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Articles 1 - 13 of 13
Full-Text Articles in Medical Sciences
Cocaine Enhances Hiv-1 Infectivity In Monocyte Derived Dendritic Cells By Suppressing Microrna-155, Jessica Napuri, Sudheesh Pilakka-Kanthikeel, Andrea Raymond, Marisela Agudelo, Adriana Yndart-Arias, Madhavan Nair, Shailendra K. Saxena
Cocaine Enhances Hiv-1 Infectivity In Monocyte Derived Dendritic Cells By Suppressing Microrna-155, Jessica Napuri, Sudheesh Pilakka-Kanthikeel, Andrea Raymond, Marisela Agudelo, Adriana Yndart-Arias, Madhavan Nair, Shailendra K. Saxena
HWCOM Faculty Publications
Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and …
In Vivo Bioluminescence Imaging To Evaluate Systemic And Topical Antibiotics Against Community-Acquired Methicillin-Resistant Staphylococcus Aureus-Infected Skin Wounds In Mice, Yi Guo, Romela Irene Ramos, John S. Cho, Niles P. Donegan, Ambrose L. Cheung, Lloyd S. Miller
In Vivo Bioluminescence Imaging To Evaluate Systemic And Topical Antibiotics Against Community-Acquired Methicillin-Resistant Staphylococcus Aureus-Infected Skin Wounds In Mice, Yi Guo, Romela Irene Ramos, John S. Cho, Niles P. Donegan, Ambrose L. Cheung, Lloyd S. Miller
Dartmouth Scholarship
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to devel
Developmental Genes Targeted For Epigenetic Variation Between Twin-Twin Transfusion Syndrome Children, Carmen J. Marsit, Devin C. Koestler, Debra Watson-Smith, Charlotte M. Boney
Developmental Genes Targeted For Epigenetic Variation Between Twin-Twin Transfusion Syndrome Children, Carmen J. Marsit, Devin C. Koestler, Debra Watson-Smith, Charlotte M. Boney
Dartmouth Scholarship
Background: Epigenetic mechanisms are thought to be critical in mediating the role of the intrauterine environment on lifelong health and disease. Twin-twin transfusion syndrome (TTTS) is a rare condition wherein fetuses share the placenta and develop vascular anastomoses, which allow blood to flow between the fetuses. The unequal flow results in reciprocal hypo- and hypervolemia in the affected twins, striking growth differences and physiologic adaptations in response to this significant stressor. The donor twin in the TTTS syndrome can be profoundly growth restricted and there is likely a nutritional imbalance between the twins. The consequences of TTTS on fetal programming …
A Simple And Computationally Efficient Approach To Multifactor Dimensionality Reduction Analysis Of Gene-Gene Interactions For Quantitative Traits, Jiang Gui, Jason H. Moore, Scott M. Williams, Peter Andrews, Hillege, Hans L. Hillege, Hans L., Pim Van Der Harst, Gerjan| Navis, Wiek H. Van Gilst, Folkert W. Asselbergs, Diane| Gilbert-Diamond
A Simple And Computationally Efficient Approach To Multifactor Dimensionality Reduction Analysis Of Gene-Gene Interactions For Quantitative Traits, Jiang Gui, Jason H. Moore, Scott M. Williams, Peter Andrews, Hillege, Hans L. Hillege, Hans L., Pim Van Der Harst, Gerjan| Navis, Wiek H. Van Gilst, Folkert W. Asselbergs, Diane| Gilbert-Diamond
Dartmouth Scholarship
We present an extension of the two-class multifactor dimensionality reduction (MDR) algorithm that enables detection and characterization of epistatic SNP-SNP interactions in the context of a quantitative trait. The proposed Quantitative MDR (QMDR) method handles continuous data by modifying MDR’s constructive induction algorithm to use a T-test. QMDR replaces the balanced accuracy metric with a T-test statistic as the score to determine the best interaction model. We used a simulation to identify the empirical distribution of QMDR’s testing score. We then applied QMDR to genetic data from the ongoing prospective Prevention of Renal and Vascular End-Stage Disease (PREVEND) study.
