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Full-Text Articles in Life Sciences

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw May 2023

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations & Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …


Paternal Ages And Genetic Diseases And Congenital Anomalies, Neda Hamood Feb 2023

Paternal Ages And Genetic Diseases And Congenital Anomalies, Neda Hamood

The Pegasus Review: UCF Undergraduate Research Journal

he purpose of this research is to investigate the link between Advanced Paternal Ages (APA) (i.e., APA ≥ 35 years and APA ≥ 50 years) and genetic diseases and congenital anomalies. Currently, the relationship between both APA and genetic diseases and congenital anomalies remains unclear. There is room for improvement, however, to investigate systematically the relationship between specific congenital anomalies in newborns and APA. More recently, the link between APA (as opposed to existing studies analyzing Advanced Maternal Age alone) and genetic diseases has been recognized by researchers, epidemiologists, and various health experts. Thus, this study serves to examine the …


Multi-Ancestry Genome-Wide Association Analyses Improve Resolution Of Genes And Pathways Influencing Lung Function And Chronic Obstructive Pulmonary Disease Risk, Nick Shrine, Abril G. Izquierdo, Jing Chen, Richard Packer, Robert J. Hall, Anna L. Guyatt, Chiara Batini, Rebecca J. Thompson, Chandan Puvuluri, Vidhi Malik, Brian D. Hobbs, Matthew Moll, Wonji Kim, Ruth Tal-Singer, Per Bakke, Katherine A. Fawcett, Catherine John, Kayesha Coley, Noemi Nicole Piga, Sinjini Sikdar, Martin D. Tobin, Et Al. Jan 2023

Multi-Ancestry Genome-Wide Association Analyses Improve Resolution Of Genes And Pathways Influencing Lung Function And Chronic Obstructive Pulmonary Disease Risk, Nick Shrine, Abril G. Izquierdo, Jing Chen, Richard Packer, Robert J. Hall, Anna L. Guyatt, Chiara Batini, Rebecca J. Thompson, Chandan Puvuluri, Vidhi Malik, Brian D. Hobbs, Matthew Moll, Wonji Kim, Ruth Tal-Singer, Per Bakke, Katherine A. Fawcett, Catherine John, Kayesha Coley, Noemi Nicole Piga, Sinjini Sikdar, Martin D. Tobin, Et Al.

Mathematics & Statistics Faculty Publications

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of …


Pulmonary Function And Blood Dna Methylation: A Multiancestry Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Tianxiao Huan, Daniel L. Mccartney, Geetha Chittoor, Maaike De Vries, Lies Lahousse, Jennifer N. Nguyen, Jennifer A. Brody, Juan Castillo-Fernandez, Natalie Terzikhan, Cancan Qi, Roby Joehanes, Josine L. Min, Gordon J. Smilnak, Jessica R. Shaw, Chen Xi Yang, Elena Colicino, Thanh T. Hoang, Mairead L. Bermingham, Hanfei Xu, Anne E. Justice, Cheng-Jian Xu, Stephen S. Rich, Simon R. Cox, Judith M. Vonk, Ivana Prokić, Nona Sotoodehnia, Pei-Chien Tsai, Joel D. Schwartz, Janice M. Leung, Sinjini Sikdar, Rosie M. Walker, Sarah E. Harris, Diana A. Van Der Plaat, David J. Van Den Berg, Traci M. Bartz, Tim D. Spector, Pantel S. Vokonas, Riccardo E. Marioni, Adele M. Taylor, Yongmei Liu, R. Graham Barr, Leslie A. Lange, Andrea A. Baccarelli, Ma'en Obeidat, Myriam Fornage, Tianyuan Wang, James M. Ward, Alison A. Motsinger-Reif, Gibran Hemani, Gerard H. Koppelman, Jordana T. Bell, Sina A. Gharib, Guy Brusselle, H. Marike Boezen, Kari E. North, Daniel Levy, Kathryn L. Evans, Josée Dupris, Charles E. Breeze, Ani Manichaikul, Stephanie J. London Jan 2022

