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Articles 121 - 150 of 638

Full-Text Articles in Genetics and Genomics

Multi-Omic Analysis Of Vegetative Propagation Induced Plant Rejuvenation In Grapevines: Implications For The Generation Of Locally Adapted Cultivars Using Epigenetics, Tajbir Raihan Jan 2023

Multi-Omic Analysis Of Vegetative Propagation Induced Plant Rejuvenation In Grapevines: Implications For The Generation Of Locally Adapted Cultivars Using Epigenetics, Tajbir Raihan

Theses and Dissertations--Plant and Soil Sciences

Epigenetic memory of the growing environment is a process capable of increasing plants’ resilience to abiotic stimuli. The cultivated grapevine is a long-living perennial species with a large corpus of research suggesting that plant adaptation to the environment has implications for the selection of genetic material in a changing climate. Moreover, vine age has been traditionally correlated with enhanced fruit quality. Recent studies have shown that environment/age-acquired traits in grapevine (e.g., adaptation to the growing environment and fruit/wine quality, respectively) are associated with epigenetic mechanisms. These studies also indicate that of propagation type affects the maintenance/erasure of the acquired traits …


Species-Specific Microsymbiont Discrimination Mediated By A Medicago Receptor Kinase, Xiaocheng Yu Jan 2023

Species-Specific Microsymbiont Discrimination Mediated By A Medicago Receptor Kinase, Xiaocheng Yu

Theses and Dissertations--Plant and Soil Sciences

Legumes form a mutualistic partnership with nitrogen-fixing bacteria to meet their nitrogen requirements. This collaboration leads to the development of root nodules, offering an ideal environment for the bacteria to convert atmospheric nitrogen into ammonia. A salient aspect of this symbiotic relationship is host range specificity, such that nodulation capacity and nitrogen fixation efficiency differ significantly between different host-bacterial combinations. Understanding the genetic basis of this specificity could pave the way for strategies to overcome the host range barrier. Sinorhizobium meliloti and Sinorhizobium medicae are two closely related species that display differential symbiotic behaviors with legume plants of the Medicago …


Placing The Evolutionary History Of Desmognathus Salamanders In Context: A Phylogeographic Approach, Kara Jones Jan 2023

Placing The Evolutionary History Of Desmognathus Salamanders In Context: A Phylogeographic Approach, Kara Jones

Theses and Dissertations--Biology

Patterns of genetic variation do not arise in a vacuum but are instead shaped by the interplay between evolutionary forces and ecological constraints. Here, I use a phylogeographic approach to examine the role that ecology played in lineage divergence in the Desmognathus quadramaculatus species complex (Family: Plethodontidae), which consists of three nominal species: D. quadramaculatus, D. marmoratus, and D. folkertsi. Previous phylogenetic studies have shown that individuals from these species do not form clades based on phenotype. My approach to reconciling phylogenetic discordance was two-fold, using (1) genome-wide markers to provide insight into the …


A Monoadduct Generating Ru(Ii) Complex Induces Ribosome Biogenesis Stress And Is A Molecular Mimic Of Phenanthriplatin, Richard Joseph Mitchell, Sarah M. Kriger, Alexander D. Fenton, Dmytro Havrylyuk, Ankit Pandeya, Yang Sun, Tami Smith, Jason E. Derouchey, David K. Heidary, Edith C. Glazer Jan 2023

A Monoadduct Generating Ru(Ii) Complex Induces Ribosome Biogenesis Stress And Is A Molecular Mimic Of Phenanthriplatin, Richard Joseph Mitchell, Sarah M. Kriger, Alexander D. Fenton, Dmytro Havrylyuk, Ankit Pandeya, Yang Sun, Tami Smith, Jason E. Derouchey, David K. Heidary, Edith C. Glazer

Markey Cancer Center Faculty Publications

Ruthenium complexes are often investigated as potential replacements for platinum-based chemotherapeutics in hopes of identifying systems with improved tolerability in vivo and reduced susceptibility to cellular resistance mechanisms. Inspired by phenanthriplatin, a non-traditional platinum agent that contains only one labile ligand, monofunctional ruthenium polypyridyl agents have been developed, but until now, few demonstrated promising anticancer activity. Here we introduce a potent new scaffold, based on [Ru(tpy)(dip)Cl]Cl (tpy = 2,20:60,200-terpyridine and dip = 4,7-diphenyl-1,10-phenanthroline) in pursuit of effective Ru(II )-based monofunctional agents. Notably, the extension of the terpyridine at the 40 position with an aromatic ring resulted in a molecule that …


