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Understanding The Effect Modifications Of 2d Materials Have On Conductivity Using Terahertz Spectroscopy, Matt David Capobianco Oct 2023

Understanding The Effect Modifications Of 2d Materials Have On Conductivity Using Terahertz Spectroscopy, Matt David Capobianco

Yale Graduate School of Arts and Sciences Dissertations

Due to the current condition of our climate, we need to continue implementing greener methods into our energy infrastructure. While green energy production has been effectively implemented, there is still a need for greener energy storage. Heterogenous photocatalysis can store energy from the sun in chemical bonds, via alternative fuel production, in order to achieve greener energy storage. 2D materials are a class of heterogenous photocatalysts that are of major interest due to their manipulability, large surface areas, and more. A key property of these heterogenous photocatalysts is photoconductivity, which directly correlates to their photocatalytic rate. Terahertz (THz) spectroscopy is …

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The Role Of Mechanical Forces In Biological Motion And Morphology, Sorosh Amiri Oct 2023

The Role Of Mechanical Forces In Biological Motion And Morphology, Sorosh Amiri

Yale Graduate School of Arts and Sciences Dissertations

Mechanical forces are essential in many life processes. The mechanical machinery of cells \textbf{--} the cytoskeleton is a complex system of force-bearing and active force-generation components. These components dynamically interact far from equilibrium in order to perform or facilitate biological functions at the cell scale such as shape change, migration, and polarization. Collectively, cells orchestrate single-cell mechanical functions to give rise to emerging mechanics at the tissue scale, such as embryo development or collective migration. Despite a good understanding of molecular mechanisms of force generation and force bearing, it is still unclear how molecular mechanics leads to cell-scale or tissue-scale …

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Environmental Surveillance Of Viral Pathogens For Identifying Infectious Disease Outbreaks, Alessandro Zulli Oct 2023

Environmental Surveillance Of Viral Pathogens For Identifying Infectious Disease Outbreaks, Alessandro Zulli

Yale Graduate School of Arts and Sciences Dissertations

The detection and quantification of viral infectious disease outbreaks is necessary for theeffective implementation of public health interventions that protect human health. Communicable viral diseases are a leading cause of morbidity and mortality worldwide and prior pandemics have had acute economic and social impacts. However, the identification and tracking of community wide outbreaks for most human viruses across the developed and developing world does not occur due to resource constraints. The goal of this dissertation’s research is to develop the science and methodology that underpin the environmental surveillance of viruses, focusing specifically on wastewater monitoring for identifying and tracking viral …

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Early And Late Stage Mechanisms Of Autophagosome Formation, Taryn J. Olivas Oct 2023

Early And Late Stage Mechanisms Of Autophagosome Formation, Taryn J. Olivas

Yale Graduate School of Arts and Sciences Dissertations

During autophagosome biogenesis, the incorporation of transmembrane proteins into the expanding phagophore is not readily observed. In addition, the membrane surface area of the organelle expands rapidly, while the volume of the autophagosome is kept low. This means that canonical methods for membrane biogenesis do not apply to autophagosomes. Exciting developments in recent years support a new mechanism that could explain these unique attributes of this double-membrane organelle. Several recent studies have suggested the autophagosome expands predominantly through the direct protein-mediated transfer of lipids through the lipid transfer protein ATG2.As these lipids are only introduced into the cytoplasmic-facing leaflet of …

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Mechanisms Of Immunopathology Following Covid-19 And Vaccination In Children & Early Life Immunity In Neonates, Anjali Ramaswamy Oct 2023

Mechanisms Of Immunopathology Following Covid-19 And Vaccination In Children & Early Life Immunity In Neonates, Anjali Ramaswamy