Pulmonary Function And Blood Dna Methylation: A Multiancestry Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Tianxiao Huan, Daniel L. Mccartney, Geetha Chittoor, Maaike De Vries, Lies Lahousse, Jennifer N. Nguyen, Jennifer A. Brody, Juan Castillo-Fernandez, Natalie Terzikhan, Cancan Qi, Roby Joehanes, Josine L. Min, Gordon J. Smilnak, Jessica R. Shaw, Chen Xi Yang, Elena Colicino, Thanh T. Hoang, Mairead L. Bermingham, Hanfei Xu, Anne E. Justice, Cheng-Jian Xu, Stephen S. Rich, Simon R. Cox, Judith M. Vonk, Ivana Prokić, Nona Sotoodehnia, Pei-Chien Tsai, Joel D. Schwartz, Janice M. Leung, Sinjini Sikdar, Rosie M. Walker, Sarah E. Harris, Diana A. Van Der Plaat, David J. Van Den Berg, Traci M. Bartz, Tim D. Spector, Pantel S. Vokonas, Riccardo E. Marioni, Adele M. Taylor, Yongmei Liu, R. Graham Barr, Leslie A. Lange, Andrea A. Baccarelli, Ma'en Obeidat, Myriam Fornage, Tianyuan Wang, James M. Ward, Alison A. Motsinger-Reif, Gibran Hemani, Gerard H. Koppelman, Jordana T. Bell, Sina A. Gharib, Guy Brusselle, H. Marike Boezen, Kari E. North, Daniel Levy, Kathryn L. Evans, Josée Dupris, Charles E. Breeze, Ani Manichaikul, Stephanie J. London

Mathematics & Statistics Faculty Publications

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication.

Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function.

Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV1, FVC, and FEV1/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics.

Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery …


The Onset Of Exercise-Associated Hyponatremia And Individual Differences In Inappropriate Arginine Vasopressin Excretion: A Review Of Proposed Mechanisms, Michelle Stehman, Stephen A. Maris Sep 2021

The Onset Of Exercise-Associated Hyponatremia And Individual Differences In Inappropriate Arginine Vasopressin Excretion: A Review Of Proposed Mechanisms, Michelle Stehman, Stephen A. Maris

Topics in Exercise Science and Kinesiology

Topics in Exercise Science and Kinesiology Volume 2: Issue 1, Article 10, 2021. Exercise-associated hyponatremia (EAH) has been reported to develop during endurance events such as triathlons and marathons. As these events become more popular, the incidence of developing EAH also increases. The development of EAH is commonly associated with the overconsumption of hypotonic fluids such as water and tends to be more prevalent in females. There is also evidence to suggest the inappropriate secretion of arginine vasopressin (AVP) leading to water retention may predispose an individual for developing EAH, especially when coupled with the overconsumption of fluids. Recent research …


Genetic Approaches For The Study Of Complex Human Diseases, Julieta Lazarte Jul 2021

Genetic Approaches For The Study Of Complex Human Diseases, Julieta Lazarte

Electronic Thesis and Dissertation Repository

The field of human genetics has evolved from its initial narrow focus on single-gene Mendelian disorders, which largely affect children, to our current understanding that for most diseases there is continuum of rare to common variants which can exert a range of phenotypic effects. Despite advances in sequencing capabilities and our overall understanding of diseases, there remains a large proportion of heritability unexplained. Through the use of next-generation sequencing technologies and DNA microarray, I have explored a spectrum of genetic variations from rare, single and structural variants to common variants in individuals with i) “lone” atrial fibrillation; ii) familial hypercholesterolemia; …


Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He May 2021

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to …


Determining The Genetic Control Of Neural Tube Malformation Through Genetic Interactions With Idgf3, Elli N. Fox May 2020

Determining The Genetic Control Of Neural Tube Malformation Through Genetic Interactions With Idgf3, Elli N. Fox

