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Intracranial Injection Of Aav Expressing Nep But Not Ide Reduces Amyloid Pathology In App+Ps1 Transgenic Mice, Nikisha Carty, Kevin R. Nash, Milene Brownlow, Dana Cruite, Donna M. Wilcock, Maj-Linda B. Selenica, Daniel C. Lee, Marcia N. Gordon, Dave Morgan Mar 2013

Intracranial Injection Of Aav Expressing Nep But Not Ide Reduces Amyloid Pathology In App+Ps1 Transgenic Mice, Nikisha Carty, Kevin R. Nash, Milene Brownlow, Dana Cruite, Donna M. Wilcock, Maj-Linda B. Selenica, Daniel C. Lee, Marcia N. Gordon, Dave Morgan

Sanders-Brown Center on Aging Faculty Publications

The accumulation of β-amyloid peptides in the brain has been recognized as an essential factor in Alzheimer's disease pathology. Several proteases, including Neprilysin (NEP), endothelin converting enzyme (ECE), and insulin degrading enzyme (IDE), have been shown to cleave β-amyloid peptides (Aβ). We have previously reported reductions in amyloid in APP+PS1 mice with increased expression of ECE. In this study we compared the vector-induced increased expression of NEP and IDE. We used recombinant adeno-associated viral vectors expressing either native forms of NEP (NEP-n) or IDE (IDE-n), or engineered secreted forms of NEP (NEP-s) or IDE (IDE-s). In a six-week study, immunohistochemistry …


Effectiveness Of A Motivational Interviewing Intervention On Weight Loss, Physical Activity And Cardiovascular Disease Risk Factors: A Randomised Controlled Trial With A 12-Month Post-Intervention Follow-Up., Sarah J. Hardcastle, Adrian H. Taylor, Martin P. Bailey, Robert A. Harley, Martin S. Hagger Mar 2013

Effectiveness Of A Motivational Interviewing Intervention On Weight Loss, Physical Activity And Cardiovascular Disease Risk Factors: A Randomised Controlled Trial With A 12-Month Post-Intervention Follow-Up., Sarah J. Hardcastle, Adrian H. Taylor, Martin P. Bailey, Robert A. Harley, Martin S. Hagger

Peninsula Medical School

BACKGROUND: Intensive diet and physical activity interventions have been found to reduce cardiovascular disease (CVD) risk, but are resource intensive. The American Heart Association recently recommended motivational interviewing (MI) as an effective approach for low-intensity interventions to promote health-related outcomes such as weight loss. However, there is limited research evaluating the long-term effectiveness of MI-based interventions on health-related outcomes associated with CVD risk. The current research evaluated the effectiveness of a six-month low-intensity MI intervention in a UK primary-care setting in maintaining reductions in CVD risk factors at12 months post-intervention. METHODS: Primary-care patients were randomised to an intervention group that …


Using Online Adverts To Increase The Uptake Of Cervical Screening Amongst "Real Eastenders": An Opportunistic Controlled Trial., Ray B. Jones, Mar Soler-Lopez, Daniel Zahra, Judith Shankleman, Esther Trenchard-Mabere Mar 2013

Using Online Adverts To Increase The Uptake Of Cervical Screening Amongst "Real Eastenders": An Opportunistic Controlled Trial., Ray B. Jones, Mar Soler-Lopez, Daniel Zahra, Judith Shankleman, Esther Trenchard-Mabere

School of Nursing and Midwifery

BACKGROUND: Cervical screening uptake has increased as a result of occurrences of cervical cancer in TV 'soap operas' and in real life celebrities such as Jade Goody. Media analysis at the time of Jade Goody's death suggested the NHS did not take sufficient advantage of this opportunity to improve cervical screening rates. Google AdWords has been used to recruit and raise awareness of health but we were not aware of its use to supplement media events. METHODS: This was an opportunistic service evaluation to accompany a cervical cancer storyline in Eastenders (a TV 'soap opera'). We ran an AdWords campaign …


Tgf-Beta Suppresses Vegfa-Mediated Angiogenesis In Colon Cancer Metastasis., Liying Geng, Anathbandhu Chaudhuri, G. Talmon, James L. Wisecarver, J. Wang Mar 2013

Tgf-Beta Suppresses Vegfa-Mediated Angiogenesis In Colon Cancer Metastasis., Liying Geng, Anathbandhu Chaudhuri, G. Talmon, James L. Wisecarver, J. Wang

