney Fay Jungers
Arts & Sciences Graduate Student Theses and Dissertations
The regulation of messenger RNA (mRNA) splicing, stability, and translation efficiency are major modes for controlling gene expression – which is essential for life. RNA-binding proteins (RBPs) and microRNAs (miRNAs) are trans-acting factors that bind to cis-elements influencing the stability and translation of the mRNA transcript. AU-rich elements (AREs) are cis-elements that are targeted by AU-rich element binding proteins (ARE-BPs). Here, I show a novel role for AREs and AU-rich element binding protein 1 (AUF1) during alternative splicing and report on interactions of RBPs and miRNAs to design a new treatment for breast cancer by interrupting these interactions in the …
A Filter-Based Model Of Visual Recognition, Olivia Rose Bockler
A Filter-Based Model Of Visual Recognition, Olivia Rose Bockler
Arts & Sciences Graduate Student Theses and Dissertations
Visual recognition, a key perceptual process, enables primates to identify faces, food, tools, and potential threats in their environment. Cortical neurons along the ventral visual stream—spanning from early visual cortex (V1) through inferotemporal cortex (IT), with long-range projections to ventrolateral prefrontal cortex (vlPFC)—are essential for visual recognition. Traditional models propose that neuronal representations increase in complexity in each stage of this pathway, culminating in object-specific representations in higher-order cortex. However, this hypothesis remains debated, particularly as artificial visual models have countered that individual neurons along this pathway may function more as filters contributing to distributed representations of objects. Thus, this …
N-Methyl-D-Aspartate (Nmda) Receptors Control Calcium Signaling In Striatal Neurons To Guide Value-Based Learning, Alex Legaria Macal
N-Methyl-D-Aspartate (Nmda) Receptors Control Calcium Signaling In Striatal Neurons To Guide Value-Based Learning, Alex Legaria Macal
Arts & Sciences Graduate Student Theses and Dissertations
N-methyl-D-aspartate receptors (NMDARs) play an essential role in neuronal function. Activation of NMDARs leads to calcium influx into postsynaptic neurons, which regu?late many fundamental aspects of neuronal physiology including synaptic plasticity, gene expression, and excitability. In the striatum, the input region of the basal ganglia, NM?DAR activity has been shown to regulate physiological function of striatal neurons, such as synaptic plasticity and excitability, and they also modulate behavior, particularly op?erant learning. However, there are many fundamental questions about the signaling and effects of NMDARs in vivo that have yet to be resolved. Moreover, the link between the physiological and behavioral …
Avian Adaptation To Thermal Gradients, Justin Wheeler Baldwin
Avian Adaptation To Thermal Gradients, Justin Wheeler Baldwin
Arts & Sciences Graduate Student Theses and Dissertations
Life on Earth has adapted to extremely different temperatures worldwide. However, across distant branches of the tree of life, animals in similar temperature environments often share similar phenotypic traits. Specifically, traits that bear on the ratio between an individual’s surface area (e.g. appendage length) and its volume (e.g. body size) are particularly important for temperature regulation and are codified in canonical biogeographical rules. Although these global patterns of finding larger-bodied (Bergmann’s Rule) and shorter-limbed (Allen’s Rule) animals in colder regions are widely upheld, they also show substantial variation. It remains poorly understood why some animals conform to these biogeographical rules …
Pmp2+ Scs Maintain The Survival And Functioning Of Large-Caliber Motor Axons, Mikolaj Kozlowski
Pmp2+ Scs Maintain The Survival And Functioning Of Large-Caliber Motor Axons, Mikolaj Kozlowski
Arts & Sciences Graduate Student Theses and Dissertations
Neurodegenerative diseases are characterized by selective neuronal vulnerability, a phenomenon in which a specific pathology induces the death of a particular subpopulation of neurons. For example, selective neuronal vulnerability in the peripheral nervous system results in sensory, motor, or mixed peripheral neuropathies. While the intrinsic differences between neuronal subtypes cannot fully explain the basis of selective neuronal vulnerability, it is plausible that it partially stems from neuron extrinsic mechanisms such as the malfunction of distinct Schwann cell (SC) subtypes. Recently, we identified an exciting subpopulation of myelinating SCs characterized by the expression of Adamtsl1, Cldn14, and Pmp2 (hereafter referred to …