Dysregulated Polycomb Repressive Complex 2 Contributes To Chronic Obstructive Pulmonary Disease By Rewiring Stem Cell Fate, Aria Byrd, Xufeng Qu, Alexsandr Lukyanchuk, Jinpeng Liu, Fan Chen, Kassandra J. Naughton, Tanner Ducote, Xiulong Song, Hannah Bowman, Yanming Zhao, Abigail R Edgin, Chi Wang, Jinze Liu, Christine Fillmore Brainson Jan 2023

Dysregulated Polycomb Repressive Complex 2 Contributes To Chronic Obstructive Pulmonary Disease By Rewiring Stem Cell Fate, Aria Byrd, Xufeng Qu, Alexsandr Lukyanchuk, Jinpeng Liu, Fan Chen, Kassandra J. Naughton, Tanner Ducote, Xiulong Song, Hannah Bowman, Yanming Zhao, Abigail R Edgin, Chi Wang, Jinze Liu, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Aberrant lung cell differentiation is a hallmark of many lung diseases including chronic obstructive pulmonary disease (COPD). The EZH2-containing Polycomb Repressive Complex 2 (PRC2) regulates embryonic lung stem cell fate, but its role in adult lung is obscure. Histological analysis of patient tissues revealed that loss of PRC2 activity was correlated with aberrant bronchiolar cell differentiation in COPD lung. Histological and single-cell RNA-sequencing analyses showed that loss of EZH2 in mouse lung organoids led to lowered self- renewal capability, increased squamous morphological development, and marked shifts in progenitor cell populations. Evaluation of in vivo models revealed that heterozygosity of Ezh2 …


Polycomb Deficiency Drives A Foxp2-High Aggressive State Targetable By Epigenetic Inhibitors, Fan Chen, Aria Byrd, Jinpeng Liu, Robert M. Flight, Tanner Ducote, Kassandra J. Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T. Dixon, Christian M. Gosser, Dave-Preston Esoe, Rani Jayswal, Stuart H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson Jan 2023

Polycomb Deficiency Drives A Foxp2-High Aggressive State Targetable By Epigenetic Inhibitors, Fan Chen, Aria Byrd, Jinpeng Liu, Robert M. Flight, Tanner Ducote, Kassandra J. Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T. Dixon, Christian M. Gosser, Dave-Preston Esoe, Rani Jayswal, Stuart H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Inhibitors of the Polycomb Repressive Complex 2 (PRC2) histone methyltransferase EZH2 are approved for certain cancers, but realizing their wider utility relies upon understanding PRC2 biology in each cancer system. Using a genetic model to delete Ezh2 in KRAS-driven lung adenocarcinomas, we observed that Ezh2 haplo-insufficient tumors were less lethal and lower grade than Ezh2 fully-insufficient tumors, which were poorly differentiated and metastatic. Using three-dimensional cultures and in vivo experiments, we determined that EZH2-deficient tumors were vulnerable to H3K27 demethylase or BET inhibitors. PRC2 loss/inhibition led to de-repression of FOXP2, a transcription factor that promotes migration and stemness, and FOXP2 …


Molecular Analysis Of Epigenetic Memory Of Stress Establishment And Long-Term Maintenance In A Perennial Woody Plant, Jia Wen Tan Jan 2023

Molecular Analysis Of Epigenetic Memory Of Stress Establishment And Long-Term Maintenance In A Perennial Woody Plant, Jia Wen Tan

Theses and Dissertations--Plant and Soil Sciences

Plants adapt to extreme environmental conditions through physiological adaptations, which are usually transient. Recent research has suggested that environmental conditions can activate a memory of stress that can result in a primed response to subsequent stress events. While the effect of priming has been observed in many plants, the underlying mechanisms are puzzling and seldom studied. A large body of research has been developed in the last decade linking response to stress, stress priming, and memory of stress with epigenetic mechanisms. This understanding of plant epigenetics has opened the door to the application of epigenetics to crop improvement, such as …