Genetic Approaches To Studying Complex Human Disease, Joseph B. Dube
Genetic Approaches To Studying Complex Human Disease, Joseph B. Dube
Electronic Thesis and Dissertation Repository
Common, complex diseases such as cardiovascular disease (CVD) represent an intricate interaction between environmental and genetic factors and now account for the leading causes of mortality in western society. By investigating the genetic component of complex disease etiology, we have gained a better understanding of the biological pathways underlying complex disease and the heterogeneity of complex disease risk. However, the development of high throughput genomic technologies and large well-phenotyped multi-ethnic cohorts has opened the door towards more in-depth and trans-disciplinary approaches to studying the genetics of complex disease pathogenesis. Accordingly, we sought to investigate select complex traits and diseases using …
Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu
Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu
Biochemistry and Microbiology
Pseudomonas aeruginosa is a Gram negative, opportunistic pathogen that uses the overproduction of alginate, a surface polysaccharide, to form biofilms in vivo. Overproduction of alginate, also known as mucoidy, affords the bacterium protection from the host's defenses and facilitates the establishment of chronic lung infections in individuals with cystic fibrosis. Expression of the alginate biosynthetic operon is primarily controlled by the alternative sigma factor AlgU (AlgT/σ22). In a nonmucoid strain, AlgU is sequestered by the transmembrane antisigma factor MucA to the cytoplasmic membrane. AlgU can be released from MucA via regulated intramembrane proteolysis by proteases AlgW and MucP …
Assessing Methods For Assigning Snps To Genes In Gene-Based Tests Of Association Using Common Variants, Ashley Petersen, Carolina Alvarez, Scott Declaire, Nathan L. Tintle
Assessing Methods For Assigning Snps To Genes In Gene-Based Tests Of Association Using Common Variants, Ashley Petersen, Carolina Alvarez, Scott Declaire, Nathan L. Tintle
Department of Biostatistics Faculty Publications
Gene-based tests of association are frequently applied to common SNPs (MAF>5%) as an alternative to single-marker tests. In this analysis we conduct a variety of simulation studies applied to five popular gene-based tests investigating general trends related to their performance in realistic situations. In particular, we focus on the impact of non-causal SNPs and a variety of LD structures on the behavior of these tests. Ultimately, we find that non-causal SNPs can significantly impact the power of all gene-based tests. On average, we find that the “noise” from 6–12 non-causal SNPs will cancel out the “signal” of one causal …
Influence Of Genetic Variation On Birth Defects In Caenorhabditis Elegans, Daniel Robert Kepple
Influence Of Genetic Variation On Birth Defects In Caenorhabditis Elegans, Daniel Robert Kepple
Honors Capstone Projects - All
In my Renee Crown Honors Capstone project, I studied how genetic variation influences birth defects that cause death in C. elegans embryos. I performed high-throughput hatching assay experiments of recombinant inbred advance intercross lines of C. elegans. These lines are genetically distinct from each other. I found significant variation in birth defects causing embryo death in these recombinant inbred advanced intercross lines. My results give evidence that gene interaction may play a significant role in causing birth defects resulting in death. My data also provides a starting point for studies making statistical arguments linking these birth defects to specific …
Identification Of Anziaic Acid, A Lichen Depside From Hypotrachyna Sp., As A New Topoisomerase Poison Inhibitor, Bokun Cheng, Shugeng Cao, Victor Vasquez, Thirunavukkarasu Annamalai, Giselle Tamayo-Castillo, Yuk-Ching Tse-Dinh
Identification Of Anziaic Acid, A Lichen Depside From Hypotrachyna Sp., As A New Topoisomerase Poison Inhibitor, Bokun Cheng, Shugeng Cao, Victor Vasquez, Thirunavukkarasu Annamalai, Giselle Tamayo-Castillo, Yuk-Ching Tse-Dinh
Department of Chemistry and Biochemistry