Understanding Sequence Determinants Of Functional Protein Dynamics Using Biophysical Simulations And Experiments, Upasana Lakshmi Mallimadugula
Understanding Sequence Determinants Of Functional Protein Dynamics Using Biophysical Simulations And Experiments, Upasana Lakshmi Mallimadugula
Arts & Sciences Graduate Student Theses and Dissertations
Mutations in the sequence of proteins associated with a disease often increase its risk or severity. They can also be a barrier to developing effective therapeutics for such diseases. One way in which mutations affect function is by altering dynamics that elude structural studies. Observing these changes requires methods that can report on movements of the protein on various timescales and is an ongoing challenge in biophysics and biochemistry. In this study I will use both experimental and computational techniques that can report on such dynamics to explore how small sequence changes shift the conformational landscape and consequently the function …
Sustainable Plastics From Plastic Metabolisms: Leveraging Purple Non-Sulfur Bacteria For Polyhydroxyalkanoate Synthesis, Eric Michael Conners
Sustainable Plastics From Plastic Metabolisms: Leveraging Purple Non-Sulfur Bacteria For Polyhydroxyalkanoate Synthesis, Eric Michael Conners
Arts & Sciences Graduate Student Theses and Dissertations
Purple non-sulfur bacteria (PNSB) are a taxonomically diverse group of gram-negative bacteria representing some of Earth’s most metabolically versatile life, with many genera capable of switching between the four major metabolic modes – chemoheterotrophy, chemoautotrophy, photoheterotrophy, and photoautotrophy. Today, we exploit this diversity to explore fundamental questions about microbial metabolism. At the same time, many researchers are eager to use PNSB as tools for biotechnological innovations. Yet there exists a gap between fundamental biology and applied science. Part of the challenge is that we rely on a handful of model organisms – namely, members of the genera Rhodopseudomonas and Rhodobacter …
Elucidating The Role Of Astrocytes In Norepinephrine Neuromodulation, Katheryn Bry Lefton
Elucidating The Role Of Astrocytes In Norepinephrine Neuromodulation, Katheryn Bry Lefton
Arts & Sciences Graduate Student Theses and Dissertations
Norepinephrine, a wakefulness-associated neuromodulator, profoundly reshapes neural systems, from synaptic circuits to behavior. Through decades of research, a substantial catalogue on the effects of noradrenergic signaling on behavior and networks has been generated. How norepinephrine remodels synaptic circuitry is widely thought to underlie the larger changes in neural networks and behavior, highlighting the need for a more thorough understanding of the circuit effects of norepinephrine neuromodulation. However, the mechanistic details of the norepinephrine on synapses are still unclear. In recent decades, a large body of work has shown that norepinephrine acts not just on neurons, but on glial cells including …
Deciphering Immune Suppression Mechanisms Of Primary And Metastatic Breast Cancer, Seunghyun Lee
Deciphering Immune Suppression Mechanisms Of Primary And Metastatic Breast Cancer, Seunghyun Lee
Arts & Sciences Graduate Student Theses and Dissertations
Immune checkpoint blockade (ICB) has revolutionized cancer treatment, receiving FDA approval for various previously incurable cancers. In breast cancer, the combination of pembrolizumab (an anti-PD-1 antibody) with chemotherapy has become the standard-of-care for early-stage (Keynote-522) and advance-stage (Keynote-355) triple-negative breast cancer (TNBC). Unfortunately, over 30% of TNBC patients fail to respond to the combined chemo-immune therapy treatment, and the causes are unknown. Furthermore, ICB has demonstrated poor results in hormone-receptor positive breast cancer. While it is well-established that breast cancer cells can evade immune responses, the specific mechanisms driving immune evasion remain unclear. Thus, deciphering the immune system's role in …
Epigenetic Mechanisms And Senescence In Aging And Cancer, Alla Karpova
Epigenetic Mechanisms And Senescence In Aging And Cancer, Alla Karpova
Arts & Sciences Graduate Student Theses and Dissertations
Aging is marked by the progressive decline of cellular and organ function. This process often manifests through DNA damage, epigenomic alterations, telomere shortening, and metabolic or mitochondrial dysfunction. As DNA damage and other stressors accumulate, cells take measures to prevent malignant transformation. One such measure is cellular senescence, a state of irreversible cell cycle arrest that halts the growth of pre-malignant cells. When cells are unable to enter senescence due to high levels of genomic alterations, they typically undergo apoptosis or necrosis. However, if mutations affect key driver genes, allowing cells to evade death, they may become malignant, continuing to …
