Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, 2018 Stanford University
Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, Sunhee Hwang, Karen Mruk, Simin Rahighi, Andrew G. Raub, Che-Hong Chen, Lisa E. Dorn, Naoki Horikoshi, Soichi Wakatsuki, James K. Chen, Daria Mochly-Rosen
Pharmacy Faculty Articles and Research
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the ...
Genetic Modification Of Inherited Retinopathy In Mice, 2018 The University of Maine
Genetic Modification Of Inherited Retinopathy In Mice, Yang Kong
Electronic Theses and Dissertations
The retina, as a critical component of the sensory system, consists of multiple cell types, of which, photoreceptors play a key role in receiving, integrating and transmitting light signals. The biofunctions of photoreceptors rely on their proper growth and development, which is predominantly governed by a cluster of molecules that comprise the transcriptional regulation for photoreceptor development. Any disruption of these molecules potentially incurs retinal pathologies.
It is known that deficiencies of nuclear receptor subfamily 2 group E member 3 (NR2E3) or neural retina leucine-zipper (NRL), two molecules in regulating photoreceptor cell development, cause photoreceptor dysplasia. In a sensitized chemical ...
Systematic Complex Haploinsufficiency-Based Genetic Analysis Of Candida Albicans Transcription Factors: Tools And Applications To Virulence-Associated Phenotypes, Virginia E. Glazier, Thomas Murante, Kristy Koselny, Daniel Murante, Marisol Esqueda, Gina A. Wall, Melanie Wellington, Chiung-Yu Hung, Anuj Kumar, Damian J. Krysan
Stead Family Department of Pediatrics Publications
Genetic interaction analysis is a powerful approach to the study of complex biological processes that are dependent on multiple genes. Because of the largely diploid nature of the human fungal pathogen
Identification Of P38 Mapk As A Novel Therapeutic Target For Friedreich's Ataxia., 2018 Marian University - Indianapolis
Identification Of P38 Mapk As A Novel Therapeutic Target For Friedreich's Ataxia., M Grazia Cotticelli, Shujuan Xia, Avinash Kaur, Daniel Lin, Yongping Wang, Eric Ruff, John W Tobias, Robert B Wilson
Student Publications and Research
Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardio-degenerative disorder caused by decreased expression of frataxin, a protein that localizes to mitochondria and is critical for iron-sulfur-cluster (ISC) assembly. There are no proven effective treatments for FRDA. We previously screened a random shRNA library and identified a synthetic shRNA (gFA11) that reverses the growth defect of FRDA cells in culture. We now report that gFA11 decreases cytokine secretion in primary FRDA fibroblasts and reverts other changes associated with cell senescence. The gene-expression profile induced by gFA11 is remarkably similar to the gene-expression profile induced by the p38 MAPK inhibitor ...
Genome-Wide Association Study Of Offspring Birth Weight In 86 577 Women Identifies Five Novel Loci And Highlights Maternal Genetic Effects That Are Independent Of Fetal Genetics, 2018 University of Iowa
Genome-Wide Association Study Of Offspring Birth Weight In 86 577 Women Identifies Five Novel Loci And Highlights Maternal Genetic Effects That Are Independent Of Fetal Genetics, Robin N. Beaumont, Nicole M. Warrington, Alana Cavadino, Jessica Tyrrell, Michael Nodzenski, Momoko Horikoshi, Frank Geller, Ronny Myhre, Rebecca C. Richmond, Lavinia Paternoster, Jonathan P. Bradfield, Eskil Kreiner-Møller, Ville Huikari, Sarah Metrustry, Kathryn L. Lunetta, Jodie N. Painter, Jouke-Jan Hottenga, Catherine Allard, Sheila J. Barton, Ana Espinosa, Julie A. Marsh, Catherine Potter, Ge Zhang, Wei Ang, Diane J. Berry, Luigi Bouchard, Shikta Das, Hakon Hakonarson, Jani Heikkinen, Øyvind Helgeland, Berthold Hocher, Albert Hofman, Hazel M. Inskip, Samuel E. Jones, Manolis Kogevinas, Penelope A. Lind, Letizia Marullo, Sarah E. Medland, Anna Murray, Jeffrey C. Murray, Pål R. Njølstad, Ellen A. Nohr, Christoph Reichetzeder, Susan M. Ring, Katherine S. Ruth, Loreto Santa-Marina, Denise M. Scholtens, Sylvain Sebert, Verena Sengpiel, Marcus A. Tuke, Marc Vaudel, Michael N. Weedon, Gonneke Willemsen, Andrew R. Wood, Hanieh Yaghootkar, Louis J. Muglia, Meike Bartels, Caroline L. Relton, Craig E. Pennell, Leda Chatzi, Xavier Estivill, John W. Holloway, Dorret I. Boomsma, Grant W. Montgomery, Joanne M. Murabito, Tim D. Spector, Christine Power, Marjo-Ritta Järvelin, Hans Bisgaard, Struan F A Grant, Thorkild I A Sørensen, Vincent W. Jaddoe, Bo Jacobsson, Mads Melbye, Mark I. Mccarthy, Andrew T. Hattersley, M Geoffery Hayes, Timothy M. Frayling, Marie-France Hivert, Janine F. Felix, Elina Hyppönen, William L. Lowe, David M. Evans, Debbie A. Lawlor, Bjarke Feenstra, Rachel M. Freathy
Stead Family Department of Pediatrics Publications
Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B ...