Journal Articles: Eppley Institute

The FET cell line, derived from an early stage colon carcinoma, is non-tumorigenic in athymic nude mice. Engineered FET cells that express TGF-α (FETα) display constitutively active EGFR/ErbB signaling. These cells readily formed xenograft tumors in athymic nude mice. Importantly, FETα cells retained their response to TGF-beta-mediated growth inhibition, and, like the parental FET cells, expression of a dominant negative TGF-beta type II receptor (DNRII) in FETα cells (FETα/DNRII) abrogated responsiveness to TGF-beta-induced growth inhibition and apoptosis under stress conditions in vitro and increased metastatic potential in an orthotopic model in vivo, which indicates metastasis suppressor activity of TGF-beta signaling …


Marked Improvement Of Cytotoxic Effects Induced By Docetaxel On Highly Metastatic And Androgen-Independent Prostate Cancer Cells By Downregulating Macrophage Inhibitory Cytokine-1., M Mimeault, Sonny L. Johansson, Surinder K. Batra Mar 2013

Marked Improvement Of Cytotoxic Effects Induced By Docetaxel On Highly Metastatic And Androgen-Independent Prostate Cancer Cells By Downregulating Macrophage Inhibitory Cytokine-1., M Mimeault, Sonny L. Johansson, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Overexpression of macrophage inhibitory cytokine-1 (MIC-1) frequently occurs during the progression of prostate cancer (PC) to androgen-independent (AI) and metastatic disease states and is associated with a poor outcome of patients.

METHODS: The gain- and loss-of-function analyses of MIC-1 were performed to establish its implications for aggressive and chemoresistant phenotypes of metastatic and AI PC cells and the benefit of its downregulation for reversing docetaxel resistance.

RESULTS: The results have indicated that an enhanced level of secreted MIC-1 protein in PC3 cells is associated with their acquisition of epithelial-mesenchymal transition features and higher invasive capacity and docetaxel resistance. Importantly, …


Effectiveness Of A Motivational Interviewing Intervention On Weight Loss, Physical Activity And Cardiovascular Disease Risk Factors: A Randomised Controlled Trial With A 12-Month Post-Intervention Follow-Up., Sarah J. Hardcastle, Adrian H. Taylor, Martin P. Bailey, Robert A. Harley, Martin S. Hagger Mar 2013

Effectiveness Of A Motivational Interviewing Intervention On Weight Loss, Physical Activity And Cardiovascular Disease Risk Factors: A Randomised Controlled Trial With A 12-Month Post-Intervention Follow-Up., Sarah J. Hardcastle, Adrian H. Taylor, Martin P. Bailey, Robert A. Harley, Martin S. Hagger

Peninsula Medical School

BACKGROUND: Intensive diet and physical activity interventions have been found to reduce cardiovascular disease (CVD) risk, but are resource intensive. The American Heart Association recently recommended motivational interviewing (MI) as an effective approach for low-intensity interventions to promote health-related outcomes such as weight loss. However, there is limited research evaluating the long-term effectiveness of MI-based interventions on health-related outcomes associated with CVD risk. The current research evaluated the effectiveness of a six-month low-intensity MI intervention in a UK primary-care setting in maintaining reductions in CVD risk factors at12 months post-intervention. METHODS: Primary-care patients were randomised to an intervention group that …


Loss Of Fbp1 By Snail-Mediated Repression Provides Metabolic Advantages In Basal-Like Breast Cancer, Chenfang Dong, Tingting Yuan, Yadi Wu, Yifan Wang, Teresa W-M Fan, Sumitra Miriyala, Yiwei Lin, Jun Yao, Jian Shi, Tiebang Kang, Pawel Lorkiewicz, Daret St. Clair, Mien-Chie Hung, B. Mark Evers, Binhua P. Zhou Mar 2013

Loss Of Fbp1 By Snail-Mediated Repression Provides Metabolic Advantages In Basal-Like Breast Cancer, Chenfang Dong, Tingting Yuan, Yadi Wu, Yifan Wang, Teresa W-M Fan, Sumitra Miriyala, Yiwei Lin, Jun Yao, Jian Shi, Tiebang Kang, Pawel Lorkiewicz, Daret St. Clair, Mien-Chie Hung, B. Mark Evers, Binhua P. Zhou

Toxicology and Cancer Biology Faculty Publications

The epithelial-mesenchymal transition (EMT) enhances cancer invasiveness and confers tumor cells with cancer stem cell (CSC)-like characteristics. We show that the Snail-G9a-Dnmt1 complex, which is critical for E-cadherin promoter silencing, is also required for the promoter methylation of fructose-1,6-biphosphatase (FBP1) in basal-like breast cancer (BLBC). Loss of FBP1 induces glycolysis and results in increased glucose uptake, macromolecule biosynthesis, formation of tetrameric PKM2, and maintenance of ATP production under hypoxia. Loss of FBP1 also inhibits oxygen consumption and reactive oxygen species production by suppressing mitochondrial complex I activity; this metabolic reprogramming results in an increased CSC-like property and tumorigenicity by enhancing …