The Challenges Of Diet Generalism In A Microbial Predator, Dictyostelium Discoideum, Shreenidhi Perukkaranai Madabhushi
The Challenges Of Diet Generalism In A Microbial Predator, Dictyostelium Discoideum, Shreenidhi Perukkaranai Madabhushi
Arts & Sciences Graduate Student Theses and Dissertations
Organisms vary widely in their diet breadth, ranging from specialists that feed on few resources to generalists that feed on many. Specialists have honed their ability to catch and process specific prey, but generalists must deal with prey that differ in nutritional quality and defensive mechanisms. Have generalist predators overcome costs associated with consuming multiple prey species or do they experience costly trade-offs when handling different prey? Generalist predators also live in environments that vary in the type and abundance of prey species. How do generalists navigate this variation in prey abundance and profitability and seek out their preferred prey? …
Accumbal Plasticity And Associated Behavioral Adaptations In The Spared Nerve Injury Model Of Chronic Neuropathic Pain, Yu-Hsuan Chang
Accumbal Plasticity And Associated Behavioral Adaptations In The Spared Nerve Injury Model Of Chronic Neuropathic Pain, Yu-Hsuan Chang
Arts & Sciences Graduate Student Theses and Dissertations
Chronic pain is a debilitating neurological disorder that affects hundreds of millions of individuals worldwide. It is associated with cognitive symptoms such as cognitive inflexibility, which is defined as the inability to adaptively update behavior in response to changing environmental conditions. To date, there are no effective treatments for these symptoms, even though they substantially contribute to the decreased quality of life of chronic pain patients and are associated with reduced efficacy of pain management strategies. Therefore, understanding the neural circuit adaptations that drive cognitive symptoms of chronic pain, like cognitive inflexibility, is essential for improving existing treatments for this …
Exploring The Role Of Tissue-Resident T Cells In Neurotropic Viral Infections And Opioid-Induced Immune Disorders During Exposure And Withdrawal, Shenjian Ai
Arts & Sciences Graduate Student Theses and Dissertations
Tissue-resident T cells play a crucial role in the immune response to neurotropic viral infections and opioid-induced immune disorders. Understanding the roles of tissue-resident T cells in these contexts is essential for developing therapeutic strategies to mitigate their detrimental effects while enhancing their protective functions. The chemokine receptor CXCR6 and its ligand CXCL16 are critical in maintaining the population of tissue-resident T cells in the CNS. CXCR6 is expressed on CD8 T cells that persist in the CNS after recovery from West Nile virus infection. Research has shown that CXCL16, produced by microglia and other myeloid cells, binds to CXCR6 …
Clock Hijackers: How Integration Of Glioblastoma Into Circadian Circuits Regulates Tumor Progression And Sensitivity To Current Therapies, Maria Felicita Gonzalez
Clock Hijackers: How Integration Of Glioblastoma Into Circadian Circuits Regulates Tumor Progression And Sensitivity To Current Therapies, Maria Felicita Gonzalez
Arts & Sciences Graduate Student Theses and Dissertations
Glioblastoma (GBM) is the most common primary brain tumor in adults with a poor prognosis despite aggressive therapy. A recent, retrospective clinical study found that administering chemotherapy with Temozolomide (TMZ) in the morning increased patient overall survival by 6 months compared to evening. Previous work has shown that murine and human models of GBM have cell-intrinsic circadian rhythms in expression of the core clock genes Bmal1 and Per2 in vitro. This suggests that GBM has circadian rhythms that entrain to the hosts’ central clock. Understanding the mechanisms underlying circadian entrainment and tumor growth in GBM is essential to determine whether …
Treatment Modifications And Development For Mucopolysaccharidosis Type I, Sarah Hurt
Treatment Modifications And Development For Mucopolysaccharidosis Type I, Sarah Hurt
Arts & Sciences Graduate Student Theses and Dissertations