Honors Projects

Genetic mutations disrupting human neural tube formation can lead to birth defects such as spina bifida and anencephaly. Defects can result in lack of neural tube closure in either the caudal (spina bifida) or cranial (anencephaly) regions. Little is known about the genes that cause these malformations. Researchers have been using the model organism Drosophila melanogaster in an attempt to determine genes responsible for neural tube malformations. Recently, an ortholog of human chitin-like protein, imaginal disc growth factor 3 (Idgf3), has been identified as important in the proper formation of Drosophila egg dorsal appendages. However, the molecular mechanism responsible for …


Advanced Phenotyping Of Otosclerosis In An Ontario Population And Two Large Newfoundland Families, Matthew B. Lucas Apr 2020

Advanced Phenotyping Of Otosclerosis In An Ontario Population And Two Large Newfoundland Families, Matthew B. Lucas

Electronic Thesis and Dissertation Repository

Otosclerosis is a relatively common hearing loss disorder characterized by abnormal bone growth in the otic capsule leading to stapes fixation. In approximately half of cases, otosclerosis is inherited as an autosomal dominant trait. Typically, gene discovery efforts rely on surgical confirmation, audiometry and occasionally acoustic reflexes to identify affected cases of otosclerosis within families, requiring that the otosclerosis was at an advanced stage to be detected. This makes it difficult to identify individuals with early otosclerosis. The use of advanced phenotyping to identify cases of otosclerosis was tested in an Ontario otosclerotic population as well as in two large …


The Influence Of Stressful Life Events On The Development Of Type 2 Diabetes, Joshua Minks Mar 2019

The Influence Of Stressful Life Events On The Development Of Type 2 Diabetes, Joshua Minks

Dissertations

This study examined the relationship between distress and the development of Type 2 diabetes mellitus (T2DM) in the presence of established risk factors. Distress secondary to mental health disparities, stressful life events, and work conditions has been shown to promote insulin resistance and the development of T2DM.

Subjects (N=79) diagnosed with T2DM within the previous six months were recruited from SSM Health Centers and VA Medical Centers in the greater St. Louis area. They completed the Recent Life Changes Questionnaire, ENRICHD Social Support Instrument, and a demographic survey and analyses were conducted to determine differences between the veteran …


Molecular Survey For The Honey Bee Trypanosome Parasites Crithidia Mellificae And Lotmaria Passim, Mary-Kate Williams Aug 2018

Molecular Survey For The Honey Bee Trypanosome Parasites Crithidia Mellificae And Lotmaria Passim, Mary-Kate Williams

Graduate Theses and Dissertations

Honey bee populations have been fluctuating within recent years. No one cause has been attributed to colony fluctuations due to the theory that multiple stressors interact with one another to impact colony health. Consequently, microorganisms such as internal parasites of honey bees have been understudied as a contributor to colony health decline.

Molecular diagnostics were utilized to detect the presence of two honey bee trypanosome parasites, Crithidia mellificae and Lotmaria passim, in managed and feral honey bee populations from eight states in the United States (USA). Because studies on trypanosome infections are lacking in the USA, it is important to …


Epigenome-Wide Association Study Of Metabolic Syndrome In African-American Adults, Tomi Akinyemiju, Anh N. Do, Amit Patki, Stella Aslibekyan, Degui Zhi, Bertha Hidalgo, Hemant K. Tiwari, Devin Absher, Xin Geng, Donna K. Arnett, Marguerite R. Irvin Apr 2018

Epigenome-Wide Association Study Of Metabolic Syndrome In African-American Adults, Tomi Akinyemiju, Anh N. Do, Amit Patki, Stella Aslibekyan, Degui Zhi, Bertha Hidalgo, Hemant K. Tiwari, Devin Absher, Xin Geng, Donna K. Arnett, Marguerite R. Irvin

Epidemiology and Environmental Health Faculty Publications

Background: The high prevalence of obesity among US adults has resulted in significant increases in associated metabolic disorders such as diabetes, dyslipidemia, and high blood pressure. Together, these disorders constitute metabolic syndrome, a clinically defined condition highly prevalent among African-Americans. Identifying epigenetic alterations associated with metabolic syndrome may provide additional information regarding etiology beyond current evidence from genome-wide association studies.