Yale Graduate School of Arts and Sciences Dissertations

Children and babies have unique infectious and inflammatory susceptibilities and are at an increased risk for developing severe disease or autoinflammatory sequelae from infections. However, many pediatric autoinflammatory diseases are poorly understood, as are mechanisms by which humans mount immune defenses in early life. We uncovered novel immunopathologic mechanisms underlying two childhood inflammatory conditions linked to COVID-19 infection and vaccination: multisystem inflammatory syndrome in children (MIS-C) and vaccine-adjacent myopericarditis, respectively. We leveraged a systems approach to study these conditions, using multiomic single-cell RNA sequencing and serum profiling. We found key signatures of MIS-C that include innate immune triggering, and an …

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Neuroimaging And Genetic Studies: Toward An Understanding Of Human Psychological Traits, Shiying Wang Oct 2023

Neuroimaging And Genetic Studies: Toward An Understanding Of Human Psychological Traits, Shiying Wang

Yale Graduate School of Arts and Sciences Dissertations

Human psychological traits involve multiple domains of individual differences in human behaviors, such as cognitive abilities, personalities, and psychiatric disorders. These psychological traits are closely linked to well-being. Therefore, studying the biological basis of psychological traits is crucial for improving the overall quality of life. Both genetics and neuroimaging are highly related to human psychological traits. Numerous studies have shown the strong genetic influence on individual differences in human psychological traits. Furthermore, neuroimaging, a non-invasive technique to examine brain structure and function, has evolved into a powerful tool for analyzing human psychological traits. The purpose of this dissertation is to …

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Tackling Fgfr Fusion-Positive Cancers With A Novel Synergistic Combination Of Fgfr And Hdac Inhibitors, Zechen Wang Oct 2023

Tackling Fgfr Fusion-Positive Cancers With A Novel Synergistic Combination Of Fgfr And Hdac Inhibitors, Zechen Wang

Yale Graduate School of Arts and Sciences Dissertations

FGFR genomic alterations have been implicated in a number of cancers as oncogenesis driver genes. However, despite the approval of several FGFR inhibitors as targeted therapies for the treatment of cancer patients with FGFR aberrations in recent years, durable responses for FGFR inhibitors are still uncommon and most patients relapse to metastatic disease. In particular, FGFR2 fusions have been detected in ~15% of intrahepatic cholangiocarcinoma (ICC) patients. ICC is a highly aggressive bile duct carcinoma, with a dismal 5-year overall survival rate for patients at advanced stages. Therefore, there is a desperate and urgent need for the development of new …

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A Multi-Modal Investigation Of The Basic Neural Processing Mechanisms Of Real Human Face Viewing, Megan Kelley Oct 2023

A Multi-Modal Investigation Of The Basic Neural Processing Mechanisms Of Real Human Face Viewing, Megan Kelley

Yale Graduate School of Arts and Sciences Dissertations

The neural processing of real human faces during direct interaction remains unknown. Prior research has established that face simulations do not capture the full breadth of processing that occurs during real face viewing, demonstrating the need for new approaches. Here we present multimodal methodological developments which combine fNIRS with EEG and eye-tracking, as well as a novel paradigm for disrupted viewing of another real face as well as a robot control, which enables probing of the impact of time and continuity on real face specific neural processing networks. We hypothesized that the spatial and temporal complexity of information extraction from …

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Data-Driven Mapping Between Functional Connectomes Using Optimal Transport, Javid Dadashkarimi Oct 2023

Data-Driven Mapping Between Functional Connectomes Using Optimal Transport, Javid Dadashkarimi

Yale Graduate School of Arts and Sciences Dissertations

Open-source, publicly available neuroimaging datasets---whether from large-scale data collection efforts or pooled from multiple smaller studies---offer unprecedented sample sizes and promote generalization efforts. Releasing data can democratize science, increase the replicability of findings, and lead to discoveries. Due to patient privacy, computational, and data storage concerns, researchers typically release preprocessed data with the voxelwise time series parcellated into a map of predefined regions, known as an atlas. However, releasing preprocessed data also limits the choices available to the end-user. This is especially true for connectomics, as connectomes created from different atlases are not directly comparable. With the absence of gold …