Understanding The Basis For Increased 2,4-D Tolerance In Red Clover (Trifolium Pratense): Field Evaluations, Metabolism, And Gene Expression, Lucas Pinheiro De Araujo Jan 2023

Understanding The Basis For Increased 2,4-D Tolerance In Red Clover (Trifolium Pratense): Field Evaluations, Metabolism, And Gene Expression, Lucas Pinheiro De Araujo

Theses and Dissertations--Plant and Soil Sciences

Incorporation of red clover (Trifolium pratense L.) into grass pastures offers several benefits. However, red clover cultivars available for Kentucky producers are highly susceptible to synthetic auxin herbicides, such as 2,4-D (2,4-dichlorophenoxy acetic acid), used for pasture broadleaf weed control. To overcome this problem, UK2014 red clover was bred for increased tolerance to 2,4-D. We compared the field performance of UK2014 to Kenland, a standard cultivar grown in the transition zone of the United States. UK2014 and Kenland were seeded in the springs of 2017 and 2018. Single applications of 0, 1.12, or 2.24 kg ae ha-1 2,4-D …


Cell-Intrinsic Melanin Fails To Protect Melanocytes From Ultraviolet-Mutagenesis In The Absence Of Epidermal Melanin, Tirzah J. Weiss, Emma R. Crawford, Valentina Posada, Hafeez Rahman, Tong Liu, Brandon M. Murphy, Tiffany E. Arnold, Shannon Gray, Zhexuan Hu, Rebecca C. Hennessey, Lianbo Yu, John August D'Orazio, Craig J. Burd, Jonathan H. Zippin, Douglas Grossman, Christin E. Burd Sep 2022

Cell-Intrinsic Melanin Fails To Protect Melanocytes From Ultraviolet-Mutagenesis In The Absence Of Epidermal Melanin, Tirzah J. Weiss, Emma R. Crawford, Valentina Posada, Hafeez Rahman, Tong Liu, Brandon M. Murphy, Tiffany E. Arnold, Shannon Gray, Zhexuan Hu, Rebecca C. Hennessey, Lianbo Yu, John August D'Orazio, Craig J. Burd, Jonathan H. Zippin, Douglas Grossman, Christin E. Burd

Markey Cancer Center Faculty Publications

Melanin is a free-radical scavenger, antioxidant, and broadband absorber of ultraviolet (UV) radiation which protects the skin from environmental carcinogenesis. However, melanin synthesis and UV-induced reactive melanin species are also implicated in melanocyte genotoxicity. Here, we attempted to reconcile these disparate functions of melanin using a UVB- sensitive, NRAS-mutant mouse model, TpN. We crossed TpN mice heterozygous for an inactivating mutation in Tyrosinase to produce albino and black littermates on a C57BL/6J background. These animals were then exposed to a single UVB dose on postnatal day three when keratinocytes in the skin have yet to be melanized. Approximately one-third (35%) …


Extracellular Vesicles Released After Cranial Radiation: An Insight Into An Early Mechanism Of Brain Injury., Suriyan Sukati, Jenni Ho, Luksana Chaiswing, Pradoldej Sompol, Harshul Pandit, Wendy Wei, Tadahide Izumi, Quan Chen, Heidi Weiss, Teresa Noel, Subbarao Bondada, D Allan Butterfield, Daret K St Clair May 2022

Extracellular Vesicles Released After Cranial Radiation: An Insight Into An Early Mechanism Of Brain Injury., Suriyan Sukati, Jenni Ho, Luksana Chaiswing, Pradoldej Sompol, Harshul Pandit, Wendy Wei, Tadahide Izumi, Quan Chen, Heidi Weiss, Teresa Noel, Subbarao Bondada, D Allan Butterfield, Daret K St Clair

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Cranial radiation is important for treating both primary brain tumors and brain metastases. A potential delayed side effect of cranial radiation is neurocognitive function decline. Early detection of CNS injury might prevent further neuronal damage. Extracellular vesicles (EVs) have emerged as a potential diagnostic tool because of their unique membranous characteristics and cargos. We investigated whether EVs can be an early indicator of CNS injury by giving C57BJ/6 mice 10 Gy cranial IR. EVs were isolated from sera to quantify: 1) number of EVs using nanoparticle tracking analysis (NTA); 2) Glial fibrillary acidic protein (GFAP), an astrocyte marker; and 3) …


