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 ...
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 ...
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 ...
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.
Pas Signaling Mechanisms In Aer And Aer2, 2017 Loma Linda University
Pas Signaling Mechanisms In Aer And Aer2, Darysbel Garcia
Loma Linda University Electronic Theses, Dissertations & Projects
PAS domains are widespread signal sensors that share a conserved three-dimensional αβ fold that consists of a central β-sheet flanked by several α- helices. The aerotaxis receptor Aer from Escherichia coli and the Aer2 chemoreceptor from Pseudomonas aeruginosa both contain PAS domains. Aer senses oxygen (O2) indirectly via an FAD cofactor bound to its PAS domain, while Aer2 directly binds O2 to its PAS b-type heme cofactor. The Aer and Aer2 PAS domains both interact with a signal transduction domain known as a HAMP domain. The PAS-HAMP arrangement differs between Aer and Aer2, with Aer- PAS residing adjacent to its ...
Investigating The Role Of Dispatched In Hedgehog Ligand Transport And Delivery, 2017 University of Tennessee Health Science Center
Investigating The Role Of Dispatched In Hedgehog Ligand Transport And Delivery, William Bodeen
Theses and Dissertations (ETD)
During the development of all metazoans, the Hedgehog (Hh) signaling pathway provides instructional cues influencing a variety of cellular processes. The pathway ligand, Hh, is dually lipidated by cholesterol and palmitate, which effectively anchors the molecule to the lipid bilayer of the signal producing cell. To complicate the Hh pathway induction process, the Hh ligand is often produced at a significant distance from the cells it influences. Only one known conserved molecule, Dispatched (Disp), can alleviate the membrane tethering imparted by Hh lipidation. Underscoring the importance of Disp protein during development, knockout animals succumb to lethality at E9.5, an ...
El Acceso Y Uso De Las Pruebas Genéticas Para La Detección Precoz De Enfermedades Congénitas En Mujeres Embarazadas En La Ciudad Autónoma De Buenos Aires En El Año 2017 \ The Access And Use Of Genetic Tests For Early Detection Of Congenital Diseases In Pregnant Women In The Autonomous City Of Buenos Aires In The Year 2017, 2017 SIT Study Abroad
El Acceso Y Uso De Las Pruebas Genéticas Para La Detección Precoz De Enfermedades Congénitas En Mujeres Embarazadas En La Ciudad Autónoma De Buenos Aires En El Año 2017 \ The Access And Use Of Genetic Tests For Early Detection Of Congenital Diseases In Pregnant Women In The Autonomous City Of Buenos Aires In The Year 2017, Anna Anna Bauer
Independent Study Project (ISP) Collection
Las pruebas genéticas son una herramienta útil para la prevención y el diagnóstico de defectos congénitos en las mujeres embarazadas. Esta investigación explora el acceso y uso de estas pruebas para mujeres que residen en la Ciudad Autónoma de Buenos Aires en el año 2017. Se trata de un tema amerita una investigación porque la tecnología para hacer estudios genéticos todavía es algo novedosa. Además, a través de las pruebas genéticas es posible detectar si el feto tiene un alto riesgo para desarrollar un defecto congénito, el cual es una de las causas más importantes de la mortalidad prenatal y ...
P33. Design And Evaluation Of An Escherichia Coli Biomarker For Indication Of Ph, 2017 Western University
P33. Design And Evaluation Of An Escherichia Coli Biomarker For Indication Of Ph, Kevin X. Zhou, Luana Langlois, Ashmita Singh, John Prince
Western Research Forum
Measuring pH is one of the most commonly used techniques in both the laboratory as well as the field due to its importance in a multitude of biochemical processes. Traditional methods of measuring pH may be highly developed in accuracy and precision but often involve disruption of the environment. Biological markers offer an alternative that allows for long-term pH monitoring. This innovative approach allows for vast applications such as in the manufacturing, food processing and research industries. Under moderate acidic conditions, the asr (acid shock RNA) gene is highly inducible and has been demonstrated to be crucial for growth at ...
