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Synergistic Action Of Synaptotagmin Family In Neurotransmitter Release., Ekaterina Stroeva Oct 2021

Synergistic Action Of Synaptotagmin Family In Neurotransmitter Release., Ekaterina Stroeva

Yale Graduate School of Arts and Sciences Dissertations

The overarching theme of my thesis work is centered around the understanding of how the Synaptotagmin (Syt) family of proteins, which are key players in neurotransmission, is regulated in the brain. Upon very briefly introducing other key molecular players, firstly, I summarize the discovery of the regulation of Syts by self-oligomerization. This work is focused on the characterization of the physiologically relevant Syt1 ring-like oligomers, which are formed in the presence of negatively charged lipids and dissociate upon calcium binding. Using the approach of hypothetical structure-guided mutagenesis, phenylalanine in position 349 is identified as critical for the oligomer formation. Importantly, …

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Specifying And Targeting Cognitive-Affective Dysfunctions In Antisocial Individuals, Allison Mary Stuppy-Sullivan Oct 2021

Specifying And Targeting Cognitive-Affective Dysfunctions In Antisocial Individuals, Allison Mary Stuppy-Sullivan

Yale Graduate School of Arts and Sciences Dissertations

Antisocial behavior includes a wide range of behaviors that violate social norms, from criminal acts to substance misuse. The adverse consequences of antisocial behavior produce a great physical and emotional burden on perpetrators, victims, and family members. This burden is not addressed adequately, with incarceration being the most common intervention for antisocial behavior. When individuals who chronically engage in antisocial behavior are offered therapeutic treatments, the majority neither complete nor benefit from them. One reason existing treatments do not fully address antisocial behavior is because they do not consider or target cognitive-affective dysfunctions driving such behavior, and mechanistic research, to …

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Proteome-Wide Screening For Mitogen-Activated Protein Kinase Docking Motifs And Interactors, Guangda Shi Oct 2021

Proteome-Wide Screening For Mitogen-Activated Protein Kinase Docking Motifs And Interactors, Guangda Shi

Yale Graduate School of Arts and Sciences Dissertations

AbstractProteome-wide screening for mitogen-activated protein kinase docking motifs and interactors Guangda Shi 2021 Kinases catalyze the transfer of phosphate to substrates, a reaction critical for many cellular events. Mitogen-activated protein kinases (MAPKs), including ERK, p38, and JNK, phosphorylate hundreds of substrates, and each plays a pivotal role in distinct processes such as cell growth, survival, differentiation, and apoptosis. To correctly respond to external stimuli, MAPKs use several mechanisms to achieve a high degree of selectivity for their target substrates. A critical aspect of MAPK specificity comes from docking interactions occurring between sites distal from the site of catalysis and short …

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On The Role Of Stability In Animal Morphology And Neural Control, Neelima Sharma Oct 2021

On The Role Of Stability In Animal Morphology And Neural Control, Neelima Sharma

Yale Graduate School of Arts and Sciences Dissertations

Mechanical stability is vital for the fitness and survival of animals and is a crucial aspect of robot design and control. Stability depends on multiple factors, including the body's intrinsic mechanical response and feedback control. But feedback control is more fragile than the body's innate mechanical response or open-loop control strategies because of sensory noise and time-delays in feedback. This thesis examines the overarching hypothesis that stability demands have played a crucial role in how animal form and function arise through natural selection and motor learning. In two examples, finger contact and overall body stability, we investigated the relationship between …

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Characterizing Photophysics Of Photoconvertible-Fluorescent Protein Meos3.2 For Quantitative Fluorescence Microscopy, Mengyuan Sun Oct 2021

Characterizing Photophysics Of Photoconvertible-Fluorescent Protein Meos3.2 For Quantitative Fluorescence Microscopy, Mengyuan Sun

Yale Graduate School of Arts and Sciences Dissertations

Photoconvertible fluorescent proteins (PCFPs) are widely used in super-resolution microscopy, and studies of cellular dynamics. Their photoconversion properties have enabled single-molecule localization microscopy (SMLM) by temporally separating closely-spaced molecules. However, our understanding of their photophysics is still limited, hampering their quantitative application. For example, counting fluorescently-tagged fusion proteins from the discrete localizations of individual molecules is still difficult. The red-to-green photoconvertible fluorescent protein mEos3.2 is favored by many due to its monomeric property, high brightness, photostability, compatibility with live cells, and 1:1 labeling stoichiometry. The fluorescent protein mEos3.2 is fused to the coding sequence of a protein of interest in …

