Digital Commons Network^™

Saturated Free Fatty Acids Induce Cholangiocyte Lipoapoptosis, Sathish Kumar Natarajan, Sally A. Ingham, Ashley M. Mohr, Cody J. Wehrkamp, Anuttoma Ray, Sohini Roy, Sophie C. Cazanave, Mary A. Smith, Justin L. Mott

Journal Articles: Biochemistry & Molecular Biology

Recent studies have identified a cholestatic variant of nonalcoholic fatty liver disease (NAFLD) with portal inflammation and ductular reaction. Based on reports of biliary damage, as well as increased circulating free fatty acids (FFAs) in NAFLD, we hypothesized the involvement of cholangiocyte lipoapoptosis as a mechanism of cellular injury. Here, we demonstrate that the saturated FFAs palmitate and stearate induced robust and rapid cell death in cholangiocytes. Palmitate and stearate induced cholangiocyte lipoapoptosis in a concentration-dependent manner in multiple cholangiocyte-derived cell lines. The mechanism of lipoapoptosis relied on the activation of caspase 3/7 activity. There was also a significant up-regulation …

The Long Non-Coding Rna Pcat-1 Promotes Prostate Cancer Cell Proliferation Through Cmyc., John R. Prensner, Wei Chen, Sumin Han, Matthew K. Iyer, Qi Cao, Vishal Kothari, Joseph R. Evans, Karen E. Knudsen, Michelle T. Paulsen, Mats Ljungman, Theodore S. Lawrence, Arul M. Chinnaiyan, Felix Y. Feng

Department of Cancer Biology Faculty Papers

Long non-coding RNAs (lncRNAs) represent an emerging layer of cancer biology, contributing to tumor proliferation, invasion, and metastasis. Here, we describe a role for the oncogenic lncRNA PCAT-1 in prostate cancer proliferation through cMyc. We find that PCAT-1-mediated proliferation is dependent on cMyc protein stabilization, and using expression profiling, we observed that cMyc is required for a subset of PCAT-1-induced expression changes. The PCAT-1-cMyc relationship is mediated through the post-transcriptional activity of the MYC 3' untranslated region, and we characterize a role for PCAT-1 in the disruption of MYC-targeting microRNAs. To further elucidate a role for post-transcriptional regulation, we demonstrate …

Exploring The Use Patterns Of A Mobile Health Application For Alcohol Addiction Before The Initial Lapse After Detoxification, Ming-Yuan Chih

Health and Clinical Sciences Faculty Publications

How patients used Addiction-Comprehensive Health Enhancement Support System (A-CHESS), a mobile health intervention, while quitting drinking is worthy exploring. This study is to explore A-CHESS use patterns prior to the initial lapse reported after discharge from inpatient detoxification programs. 142 patients with alcohol addiction from two treatment agencies in the U.S. were included. A comprehensive set of A-CHESS use measures were developed based on a three-level system use framework and three A-CHESS service categories. In latent profile analyses, three A-CHESS system use patterns-inactive, passive, and active users-were found. Compared to the passive users (with the highest chance of the initial …

Alzheimer's Therapeutics Targeting Amyloid Beta 1-42 Oligomers I: Abeta 42 Oligomer Binding To Specific Neuronal Receptors Is Displaced By Drug Candidates That Improve Cognitive Deficits, Nicholas J. Izzo, Agnes Staniszewski, Lillian To, Mauro Fa, Andrew F. Teich, Faisal Saeed, Harrison Wostein, Thomas Walko Iii, Anisha Vaswani, Meghan Wardius, Zanobia Syed, Jessica Ravenscroft, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Patricia Finn, Gary Look, Gilbert Rishton, Hank Safferstein, Miles Miller, Conrad Johanson, Edward Stopa, Manfred Windisch, Birgit Hutter-Paier, Mehrdad Shamloo, Ottavio Arancio, Harry Levine Iii, Susan M. Catalano