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Religion And The Politics Of Gender, Radha Sarkar Oct 2023

Religion And The Politics Of Gender, Radha Sarkar

Yale Graduate School of Arts and Sciences Dissertations

This dissertation seeks to understand how religion shapes political outcomes related to women's participation. Much political science scholarship emphasizes the material or structural aspects of religion in shaping political commitments. In contrast, I highlight the importance of religious norms and beliefs, conveyed chiefly by clerical leaders. I delve into the Colombian case and compare the effects of Catholic and Pentecostal teachings about women's roles and attributes. With survey experimental data, text-as-data techniques, and interview-based fieldwork, I demonstrate that Catholic sermons tend to elicit benevolent sexism, a mindset that seeks to protect women who occupy traditional male roles in the public …

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Novel Methods For Identification And Inference In Public Health, Jinghao Sun Oct 2023

Novel Methods For Identification And Inference In Public Health, Jinghao Sun

Yale Graduate School of Arts and Sciences Dissertations

This dissertation consists of three essays, each one tackling issues related to "identification'' in the statistical methods used in public health research. In the context of statistics, ``identification'' refers to the process of learning the values of the parameters or characteristics of a model or system after obtaining an infinite number of observations from it. In these essays, I draw attention to the limitations of current methods, which often hinge on specifying a limited set of data generating processes (DGPs). However, these DGPs may fail to correspond accurately with the intricacies of actual situations or with the pre-existing knowledge within …

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'Force And Understanding' And Instability, Hugo William Havranek Oct 2023

'Force And Understanding' And Instability, Hugo William Havranek

Yale Graduate School of Arts and Sciences Dissertations

Critics agree that ‘Force and Understanding’ in Hegel’s Phenomenology of Spirit is of crucial importance for understanding Hegel’s considered position; but the interpretation of the content of the chapter remains highly controversial. In this dissertation, I adopt a reading of ‘Force and Understanding’ on which Hegel is introducing his idiosyncratic notions of atemporal change and identity-in-opposition. Readings that take this approach enjoy prima facie textual support, but have up to now suffered because the views they attribute to Hegel appear obviously philosophically confused. The purpose of the dissertation, therefore, is to argue that Hegel’s use of atemporal change and identity-in-opposition …

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Accelerator-Rich Computer Architectures For Brain-Computer Interfaces, Karthik Sriram Oct 2023

Accelerator-Rich Computer Architectures For Brain-Computer Interfaces, Karthik Sriram

Yale Graduate School of Arts and Sciences Dissertations

Brain-Computer Interfaces (BCIs) are our means of communicating directly with the brain. BCIs implanted on brain tissue offer the highest fidelity communication with the brain and can treat debilitating neurological disorders, control digital devices and improve our understanding of the brain. Unlocking their full potential requires devices capable of processing high data rates sensed from multiple brain regions. However, current BCIs are restricted to a single region, task/treatment, and process low data rates. This is because implantable BCIs must operate within milliwatts of power and respond in real-time within milliseconds to deliver safe treatment. These constraints run counter to the …

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The Role Of The Protection Of Telomeres 1b (Pot1b) Protein In The Protection Of Telomeric Overhangs And The Regulation Of Telomere Length, Taylor Nicholas Takasugi Oct 2023

The Role Of The Protection Of Telomeres 1b (Pot1b) Protein In The Protection Of Telomeric Overhangs And The Regulation Of Telomere Length, Taylor Nicholas Takasugi