Mucopolysaccharidosis type I (MPS I) is a pediatric lysosomal storage disorder caused by biallelic pathogenic variants in the α-L-iduronidase (IDUA) gene that lead to the loss of a functional form of IDUA enzyme. Loss of this necessary enzyme leads to pathogenic accumulation of glycosaminoglycans (GAG) in lysosomes, leading to cellular distention and dysfunction. IDUA is necessary in every cell of the body and, as a result, a loss of function leads to clinical manifestations of the disease such as developmental delay, cardiac dysfunction, bone disease (dysostosis multiplex), upper respiratory complications, and premature death. A range of severity occurs, with Hurler …
Treatment Modifications And Development For Mucopolysaccharidosis Type I, Sarah Hurt
Treatment Modifications And Development For Mucopolysaccharidosis Type I, Sarah Hurt
Arts & Sciences Graduate Student Theses and Dissertations
Mucopolysaccharidosis type I (MPS I) is a pediatric lysosomal storage disorder caused by biallelic pathogenic variants in the α-L-iduronidase (IDUA) gene that lead to the loss of a functional form of IDUA enzyme. Loss of this necessary enzyme leads to pathogenic accumulation of glycosaminoglycans (GAG) in lysosomes, leading to cellular distention and dysfunction. IDUA is necessary in every cell of the body and, as a result, a loss of function leads to clinical manifestations of the disease such as developmental delay, cardiac dysfunction, bone disease (dysostosis multiplex), upper respiratory complications, and premature death. A range of severity occurs, with Hurler …
Elucidating The Heterogeneity And Epigenetic Determinants Of Memory-Like Natural Killer Cell Differentiation, Jennifer Tran
Elucidating The Heterogeneity And Epigenetic Determinants Of Memory-Like Natural Killer Cell Differentiation, Jennifer Tran
Arts & Sciences Graduate Student Theses and Dissertations
Natural killer (NK) cells are innate lymphoid cells that are a first line of defense against virally infected or malignant cells. Their ability to recognize and kill target cells is controlled by engagement of inhibitory, activating, and cytokine receptors. This leads to release of granules that contain perforin and granzymes, expression of death receptor ligands, and production of cytokines and chemokines. An effective NK cell response results in target cell death, along with changes in the nearby cellular microenvironment to promote immunity. As such NK cells play an essential role in tumor immunosurveillance, and there is an inverse correlation between …
Elucidating The Heterogeneity And Epigenetic Determinants Of Memory-Like Natural Killer Cell Differentiation, Jennifer Tran
Elucidating The Heterogeneity And Epigenetic Determinants Of Memory-Like Natural Killer Cell Differentiation, Jennifer Tran
Arts & Sciences Graduate Student Theses and Dissertations
Natural killer (NK) cells are innate lymphoid cells that are a first line of defense against virally infected or malignant cells. Their ability to recognize and kill target cells is controlled by engagement of inhibitory, activating, and cytokine receptors. This leads to release of granules that contain perforin and granzymes, expression of death receptor ligands, and production of cytokines and chemokines. An effective NK cell response results in target cell death, along with changes in the nearby cellular microenvironment to promote immunity. As such NK cells play an essential role in tumor immunosurveillance, and there is an inverse correlation between …
Rapid Unleashing Macrophage Efferocytic Capacity By Transcriptional Pause Release, Turan Tufan
Rapid Unleashing Macrophage Efferocytic Capacity By Transcriptional Pause Release, Turan Tufan
Arts & Sciences Graduate Student Theses and Dissertations
During development, inflammation or tissue injury, macrophages engulf multiple apoptotic cells via efferocytosis to maintain tissue homeostasis. The mechanism by which macrophages rapidly adapt their transcription for continuous corpse uptake is not well understood. Transcriptional pause/release is a conserved mechanism, in which RNA polymerase (Pol) II initiates transcription for 20-60 nucleotides, is paused for minutes to hours and is then released to the elongation phase. We show that macrophages quickly use Pol II pause/release upon encountering corpses to trigger a rapid transcriptional response. This mechanism is essential for continuous efferocytosis but does not affect other forms of phagocytosis. Genomic data …
The Role Of Group 2 Innate Lymphoid Cells In Restoring Lung Health And Chitinase Function After Epithelial Injury, Haerin Jung
The Role Of Group 2 Innate Lymphoid Cells In Restoring Lung Health And Chitinase Function After Epithelial Injury, Haerin Jung
Arts & Sciences Graduate Student Theses and Dissertations