Methods: Data on metabolic syndrome and DNA methylation was assessed on 614 African-Americans from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Metabolic syndrome was defined using the joint harmonized criteria, and DNA methylation was assessed using the Illumina HumanMethylation450K Bead …


Qatar: Diabetes, Diangelo Gonzalez Jan 2018

Qatar: Diabetes, Diangelo Gonzalez

Global Public Health

The State of Qatar is a developed nation that is located in the Middle East and borders the Persian Gulf and Saudi Arabia. The nation is a constitutional monarchy and is currently led by Amir Tamim bin Hamad Al Thani. The 2,300,000+ people of Qatar face many major challenges. Although it is one of the wealthiest nations in the Middle East, Qatar faces issues of human trafficking, migrants willing to work in poor conditions, and Middle Eastern Respiratory Syndrome (MERS). The most critical issue that plagues this county is diabetes, both I and II. Diabetes is a disease that is …


Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease, David W. Fardo, Laura E. Gibbons, Shubhabrata Mukherjee, M. Maria Glymour, Wayne Mccormick, Susan M. Mccurry, James D. Bowen, Eric B. Larson, Paul K. Crane Aug 2017

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease, David W. Fardo, Laura E. Gibbons, Shubhabrata Mukherjee, M. Maria Glymour, Wayne Mccormick, Susan M. Mccurry, James D. Bowen, Eric B. Larson, Paul K. Crane

Biostatistics Faculty Publications

INTRODUCTION—Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS—We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS …


Alzheimer's Disease Genetics And Abca7 Splicing, Jared B. Vasquez, James F. Simpson, Ryan Harpole, Steven Estus Jul 2017

Alzheimer's Disease Genetics And Abca7 Splicing, Jared B. Vasquez, James F. Simpson, Ryan Harpole, Steven Estus

Physiology Faculty Publications

Both common and rare polymorphisms within ABCA7 have been associated with Alzheimer’s disease (AD). In particular, the rare AD associated polymorphism rs200538373 was associated with altered ABCA7 exon 41 splicing and an AD risk odds ratio of ∼1.9. To probe the role of this polymorphism in ABCA7 splicing, we used minigene studies and qPCR of human brain RNA. We report aberrant ABCA7 exon 41 splicing in the brain of a carrier of the rs200538373 minor C allele. Moreover, minigene studies show that rs200538373 acts as a robust functional variant in vitro. Lastly, although the ABCA7 isoform with an extended …


Neuropathological And Genetic Correlates Of Survival And Dementia Onset In Synucleinopathies: A Retrospective Analysis, David J. Irwin, Murray Grossman, Daniel Weintraub, Howard I. Hurtig, John E. Duda, Sharon X. Xie, Edward B. Lee, Vivianna M. Van Deerlin, Oscar L. Lopez, Julia K. Kofler, Peter T. Nelson, Gregory A. Jicha, Randy Woltjer, Joseph F. Quinn, Jeffery Kaye, James B. Leverenz, Debby Tsuang, Katelan Longfellow, Dora Yearout, Walter Kukull, C. Dirk Keene, Thomas J. Montine, Cyrus P. Zabetian, John Q. Trojanowski Jan 2017

Neuropathological And Genetic Correlates Of Survival And Dementia Onset In Synucleinopathies: A Retrospective Analysis, David J. Irwin, Murray Grossman, Daniel Weintraub, Howard I. Hurtig, John E. Duda, Sharon X. Xie, Edward B. Lee, Vivianna M. Van Deerlin, Oscar L. Lopez, Julia K. Kofler, Peter T. Nelson, Gregory A. Jicha, Randy Woltjer, Joseph F. Quinn, Jeffery Kaye, James B. Leverenz, Debby Tsuang, Katelan Longfellow, Dora Yearout, Walter Kukull, C. Dirk Keene, Thomas J. Montine, Cyrus P. Zabetian, John Q. Trojanowski

Sanders-Brown Center on Aging Faculty Publications

Background

Great heterogeneity exists in survival and the interval between onset of motor symptoms and dementia symptoms across synucleinopathies. We aimed to identify genetic and pathological markers that have the strongest association with these features of clinical heterogeneity in synucleinopathies.