Yale Graduate School of Arts and Sciences Dissertations

Malignant cancers must activate telomere maintenance mechanisms to achieve replicative immortality. Mutations in the human Protection of Telomeres 1 (POT1) gene are frequently detected in cancers with abnormally long telomeres, suggesting that the loss of POT1 function disrupts the regulation of telomere length homeostasis to promote telomere elongation. However, our understanding of the mechanisms leading to elongated telomeres remains incomplete. The mouse genome encodes two POT1 proteins, POT1a and POT1b possessing separation of hPOT1 functions. We performed serial transplantation of Pot1b-/- sarcomas to better understand the role of POT1b in regulating telomere length maintenance. While early-generation Pot1b-/- sarcomas initially possessed …

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Computational Methods For Single-Cell Data: From Decomposition, Integration, To Label Transfer, Yuge Wang Oct 2023

Computational Methods For Single-Cell Data: From Decomposition, Integration, To Label Transfer, Yuge Wang

Yale Graduate School of Arts and Sciences Dissertations

Over the past decade, significant advancements have been made in high-throughput single-cell sequencing technologies, revolutionizing our ability to investigate cellular heterogeneity across multiple molecular levels, including gene expression measured by scRNA-seq and chromatin accessibility measured by scATAC-seq. Unlike traditional bulk sequencing approaches, single-cell sequencing techniques enable the characterization of diverse cell types or states within a sample, shedding light on complex biological processes. However, the analysis of single-cell data presents several challenges, including high dimensionality, large-scale datasets, high sparsity, and batch effects arising from both intra- and inter-modalities. Failure to address these challenges can significantly impact downstream applications, such as …

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Exploring 3d Genomics And Its Regulation: Spatial Crispr Screening Reveals Regulators Of 3d Genome Architectures And Chromatin Tracing Unfolds X Chromosome Conformations In Human Pluripotent Stem Cells, Bing Yang Oct 2023

Exploring 3d Genomics And Its Regulation: Spatial Crispr Screening Reveals Regulators Of 3d Genome Architectures And Chromatin Tracing Unfolds X Chromosome Conformations In Human Pluripotent Stem Cells, Bing Yang

Yale Graduate School of Arts and Sciences Dissertations

3D genomics is a rapidly emerging field that seeks to understand the role of the three-dimensional organization of the genome in gene regulation, cellular function, and biological processes. Chromatin tracing has recently emerged as an image-based highly multiplexed fluorescent in-situ hybridization method to detect 3D genome architectures in various biological contexts. However, the regulation of 3D genomics remains less understood. Recent advances in CRISPR screening have enabled systematic identification of genetic perturbations critical to cellular phenotypes and diseases. Yet, the phenotype readouts provided by current CRISPR screens are limited to low content, posing challenges for detection of complex 3D genome …

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Investigation Of Variant Guanine Riboswitches And Other Nucleic Acid Motifs That Sense Metal Ions, Siddhartha Hamal Dhakal Oct 2023

Investigation Of Variant Guanine Riboswitches And Other Nucleic Acid Motifs That Sense Metal Ions, Siddhartha Hamal Dhakal

Yale Graduate School of Arts and Sciences Dissertations

Riboswitches are regulatory RNA elements commonly present in the 5′ untranslated regions (UTRs) of certain mRNA molecules. They carry a conserved aptamer region that binds to metabolites or elemental ions. The binding of ligand promotes distinct folding pathway in the RNA structure which is translated into a regulatory response that either activates or inhibits the expression of downstream genes. Over 55 different classes of riboswitches have been experimentally validated so far that govern various aspects of biology in bacteria, archaea, and select eukaryotes. These RNA elements are thought have played crucial roles in gene regulation during the RNA World era, …

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Determining The Role Of Beta-Tubulin 4b In Cilia And Development, Mycah Theair Sewell Oct 2023

Determining The Role Of Beta-Tubulin 4b In Cilia And Development, Mycah Theair Sewell