Sanders-Brown Center on Aging Faculty Publications

Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1-42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce …

Alzheimer's Therapeutics Targeting Amyloid Beta 1–42 Oligomers Ii: Sigma-2/Pgrmc1 Receptors Mediate Abeta 42 Oligomer Binding And Synaptotoxicity, Nicholas J. Izzo, Jinbin Xu, Chenbo Zeng, Molly J. Kirk, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Gary Look, Gilbert Rishton, Hank Safferstein, Carlos Cruchaga, Alison Goate, Michael A. Cahill, Ottavio Arancio, Robert H. Mach, Rolf Craven, Elizabeth Head, Harry Levine Iii, Tara L. Spires-Jones, Susan M. Catalano

Sanders-Brown Center on Aging Faculty Publications

Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic …

Unencapsulated Streptococcus Pneumoniae From Conjunctivitis Encode Variant Traits And Belong To A Distinct Phylogenetic Cluster, Michael D. Valentino, Abigail Manson Mcguire, Jason W. Rosch, Paulo J.M Bispo, Corinna Burnham, Christine M. Sanfilippo, Robert A. Carter, Michael E. Zegans, Bernard Beall, Ashlee M. Earl, Elaine I. Tuomanen, Timothy W. Morris, Wolfgaang Haas, Michael S. Gilmore

Dartmouth Scholarship

Streptococcus pneumoniae, an inhabitant of the upper respiratory mucosa, causes respiratory and invasive infections as well as conjunctivitis. Strains that lack the capsule, a main virulence factor and the target of current vaccines, are often isolated from conjunctivitis cases. Here we perform a comparative genomic analysis of 271 strains of conjunctivitis-causing S. pneumoniae from 72 postal codes in the United States. We find that the vast majority of conjunctivitis strains are members of a distinct cluster of closely related unencapsulated strains. These strains possess divergent forms of pneumococcal virulence factors (such as CbpA and neuraminidases) that are not shared with …

Use Of Social Media In Dental Schools: Pluses, Perils, And Pitfalls From A Legal Perspective, Joseph W. Parkinson, Sharon P. Turner

Oral Health Practice Faculty Publications

One of the ways dental education is changing the way it is preparing the next generation of learners is through efficient utilization of interactive social media. Social media, which facilitates interaction and sharing of new ideas, is being utilized to educate students, residents, and faculty. Unfortunately, as with most improvements in technology, there are growing pains. Faculty, student, and patient interaction on social media platforms, such as Facebook and Twitter, can lead to inappropriate or embarrassing situations. Striking the appropriate balance between free speech rights of students and faculty and the need for colleges and universities to have efficient operations …

Human Cytomegalovirus-Encoded Pul7 Is A Novel Ceacam1-Like Molecule Responsible For Promotion Of Angiogenesis., Jason D. Macmaniman, Andrew Meuser, Sara Botto, Patricia P. Smith, Fenyong Liu, Michael A. Jarvis, Jay A. Nelson, Patrizia Caposio

School of Biomedical Sciences

UNLABELLED: Persistent human cytomegalovirus (HCMV) infection has been linked to several diseases, including atherosclerosis, transplant vascular sclerosis (TVS), restenosis, and glioblastoma. We have previously shown that factors secreted from HCMV-infected cells induce angiogenesis and that this process is due, at least in part, to increased secretion of interleukin-6 (IL-6). In order to identify the HCMV gene(s) responsible for angiogenesis promotion, we constructed a large panel of replication-competent HCMV recombinants. One HCMV recombinant deleted for UL1 to UL10 was unable to induce secretion of factors necessary for angiogenesis. Fine mapping using additional HCMV recombinants identified UL7 as a viral gene required …

