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Increasing Gene Targeting Efficiency Through T-Dna Amplification In Plants, Lauren Dickinson

Yale Graduate School of Arts and Sciences Dissertations

In gene targeting, a double strand DNA break is created in a gene ofinterest, and the break is repaired via homologous recombination using an exogenous DNA donor template (DT) harboring a desired modification flanked by sequences homologous to the target locus. If the cell undergoes homologous repair using the template, the desired modification can be copied onto the gene of interest. This is a highly worthwhile process, given that virtually any modification could potentially be made to an endogenous target. However, in plants, the process of gene targeting is extremely inefficient, often to the point that it is impossible, or …

Improved Computational Strategies To Investigate Mechanisms Of Immune Response In The Tumor And Wound Healing Microenvironments From Single-Cell Data, Kathryn Helen Bridges

Yale Graduate School of Arts and Sciences Dissertations

Advances in single-cell RNA-sequencing (scRNA-seq) technology enable unbiased, whole transcriptome profiling of tissues, which have revolutionized systems-level studies of these complex microenvironments. Computational analyses of scRNA-seq data have the potential to provide a tissue-level snapshot of cell types, their associated cell states, and a map of their interactions with other cells in the tissue. However, choosing the optimal approach to reconstruct biologically interpretable cell communities from the sparse single-cell transcriptomes collected in scRNA-seq data, especially in the context of dynamic biologically processes, remains a challenge. This is especially true when analyzing dynamic immune processes, which include many cell types, cell …

Identification And Characterization Of Regulators In The Developmental Process Leading To Infectious Trypanosoma Brucei, Justin Toh

Yale Graduate School of Arts and Sciences Dissertations

Trypanosoma brucei is a protozoan parasite responsible for causing vector-borne diseases in vertebrate animals. The parasite is transmitted by the tsetse fly in sub-Saharan Africa. According to the Food and Agriculture Organization (FAO) of the United Nations, T. brucei significantly impacts Africa’s agriculture-based economy, causing approximately 3 million deaths in cattle per year estimated to cost up to $1.2 billion USD. The effects of trypanosomiasis on the economy are far-reaching as this reduces the supply of milk, meat, and draught power, and decreases soil fertility and employment income (Abro et al., 2021). Thus, there is a pressing need for research …

Sensory Changes Underlying The Egg-Laying Preference Shift Of The Agricultural Pest Drosophila Suzukii, Wanyue Wang

Yale Graduate School of Arts and Sciences Dissertations

Drosophila suzukii, also known as the spotted wing Drosophila, is an agricultural pest of fruits that has caused severe economic losses for a wide variety of fruit industries. It invaded the United States and Europe in 2008, and since then it spread at an unprecedented rate. D. suzukii devastates many fruit crops, including strawberries, raspberries, and blueberries. Unlike most Drosophila species, including D. melanogaster, which lay eggs in overripe fruit, D. suzukii has an egg-laying preference for intact ripe fruit and thus it is destructive. D. suzukii females possess an enlarged saw-like ovipositor, the egg-laying organ, that is able to …

The Role Of O-Glcnac Transferase In Ventromedial Hypothalamic Control Of Energy Balance, Qi Wang

Yale Graduate School of Arts and Sciences Dissertations

The central nervous system plays a vital role in the homeostatic control of body weight and metabolism. Among brain nuclei, the ventromedial hypothalamus (VMH) is an important hypothalamic nucleus known to regulate body weight, energy balance, and counterregulatory response. However, the pathways for VMH neurons to regulate lipid metabolism and the mechanisms by which VMH neurons sense nutrients and hormones remain obscure. O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of stress, nutrients, and hormones, regulating a variety of cellular activities. Here we report that mice with VMH neuron-specific OGT deletion exhibit rapid development …

Risk Factors Associated With Suicide Among Veterans With Hiv In The Veterans Aging Cohort Study, Alexandria Catherine Smith