Methods

In this retrospective study, we examined symptom onset, and genetic and neuropathological data from a cohort of patients with Lewy body disorders with autopsy-confirmed α synucleinopathy (as of Oct 1, 2015) who were previously included in other studies from five academic institutions in five cities in the USA. We used histopathology techniques and markers to assess the burden of …


Bois 412/812: Human Genetics—A Peer Review Of Teaching Project Benchmark Portfolio, Colin D. Meiklejohn Jan 2016

Bois 412/812: Human Genetics—A Peer Review Of Teaching Project Benchmark Portfolio, Colin D. Meiklejohn

UNL Faculty Course Portfolios

This portfolio focuses on Human Genetics, an upper-division course taken primarily by biology majors to fulfill elective credit in their degree. This course studies the genetic basis for human variation, with the goal of placing this variation in the context of human evolutionary history and the consequences of this variation for medical understanding and treatments. In Human Genetics, students complete an original synthetic research paper on a human genetic disorder. Through writing this paper, students are expected to learn how to navigate electronic databases and online resources on human genetic diseases, and to read and synthesize the primary scientific literature. …


Systems Level Analysis Of Systemic Sclerosis Shows A Network Of Immune And Profibrotic Pathways Connected With Genetic Polymorphisms, J. Matthew Mahoney, Jaclyn Taroni, Viktor Martyanov, Tammara A. A. Wood, Casey S. Greene, Patricia A. Pioli, Monique E. Hinchcliff, Michael L. Whitfield Jan 2015

Systems Level Analysis Of Systemic Sclerosis Shows A Network Of Immune And Profibrotic Pathways Connected With Genetic Polymorphisms, J. Matthew Mahoney, Jaclyn Taroni, Viktor Martyanov, Tammara A. A. Wood, Casey S. Greene, Patricia A. Pioli, Monique E. Hinchcliff, Michael L. Whitfield

Dartmouth Scholarship

Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited) are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes …


Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan Jun 2014

Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan

Dartmouth Scholarship

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and …


Methylation Of Leukocyte Dna And Ovarian Cancer: Relationships With Disease Status And Outcome, Brooke L. Fridley, Sebastian M. Armasu, Mine S. Cicek, Melissa C. Larson, Chen Wang, Stacey J. Winham, Kimberly R. Kalli, Devin C. Koestler Apr 2014

Methylation Of Leukocyte Dna And Ovarian Cancer: Relationships With Disease Status And Outcome, Brooke L. Fridley, Sebastian M. Armasu, Mine S. Cicek, Melissa C. Larson, Chen Wang, Stacey J. Winham, Kimberly R. Kalli, Devin C. Koestler

Dartmouth Scholarship

Genome-wide interrogation of DNA methylation (DNAm) in blood-derived leukocytes has become feasible with the advent of CpG genotyping arrays. In epithelial ovarian cancer (EOC), one report found substantial DNAm differences between cases and controls; however, many of these disease-associated CpGs were attributed to differences in white blood cell type distributions. We examined blood-based DNAm in 336 EOC cases and 398 controls; we included only high-quality CpG loci that did not show evidence of association with white blood cell type distributions to evaluate association with case status and overall survival.


How To Get The Most From Microarray Data: Advice From Reverse Genomics, Ivan P. Gorlov, Ji-Yeon Yang, Jinyoung Byun, Christopher Logothetis, Olga Y. Gorlova, Kim-Anh Do, Christopher Amos Mar 2014

How To Get The Most From Microarray Data: Advice From Reverse Genomics, Ivan P. Gorlov, Ji-Yeon Yang, Jinyoung Byun, Christopher Logothetis, Olga Y. Gorlova, Kim-Anh Do, Christopher Amos