Alveolar epithelial cells provide oxygen transport and act as a first line of defense against pathogens and environmental triggers that disturb tissue homeostasis. However, in the context of epithelial injury, fibrotic and inflammatory lung diseases develop where regenerative responses may become dysregulated or recurrently engaged. One cause of lung injury is infection with cytopathic respiratory viruses such as influenza and SARS-CoV-2 viruses, which induce lung inflammation, tissue damage, and epithelial cell injury and loss. Restoration of barrier integrity after lung injury is critical for re-establishing healthy lung function but the underlying mechanisms are unclear. In the steady state, lung epithelial …
The Role Of Group 2 Innate Lymphoid Cells In Restoring Lung Health And Chitinase Function After Epithelial Injury, Haerin Jung
The Role Of Group 2 Innate Lymphoid Cells In Restoring Lung Health And Chitinase Function After Epithelial Injury, Haerin Jung
Arts & Sciences Graduate Student Theses and Dissertations
Alveolar epithelial cells provide oxygen transport and act as a first line of defense against pathogens and environmental triggers that disturb tissue homeostasis. However, in the context of epithelial injury, fibrotic and inflammatory lung diseases develop where regenerative responses may become dysregulated or recurrently engaged. One cause of lung injury is infection with cytopathic respiratory viruses such as influenza and SARS-CoV-2 viruses, which induce lung inflammation, tissue damage, and epithelial cell injury and loss. Restoration of barrier integrity after lung injury is critical for re-establishing healthy lung function but the underlying mechanisms are unclear. In the steady state, lung epithelial …
Rapid Unleashing Macrophage Efferocytic Capacity By Transcriptional Pause Release, Turan Tufan
Rapid Unleashing Macrophage Efferocytic Capacity By Transcriptional Pause Release, Turan Tufan
Arts & Sciences Graduate Student Theses and Dissertations
During development, inflammation or tissue injury, macrophages engulf multiple apoptotic cells via efferocytosis to maintain tissue homeostasis. The mechanism by which macrophages rapidly adapt their transcription for continuous corpse uptake is not well understood. Transcriptional pause/release is a conserved mechanism, in which RNA polymerase (Pol) II initiates transcription for 20-60 nucleotides, is paused for minutes to hours and is then released to the elongation phase. We show that macrophages quickly use Pol II pause/release upon encountering corpses to trigger a rapid transcriptional response. This mechanism is essential for continuous efferocytosis but does not affect other forms of phagocytosis. Genomic data …
Aging Drives Cd8 T Cells To Functional Extremes: From Non-Specific Cytotoxicity To Tissue-Mediated Exhaustion, Irina Shchukina
Aging Drives Cd8 T Cells To Functional Extremes: From Non-Specific Cytotoxicity To Tissue-Mediated Exhaustion, Irina Shchukina
Arts & Sciences Graduate Student Theses and Dissertations
CD8 T cells are a crucial component of the immune system, primarily responsible for executing the effector response against viral infections and cancer. Aging significantly impacts most immune cell types, with particularly dramatic changes observed in CD8 T cells. One major age-related difference is the marked decline in thymus activity, which leads to a substantial reduction in naive CD8 T cells and an increased abundance of memory CD8 T cells. Furthermore, recent work from our lab demonstrated that while young memory CD8 T cells are relatively homogeneous, memory CD8 T cells diverge into two subpopulations: PD1- memory CD8 T cells …
Aging Drives Cd8 T Cells To Functional Extremes: From Non-Specific Cytotoxicity To Tissue-Mediated Exhaustion, Irina Shchukina
Aging Drives Cd8 T Cells To Functional Extremes: From Non-Specific Cytotoxicity To Tissue-Mediated Exhaustion, Irina Shchukina
Arts & Sciences Graduate Student Theses and Dissertations
CD8 T cells are a crucial component of the immune system, primarily responsible for executing the effector response against viral infections and cancer. Aging significantly impacts most immune cell types, with particularly dramatic changes observed in CD8 T cells. One major age-related difference is the marked decline in thymus activity, which leads to a substantial reduction in naive CD8 T cells and an increased abundance of memory CD8 T cells. Furthermore, recent work from our lab demonstrated that while young memory CD8 T cells are relatively homogeneous, memory CD8 T cells diverge into two subpopulations: PD1- memory CD8 T cells …
Mechanisms Of Uropathogenic E. Coli Reservoir Formation In The Gastrointestinal Tract, Philippe Nimma Azimzadeh
