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Mediofrontal Event-Related Potentials In Response To Positive, Negative And Unsigned Prediction Errors., Thomas D. Sambrook, Jeremy Goslin Jan 2014

Mediofrontal Event-Related Potentials In Response To Positive, Negative And Unsigned Prediction Errors., Thomas D. Sambrook, Jeremy Goslin

School of Psychology

Reinforcement learning models make use of reward prediction errors (RPEs), the difference between an expected and obtained reward. There is evidence that the brain computes RPEs, but an outstanding question is whether positive RPEs ("better than expected") and negative RPEs ("worse than expected") are represented in a single integrated system. An electrophysiological component, feedback related negativity, has been claimed to encode an RPE but its relative sensitivity to the utility of positive and negative RPEs remains unclear. This study explored the question by varying the utility of positive and negative RPEs in a design that controlled for other closely related …


Using Forced Choice To Test Belief Bias In Syllogistic Reasoning., Dries Trippas, Michael F. Verde, Simon J. Handley Jan 2014

Using Forced Choice To Test Belief Bias In Syllogistic Reasoning., Dries Trippas, Michael F. Verde, Simon J. Handley

School of Psychology

In deductive reasoning, believable conclusions are more likely to be accepted regardless of their validity. Although many theories argue that this belief bias reflects a change in the quality of reasoning, distinguishing qualitative changes from simple response biases can be difficult (Dube, Rotello, & Heit, 2010). We introduced a novel procedure that controls for response bias. In Experiments 1 and 2, the task required judging which of two simultaneously presented syllogisms was valid. Surprisingly, there was no evidence for belief bias with this forced choice procedure. In Experiment 3, the procedure was modified so that only one set of premises …


Implicit Meaning In 18-Month-Old Toddlers., Luche C Delle, Samantha Durrant, Caroline Floccia, Kim Plunkett Jan 2014

Implicit Meaning In 18-Month-Old Toddlers., Luche C Delle, Samantha Durrant, Caroline Floccia, Kim Plunkett

School of Psychology

A substantial body of evidence demonstrates that infants understand the meaning of spoken words from as early as 6 months. Yet little is known about their ability to do so in the absence of any visual referent, which would offer diagnostic evidence for an adult-like, symbolic interpretation of words and their use in language mediated thought. We used the head-turn preference procedure to examine whether infants can generate implicit meanings from word forms alone as early as 18 months of age, and whether they are sensitive to meaningful relationships between words. In one condition, toddlers were presented with lists of …


Enrichment And Training Improve Cognition In Rats With Cortical Malformations, Kyle R. Jenks, Marcella M. Lucas, Ben A. Duffy, Ashlee A. Robbins, Barjor Gimi, Jeremy M. Barry, Rod C. Scott Dec 2013

Enrichment And Training Improve Cognition In Rats With Cortical Malformations, Kyle R. Jenks, Marcella M. Lucas, Ben A. Duffy, Ashlee A. Robbins, Barjor Gimi, Jeremy M. Barry, Rod C. Scott

Dartmouth Scholarship

Children with malformations of cortical development (MCD) frequently have associated cognitive impairments which reduce quality of life. We hypothesized that cognitive deficits associated with MCD can be improved with environmental manipulation or additional training. The E17 methylazoxymethanol acetate (MAM) exposure model bears many anatomical hallmarks seen in human MCDs as well as similar behavioral and cognitive deficits. We divided control and MAM exposed Sprague-Dawley rats into enriched and non-enriched groups and tested performance in the Morris water maze. Another group similarly divided underwent sociability testing and also underwent Magnetic Resonance Imaging (MRI) scans pre and post enrichment. A third group …


Targeting Inflammation Using Salsalate In Patients With Type 2 Diabetes: Effects On Flow-Mediated Dilation (Tinsal-Fmd)., Allison B Goldfine, J Stewart Buck, Cyrus Desouza, Vivian Fonseca, Yii-Der Ida Chen, Steven E Shoelson, Kathleen A. Jablonski, Mark A Creager, The Tinsal-Fmd Team Dec 2013

Targeting Inflammation Using Salsalate In Patients With Type 2 Diabetes: Effects On Flow-Mediated Dilation (Tinsal-Fmd)., Allison B Goldfine, J Stewart Buck, Cyrus Desouza, Vivian Fonseca, Yii-Der Ida Chen, Steven E Shoelson, Kathleen A. Jablonski, Mark A Creager, The Tinsal-Fmd Team

GW Biostatistics Center

OBJECTIVE: To test whether inhibiting inflammation with salsalate improves endothelial function in patients with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: We conducted an ancillary study to the National Institutes of Health-sponsored, multicenter, randomized, double-masked, placebo-controlled trial evaluating the safety and efficacy of salsalate in targeting inflammation to improve glycemia in patients with T2D. Flow-mediated, endothelium-dependent dilation (FMD) and endothelium-independent, nitroglycerin-mediated dilation (NMD) of the brachial artery were assessed at baseline and 3 and 6 months following randomization to either salsalate 3.5 g/day or placebo. The primary end point was change in FMD at 6 months.

