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Articles 121 - 150 of 155

Full-Text Articles in Genetics

Inhibition Of The Integrin/Fak Signaling Axis And C-Myc Synergistically Disrupts Ovarian Cancer Malignancy, B. Xu, Jason R. Lefringhouse, Z. Liu, D. West, Lauren A. Baldwin, C. Ou, L. Chen, Dana L. Napier, Luksana Chaiswing, Lawrence D. Brewer, Daret K. St Clair, Olivier Thibault, John R. Van Nagell, Binhua P. Zhou, R. Drapkin, J.-A. Huang, M. L. Lu, Frederick R. Ueland, X. H. Yang Jan 2017

Inhibition Of The Integrin/Fak Signaling Axis And C-Myc Synergistically Disrupts Ovarian Cancer Malignancy, B. Xu, Jason R. Lefringhouse, Z. Liu, D. West, Lauren A. Baldwin, C. Ou, L. Chen, Dana L. Napier, Luksana Chaiswing, Lawrence D. Brewer, Daret K. St Clair, Olivier Thibault, John R. Van Nagell, Binhua P. Zhou, R. Drapkin, J.-A. Huang, M. L. Lu, Frederick R. Ueland, X. H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor. From this screening, JQ1, a potent inhibitor of Myc oncogenic network, emerged as the most robust collaborator. Treatment with a combination of VS-6063 …


Association Of Body Mass Index With Dna Methylation And Gene Expression In Blood Cells And Relations To Cardiometabolic Disease: A Mendelian Randomization Approach, Michael M. Mendelson, Riccardo E. Marioni, Roby Joehanes, Chunyu Liu, Åsa K. Hedman, Stella Aslibekyan, Ellen W. Demerath, Weihua Guan, Degui Zhi, Chen Yao, Tianxiao Huan, Christine Willinger, Brian Chen, Paul Courchesne, Michael Multhaup, Marguerite R. Irvin, Ariella Cohain, Eric E. Schadt, Megan L. Grove, Jan Bressler, Kari North, Johan Sundström, Stefan Gustafsson, Sonia Shah, Allan F. Mcrae, Sarah E. Harris, Jude Gibson, Paul Redmond, Janie Corley, Lee Murphy, Donna K. Arnett Jan 2017

Association Of Body Mass Index With Dna Methylation And Gene Expression In Blood Cells And Relations To Cardiometabolic Disease: A Mendelian Randomization Approach, Michael M. Mendelson, Riccardo E. Marioni, Roby Joehanes, Chunyu Liu, Åsa K. Hedman, Stella Aslibekyan, Ellen W. Demerath, Weihua Guan, Degui Zhi, Chen Yao, Tianxiao Huan, Christine Willinger, Brian Chen, Paul Courchesne, Michael Multhaup, Marguerite R. Irvin, Ariella Cohain, Eric E. Schadt, Megan L. Grove, Jan Bressler, Kari North, Johan Sundström, Stefan Gustafsson, Sonia Shah, Allan F. Mcrae, Sarah E. Harris, Jude Gibson, Paul Redmond, Janie Corley, Lee Murphy, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background

The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.

Methods and Findings

We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs …


Predictive Screening Of M1 And M2 Macrophages Reveals The Immunomodulatory Effectiveness Of Post Spinal Cord Injury Azithromycin Treatment, John C. Gensel, Timothy J. Kopper, Bei Zhang, Michael B. Orr, William M. Bailey Jan 2017

Predictive Screening Of M1 And M2 Macrophages Reveals The Immunomodulatory Effectiveness Of Post Spinal Cord Injury Azithromycin Treatment, John C. Gensel, Timothy J. Kopper, Bei Zhang, Michael B. Orr, William M. Bailey

Spinal Cord and Brain Injury Research Center Faculty Publications

Spinal cord injury (SCI) triggers a heterogeneous macrophage response that when experimentally polarized toward alternative forms of activation (M2 macrophages) promotes tissue and functional recovery. There are limited pharmacological therapies that can drive this reparative inflammatory state. In the current study, we used in vitrosystems to comprehensively defined markers of macrophages with known pathological (M1) and reparative (M2) properties in SCI. We then used these markers to objectively define the macrophage activation states after SCI in response to delayed azithromycin treatment. Mice were subjected to moderate-severe thoracic contusion SCI. Azithromycin or vehicle was administered beginning 30 minutes post-SCI and …