Candida Albicans Ethanol Stimulates Pseudomonas Aeruginosa Wspr-Controlled Biofilm Formation As Part Of A Cyclic Relationship Involving Phenazines, Annie I. Chen, Emily F. Dolben, Chinweike Okegbe, Colleen E. Harty, Yuriy Golub, Sandy Thao, Dae Gon Ha, Sven D. Willger, George A. O'Toole, Caroline S. Harwood, Lars E. P Dietrich, Deborah A. Hogan

Dartmouth Scholarship

In chronic infections, pathogens are often in the presence of other microbial species. For example, Pseudomonas aeruginosa is a common and detrimental lung pathogen in individuals with cystic fibrosis (CF) and co-infections with Candida albicans are common. Here, we show that P. aeruginosa biofilm formation and phenazine production were strongly influenced by ethanol produced by the fungus C. albicans. Ethanol stimulated phenotypes that are indicative of increased levels of cyclic- di-GMP (c-di-GMP), and levels of c-di-GMP were 2-fold higher in the presence of ethanol. Through a genetic screen, we found that the diguanylate cyclase WspR was required for ethanol …

Naturally Occurring Peer Support Through Social Media: The Experiences Of Individuals With Severe Mental Illness Using Youtube, John A. Naslund, Stuart W. Grande, Kelly A. Aschbrenner, Glyn Elwyn

Dartmouth Scholarship

Increasingly, people with diverse health conditions turn to social media to share their illness experiences or seek advice from others with similar health concerns. This unstructured medium may represent a platform on which individuals with severe mental illness naturally provide and receive peer support. Peer support includes a system of mutual giving and receiving where individuals with severe mental illness can offer hope, companionship, and encouragement to others facing similar challenges. In this study we explore the phenomenon of individuals with severe mental illness uploading videos to YouTube, and posting and responding to comments as a form of naturally occurring …

Successful Mdr-Tb Treatment Regimens Including Amikacin Are Associated With High Rates Of Hearing Loss, Chawangwa Modongo, Rafal S. Sobota, Boikobo Kesenogile, Ronald Ncube

Dartmouth Scholarship

Aminoglycosides are a critical component of multidrug-resistant tuberculosis (MDR-TB) treatment but data on their efficacy and adverse effects in Botswana is scarce. We determined the effect of amikacin on treatment outcomes and development of hearing loss in MDR-TB patients. Patients started on MDR-TB treatment between 2006 and 2012 were included. Multivariate analysis was used to determine the effect of amikacin on treatment outcomes and development of hearing loss.

Chess Improves Cancer Caregivers' Burden And Mood: Results Of An Ehealth Rct, Lori L. Dubenske, David H. Gustafson, Kang Namkoong, Robert P. Hawkins, Amy K. Atwood, Roger L. Brown, Ming-Yuan Chih, Fiona Mctavish, Cindy L. Carmack, Mary K. Buss, Ramaswamy Govindan, James F. Cleary

Community & Leadership Development Faculty Publications

OBJECTIVE: Informal caregivers (family and friends) of people with cancer are often unprepared for their caregiving role, leading to increased burden or distress. Comprehensive Health Enhancement Support System (CHESS) is a Web-based lung cancer information, communication, and coaching system for caregivers. This randomized trial reports the impact on caregiver burden, disruptiveness, and mood of providing caregivers access to CHESS versus the Internet with a list of recommended lung cancer websites.

METHODS: A total of 285 informal caregivers of patients with advanced nonsmall cell lung cancer were randomly assigned to a comparison group that received Internet or a treatment group that …

Systematic Review Of Potential Health Risks Posed By Pharmaceutical, Occupational And Consumer Exposures To Metallic And Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide And Its Soluble Salts, Calvin C. Willhite, Nataliya A. Karyakina, Robert A. Yokel, Nagarajkumar Yenugadhati, Thomas M. Wisniewski, Ian M. F. Arnold, Franco Momoli, Daniel Krewski

Pharmaceutical Sciences Faculty Publications

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007).