Experimental And Natural Warming Elevates Mercury Concentrations In Estuarine Fish, Jennifer A. Dijkstra, Kate L. Buckman, Darren Ward, David W. Evans, Michele Dionne, Celia Y. Chen Mar 2013

Experimental And Natural Warming Elevates Mercury Concentrations In Estuarine Fish, Jennifer A. Dijkstra, Kate L. Buckman, Darren Ward, David W. Evans, Michele Dionne, Celia Y. Chen

Dartmouth Scholarship

Marine food webs are the most important link between the global contaminant, methylmercury (MeHg), and human exposure through consumption of seafood. Warming temperatures may increase human exposure to MeHg, a potent neurotoxin, by increasing MeHg production as well as bioaccumulation and trophic transfer through marine food webs. Studies of the effects of temperature on MeHg bioaccumulation are rare and no study has specifically related temperature to MeHg fate by linking laboratory experiments with natural field manipulations in coastal ecosystems. We performed laboratory and field experiments on MeHg accumulation under varying temperature regimes using the killifish, Fundulus heteroclitus. Temperature treatments …


Feasibility Of Tomotherapy-Based Image-Guided Radiotherapy To Reduce Aspiration Risk In Patients With Non-Laryngeal And Non-Pharyngeal Head And Neck Cancer, Nam P. Nguyen, Lexie Smith-Raymond, Vincent Vinh-Hung, Paul Vos, Rick Davis, Anand Desai, Thomas Sroka Mar 2013

Feasibility Of Tomotherapy-Based Image-Guided Radiotherapy To Reduce Aspiration Risk In Patients With Non-Laryngeal And Non-Pharyngeal Head And Neck Cancer, Nam P. Nguyen, Lexie Smith-Raymond, Vincent Vinh-Hung, Paul Vos, Rick Davis, Anand Desai, Thomas Sroka

Dartmouth Scholarship

Purpose: The study aims to assess the feasibility of Tomotherapy-based image-guided radiotherapy (IGRT) to reduce the aspiration risk in patients with non-laryngeal and non-hypopharyngeal cancer. A retrospective review of 48 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers was conducted. All patients had a modified barium swallow (MBS) prior to treatment, which was repeated one month following radiotherapy. Mean middle and inferior pharyngeal dose was recorded and correlated with the MBS results to determine aspiration risk.


The Walking Index For Spinal Cord Injury (Wisci/Wisci Ii): Nature, Metric Properties, Use And Misuse., J. F. Ditunno, Jr, P. L. Ditunno, G. Scivoletto, M. Patrick, M. Dijkers, H. Barbeau, A. S. Burns, R. J. Marino, M. Schmidt-Read Mar 2013

The Walking Index For Spinal Cord Injury (Wisci/Wisci Ii): Nature, Metric Properties, Use And Misuse., J. F. Ditunno, Jr, P. L. Ditunno, G. Scivoletto, M. Patrick, M. Dijkers, H. Barbeau, A. S. Burns, R. J. Marino, M. Schmidt-Read

Department of Rehabilitation Medicine Faculty Papers

STUDY DESIGN: Literature review.

OBJECTIVE: To critically review all publications/internet sites that have described/used the Walking Index for Spinal Cord Injury (WISCI II), as a measure of impairment of walking function after spinal cord injury (SCI), in order to identify its psychometric properties, clarify its nature, specify misuse and incorporate the findings in an updated guide.

METHOD: A systematic literature search was done of Ovid MEDLINE, CINAHL, PsychINFO, Cochrane Central Register of Controlled Trials, Scopus and electronic sites using key words: WISCI or WISCI II, SCI, paraplegia/ tetraplegia/ quadriplegia and ambulation/gait/walking. Among 1235 citations retrieved, 154 relevant articles/sites were identified, …


Detection And Quantification Of Methylation In Dna Using Solid-State Nanopores., Jiwook Shim, Gwendolyn I Humphreys, Bala Murali Venkatesan, Jan Marie Munz, Xueqing Zou, Chaitanya Sathe, Klaus Schulten, Farhad Kosari, Ann M Nardulli, George Vasmatzis, Rashid Bashir Mar 2013

Detection And Quantification Of Methylation In Dna Using Solid-State Nanopores., Jiwook Shim, Gwendolyn I Humphreys, Bala Murali Venkatesan, Jan Marie Munz, Xueqing Zou, Chaitanya Sathe, Klaus Schulten, Farhad Kosari, Ann M Nardulli, George Vasmatzis, Rashid Bashir

