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Symptoms Of Schizophrenia And Their Relationship With Pharmacology And Learning Processes Across Species, Leah Fleming Oct 2022

Symptoms Of Schizophrenia And Their Relationship With Pharmacology And Learning Processes Across Species, Leah Fleming

Yale Graduate School of Arts and Sciences Dissertations

Schizophrenia is a debilitating psychiatric illness affecting roughly 1 percent of the global population. Psychiatry classifies schizophrenia, along with several other diagnoses, as a psychotic illness because patients experience a loss of touch with reality (psychosis). The current diagnostic criteria involve broad domains of symptoms including: Hallucinations, delusions, disorganized speech, grossly disorganized or catatonic behavior and negative symptoms (defined broadly by a lack of mental functioning). If a person experiences symptoms in two or more of these domains, they can be diagnosed with schizophrenia. This expansive definition makes schizophrenia difficult to investigate and treat. When examining the cause of schizophrenia, …

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A Semiparametric Efficient Approach To Label Shift Estimation And Quantification, Brandon Tse Wei Chow Oct 2022

A Semiparametric Efficient Approach To Label Shift Estimation And Quantification, Brandon Tse Wei Chow

Yale Graduate School of Arts and Sciences Dissertations

Transfer Learning is an area of statistics and machine learning research that seeks answers to the following question: how do we build successful learning algorithms when the data available for training our model is qualitatively different from the data we hope the model will perform well on? In this thesis, we focus on a specific area of Transfer Learning called label shift, also known as quantification. In quantification, the aforementioned discrepancy is isolated to a shift in the distribution of the response variable. In such a setting, accurately inferring the response variable’s new distribution is both an important estimation task …

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Essays In Political Economy, Johannes Wiedemann Oct 2022

Essays In Political Economy, Johannes Wiedemann

Yale Graduate School of Arts and Sciences Dissertations

This dissertation contains three essays that employ causal identification strategies using novel observational data to study three substantive topics in political economy: in the first paper, I examine firm lobbying in the European Union, particularly the effects of lobbying on firms’ financial performance, EU Commission procurement and grant allocation across firms, and on regulatory benefits for companies. Secondly, I study the effects of firms’ political connections to state attorneys general in the US on investigation probabilities and firms’ investment. In the third essay (joint with Daniel Goldstein), I investigate the roles of citizens’ partisanship and social and political trust at …

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The Optics Of Hatred: Visualizing The Vietnamese Other In Cambodia, Ngoc Tram Luong Oct 2022

The Optics Of Hatred: Visualizing The Vietnamese Other In Cambodia, Ngoc Tram Luong

Yale Graduate School of Arts and Sciences Dissertations

Informed by scholarship on the phenomenon of anti-Vietnamese violence and discrimination in Cambodia, this dissertation probes the construction of Vietnamese Otherness throughout Cambodian history and its imprints upon the lived reality of an eclectic population colloquially dubbed Yuon. It investigates the ways diverse groups of people identified as Vietnamese, either by themselves or others, can be construed within a Khmer ethno-nationalist discourse as the source of sociopolitical troubles—enemies from within, invaders of Cambodian land, strangers in our midst—that threaten the stability and survival of the Cambodian nation. This multilayered way of seeing has inspired waves of genocidal violence against the …

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Institutional Fault Lines: Crises, Norms, And The Informal Foundations Of The State, Daniel Alexander Novick Goldstein Oct 2022

Institutional Fault Lines: Crises, Norms, And The Informal Foundations Of The State, Daniel Alexander Novick Goldstein

Yale Graduate School of Arts and Sciences Dissertations

This dissertation is composed of three research articles that analyze how informal factors impact the effectiveness and stability of a subset of political institutions. In the first chapter, I examine how social norms within government agencies impact state capacity. In the second chapter, I consider how norms that operate among citizens augment the survival of democratic institutions. Finally, the third chapter considers how crises affect checks-and-balances in separation-of-powers systems as well as the effectiveness of electoral institutions. Reversals of State Capacity: Norms and Political Disruption State capacity research generally focuses on improvements to a government's ability to deliver on its …

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Three Essays On Representative Democracy, Hikaru Yamagishi Oct 2022