Topoisomerase inhibitors are effective for antibacterial and anticancer therapy because they can lead to the accumulation of the intermediate DNA cleavage complex formed by the topoisomerase enzymes, which trigger cell death. Here we report the application of a novel enzyme-based high-throughput screening assay to identify natural product extracts that can lead to increased accumulation of the DNA cleavage complex formed by recombinant Yersinia pestistopoisomerase I as part of a larger effort to identify new antibacterial compounds. Further characterization and fractionation of the screening positives from the primary assay led to the discovery of a depside, anziaic acid, from the lichen …
Neuroscience And The Future Of Personhood And Responsibility, Stephen J. Morse
Neuroscience And The Future Of Personhood And Responsibility, Stephen J. Morse
All Faculty Scholarship
This is a chapter in a book, Constitution 3.0: Freedom and Technological Change, edited by Jeffrey Rosen and Benjamin Wittes and published by Brookings. It considers whether likely advances in neuroscience will fundamentally alter our conceptions of human agency, of what it means to be a person, and of responsibility for action. I argue that neuroscience poses no such radical threat now and in the immediate future and it is unlikely ever to pose such a threat unless it or other sciences decisively resolve the mind-body problem. I suggest that until that happens, neuroscience might contribute to the reform of …
Systems Biology Of The Functional And Dysfunctional Endothelium, Jennifer Frueh, Nataly Maimari, Takayuki Homma, Sandra M. Bovens, Ryan M. Pedrigi, Leila Towhidi, Rob Krams
Systems Biology Of The Functional And Dysfunctional Endothelium, Jennifer Frueh, Nataly Maimari, Takayuki Homma, Sandra M. Bovens, Ryan M. Pedrigi, Leila Towhidi, Rob Krams
Department of Mechanical and Materials Engineering: Faculty Publications
This review provides an overview of the effect of blood flow on endothelial cell (EC) signalling pathways, applying microarray technologies to cultured cells, and in vivo studies of normal and atherosclerotic animals. It is found that in cultured ECs, 5–10% of genes are up- or down-regulated in response to fluid flow, whereas only 3–6% of genes are regulated by varying levels of fluid flow. Of all genes, 90%are regulated by the steady part of fluid flow and 10% by pulsatile components. The associated gene profiles show high variability from experiment to experiment depending on experimental conditions, and importantly, the bioinformatical …
Health Insurance, Employment, And The Human Genome: Genetic Discrimination And Biobanks In The United States, Eric A. Feldman, Chelsea Darnell
Health Insurance, Employment, And The Human Genome: Genetic Discrimination And Biobanks In The United States, Eric A. Feldman, Chelsea Darnell
All Faculty Scholarship
Does genetic information warrant special legal protection, and if so how should it be protected? This essay examines the most recent (and indeed only) significant effort by the US government to prohibit genetic discrimination, the Genetic Information Nondiscrimination Act (GINA). We argue that the legislation is unlikely to have the positive impact sought by advocates of genetic privacy and proponents of biobanks. In part, GINA disappoints because it does too little. Hailed by its promoters as “the first civil rights act of the 21st century,” GINA’s reach is in fact quite modest and its grasp even more so. But …
The Roles Of Primary Cilia In Polycystic Kidney Disease, Samred H. Kathem, Ashraf M. Mohieldin, Surya M. Nauli
The Roles Of Primary Cilia In Polycystic Kidney Disease, Samred H. Kathem, Ashraf M. Mohieldin, Surya M. Nauli
Pharmacy Faculty Articles and Research
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited genetic disorder that results in progressive renal cyst formation with ultimate loss of renal function and other systemic disorders. These systemic disorders include abnormalities in cardiovascular, portal, pancreatic and gastrointestinal systems. ADPKD is considered to be among the ciliopathy diseases due to the association with abnormal primary cilia function. In order to understand the full course of primary cilia and its association with ADPKD, the structure, functions and role of primary cilia have been meticulously investigated. As a result, the focus on primary cilia has emerged to support the vital roles …