Challenges encountered in carrying out the present review reflected the experimental use of different physical …

Effect Of Electrocautery On Endothelial Integrity Of The Internal Thoracic Artery: Ultrastructural Analysis With Transmission Electron Microscopy, Burak Onan, Mehmet Yeniterzi, Ismihan Selen Onan, Burak Ersoy, Suheyla Gonca, Elif Gelenli, Seyhun Solakoglu, Ihsan Bakir

The Texas Heart Institute Journal

The internal thoracic artery (ITA) is typically harvested from the chest wall by means of conventional electrocautery. We investigated the effects of electrocautery on endothelial-cell and vessel-wall morphology at the ultrastructural level during ITA harvesting. Internal thoracic artery specimens from 20 patients who underwent elective coronary artery bypass grafting were investigated in 2 groups. The ITA grafts were sharply dissected with use of a scalpel and clips in the control group (n=10) and were harvested by means of electrocautery in the study group (n=10). Each sample was evaluated for intimal, elastic-tissue, muscular-layer, and adventitial changes. Free flow was measured intraoperatively. …

Myeloid Derived Hypoxia Inducible Factor 1-Alpha Is Required For Protection Against Pulmonary Aspergillus Fumigatus Infection, Kelly M. Shepardson, Anupam Jhingran, Alayna Caffrey, Joshua J. Obar, Benjamin T. Suratt, Brent L. Berwin, Tobias M. Hohl, Robert A. Cramer

Dartmouth Scholarship

Hypoxia inducible factor 1α (HIF1α) is the mammalian transcriptional factor that controls metabolism, survival, and innate immunity in response to inflammation and low oxygen. Previous work established that generation of hypoxic microenvironments occurs within the lung during infection with the human fungal pathogen Aspergillus fumigatus. Here we demonstrate that A. fumigatus stabilizes HIF1α protein early after pulmonary challenge that is inhibited by treatment of mice with the steroid triamcinolone. Utilizing myeloid deficient HIF1α mice, we observed that HIF1α is required for survival and fungal clearance early following pulmonary challenge with A. fumigatus. Unlike previously reported research with bacterial …

Noble Gases Identify The Mechanisms Of Fugitive Gas Contamination In Drinking-Water Wells Overlying The Marcellus And Barnett Shales, Thomas H. Darrah, Avner Vengosh, Robert B. Jackson, Nathaniel R. R. Warner, Robert J. Poreda

Dartmouth Scholarship

Horizontal drilling and hydraulic fracturing have enhanced energy production but raised concerns about drinking-water contamination and other environmental impacts. Identifying the sources and mechanisms of contamination can help improve the environmental and economic sustainability of shale-gas extraction. We analyzed 113 and 20 samples from drinking-water wells overlying the Marcellus and Barnett Shales, respectively, examining hydrocarbon abundance and isotopic compositions (e.g., C2H6/CH4, δ13C-CH4) and providing, to our knowledge, the first comprehensive analyses of noble gases and their isotopes (e.g., 4He, 20Ne, 36Ar) in groundwater near shale-gas wells. We addressed two questions. (i) Are elevated levels of hydrocarbon gases in …

Annotated Bibliography: Attitudes Toward Animals (1998-2013), Erich Yahner

BIBLIOGRAPHIES

No abstract provided.

Unbiased Analysis Of Pancreatic Cancer Radiation Resistance Reveals Cholesterol Biosynthesis As A Novel Target For Radiosensitisation., Joshua J. Souchek, Michael J. Baine, Chi Lin, Satyanarayana Rachagani, Suprit Gupta, Sukhwinder Kaur, K Lester, D Zheng, S Chen, Lynette Smith, A Lazenby, Sonny L. Johansson, Maneesh Jain, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Despite its promise as a highly useful therapy for pancreatic cancer (PC), the addition of external beam radiation therapy to PC treatment has shown varying success in clinical trials. Understanding PC radioresistance and discovery of methods to sensitise PC to radiation will increase patient survival and improve quality of life. In this study, we identified PC radioresistance-associated pathways using global, unbiased techniques.