Yale Graduate School of Arts and Sciences Dissertations

With advancements in treatment, HIV has transitioned from a terminal diagnosis to a chronic illness. Yet, despite improvement in life expectancy, people living with HIV (PWH) remain at high risk of suicide compared to the general population [1-8]. Moreover, the risk of suicide among PWH is greater compared to individuals with other chronic conditions [9]. Given the persistently elevated rate of suicide among PWH, the goal of this dissertation is to further advance our knowledge of risk factors contributing to suicide among PWH. For this dissertation, I first reviewed the existing peer-reviewed literature from 1996 through 2020 and identified known …

Investigations Of The Silatrane Anchoring Group For Solar Fuel Applications, Jennifer L. Troiano

Yale Graduate School of Arts and Sciences Dissertations

Solar energy is an incredibly abundant, renewable resource with the ability to meet our growing energy needs, but its diffuseness and intermittency has limited its potential. Taking note from photosynthesis in nature, we can design artificial systems that carry out similar processes in order to store solar energy in the form of chemical bonds as “solar fuels.” Molecular and materials approaches can be combined in heterogenized molecular WS-DSPECs where small molecules are attached to metal oxide surfaces to carry out water oxidation and fuel forming reactions. In this dissertation, small molecule surface attachment is investigated using the silatrane anchor to …

Discovery And Synthesis Of N-Heterocyclic Drug-Like Compounds By Leveraging Novel Rh(I)-Catalyzed C-H Activation Methods, Oh Sang Kweon

Yale Graduate School of Arts and Sciences Dissertations

Nitrogen heterocycles are present in almost two-thirds of U.S. FDA approved pharmaceuticals, as well as biologically active natural products. The first two chapters discuss the application of C-H activation methodology to explore novel, nitrogen heterocycle containing molecules as potent and selective ligands towards different protein targets. The third chapter depicts the design of new N-heterocyclic covalent molecular probes that uniquely labels a serine hydrolase protein in a chemoproteomics screen. Chapter 1 details an investigation using structure-based docking with a virtual library of tetrahydropyridines (THPs) to identify unique agonists for the serotonin 5-HT2A receptor (5-HT2AR). Based around combinations of three inputs, …

Specificity And Regulation Of Sodium Channel Trafficking: Exploring A Novel Therapeutic Strategy For Pain, Grant Philip Higerd-Rusli

Yale Graduate School of Arts and Sciences Dissertations

The burden of pain is significant and current pain treatments are often ineffective. Opiate use has led to an epidemic, requiring alternative pain medications that are more effective and non-addictive. Voltage-gated sodium channel NaV1.7 is preferentially expressed in pain-sensing neurons. Mutations in NaV1.7 can cause disorders ranging from intense pain to complete painlessness in humans, suggesting that its inhibition could provide analgesia without CNS side-effects or addictive potential. Indeed, existing non-selective NaV channels blockers prevent pain, but their utility is limited due to serious side-effects caused by inhibition of NaV isoforms expressed in the heart and brain. Selective inhibition of …

Molecular Mechanisms Of Microbial Adaptation To The Host, Daniel G. Dumitrescu

Yale Graduate School of Arts and Sciences Dissertations

All host-associated microorganisms require mechanisms to adapt to stress encountered in the host. In particular, host immunity generates reactive oxygen species (ROS) as a measure to regulate microbial expansion in the gut and to kill invading pathogens. ROS are broadly toxic to cellular biomolecules, and consequently both microorganisms and the host employ molecular mechanisms to contend with their harmful properties. Accordingly, all life forms rely on low- molecular-weight (LMW) thiols, a family of ubiquitous small molecule antioxidants, to maintain intracellular redox homeostasis and resist oxidative damage caused by ROS. Chapter 1 reviews the molecular and biological functions of LMW thiols, …

The Evolutionary Origins Of Social Evaluation, Zachary A. Silver

Yale Graduate School of Arts and Sciences Dissertations

Social evaluation refers to the process of using observed social behavior to determine who will be a suitable social partner. While this phenomenon is well-documented in this human species, less is known regarding how we acquired the cognitive abilities needed to make this assessment of with whom we should affiliate. To better understand the evolutionary origins of social evaluation abilities in the human species, researchers have explored nonhuman animals’ capacities for social evaluation. In this dissertation, I present three experiments designed to explore whether domestic dogs, a species who evolved alongside humans and who share our social environment demonstrate human-like …

Yale Medicine Magazine Spring 2023, Issue 170, Yale University. School Of Medicine

Yale Medicine Magazine - alumni bulletin and magazine

This is the Spring 2023 issue of Yale Medicine Magazine, issue 170. Prepared in cooperation with the alumni and development offices at the School of Medicine. Earlier volumes are called Yale School of Medicine alumni bulletins, dating from v.1 (1953) through v.13 (1965) and Yale Medicine: alumni bulletin of the School of Medicine, v.1 (1965) through v. 52, no.1. (Autumn 2017).