Rare Coding Variants In Rcn3 Are Associated With Blood Pressure, Karen Y. He, Tanika N. Kelly, Heming Wang, Jingjing Liang, Luke Zhu, Brian E. Cade, Themistocles L. Assimes, Lewis C. Becker, Amber L. Beitelshees, Lawrence F. Bielak, Adam P. Bress, Jennifer A. Brody, Yen-Pei Christy Chang, Yi-Cheng Chang, Paul S. De Vries, Ravindranath Duggirala, Ervin R. Fox, Nora Franceschini, Anna L. Furniss, Yan Gao, Donna K. Arnett Feb 2022

Rare Coding Variants In Rcn3 Are Associated With Blood Pressure, Karen Y. He, Tanika N. Kelly, Heming Wang, Jingjing Liang, Luke Zhu, Brian E. Cade, Themistocles L. Assimes, Lewis C. Becker, Amber L. Beitelshees, Lawrence F. Bielak, Adam P. Bress, Jennifer A. Brody, Yen-Pei Christy Chang, Yi-Cheng Chang, Paul S. De Vries, Ravindranath Duggirala, Ervin R. Fox, Nora Franceschini, Anna L. Furniss, Yan Gao, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of …


The Low Abundance Of Cpg In The Sars-Cov-2 Genome Is Not An Evolutionarily Signature Of Zap, Ali Afrasiabi, Hamid Alinejad-Rokny, Azad Khosh, Mostafa Rahnama, Nigel Lovell, Zhenming Xu, Diako Ebrahimi Feb 2022

The Low Abundance Of Cpg In The Sars-Cov-2 Genome Is Not An Evolutionarily Signature Of Zap, Ali Afrasiabi, Hamid Alinejad-Rokny, Azad Khosh, Mostafa Rahnama, Nigel Lovell, Zhenming Xu, Diako Ebrahimi

Plant Pathology Faculty Publications

The zinc finger antiviral protein (ZAP) is known to restrict viral replication by binding to the CpG rich regions of viral RNA, and subsequently inducing viral RNA degradation. This enzyme has recently been shown to be capable of restricting SARS-CoV-2. These data have led to the hypothesis that the low abundance of CpG in the SARS-CoV-2 genome is due to an evolutionary pressure exerted by the host ZAP. To investigate this hypothesis, we performed a detailed analysis of many coronavirus sequences and ZAP RNA binding preference data. Our analyses showed neither evidence for an evolutionary pressure acting specifically on CpG …


Long-Read Sequencing Of The Zebrafish Genome Reorganizes Genomic Architecture, Yelena Chernyavskaya, Xiaofei Zhang, Jinze Liu, Jessica S. Blackburn Feb 2022

Long-Read Sequencing Of The Zebrafish Genome Reorganizes Genomic Architecture, Yelena Chernyavskaya, Xiaofei Zhang, Jinze Liu, Jessica S. Blackburn

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Nanopore sequencing technology has revolutionized the field of genome biology with its ability to generate extra-long reads that can resolve regions of the genome that were previously inaccessible to short-read sequencing platforms. Over 50% of the zebrafish genome consists of difficult to map, highly repetitive, low complexity elements that pose inherent problems for short-read sequencers and assemblers.

RESULTS: We used long-read nanopore sequencing to generate a de novo assembly of the zebrafish genome and compared our assembly to the current reference genome, GRCz11. The new assembly identified 1697 novel insertions and deletions over one kilobase in length and placed …


Apoe Genetics Influence Murine Gut Microbiome, Diana J. Zajac, Stefan J. Green, Lance A. Johnson, Steven Estus Feb 2022

Apoe Genetics Influence Murine Gut Microbiome, Diana J. Zajac, Stefan J. Green, Lance A. Johnson, Steven Estus

Physiology Faculty Publications

Apolipoprotein E (APOE) alleles impact pathogenesis and risk for multiple human diseases, making them primary targets for disease treatment and prevention. Previously, we and others reported an association between APOE alleles and the gut microbiome. Here, we evaluated effects of APOE heterozygosity and tested whether these overall results extended to mice maintained under ideal conditions for microbiome analyses. To model human APOE alleles, this study used APOE targeted replacement (TR) mice on a C57Bl/6 background. To minimize genetic drift, homozygous APOE3 mice were crossed to homozygous APOE2 or homozygous APOE4 mice prior to the study, and the resulting …