Genetic Analysis Of Serf Gene Function In Drosophila Melanogaster And Its Contribution To A Fly Model Of Spinal Muscular Atrophy, Swagata Ghosh Jan 2017

Genetic Analysis Of Serf Gene Function In Drosophila Melanogaster And Its Contribution To A Fly Model Of Spinal Muscular Atrophy, Swagata Ghosh

Theses and Dissertations--Biology

The Serf gene is evolutionarily highly conserved but its biological function is not known in any organism. In human, SERF1/H4F5 was first identified as a modifier of the disease Spinal Muscular Atrophy (SMA). SMA is caused by mutations in the Survival Motor Neuron 1(SMN1) gene leading to diminished levels of the Smn protein. More than 90% of patients with the most severe form of SMA have deletions that remove SERF1 as well as mutaions within SMN1. Hence, loss of Serf activity is hypothesized to exacerbate SMA disease progression. The primary motivation of this thesis was to test …


Statistical Analyses To Detect And Refine Genetic Associations With Neurodegenerative Diseases, Yuriko Katsumata Jan 2017

Statistical Analyses To Detect And Refine Genetic Associations With Neurodegenerative Diseases, Yuriko Katsumata

Theses and Dissertations--Epidemiology and Biostatistics

Dementia is a clinical state caused by neurodegeneration and characterized by a loss of function in cognitive domains and behavior. Alzheimer’s disease (AD) is the most common form of dementia. Although the amyloid β (Aβ) protein and hyperphosphorylated tau aggregates in the brain are considered to be the key pathological hallmarks of AD, the exact cause of AD is yet to be identified. In addition, clinical diagnoses of AD can be error prone. Many previous studies have compared the clinical diagnosis of AD against the gold standard of autopsy confirmation and shown substantial AD misdiagnosis Hippocampal sclerosis of aging (HS-Aging) …


Identification Of Novel Sleep Related Genes From Large Scale Phenotyping Experiments In Mice, Shreyas Joshi Jan 2017

Identification Of Novel Sleep Related Genes From Large Scale Phenotyping Experiments In Mice, Shreyas Joshi

Theses and Dissertations--Biology

Humans spend a third of their lives sleeping but very little is known about the physiological and genetic mechanisms controlling sleep. Increased data from sleep phenotyping studies in mouse and other species, genetic crosses, and gene expression databases can all help improve our understanding of the process. Here, we present analysis of our own sleep data from the large-scale phenotyping program at The Jackson Laboratory (JAX), to identify the best gene candidates and phenotype predictors for influencing sleep traits.

The original knockout mouse project (KOMP) was a worldwide collaborative effort to produce embryonic stem (ES) cell lines with one of …


Dna Methylation Signatures Of Chronic Low-Grade Inflammation Are Associated With Complex Diseases, Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M. Mendelson, Karen N. Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L. Waite, Roby Joehanes, Weihua Guan, Jennifer A. Brody, Cathy Elks, Riccardo Marioni, Min A. Jhun, Golareh Agha, Jan Bressler, Cavin K. Ward-Caviness, Brian H. Chen, Tianxiao Huan, Kelly Bakulski, Elias L. Salfati, Whi-Empc Investigators, Giovanni Fiorito, Charge Epigenetics Of Coronary Heart Disease, Simone Wahl, Katharina Schramm, Jin Sha, Dena G. Hernandez, Allan C. Just, Jennifer A. Smith, Donna K. Arnett Dec 2016

Dna Methylation Signatures Of Chronic Low-Grade Inflammation Are Associated With Complex Diseases, Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M. Mendelson, Karen N. Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L. Waite, Roby Joehanes, Weihua Guan, Jennifer A. Brody, Cathy Elks, Riccardo Marioni, Min A. Jhun, Golareh Agha, Jan Bressler, Cavin K. Ward-Caviness, Brian H. Chen, Tianxiao Huan, Kelly Bakulski, Elias L. Salfati, Whi-Empc Investigators, Giovanni Fiorito, Charge Epigenetics Of Coronary Heart Disease, Simone Wahl, Katharina Schramm, Jin Sha, Dena G. Hernandez, Allan C. Just, Jennifer A. Smith, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.