Mechanisms Of Uropathogenic E. Coli Reservoir Formation In The Gastrointestinal Tract, Philippe Nimma Azimzadeh
Arts & Sciences Graduate Student Theses and Dissertations
Urinary tract infections (UTI) are an extremely common affliction affecting 150 million people worldwide each year. UTIs are a leading cause of antibiotic therapy among otherwise healthy adult women, accounting for 15% of all outpatient antibiotic prescriptions. Uropathogenic Escherichia coli (UPEC) cause over 80% of community-acquired UTIs. Even when infection is cleared from the urine by clinical antibiotic regimens, 27% of women will experience recurrent UTI (rUTI) within months. Greater than 60% of rUTIs are caused by the same strain of E. coli that caused the initial infection, suggesting that one or more host-associated reservoirs of UPEC can re-inoculate the …
Mechanisms Of Uropathogenic E. Coli Reservoir Formation In The Gastrointestinal Tract, Philippe Nimma Azimzadeh
Mechanisms Of Uropathogenic E. Coli Reservoir Formation In The Gastrointestinal Tract, Philippe Nimma Azimzadeh
Arts & Sciences Graduate Student Theses and Dissertations
Urinary tract infections (UTI) are an extremely common affliction affecting 150 million people worldwide each year. UTIs are a leading cause of antibiotic therapy among otherwise healthy adult women, accounting for 15% of all outpatient antibiotic prescriptions. Uropathogenic Escherichia coli (UPEC) cause over 80% of community-acquired UTIs. Even when infection is cleared from the urine by clinical antibiotic regimens, 27% of women will experience recurrent UTI (rUTI) within months. Greater than 60% of rUTIs are caused by the same strain of E. coli that caused the initial infection, suggesting that one or more host-associated reservoirs of UPEC can re-inoculate the …
Sleep Restores An Optimal Computational Regime In Cortical Networks, Yifan Xu
Sleep Restores An Optimal Computational Regime In Cortical Networks, Yifan Xu
Arts & Sciences Graduate Student Theses and Dissertations
Computation within the brain necessitates consistency and robustness, as no complex system can function effectively without these fundamental attributes. However, maintaining this robustness requires active efforts due to the inevitable perturbations (Turrigiano & Nelson, 2004). To unlock the unifying principle of how brain works, it is essential to identify an optimal set point that the system strives to maintain and restore, ensuring stability and functionality. Our lab recently demonstrated that cortical dynamics are homeostatically organized around criticality (Ma et al., 2019), a computational regime that optimizes information processing, such as information capacity and dynamic range (Shew & Plenz, 2013). This …
Germline Genetic Determinates Of Cancer And Pre-Malignant Conditions, Jie Liu
Germline Genetic Determinates Of Cancer And Pre-Malignant Conditions, Jie Liu
Arts & Sciences Graduate Student Theses and Dissertations
Cancer is a genetic disease stemming from a combination of inherited and acquired mutations. In my thesis, we sought to characterize how germline genetic variation affects acquired clonal expansions in normal tissues and its progression to malignancy. In Chapter 2, we studied the impact of germline genetic variation on clonal hematopoiesis (CH) in 731,835 individuals. We identified 22 novel CH predisposition genes, most of which predispose to CH driven by specific mutational events. CH predisposition genes contribute to unique somatic landscapes reflecting the influence of germline genetic backdrop on gene-specific CH fitness. Correspondingly, somatic-germline interactions influence the risk of CH …
Developing Tools To Study The Effect Of The Mechanical Environment On Plant Cell Growth And Morphogenesis, Ryan Calcutt
Developing Tools To Study The Effect Of The Mechanical Environment On Plant Cell Growth And Morphogenesis, Ryan Calcutt
Arts & Sciences Graduate Student Theses and Dissertations
Mechanical forces are omnipresent in life on Earth and responses to force can be found across all three domains of life. The colonization of land by plants approximately 500 million years ago, an event that shaped life on Earth as we know it, involved adaptation from a relatively homogeneous fluid mechanical environment to a highly heterogeneous and mechanically diverse terrestrial environment. Evolution of multicellularity would present new mechanical challenges for land plants, not only from externally generated forces, but also from mechanical linkage to neighboring cells through the cell wall. Coordination of cell growth and an indeterminate body plan requires …