RESULTS: A total …


Patients’ Attitudes Towards Patient Involvement In Safety Interventions: Results Of Two Exploratory Studies, Rachel Davis, Nick Sevdalis, Anna Pinto, Ara Darzi, Charles A. Vincent Dec 2013

Patients’ Attitudes Towards Patient Involvement In Safety Interventions: Results Of Two Exploratory Studies, Rachel Davis, Nick Sevdalis, Anna Pinto, Ara Darzi, Charles A. Vincent

Faculty Publications

BACKGROUND: In recent years, patient-focused interventions have been introduced aimed at increasing patient involvement in safety-related behaviours. However, patients' attitudes towards these interventions and comfort in participating in the recommended behaviours remain largely unexplored. OBJECTIVE: To evaluate patients' attitudes towards a video and leaflet aimed at encouraging patient involvement in safety-related behaviours. DESIGN: Two exploratory studies employing a within-subjects mixed-methods design. SETTING: Six hospital wards on an inner-city London teaching hospital. PARTICIPANTS: Medical and surgical inpatients: 80 patients in study 1 (mean age 55; 69% men) and 80 patients in study 2 (mean age 52; 60% men). INTERVENTION: Patients watched …


Diagnosis And Acute Management Of Patients With Concussion At Children's Hospitals., Jeffrey D. Colvin, Cary Thurm, Brian M. Pate, Jason G. Newland, Matt Hall, William P. Meehan Iii Dec 2013

Diagnosis And Acute Management Of Patients With Concussion At Children's Hospitals., Jeffrey D. Colvin, Cary Thurm, Brian M. Pate, Jason G. Newland, Matt Hall, William P. Meehan Iii

Manuscripts, Articles, Book Chapters and Other Papers

Objectives: To describe the number of hospital admissions for concussion at paediatric hospitals in the USA. To describe the use of imaging and medications for acute concussion paediatric patients.

Design: Cross-sectional study.

Setting: Children's hospitals participating in the Pediatric Health Information System in the USA during a 10-year period.

Patients: All emergency department (ED) visits and inpatient admissions with the primary diagnosis of concussion, defined as International Classification of Diseases, Ninth Revision, Clinical Modification codes for: (1) concussion, (2) postconcussion syndrome or (3) skull fracture without mention of intracranial injury with concussion.

Main outcome measures: The proportion of concussion patients …


Association Between In Utero Arsenic Exposure, Placental Gene Expression, And Infant Birth Weight: A Us Birth Cohort Study, Dennis Liang Fei, Devin C. Koestler, Zhigang Li, Camilla Giambelli, Avencia Sanchez-Mejias, Julie Gosse, Carmen J. Marsit, Margaret R. Karagas, David J. Robbins Dec 2013

Association Between In Utero Arsenic Exposure, Placental Gene Expression, And Infant Birth Weight: A Us Birth Cohort Study, Dennis Liang Fei, Devin C. Koestler, Zhigang Li, Camilla Giambelli, Avencia Sanchez-Mejias, Julie Gosse, Carmen J. Marsit, Margaret R. Karagas, David J. Robbins

Dartmouth Scholarship

Epidemiologic studies and animal models suggest that in utero arsenic exposure affects fetal health, with a negative association between maternal arsenic ingestion and infant birth weight often observed. However, the molecular mechanisms for this association remain elusive. In the present study, we aimed to increase our understanding of the impact of low-dose arsenic exposure on fetal health by identifying possible arsenic-associated fetal tissue biomarkers in a cohort of pregnant women exposed to arsenic at low levels.

Methods: Arsenic concentrations were determined from the urine samples of a cohort of 133 pregnant women from New Hampshire. Placental tissue samples collected from …


Occupational Injuries On Thoroughbred Horse Farms: A Description Of Latino And Non-Latino Workers' Experiences, Jennifer E. Swanberg, Jessica M. Clouser, Susan C. Westneat, Mary W. Marsh, Deborah B. Reed Nov 2013

Occupational Injuries On Thoroughbred Horse Farms: A Description Of Latino And Non-Latino Workers' Experiences, Jennifer E. Swanberg, Jessica M. Clouser, Susan C. Westneat, Mary W. Marsh, Deborah B. Reed