Yale Graduate School of Arts and Sciences Dissertations

Microtubules (MTs) are a key component of the cytoskeleton and participate in multiple cellular functions and processes. MTs are made of α- and β-tubulin proteins that are encoded by multiple, individual isotype genes. Over the recent decades there has been mounting evidence that despite the high similarity among tubulin proteins, these various isotypes have unique functions rather than being functionally redundant. First, tubulins have different expression and localization patterns. Second, mutations in different tubulin genes result in a variety of disease phenotypes, some of which are exclusively tied to specific tubulins. Finally, multiple tubulin studies have shown that tubulin composition …

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Computational And Evolutionary Approaches For Translational Cancer Research, J Nic Fisk Oct 2023

Computational And Evolutionary Approaches For Translational Cancer Research, J Nic Fisk

Yale Graduate School of Arts and Sciences Dissertations

The progression of cancer, including the acquisition of therapeutic resistance and the mortality-inducing metastatic spread of therapy-resistant cell populations, is fundamentally an evolutionary process. To contribute to the development of effective treatments against this evolving scourge, this work leverages phylogenetics, statistics, and machine learning techniques to quantify the effects of genetic variants responsible for therapeutic resistance, resolve the timing of their occurrence, understand evolutionary trajectories, and profile the role of neoantigens in varied cancer systems. First, a bioinformatics pipeline for quantifying selection on neoantigens—tumor-specific antigens and potential targets of the immune systems—is detailed. Second, the evolutionary history of two patients …

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Gradient-Free Magnetic Resonance Imaging In A Nonuniform B0, With A Novel Low-Field Magnet System, Kartiga Selvaganesan Oct 2023

Gradient-Free Magnetic Resonance Imaging In A Nonuniform B0, With A Novel Low-Field Magnet System, Kartiga Selvaganesan

Yale Graduate School of Arts and Sciences Dissertations

Over the last 50 years Magnetic Resonance Imaging (MRI) has become a mainstay of modern medicine as a noninvasive diagnostic imaging tool. Most clinical and research MR scanners have trended towards higher field strengths as a means of improving spatial resolution while minimizing scan time. However, widespread availability of these systems is limited, with 90% of people worldwide still lacking access to MRI. Much of this discrepancy comes from the high cost and complexity associated with installing, operating, and maintaining conventional MR scanners. By relaxing the hardware requirements, moving to lower field-strengths, and creating more open-bore systems, MRI can become …

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Exitron Splicing Of Odor Receptors In Drosophila, Xueying Shang Oct 2023

Exitron Splicing Of Odor Receptors In Drosophila, Xueying Shang

Yale Graduate School of Arts and Sciences Dissertations

Odor receptors (Ors) are the major olfactory receptors in Drosophila. They signalthe presence of food, mates, and predators. Proper expression of Ors is critical for the function of olfactory receptor neurons (ORNs). In this study we discovered exitrons in five of the 39 Ors expressed in the adult antennae. Exitrons (exonic introns) are sequences that can be spliced from within a protein-coding exon, thereby altering the resulting protein. Exitrons have not been identified previously in Drosophila to our knowledge. We focused on Or88a, which encodes a pheromone receptor, and found that exitron splicing of Or88a is conserved across five Drosophila …

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Integrating Genetics And Brain Connectivity: Overcoming Statistical Challenges To Uncover The Neural Basis Of Psychiatric And Behavioral Disorders, Wei Dai Oct 2023

Integrating Genetics And Brain Connectivity: Overcoming Statistical Challenges To Uncover The Neural Basis Of Psychiatric And Behavioral Disorders, Wei Dai

Yale Graduate School of Arts and Sciences Dissertations

The exploration of the associations between genetic variants or single nucleotide polymor- phisms (SNPs), brain connectivity, and mental disorders is crucial for comprehending the biological origins of psychiatric and behavioral conditions. Biomedical technologies, such as magnetic resonance imaging (MRI) and next-generation sequencing (NGS), can help elu- cidate the underlying biological processes. Resting state functional MRI (rsfMRI) studies have demonstrated altered functional connectivity in numerous psychiatric and behavioral disorders, which is moderately heritable and can be linked to genetic variants. Diffusion tensor imaging (DTI) can be employed to investigate the structural foundation of func- tional networks. However, challenges remain in analyzing …