College of Science & Mathematics Departmental Research

Epigenetic modifications in eukaryotic genomes occur primarily in the form of 5-methylcytosine (5 mC). These modifications are heavily involved in transcriptional repression, gene regulation, development and the progression of diseases including cancer. We report a new single-molecule assay for the detection of DNA methylation using solid-state nanopores. Methylation is detected by selectively labeling methylation sites with MBD1 (MBD-1x) proteins, the complex inducing a 3 fold increase in ionic blockage current relative to unmethylated DNA. Furthermore, the discrimination of methylated and unmethylated DNA is demonstrated in the presence of only a single bound protein, thereby giving a resolution of a single …


Chronic Obstructive Pulmonary Disease: More Imaging, More Phenotyping...Better Care?, Damien Pike, Grace Parraga Mar 2013

Chronic Obstructive Pulmonary Disease: More Imaging, More Phenotyping...Better Care?, Damien Pike, Grace Parraga

Medical Biophysics Publications

No abstract provided.


John Chalmers Dacosta (1863-1933): Restoration Of The Old Operating Table., Madalyn G. Peters, Md, Adam C. Berger, Md, Gordon Schwartz, Md, Mba, Facs, Charles J. Yeo, Md, Scott W. Cowan, Md Mar 2013

John Chalmers Dacosta (1863-1933): Restoration Of The Old Operating Table., Madalyn G. Peters, Md, Adam C. Berger, Md, Gordon Schwartz, Md, Mba, Facs, Charles J. Yeo, Md, Scott W. Cowan, Md

Department of Surgery Gibbon Society Historical Profiles

John Chalmers DaCosta was an influential chairman and the first Samuel D. Gross Professor of Surgery at Jefferson Medical College in Philadelphia. He was well known throughout the field as a skilled surgeon, passionate speaker, and exceptional writer. In addition to countless accomplishments during his career, DaCosta was deeply dedicated to the preservation and commemoration of surgical history. This ideology was exemplified when he set out on a mission to recover the old wooden operating table used by many of his iconic mentors including Samuel D. Gross, Joseph Pancoast, and William W. Keen. This table was originally used for surgical …


The Adipose Tissue Production Of Adiponectin Is Increased In End-Stage Renal Disease., Maria P Martinez Cantarin, Scott A Waldman, Cataldo Doria, Adam M Frank, Warren R Maley, Carlo B Ramirez, Scott W Keith, Bonita Falkner Mar 2013

The Adipose Tissue Production Of Adiponectin Is Increased In End-Stage Renal Disease., Maria P Martinez Cantarin, Scott A Waldman, Cataldo Doria, Adam M Frank, Warren R Maley, Carlo B Ramirez, Scott W Keith, Bonita Falkner

Department of Medicine Faculty Papers

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis …


Awareness And Beliefs Regarding Intimate Partner Violence Among First-Year Dental Students, Rhonda J. Everett, Karl Kingsley, Christina A. Demopoulos, Edward E. Herschaft, Christine Lamun, Sheniz Moonie, Timothy J. Bungum, Michelle Chino Mar 2013

Awareness And Beliefs Regarding Intimate Partner Violence Among First-Year Dental Students, Rhonda J. Everett, Karl Kingsley, Christina A. Demopoulos, Edward E. Herschaft, Christine Lamun, Sheniz Moonie, Timothy J. Bungum, Michelle Chino

Environmental & Global Health Faculty Research

Intimate partner violence (IPV) may affect one to four million individuals per year in the United States, with women accounting for the majority of both reported and unreported cases. Dental professionals are in a unique position to identify many types of IPV because injuries to the head and neck may be indicators or predictors of IPV abuse. Fewer than half of dental programs surveyed have reported having IPV-specific curricula, and most dental students surveyed have reported having little experience or training to recognize IPV. Based on this information, this pilot study sought to assess the awareness and beliefs regarding IPV …


Kerlan-Jobe Orthopaedic Clinic Overhead Athlete Scores In Asymptomatic Professional Baseball Pitchers., Matthew J Kraeutler, Michael G Ciccotti, Christopher C Dodson, Robert W Frederick, Brian Cammarota, Steven B. Cohen Mar 2013

Kerlan-Jobe Orthopaedic Clinic Overhead Athlete Scores In Asymptomatic Professional Baseball Pitchers., Matthew J Kraeutler, Michael G Ciccotti, Christopher C Dodson, Robert W Frederick, Brian Cammarota, Steven B. Cohen

Rothman Institute Papers

BACKGROUND: The Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow score is a subjective questionnaire that has been validated and been shown to be more specific in overhead athletes than the American Shoulder and Elbow Surgeons scale. The purpose of this study was to determine a mean KJOC score and reasonable range of KJOC scores within which a healthy asymptomatic professional baseball pitcher will fall. It was hypothesized that healthy professional baseball pitchers would have very high KJOC scores.