Health, Behavior & Society Faculty Publications

Animal production is a dangerous industry and increasingly reliant on a Latino workforce. Within animal production, little is known about the risks or the occupational hazards of working on farms involved in various aspects of thoroughbred horse breeding. Extant research suggests that horse workers are at risk of musculoskeletal and respiratory symptoms, kicks, and other injuries. However, limited known research has examined the experiences of the industry's workers, including immigrant workers, despite their prominence and increased vulnerability. Using data collected from thoroughbred farm representatives via a phone-administered survey, a 2-hour face-to-face semi-structured interview, and farm injury logs, this article identifies …


Findings From The Peutz-Jeghers Syndrome Registry Of Uruguay, Asadur Tchekmedyian, Christopher I. Amos, Sherri J. Bale, Dakai Zhu, Stefan Arold, Joaquin Berrueta, Natalie Nabon, Thomas Mcgarrity Nov 2013

Findings From The Peutz-Jeghers Syndrome Registry Of Uruguay, Asadur Tchekmedyian, Christopher I. Amos, Sherri J. Bale, Dakai Zhu, Stefan Arold, Joaquin Berrueta, Natalie Nabon, Thomas Mcgarrity

Dartmouth Scholarship

Background: Peutz-Jeghers syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased cancer risk, usually caused by mutations of the STK11 gene. This study collected epidemiological, clinical and genetic data from all Uruguayan PJS patients. Methods: Clinical data were obtained from public and private medical centers and updated annually. Sequencing of the STK11 gene in one member of each family was performed. Results and discussion: 25 cases in 11 unrelated families were registered (15 males, 10 females). The average age of diagnosis and death was 18 and 41 years respectively. All patients had characteristic PJS pigmentation and gastrointestinal …


Evidence For Finely-Regulated Asynchronous Growth Of Toxoplasma Gondii Cysts Based On Data-Driven Model Selection, Adam M. Sullivan, Xiaopeng Zhao, Yasuhiro Suzuki, Eri Ochiai, Stephen Crutcher, Michael A. Gilchrist Nov 2013

Evidence For Finely-Regulated Asynchronous Growth Of Toxoplasma Gondii Cysts Based On Data-Driven Model Selection, Adam M. Sullivan, Xiaopeng Zhao, Yasuhiro Suzuki, Eri Ochiai, Stephen Crutcher, Michael A. Gilchrist

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system. Analyzing these interactions is important for understanding the pathogenesis of this common infection. We developed a differential equation framework of cyst growth and employed Akaike Information Criteria (AIC) to determine the growth and removal functions that best describe …


Two Phase 3, Multicenter, Randomized, Placebo-Controlled Clinical Trials Of Fampridine-Sr For Treatment Of Spasticity In Chronic Spinal Cord Injury., D. D. Cardenas, J. F. Ditunno, V. Graziani, A. B. Mclain, D. P. Lammertse, P. J. Potter, M. S. Alexander, R. Cohen, A. R. Blight Nov 2013

Two Phase 3, Multicenter, Randomized, Placebo-Controlled Clinical Trials Of Fampridine-Sr For Treatment Of Spasticity In Chronic Spinal Cord Injury., D. D. Cardenas, J. F. Ditunno, V. Graziani, A. B. Mclain, D. P. Lammertse, P. J. Potter, M. S. Alexander, R. Cohen, A. R. Blight

Department of Rehabilitation Medicine Faculty Papers

STUDY DESIGN: Two randomized, double-blind, placebo-controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of fampridine sustained-release tablets (fampridine-SR) 25 mg twice daily for moderate-to-severe spasticity in patients with chronic spinal cord injury (SCI).

SETTING: United States and Canada.

METHODS: Patients with incomplete chronic SCI were randomized to twice daily fampridine-SR 25 mg or placebo, with a 2-week single-blind placebo run-in, a 2-week titration, 12 weeks of stable dosing, 2 weeks of downward titration and 2 weeks of untreated follow-up. Co-primary end points were the change from baseline, averaged over the double-blind treatment period, for Ashworth score (bilateral knee flexors …


Adam17-Mediated Processing Of Tnf-Α Expressed By Antiviral Effector Cd8+ T Cells Is Required For Severe T-Cell-Mediated Lung Injury, Matthew P. Deberge, Kenneth H. Ely, Guang-Shing Cheng, Richard I. Enelow Nov 2013

Adam17-Mediated Processing Of Tnf-Α Expressed By Antiviral Effector Cd8+ T Cells Is Required For Severe T-Cell-Mediated Lung Injury, Matthew P. Deberge, Kenneth H. Ely, Guang-Shing Cheng, Richard I. Enelow

