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Full-Text Articles in Medicine and Health Sciences

Syndecan 4 Is Required For Endothelial Alignment In Flow And Atheroprotective Signaling, Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, David D. Simon, Tyler D. Ross, John M. Rhodes, Thomas Z. Wang Dec 2014

Syndecan 4 Is Required For Endothelial Alignment In Flow And Atheroprotective Signaling, Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, David D. Simon, Tyler D. Ross, John M. Rhodes, Thomas Z. Wang

Dartmouth Scholarship

Atherosclerotic plaque localization correlates with regions of disturbed flow in which endothelial cells (ECs) align poorly, whereas sustained laminar flow correlates with cell alignment in the direction of flow and resistance to atherosclerosis. We now report that in hypercholesterolemic mice, deletion of syndecan 4 (S4−/−) drastically increased atherosclerotic plaque burden with the appearance of plaque in normally resistant locations. Strikingly, ECs from the thoracic aortas of S4−/− mice were poorly aligned in the direction of the flow. Depletion of S4 in human umbilical vein endothelial cells (HUVECs) using shRNA also inhibited flow-induced alignment in vitro, which was rescued by re-expression …


E2f4 Regulatory Program Predicts Patient Survival Prognosis In Breast Cancer, Sari S. Khaleel, Erik H. Andrews, Matthew Ung, James Direnzo, Chao Chung Dec 2014

E2f4 Regulatory Program Predicts Patient Survival Prognosis In Breast Cancer, Sari S. Khaleel, Erik H. Andrews, Matthew Ung, James Direnzo, Chao Chung

Dartmouth Scholarship

Genetic and molecular signatures have been incorporated into cancer prognosis prediction and treatment decisions with good success over the past decade. Clinically, these signatures are usually used in early-stage cancers to evaluate whether they require adjuvant therapy following surgical resection. A molecular signature that is prognostic across more clinical contexts would be a useful addition to current signatures. We defined a signature for the ubiquitous tissue factor, E2F4, based on its shared target genes in multiple tissues. These target genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) experiments using a probabilistic method. We then computationally calculated the regulatory activity score …


Rationale, Design, And Method Of The Diabetes & Women’S Health Study – A Study Of Long-Term Health Implications Of Glucose Intolerance In Pregnancy And Their Determinants, Cuilin Zhang, Frank B. Hu, Sjurdur F. Olsen, Allan Vaag, Robert Gore-Langton, Jorge E. Chavarro, Wei Bao, Edwina Yeung, Katherine Bowers, Louise Groth Grunnet, Seth Sherman, Michele Kiely, Marin Strøm, Susanne Hansen, Aiyi Liu, James Mills, Ruzong Fan Nov 2014

Rationale, Design, And Method Of The Diabetes & Women’S Health Study – A Study Of Long-Term Health Implications Of Glucose Intolerance In Pregnancy And Their Determinants, Cuilin Zhang, Frank B. Hu, Sjurdur F. Olsen, Allan Vaag, Robert Gore-Langton, Jorge E. Chavarro, Wei Bao, Edwina Yeung, Katherine Bowers, Louise Groth Grunnet, Seth Sherman, Michele Kiely, Marin Strøm, Susanne Hansen, Aiyi Liu, James Mills, Ruzong Fan

Publications and Research

Women who develop gestational diabetes mellitus or impaired glucose tolerance during pregnancy are at substantially increased risk for type 2 diabetes and comorbidities after pregnancy. Little is known about the role of genetic factors and their interactions with environmental factors in determining the transition from gestational diabetes mellitus to overt type 2 diabetes mellitus. These critical data gaps served as the impetus for this Diabetes & Women’s Health study with the overall goal of investigating genetic factors and their interactions with risk factors amenable to clinical or public health interventions in relation to the transition of gestational diabetes mellitus to …


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 …


Diabetes And Obesity Induce Transcriptomic And Metabolomic Changes Enhancing Pancreatic Cancer Aggressiveness, Guermarie Velázquez Torres May 2014

Diabetes And Obesity Induce Transcriptomic And Metabolomic Changes Enhancing Pancreatic Cancer Aggressiveness, Guermarie Velázquez Torres

Dissertations & Theses (Open Access)

Pancreatic cancer is one of the most aggressive types of cancer, with poor prognosis that lacks effective diagnostic markers and therapies. It is expected that in 2014 the incidence and the mortality of pancreatic cancer in the United States will be 46,420 and 39,590 respectively. Diabetes and obesity are modifiable risk factors associated with accelerated pancreatic carcinogenesis and tumor progression, but the biological mechanisms are not completely understood. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating these epidemiologic phenomena. Our hypothesis is that obesity and diabetes mellitus type 2 (DM2) accelerate pancreatic cancer 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.


Galactose-1-Phosphate Uridyl Transferase (Galt) And Galactosemia A Review Of Galt Function And Current Theories On Galactosemia Pathogenesis, Lydia R. Rehrer Apr 2014

Galactose-1-Phosphate Uridyl Transferase (Galt) And Galactosemia A Review Of Galt Function And Current Theories On Galactosemia Pathogenesis, Lydia R. Rehrer

Senior Honors Theses

All living organisms depend on the metabolism of carbohydrates for energy and the biosynthesis of necessary glycoconjugates. One of these carbohydrates is the monosaccharide galactose. Galactose is metabolized by humans through the Leloir pathway of galactose metabolism, which contains three enzymes to modify galactose so that it can be incorporated into glycolysis for the production of cellular energy. The middle enzyme of this pathway, galactose-1-phosphate uridyltransferase, produces uridine diphosphogalactose (UDP-gal) from galactose-1-phosphate (gal-1P), and a deficiency of this enzyme results in the human disease galactosemia. Galactosemia is diagnosed soon after an infant begins feeding, and although a galactose-restricted diet eliminates …