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Oops! My Brain Did It Again! How Music, Smell, And Sight Rekindle The Past, Lana Hunt

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

The Anatomy Of Art: Visual Art And The Brain, Shea Wilt

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

Saying "Goodbye" To The Deficits Of Spinal Cord Injury: Exploring The Inflammatory Mechanisms Underlying Spinal Cord Injury And Related Mood Disorders, Elsie Groebner

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

Investigating Relatedness Within Breeding Units Of The Highly Social Bushtit (Psaltriparus Minimus), Fiona Skye Connelly

Theses and Dissertations--Biology

Cooperative breeding systems represent an array of varied reproductive strategies and remain a topic of interest in behavioral ecology (i.e., Riehl 2013, Cornwallis et al. 2017). Different manifestations of cooperative breeding, such as cooperative polyandry, no doubt have unique evolutionary pressures tied to local ecologies which have led to their proliferation. Of particular interest are species that show flexibility in their use of reproductive strategies, wherein individuals may choose one strategy over another given a specific circumstance. Here, I used double-digest restriction site-associated DNA sequencing (i.e., ddRAD-seq) to investigate bushtit (Psaltriparus minimus) reproductive strategies and the relatedness between …

Temporal Dynamics Of Programmed Genome Rearrangement In Sea Lamprey Embryogenesis: A Deep Learning & Lightsheet Imaging Approach To Studying Early Developmental Transitions, Kasturi Rajandran

Theses and Dissertations--Biology

Programmed genome rearrangement (PGR) in the sea lamprey (Petromyzon marinus) leads to the elimination of ~0.5Gb (20%) of the germline genome during early embryogenesis, yet its timing relative to the maternal-to-zygotic transition (MZT) remains unclear. In this study, we imaged embryos cleared at 3-hour intervals (up to 72 hours post fertilization (hpf)) using high-resolution lightsheet fluorescence microscopy and a custom deep-learning image-analysis pipeline (~80% accuracy) to quantify nuclei and micronuclei counts. Micronuclei, which are the hallmarks of PGR first appear between 24 to 27hpf (vs ~36hpf previously reported) indicating PGR starts earlier than previously reported in the sea …

The Role Of Metabolic Gate Keepers In Cell Fate Decision Making, Brian Kelly

Theses and Dissertations--Biology

Maintaining cellular energy balance and redox stability is crucial to cell survival, with glutamine metabolism playing a central role. While extensively studied in cancer, where it supports biosynthesis and reduces oxidative stress to promote tumor growth, its function in non-cancerous contexts like tissue development and muscle regeneration remains less understood. A key aspect of stem cell biology is quiescence, a metabolically dormant state that preserves the stem cell pool, yet the mechanisms regulating this state are not fully clear. Here, we identify glutamine metabolism as a critical factor governing myoblast proliferation and quiescence through a metabolic program distinct from that …

Ai Think, Therefore, Ai Am?, Bineth Abeysekera

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

Please, Put Away That Plastic! A Plea From Your Grandchildren, Finn Anders

Scientific Kenyon: The Neuroscience Edition

No abstract provided.

Design And Synthesis Of Crosslinkable Amphiphilic Pegylated Poly(Amino Acid) Copolymers For Spion Encapsulation, Adekunle Titus Akinmola

Dissertations

The development of polymeric micelles for biomedical applications has been of significant interest due to their potential for targeted delivery for therapeutic and diagnostic agents. This dissertation focusses on the synthesis, characterization, and application of amphiphilic PEGylated poly(amino acid) block copolymers as nanocarriers for superparamagnetic iron oxide nanoparticles (SPIONs) in magnetic particle imaging (MPI). Series of novel diblock and triblock copolymers were synthesized through ring-opening polymerization of amino acid N-Carboxyanhydrides (NCAs) to afford HO-PEG77-b-p(L-Leu)m and HO-PEGx-b-p(Allyl-L-Gly)10-b-p(L-Leu)n. These polymers were further functionalized to yield their folate conjugates through dicyclohexylcarbodiimide (DCC) coupling. NMR and FTIR were used to verify the chemical structures …

Insights Into How A C. Elegans Neural Circuit Transitions Between Two Internal States To Produce Egg-Laying Behavior, Shavanie Prashad

Yale Graduate School of Arts and Sciences Dissertations

A challenge in neuroscience is understanding how neural circuits generate and sustain behavior over time. Neural circuits consist of interconnected groups of neurons that process and integrate sensory information to perform specific tasks and behaviors. These circuits organize behaviors by maintaining internal states—stable neural activity patterns influenced by sensory and physiological contexts, as discussed in Chapter One.