Dartmouth Scholarship

Influenza infection in humans evokes a potent CD8+ T-cell response, which is important for clearance of the virus but may also exacerbate pulmonary pathology. We have previously shown in mice that CD8+ T-cell expression of TNF-a is required for severe and lethal lung injury following recognition of an influenza antigen expressed by alveolar epithelial cells. Since TNF-a is first expressed as a transmembrane protein that is then proteolytically processed to release a soluble form, we sought to characterize the role of TNF-a processing in CD8+ T-cell-mediated injury. In this study we observed that inhibition of ADAM17-mediated processing of TNF-a by …


Multicenter Study Comparing Shunt Type In The Norwood Procedure For Single-Ventricle Lesions: Three-Dimensional Echocardiographic Analysis., Gerald R. Marx, Girish S. Shirali, Jami C. Levine, Lin T. Guey, James F. Cnota, Jeanne M. Baffa, William L. Border, Steve Colan, Gregory Ensing, Mark K. Friedberg, David J. Goldberg, Salim F. Idriss, J Blaine John, Wyman W. Lai, Minmin Lu, Shaji C. Menon, Richard G. Ohye, David Saudek, Pierre C. Wong, Gail D. Pearson, Pediatric Heart Network Investigators Nov 2013

Multicenter Study Comparing Shunt Type In The Norwood Procedure For Single-Ventricle Lesions: Three-Dimensional Echocardiographic Analysis., Gerald R. Marx, Girish S. Shirali, Jami C. Levine, Lin T. Guey, James F. Cnota, Jeanne M. Baffa, William L. Border, Steve Colan, Gregory Ensing, Mark K. Friedberg, David J. Goldberg, Salim F. Idriss, J Blaine John, Wyman W. Lai, Minmin Lu, Shaji C. Menon, Richard G. Ohye, David Saudek, Pierre C. Wong, Gail D. Pearson, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The Pediatric Heart Network's Single Ventricle Reconstruction (SVR) trial randomized infants with single right ventricles (RVs) undergoing a Norwood procedure to a modified Blalock-Taussig or RV-to-pulmonary artery shunt. This report compares RV parameters in the 2 groups using 3-dimensional echocardiography.

METHODS AND RESULTS: Three-dimensional echocardiography studies were obtained at 10 of 15 SVR centers. Of the 549 subjects, 314 underwent 3-dimensional echocardiography studies at 1 to 4 time points (pre-Norwood, post-Norwood, pre-stage II, and 14 months) for a total of 757 3-dimensional echocardiography studies. Of these, 565 (75%) were acceptable for analysis. RV volume, mass, mass:volume ratio, ejection fraction, …


The G-Protein-Coupled Estrogen Receptor Agonist G-1 Suppresses Proliferation Of Ovarian Cancer Cells By Blocking Tubulin Polymerization., Cheng Wang, Xiangmin Lv, Chunbo He, G Hua, M-Y Tsai, John S. Davis Oct 2013

The G-Protein-Coupled Estrogen Receptor Agonist G-1 Suppresses Proliferation Of Ovarian Cancer Cells By Blocking Tubulin Polymerization., Cheng Wang, Xiangmin Lv, Chunbo He, G Hua, M-Y Tsai, John S. Davis

Journal Articles: Obstetrics & Gynecology

The G-protein-coupled estrogen receptor 1 (GPER) has recently been reported to mediate the non-genomic action of estrogen in different types of cells and tissues. G-1 (1-[4-(6-bromobenzo[1,3] dioxol-5yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]-ethanone) was developed as a potent and selective agonist for GPER. G-1 has been shown to induce the expression of genes and activate pathways that facilitate cancer cell proliferation by activating GPER. Here we demonstrate that G-1 has an anticancer potential with a mechanism similar to vinca alkaloids, the commonly used chemotherapy drugs. We found that G-1 blocks tubulin polymerization and thereby interrupts microtubule assembly in ovarian cancer cells leading to the arrest of …


Recommendations For High-Priority Research On Cancer-Related Fatigue In Children And Adults., Andrea M. Barsevick, Michael R. Irwin, Pamela Hinds, Andrew Miller, Ann Berger, Paul Jacobsen, Sonia Ancoli-Israel, Bryce B Reeve, Karen Mustian, Ann O'Mara, Jin-Shei Lai, Michael Fisch, David Cella Oct 2013

Recommendations For High-Priority Research On Cancer-Related Fatigue In Children And Adults., Andrea M. Barsevick, Michael R. Irwin, Pamela Hinds, Andrew Miller, Ann Berger, Paul Jacobsen, Sonia Ancoli-Israel, Bryce B Reeve, Karen Mustian, Ann O'Mara, Jin-Shei Lai, Michael Fisch, David Cella