Novel Combination Bmp7 And Hgf Gene Therapy Instigates Selective Myofibroblast Apoptosis And Reduces Corneal Haze In Vivo, 2018 Harry S. Truman Memorial Veterans’ Hospital
Novel Combination Bmp7 And Hgf Gene Therapy Instigates Selective Myofibroblast Apoptosis And Reduces Corneal Haze In Vivo, Suneel Gupta, Michael K. Fink, Arkasubhra Ghosh, Ratnakar Tripathi, Prashant R. Sinha, Ajay Sharma, Nathan P. Hesemann, Shyam S. Chaurasia, Elizabeth A. Giuliano, Rajiv R. Mohan
Pharmacy Faculty Articles and Research
PURPOSE. We tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models.
METHODS. Eighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n ¼ 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n ¼ 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n ¼ 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic ...
Microrna 1207-3p In Prostate Cancer, 2018 The Graduate Center, City University of New York
Microrna 1207-3p In Prostate Cancer, Dibash Das
All Dissertations, Theses, and Capstone Projects
Prostate cancer (PCa) is the most commonly diagnosed male cancer and the second leading cause of cancer-related death for men in the United States. Understanding the molecular mechanisms involved in progression from the asymptomatic androgen-dependent PCa to the lethal castration resistant prostate cancer (CRPC) is a major challenge. MicroRNAs (miRNAs), are known to be dysregulated in PCa. MicroRNA-1207-3p (miR-1207-3p) is encoded by the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of miR-1207-3p in PCa is unclear. We have discovered that miR-1207-3p is significantly underexpressed in PCa cell lines ...
Streamlined Ex Vivo And In Vivo Genome Editing In Mouse Embryos Using Recombinant Adeno-Associated Viruses, 2018 University of Massachusetts Medical School
Streamlined Ex Vivo And In Vivo Genome Editing In Mouse Embryos Using Recombinant Adeno-Associated Viruses, Yeonsoo Yoon, Dan Wang, Phillip W. L. Tai, Joy Riley, Guangping Gao, Jaime A. Rivera-Perez
Pediatric Publications and Presentations
Recent advances using CRISPR-Cas9 approaches have dramatically enhanced the ease for genetic manipulation in rodents. Notwithstanding, the methods to deliver nucleic acids into pre-implantation embryos have hardly changed since the original description of mouse transgenesis more than 30 years ago. Here we report a novel strategy to generate genetically modified mice by transduction of CRISPR-Cas9 components into pre-implantation mouse embryos via recombinant adeno-associated viruses (rAAVs). Using this approach, we efficiently generated a variety of targeted mutations in explanted embryos, including indel events produced by non-homologous end joining and tailored mutations using homology-directed repair. We also achieved gene modification in vivo ...
A Plasma Telomeric Cell-Free Dna Level In Unaffected Women With Brca1 Or/And Brca2 Mutations: A Pilot Study, Shatovisha Dey, Natascia Marino, Kanokwan Bishop, Paige N. Dahlgren, Aditi Shendre, Anna Maria Storniolo, Chunyan He, Hiromi Tanaka
Internal Medicine Faculty Publications
Plasma cell-free DNA (cfDNA) is a small DNA fragment circulating in the bloodstream originating from both non-tumor- and tumor-derived cells. A previous study showed that a plasma telomeric cfDNA level decreases in sporadic breast cancer patients compared to controls. Tumor suppressor gene products including BRCA1 and BRCA2 (BRCA1&2) play an important role in telomere maintenance. In this study, we hypothesized that the plasma telomeric cfDNA level is associated with the mutation status of BRCA1&2 genes. To test this hypothesis, we performed plasma telomeric cfDNA quantitative PCR (qPCR)-based assays to compare 28 women carriers of the BRCA1&2 ...