Results: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10–7) in the discovery panel …


Causal Effect Estimation In Sequencing Studies: A Bayesian Method To Account For Confounder Adjustment Uncertainty, Chi Wang, Jinpeng Liu, David W. Fardo Oct 2016

Causal Effect Estimation In Sequencing Studies: A Bayesian Method To Account For Confounder Adjustment Uncertainty, Chi Wang, Jinpeng Liu, David W. Fardo

Biostatistics Faculty Publications

Estimating the causal effect of a single nucleotide variant (SNV) on clinical phenotypes is of interest in many genetic studies. The effect estimation may be confounded by other SNVs as a result of linkage disequilibrium as well as demographic and clinical characteristics. Because a large number of these other variables, which we call potential confounders, are collected, it is challenging to select and adjust for the variables that truly confound the causal effect. The Bayesian adjustment for confounding (BAC) method has been proposed as a general method to estimate the average causal effect in the presence of a large number …


Weighted-Samgsr: Combining Significance Analysis Of Microarray-Gene Set Reduction Algorithm With Pathway Topology-Based Weights To Select Relevant Genes, Suyan Tian, Howard H. Chang, Chi Wang Sep 2016

Weighted-Samgsr: Combining Significance Analysis Of Microarray-Gene Set Reduction Algorithm With Pathway Topology-Based Weights To Select Relevant Genes, Suyan Tian, Howard H. Chang, Chi Wang

Biostatistics Faculty Publications

Background: It has been demonstrated that a pathway-based feature selection method that incorporates biological information within pathways during the process of feature selection usually outperforms a gene-based feature selection algorithm in terms of predictive accuracy and stability. Significance analysis of microarray-gene set reduction algorithm (SAMGSR), an extension to a gene set analysis method with further reduction of the selected pathways to their respective core subsets, can be regarded as a pathway-based feature selection method.

Methods: In SAMGSR, whether a gene is selected is mainly determined by its expression difference between the phenotypes, and partially by the number of pathways to …


Chromosome-End Knockoff Strategy To Reshape Alkaloid Profiles Of A Fungal Endophyte, Simona Florea, Timothy D. Phillips, Daniel G. Panaccione, Mark L. Farman, Christopher L. Schardl Aug 2016

Chromosome-End Knockoff Strategy To Reshape Alkaloid Profiles Of A Fungal Endophyte, Simona Florea, Timothy D. Phillips, Daniel G. Panaccione, Mark L. Farman, Christopher L. Schardl

Plant Pathology Faculty Publications

Molecular genetic techniques to precisely eliminate genes in asexual filamentous fungi require the introduction of a marker gene into the target genome. We developed a novel strategy to eliminate genes or gene clusters located in subterminal regions of chromosomes, and then eliminate the marker gene and vector backbone used in the transformation procedure. Because many toxin gene clusters are subterminal, this method is particularly suited to generating nontoxic fungal strains. We tested this technique on Epichloë coenophiala, a seed-transmissible symbiotic fungus (endophyte) of the important forage grass, tall fescue (Lolium arundinaceum). The endophyte is necessary for maximal …


Large Deletions At The Shox Locus In The Pseudoautosomal Region Are Associated With Skeletal Atavism In Shetland Ponies, Nima Rafati, Lisa S. Andersson, Sofia Mikko, Chungang Feng, Terje Raudsepp, Jessica Pettersson, Jan Janecka, Ove Wattle, Adam Ameur, Gunilla Thyreen, John E. Eberth, John Huddleston, Maika Malig, Ernest Bailey, Evan E. Eichler, Göran Dalin, Bhanu Chowdary, Leif Andersson, Gabriella Lindgren, Carl-Johan Rubin Jul 2016

Large Deletions At The Shox Locus In The Pseudoautosomal Region Are Associated With Skeletal Atavism In Shetland Ponies, Nima Rafati, Lisa S. Andersson, Sofia Mikko, Chungang Feng, Terje Raudsepp, Jessica Pettersson, Jan Janecka, Ove Wattle, Adam Ameur, Gunilla Thyreen, John E. Eberth, John Huddleston, Maika Malig, Ernest Bailey, Evan E. Eichler, Göran Dalin, Bhanu Chowdary, Leif Andersson, Gabriella Lindgren, Carl-Johan Rubin