Dichloroacetate As A Metabolic Treatment For Glioblastoma, Megan Macia

Yale School of Medicine Physician Associate Program Theses

Glioblastoma is the most common aggressive primary brain tumor in adults, and there is no current standard of care for progression. The Warburg effect is a known part of cancer’s metabolic reprogramming and has been studied as a possible target for limiting tumor growth. Dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, has been proposed as a treatment for glioblastoma, and the drug has had success in phase 1 trials. The proposed study is an open-label, randomized phase 2 clinical trial. Participants will be randomized to oral dichloroacetate, with dosing based on genetic testing, or to a control group treated with lomustine. …

Signature Event: Jane Fraser With David M. Rubenstein, Economic Club Of Washington D.C., Jane Fraser, David M. Rubenstein

Documents

No abstract provided.

Utility Of Shear Wave Elastography In Breast Cancer Diagnosis: A Systematic Review And Meta-Analysis, Aishwarya Pillai

Yale Medicine Thesis Digital Library

In the United States, breast cancer is one of the most diagnosed cancers in women. Early detection, often via mammography, and intervention have been shown to reduce mortality. However, not all cancers are mammographically evident in early stages, if at all. As a result, ultrasound has been increasingly used to supplement mammography for breast cancer detection and assessment, particularly in dense breasts. Recent advancements in ultrasonography include the ability to characterize the stiffness of biological tissues. Shear Wave Elastography (SWE) is one such development used to quantify tissue stiffness within a region of interest.

The resistance of soft tissue to …

Sense-Able Hauntings: Ethics And Narratives In Ornithological Specimen Preservation At Yale's Peabody Museum, Elaina Foley

Kaplan Senior Essay Prize for Use of Library Special Collections

Until I was standing in between the rows of towering metal specimen cabinets, I didn’t understand how many birds the Yale Peabody Museum holds. Like most people, I had only experienced the display side of museums: its dioramas and glass cases. These displays, while made to embody a certain set of interests, priorities, and values, still serve an obscuring function—they vastly underrepresent the museum’s total collections. In their ornithology collection alone, the Peabody currently holds more than 152,000 bird skins, bones, eggs, nests, and other avian fragments. The Peabody staff members who maintain the ornithology specimen collections are distinct from …

Clinical Trials Related To The Spine & Shoulder/Elbow: Rates, Predictors, & Reasons For Termination, Dennis Louis Caruana

Yale Medicine Thesis Digital Library

Clinical trials are key to the advancement of products and procedures related to musculoskeletal conditions. Unfortunately, many trials are terminated prior to completion. ClinicalTrials.gov is a registry and results database maintained by the National Library of Medicine that catalogs trial characteristics and tracks overall recruitment status (e.g., ongoing, completed, terminated) for each study as well as reasons for termination. Reasons for termination have not been specifically evaluated for musculoskeletal trials and those related to the spine and shoulder/elbow were selected for characterization and assessment of independent predictors of termination by comparing characteristics of completed and terminated trials.