To understand how neural circuits generate internal states, we examined how the well-characterized C. elegans egg-laying circuit transitions between inactive and active states to produce egg-laying behavior. The active internal state lasts approximately 2 to 3 minutes, during which one or more eggs …

Identifying How Pseudomonas Aeruginosa Cells Become Primed For Expression Of Type Iii Secretion System Genes, Kristen Alicia Ramsey

Yale Graduate School of Arts and Sciences Dissertations

Pseudomonas aeruginosa is an opportunistic pathogen known to cause acute infections in individuals with epithelial damage or medically placed devices, leading to sepsis or death in immunocompetent and immunocompromised individuals. Like many other Gram-negative bacteria, P. aeruginosa uses a Type III Secretion System (T3SS) to intoxicate eukaryotic cells. This T3SS is essential for P. aeruginosa to establish an infection and avoid clearance by immune cells and is also linked to increased morbidity and mortality in infections. Despite this necessity, activation of the T3SS slows P. aeruginosa’s cell growth and permits innate immune system detection and resulting inflammation. To balance …

Extracellular Vesicles Released By All Patients Contain Hne-Adducted Proteins: Implications Of Collateral Damage, Jenni Ho, Suriyan Sukati, Tamara Taylor, Sherry Carter, Brittany Fuller, Amy Marmo, Caryn Sorge, John A. D'Orazio, D. Allan Butterfield, Subbarao Bondada, Heidi Weiss, Daret K. St. Clair, Luksana Chaiswing

Markey Cancer Center Faculty Publications

Off-target neuronal injury is a serious side-effect observed in cancer survivors. It has previously been shown that pediatric acute lymphoblastic leukemia (ALL) survivors have a decline in neurocognition compared to healthy age-matched counterparts. Elevated oxidative stress has been documented to be a mediator in off- target tissue damage in cancer survivors. Early detection of oxidative stress markers may provide an opportunity to prevent off-target tissue damage. Extracellular vesicles (EVs) have surfaced as a potential diagnostic tool due to molecular cargo they contain. We investigated the potential for EVs to be a sensitive indicator of oxidative stress and off-target tissue damage …

Pharmacological Or Genetic Inhibition Of Ltcc Promotes Cardiomyocyte Proliferation Through Inhibition Of Calcineurin Activity, Lynn A. C. Devilée, Abou Bakr M. Salama, Jessica M. Miller, Janice D. Reid, Qinghui Ou, Nourhan M. Baraka, Kamal Abou Farraj, Madiha Jamal, Yibing Nong, Todd K. Rosengart, Douglas A. Andres, Jonathan Satin, Tamer M. A. Mohamed, James E. Hudson, Riham R. E. Abouleisa

Markey Cancer Center Faculty Publications

Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC) induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle …

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M. Kusminski, Terry D. Hinds Jr., Philipp E. Scherer

Markey Cancer Center Faculty Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …

Urobilin Derived From Bilirubin Bioconversion Binds Albumin And May Interfere With Bilirubin Interacting With Albumin: Implications For Disease Pathology, Kevin I. Williams, Priyanka Suryadevara, Chang-Guo Zhan, Terry D. Hinds Jr., Zachary A. Kipp

Markey Cancer Center Faculty Publications

Background/Objectives: Bilirubin is a hydrophobic molecule that binds the carrier protein albumin for transport through systemic circulation. Bilirubin is cleared from the body through the liver and excreted into the intestines, where the microbiota modifies the chemical structure, forming urobilin, which can be reabsorbed into circulation by the hepatic portal vein. Urobilin has no known function. It is also unknown whether urobilin binds albumin for transport in circulation. We hypothesized that because of the likeness of their chemical structures, urobilin would also bind albumin like bilirubin does. Methods: First, we used in silico docking to predict if urobilin would bind …

Dissecting The Biophysical Mechanisms Of Oleate Hydratase Association With Membranes, William A. Lathram, Robert J. Neff, Ashley N. Zalla, James D. Brien, Vivekanandan Subramanian, Christopher D. Radka