Dartmouth Scholarship

Whole-genome profiling of gene expression is a powerful tool for identifying cancer-associated genes. Genes differentially expressed between normal and tumorous tissues are usually considered to be cancer associated. We recently demonstrated that the analysis of interindividual variation in gene expression can be useful for identifying cancer associated genes. The goal of this study was to identify the best microarray data–derived predictor of known cancer associated genes. We found that the traditional approach of identifying cancer genes—identifying differentially expressed genes—is not very efficient. The analysis of interindividual variation of gene expression in tumor samples identifies cancer-associated genes more effectively. The results …


Bioengineered Lysozyme Reduces Bacterial Burden And Inflammation In A Murine Model Of Mucoid Pseudomonas Aeruginosa Lung Infection, Charlotte C. Teneback, Thomas C. Scanlon, Matthew J. Wargo, Jenna L. Bement, Karl E. Griswold, Laurie W. Leclair Aug 2013

Bioengineered Lysozyme Reduces Bacterial Burden And Inflammation In A Murine Model Of Mucoid Pseudomonas Aeruginosa Lung Infection, Charlotte C. Teneback, Thomas C. Scanlon, Matthew J. Wargo, Jenna L. Bement, Karl E. Griswold, Laurie W. Leclair

Dartmouth Scholarship

The spread of drug-resistant bacterial pathogens is a growing global concern and has prompted an effort to explore potential adjuvant and alternative therapies derived from nature's repertoire of bactericidal proteins and peptides. In humans, the airway surface liquid layer is a rich source of antibiotics, and lysozyme represents one of the most abundant and effective antimicrobial components of airway secretions. Human lysozyme is active against both Gram-positive and Gram-negative bacteria, ac


Inhibition Of The Host Translation Shutoff Response By Herpes Simplex Virus 1 Triggers Nuclear Envelope-Derived Autophagy, Kerstin Radtke, Luc English, Christiane Rondeau, David Leib Jan 2013

Inhibition Of The Host Translation Shutoff Response By Herpes Simplex Virus 1 Triggers Nuclear Envelope-Derived Autophagy, Kerstin Radtke, Luc English, Christiane Rondeau, David Leib

Dartmouth Scholarship

Macroautophagy is a cellular pathway that degrades intracellular pathogens and contributes to antigen presentation. Herpes simplex virus 1 (HSV-1) infection triggers both macroautophagy and an additional form of autophagy that uses the nuclear envelope as a source of membrane. The present study constitutes the first in-depth analysis of nuclear envelope-derived autophagy (NEDA). We established LC3a as a marker that allowed us to distinguish between NEDA and macroautophagy in both immunofluorescence and flow cytometry. NEDA was observed in many different cell types, indicating that it is a general response to HSV-1 infection. This autophagic pathway is known to depend on the …


Interleukin-1Β Mediates Metalloproteinase-Dependent Renal Cell Carcinoma Tumor Cell Invasion Through The Activation Of Ccaat Enhancer Binding Protein Β, Brenda L. Petrella, Matthew P. P. Vincenti May 2012

Interleukin-1Β Mediates Metalloproteinase-Dependent Renal Cell Carcinoma Tumor Cell Invasion Through The Activation Of Ccaat Enhancer Binding Protein Β, Brenda L. Petrella, Matthew P. P. Vincenti

Dartmouth Scholarship

Effective treatment of metastatic renal cell carcinoma (RCC) remains a major medical concern, as these tumors are refractory to standard therapies and prognosis is poor. Although molecularly targeted therapies have shown some promise in the treatment of this disease, advanced RCC tumors often develop resistance to these drugs. Dissecting the molecular mechanisms underlying the progression to advanced disease is necessary to design alternative and improved treatment strategies. Tumor-associated macrophages (TAMs) found in aggressive RCC tumors produce a variety of inflammatory cytokines, including interleukin-1 b (IL-1b). Moreover, the presence of TAMs and high serum levels of IL-1b in RCC patients correlate …


Variations In Mre11/Rad50/Nbs1 Status And Dna Damage-Induced S-Phase Arrest In The Cell Lines Of The Nci60 Panel, Kristen M. K. Garner, Alan Eastman May 2011

Variations In Mre11/Rad50/Nbs1 Status And Dna Damage-Induced S-Phase Arrest In The Cell Lines Of The Nci60 Panel, Kristen M. K. Garner, Alan Eastman

Dartmouth Scholarship

The Mre11/Rad50/Nbs1 (MRN) complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged. Such defects may elicit sensitivity to selected drugs providing a chemical synthetic lethal interaction that could be used to target therapy to tumors with these defects. The goal of this study was to identify these defects in the NCI60 panel of cell lines and identify compounds that might elicit selective cytotoxicity.