Three Essays On Representative Democracy, Hikaru Yamagishi

Yale Graduate School of Arts and Sciences Dissertations

This essay presents three essays on representative democracy and its consequences. The first essay, "The Asymmetric Negative Turnout Effects of Party Fragmentation: One-Party Dominance in Japan Through Opposition Weakness'" addresses the puzzle of why an unpopular party wins in the context of contemporary Japan. The essay provides a theory of the mechanism between opposition fragmentation and opposition weakness through decreased turnout for opposition supporters. I argue that under Japan's parliamentary system and Mixed-Member Majoritarian rules, party fragmentation decreases turnout for those who perceive elections as methods of choosing which party shall rule. The potential voter who derives utility from the …

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Rare Event Searches In Liquid Xenon With Exo-200, Nexo And Beyond, Ako Jamil Oct 2022

Rare Event Searches In Liquid Xenon With Exo-200, Nexo And Beyond, Ako Jamil

Yale Graduate School of Arts and Sciences Dissertations

Liquid Xenon detectors operated as time projection chambers have emerged as a key technology over the past decades in the search for extremely rare events, such as the interaction of dark matter or neutrinoless double beta decay Xe-136. These experiments need to operate in an ultra-low background regime. The remaining backgrounds need not only to be reliably and accurately modeled but also rejected using sophisticated reconstruction techniques that distinguish signal from background. In this work, three generations of liquid xenon experiments are examined. Data from the decommissioned ~200 kg EXO-200 experiment was analyzed for a recently-proposed interaction mechanism of fermionic …

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Studies Of Colloidal Iron Carbide Nanoparticle Fischer-Tropsch Catalysts: Characterizing Adsorption Sites And Reactivity Towards Hydrogen Atom Transfers, Nicolas Stephen Dwarica Oct 2022

Studies Of Colloidal Iron Carbide Nanoparticle Fischer-Tropsch Catalysts: Characterizing Adsorption Sites And Reactivity Towards Hydrogen Atom Transfers, Nicolas Stephen Dwarica

Yale Graduate School of Arts and Sciences Dissertations

Iron carbide catalysts have been used for nearly 100 years in the Fischer-Tropsch process (FTP), yet the atomic nature of the active site(s) for H2 and CO have not been fully characterized. The FTP has recently gained interest as a method for the sustainable production of aviation fuels; however, this process suffers from limited product selectivity. A better understanding of the active site(s) could allow for more rational design of iron carbide catalysts, where changes in active site structure(s) could be correlated with catalyst activity. Here, we present the synthesis, characterization, and catalysis by a well-defined dodecylamine-capped colloidal iron carbide …

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Understanding Crystal Nucleation Using Molecular Simulations And Path Sampling Techniques: From Method Development To Atmospheric Contact Freezing, Sarwar Hussain Oct 2022

Understanding Crystal Nucleation Using Molecular Simulations And Path Sampling Techniques: From Method Development To Atmospheric Contact Freezing, Sarwar Hussain

Yale Graduate School of Arts and Sciences Dissertations

Crystal nucleation occurs during the initial stages of crystallization and constitutes the emergence of sufficiently large crystalline regions– known as critical nuclei– within the metastable liquid or the supersaturated solution. Nucleation plays an important role in a wide variety of areas such as cloud microphysics, semiconductor and solar cell manufacturing and the production of pharmaceuticals. In the absence of any external impurity, nucleation proceeds via homogeneous nucleation. Heterogeneous nucleation over an external surface, however, is the predominant mode of nucleation on the planet due to the abundance of a wide variety of impurities or crystal nucle- ation agents (CNA’s). Despite …

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Biophysical Signatures In Cancer And Sickle Cell Disease, Xingjian Zhang Oct 2022

Biophysical Signatures In Cancer And Sickle Cell Disease, Xingjian Zhang

Yale Graduate School of Arts and Sciences Dissertations

Physical cues are ubiquitous in biological systems, from the formation of molecules to the activities of living organisms. While bioprocessing requires functional and efficient biophysics, anomalies in biophysics also present medical challenges. My research integrated biophysical phenotyping and bioinformatics to investigate the physical cues in cancer and sickle cell disease. Cancer is one disease with a wide range of physical challenges. Numerous internal and environmental factors contribute to the heterogeneity of the tumor population. The development of tumor results in numerous physical stresses, which compress tumor cells. In addition, some aggressive tumor cells can migrate through the dense pores in …

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The Functional Neuroanatomy Of Bipolar Depression In Adolescents And Young Adults, Danielle Ann Goldman Oct 2022

The Functional Neuroanatomy Of Bipolar Depression In Adolescents And Young Adults, Danielle Ann Goldman