MATERIALS AND METHODS: KJOC questionnaires were given to all healthy pitchers before the start of the season at all levels in 1 …


Single-Cell Measurements Of Ige-Mediated Fcεri Signaling Using An Integrated Microfluidic Platform, Yanli Liu, Dipak Barua, Peng Liu, Bridget S. Wilson, Janet M. Oliver, William S. Hlavacek, Anup K. Singh Mar 2013

Single-Cell Measurements Of Ige-Mediated Fcεri Signaling Using An Integrated Microfluidic Platform, Yanli Liu, Dipak Barua, Peng Liu, Bridget S. Wilson, Janet M. Oliver, William S. Hlavacek, Anup K. Singh

Chemical and Biochemical Engineering Faculty Research & Creative Works

Heterogeneity in responses of cells to a stimulus, such as a pathogen or allergen, can potentially play an important role in deciding the fate of the responding cell population and the overall systemic response. Measuring heterogeneous responses requires tools capable of interrogating individual cells. Cell signaling studies commonly do not have single-cell resolution because of the limitations of techniques used such as Westerns, ELISAs, mass spectrometry, and DNA microarrays. Microfluidics devices are increasingly being used to overcome these limitations. Here, we report on a microfluidic platform for cell signaling analysis that combines two orthogonal single-cell measurement technologies: on-chip flow cytometry …


Melanopsin, Photosensitive Ganglion Cells, And Seasonal Affective Disorder., Kathryn A Roecklein, Patricia M Wong, Megan A Miller, Shannon D Donofry, Marissa L Kamarck, George C Brainard Mar 2013

Melanopsin, Photosensitive Ganglion Cells, And Seasonal Affective Disorder., Kathryn A Roecklein, Patricia M Wong, Megan A Miller, Shannon D Donofry, Marissa L Kamarck, George C Brainard

Department of Neurology Faculty Papers

In two recent reports, melanopsin gene variations were associated with seasonal affective disorder (SAD), and in changes in the timing of sleep and activity in healthy individuals. New studies have deepened our understanding of the retinohypothalamic tract, which translates environmental light received by the retina into neural signals sent to a set of nonvisual nuclei in the brain that are responsible for functions other than sight including circadian, neuroendocrine and neurobehavioral regulation. Because this pathway mediates seasonal changes in physiology, behavior, and mood, individual variations in the pathway may explain why approximately 1-2% of the North American population develops mood …


Ccl3 And Cxcl12 Production In Vitro By Dental Pulp Fibroblasts From Permanent And Deciduous Teeth Stimulated By Porphyromonas Gingivalis Lps, Carla Renata Sipert, Ana Carolina Morandini, Karin Cristina Da Silva Modena, Thiago José Dionísio, Maria Aparecida Andrade Moreira Machado, Sandra Helena Penha Oliveira, Ana Paula Campanelli, Carlos Ferreira Santos Mar 2013

Ccl3 And Cxcl12 Production In Vitro By Dental Pulp Fibroblasts From Permanent And Deciduous Teeth Stimulated By Porphyromonas Gingivalis Lps, Carla Renata Sipert, Ana Carolina Morandini, Karin Cristina Da Silva Modena, Thiago José Dionísio, Maria Aparecida Andrade Moreira Machado, Sandra Helena Penha Oliveira, Ana Paula Campanelli, Carlos Ferreira Santos

All Dugoni School of Dentistry Faculty Articles

OBJECTIVE: The aim of this study was to compare the production of the chemokines CCL3 and CXCL12 by cultured dental pulp fibroblasts from permanent (PDPF) and deciduous (DDPF) teeth under stimulation by Porphyromonas gingivalis LPS (PgLPS).

MATERIAL AND METHODS: Primary culture of fibroblasts from permanent (n=3) and deciduous (n=2) teeth were established using an explant technique. After the fourth passage, fibroblasts were stimulated by increasing concentrations of PgLPS (0-10 µg/mL) at 1, 6 and 24 h. The cells were tested for viability through MTT assay, and production of the chemokines CCL3 and CXCL12 was determined through ELISA. Comparisons among samples …


Preparation And Technical Considerations For Percutaneous Cannulation For Veno-Arterial Extracorporeal Membrane Oxygenation., Kathleen Lamb, Hitoshi Hirose, Nicholas C. Cavarocchi Mar 2013

Preparation And Technical Considerations For Percutaneous Cannulation For Veno-Arterial Extracorporeal Membrane Oxygenation., Kathleen Lamb, Hitoshi Hirose, Nicholas C. Cavarocchi

Department of Surgery Faculty Papers

BACKGROUND: The most frequent limb complications from peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are limb ischemia and localized bleeding. To minimize these risks, perfusion of the distal limb with peripheral percutaneous cannulation was done.