Sleep Disturbances And Depression: The Role Of Genes And Trauma, 2017 Virginia Commonwealth University
Sleep Disturbances And Depression: The Role Of Genes And Trauma, Mackenzie J. Lind
Theses and Dissertations
Sleep disturbances and insomnia are prevalent, with around 33% of adults indicating that they experience at least one main symptom of insomnia, and bidirectional relationships exist with common psychopathology, particularly major depressive disorder (MDD). However, genetic and environmental (e.g., traumatic event exposure) contributions to the etiology of these phenotypes are not yet well understood. A genetically informative sample of approximately 12,000 Han Chinese women aged 30-60 (50% with recurrent MDD) was used to address several gaps within the sleep literature. Sleep disturbances were assessed in all individuals using a general item addressing sleeplessness (GS). A sleep within depression ...
Adoptees’ Experiences With Direct-To-Consumer Genetic Testing: Emotions, Satisfaction, And Motivating Factors, 2017 University of South Carolina
Adoptees’ Experiences With Direct-To-Consumer Genetic Testing: Emotions, Satisfaction, And Motivating Factors, Anna Childers
Theses and Dissertations
Public awareness of the role of genetics in disease continues to expand along with the use of direct-to-consumer genetic testing (DTC-GT). One subset of customers taking advantage of the growing DTC-GT market is adoptees. Prior research has shown that adoptees appear to be more motivated than non-adoptees to learn about their genetic disease risk but have similar responses to health-related information acquired through DTC-GT. In this exploratory qualitative study, fourteen adoptees were asked about their motivations for pursuing DTC-GT; satisfaction with results; emotions throughout the process; and interest in meeting with a genetic counselor. Motivations for pursuing DTCGT fell into ...
Assessment Of Patient Satisfaction With The Provision Of Fertility Information In Women With Lynch Syndrome, 2017 University of South Carolina
Assessment Of Patient Satisfaction With The Provision Of Fertility Information In Women With Lynch Syndrome, Rachel Elizabeth Hickey
Theses and Dissertations
Lynch Syndrome (LS), one of the most common hereditary cancer syndromes, is primarily known for its substantially increased risks for colorectal cancer. The incidence of gynecologic cancers (endometrial and ovarian cancers) equals or exceeds the incidence of colorectal cancers in female patients with LS. The prevention and treatment methods for these cancers can drastically affect fertility and reproduction. Previous studies with cancer patients have revealed challenges in acquiring information related to these topics; thus far, no research has assessed whether there is an informational gap regarding fertility information for women in the LS population. The purpose of this study was ...
Reliability Issues In Imaging Genetics, 2017 Oregon Health & Science University
Reliability Issues In Imaging Genetics, Annika Eriksson
No abstract provided.
Integrative Genomic And Transcriptomic Analysis For Pinpointing Recurrent Alterations Of Plant Homeodomain Genes And Their Clinical Significance In Breast Cancer, 2016 Department of Oncology, Wayne State University School of Medicine
Integrative Genomic And Transcriptomic Analysis For Pinpointing Recurrent Alterations Of Plant Homeodomain Genes And Their Clinical Significance In Breast Cancer, Huimei Yu, Yuanyuan Jiang, Lanxin Liu, Wenqi Shan, Xiaofang Chu, Zhe Yang, Zeng-Quan Yang
Oncology Faculty Publications
A wide range of the epigenetic effectors that regulate chromatin modification, gene expression, genomic stability, and DNA repair contain structurally conserved domains called plant homeodomain (PHD) fingers. Alternations of several PHD finger-containing proteins (PHFs) due to genomic amplification, mutations, deletions, and translocations have been linked directly to various types of cancer. However, little is known about the genomic landscape and the clinical significance of PHFs in breast cancer. Hence, we performed a large-scale genomic and transcriptomic analysis of 98 PHF genes in breast cancer using TCGA and METABRIC datasets and correlated the recurrent alterations with clinicopathological features and survival of ...