Accumulation Of Rhodopsin In Late Endosomes Triggers Photoreceptor Cell Degeneration, Yashodhan Chinchore, Amitavo Mitra, Patrick J. Dolph, Norbert Perrimon Feb 2009

Accumulation Of Rhodopsin In Late Endosomes Triggers Photoreceptor Cell Degeneration, Yashodhan Chinchore, Amitavo Mitra, Patrick J. Dolph, Norbert Perrimon

Dartmouth Scholarship

Progressive retinal degeneration is the underlying feature of many human retinal dystrophies. Previous work using Drosophila as a model system and analysis of specific mutations in human rhodopsin have uncovered a connection between rhodopsin endocytosis and retinal degeneration. In these mutants, rhodopsin and its regulatory protein arrestin form stable complexes, and endocytosis of these complexes causes photoreceptor cell death. In this study we show that the internalized rhodopsin is not degraded in the lysosome but instead accumulates in the late endosomes. Using mutants that are defective in late endosome to lysosome trafficking, we were able to show that rhodopsin accumulates …


Sheep Updates 2008 - Part 3, L. J. E. Karlsson, J. C. Greeff, L. Slocombe, K. Jones, N. Underwood, Fred Wilkinson, W. D. Hoffman, W. A. Mckiernan, V. H. Oddy, M. J. Mcphee, B. L. Mcintyre, P. F. Parnell, R. A. Clark, J. Timms, G. Griffith, C. Mulholland, P. Hyland, Danielle England, Fiona Jones, John Lucey, Martin Staines, Richard Morris, Megan Abrahams, Caroline Peek, Dennis Van Gool, Daniel Gardiner, Kari-Lee Falconer, Sandra Prosser, Mario D'Antuono, John Young, Andrew Thompson, Chris Oldham, Brown Besier, Angus Campbell, Ralph Behrendt Jul 2008

Sheep Updates 2008 - Part 3, L. J. E. Karlsson, J. C. Greeff, L. Slocombe, K. Jones, N. Underwood, Fred Wilkinson, W. D. Hoffman, W. A. Mckiernan, V. H. Oddy, M. J. Mcphee, B. L. Mcintyre, P. F. Parnell, R. A. Clark, J. Timms, G. Griffith, C. Mulholland, P. Hyland, Danielle England, Fiona Jones, John Lucey, Martin Staines, Richard Morris, Megan Abrahams, Caroline Peek, Dennis Van Gool, Daniel Gardiner, Kari-Lee Falconer, Sandra Prosser, Mario D'Antuono, John Young, Andrew Thompson, Chris Oldham, Brown Besier, Angus Campbell, Ralph Behrendt

Sheep Updates

This session covers fiveteen papers from different authors:

CONTROLLING FLY STRIKE

1. Breeding for Blowfly Resistance - Indicatoe Traits, LJE Karlsson, JC Greeff, L Slocombe, Department of Agriculture & Food, Western Australia

2.A practical method to select for breech strike resistance in non-pedigreed Merino flocks, LJE Karlsson, JC Greeff, L Slocombe, K. Jones, N. Underwood, Department of Agriculture & Food, Western Australia

3. Twice a year shearing - no mulesing, Fred Wilkinson, Producer, Brookton WA

BEEF

4. Commercial testing of a new tool for prediction of fatness in beef cattle, WD HoffmanA, WA McKiernanA, VH Oddy …


Sheep Updates 2007 - Part 2, Ian Mcfarland, Catherine Stockman, Anne Barnes, David Pethick, Jenny Davis, Brett Thompson, Ron Leng, Sally Pieruzzini, Elizabeth Jackson, Mohammed Quaddus, Nazrul Islam, John Stanton, Melanie Dowling Jul 2007