Yale Graduate School of Arts and Sciences Dissertations

Bipolar depression is associated with profound suffering and disability, and increased risk for suicide thoughts and behaviors. Key in understanding its complexities is its characterization in relation to other mood states of bipolar disorder (BD) as well as the depression of major depressive disorder (MDD). Adolescents and young adults often present to clinicians with symptoms of depression; however, there are no symptoms known currently to reliably distinguish whether the symptoms are resulting from BD or MDD. This can lead to misdiagnosis, improper treatments, and disease worsening. Study of functional brain system connectivity provide insights into identifying markers of depression in …

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Adapting To Change: The U.N. Security Council, Decolonization, And The Cold War, Viva Iemanjá Jerónimo Oct 2022

Adapting To Change: The U.N. Security Council, Decolonization, And The Cold War, Viva Iemanjá Jerónimo

Yale Graduate School of Arts and Sciences Dissertations

Conventional wisdom holds that the Cold War almost immediately held hostage the United Nations Security Council’s ability to pass resolutions and usher in a world of peace through law. Policymakers and scholars have long believed that the Council was largely unable to pass resolutions on important issues until after the Cold War ended in 1991. Using both existing data and my novel dataset of never-before-published statistics about Security Council voting, I show that the empirics of Security Council voting are inconsistent with this view; in fact, the passage of resolutions improved as the Cold War progressed, even during periods of …

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Rational Design Of Mixed-Graft Block Copolymers For Hierarchical Nanostructure Fabrication, Ruiqi Liang Oct 2022

Rational Design Of Mixed-Graft Block Copolymers For Hierarchical Nanostructure Fabrication, Ruiqi Liang

Yale Graduate School of Arts and Sciences Dissertations

Bottom-up fabrication of hierarchically structured materials with precisely controlled molecular arrangements is desirable for numerous advanced applications, ranging from separations, microelectronics, photonics, to energy storage. However, the inability to synthesize hierarchical structures with independently tunable lattices across multiple length scales limits the discovery of next-generation multifunctional materials. This thesis aims to develop a molecular self-assembly strategy based on multicomponent mixed-graft block copolymers (mGBCPs) to fabricate nanostructured materials with a variety of phase-in-phase hierarchical morphologies that combine nano- and mesoscale features. In this thesis, mGBCPs containing sequence-defined side chains can phase-separate to form ordered hierarchical structures with intramolecularly defined interfaces and …

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A Comparison Of Object Representations In The Primate Visual System And Convolutional Neural Networks, Viola Mocz Oct 2022

A Comparison Of Object Representations In The Primate Visual System And Convolutional Neural Networks, Viola Mocz

Yale Graduate School of Arts and Sciences Dissertations

Convolutional neural networks (CNNs) are the state-of-the-art artificial vision models for object recognition tasks. Their architecture is inspired by the organization of the ventral visual system of the brain, and although the way they are trained is not constrained by neural responses, the activations of artificial neural networks nevertheless show some similarities to activations of primate visual regions. Here, across three different studies, I compare the representation of objects in CNNs with that of the primate visual system in two different ways: (1) examining the relationship between object identity and non-identity information and (2) examining the representation of multiple objects. …

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The Fall Of The Angels In Western Patristic Thought, Christopher T.M. West Oct 2022

The Fall Of The Angels In Western Patristic Thought, Christopher T.M. West

Yale Graduate School of Arts and Sciences Dissertations

This dissertation reconstructs patristic narratives of the angelic fall while historically contextualizing these literary projects and evaluating their theological ramifications. The project shows that patristic authors rehearsed diverse versions of events for the fall of the angels in response to exigencies of their own unique historical settings. Adapting Jewish narratives, some authors (e.g. Justin Martyr, Clement of Alexandria, Tertullian) recounted that the primal sin of the angels was “lust” prompted by a desire for human women. Others (e.g. Irenaeus and Tertullian) focused on the specific character of the Devil by relating that Satan’s fall occurred when he tempted Adam and …

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Precision Measurement Of The $^{235}U Antineutrino Spectrum With Prospect And Stereo, Benjamin Taylor Foust Oct 2022

Precision Measurement Of The $^{235}U Antineutrino Spectrum With Prospect And Stereo, Benjamin Taylor Foust