Department of Medical Oncology Faculty Papers

Over the past decades, some scientific progress has been made in understanding and treating cancer-related fatigue (CRF). However, three major problems have limited further progress: lack of agreement about measurement, inadequate understanding of the underlying biology, and problems in the conduct of clinical trials for CRF. This commentary reports the recommendations of a National Cancer Institute Clinical Trials Planning Meeting and an ongoing National Cancer Institute working group to address these problems so that high-priority research and clinical trials can be conducted to advance the science of CRF and its treatment. Recommendations to address measurement issues included revising the current …


Randomized Clinical Trial Examining Duration Of Voucher-Based Reinforcement Therapy For Cocaine Abstinence., Kimberly C Kirby, Carolyn M Carpenedo, Karen L Dugosh, Beth J Rosenwasser, Lois A Benishek, Alicia Janik, Rachel Keashen, Elena Bresani, Kenneth Silverman Oct 2013

Randomized Clinical Trial Examining Duration Of Voucher-Based Reinforcement Therapy For Cocaine Abstinence., Kimberly C Kirby, Carolyn M Carpenedo, Karen L Dugosh, Beth J Rosenwasser, Lois A Benishek, Alicia Janik, Rachel Keashen, Elena Bresani, Kenneth Silverman

College of Science & Mathematics Departmental Research

BACKGROUND: This is the first study to systematically manipulate duration of voucher-based reinforcement therapy (VBRT) to see if extending the duration increases abstinence during and following VBRT.

METHODS: We randomized cocaine-dependent methadone-maintained adults to Standard (12 weeks; n=62) or Extended (36 weeks; n=68) VBRT and provided escalating voucher amounts contingent upon urinalysis verification of cocaine abstinence. Urinalysis was scheduled at least every 2 weeks during the 48-week study and more frequently during VBRT (3/week) and 12 weeks of Aftercare (2/week).

RESULTS: Extended VBRT produced longer durations of continuous cocaine abstinence during weeks 1-24 (5.7 vs 2.7 weeks; p=0.003) and proportionally …


Increased Abundance Of Frost Mrna During Recovery From Cold Stress Is Not Essential For Cold Tolerance In Adult Drosophila Melanogaster., H Udaka, A Percival-Smith, B J Sinclair Oct 2013

Increased Abundance Of Frost Mrna During Recovery From Cold Stress Is Not Essential For Cold Tolerance In Adult Drosophila Melanogaster., H Udaka, A Percival-Smith, B J Sinclair

Biology Publications

Frost (Fst) is a candidate gene associated with the response to cold in Drosophila melanogaster because Fst mRNA accumulation increases during recovery from low temperature exposure. We investigated the contribution of Fst expression to chill-coma recovery time, acute cold tolerance and rapid cold hardening (RCH) in adult D. melanogaster by knocking down Fst mRNA expression using GAL4/UAS-mediated RNA interference. In this experiment, four UAS-Fst and one tubulin-GAL4 lines were used. We predicted that if Fst is essential for cold tolerance phenotypes, flies with low Fst mRNA levels should be less cold tolerant than flies with normal levels of cold-induced Fst …


Impact Of Treatment Response Metrics On Photodynamic Therapy Planning And Outcomes In A Three-Dimensional Model Of Ovarian Cancer, Sriram Anbil, Imran Rizvi, Jonathan P. Celli, Nermina Alagic, Brian W. Pogue, Tayyaba Hasan Sep 2013

Impact Of Treatment Response Metrics On Photodynamic Therapy Planning And Outcomes In A Three-Dimensional Model Of Ovarian Cancer, Sriram Anbil, Imran Rizvi, Jonathan P. Celli, Nermina Alagic, Brian W. Pogue, Tayyaba Hasan

Dartmouth Scholarship

Common methods to characterize treatment efficacy based on morphological imaging may misrepresent outcomes and exclude effective therapies. Using a three-dimensional model of ovarian cancer, two functional treatment response metrics are used to evaluate photodynamic therapy (PDT) efficacy: total volume, calculated from viable and nonviable cells, and live volume, calculated from viable cells. The utility of these volume-based metrics is corroborated using independent reporters of photodynamic activity: viability, a common fluorescence-based ratiometric analysis, and photosensitizer photobleaching, which is characterized by a loss of fluorescence due in part to the production of reactive species during PDT. Live volume correlated with both photobleaching …


Ultrasonic Incisions Produce Less Inflammatory Mediator Response During Early Healing Than Electrosurgical Incisions., Bindu Nanduri, Ken Pendarvis, Leslie A. Shack, Ranjit Kumar, Jeffrey W. Clymer, Donna L. Korvick, Shane C. Burgess Sep 2013