METHODS: Radioresistant cells were generated by sequential irradiation and recovery, and global genome cDNA microarray analysis was performed to identify differentially expressed genes in radiosensitive and radioresistant cells. Ingenuity pathway analysis was performed to discover cellular pathways …

Multiple Metabolomics Of Uropathogenic E. Coli Reveal Different Information Content In Terms Of Metabolic Potential Compared To Virulence Factors., Haitham Alrabiah, Yun Xu, Nicholas J.W. Rattray, Andrew A. Vaughan, Tarek Gibreel, Ali Sayqal, Mathew Upton, J. William Allwood, Royston Goodacre

School of Biomedical Sciences

No single analytical method can cover the whole metabolome and the choice of which platform to use may inadvertently introduce chemical selectivity. In order to investigate this we analysed a collection of uropathogenic Escherichia coli. The selected strains had previously undergone extensive characterisation using classical microbiological methods for a variety of metabolic tests and virulence factors. These bacteria were analysed using Fourier transform infrared (FT-IR) spectroscopy; gas chromatography mass spectrometry (GC-MS) after derivatisation of polar non-volatile analytes; as well as reversed-phase liquid chromatography mass spectrometry in both positive (LC-MS(+ve)) and negative (LC-MS(-ve)) electrospray ionisation modes. A comparison of the discriminatory …

Fructose-2,6-Bisphosphate Synthesis By 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 4 (Pfkfb4) Is Required For The Glycolytic Response To Hypoxia And Tumor Growth, Jason Chesney, Jennifer Clark, Alden C. Klarer, Yoannis Imbert-Fernandez, Andrew N. Lane, Sucheta Telang

Markey Cancer Center Faculty Publications

Fructose-2,6-bisphosphate (F2,6BP) is a shunt product of glycolysis that allosterically activates 6-phosphofructo-1-kinase (PFK-1) resulting in increased glucose uptake and glycolytic flux to lactate. The F2,6BP concentration is dictated by four bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) with distinct kinase:phosphatase activities. PFKFB4 is over-expressed in human cancers, induced by hypoxia and required for survival and growth of several cancer cell lines. Although PFKFB4 appears to be a rational target for anti-neoplastic drug development, it is not clear whether its kinase or phosphatase activity is required for cancer cell survival. In this study, we demonstrate that recombinant human PFKFB4 kinase activity is 4.3-fold greater than …

The Jak2 Small Molecule Inhibitor, G6, Reduces The Tumorigenic Potential Of T98g Glioblastoma Cells In Vitro And In Vivo, Rebekah Baskin, Sung O. Park, György M. Keserű, Kirpal S. Bisht, Heather L. Wamsley, Peter P. Sayeski

Chemistry Faculty Publications

Glioblastoma multiforme (GBM) is the most common and the most aggressive form of primary brain tumor. Jak2 is a non-receptor tyrosine kinase that is involved in proliferative signaling through its association with various cell surface receptors. Hyperactive Jak2 signaling has been implicated in numerous hematological disorders as well as in various solid tumors including GBM. Our lab has developed a Jak2 small molecule inhibitor known as G6. It exhibits potent efficacy in vitro and in several in vivo models of Jak2-mediated hematological disease. Here, we hypothesized that G6 would inhibit the pathogenic growth of GBM cells expressing hyperactive Jak2. To …

Thiosulfoxide (Sulfane) Sulfur: New Chemistry And New Regulatory Roles In Biology, John Toohey, Arthur J L Cooper

NYMC Faculty Publications

The understanding of sulfur bonding is undergoing change. Old theories on hypervalency of sulfur and the nature of the chalcogen-chalcogen bond are now questioned. At the same time, there is a rapidly expanding literature on the effects of sulfur in regulating biological systems. The two fields are inter-related because the new understanding of the thiosulfoxide bond helps to explain the newfound roles of sulfur in biology. This review examines the nature of thiosulfoxide (sulfane, S0) sulfur, the history of its regulatory role, its generation in biological systems, and its functions in cells. The functions include synthesis of cofactors (molybdenum cofactor, …