Yale Graduate School of Arts and Sciences Dissertations

Neutrino experimentation is an important pathway to physics beyond the standard model, raising questions on how neutrinos obtain their vanishingly small but non-zero mass, what that mass is, and if they are their own antiparticle.Antineutrinos, as an abundant product of nuclear decay chains, are also important to advancing our understanding of nuclear physics and verifying nuclear databases. In the field of reactor antineutrinos, there are two outstanding anomalies experiments are attempting to address.Previous antineutrino experiments at low enriched uranium power reactors have shown a global flux deficit at various baselines from reactors, hinting at a possible new type of neutrino …

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Structural Basis For The Assembly Of Omcs And Omcs-Like Cytochrome Nanowires In Diverse Microbial Species, Vishok Srikanth Oct 2022

Structural Basis For The Assembly Of Omcs And Omcs-Like Cytochrome Nanowires In Diverse Microbial Species, Vishok Srikanth

Yale Graduate School of Arts and Sciences Dissertations

Microbial extracellular electron transfer (EET) via surface appendages called microbial nanowires is important in a wide range of globally significant environmental phenomena and for applications in bioremediation, bioenergy, and biofuels. Since 2005, these nanowires have been thought to be type IV pili composed solely of PilA-N protein. However, structural analyses demonstrated that during EET, rather than pili, cells produce nanowires made up of cytochromes OmcS and OmcZ. The micrometer-scale OmcS nanowires show seamless heme stacking along the length of the filament, allowing for efficient electron transfer to extracellular acceptors or syntrophic partner cells.Polymerization of cytochromes is important in several biological …

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Abl2 Regulates Microtubule Dynamics Through Interaction With Both The Microtubule Lattice And Tubulin Dimers., Wanqing Lyu Oct 2022

Abl2 Regulates Microtubule Dynamics Through Interaction With Both The Microtubule Lattice And Tubulin Dimers., Wanqing Lyu

Yale Graduate School of Arts and Sciences Dissertations

Abl family kinases are believed to serve as central signaling nodes to transduce signals from upstream receptors to downstream signaling and cytoskeletal-associated proteins. Genetic studies in Drosophila indicate that Abl2 interacts functionally with microtubules (MTs), but the underlying mechanism(s) is (are) completely unclear. Here, I report that Abl2 directly binds MTs and tubulin to regulate MT dynamics. Abl2 binds with MTs via the C-terminal half, which is also mediated by the phosphorylation level of the N-terminus. Abl2 recognizes different MT lattice states, with a higher preference for GMPCPP-MTs than GDP-MTs. Abl2 also binds tightly to tubulin dimers, which is mediated …

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A History Of The Ottoman Atlas: The Material Culture Of Geographical Knowledge In The Ottoman Empire, Isin Taylan Cakmak Oct 2022

A History Of The Ottoman Atlas: The Material Culture Of Geographical Knowledge In The Ottoman Empire, Isin Taylan Cakmak

Yale Graduate School of Arts and Sciences Dissertations

“A History of the Ottoman Atlas: The Material Culture of Geographical Knowledge in the Ottoman Empire” examines the material manifestations of scientific changes in the Ottoman reading world. Looking at the relationship between the atlas and geography, it argues that the transformation of the material form of the atlas informed Ottoman intellectuals’ understanding of the scope and methodology of geographical knowledge. Early Ottoman atlases adhered to centuries-old traditions of cosmographies and topographical histories, which were predominantly textual. This dissertation investigates the cartographical changes taking place against the backdrop of a manuscript culture and examines the visual and material changes in …

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Data-Driven Analyses In Obesity And Chemosensory Neuroimaging, Michael Charles Farruggia Oct 2022

Data-Driven Analyses In Obesity And Chemosensory Neuroimaging, Michael Charles Farruggia

Yale Graduate School of Arts and Sciences Dissertations

Data-driven functional connectivity analyses in the chemical senses are relatively uncommon, with current literature largely predominated by Psychophysiological Interaction (PPI), Dynamic Causal Modeling (DCM), or Structural Equation Modeling (SEM) techniques. The aim of this dissertation is to expand data-driven analyses in the chemical senses (and using chemosensory stimuli) to promote the use of techniques not based on a priori hypotheses or derived from potentially irreproducible literature.Chapter One details a systematic review of functional connectivity analysis in the chemosenses, which demonstrates that, out of 103 studies examined, the vast majority use hypothesis-driven techniques. Moreover, these studies comprise topics of olfaction, gustation, …

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Monitoring Translation Regulation By Structured Rna Elements, Caroline Focht Oct 2022