Markey Cancer Center Faculty Publications

This study investigates the dynamics of oleate hydratase (OhyA), a bacterial flavoenzyme from Staphylococcus aureus, and its interactions with lipid membranes, focusing on the factors influencing membrane binding and oligomerization. OhyA catalyzes the hydration of unsaturated fatty acids, playing a key role in bacterial pathogenesis by neutralizing host antimicrobial fatty acids. OhyA binds the membrane bilayer to access membrane-embedded substrates for catalysis, and structural studies have revealed that OhyA forms oligomers on membrane surfaces, stabilized by both protein-protein and protein-lipid interactions. Using fluorescence correlation spectroscopy (FCS), we examined the effects of membrane curvature and lipid availability on OhyA binding to …

Advances In Magnetic Nanoparticles For Molecular Medicine, Xiaoyue Yang, Sarah E. Kubican, Zhongchao Yi, Sheng Tong

Markey Cancer Center Faculty Publications

Magnetic nanoparticles (MNPs) are highly versatile nanomaterials in nanomedicine, owing to their diverse magnetic properties, which can be tailored through variations in size, shape, composition, and exposure to inductive magnetic fields. Over four decades of research have led to the clinical approval or ongoing trials of several MNP formulations, fueling continued innovation. Beyond traditional applications in drug delivery, imaging, and cancer hyperthermia, MNPs have increasingly advanced into molecular medicine. Under external magnetic fields, MNPs can generate mechano- or thermal stimuli to modulate individual molecules or cells deep within tissue, offering precise, remote control of biological processes at cellular and molecular …

Mir-27a-3p Regulates Intestinal Cell Proliferation And Differentiation Through Wnt/Β-Catenin Signalling, Chang Li, Yuning Zhou, Yinping Jiang, Zhijie Yin, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differentiation. Repression of endogenous miR-27a-3p leads to increased enterocyte differentiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell differentiation and proliferation at …

Association Between Education And Allostatic Load With Risk Of Cancer Mortality Among Hispanic Women, Melissa Lopez-Pentecost, Cynthia Li, Marlo Vernon, Sydney P. Howard, Jessica Amezcua, Justin Xavier Moore

Markey Cancer Center Faculty Publications

Purpose: Cancer remains the leading cause of death among Hispanics in the US. While social determinants of health, such as educational attainment, have been linked to negative health outcomes, their biological mechanisms remain poorly understood. We evaluated the association between educational attainment and allostatic load (AL), a measure of chronic physiologic stress, with risk of cancer mortality in Hispanic women from the National Health and Nutrition Examination Survey (NHANES).

Methods: We performed a retrospective analysis among 5637 Hispanic women in NHANES from 1988 to 2010 with follow-up data through 2019. Educational attainment was categorized into a two-level variable: less than …

Tracking Community Outreach And Engagement Activities Among National Cancer Institute-Designated Cancer Centers, Todd Burus, Caree R. Mcafee, Pamela C. Hull, Amy E. Leader, Christopher Mcnair

Markey Cancer Center Faculty Publications

The National Cancer Institute’s (NCI) Cancer Center Support Grant mandates that NCI-designated cancer centers establish a Community Outreach and Engagement (COE) component to help direct efforts at reducing cancer burden within their catchment areas. Despite the critical role of COE offices, little is known about how they track and evaluate outreach activities and outcomes. We gathered information on current practices from representatives of 40 out of 65 COE offices using an online survey. Although nearly all responding centers (97.5%) tracked COE activities, no consensus existed on resources used, and satisfaction with current solutions was mixed (51.0% not satisfied). Respondents expressed …

Biparental Inheritance Of Germline-Specific Chromosomes In The Sea Lamprey And Their Roles In Oocytes, Vladimir A. Timoshevskiy, Nataliya Timoshevskaya, Kaan İ. Eşkut, Kasturi Rajandran, Jeramiah J. Smith

Markey Cancer Center Faculty Publications

Many eukaryotic species undergo programmed elimination of specific chromosomes during embryogenesis, typically retaining these chromosomes only in their germ cells. In some species, programmatic elimination of GRCs, or sex chromosomes, also occurs in a sex-specific manner, with specific chromosomes being transmitted or eliminated by only one sex. As such, these chromosomes provide a unique perspective on the evolution of gene functions that are advantageous to the germline and genetic tradeoffs between somatic vs germline or oocyte vs sperm biology. While GRCs have been extensively characterized in male sea lampreys (Petromyzon marinus), the status of GRCs in females has not yet …