Maxwell H. Gluck Equine Research Center Faculty Publications

Skeletal atavism in Shetland ponies is a heritable disorder characterized by abnormal growth of the ulna and fibula that extend the carpal and tarsal joints, respectively. This causes abnormal skeletal structure and impaired movements, and affected foals are usually killed. In order to identify the causal mutation we subjected six confirmed Swedish cases and a DNA pool consisting of 21 control individuals to whole genome resequencing. We screened for polymorphisms where the cases and the control pool were fixed for opposite alleles and observed this signature for only 25 SNPs, most of which were scattered on genome assembly unassigned scaffolds. …


Melanocortin 1 Receptor: Structure, Function, And Regulation, Erin M. Wolf Horrell, Mary C. Boulanger, John A. D'Orazio May 2016

Melanocortin 1 Receptor: Structure, Function, And Regulation, Erin M. Wolf Horrell, Mary C. Boulanger, John A. D'Orazio

Physiology Faculty Publications

The melanocortin 1 receptor (MC1R) is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV …


Ubr3, A Novel Modulator Of Hh Signaling Affects The Degradation Of Costal-2 And Kif7 Through Poly-Ubiquitination, Tongchao Li, Junkai Fan, Bernardo Blanco-Sánchez, Nikolaos Giagtzoglou, Guang Lin, Shinya Yamamoto, Manish Jaiswal, Kuchuan Chen, Jie Zhang, Wei Wei, Michael T. Lewis, Andrew K. Groves, Monte Westerfield, Jianhang Jia, Hugo J. Bellen May 2016

Ubr3, A Novel Modulator Of Hh Signaling Affects The Degradation Of Costal-2 And Kif7 Through Poly-Ubiquitination, Tongchao Li, Junkai Fan, Bernardo Blanco-Sánchez, Nikolaos Giagtzoglou, Guang Lin, Shinya Yamamoto, Manish Jaiswal, Kuchuan Chen, Jie Zhang, Wei Wei, Michael T. Lewis, Andrew K. Groves, Monte Westerfield, Jianhang Jia, Hugo J. Bellen

Markey Cancer Center Faculty Publications

Hedgehog (Hh) signaling regulates multiple aspects of metazoan development and tissue homeostasis, and is constitutively active in numerous cancers. We identified Ubr3, an E3 ubiquitin ligase, as a novel, positive regulator of Hh signaling in Drosophila and vertebrates. Hh signaling regulates the Ubr3-mediated poly-ubiquitination and degradation of Cos2, a central component of Hh signaling. In developing Drosophila eye discs, loss of ubr3 leads to a delayed differentiation of photoreceptors and a reduction in Hh signaling. In zebrafish, loss of Ubr3 causes a decrease in Shh signaling in the developing eyes, somites, and sensory neurons. However, not all tissues that require …


Novel Interactome Of Saccharomyces Cerevisiae Myosin Type Ii Identified By A Modified Integrated Membrane Yeast Two-Hybrid (Imyth) Screen, Ednalise Santiago, Pearl Akamine, Jamie Snider, Victoria Wong, Matthew Jessulat, Viktor Deineko, Alla Gagarinova, Hiroyuki Aoki, Zoran Minic, Sadhna Phanse, Andrea San Antonio, Luis A Cubano, Brian C. Rymond, Mohan Babu, Igor Stagljar, Jose R. Rodriguez-Medina May 2016

Novel Interactome Of Saccharomyces Cerevisiae Myosin Type Ii Identified By A Modified Integrated Membrane Yeast Two-Hybrid (Imyth) Screen, Ednalise Santiago, Pearl Akamine, Jamie Snider, Victoria Wong, Matthew Jessulat, Viktor Deineko, Alla Gagarinova, Hiroyuki Aoki, Zoran Minic, Sadhna Phanse, Andrea San Antonio, Luis A Cubano, Brian C. Rymond, Mohan Babu, Igor Stagljar, Jose R. Rodriguez-Medina

Biology Faculty Publications

Nonmuscle myosin type II (Myo1p) is required for cytokinesis in the budding yeast Saccharomyces cerevisiae. Loss of Myo1p activity has been associated with growth abnormalities and enhanced sensitivity to osmotic stress, making it an appealing antifungal therapeutic target. The Myo1p tail-only domain was previously reported to have functional activity equivalent to the full-length Myo1p whereas the head-only domain did not. Since Myo1p tail-only constructs are biologically active, the tail domain must have additional functions beyond its previously described role in myosin dimerization or trimerization. The identification of new Myo1p-interacting proteins may shed light on the other …