Rapidly Self-Renewing Human Multipotent Marrow Stromal Cells (Hmsc) Express Sialyl Lewis X And Actively Adhere To Arterial Endothelium In A Chick Embryo Model System, Harris E. Mcferrin, Scott D. Olson, Miriam V. Gutschow, Julie A. Semon, Deborah E. Sullivan, Darwin J. Prockop

Biological Sciences Faculty Research & Creative Works

Background: There have been conflicting observations regarding the receptors utilized by human multipotent mesenchymal bone marrow stromal cells (hMSC) to adhere to endothelial cells (EC). To address the discrepancies, we performed experiments with cells prepared with a standardized, low-density protocol preserving a sub-population of small cells that are rapidly self-renewing.

Methods: Sialyl Lewis X (SLeX) and α4 integrin expression were determined by flow cytometry. Fucosyltransferase expression was determined by quantitative realtime RT-PCR. Cell adhesion assays were carried out with a panel of endothelial cells from arteries, veins and the microvasculature in vitro. In Vivo experiments were performed to determine …

Rules And Values: A Coordinated Regulatory And Educational Approach To The Public Health Crises Of Chronic Pain And Addiction, Joanna G. Katzman, George D. Comerci, Michael Landen, Larry Loring, Steven M. Jenkusky, Sanjeev Arora, Summers Kalishman, Lisa Marr, Chris Camarata, Daniel Duhigg, Jennifer Dillow, Eugene Koshkin, Denise E. Taylor, Cynthia M A Geppert

Project ECHO Bibliography

Chronic pain and opioid addiction are 2 pressing public health problems, and prescribing clinicians often lack the skills necessary to manage these conditions. Our study sought to address the benefits of a coalition of an academic medical center pain faculty and government agencies in addressing the high unintentional overdose death rates in New Mexico. New Mexico's 2012-2013 mandated chronic pain and addiction education programs studied more than 1000 clinicians. Positive changes were noted in precourse and postcourse surveys of knowledge, self-efficacy, and attitudes. Controlled substance dispensing data from the New Mexico Board of Pharmacy also demonstrated safer prescribing. The total …

Nontyphoidal Cardiac Salmonellosis: Two Case Reports And A Review Of The Literature, Daniel Ortiz, Eric M Siegal, Christopher Kramer, Bijoy K Khandheria, Ernesto Brauer

The Texas Heart Institute Journal

Nontyphoidal Salmonella, especially Salmonella enterica, is a rare cause of endocarditis and pericarditis that carries a high mortality rate. Proposed predisposing conditions include immunodeficiency states, congenital heart defects, and cardiac valve diseases. We present 2 cases of cardiovascular salmonellosis. The first case is that of a 73-year-old woman with mechanical mitral and bioprosthetic aortic valves who died from sequelae of nontyphoidal Salmonella mitral valve vegetation, aortic valve abscess, and sepsis. The second case is that of a 62-year-old man with a recent systemic lupus erythematosus exacerbation treated with oral steroids, who presented with obstructive features of tamponade and sepsis secondary …

Novel Role Of Pancreatic Differentiation 2 In Facilitating Self-Renewal And Drug Resistance Of Pancreatic Cancer Stem Cells., Arokia P. Vaz, Moorthy P. Ponnusamy, Satyanarayana Rachagani, P Dey, Apar Kishor Ganti, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Cancer stem cells (CSCs) contribute towards disease aggressiveness and drug resistance. Specific identification of CSC maintenance genes and targeting can improve the efficiency of currently available treatment modalities. Pancreatic differentiation 2 (PD2) has a major role in the self-renewal of mouse embryonic stem cells. In the present study, we investigated the role of PD2 in pancreatic CSCs.