Cabozantinib Selectively Induces Proteasomal Degradation Of P53 Somatic Mutant Y220c And Impedes Tumor Growth, Fang Lin Lv, Lu Zhang, Cheng Ji, Lei Peng, Mingxian Zhu, Shumin Yang, Shunli Dong, Mingxuan Zhou, Fanfan Guo, Zhenyun Li, Fang Wang, Youguo Chen, Jinhua Zhou, Xingcong Ren, Genhai Shen, Jin-Ming Yang, Bin Li, Yi Zhang

Markey Cancer Center Faculty Publications

Inactivation of p53 by mutations commonly occurs in human cancer. The mutated p53 proteins may escape proteolytic degradation and exhibit high expression in tumors and acquire gain-of-function activity that promotes tumor progression and chemo-resistance. Therefore, selectively targeting of the gain-of-function p53 mutants may serve as a promising therapeutic strategy for cancer prevention and treatment. In this study, we identified cabozantinib, a multikinase inhibitor currently used in the clinical treatment of several types of cancer, as a selective inducer of proteasomal degradation of the p53-Y220C mutant. We demonstrate that cabozantinib disrupts the interaction between p53Y220C and USP7, a deubiquitylating enzyme, resulting …

Cisplatin-Loaded M1 Macrophage-Derived Vesicles Have Anti-Cancer Activity In Osteosarcoma, Namrata Anand, Joseph Robert Mccorkle, David Schweer, Lan Li, Kristen S. Hill, Melissa A. Fath, Derek B. Allison, Christopher L. Richards, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Osteosarcoma (OS) is a relatively rare bone malignancy that primarily affects children and young adults and is associated with significant morbidity and mortality. Cisplatin is a mainstay of treatment, but its efficacy is limited by off-target toxicities. Immunotherapy is not effective due to a poor antigenic tumor microenvironment. Here, we address these challenges by using manufactured M1 macrophage-derived vesicles (MVs) loaded with cisplatin. Human blood and mouse RAW 264.7 M1 macrophages were used to prepare empty (E-MVs) and cisplatin-loaded MVs (C-MVs). Human OS cell lines were used in vitro and in a tibia xenograft mouse model to evaluate the anti-cancer …

Examining Associations Between Sociodemographic Characteristics And Ever Breastfed Children, Nhanes 1999–2020, Jessica Amezcua, Lindsey M. West, Camelia Malkami, Marlo M. Vernon, Elinita Pollard, Justin X. Moore

Markey Cancer Center Faculty Publications

Although breastfeeding provides health benefits to both mother and child, this study aimed to explore whether disparities in breastfeeding continue to exist, particularly among non-Hispanic Black (NHB) mothers and children. We performed a cross-sectional analysis among 19,830 children in the United States (US) using the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2020. Breastfeeding initiation and duration rates increased overall from 1999 to 2020. Children who were ever breastfed were more likely to have higher body weight, older mothers, mothers who did not smoke during pregnancy, a higher family poverty–income ratio (PIR), food security, mothers in …

Examining Geographic Disparity: Variation In Cancer Outcomes Within Appalachia, Todd Burus, Pamela C. Hull, Krystle A. Lang Kuhs, Tianyan Gao, Christine F. Brainson, B. Mark Evers

Markey Cancer Center Faculty Publications

BACKGROUND: 

The Appalachian region of the US extends from the Mississippi Delta to southern New York. Although disparities in Appalachian cancer outcomes have long been observed, recent rates and trends have not been assessed.

STUDY DESIGN: 

We calculated 5-year age-adjusted US cancer incidence and mortality rates for 2017 to 2021, stratified into Appalachian and non-Appalachian populations, as well as Appalachian subregions, using the US Cancer Statistics Incidence Analytics Database and National Center for Health Statistics mortality files. Annual rates for 2004 to 2021 were also calculated.