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Commerce And Justice: Ottoman And Venetian Courts In Istanbul During The Seventeenth Century, Tommaso Stefini Oct 2021

Commerce And Justice: Ottoman And Venetian Courts In Istanbul During The Seventeenth Century, Tommaso Stefini

Yale Graduate School of Arts and Sciences Dissertations

"Commerce and Justice: Ottoman and Venetian Courts in Istanbul during the Seventeenth Century” analyzes legal disputes and economic transactions between Ottoman and Venetian merchants in Istanbul on a daily basis between 1600 and1620. At that time, the Venetians constituted the largest European community in the Ottoman capital, and they engaged intensively in trade ventures with Ottoman businessmen belonging to different religious and ethnic communities, including Muslim Turks, Sephardic Jews, and Orthodox Greeks. This dissertation asks how Ottomans and Venetians cooperated in commercial undertakings and solved controversies despite the absence of a system of inter-polity law and secular legal regimes in …

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Graph Priors, Optimal Transport, And Deep Learning In Biomedical Discovery, Alexander Tong Oct 2021

Graph Priors, Optimal Transport, And Deep Learning In Biomedical Discovery, Alexander Tong

Yale Graduate School of Arts and Sciences Dissertations

Recent advances in biomedical data collection allows the collection of massive datasets measuring thousands of features in thousands to millions of individual cells. This data has the potential to advance our understanding of biological mechanisms at a previously impossible resolution. However, there are few methods to understand data of this scale and type. While neural networks have made tremendous progress on supervised learning problems, there is still much work to be done in making them useful for discovery in data with more difficult to represent supervision. The flexibility and expressiveness of neural networks is sometimes a hindrance in these less …

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Development Of Enantioselective Synthetic Routes To (–)-Myrocin G And (–)-Euonyminol., Martin Tomanik Oct 2021

Development Of Enantioselective Synthetic Routes To (–)-Myrocin G And (–)-Euonyminol., Martin Tomanik

Yale Graduate School of Arts and Sciences Dissertations

In the first chapter, I describe the development of a synthetic strategy towards (–)-myrocin G (8), the putative active form of the antiproliferative fungal metabolite (+)-myrocin C (4). Myrocin C (4) has been proposed to cross-link DNA by two-fold nucleotide addition; however, this proposed bioalkylation hypothesis has not been tested with native DNA. Our synthetic efforts provided a highly convergent total synthesis of myrocin G (8) in 15 steps from simple starting materials. A key steps in the sequence involved a carefully designed fragment coupling–cyclization cascade (see 85 + 89 → 90). This transformation effectively unites the iodocyclopropane 85 with …

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Linguistic Variation From Cognitive Variability: The Case Of English 'Have', Muye Zhang Oct 2021

Linguistic Variation From Cognitive Variability: The Case Of English 'Have', Muye Zhang

Yale Graduate School of Arts and Sciences Dissertations

In this dissertation, I seek to construct a model of meaning variation built upon variability in linguistic structure, conceptual structure, and cognitive makeup, and in doing so, exemplify an approach to studying meaning that is both linguistically principled and neuropsychologically grounded. As my test case, I make use of the English lexical item 'have' by proposing a novel analysis of its meaning based on its well-described variability in English and its embedding into crosslinguistically consistent patterns of variation and change. I support this analysis by investigating its real-time comprehension patterns through behavioral, electropsychophysiological, and hemodynamic brain data, thereby incorporating dimensions …

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The Path To Extreme Precision Radial Velocity With Expres, Lily Ling Zhao Oct 2021

The Path To Extreme Precision Radial Velocity With Expres, Lily Ling Zhao

Yale Graduate School of Arts and Sciences Dissertations

The field of exoplanets is currently poised to benefit hugely from improved radial velocity (RV) precision. Extreme precision radial-velocity (EPRV) measurements, capable of detecting planetary signals on the order of 10-30 cm/s, will deliver integral planetary parameters, be sensitive to a missing category of lower-mass planets, grant a deeper understanding of multi-planet architectures, and support both current and future space missions such as TESS and JWST. The ability of EPRV to deliver mass estimates is essential for comprehensively characterizing planets, understanding formation histories, and interpreting atmospheric spectra. Until recently, RV precision had stalled at around 1 m/s, i.e. signals with …

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Developmental Participation Of Vip Interneurons In Cortical Dynamics, Daniel Barson Oct 2021