Family Planning Decisions After A Child’S Diagnosis Of Rett Syndrome: A Pilot Study, 2018 University of South Carolina
Family Planning Decisions After A Child’S Diagnosis Of Rett Syndrome: A Pilot Study, Erin E. Huggins
Theses and Dissertations
Rett syndrome (RTT) is a rare neurodevelopmental disorder that primarily affects females. In 99% of cases, RTT is believed to occur sporadically, or de novo. However, in rare cases, RTT can be passed down from parent to child through gonadal mosaicism or asymptomatic carrier mothers. It is known that having a child with an inherited genetic condition can lead to changes in family planning; however, little research has investigated this phenomenon in sporadic genetic conditions, such as RTT. This present study used a questionnaire to assess family planning decisions of parents of children with RTT. Forty-three percent of respondents reported ...
Spiritual Care In Cancer Genetic Counseling: Patient Perceptions Of Methods, 2018 University of South Carolina
Spiritual Care In Cancer Genetic Counseling: Patient Perceptions Of Methods, Christopher Michael Spencer
Theses and Dissertations
The integration of spirituality into medical care is a growing area of debate among professionals, involving a delicate balance between serving patients who may benefit from this without alienating those who would not. To date, little research has targeted spirituality in cancer genetic counseling, particularly concerning the various methods a genetic counselor can use to address spirituality with their patients. A paper questionnaire was created and distributed to patients following their cancer genetic counseling appointments to gain insight on their perception of these methods. Fifty-two participants completed this questionnaire. The eight different spiritual integration methods presented each showed positive responses ...
The Effect Of Dna Methylation On Tp73 Expression In Tumorgenesis, 2018 Virginia Commonwealth University
The Effect Of Dna Methylation On Tp73 Expression In Tumorgenesis, Nujuma A. Moussa
Undergraduate Research Posters
Abstract: The Effect of DNA Methylation on TP73 Expression in Tumorgenesis
Nujuma Moussa, Zhixing Yao, Zaki A. Sherif
Department of Biochemistry & Molecular Biology, Howard University College of Medicine
TP73 is a member of the TP53 family of proteins that acts as a transcription factor to help regulate cellular distress. This tumor protein may play a dual role as a tumor suppressor and tumor promoter. The TP73 gene is mapped to chromosome 1p36, a frequently deleted region in neuroblastoma and other types of tumors. While mutations in the TP53 gene are commonly known to cause noxious cancers, 30% of cancers result ...
Inactivation Of Endoplasmic Reticulum Stress And The Prevention Of Neurodegenerative Diseases, 2018 Edith Cowan University
Inactivation Of Endoplasmic Reticulum Stress And The Prevention Of Neurodegenerative Diseases, Ian James Martins
ECU Publications Post 2013
Biotherapeutics and nutritional therapy are essential for the treatment of endoplasmic reticulum (ER) stress in diabetes and neurodegenerative diseases. Oxidative stress and nutrient excess may induce ER stress associated with activation of the unfolded protein response and connected to cell death. The heat shock gene Sirtuin 1 (Sirt 1) is important to the heat shock response with amyloid beta aggregation associated with the induction of mitophagy and ER stress in neuron cells. Genomic medicine that activates nuclear Sirt 1 is essential for the prevention of mitochondrial apoptosis and ER stress. Inhibitors such as drugs, alcohol, excess caffeine and palmitic acid ...
An Overview Of Technical Considerations When Using Quantitative Real-Time Pcr Analysis Of Gene Expression In Human Exercise Research, Jujiao Kuang, Xu Yan, Amanda Genders, Cesare Granata, David J. Bishop
ECU Publications Post 2013
Gene expression analysis by quantitative PCR in skeletal muscle is routine in exercise studies. The reproducibility and reliability of the data fundamentally depend on how the experiments are performed and interpreted. Despite the popularity of the assay, there is a considerable variation in experimental protocols and data analyses from different laboratories, and there is a lack of consistency of proper quality control steps throughout the assay. In this study, we present a number of experiments on various steps of quantitative PCR workflow, and demonstrate how to perform a quantitative PCR experiment with human skeletal muscle samples in an exercise study ...