The ClinicalTrials.gov database …

Multi-Omic Differences Between Right And Left Sided Colorectal Cancer Liver Metastases, Montana Tremaine Morris

Yale Medicine Thesis Digital Library

Colorectal cancer (CRC) is the second leading cause of cancer-related death both in the United States and worldwide, making it an urgent area of investigation for the oncology community. The inferior survival of patients with right-sided colon cancer (RCC) compared to left (LCC), particularly in metastatic disease, as well as the resistance of RCC to certain targeted systemic therapies, represent clinically important features relevant to the development of improved targeted therapies for CRC. Given the high probability that there is a biological component underpinning the differing clinical behaviors of CRC across anatomic laterality, we conducted a multi-omic analysis on frozen …

Yale School Of Medicine Facts & Figures 2023-2024, Yale School Of Medicine Office Of Communications

Facts & Figures – annual Yale School of Medicine numbers

Provided by the Office of Communications, the Facts and Figures brochure is produced annually as a way to provide a snapshot of key facts and data related to the School of Medicine as well as the Medical Campus. This includes enrollment data, research activity, financial summaries, and more.

Baseline Skin Cytokine Profiles Determined By Rna In Situ Hybridization Correlate With Response To Dupilumab In Patients With Eczematous Dermatitis, Katelyn Singh

Yale Medicine Thesis Digital Library

Dupilumab, a monoclonal antibody that inhibits IL4 and IL13, has revolutionized the treatment of atopic dermatitis (AD). However, not all patients respond optimally, and this may relate to underlying molecular heterogeneity. Yet, clinically useful and accessible methods to assess such heterogeneity have not been developed. Additionally, As the number of targeted medications continues to expand, the choice of which specific therapy to initiate in any individual patient will become increasingly difficult. Currently, there are no biomarkers that can be used to guide treatment selection in common inflammatory diseases such as atopic dermatitis (AD) and psoriasis. This study aims to determine …

Comparison Of Clinical Study Results Reported In Medrxiv Preprints Vs Peer-Reviewed Journal Articles, Guneet Singh Janda

Yale Medicine Thesis Digital Library

The aim of this project was to evaluate the concordance among study characteristics, results, and interpretations described in preprints of clinical studies that are subsequently published in peer-reviewed journals (preprint-journal article pairs).

In this cross-sectional analysis, preprints posted on medRxiv in September 2020 were identified. Four evaluators determined how many preprints were subsequently published in peer-reviewed journals as of September 2022, calculating the time from preprint posting to publication. For preprints with multiple versions, the most recent version prior to journal acceptance was selected. Preprints updated after journal acceptance were excluded. For preprint-journal article pairs describing clinical trials, observational studies, …

Wildfires And Their Impacts On Immigrant Farmworker Women Of Childbearing Age, Rosa Gonzalez Juarez

Public Health Theses

Wildfires have been increasing in recent years due to the climate change that has been affecting the nation and across the globe. The Western part of the United States has been greatly affected, especially California. In 2022 there were 68,988 wildfires reported which consumed 7,577,183 acres nationwide, this was strikingly higher than the 10-year average (National Interagency Coordination Center Wildland Fire Summary and Statistics Annual Report 2022, 2022). The California Wildfires have been detrimental to its residents; however, they have specifically disproportionately affected the Latino population either due to the location of their homes, citizenship status or socioeconomic status (Rosenthal …

Exploring Shared And Unique Barriers To Housing Stability For Spanish Speakers In Connecticut, Gabriela Olea Vargas

Public Health Theses

Throughout the United States, rent costs and eviction increases leave low-income people of color more rent-burdened than their white counterparts; these challenges may result in further complex barriers to housing stability for Spanish speakers. In this explorative study, I examined the shared and unique barriers to housing stability for Spanish speakers in Connecticut. I conducted a rapid qualitative analysis of semi-structured individual interviews and focus groups with (N = 14) participants from three larger research projects (Right to Counsel Evaluation, Project ReSIDe, and Tenant Energy Advocacy). This study included Spanish-speaking individuals living in CT who had participated in at least …

Healthcare Costs For Patients With Severe Alpha-1 Antitrypsin Deficiency Among Augmentation Therapy Users And Non-Users And Impact Of Therapy Frequency, Nikita Raina

Public Health Theses

Background: Alpha-1 antitrypsin deficiency (AATD) is a rare disease caused by a genetic mutation in the SERPINA1 gene which causes low levels of or no working alpha-1 antitrypsin protein to be made. This results in a number of clinical manifestations, most prominently pulmonary issues such as emphysema. An intravenous infusion of human plasma-derived AAT (augmentation therapy) is sometimes prescribed to patients with emphysema, but there is a need for a greater understanding of the resulting economic burden in this patient population.