Developmental Participation Of Vip Interneurons In Cortical Dynamics, Daniel Barson

Yale Graduate School of Arts and Sciences Dissertations

In the mammalian cerebral cortex, local and long-range synaptic connections are believed to relay information related a diverse array of cognitive, emotional, and physiological functions to influence the computations performed by single neurons. While the anatomical connectivity of a single neuron is static on short timescales, its functional involvement in distributed networks may fluctuate rapidly to subserve moment-to-moment changes in behavior. A sparse class of interneurons that express vasoactive intestinal polypeptide (VIP) has been hypothesized to mediate these fluctuations by modulating the gain of cortical micro-circuits in response to neuromodulatory and long-range cortico-cortical inputs. To test this hypothesis, we developed …

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Modulation Of T Cell Response Hierarchy By Coinhibition And Costimulation With Cancer Immunotherapy, Yu Zhang Oct 2021

Modulation Of T Cell Response Hierarchy By Coinhibition And Costimulation With Cancer Immunotherapy, Yu Zhang

Yale Graduate School of Arts and Sciences Dissertations

Cancer is a significant cause of morbidity and mortality worldwide. Cancer immunotherapy with coinhibition antagonist antibodies blocking the Program Death 1 (PD-1) and Program Death Ligand 1 (PD-L1) coinhibitory pathway (anti-PD therapy) have improved the survival for millions of patients with advanced cancers providing the possibility of achieving a prolonged durable response. However, few patients are considered to be clinically cured with anti-PD therapy. Many patients who initially respond to anti-PD therapy eventually develop tumor progression or recurrence in a clinical observation collectively called acquired immune resistance (AIR). Many potential mechanisms of AIR are being studied, such as the loss …

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Synaptic Density Imaging With Sv2a Using Positron Emission Tomography: Optimization Of Reference Region Analysis And Applications In The Human Spinal Cord And The Developing Nonhuman Primate Brain, Samantha Rossano Oct 2021

Synaptic Density Imaging With Sv2a Using Positron Emission Tomography: Optimization Of Reference Region Analysis And Applications In The Human Spinal Cord And The Developing Nonhuman Primate Brain, Samantha Rossano

Yale Graduate School of Arts and Sciences Dissertations

Positron emission tomography (PET) is a functional imaging modality in which radioactive ligands are used to target physiological functions, including metabolism or receptor densities, in vivo. Once administered into a subject, the PET radioligand distributes throughout the body and undergoes radioactive decay, emitting two gamma rays 180 degree from each other. These gamma rays are detected by the PET camera as coincidence events, and the PET raw data are reconstructed into 4-dimenstional images (x, y, z, t). Dynamic PET images can be quantified by applying various kinetic models to radioactivity concentrations in a volume or region of interest (ROI) over …

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Deconvolution: From Transcriptomics To Immunomics, Daiwei Tang Oct 2021

Deconvolution: From Transcriptomics To Immunomics, Daiwei Tang

Yale Graduate School of Arts and Sciences Dissertations

The developments of sequencing technologies in the past two decades have enabled exciting findings and rapid accumulations of many kinds of -omics data. Each type of -omics data is designated to measure a specific characteristic of the biological systems, e.g. DNA-sequencing for mutations and RNA-sequencing for gene expression. With proper statistical and computational methods, these data can be integrated to answer new questions. This data reproposing is possible because the target signals are already encoded in the data and require proper tools to decode. In this regard, these methods are often called ``deconvolution" methods. In this dissertation, I will present …

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Viral Subjects: Stigma, Civil Society Activism, And The Making Of Hiv/Aids In Lebanon, Elizabeth Berk Oct 2021

Viral Subjects: Stigma, Civil Society Activism, And The Making Of Hiv/Aids In Lebanon, Elizabeth Berk

Yale Graduate School of Arts and Sciences Dissertations

This dissertation examines HIV/AIDS in Lebanon. It asks how people living with this illness do so in light of civil society activism to overcome social stigma associated with HIV/AIDS and related issues. The first full-length ethnographic study of HIV/AIDS in the Middle East region, research for this project was conducted at various periods throughout 2015-2018 at civil society organizations, among physicians, and among people living with HIV. This dissertation employs the research techniques of semi-structured interviews, participant observation, and media analysis. It argues, overall, that the subjectivities of those living with, treating, and advocating for HIV/AIDS cannot be understood without …