Chromomap: An R Package For Interactive Visualization Of Multi-Omics Data And Annotation Of Chromosomes, Lakshay Anand, Carlos M. Rodriguez Lopez Jan 2022

Chromomap: An R Package For Interactive Visualization Of Multi-Omics Data And Annotation Of Chromosomes, Lakshay Anand, Carlos M. Rodriguez Lopez

Horticulture Faculty Publications

BACKGROUND: The recent advancements in high-throughput sequencing have resulted in the availability of annotated genomes, as well as of multi-omics data for many living organisms. This has increased the need for graphic tools that allow the concurrent visualization of genomes and feature-associated multi-omics data on single publication-ready plots.

RESULTS: We present chromoMap, an R package, developed for the construction of interactive visualizations of chromosomes/chromosomal regions, mapping of any chromosomal feature with known coordinates (i.e., protein coding genes, transposable elements, non-coding RNAs, microsatellites, etc.), and chromosomal regional characteristics (i.e. genomic feature density, gene expression, DNA methylation, chromatin modifications, etc.) of organisms …


Use Of Heterothallic Mat Deletion Strains Of Fusarium Graminearum As Test Mates In Crosses To Evaluate The Genetics Of Pathogenicity And Fitness, Gabdiel Emmanuel Yulfo-Soto Jan 2022

Use Of Heterothallic Mat Deletion Strains Of Fusarium Graminearum As Test Mates In Crosses To Evaluate The Genetics Of Pathogenicity And Fitness, Gabdiel Emmanuel Yulfo-Soto

Theses and Dissertations--Plant Pathology

Fusarium Head Blight (FHB), caused by Fusarium graminearum sensu stricto and other members of the F. graminearum species complex (FGSC), is a plant disease that occurs on cereal crops worldwide. FHB causes yield losses not only by reducing grain weight, but also by contaminating the kernels with dangerous trichothecene mycotoxins, especially deoxynivalenol (DON). There is a high degree of genotypic and phenotypic variation among pathogen species and strains, but current FHB risk assessment models and treatments do not account for pathogen diversity. Therefore, it is difficult to predict what will happen if a new, potentially more aggressive variant is introduced, …


Sex Dimorphism In Hematopoiesis And Bone Marrow Niche, Xiaojing Cui Jan 2022

Sex Dimorphism In Hematopoiesis And Bone Marrow Niche, Xiaojing Cui

Theses and Dissertations--Toxicology and Cancer Biology

Hematopoietic stem cells (HSC), which are a rare population of cells existing in human circulating blood and bone marrow, can form the whole-blood system by their self-renewal capacity and differentiation ability. Sex dimorphism can be found in hematopoietic stem and progenitor cells, and in the development of hematopoietic lineages. Also, males are at higher risk and have a worse prognosis for most hematologic malignancies than females. Under normal conditions, the number of circulating progenitor cells in women is lower than in men. Furthermore, female mice have a higher rate of HSC division than male mice. A dramatic gender difference exists …


Investigating The Role Of Chd7 And Sox11 In Retinal Cell Development And The Ocular Complications Of Charge Syndrome, Laura Krueger Jan 2022

Investigating The Role Of Chd7 And Sox11 In Retinal Cell Development And The Ocular Complications Of Charge Syndrome, Laura Krueger

Theses and Dissertations--Biology

Proper formation of the visual system requires the precise interaction of several embryonic cell lineages, including the neuroectoderm (forms the retina and retinal pigment epithelium), surface ectoderm (forms the lens), mesoderm and cranial neural crest cells (form the ocular blood vessels and anterior ocular structures). When this process is disrupted structural birth defects such as coloboma result, leading to pediatric visual deficits. Ocular developmental defects are often present in larger syndromic disorders. One example is CHARGE syndrome, a genetic disorder characterized by coloboma, heart defects, choanal atresia, growth retardation, genital abnormalities, and ear abnormalities. Pathogenic variants in CHD7 have been …


Immunoregulatory Receptor Genetics, Expression, And Splicing Studies In Alzheimer’S Disease, Benjamin C. Shaw Jan 2022