Methods: A retrospective observational cohort study was conducted using the PearlDiver Mariner Patient Claims Database to analyze healthcare costs …

Examining Genetically Regulated Gene Expression As A Potential Biomarker For Postpartum Depression Screening, Eileen Zhu

Public Health Theses

Background: PPD is one of most common complications of pregnancy but is underdiagnosed and undertreated with less than 10% of women with PPD receiving adequate treatment. Currently, the most well-validated screening questionnaire for perinatal depression, the EPDS, produces a high false positive rate and results in a large number of unnecessary referrals. Objective: The principal emphasis of this investigation will center upon the estrogen sensitivity, which hypothesizes that individuals with a history of PPD will have differences in estrogen receptor gene (ESR1 and ESR2) mediated responses to estradiol and thus, are likely to be more sensitive to the abrupt drop …

A Novel Smarcc1-Mutant Bafopathy Implicates Epigenetic Dysregulation Of Fetal Neural Progenitors In The Pathogenesis Of Congenital Hydrocephalus, Amrita K. Singh

Yale Medicine Thesis Digital Library

Congenital hydrocephalus (CH) is a common disorder requiring neurosurgery in children, however its pathogenesis is poorly understood. Recent studies have implicated SMARCC1 as a candidate CH gene but variants have not been conclusively linked with a human syndrome, nor functionally validated in vivo. This study aims to (i) assess the extent of CH risk associated with SMARCC1 variants; (ii) describe associated clinical and radiographic phenotypes; and (iii) assess the pathogenicity and mechanisms of SMARCC1 depletion in a novel animal model of CH. A genetic association study was conducted using whole-exome sequencing from a CH discovery cohort consisting of 492 neurosurgically-treated …

Difference Between Scheduled And Non Scheduled Banks [Upsc Notes], Byju's

Documents

No abstract provided.

How Are Dietary Patterns Associated With The Onset Of Diabetes In Samoan Children?, Cassie Lam Du

Public Health Theses

Background: In recent years, Samoa has been experiencing rapid increases in diabetes, especially among children. Objective: The aim of this study was to investigate the association between dietary patterns (glycemic load scores) and HbA1c levels in children using a 117 item food frequency questionnaire (FFQ). Methods: Foods from the FFQ were categorized into food groups to run a reduced rank regression, modeling glycemic load as the outcome. The RRR generated a dietary score for each child, which was then categorized into tertiles (based on the score distribution). Bivariate analysis of glycemic load factor score was performed on the child, family, …

Subcutaneous Lesions And Systemic Infections: A Scoping Review Of The Clinical Implications Of Illicit Xylazine Use, Fatimah Maiga

Public Health Theses

Xylazine, a clonidine analog, is a potent alpha-2 adrenergic agonist used as an analgesic sedative in veterinary medicine. Known to people who inject drugs (PWID) as “tranq”, xylazine has recently infiltrated the U.S. illicit opiate drug supply and has been associated with severe, necrotic lesions, sedation, and respiratory depression. Unlike opiates, xylazine has no human reversal agent or standardized withdrawal treatment protocol and its effects are unclear.

The objective of this study was to conduct a scoping review synthesizing the available clinical research and reporting on xylazine associated subcutaneous lesions and systemic infections. The study also sought to identify gaps …

Factorial Validation Analysis Of The Children’S Eating Behavior Questionnaires And Association With Weight Status: The Ola Tuputupua’E Cohort Study, Wenya Tian

Public Health Theses

Background: Childhood obesity is a pressing issue requiring a reliable tool for assessing health-related eating behaviors. The Child Eating Behavior Questionnaire (CEBQ) is a parent-reporting measure designed to assess multiple dimensions of children's eating behavior. This study aimed to assess CEBQ factor structure with data collected from Ola Tuputupua's Cohort and analyze the association between children's eating behavior and weight.

Methods: The confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were conducted. Multinominal logistic regression analyses were conducted to examine associations between the CEBQ subscales with children's weight (healthy weight/overweight/obesity) as the dependent variable.

Results: The original eight-factor CEBQ …