Ultrasonic Incisions Produce Less Inflammatory Mediator Response During Early Healing Than Electrosurgical Incisions., Bindu Nanduri, Ken Pendarvis, Leslie A. Shack, Ranjit Kumar, Jeffrey W. Clymer, Donna L. Korvick, Shane C. Burgess

CVM Publications

As the use of laparoscopic surgery has become more widespread in recent years, the need has increased for minimally-invasive surgical devices that effectively cut and coagulate tissue with reduced tissue trauma. Although electrosurgery (ES) has been used for many generations, newly-developed ultrasonic devices (HARMONIC? Blade, HB) have been shown at a macroscopic level to offer better coagulation with less thermally-induced tissue damage. We sought to understand the differences between ES and HB at a microscopic level by comparing mRNA transcript and protein responses at the 3-day timepoint to incisions made by the devices in subcutaneous fat tissue in a porcine …


Patterning In Placental 11-B Hydroxysteroid Dehydrogenase Methylation According To Prenatal Socioeconomic Adversity, Allison A. Appleton, David A. Armstrong, Corina Lesseur, Joyce Lee, James F. Padbury, Barry M. Lester Sep 2013

Patterning In Placental 11-B Hydroxysteroid Dehydrogenase Methylation According To Prenatal Socioeconomic Adversity, Allison A. Appleton, David A. Armstrong, Corina Lesseur, Joyce Lee, James F. Padbury, Barry M. Lester

Dartmouth Scholarship

Background:

Prenatal socioeconomic adversity as an intrauterine exposure is associated with a range of perinatal outcomes although the explanatory mechanisms are not well understood. The development of the fetus can be shaped by the intrauterine environment through alterations in the function of the placenta. In the placenta, the HSD11B2 gene encodes the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol thereby protecting the developing fetus from this exposure. This gene is regulated by DNA methylation, and this methylation and the expression it controls has been shown to be susceptible to a variety of stressors from …


Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell Sep 2013

Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell

Department of Cancer Biology Faculty Papers

The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein. Although it is known that cyclin D1 regulates estrogen receptor (ER)α transactivation using heterologous reporter systems, the in vivo biological significance of cyclin D1 to estrogen-dependent signaling, and the molecular mechanisms by which cyclin D1 is involved, are yet to be elucidated. Herein, genome-wide expression profiling conducted of 17β-estradiol-treated castrated virgin mice deleted of the Ccnd1 gene demonstrated that cyclin D1 determines estrogen-dependent gene expression for 88% of estrogen-responsive genes in vivo. In addition, expression profiling of 17β-estradiol-stimulated cyclin …


Stress-Inducible Phosphoprotein 1 Has Unique Cochaperone Activity During Development And Regulates Cellular Response To Ischemia Via The Prion Protein., Flavio H Beraldo, Iaci N Soares, Daniela F Goncalves, Jue Fan, Anu A Thomas, Tiago G Santos, Amro H Mohammad, Martin Roffé, Michele D Calder, Simona Nikolova, Glaucia N Hajj, Andre L Guimaraes, Andre R Massensini, Ian Welch, Dean H Betts, Robert Gros, Maria Drangova, Andrew J Watson, Robert Bartha, Vania F Prado, Vilma R Martins, Marco A M Prado Sep 2013

Stress-Inducible Phosphoprotein 1 Has Unique Cochaperone Activity During Development And Regulates Cellular Response To Ischemia Via The Prion Protein., Flavio H Beraldo, Iaci N Soares, Daniela F Goncalves, Jue Fan, Anu A Thomas, Tiago G Santos, Amro H Mohammad, Martin Roffé, Michele D Calder, Simona Nikolova, Glaucia N Hajj, Andre L Guimaraes, Andre R Massensini, Ian Welch, Dean H Betts, Robert Gros, Maria Drangova, Andrew J Watson, Robert Bartha, Vania F Prado, Vilma R Martins, Marco A M Prado

Obstetrics & Gynaecology Publications

Stress-inducible phosphoprotein 1 (STI1) is part of the chaperone machinery, but it also functions as an extracellular ligand for the prion protein. However, the physiological relevance of these STI1 activities in vivo is unknown. Here, we show that in the absence of embryonic STI1, several Hsp90 client proteins are decreased by 50%, although Hsp90 levels are unaffected. Mutant STI1 mice showed increased caspase-3 activation and 50% impairment in cellular proliferation. Moreover, placental disruption and lack of cellular viability were linked to embryonic death by E10.5 in STI1-mutant mice. Rescue of embryonic lethality in these mutants, by transgenic expression of the …


Endogenous Folate Accumulation In Oocytes And Preimplantation Embryos And Its Epigenetic Implications., Mellissa R W Mann, Andrew J Watson Sep 2013

Endogenous Folate Accumulation In Oocytes And Preimplantation Embryos And Its Epigenetic Implications., Mellissa R W Mann, Andrew J Watson

Obstetrics & Gynaecology Publications

No abstract provided.