Immunoregulatory Receptor Genetics, Expression, And Splicing Studies In Alzheimer’S Disease, Benjamin C. Shaw

Theses and Dissertations--Physiology

Microglia are the resident immune cells of the brain, undertaking many critical tissue maintenance functions such as immune surveillance and phagocytosis. Microglial dysfunction has recently been identified as a multi-stage signature of many neurodegenerative diseases, including late-onset Alzheimer’s Disease (LOAD). Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in over thirty genes that modulate risk of developing LOAD. In the central nervous system, roughly half of these LOAD-associated genes are primarily expressed in microglia. The proteins encoded by these genes include cell surface receptors that contain either immunomodulatory tyrosine-phosphorylated activating motifs (ITAMs) or inhibitory motifs (ITIMs), including TREM2 …


The Role Of Nitric Oxide In Inter- And Intra- Cellular Signaling In Plant Defense, Fan Xia Jan 2022

The Role Of Nitric Oxide In Inter- And Intra- Cellular Signaling In Plant Defense, Fan Xia

Theses and Dissertations--Plant Pathology

Plants have evolved a sophisticated immune system to defend themselves against pathogens. This immune response can be triggered in response to pathogen-associated molecular patterns (PAMP) or specialized effectors that are recognized by the plant resistance (R) proteins. The latter, commonly referred to as effector-triggered immunity (ETI), is well known to induce broad-spectrum resistance throughout the plants. This phenomenon known as systemic acquired resistance (SAR) is regulated by several chemical signals including salicylic acid (SA), and free radical nitric oxide (NO) and reactive oxygen species (ROS). These signals operate in two parallel branches with NO/ROS functioning downstream of pipecolic acid (Pip) …


A Functional Genomics Approach To Overwintering Mechanisms In Insects, Emily Allison Wheeler Nadeau Jan 2022

A Functional Genomics Approach To Overwintering Mechanisms In Insects, Emily Allison Wheeler Nadeau

Theses and Dissertations--Entomology

Insects living in temperate and polar environments have developed numerous adaptations to increase survival at low temperatures. A majority of insects are freeze-intolerant and die from internal ice formation, but some are freeze-tolerant and can survive ice formation in extracellular spaces. Both categories of insects prepare for winter with a combination of seasonal and rapid acclimation responses, which differ both in time course and in underlying mechanisms. In this dissertation, I examine adaptations for winter survival in several insect species with a specific focus on molecular mechanisms. To better understand the underpinning mechanisms of these adaptations, I leverage functional genomics …


Identifying Epidermal Enriched Genes Required For Planarian Regeneration- Sp. Schmidtea Mediterranea, Pallob Barai Jan 2022

Identifying Epidermal Enriched Genes Required For Planarian Regeneration- Sp. Schmidtea Mediterranea, Pallob Barai

Theses and Dissertations--Biology

The outer epithelial layer covering an organism, commonly known as the epidermis, is crucial for maintaining homeostasis and for the wound healing processes after injury. The planarian epidermis allows flatworms to heal their wounds and virtually restore any missing tissues. Immediately after amputation, planarians contract their muscle and stretch their epidermis to heal the wound area. However, how the planarian epidermis coordinates with other tissues and mechanisms after the initial wound healing processes begins is not understood in detail. I hypothesized that epidermal cell stretching upon wound healing induces transcriptional changes that are required for effective regeneration. To test this …


Editorial For The Genetics Of Alzheimer’S Disease Special Issue: October 2021, Laura Ibanez, Justin B. Miller Nov 2021

Editorial For The Genetics Of Alzheimer’S Disease Special Issue: October 2021, Laura Ibanez, Justin B. Miller

Sanders-Brown Center on Aging Faculty Publications

No abstract provided.