Sheep Updates 2007 - Part 2, Ian Mcfarland, Catherine Stockman, Anne Barnes, David Pethick, Jenny Davis, Brett Thompson, Ron Leng, Sally Pieruzzini, Elizabeth Jackson, Mohammed Quaddus, Nazrul Islam, John Stanton, Melanie Dowling

Sheep Updates

This session covers six papers from different authors:

CONCURRENT SESSIONS

FINISHING LAMB AND BEEF

1. Precision Feedlot Lamb, Ian McFarland, Department of Agriculture and Food, Western Australia

2. Feeding sheep under high heat load did not decrease intake of feedlot rations, Catherine Stockman, Department of Agriculture and Food, Western Australia & Murdoch University, Anne Barnes, Murdoch University David Pethick, Murdoch University

3. Taking the stress out of fifishing lambs and cattle - EasyFeed solutions, Jenny Davis, Brett Thomson, Milne AgriGroup, Welshpool WA, Ron Leng, Emeritus Professor, University of New England, Armidale, NSW

WOOL

4. DAFWA …


A Role For Cetp Taqib Polymorphism In Determining Susceptibility To Atrial Fibrillation: A Nested Case Control Study, Folkert W. Asselbergs, Jason H. Moore, Maarten P. Van Den Berg, Eric B. Rimm Apr 2006

A Role For Cetp Taqib Polymorphism In Determining Susceptibility To Atrial Fibrillation: A Nested Case Control Study, Folkert W. Asselbergs, Jason H. Moore, Maarten P. Van Den Berg, Eric B. Rimm

Dartmouth Scholarship

Studies investigating the genetic and environmental characteristics of atrial fibrillation (AF) may provide new insights in the complex development of AF. We aimed to investigate the association between several environmental factors and loci of candidate genes, which might be related to the presence of AF. A nested case-control study within the PREVEND cohort was conducted. Standard 12 lead electrocardiograms were recorded and AF was defined according to Minnesota codes. For every case, an age and gender matched control was selected from the same population (n = 194). In addition to logistic regression analyses, the multifactor-dimensionality reduction (MDR) method and interaction …


Sheep Updates 2005 - Part 5, Geoff Duddy, Brent Mcloud, John Sullivan, T. J. Mahar, A. Balasingam, J. H. Stanton, K. M. S. Curtis, P. R. Lamb, Eliza Dowling, Ned Crossley, Surrender Mann, Lucy Anderton, Matthew Kelly, Andrew Swan, Ian Mcfarland, Di Evans, K. Bell, D. Sackett, Robin Jacob Jul 2005

Sheep Updates 2005 - Part 5, Geoff Duddy, Brent Mcloud, John Sullivan, T. J. Mahar, A. Balasingam, J. H. Stanton, K. M. S. Curtis, P. R. Lamb, Eliza Dowling, Ned Crossley, Surrender Mann, Lucy Anderton, Matthew Kelly, Andrew Swan, Ian Mcfarland, Di Evans, K. Bell, D. Sackett, Robin Jacob

Sheep Updates

This session covers eleven papers from different authors; MARKET INFORMATION 1. Crystal Spring - Crystal clear and consistant, Geoff Duddy, Livestock Officer (Sheep & Wool) Yanco, NSW, Brent McLoud, (Product Development Officer) Cowra, NSW, John Sullivan, J.J Dresser and Co (Agent), Woodstock, NSW 2. An overview of Recent Developments in Dark and Medullated Fibre Testing, T.J. Mahar, A. Balasingam, AWTA Ltd 3. Opportunities and Implications for Wool Producers of the TEAM3 Prediction Equations, J.H. Stanton12 K.M.S. Curtis1 , 1Department of Agriculture Western Australia, 2 Curtin University, WA 4. Premiums and Discounts for Fibre Properties in Superfine Wool, Now and in …