Monitoring Translation Regulation By Structured Rna Elements, Caroline Focht

Yale Graduate School of Arts and Sciences Dissertations

Translation initiation across domains of life is a tightly regulated process, and functional RNA motifs are critical regulatory features. This dissertation largely focuses on developing a novel technique with which to quantify the effect these RNA elements have on translation initiation and on unraveling the functional requirements of these structures. I have leveraged RelE’s ribosome-dependent endonuclease activity to develop a quantitative assay for translationally regulated mRNAs and validated this method on two bacterial translational riboswitches. I have also demonstrated its applicability to eukaryotic systems by showing that RelE can measure isoform-driven differences in ribosome loading between yeast 5′ leader sequences. …

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Diminished Citizens: Reproductive Sovereignty Through Historical Memory And Health Data In Peru, 1995-2006, Emilie E. Egger Oct 2022

Diminished Citizens: Reproductive Sovereignty Through Historical Memory And Health Data In Peru, 1995-2006, Emilie E. Egger

Yale Graduate School of Arts and Sciences Dissertations

This dissertation brings together key moments of reproductive violence inflicted on Indigenous Peruvian women between 1995 and 2002 and their relationship to the Peruvian State’s Programa Nacional de Salud Reproductiva y Planificación Familiar (PNSRPF). Each chapter focuses on how the violent constraining of Indigenous Peruvian women’s reproduction through PNSRPF linked that campaign to longstanding patterns of reproductive violence against Indigenous Peruvians. It argues these events are connected through reproductive sovereignty as produced by public health data and historical memory. Reproductive sovereignty explains how the Peruvian state has coerced, restricted, and neglected the reproduction of Indigenous Peruvian women who it has …

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Discovery Of Novel Covalent And Non-Covalent Inhibitors Of Hiv-1 Reverse Transcriptase, Zachary Carter Oct 2022

Discovery Of Novel Covalent And Non-Covalent Inhibitors Of Hiv-1 Reverse Transcriptase, Zachary Carter

Yale Graduate School of Arts and Sciences Dissertations

The HIV/AIDS crisis remains a major world health problem, particularly in under-developed countries. Though advancements made in highly active retroviral therapy (HAART) in recent years have significantly reduced the annual deaths, the emergence of problematic mutant variants, coupled with issues of dosing, pill burden, and compliance, have necessitated the continued improvement of these therapeutics. Diversifying the scaffolds of non-nucleoside reverse transcriptase inhibitors (NNRTIs) used in combination therapy has the benefit of overwhelming the virion and raising the genetic barrier to resistance-associated mutations (RAMs). Additionally, the emergence of covalent RT inhibitors (CRTIs) opens the possibility of complete, irreversible eradication of the …

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Design, Synthesis, And Characterization Of Novel Mgmt-Dependent, Mmr-Independent Agents For The Treatment Of Glioblastoma Multiforme, Kingson Lin Oct 2022

Design, Synthesis, And Characterization Of Novel Mgmt-Dependent, Mmr-Independent Agents For The Treatment Of Glioblastoma Multiforme, Kingson Lin

Yale Graduate School of Arts and Sciences Dissertations

Glioblastoma multiforme (GBM) is a devastating disease afflicting over 20,000 new patients per year in the US with a 5-year survival rate of ~5%. The current standard of care treatment for GBMs consists of radiation therapy with concurrent and adjuvant chemotherapy with temozolomide (TMZ). TMZ is a prodrug that generates methyl diazonium in vivo, which in turn methylates DNA. O6-Guanine is the clinically significant site of DNA alkylation by TMZ. In healthy cells these lesions are reversed by O6-methylguanine methyltransferase (MGMT), a suicide DNA repair enzyme. However, loss of MGMT expression is common in many cancers such as grade 2/3 …

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The Immunologic And Epigenomic Regulation Of Hiv-1 Persistence, Jack A. Collora Oct 2022

The Immunologic And Epigenomic Regulation Of Hiv-1 Persistence, Jack A. Collora

Yale Graduate School of Arts and Sciences Dissertations

Curing HIV-1 is challenging due to the presence and persistence of CD4+ T cells harboring HIV-1 proviruses. Understanding the epigenetic and transcriptional regulation that enables HIV-1 to persist despite antiretroviral therapy (ART) and immune pressure is critical to counteracting this latent reservoir. A first chapter consists of an edited published review and preview covering a relevant subset of known features of HIV-1 persistence and HIV-1-T cell interaction biology. The remaining three chapters are parallel projects to understand the multifaceted nature of HIV-1: the interrogation and longitudinal tracking of HIV-1 RNA+ cells from infected individuals, the identification HIV-1 silencing host factors …