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Latent Space Construction For Analyzing Large Genomic Data Sets, Wenlan N/A Zang Oct 2021

Latent Space Construction For Analyzing Large Genomic Data Sets, Wenlan N/A Zang

Yale Graduate School of Arts and Sciences Dissertations

This dissertation presents a new framework for extracting signal from high-dimensional data using a latent-space construction with applications in genomic data sets. This construction follows the standard approach of considering the rank of a matrix containing useful information (signal) with the addition of noise. While the rank estimation usually depends on ill-posed methods that may result in an overabundance of noise or an under-abundance of signal, our approach provides accurate and robust estimates of the detectable signal, including distributional bounds for the magnitude of signal required for it to be detectable in the presence of noise. Along with the proposed …

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Next Generation Phenotyping In Clinical Trial Based On Real-World Data, Guannan Gong Oct 2021

Next Generation Phenotyping In Clinical Trial Based On Real-World Data, Guannan Gong

Yale Graduate School of Arts and Sciences Dissertations

Real-world data (RWD) or information generated outside of a traditional clinical trial, including electronic health records (EHRs), insurance claims and billing activity, product and disease registries, medical devices used in the home, and applications (apps) on mobile devices, provide a key analyte that can be used to advance biomedical investigation and drive discovery. While RWD can have significant value, analysis of these data has limitations and often requires new analytic approaches. One of the key areas in utilizing RWD is identifying patients with certain characteristics of interest through a process known as digital phenotyping. Although great benefits and potentials, identifying …

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Cross-Kingdom Expression Of Synthetic Genetic Elements Promotes The Discovery Of A New Class Of Nucleotide Analogs From The Human Microbiome, Jaymin Patel Oct 2021

Cross-Kingdom Expression Of Synthetic Genetic Elements Promotes The Discovery Of A New Class Of Nucleotide Analogs From The Human Microbiome, Jaymin Patel

Yale Graduate School of Arts and Sciences Dissertations

The ability to mobilize functional genetic cargo into a versatile array of hosts is a defining challenge, as scientists increasingly reprogram diverse organisms as living therapeutics, for bioremediation, and as foundries for producing materials and molecules. However porting genetic material to diverse recipients is challenged by barriers to robust expression and mobilization. To address these challenges, we have developed an approach that integrates computer aided redesign of genetic sequences that are subsequently mobilized, expressed, and characterized cross-kingdom in diverse microbial hosts, including Gram negative and positive bacteria and yeast. Using the technology developed in this thesis, we were able to …

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Writing Union Into Resistance: How Committees Of Correspondence Forged A Continental Community, Catherine Treesh Oct 2021

Writing Union Into Resistance: How Committees Of Correspondence Forged A Continental Community, Catherine Treesh

Yale Graduate School of Arts and Sciences Dissertations

Committees of correspondence, made famous by Samuel Adams and his cohort in Boston during the American Revolution, actually operated in the large majority of Britain’s Atlantic colonies in the eighteenth century. Before 1764, colonists used these committees to make their political opinions known to lobbyists in England; after 1764, colonists largely used committees to discuss politics amongst themselves. Colonial assemblies, private groups of political radicals or merchants, and local town meetings all chose committees of correspondence – groups of 3-15 men who met regularly – to share their political opinions and organize protests over the following decade. In “Writing Union …

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New Petrogenetic Approaches To The Study Of Ultrahigh-Temperature And Ultrahigh-Pressure Rocks, Duncan Sutherland Keller Oct 2021

New Petrogenetic Approaches To The Study Of Ultrahigh-Temperature And Ultrahigh-Pressure Rocks, Duncan Sutherland Keller

Yale Graduate School of Arts and Sciences Dissertations

The degree to which rocks are heated and pressurized during mountain building controls fundamental characteristics of Earth’s lithosphere such as density and chemical composition, and influences cycling of life-essential elements (e.g. H, C, N, P). “Extreme” metamorphic rocks that reached exceptionally high pressures and/or temperatures compared to common examples are key to plumbing the limits of metamorphic processes. Extreme metamorphism encompasses high-pressure granulites (HPGs) formed during orogenic crustal overthickening, ultrahigh-temperature (UHT) rocks formed during intense heat flow, and deeply subducted ultrahigh-pressure (UHP) rocks returned to the surface. Critically, methods for recognizing these rocks are debated. This dissertation presents a series …

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Probing The Upper Limits To Light-Matter Interactions: From Spontaneous Emission To Superresolution, Hyungki Shim Oct 2021