Tricellulin Deficiency Affects Tight Junction Architecture And Cochlear Hair Cells, Gowri Nayak, Sue I. Lee, Rizwan Yousaf, Stephanie E. Edelmann, Claire Trincot, Christina M. Van Itallie, Ghanshyam P. Sinha, Maria Rafeeq, Sherri M. Jones, Inna A. Belyantseva, James M. Anderson, Andrew Forge, Gregory I. Frolenkov, Saima Riazuddin Aug 2013

Tricellulin Deficiency Affects Tight Junction Architecture And Cochlear Hair Cells, Gowri Nayak, Sue I. Lee, Rizwan Yousaf, Stephanie E. Edelmann, Claire Trincot, Christina M. Van Itallie, Ghanshyam P. Sinha, Maria Rafeeq, Sherri M. Jones, Inna A. Belyantseva, James M. Anderson, Andrew Forge, Gregory I. Frolenkov, Saima Riazuddin

Physiology Faculty Publications

The two compositionally distinct extracellular cochlear fluids, endolymph and perilymph, are separated by tight junctions that outline the scala media and reticular lamina. Mutations in TRIC (also known as MARVELD2), which encodes a tricellular tight junction protein known as tricellulin, lead to nonsyndromic hearing loss (DFNB49). We generated a knockin mouse that carries a mutation orthologous to the TRIC coding mutation linked to DFNB49 hearing loss in humans. Tricellulin was absent from the tricellular junctions in the inner ear epithelia of the mutant animals, which developed rapidly progressing hearing loss accompanied by loss of mechanosensory cochlear hair cells, while …


Differential Dna Methylation In Umbilical Cord Blood Of Infants Exposed To Low Levels Of Arsenic In Utero, Devin C. Koestler, Michele Avissar-Whiting, E. Andres Houseman, Margaret R. Karagas, Carmen J. Marsit Aug 2013

Differential Dna Methylation In Umbilical Cord Blood Of Infants Exposed To Low Levels Of Arsenic In Utero, Devin C. Koestler, Michele Avissar-Whiting, E. Andres Houseman, Margaret R. Karagas, Carmen J. Marsit

Dartmouth Scholarship

Background: There is increasing epidemiologic evidence that arsenic exposure in utero, even at low levels found throughout much of the world, is associated with adverse reproductive outcomes and may contribute to long-term health effects. Animal models, in vitro studies, and human cancer data suggest that arsenic may induce epigenetic alterations, specifically by altering patterns of DNA methylation.

Objectives: In this study we aimed to identify differences in DNA methylation in cord blood samples of infants with in utero, low-level arsenic exposure.

Methods: DNA methylation of cord-blood derived DNA from 134 infants involved in a prospective birth cohort in …


Online Healthy Lifestyle Support In The Perinatal Period: What Do Women Want And Do They Use It?, Lydia A. Hearn, Margaret R. Miller, Anna Fletcher Jul 2013

Online Healthy Lifestyle Support In The Perinatal Period: What Do Women Want And Do They Use It?, Lydia A. Hearn, Margaret R. Miller, Anna Fletcher

Research outputs 2013

Unhealthy weight gain and retention during pregnancy and postpartum is detrimental to mother and child. Although various barriers limit the capacity for perinatal health care providers (PHCPs) to offer healthy lifestyle counselling, they could guide women to appropriate online resources. This paper presents a project designed to provide online information to promote healthy lifestyles in the perinatal period. Focus groups or interviews were held with 116 perinatal women and 76 PHCPs to determine what online information perinatal women and PHCPs want, in what form, and how best it should be presented. The results indicated that women wanted smartphone applications (apps) …


Estradiol Regulation Of Nucleotidases In Female Reproductive Tract Epithelial Cells And Fibroblasts, Zheng Shen, John V. Fahey, Jack E. Bodwell, Marta Rodriguez-Garcia, Richard M. Rossoll, Sarah G. Crist, Mickey V. Patel, Charles R. Wira Jul 2013

Estradiol Regulation Of Nucleotidases In Female Reproductive Tract Epithelial Cells And Fibroblasts, Zheng Shen, John V. Fahey, Jack E. Bodwell, Marta Rodriguez-Garcia, Richard M. Rossoll, Sarah G. Crist, Mickey V. Patel, Charles R. Wira