TECHNIQUE: Percutaneous cannulation with a distal perfusion port was performed in all patients. During the VA-ECMO, distal limb perfusion was monitored using near-infrared spectroscopy to assess tissue oxygenation. At the decannulation, patch angioplasty was performed to prevent the development of narrowing of the artery at the cannulation site.

CONCLUSIONS: Using our standard technique, we have not experienced any limb loss related to ischemia or bleeding.


Simultaneous Measurement Of Deep Tissue Blood Flow And Oxygenation Using Noncontact Diffuse Correlation Spectroscopy Flow-Oximeter, Ting Li, Yu Lin, Yu Shang, Lian He, Chong Huang, Margaret M. Szabunio, Guoqiang Yu Feb 2013

Simultaneous Measurement Of Deep Tissue Blood Flow And Oxygenation Using Noncontact Diffuse Correlation Spectroscopy Flow-Oximeter, Ting Li, Yu Lin, Yu Shang, Lian He, Chong Huang, Margaret M. Szabunio, Guoqiang Yu

Biomedical Engineering Faculty Publications

We report a novel noncontact diffuse correlation spectroscopy flow-oximeter for simultaneous quantification of relative changes in tissue blood flow (rBF) and oxygenation (Δ[oxygenation]). The noncontact probe was compared against a contact probe in tissue-like phantoms and forearm muscles (n = 10), and the dynamic trends in both rBF and Δ[oxygenation] were found to be highly correlated. However, the magnitudes of Δ[oxygenation] measured by the two probes were significantly different. Monte Carlo simulations and phantom experiments revealed that the arm curvature resulted in a significant underestimation (~-20%) for the noncontact measurements in Δ[ …


Mir203 Mediates Subversion Of Stem Cell Properties During Mammary Epithelial Differentiation Via Repression Of Δnp63Α And Promotes Mesenchymal-To-Epithelial Transition, A J. Decastro, K A. Dunphy, J Hutchinson, A L. Balboni, P Cherukuri, D J. Jerry, J Direnzo Feb 2013

Mir203 Mediates Subversion Of Stem Cell Properties During Mammary Epithelial Differentiation Via Repression Of Δnp63Α And Promotes Mesenchymal-To-Epithelial Transition, A J. Decastro, K A. Dunphy, J Hutchinson, A L. Balboni, P Cherukuri, D J. Jerry, J Direnzo

Dartmouth Scholarship

During reproductive life, the mammary epithelium undergoes consecutive cycles of proliferation, differentiation and apoptosis. Doing so relies on the retained proliferative capacity, prolonged lifespan and developmental potency of mammary stem cells (MaSCs). ΔNp63α, the predominant TP63 isoform in mammary epithelia, is robustly expressed in MaSCs and is required for preservation of self-renewing capacity in diverse epithelial structures. However, the mechanism(s) underlying subversion of this activity during forfeiture of self-renewing capacity are poorly understood. MicroRNAs (miRNAs) govern critical cellular functions including stem cell maintenance, development, cell cycle regulation and differentiation by disrupting translation of target mRNAs. Data presented here …


An Acacb Variant Implicated In Diabetic Nephropathy Associates With Body Mass Index And Gene Expression In Obese Subjects, Lijun Ma, Mariana Murea, James A. Snipes, Alejandra Marinelarena, Jacqueline Krüger, Pamela J. Hicks, Kurt A. Langberg, Meredith A. Bostrom, Jessica N. Cooke, Daisuke Suzuki, Tetsuya Babazono, Takashi Uzu, Sydney C. W. Tang, Ashis K. Mondal, Neeraj K. Sharma, Sayuko Kobes, Peter A. Antinozzi, Matthew Davis, Swapan K. Das, Neda Rasouli, Philip A. Kern, Nathan J. Shores, Lawrence L. Rudel, Matthias Blüher, Michael Stumvoll, Donald W. Bowden, Shiro Maeda, John S. Parks, Peter Kovacs, Robert L. Hanson, Leslie J. Baier, Steven C. Elbein, Barry I. Freedman Feb 2013