Genomics Of Postprandial Lipidomics In The Genetics Of Lipid-Lowering Drugs And Diet Network Study, Marguerite R. Irvin, May E. Montasser, Tobias Kind, Sili Fan, Dinesh K. Barupal, Amit Patki, Rikki M. Tanner, Nicole D. Armstrong, Kathleen A. Ryan, Steven A. Claas, Jeffrey R. O’Connell, Hemant K. Tiwari, Donna K. Arnett Nov 2021

Genomics Of Postprandial Lipidomics In The Genetics Of Lipid-Lowering Drugs And Diet Network Study, Marguerite R. Irvin, May E. Montasser, Tobias Kind, Sili Fan, Dinesh K. Barupal, Amit Patki, Rikki M. Tanner, Nicole D. Armstrong, Kathleen A. Ryan, Steven A. Claas, Jeffrey R. O’Connell, Hemant K. Tiwari, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled …


Interleukin-10 Suppression Enhances T-Cell Antitumor Immunity And Responses To Checkpoint Blockade In Chronic Lymphocytic Leukemia., J R Rivas, Y Liu, S S Alhakeem, J M Eckenrode, F Marti, J P Collard, Y Zhang, K A Shaaban, N Muthusamy, G C Hildebrandt, L Chen, J S Thorson, M Leggas, Subbarao Bondada Nov 2021

Interleukin-10 Suppression Enhances T-Cell Antitumor Immunity And Responses To Checkpoint Blockade In Chronic Lymphocytic Leukemia., J R Rivas, Y Liu, S S Alhakeem, J M Eckenrode, F Marti, J P Collard, Y Zhang, K A Shaaban, N Muthusamy, G C Hildebrandt, L Chen, J S Thorson, M Leggas, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

T-cell dysfunction is a hallmark of B-cell Chronic Lymphocytic Leukemia (CLL), where CLL cells downregulate T-cell responses through regulatory molecules including programmed death ligand-1 (PD-L1) and Interleukin-10 (IL-10). Immune checkpoint blockade (ICB) aims to restore T-cell function by preventing the ligation of inhibitory receptors like PD-1. However, most CLL patients do not respond well to this therapy. Thus, we investigated whether IL-10 suppression could enhance antitumor T-cell activity and responses to ICB. Since CLL IL-10 expression depends on Sp1, we utilized a novel, better tolerated analogue of the Sp1 inhibitor mithramycin (MTM


Decoding The Equine Genome: Lessons From Encode, Sichong Peng, Jessica L. Petersen, Rebecca R. Bellone, Theodore S. Kalbfleisch, N. B. Kingsley, Alexa M. Barber, Eleonora Cappelletti, Elena Giulotto, Carrie J. Finno Oct 2021

Decoding The Equine Genome: Lessons From Encode, Sichong Peng, Jessica L. Petersen, Rebecca R. Bellone, Theodore S. Kalbfleisch, N. B. Kingsley, Alexa M. Barber, Eleonora Cappelletti, Elena Giulotto, Carrie J. Finno

Veterinary Science Faculty Publications

The horse reference genome assemblies, EquCab2.0 and EquCab3.0, have enabled great advancements in the equine genomics field, from tools to novel discoveries. However, significant gaps of knowledge regarding genome function remain, hindering the study of complex traits in horses. In an effort to address these gaps and with inspiration from the Encyclopedia of DNA Elements (ENCODE) project, the equine Functional Annotation of Animal Genome (FAANG) initiative was proposed to bridge the gap between genome and gene expression, providing further insights into functional regulation within the horse genome. Three years after launching the initiative, the equine FAANG group has generated data …


Chemotherapy-Induced Cognitive Impairment: Focus On The Intersection Of Oxidative Stress And Tnfα., Nicole G Rummel, Luksana Chaiswing, Subbarao Bondada, Daret K St Clair, D Allan Butterfield Oct 2021

Chemotherapy-Induced Cognitive Impairment: Focus On The Intersection Of Oxidative Stress And Tnfα., Nicole G Rummel, Luksana Chaiswing, Subbarao Bondada, Daret K St Clair, D Allan Butterfield

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chemotherapy-induced cognitive impairment (CICI) has been observed in a large fraction of cancer survivors. Although many of the chemotherapeutic drugs do not cross the blood-brain barrier, following treatment, the structure and function of the brain are altered and cognitive dysfunction occurs in a significant number of cancer survivors. The means by which CICI occurs is becoming better understood, but there still remain unsolved questions of the mechanisms involved. The hypotheses to explain CICI are numerous. More than 50% of FDA-approved cancer chemotherapy agents are associated with reactive oxygen species (ROS) that lead to oxidative stress and activate a myriad of …