Network-Driven Plasma Proteomics Expose Molecular Changes In The Alzheimer's Brain, Philipp A. Jaeger, Kurt M. Lucin, Markus Britschgi, Badri Vardarajan, Ruo-Pan Huang, Elizabeth D. Kirby, Rachelle Abbey, Bradley F. Boeve, Adam L. Boxer, Lindsay A. Farrer, Nicole Finch, Neill R. Graff-Radford, Elizabeth Head, Matan Hofree, Ruochun Huang, Hudson Johns, Anna Karydas, David S. Knopman, Andrey Loboda, Eliezer Masliah, Ramya Narasimhan, Ronald C. Petersen, Alexei Podtelezhnikov, Suraj Pradhan, Rosa Rademakers, Chung-Huan Sun, Steven G. Younkin, Bruce L. Miller, Trey Ideker, Tony Wyss-Coray Apr 2016

Network-Driven Plasma Proteomics Expose Molecular Changes In The Alzheimer's Brain, Philipp A. Jaeger, Kurt M. Lucin, Markus Britschgi, Badri Vardarajan, Ruo-Pan Huang, Elizabeth D. Kirby, Rachelle Abbey, Bradley F. Boeve, Adam L. Boxer, Lindsay A. Farrer, Nicole Finch, Neill R. Graff-Radford, Elizabeth Head, Matan Hofree, Ruochun Huang, Hudson Johns, Anna Karydas, David S. Knopman, Andrey Loboda, Eliezer Masliah, Ramya Narasimhan, Ronald C. Petersen, Alexei Podtelezhnikov, Suraj Pradhan, Rosa Rademakers, Chung-Huan Sun, Steven G. Younkin, Bruce L. Miller, Trey Ideker, Tony Wyss-Coray

Pharmacology and Nutritional Sciences Faculty Publications

Background: Biological pathways that significantly contribute to sporadic Alzheimer’s disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes.

Results: To access this information we probed relative levels of close to 600 secreted signaling proteins from patients’ blood samples using …


Pi(4)P Promotes Phosphorylation And Conformational Change Of Smoothened Through Interaction With Its C-Terminal Tail, Kai Jiang, Yajuan Liu, Junkai Fan, Jie Zhang, Xiang-An Li, B. Mark Evers, Haining Zhu, Jianhang Jia Feb 2016

Pi(4)P Promotes Phosphorylation And Conformational Change Of Smoothened Through Interaction With Its C-Terminal Tail, Kai Jiang, Yajuan Liu, Junkai Fan, Jie Zhang, Xiang-An Li, B. Mark Evers, Haining Zhu, Jianhang Jia

Markey Cancer Center Faculty Publications

In Hedgehog (Hh) signaling, binding of Hh to the Patched-Interference Hh (Ptc-Ihog) receptor complex relieves Ptc inhibition on Smoothened (Smo). A longstanding question is how Ptc inhibits Smo and how such inhibition is relieved by Hh stimulation. In this study, we found that Hh elevates production of phosphatidylinositol 4-phosphate (PI(4)P). Increased levels of PI(4)P promote, whereas decreased levels of PI(4)P inhibit, Hh signaling activity. We further found that PI(4)P directly binds Smo through an arginine motif, which then triggers Smo phosphorylation and activation. Moreover, we identified the pleckstrin homology (PH) domain of G protein-coupled receptor kinase 2 (Gprk2) as an …


Expression Of Zinc Fingers And Homeoboxes 2 (Zhx2) And Zhx2 Target Genes In Multiple Tissues Of Wild-Type And Zhx2 Knockout Mice, Minen Al-Kafajy Jan 2016

Expression Of Zinc Fingers And Homeoboxes 2 (Zhx2) And Zhx2 Target Genes In Multiple Tissues Of Wild-Type And Zhx2 Knockout Mice, Minen Al-Kafajy

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

The Spear lab has had a long-standing interest in gene regulation in the liver during development and disease. Several years ago, these studies identified a novel transcriptional regulator called Zinc fingers and homeoboxes 2 (Zhx2), which is a member of a small family that includes Zhx1 and Zhx3. All Zhx proteins contain two amino-terminal C2-H2 zinc fingers and four or five carboxy-terminal homeodomains. Previous studies indicate that Zhx proteins can form homodimers and heterodimers with each other.