METHODS: Characterisation of CSCs and non-CSCs from mouse models, pancreatic cancer cells and human tissues by CSC and self-renewal marker analysis using confocal assay. Effect of PD2 knockdown in CSCs (after gemcitabine treatment) was studied by immunoblot and apoptosis assays.

RESULTS: A …

Three-Dimensional Carotid Ultrasound Plaque Texture Predicts Vascular Events, Arna Van Engelen, Thapat Wannarong, Grace Parraga, Wiro J Niessen, Aaron Fenster, J David Spence, Marleen De Bruijne

Medical Biophysics Publications

BACKGROUND AND PURPOSE: Carotid ultrasound atherosclerosis measurements, including those of the arterial wall and plaque, provide a way to monitor patients at risk of vascular events. Our objective was to examine carotid ultrasound plaque texture measurements and the change in carotid plaque texture during 1 year in patients at risk of events and to compare these with measurements of plaque volume and other risk factors as predictors of vascular events.

METHODS: We evaluated 298 patients with carotid atherosclerosis using 3-dimensional (3D) ultrasound at baseline and after 1 year and measured carotid plaque volume and 376 measures of plaque texture. Patients …

Inactivating Ube2m Impacts The Dna Damage Response And Genome Integrity Involving Multiple Cullin Ligases, Scott Cukras, Nicholas Morffy, Takbum Ohn, Younghoon Kee

Molecular Biosciences Faculty Publications

Protein neddylation is involved in a wide variety of cellular processes. Here we show that the DNA damage response is perturbed in cells inactivated with an E2 Nedd8 conjugating enzyme UBE2M, measured by RAD51 foci formation kinetics and cell based DNA repair assays. UBE2M knockdown increases DNA breakages and cellular sensitivity to DNA damaging agents, further suggesting heightened genomic instability and defective DNA repair activity. Investigating the downstream Cullin targets of UBE2M revealed that silencing of Cullin 1, 2, and 4 ligases incurred significant DNA damage. In particular, UBE2M knockdown, or defective neddylation of Cullin 2, leads to a blockade …

Sex Hormones Regulate Tenofovir-Diphosphate In Female Reproductive Tract Cells In Culture, Zheng Shen, John V. Fahey, Jack E. Bodwell, Marta Rodriguez-Garcia, Angela D.M Kashuba, Charles R. Wira

Dartmouth Scholarship

The conflicting results of recent pre-exposure prophylaxis (PrEP) trials utilizing tenofovir (TFV) to prevent HIV infection in women led us to evaluate the accumulation of intracellular TFV-diphosphate (TFV-DP) in cells from the female reproductive tract (FRT) and whether sex hormones influence the presence of TFV-DP in these cells. Following incubation with TFV, isolated epithelial cells, fibroblasts, CD4⁺ T cells and CD14⁺ cells from the FRT as well as blood CD4⁺ T cells and monocyte-derived macrophages convert TFV to TFV-DP. Unexpectedly, we found that TFV-DP concentrations (fmol/million cells) vary significantly with the cell type analyzed and the site …

Francis F. Maury, M.D. (1840 To 1879): An Often Forgotten Pioneer In Early American Surgery., Guillaume S. Chevrollier, B.S., Scott W. Cowan, Md, Charles J. Yeo, Md, John C. Kairys, Md

Department of Surgery Gibbon Society Historical Profiles

Francis F. Maury (Fig. 1) was born on August 9, 1840, in Danville, Kentucky, where he was raised on a farm by his mother and father. His father was an Episcopal clergyman of Huguenot descent, whose forefathers had fled from France to escape religious persecution. After receiving a Bachelor of Arts degree from Center College in the summer of 1860, he entered medical school at the University of Virginia. After one full term, he matriculated to Philadelphia’s Jefferson Medical College and completed his medical education as a private student under the direction of Dr. Samuel D. Gross.1, 2 He obtained …