Regulation Of Cancer Metastasis By Protein Kinase D1: A Global Regulatory Cascade, 2016 University of Tennessee Health Science Center
Regulation Of Cancer Metastasis By Protein Kinase D1: A Global Regulatory Cascade, Aditya Ganju
Theses and Dissertations (ETD)
Protein Kinase D1 (PKD1) is a serine threonine kinase which is downregulated in Prostate, Breast and Colon Cancer. It functions as a tumor suppressor in different cancer cells. Downregulation of PKD1 is known to be associated with aggressiveness of the cancer. PKD1 is known to regulate many key oncogenic signaling pathways such as E-cadherin, β-catenin and Androgen Receptor signaling pathways. Aberrant expression of these oncogenic pathways leads to transformation of cells from normal to malignant phenotype, thereby leading to increased proliferation, growth and metastasis to distant organs of these cancer cells. Literature evidence also points to the fact that E-cadherin ...
A Tale Of Two Species: Evolvability, Genomic Context, And Pathogen Forecasting, 2016 University of New England
A Tale Of Two Species: Evolvability, Genomic Context, And Pathogen Forecasting, Meghan May
Biomedical Sciences Faculty Presentations
Dr. Meghan May gives an overview presentation of her research on evolution of virulence and pathogen prediction. The focus of the presentation is a group of organisms called mycoplasmas, and covered subjects include: Mycoplasma synoviae, Mycoplasma gallisepticum, genomic context, predictive modeling, sequence evolution, and genome reduction.
High-Throughput Allele-Specific Expression Across 250 Environmental Conditions, 2016 Wayne State Center for Molecular Medicine and Genetics, Wayne State University
High-Throughput Allele-Specific Expression Across 250 Environmental Conditions, Gregory A. Moyerbrailean, Allison L. Richards, Daniel Kurtz, Cynthia A. Kalita, Gordon O. Davis, Chris T. Harvey, Adnan Alazizi, Donovan Watza, Yoram Sorokin, Nancy J. Hauff, Xiang Zhou, Xiaoquan Wen, Roger Pique-Regi, Francesca Luca
Center for Molecular Medicine and Genetics
Gene-by-environment (GxE) interactions determine common disease risk factors and biomedically relevant complex traits. However, quantifying how the environment modulates genetic effects on human quantitative phenotypes presents unique challenges. Environmental covariates are complex and difficult to measure and control at the organismal level, as found in GWAS and epidemiological studies. An alternative approach focuses on the cellular environment using in vitro treatments as a proxy for the organismal environment. These cellular environments simplify the organism-level environmental exposures to provide a tractable influence on subcellular phenotypes, such as gene expression. Expression quantitative trait loci (eQTL) mapping studies identified GxE interactions in response ...
Regulation Of Polycystin-1 Function By Calmodulin Binding, 2016 University of California, Santa Barbara
Regulation Of Polycystin-1 Function By Calmodulin Binding, Nicholas Doerr, Yidi Wang, Kevin R. Kipp, Guangyi Liu, Jesse J. Benza, Vladimir Pletnev, Tengis S. Pavlov, Alexander Staruschenko, Ashraf M. Mohieldin, Maki Takahashi, Surya M. Nauli, Thomas Weimbs
Pharmacy Faculty Articles and Research
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common genetic disease that leads to progressive renal cyst growth and loss of renal function, and is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The PC1/PC2 complex localizes to primary cilia and can act as a flow-dependent calcium channel in addition to numerous other signaling functions. The exact functions of the polycystins, their regulation and the purpose of the PC1/PC2 channel are still poorly understood. PC1 is an integral membrane protein with a large extracytoplasmic N-terminal domain and a short, ~200 amino acid C-terminal ...