An Acacb Variant Implicated In Diabetic Nephropathy Associates With Body Mass Index And Gene Expression In Obese Subjects, Lijun Ma, Mariana Murea, James A. Snipes, Alejandra Marinelarena, Jacqueline Krüger, Pamela J. Hicks, Kurt A. Langberg, Meredith A. Bostrom, Jessica N. Cooke, Daisuke Suzuki, Tetsuya Babazono, Takashi Uzu, Sydney C. W. Tang, Ashis K. Mondal, Neeraj K. Sharma, Sayuko Kobes, Peter A. Antinozzi, Matthew Davis, Swapan K. Das, Neda Rasouli, Philip A. Kern, Nathan J. Shores, Lawrence L. Rudel, Matthias Blüher, Michael Stumvoll, Donald W. Bowden, Shiro Maeda, John S. Parks, Peter Kovacs, Robert L. Hanson, Leslie J. Baier, Steven C. Elbein, Barry I. Freedman

Internal Medicine Faculty Publications

Acetyl coenzyme A carboxylase B gene (ACACB) single nucleotide polymorphism (SNP) rs2268388 is reproducibly associated with type 2 diabetes (T2DM)-associated nephropathy (DN). ACACB knock-out mice are also protected from obesity. This study assessed relationships between rs2268388, body mass index (BMI) and gene expression in multiple populations, with and without T2DM. Among subjects without T2DM, rs2268388 DN risk allele (T) associated with higher BMI in Pima Indian children (n = 2021; p-additive = 0.029) and African Americans (AAs) (n = 177; p-additive = 0.05), with a trend in European Americans (EAs) (n = 512; p-additive = 0.09), but not Germans (n …


Molecular Basis Of Differential Sensitivity Of Myeloma Cells To Clinically Relevant Bolus Treatment With Bortezomib, Tamer B. Shabaneh, Sondra L. Downey, Ayrton L. Goddard, Michael Screen, Marcella M. Lucas, Alan Eastman, Alexei F. Kisselev Feb 2013

Molecular Basis Of Differential Sensitivity Of Myeloma Cells To Clinically Relevant Bolus Treatment With Bortezomib, Tamer B. Shabaneh, Sondra L. Downey, Ayrton L. Goddard, Michael Screen, Marcella M. Lucas, Alan Eastman, Alexei F. Kisselev

Dartmouth Scholarship

The proteasome inhibitor bortezomib (Velcade) is prescribed for the treatment of multiple myeloma. Clinically achievable concentrations of bortezomib cause less than 85% inhibition of the chymotrypsin-like activity of the proteasome, but little attention has been paid as to whether in vitro studies are representative of this level of inhibition. Patients receive bortezomib as an intravenous or subcutaneous bolus injection, resulting in maximum proteasome inhibition within one hour followed by a gradual recovery of activity. In contrast, most in vitro studies use continuous treatment so that activity never recovers. Replacing continuous treatment with 1 h-pulse treatment increases differences in sensitivity in …


Observational Intensity Bias Associated With Illness Adjustment: Cross Sectional Analysis Of Insurance Claims, J. E. Wennberg, D. O. Staiger, S. M. Sharp, D. J. Gottlieb Feb 2013

Observational Intensity Bias Associated With Illness Adjustment: Cross Sectional Analysis Of Insurance Claims, J. E. Wennberg, D. O. Staiger, S. M. Sharp, D. J. Gottlieb

Dartmouth Scholarship

Objective: To determine the bias associated with frequency of visits by physicians in adjusting for illness, using diagnoses recorded in administrative databases.

Setting: Claims data from the US Medicare program for services provided in 2007 among 306 US hospital referral regions.

Design: Cross sectional analysis. Participants 20% sample of fee for service Medicare beneficiaries residing in the United States in 2007 (n=5 153 877).


Implicitly Priming The Social Brain: Failure To Find Neural Effects, Katherine E. Powers, Todd F. Heatherton Feb 2013

Implicitly Priming The Social Brain: Failure To Find Neural Effects, Katherine E. Powers, Todd F. Heatherton

Dartmouth Scholarship

Humans have a fundamental need for social relationships. Rejection from social groups is especially detrimental, rendering the ability to detect threats to social relationships and respond in adaptive ways critical. Indeed, previous research has shown that experiencing social rejection alters the processing of subsequent social cues in a variety of socially affiliative and avoidant ways. Because social perception and cognition occurs spontaneously and automatically, detecting threats to social relationships may occur without conscious awareness or control. Here, we investigated the automaticity of social threat detection by examining how implicit primes affect neural responses to social stimuli. However, despite using a …