Probing The Upper Limits To Light-Matter Interactions: From Spontaneous Emission To Superresolution, Hyungki Shim

Yale Graduate School of Arts and Sciences Dissertations

As newly emerging optical devices and metamaterials enrich the photonic landscape, there is a growing need to understand the limits to optical response. Are current, physical-intuition-based designs already near the frontiers of what is possible, or can they be significantly further improved? New approaches are needed to explore the vast, physical design space. In this thesis, we will establish fundamental limits to light-matter interactions at three levels: in free space, where beam-shaping can be used for wide-ranging applications including superresolution, for arbitrary scattering structures, where we develop new tools for identifying "power-bandwidth limits" to near-field optical response, and, finally, at …

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Cell Biology Of Axon Degeneration And Regeneration In Vivo, Chen Ding Oct 2021

Cell Biology Of Axon Degeneration And Regeneration In Vivo, Chen Ding

Yale Graduate School of Arts and Sciences Dissertations

Axons are fundamental connective units that mediate information flow in nervous systems. Axon degeneration breaks neural circuits and is a hallmark of neurodegenerative diseases. Axon regeneration has the potential to repair damaged circuits. Here I investigate the molecular and cellular mechanisms underlying both axon degeneration and regeneration in C. elegans in vivo. In the first part of the dissertation, I examine a specific type of axon degeneration that is caused by mitochondria defects. I describe a novel calsyntenin-CaMKII-Sarm1-MAPK pathway involved in this type of axon degeneration. I further demonstrate that by modulating this signaling pathway, degeneration can be dramatically delayed. …

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Binary Logic: Race, Expertise, And The Persistence Of Uncertainty In American Sex Research, Beans Velocci Oct 2021

Binary Logic: Race, Expertise, And The Persistence Of Uncertainty In American Sex Research, Beans Velocci

Yale Graduate School of Arts and Sciences Dissertations

Between the mid-nineteenth and mid-twentieth centuries, American researchers tried to sort the living world by sex. Their efforts created more taxonomic problems than they solved, but as they encountered vast quantities of evidence that did not at all show an obvious or stable division between male and female bodies, they used sexual uncertainty to their professional and ideological advantage. This dissertation traces a network of scientists who built their own claims to expertise, as well as theories of racial hierarchy rooted in sexual difference, out of sexually unruly bodies. While much scholarship on the history of sex science describes the …

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Characterizing Brain-Phenotype Relationships In Health And Disease, Abigail Sara Greene Oct 2021

Characterizing Brain-Phenotype Relationships In Health And Disease, Abigail Sara Greene

Yale Graduate School of Arts and Sciences Dissertations

Relating whole-brain activity patterns to human behaviors, traits, and clinical symptoms holds the promise of revealing the macroscale neural bases of these complex phenotypes. In this work, I advance predictive modeling approaches to characterize such brain-phenotype relationships. In the first empirical chapter, I demonstrate that in-scanner tasks amplify these relationships; models built from fMRI data acquired while participants performed various tasks better predict intelligence measures than do models built from resting-state fMRI data. In the second empirical chapter, I explore how tasks have this effect, using psychophysiological interaction (PPI) and predictive modeling analyses to show that spatially distributed, task-induced changes …

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Iron Archipelago: Environment And Industry In Early Modern And Modern Japan, Joanna Morgan Linzer Oct 2021

Iron Archipelago: Environment And Industry In Early Modern And Modern Japan, Joanna Morgan Linzer

Yale Graduate School of Arts and Sciences Dissertations

This dissertation examines Japan's homegrown iron industry during its heyday in the Tokugawa period (1603-1868) and as it persisted deep into the twentieth century, paying particular attention to its environmental consequences. Other societies have seen their metals industries grow and develop in times of war. During the long-lasting peace of the Tokugawa period, the inhabitants of the mountains of Chūgoku developed technologies of mining and smelting to produce increasing quantities of iron. This one region supplied most of the iron used across the archipelago for such fundamental purposes as farming implements, tools, and samurai swords. Chapter 1 explores how local …

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The Biophysical Impacts Of Aerosols On Surface Climate, Tirthankar Chakraborty Oct 2021