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On The Evolution Of Crassulacean Acid Metabolism: Diversity, Anatomy, And Genetic Components, Ian Spencer Gilman Oct 2023

On The Evolution Of Crassulacean Acid Metabolism: Diversity, Anatomy, And Genetic Components, Ian Spencer Gilman

Yale Graduate School of Arts and Sciences Dissertations

Crassulacean acid metabolism (CAM) is an adaption to water- and CO2-limitation that has evolved independently in dozens of vascular plant lineages. The study of CAM began with 18th and 19th botanists, who noted curious changes in plant sap acidity and dark-period gas exchange in succulent plants, and continues into the genomics age with goals of engineering CAM into crops in light of global climate change. The major enzymes, metabolites, and day-night rhythms of CAM have long been established, but many fundamental questions remain, and modern molecular and computational tools allow us to ask new questions about the evolution and genetic …

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Deciphering Immune Interactions In The Tumor Microenvironment, Orr-El Weizman Oct 2023

Deciphering Immune Interactions In The Tumor Microenvironment, Orr-El Weizman

Yale Graduate School of Arts and Sciences Dissertations

Deciphering the Tumor Immune Interactome Cancerous transformations are initiated in normal healthy cells by oncogenic hits. Subsequent acquisition of somatic mutations over time results in the transformation of aberrant cells to cancerous outgrowth to eventual metastatic dissemination. Since the multistep process of oncogenesis does not exist in a vacuum, as these cells arise within the context of a tissue, how does host defenses interact with aberrant transformed cancerous cells? As early as 1909, Paul Ehrlich offered the first hypothesis of immune interaction with tumor cells, arguing that the immune cells can recognize and protect against cancer cells. Further developed by …

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Identifying Cellular And Molecular Mechanisms Contributing Towards Neuronal Vulnerability In Spinocerebellar Ataxia Type 1, Kimberly Petra Luttik Oct 2023

Identifying Cellular And Molecular Mechanisms Contributing Towards Neuronal Vulnerability In Spinocerebellar Ataxia Type 1, Kimberly Petra Luttik

Yale Graduate School of Arts and Sciences Dissertations

Neurodegenerative disorders are highly complex, progressive disorders often involving interactions of multiple cell types, disease-causing genes and pathways, and brain regions. For the majority of neurodegenerative disorders, no effective therapeutics are currently available to slow disease onset or progression, and the mechanisms underlying the degeneration of specific cellular populations remain largely unknown. Here, we use spinocerebellar ataxia type 1 (SCA1) as a model to investigate the impact of the disease-causing gene, ATAXIN-1 (ATXN1), in diverse cell types and brain regions. We identify region-specific differences in disease signatures, and investigate the mechanistic contribution of glia, specifically astrocytes, towards SCA1 pathology and …

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Uncovering A Novel Role For Lsr2 In Mycobacterial Mutagenesis And Deciphering The Determinants Of Lsr2 Transcriptional Regulation, Wei Lynn Ng Oct 2023

Uncovering A Novel Role For Lsr2 In Mycobacterial Mutagenesis And Deciphering The Determinants Of Lsr2 Transcriptional Regulation, Wei Lynn Ng

Yale Graduate School of Arts and Sciences Dissertations

Chromosomal mutations drive the evolution of antibiotic resistance in M. tuberculosis. Unlike many other pathogens, M. tuberculosis has no demonstrated ability for horizontal gene transfer, a major mechanism for developing antibiotic resistance. The error-prone translesion polymerase complex DnaE2/ImuA’/ImuB is one of the primary mediators of mutagenesis and antibiotic resistance in vitro and possibly in vivo. To catalyze error-prone DNA synthesis, DnaE2/ImuA’/ImuB must be able to access the DNA by binding the β2-sliding clamp of the replisome, and potentially compete with other polymerases, including the high-fidelity replicative polymerase DnaE1. However, the mechanisms that govern polymerase switching are not well understood, especially …