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Identifying Immunological Biomarkers In Massive Public Data, Daniel G. Chawla Oct 2022

Identifying Immunological Biomarkers In Massive Public Data, Daniel G. Chawla

Yale Graduate School of Arts and Sciences Dissertations

Recent advances in high-throughput experiments and systems biology approaches have resulted in hundreds of publications profiling immune responses to exposures such as pathogens and vaccines. Immune profiling is important for an emerging class of disease diagnostic technologies, as well as for understanding the mechanisms underlying disease pathogenesis and vaccine response. Massive amounts of public data are available for biomarker discovery and mechanistic profiling, including both datasets capturing transcriptional profiles of the immune system as well as published signatures describing changes that occur (e.g., in gene expression or cellular phenotypes) following infection or vaccination. This wealth of public data presents both …

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Navigating The Social World: Children’S Developing Understanding Of Groups And Inequalities, Xin Yang Oct 2022

Navigating The Social World: Children’S Developing Understanding Of Groups And Inequalities, Xin Yang

Yale Graduate School of Arts and Sciences Dissertations

Children are born into a social world with a dizzying array of groups. These groups are often hierarchically structured in the society, leading to social inequalities. For example, children interact with and are also members of social groups like the wealthy and the poor, males and females, and different national and ethnic groups. This dissertation consists of three bodies of work that contribute to our broader scientific understanding of how children reason about social groups and inequalities. Specifically, I show that children imbue randomly assigned, meaningless groups with rich affiliative meanings, develop complex conceptualizations of wealth, poverty, and inequality, and …

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Essays In Development Economics, Viraj Rajeev Jorapur Oct 2022

Essays In Development Economics, Viraj Rajeev Jorapur

Yale Graduate School of Arts and Sciences Dissertations

Although many developing countries have made significant progress in terms of economic growth, many other indicators of development do not show such an upward trend. In particular, the status of women remains challenged and the benefits from economic development might not accrue to this section of the population. One mechanism to tackle this issue is to design and implement policies incentivizing recipients towards desired outcomes. My dissertation is an attempt to study the effectiveness of two such policies that target different outcomes rolled out in India, and show the impact of policy designs on the outcomes they target. The overarching …

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Leveraging Individual Differences To Gain Insight Into The Developing Functional Connectome, Corey Horien Oct 2022

Leveraging Individual Differences To Gain Insight Into The Developing Functional Connectome, Corey Horien

Yale Graduate School of Arts and Sciences Dissertations

Studying individual differences in functional connectomes provides a powerful framework to tackle questions in developmental human neuroscience. In this work, I use such a framework to study a multitude of factors, ranging from data quality control issues to building predictive models of clinically relevant phenotypes in neurodiverse youth. The first empirical chapter explores how factors related to the reliability of functional connections, namely the amount of scan data, in-scanner head motion, and the spatiotemporal resolution of data acquisition affect the detection of individual differences. In the second empirical chapter, I demonstrate that individual differences in connectomes are stable in developing …

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Elements Of The Ubiquitin Ligase Doa10 Regulating Protein Ubiquitylation And Er Membrane Extraction, Adrian Mehrtash Oct 2022

Elements Of The Ubiquitin Ligase Doa10 Regulating Protein Ubiquitylation And Er Membrane Extraction, Adrian Mehrtash

Yale Graduate School of Arts and Sciences Dissertations

In endoplasmic reticulum-associated degradation (ERAD), misfolded proteins at the endoplasmic reticulum (ER) are degraded by the proteasome after undergoing ubiquitylation. In yeast, Doa10 (MARCHF6/TEB4 in humans) is a conserved membrane-embedded E3 ubiquitin ligase that functions with the E2 ubiquitin-conjugating enzymes Ubc6 and Ubc7. These E2s use a sequential E2 mechanism where Ubc6 attaches a single ubiquitin molecule to a lysine, serine, or threonine residue of a substrate that is subsequently elongated by Ubc7 to form a poly-ubiquitin chain. How the Doa10 complex mediates non-canonical and sequential poly-ubiquitylation of its substrates is unclear. I determine the conserved 16-residue C-terminal element (CTE) …

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