Zhx2 regulates numerous hepatic genes, including alpha-fetoprotein (AFP) and H19. Genes controlling lipid and cholesterol homeostasis are also regulated by …


The Role Of Rapgap1 In Sxl Activation In Drosophila Melanogaster, Katherine M. Barnes Jan 2016

The Role Of Rapgap1 In Sxl Activation In Drosophila Melanogaster, Katherine M. Barnes

Lewis Honors College Capstone Collection

The master switch of the sexual differentiation and dosage compensation pathway in Drosophila is the sex lethal gene, Sxl. The early promoter, SxlPe, is activated in females, resulting in female-specific splicing of later transcripts (notably the late Sxl transcript SxlPm), while inactive in males. Chromatin immunoprecipitation (ChIP) assays have previously shown association of two conventionally heterochromatin-localized proteins, HOAP and HP1, at SxlPe, and in situ hybridization as well as RT-PCR assays have confirmed a repressive role for HOAP and both repressive and activating roles for HP1. The mechanism for the activity shift of HP1 is currently unknown. Deletions in the …


The Role Of Sox4 In Regulating Choroid Fissure Closure And Retinal Neurogenesis, Wen Wen Jan 2016

The Role Of Sox4 In Regulating Choroid Fissure Closure And Retinal Neurogenesis, Wen Wen

Theses and Dissertations--Biology

The development of the vertebrate eye is tightly controlled by precise genetic regulations. From a single ocular primordium to bilateral eyes with complex structures and cell types, it requires intensive proliferation and migration for cells in both the ectoderm and mesoderm to accomplish ocular morphogenesis, and during this process cell differentiation and interaction takes place to establish the complex composition of ocular cell types and cellular connections. Genetic defects can lead to severe abnormalities in eye morphogenesis and cell differentiation during ocular development. A tremendous amount of work has been done to identify both intrinsic and extrinsic factors that regulate …


What’S In A Gene: Undergraduates’ Ideas And Misconceptions About Gene Function, Justin M. Levaughn Jan 2016

What’S In A Gene: Undergraduates’ Ideas And Misconceptions About Gene Function, Justin M. Levaughn

Theses and Dissertations--Science, Technology, Engineering, and Mathematics (STEM) Education

The purpose of this study was to field test a two-tiered instrument including multiple-choice and short answer tasks to assess college students’ ideas and level of understanding in genetics. The instrument was constructed from previously tested assessment tasks and findings from the current research literature. Ninety-seven freshmen enrolled in a biology lab course were surveyed. Test validity and reliability were measured using Chronbach coefficients. Multiple-choice and short answer responses were analyzed using descriptive statistics to identify frequencies of answer selections. Written responses were independently evaluated using a five-point scoring rubric by three researchers to identify common misconceptions revealed in students’ …


Population Genetic Structure Of Necturus Maculosus In Central And Eastern Kentucky, Mason Owen Murphy Jan 2016

Population Genetic Structure Of Necturus Maculosus In Central And Eastern Kentucky, Mason Owen Murphy

Theses and Dissertations--Biology

Population structure is influenced by extrinsic factors, such as landscape architecture and dispersal barriers. Lotic network architecture is known to constrain ecological, demographic and evolutionary processes, including population genetic structure. I assessed the population structure of a widespread aquatic salamander, Necturus maculosus, across three river basins in central and eastern Kentucky. I examined the role of network architecture, anthropogenic barriers, and spatial scale on patterns of population structure. I also provided a review of N. maculosus capture methods and offer an improved trap design. I identified significant structuring between the combined Licking/Kinniconick basin and the Kentucky River basin, with …


Role Of Sox11 During Vertebrate Ocular Morphogenesis And Retinal Neurogenesis, Lakshmi Shashidharan Pillai Jan 2015

Role Of Sox11 During Vertebrate Ocular Morphogenesis And Retinal Neurogenesis, Lakshmi Shashidharan Pillai

Theses and Dissertations--Biology

Microphthalmia, anophthalmia, and coloboma (MAC) are distinct abnormalities demonstrating a continuum of developmental eye defects that contribute to 15-20% of blindness and severe vision deficiencies in children worldwide. The genetic etiology of MAC is large, complex and encompasses the whole developmental biology of the eye. Understanding how the eye develops will aid in identifying genes and developmental pathways involved in MAC. Although investigation of the genetic architecture of congenital anomalies is growing exponentially, much work remains to be accomplished to understand the complex, genetically heterogeneous congenital anomalies, which significantly impact childhood vision.