RESULTS: 

In 2017 to 2021, all-site cancer incidence (466.6; 95% CI 465.5 to 467.6) …

Health Care Access Domains And Treatment As Mediators Of Ovarian Cancer Racial Disparities In Survival: A Structural Equation Modeling Analysis In Seer-Medicare, Clare Meernik, Quan Chen, Lauren E. Wilson, Ashwini Joshi, Fariha Rahman, Maria Pisu, Margaret Liang, Kevin C. Ward, Margaret Gates Kuliszewski, Thomas Tucker, Andrew Berchuck, Bin Huang, Tomi Akinyemiju

Markey Cancer Center Faculty Publications

Racial differences in health care access (HCA) may contribute to disparities in ovarian cancer (OC) survival. We used structural equation models (SEMs) to examine associations between race and HCA domains (affordability, availability, accessibility) in relation to overall and OC-specific mortality. Non-Hispanic (NH)–Black and non-Black (Hispanic, NH-White) women diagnosed with OC in 2008-2015 were identified from Surveillance, Epidemiology, and End Results–Medicare. Cox proportional hazards regression was used to conduct mediation analysis for associations between race and HCA domains with overall and OC-specific mortality. SEM models adjusting for demographic and clinical covariates were used to estimate hazard ratios (HRs) and 95% CIs. …

Development Of Genome-Scale Technologies For Writing And Recoding Cyanobacteria, Laura Beth Quinto

Yale Graduate School of Arts and Sciences Dissertations

Diverse microorganisms have delivered unique solutions in medicine, food, energy, and nutrient cycling through atmospheric gas fixation. Yet despite tremendous progress in model organisms like E. coli and S. cerevisiae, tools for editing and predictably manipulating undomesticated species – which comprise the vast majority of microbes1 – remain scarce. Cyanobacteria, with their light- and CO₂-powered metabolism, hold particular promise for bioproduction, bioremediation, and in situ fertilization, but have been difficult to engineer. Furthermore, many of the most valuable applications of cyanobacteria would involve implementation in an open system. Such strains require two critical safeguards: biocontainment to ensure that their propagation …

Characterizing Somatic Variants In Nanopore Data With Machine Learning, Shwethal Sayeeram Trikannad

Master's Projects

Oxford Nanopore Technology (ONT) is a popular long-read sequencer in genomics. However, its high base-calling error rate produces several sequencing artifacts. Detection of somatic variants in ONT sequenced tumor-normal samples remains challenging due to low frequencies. In this study, machine learning was applied to a dataset created by benchmarking ClairS output against HCC1395 and colo829 truth sets to classify variants and artifacts. Relevant features were engineered from sequence context and variant site characteristics to model artifact profiles. HistGradientBoostingClassifier achieved 0.876950 accuracy, outperforming all other models. Variant quality was the top predictor with an aggregate accuracy of over 85%. This work …

Leadership And Management In Action Program (L-Map) Supplement: Case Studies For Humanities And Social Sciences, Giovanna Bonadonna Ph.D., Kevin Kadowaki Ph.D., A. Patricia Mendoza Ph.D., Matthew Thompson Ph.D., Shirl Yang Ph.D.

Office of Postdoctoral Affairs

The Leadership and Management in Action Program (L-MAP) Workbook and Facilitator Guide are authored by Erin Heckler, Ph.D., Jessica A. Hutchins, Ph.D., Molly Grisham, M.A., and Elizabeth Luckman, Ph.D., M.B.A. The L-MAP Project was supported by a Burroughs Wellcome Fund (BWF) Career Guidance for Trainees grant to Washington University in St. Louis, 2019-2021 (co-principal investigators: Erin Heckler, Ph.D., and Jessica Hutchins, Ph.D.).

This Supplement does not (nor does it intend to) replace the L-MAP curriculum. The case studies in this document are designed to accompany the theory in the L-MAP curriculum applying it to discipline-specific situations in the humanities and …

Social Support And Gratitude In Adolescents: An Exploratory Study, Mimi Webb Kurtz

Theses and Dissertations

Dispositional gratitude is a construct associated with numerous benefits in youth. However, existing research has primarily focused on the outcomes of gratitude, with limited exploration of the underlying factors that may contribute to individual differences in its development. Because gratitude is considered malleable, identifying key factors associated with its growth in youth is essential. The present study aims to address this gap by exploring perceived social support as a presumed antecedent of dispositional gratitude in older adolescents. Cross-sectional, self-report data and structural equation modeling were used to assess the relationship of perceived social support with gratitude levels among high school …