Evolutionarily Novel Functional Networks In The Human Brain?, Dante Mantini, Maurizio Corbetta, Gian Luca Romani, Guy A. Orban, Wim Vanduffel Feb 2013

Evolutionarily Novel Functional Networks In The Human Brain?, Dante Mantini, Maurizio Corbetta, Gian Luca Romani, Guy A. Orban, Wim Vanduffel

Open Access Publications

Primate evolution has been accompanied by complex reorganizations in brain anatomy and function. Little is known, however, about the relationship between anatomical and functional changes induced through primate evolution. Using functional magnetic resonance imaging, we assessed spatial and temporal correspondences of cortical networks in humans and monkeys. We provided evidence for topologically and functionally correspondent networks in sensory-motor and attention regions. More specifically, we revealed a possible monkey equivalent of the human ventral attention network. For other human networks, such as the language and the default-mode networks, we detected topological correspondent networks in the monkey, but with different functional signatures. …


The Disruption Of Celf6, A Gene Identified By Translational Profiling Of Serotonergic Neurons, Results In Autism-Related Behaviors, Joseph D. Dougherty, Susan E. Maloney, David F. Wozniak, Michael A. Rieger, Lisa Sonnenblick, Giovanni Coppola, Nathaniel G. Mahieu, Juliet Zhang, Jinlu Cai, Gary J. Patti, Brett S. Abrahams, Daniel H. Geschwind, Nathaniel Heintz Feb 2013

The Disruption Of Celf6, A Gene Identified By Translational Profiling Of Serotonergic Neurons, Results In Autism-Related Behaviors, Joseph D. Dougherty, Susan E. Maloney, David F. Wozniak, Michael A. Rieger, Lisa Sonnenblick, Giovanni Coppola, Nathaniel G. Mahieu, Juliet Zhang, Jinlu Cai, Gary J. Patti, Brett S. Abrahams, Daniel H. Geschwind, Nathaniel Heintz

Open Access Publications

The immense molecular diversity of neurons challenges our ability to understand the genetic and cellular etiology of neuropsychiatric disorders. Leveraging knowledge from neurobiology may help parse the genetic complexity: identifying genes important for a circuit that mediates a particular symptom of a disease may help identify polymorphisms that contribute to risk for the disease as a whole. The serotonergic system has long been suspected in disorders that have symptoms of repetitive behaviors and resistance to change, including autism. We generated a bacTRAP mouse line to permit translational profiling of serotonergic neurons. From this, we identified several thousand serotonergic-cell expressed transcripts, …


A Genetic Resource For Rapid And Comprehensive Phenotype Screening Of Nonessential Staphylococcus Aureus Genes., Paul D. Fey, Jennifer L. Endres, Vijaya Kumar Yajjala, Todd J. Widhelm, Robert J. Boissy, Jeffrey L. Bose, Kenneth W. Bayles Feb 2013

A Genetic Resource For Rapid And Comprehensive Phenotype Screening Of Nonessential Staphylococcus Aureus Genes., Paul D. Fey, Jennifer L. Endres, Vijaya Kumar Yajjala, Todd J. Widhelm, Robert J. Boissy, Jeffrey L. Bose, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

UNLABELLED: To enhance the research capabilities of investigators interested in Staphylococcus aureus, the Nebraska Center for Staphylococcal Research (CSR) has generated a sequence-defined transposon mutant library consisting of 1,952 strains, each containing a single mutation within a nonessential gene of the epidemic community-associated methicillin-resistant S. aureus (CA-MRSA) isolate USA300. To demonstrate the utility of this library for large-scale screening of phenotypic alterations, we spotted the library on indicator plates to assess hemolytic potential, protease production, pigmentation, and mannitol utilization. As expected, we identified many genes known to function in these processes, thus validating the utility of this approach. Importantly, we …


Dr. Robert L. Bennett: Pioneer And Definer Of Modern Physiatry., John F. Ditunno, Jr, Richard E. Verville Feb 2013

Dr. Robert L. Bennett: Pioneer And Definer Of Modern Physiatry., John F. Ditunno, Jr, Richard E. Verville

Department of Rehabilitation Medicine Faculty Papers

Few physiatrists today would appreciate Dr. Robert L. Bennett’s contributions to our specialty, since he most commonly was associated with poliomyelitis, a cured disease for over a half century. Less are aware of the pioneering fusion of physical medicine in 1941 by Krusen’s first resident with the independent living environment of the Georgia Warm Spring Foundation (GWSF) created by a USA president. Bennett recognized polio/GWSF as the workshop and laboratory for showcasing the new specialty of Physical Medicine and Rehabilitation (PMR). He taught us that accurate muscle testing determined the plan of muscle reeducation, which led to functional training with …