Against The Odds: Hybrid Zones Between Mangrove Killifish Species With Different Mating Systems, Waldir M. Berbel-Filho, Andrey Tatarenkov, George Pacheco, Helder M. V. Espírito-Santo, Mateus G. Lira, Carlos Garcia De Leaniz, John C. Avise, Sergio M. Q. Lima, Carlos M. Rodriguez Lopez, Sofia Consuegra Sep 2021

Against The Odds: Hybrid Zones Between Mangrove Killifish Species With Different Mating Systems, Waldir M. Berbel-Filho, Andrey Tatarenkov, George Pacheco, Helder M. V. Espírito-Santo, Mateus G. Lira, Carlos Garcia De Leaniz, John C. Avise, Sergio M. Q. Lima, Carlos M. Rodriguez Lopez, Sofia Consuegra

Horticulture Faculty Publications

Different mating systems are expected to affect the extent and direction of hybridization. Due to the different levels of sexual conflict, the weak inbreeder/strong outbreeder (WISO) hypothesis predicts that gametes from self-incompatible (SI) species should outcompete gametes from self-compatible (SC) ones. However, other factors such as timing of selfing and unilateral incompatibilities may also play a role on the direction of hybridization. In addition, differential mating opportunities provided by different mating systems are also expected to affect the direction of introgression in hybrid zones involving outcrossers and selfers. Here, we explored these hypotheses with a unique case of recent hybridization …


Set1 Targets Genes With Essential Identity And Tumor-Suppressing Functions In Planarian Stem Cells, Prince Verma, Courtney K. M. Waterbury, Elizabeth M. Duncan Jul 2021

Set1 Targets Genes With Essential Identity And Tumor-Suppressing Functions In Planarian Stem Cells, Prince Verma, Courtney K. M. Waterbury, Elizabeth M. Duncan

Biology Faculty Publications

Tumor suppressor genes (TSGs) are essential for normal cellular function in multicellular organisms, but many TSGs and tumor-suppressing mechanisms remain unknown. Planarian flatworms exhibit particularly robust tumor suppression, yet the specific mechanisms underlying this trait remain unclear. Here, we analyze histone H3 lysine 4 trimethylation (H3K4me3) signal across the planarian genome to determine if the broad H3K4me3 chromatin signature that marks essential cell identity genes and TSGs in mammalian cells is conserved in this valuable model of in vivo stem cell function. We find that this signature is indeed conserved on the planarian genome and that the lysine methyltransferase Set1 …


Highly Contiguous Assemblies Of 101 Drosophilid Genomes, Bernard Y. Kim, Jeremy R. Wang, Danny E. Miller, Olga Barmina, Emily Delaney, Ammon Thompson, Aaron A. Comeault, David Peede, Emmanuel R. R. D'Agostino, Julianne Pelaez, Jessica M. Aguilar, Diler Haji, Teruyuki Matsunaga, Ellie E. Armstrong, Molly Zych, Yoshitaka Ogawa, Marina Stamenković-Radak, Mihailo Jelić, Marija Savić Veselinović, Marija Tanasković, Jeremy S. Davis Jul 2021

Highly Contiguous Assemblies Of 101 Drosophilid Genomes, Bernard Y. Kim, Jeremy R. Wang, Danny E. Miller, Olga Barmina, Emily Delaney, Ammon Thompson, Aaron A. Comeault, David Peede, Emmanuel R. R. D'Agostino, Julianne Pelaez, Jessica M. Aguilar, Diler Haji, Teruyuki Matsunaga, Ellie E. Armstrong, Molly Zych, Yoshitaka Ogawa, Marina Stamenković-Radak, Mihailo Jelić, Marija Savić Veselinović, Marija Tanasković, Jeremy S. Davis

Biology Faculty Publications

Over 100 years of studies in Drosophila melanogaster and related species in the genus Drosophila have facilitated key discoveries in genetics, genomics, and evolution. While high-quality genome assemblies exist for several species in this group, they only encompass a small fraction of the genus. Recent advances in long-read sequencing allow high-quality genome assemblies for tens or even hundreds of species to be efficiently generated. Here, we utilize Oxford Nanopore sequencing to build an open community resource of genome assemblies for 101 lines of 93 drosophilid species encompassing 14 species groups and 35 sub-groups. The genomes are highly contiguous and complete, …