The Biophysical Impacts Of Aerosols On Surface Climate, Tirthankar Chakraborty

Yale Graduate School of Arts and Sciences Dissertations

Aerosols, tiny suspended solid or liquid particles in the atmosphere, are important drivers of atmospheric processes. Aerosols affect the climate as well as local weather by modulating the Earth’s energy budget. Previous studies have quantified the impact of aerosols on global climate change, with a focus on the atmospheric radiation budget. However,aerosols have a disproportionately higher impact on the Earth’s surface, where we reside. This dissertation isolated this impact of aerosols on the surface climate to better understand the mechanisms that modulate the overall climate response to aerosol loading. This work developed a surface energy budget perspective to aerosol-climate interactions …

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Pictures As Mirrors For Shah Tahmasb: How Manuscript Paintings Shaped Court Culture In Early Modern Iran, Selin Unluonen Oct 2021

Pictures As Mirrors For Shah Tahmasb: How Manuscript Paintings Shaped Court Culture In Early Modern Iran, Selin Unluonen

Yale Graduate School of Arts and Sciences Dissertations

This dissertation investigates how sixteenth-century manuscript paintings shaped courtly identity and behavior at a time of sweeping political change in Iran. During the first half of the sixteenth century, rulers of the new Safavid dynasty in Iran commissioned richly illustrated manuscripts. Turning to a corpus of paintings from a royal copy of the medieval Persian epic Khamsa, this study examines these paintings in light of the numerous extratextual inscriptions incorporated into the pictorial world (an unstudied body of evidence despite the book’s renown), and puts them in dialogue with autobiographical writings, court chronicles, diplomatic letters, and literary anthologies from the …

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Mutations In Α And Β Subunits Of Voltage-Gated Sodium Channels In Neuropathic Pain: Functional Assessment In Rodent And Human Ipsc-Derived Sensory Neurons, Matthew Alsaloum Oct 2021

Mutations In Α And Β Subunits Of Voltage-Gated Sodium Channels In Neuropathic Pain: Functional Assessment In Rodent And Human Ipsc-Derived Sensory Neurons, Matthew Alsaloum

Yale Graduate School of Arts and Sciences Dissertations

Voltage-gated sodium (NaV) channels are key mediators of excitability in dorsal root ganglion (DRG) neurons, the primary afferents responsible for transmitting pain signals into the central nervous system. NaV channels are found as heterotrimeric complexes in humans, comprised of one pore-forming α-subunit and two non-ion conducting β-subunits. Gain-of-function mutations in NaV1.7, NaV1.8, and NaV1.9, the NaV channels preferentially expressed in the peripheral nervous system, confer hyperexcitability to DRG neurons and have been linked to the development of neuropathic pain. In this dissertation, I utilize dynamic clamp electrophysiology to precisely quantify the contribution of NaV1.8 and NaV1.9 to neuronal excitability. Furthermore, …

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Physics Of The Electronic Structure And Collective Excitations In Transition Metal Compounds, Sangjae Lee Oct 2021

Physics Of The Electronic Structure And Collective Excitations In Transition Metal Compounds, Sangjae Lee

Yale Graduate School of Arts and Sciences Dissertations

In condensed matter systems, novel phenomena such as superconductivity and magnetism can emerge from an intricate interplay between the materials lattice, spin, charge, and orbital degrees of freedom. Understanding how the structural and electronic degrees of freedom are coupled in transition metal compounds is crucial not only from the viewpoint of fundamental condensed matter physics, but also to establish a potential groundwork for substantial technological advancement through the discovery of exotic phases. In this dissertation, I illustrate how the electronic structure and collective excitations can be manipulated by controlling the dimensionality and interfacial structure using molecular beam epitaxy (MBE). Specifically, …

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Interplay Between Oxidative Stress, Pax6 And The Immune Response In The Developing Eye, Brian S. Thompson Oct 2021

Interplay Between Oxidative Stress, Pax6 And The Immune Response In The Developing Eye, Brian S. Thompson

Yale Graduate School of Arts and Sciences Dissertations

Eye development and lens morphogenesis are complex processes that are carefully orchestrated by a multitude of factors including extracellular signals, local activators and signal-regulated DNA-binding transcription factors. Any perturbation to these factors can impair eye development and lens morphogenesis and result in a range of structural abnormalities of the lens (and other ocular structures) and a spectrum of human disease ranging from the complete absence of the eye (anophthalmia), reduced eye size (microphthalmia) or optic fissure closure defect (coloboma). Oxidative stress, an imbalance between oxidants (e.g., reactive oxygen species (ROS)) and antioxidants (e.g., glutathione) in favor of the oxidants, may …

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