Dartmouth Scholarship

The use of topical and oral adenosine derivatives in HIV prevention that need to be maintained in tissues and cells at effective levels to prevent transmission prompted us to ask whether estradiol could influence the regulation of catabolic nucleotidase enzymes in epithelial cells and fibroblasts from the upper and lower female reproductive tract (FRT) as these might affect cellular TFV-DP levels. Epithelial cells and fibroblasts were isolated from endometrium (EM), endocervix (CX) and ectocervix (ECX) tissues from hysterectomy patients, grown to confluence and treated with or without estradiol prior to RNA isolation. The expression of nucleotidase (NT) genes was measurable …


An Integrated Clinico-Metabolomic Model Improves Prediction Of Death In Sepsis., Raymond J. Langley, Ephraim L. Tsalik, Jennifer C. Van Velkinburgh, Seth W. Glickman, Brandon J. Rice, Chunping Wang, Bo Chen, Lawrence Carin, Arturo Suarez, Robert P. Mohney, Debra H. Freeman, Mu Wang, Jinsam You, Jacob Wulff, J Will Thompson, M Arthur Moseley, Stephanie Reisinger, Brian T. Edmonds, Brian Grinnell, David R. Nelson, Darrell L. Dinwiddie, Neil A. Miller, Carol J. Saunders, Sarah Soden, Angela J. Rogers, Lee Gazourian, Laura E. Fredenburgh, Anthony F. Massaro, Rebecca M. Baron, Augustine M K Choi, G Ralph Corey, Geoffrey S. Ginsburg, Charles B. Cairns, Ronny M. Otero, Vance G. Fowler, Emanuel P. Rivers, Christopher W. Woods, Stephen F. Kingsmore Jul 2013

An Integrated Clinico-Metabolomic Model Improves Prediction Of Death In Sepsis., Raymond J. Langley, Ephraim L. Tsalik, Jennifer C. Van Velkinburgh, Seth W. Glickman, Brandon J. Rice, Chunping Wang, Bo Chen, Lawrence Carin, Arturo Suarez, Robert P. Mohney, Debra H. Freeman, Mu Wang, Jinsam You, Jacob Wulff, J Will Thompson, M Arthur Moseley, Stephanie Reisinger, Brian T. Edmonds, Brian Grinnell, David R. Nelson, Darrell L. Dinwiddie, Neil A. Miller, Carol J. Saunders, Sarah Soden, Angela J. Rogers, Lee Gazourian, Laura E. Fredenburgh, Anthony F. Massaro, Rebecca M. Baron, Augustine M K Choi, G Ralph Corey, Geoffrey S. Ginsburg, Charles B. Cairns, Ronny M. Otero, Vance G. Fowler, Emanuel P. Rivers, Christopher W. Woods, Stephen F. Kingsmore

Manuscripts, Articles, Book Chapters and Other Papers

Sepsis is a common cause of death, but outcomes in individual patients are difficult to predict. Elucidating the molecular processes that differ between sepsis patients who survive and those who die may permit more appropriate treatments to be deployed. We examined the clinical features and the plasma metabolome and proteome of patients with and without community-acquired sepsis, upon their arrival at hospital emergency departments and 24 hours later. The metabolomes and proteomes of patients at hospital admittance who would ultimately die differed markedly from those of patients who would survive. The different profiles of proteins and metabolites clustered into the …


Pilot Study Assessment Of Dynamic Vascular Changes In Breast Cancer With Near-Infrared Tomography From Prospectively Targeted Manipulations Of Inspired End-Tidal Partial Pressure Of Oxygen And Carbon Dioxide, Shudong Jiang, Brian W. Pogue, Kelly E. Michaelsen, Michael Jermyn, Michael A. Mastanduno, Tracy E. Frazee, Peter A. Kaufman, Keith D. Paulsen Jul 2013

Pilot Study Assessment Of Dynamic Vascular Changes In Breast Cancer With Near-Infrared Tomography From Prospectively Targeted Manipulations Of Inspired End-Tidal Partial Pressure Of Oxygen And Carbon Dioxide, Shudong Jiang, Brian W. Pogue, Kelly E. Michaelsen, Michael Jermyn, Michael A. Mastanduno, Tracy E. Frazee, Peter A. Kaufman, Keith D. Paulsen

Dartmouth Scholarship

The dynamic vascular changes in the breast resulting from manipulation of both inspired end-tidal partial pressure of oxygen and carbon dioxide were imaged using a 30 s per frame frequency-domain near-infrared spectral (NIRS) tomography system. By analyzing the images from five subjects with asymptomatic mammography under different inspired gas stimulation sequences, the mixture that maximized tissue vascular and oxygenation changes was established. These results indicate maximum changes in deoxy-hemoglobin, oxygen saturation, and total hemoglobin of 21, 9, and 3%, respectively. Using this inspired gas manipulation sequence, an individual case study of a subject with locally advanced breast cancer undergoing neoadjuvant …