Rare Single Gene Disorders: Estimating Baseline Prevalence And Outcomes Worldwide, 2018 Edith Cowan University
Rare Single Gene Disorders: Estimating Baseline Prevalence And Outcomes Worldwide, Hannah Blencowe, Sowmiya Moorthie, Mary Petrou, Hanan Hamamy, Alan Bittles, Stephen Gibbons, Matthew Darlison, Bernadette Modell, Congenital Disorders Expert Group .
ECU Publications Post 2013
As child mortality rates overall are decreasing, non-communicable conditions, such as genetic disorders, constitute an increasing proportion of child mortality, morbidity and disability. To date, policy and public health programmes have focused on common genetic disorders. Rare single gene disorders are an important source of morbidity and premature mortality for affected families. When considered collectively, they account for an important public health burden, which is frequently under-recognised. To document the collective frequency and health burden of rare single gene disorders, it is necessary to aggregate them into large manageable groupings and take account of their family implications, effective interventions and ...
Experiences Of Persons With Parkinson’S Disease Engaged In Group Therapeutic Singing, 2017 Iowa State University
Experiences Of Persons With Parkinson’S Disease Engaged In Group Therapeutic Singing, Elizabeth L. Stegemoller, Tera R. Hurt, Margaret C. Shirley, Randie D. Camp, Chrishelda W. Green, Jenna C. Pattee, Ebony Williams
Human Development and Family Studies Publications
Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder that leads to altered neural control of movement, including the control of voice, respiration, and swallowing. There is a prevalent need to provide therapy for voice, respiration, and swallowing difficulties because current pharmacological and surgical treatments do not effectively treat these impairments. Previous research has demonstrated that singing may be a treatment option to target voice, respiratory, and swallowing impairments, as well as quality of life. However, participants’ perspectives related to reasons for enrolling and engaging in programs as well as evaluation of singing programs have been neglected.
Objective The ...
Analysis Of Diagnostic, Preventive, And Disease-Modifying Therapeutic Measures Of Alzheimer’S Disease, 2017 Nova Southeastern University
Analysis Of Diagnostic, Preventive, And Disease-Modifying Therapeutic Measures Of Alzheimer’S Disease, Ghazal Habib Havoutis
HCNSO Student Capstones
Alzheimer’s disease (AD) is the most common late-onset neurodegenerative disorder and cause of dementia, characterized by the formation of neurofibrillary tangles and senile plaque deposits. The heterogeneous nature of the disease (both genetically and environmentally) makes it difficult to prevent or cure. Without prevention, the prevalence of AD is expected to triple by 2050. However, because the diagnosis of AD is usually preceded by years of cognitive impairment, early detection may aid in reducing prevalence. Thus, there is a need for validated diagnostic measures for early and improved diagnosis and prevention. In this review, current and ongoing classifiers of ...
Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, 2017 The University of Western Ontario
Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque
Electronic Thesis and Dissertation Repository
Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show ...
Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, 2017 University of Nebraska Medical Center
Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, Garland Michael Upchurch
Theses & Dissertations
DNA methyltransferase 3A (DNMT3A) is a master epigenetic regulator of benign and malignant hematopoiesis. To dissect the biological consequences of homozygous and heterozygous Dnmt3a inactivation in malignant hematopoiesis, we generated Dnmt3a homozygous null (Dnmt3aΔ/Δ) and Dnmt3a heterozygous (Dnmt3a+/–) mice and compared the presentations of hematologic malignancies between cohorts. Bi-allelic inactivation of Dnmt3a results in the presentation of mature lymphoid neoplasms resembling chronic lymphocytic leukemia (CLL; B220+CD19+CD5+; 88% penetrance (37/42)) and CD8+ peripheral T-cell lymphoma (PTCL; TCRβ+CD3+CD8+CD4—; 40% penetrance (17/42)). In contrast, mono-allelic inactivation of Dnmt3a results in the presentation of CLL ...
Germ-Line Gene Editing And Congressional Reaction In Context: Learning From Almost 50 Years Of Congressional Reactions To Biomedical Breakthroughs, Russell A. Spivak, J.D., I. Glenn Cohen, J.D., Eli Y. Adashi, M.D., M.S.
Journal of Law and Health
On December 18, 2015, President Obama signed into law a policy rider forestalling the therapeutic modification of the human germ line. The rider, motivated by the science’s potential unethical ends, is only the most recent instance in which the legislature cut short the ongoing national conversation on the acceptability of a developing science. This essay offers historical perspective on what bills were proposed and passed surrounding four other then-developing scientific breakthroughs—Recombinant DNA, in vitro fertilization, Cloning, Stem Cells—to better analyze how Congress is, and should, regulate this exciting and promising science.