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Learning Latent Representations For Biological Molecules, Tianxiao Li Oct 2023

Learning Latent Representations For Biological Molecules, Tianxiao Li

Yale Graduate School of Arts and Sciences Dissertations

Recent progresses in machine learning have achieved phenomenal successes in the prediction of properties of biological molecules from large biological data. However, how much the models really “understand” the nature of the data remains an important question. Representation learning aims at extracting information-rich, low dimensional vector representations from complex high dimensional data. Such representations not only facilitate visualization and interpretation of the data, but also flexibly and efficiently generalized to other downstream tasks without having to re-learn universal patterns in every application. Furthermore, in generative modelling, the latent representations can be directly manipulated to direct the generation towards desired properties. …

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Disruption Of Trio Gef Function And Regulation In Neurodevelopmental Disorders, Ellen Elizabeth Corcoran Oct 2023

Disruption Of Trio Gef Function And Regulation In Neurodevelopmental Disorders, Ellen Elizabeth Corcoran

Yale Graduate School of Arts and Sciences Dissertations

There is a critical need to elucidate the biochemical events that control dendrite and synapse function to develop better targeted therapeutic strategies for neurodevelopmental disorders. Functionally damaging mutations in TRIO are enriched in individuals with neurodevelopmental disorders. TRIO encodes a synaptic regulatory protein with three catalytic domains (Hence the name, TRIO) - two guanine nucleotide exchange factor domains, GEF1 (Rac1 and RhoG) and GEF2 (RhoA), and a putative kinase domain. Broadly speaking, Trio serves as a signaling hub to integrate signals from cell surface receptors and coordinate cytoskeletal rearrangements by activating small GTPases. However, the mechanistic details of how Trio …

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Autoregulation Mechanism Of Lim Domain Kinases, Gabriela Casanova Sepulveda Oct 2023

Autoregulation Mechanism Of Lim Domain Kinases, Gabriela Casanova Sepulveda

Yale Graduate School of Arts and Sciences Dissertations

LIM kinases 1 (LIMK1) and 2 (LIMK2) are major regulators of cytoskeletal dynamics in the cell. LIMK regulates actin dynamics by phosphorylating the actin-depolymerizing factor (ADF)/cofilin family of actin-binding proteins. Cofilin proteins bind preferentially and cooperatively to ADP-bound subunits in F-actin. This binding event changes the helical rotation of actin filaments, promoting actin filament severing. LIMKs promote actin filament stabilization by inactivating cofilin through phosphorylation of Ser3. Phosphorylation of cofilin at Ser3 deactivates cofilin severing activity by inhibition of cofilin binding to actin filaments. This cycling between actin depolymerization and polymerization impacts higher-order cellular processes, including motility, differentiation, and metastasis. …

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A Multidisciplinary Approach With Dogs As The Model Organism To Identify Whole-Genome Breed-Specific Genotypes Potentially Relating To Human Complex Traits, Zicheng Li Oct 2023

A Multidisciplinary Approach With Dogs As The Model Organism To Identify Whole-Genome Breed-Specific Genotypes Potentially Relating To Human Complex Traits, Zicheng Li

Yale Graduate School of Arts and Sciences Dissertations

Background: Domestic dogs (Canis lupus familiaris) share more than 300 common diseases and similar spontaneous disease development characteristics with humans, making them an excellent animal model to study human heritable diseases. Besides, dogs as a model organism also have been favored for mapping complex traits that are hard to map in humans benefiting from drastically different phenotypes and limited genetic heterogeneity across breeds as results of intensive artificial selection. In light of previous studies that profiled breed-specific traits or used genome-wide association studies (GWAS) to refine loci associated with characteristic morphological features in dogs, the field has gained tremendous genetic …

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