With an interest in elucidating the mechanisms that …


Renal Humoral, Genetic And Genomic Mechanisms Underlying Spontaneous Hypertension, Jason A. Collett Jan 2014

Renal Humoral, Genetic And Genomic Mechanisms Underlying Spontaneous Hypertension, Jason A. Collett

Theses and Dissertations--Biology

In spite of significant progress in our knowledge of mechanisms that control blood pressure, our understanding of the pathogenesis of hypertension, its genetics, and population efforts to control blood pressure, hypertension remains the leading risk factor for mortality worldwide. It’s estimated that 1 out of every 3 adults has hypertension. Hypertension is a major risk factor for cardiovascular disease and stroke, and is considered a primary or contributing cause of death to more than 2.4 million US deaths each year. Although spontaneous hypertension has been the subject of substantial research, many critical questions remain unanswered.

To investigate mechanisms underlying spontaneous …


Use Of Genomic Tools To Discover The Cause Of Champagne Dilution Coat Color In Horses And To Map The Genetic Cause Of Extreme Lordosis In American Saddlebred Horses, Deborah G. Cook Jan 2014

Use Of Genomic Tools To Discover The Cause Of Champagne Dilution Coat Color In Horses And To Map The Genetic Cause Of Extreme Lordosis In American Saddlebred Horses, Deborah G. Cook

Theses and Dissertations--Veterinary Science

Champagne dilution of coat color in horses is caused by dominant gene action. Three sire families were identified as segregating for this trait. Genome wide linkage analysis using 104 microsatellite DNA markers was used to map the gene to ECA14 (LOD > 11.0). Four genes, namely SPARC, SLC36A1, SLC36A2 and SLC36A3, were selected from the region implicated by linkage and their exons sequenced. DNA sequences were compared for two homozygotes for Champagne dilution, two heterozygotes and two horses without dilution. A single base change in exon 2 of SLC36A1 was found unique to horses exhibiting Champagne dilution. This change in base …


Small Rna Expression During Programmed Rearragement Of A Vertebrate Genome, Joseph R. Herdy Iii Jan 2014

Small Rna Expression During Programmed Rearragement Of A Vertebrate Genome, Joseph R. Herdy Iii

Theses and Dissertations--Biology

The sea lamprey (Petromyzon marinus) undergoes programmed genome rearrangements (PGRs) during embryogenesis that results in the deletion of ~0.5 Gb of germline DNA from the somatic lineage. The underlying mechanism of these rearrangements remains largely unknown. miRNAs (microRNAs) and piRNAs (PIWI interacting RNAs) are two classes of small noncoding RNAs that play important roles in early vertebrate development, including differentiation of cell lineages, modulation of signaling pathways, and clearing of maternal transcripts. Here, I utilized next generation sequencing to determine the temporal expression of miRNAs, piRNAs, and other small noncoding RNAs during the first five days of lamprey …


Fusarium Head Blight Resistance And Agronomic Performance In Soft Red Winter Wheat Populations, Daniela Sarti Dvorjak Jan 2014

Fusarium Head Blight Resistance And Agronomic Performance In Soft Red Winter Wheat Populations, Daniela Sarti Dvorjak

Theses and Dissertations--Plant and Soil Sciences

Fusarium head blight (FHB), caused by Fusarium graminearum Schwabe [telomorph: Gibberella zeae Schwein.(Petch)], is recognized as one of the most destructive diseases of wheat (Triticum aestivum L. and T. durum L.) and barley (Hordeum vulgare L.) worldwide. Breeding for FHB resistance must be accompanied by selection for desirable agronomic traits. Donor parents with two FHB resistance quantitative trait loci (QTL) Fhb1 (chromosome 3BS) and QFhs.nau-2DL (chromosome 2DL) were crossed to four adapted SRW wheat lines to generate backcross and forward cross progeny. F2 individuals were genotyped and assigned to 4 different groups according to presence/ absence of …


An Intergenic Region Shared By At4g35985 And At4g35987 In Arabidopsis Thaliana Is A Tissue Specific And Stress Inducible Bidirectional Promoter Analyzed In Transgenic Arabidopsis And Tobacco Plants, Joydeep Banerjee, Dipak K. Sahoo, Nrisingha Dey, Robert Houtz, Indu B. Maiti Nov 2013

An Intergenic Region Shared By At4g35985 And At4g35987 In Arabidopsis Thaliana Is A Tissue Specific And Stress Inducible Bidirectional Promoter Analyzed In Transgenic Arabidopsis And Tobacco Plants, Joydeep Banerjee, Dipak K. Sahoo, Nrisingha Dey, Robert Houtz, Indu B. Maiti

Kentucky Tobacco Research and Development Center Faculty Publications

On chromosome 4 in the Arabidopsis genome, two neighboring genes (calmodulin methyl transferase At4g35987 and senescence associated gene At4g35985) are located in a head-to-head divergent orientation sharing a putative bidirectional promoter. This 1258 bp intergenic region contains a number of environmental stress responsive and tissue specific cis-regulatory elements. Transcript analysis of At4g35985 and At4g35987 genes by quantitative real time PCR showed tissue specific and stress inducible expression profiles. We tested the bidirectional promoter-function of the intergenic region shared by the divergent genes At4g35985 and At4g35987 using two reporter genes (GFP and GUS) in both orientations in transient tobacco protoplast and …


Characterization And Distribution Of Novel Non-Ltr Retroelements Driving High Telomere Rflp Diversity In Clonal Lines Of Magnaporthe Oryzae, John H. Starnes Jan 2013

Characterization And Distribution Of Novel Non-Ltr Retroelements Driving High Telomere Rflp Diversity In Clonal Lines Of Magnaporthe Oryzae, John H. Starnes

Theses and Dissertations--Plant Pathology

The filamentous ascomycete fungus Magnaporthe oryzae is a pathogen of over 50 genera of grasses. Two important diseases it can cause are gray leaf spot in Lolium perenne (perennial ryegrass) and blast in Oryza sativa (rice). The telomeres of M. oryzae isolates causing gray leaf spot are highly variable, and can spontaneously change during fungal culture. In this dissertation, it is shown that a rice-infecting isolate is much more stable at the telomeres than an isolate from gray leaf spot. To determine the molecular basis of telomere instability several gray leaf spot isolates telomeres were cloned, which revealed two non-LTR …


Comparison Of Th1 Cytokines And T Cell Markers Gene Expressions Between Virulent And An Attenuated Eiav Vaccine Strain, Talia R. Henkle Jan 2013

Comparison Of Th1 Cytokines And T Cell Markers Gene Expressions Between Virulent And An Attenuated Eiav Vaccine Strain, Talia R. Henkle

Lewis Honors College Capstone Collection

The equine infectious anemia virus (EIAV) is closely related to HIV and has been used as a model to identify protective mechanisms against lentivirus infection. In horses, EIA infection progresses for about a year before infected horses manage to control virus replication. This naturally-gained protection is absolutely dependent on active immune responses as evidenced by the fact that immunosuppressive drugs can induce the recurrence of disease. As the resolution of initial viremia correlates with the appearance of virus specific cytotoxic T lymphocytes (CTL), we believe that cellular immune responses play a key role in controlling EIAV in the horse. In …


The Causes And Consequences Of Individual Variation In Parental Care Behavior, Daniel P. Wetzel Jan 2013

The Causes And Consequences Of Individual Variation In Parental Care Behavior, Daniel P. Wetzel

Theses and Dissertations--Biology

Behavioral traits can be remarkably flexible depending on the conditions in which they are expressed, yet, in spite of this flexibility, persistent differences between individuals appear to limit the potential expression of behaviors. For example, despite evidence that parents provide variable amounts of parental care in response to changing environmental conditions, they also differ in the overall level of care they provide. I used a behavioral reaction norm approach to study individual variation in parental care behavior in free-living house sparrows (Passer domesticus). I investigated the nature of this variation by studying the relationship between different forms of …