Digital Commons Network^™

Quantifying Unnecessary Normal Tissue Complication Risks Due To Suboptimal Planning: A Secondary Study Of Rtog 0126., Kevin L. Moore, Rachel Schmidt, Vitali Moiseenko, Lindsey A. Olsen, Jun Tan, Ying Xiao, James Galvin, Stephanie Pugh, Michael J Seider, Adam P. Dicker, Walter Bosch, Jeff Michalski, Sasa Mutic

Department of Radiation Oncology Faculty Papers

PURPOSE: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol.

METHODS AND MATERIALS: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative …

Spatial Heterogeneity, Host Movement And Mosquito-Borne Disease Transmission, Miguel A. Acevedo, Olivia Prosper, Kenneth Lopiano, Nick Ruktanonchai, T. Trevor Caughlin, Maia Martcheva, Craig W. Osenberg, David L. Smith

Dartmouth Scholarship

Mosquito-borne diseases are a global health priority disproportionately affecting low-income populations in tropical and sub-tropical countries. These pathogens live in mosquitoes and hosts that interact in spatially heterogeneous environments where hosts move between regions of varying transmission intensity. Although there is increasing interest in the implications of spatial processes for mosquito-borne disease dynamics, most of our understanding derives from models that assume spatially homogeneous transmission. Spatial variation in contact rates can influence transmission and the risk of epidemics, yet the interaction between spatial heterogeneity and movement of hosts remains relatively unexplored. Here we explore, analytically and through numerical simulations, how …

Iarc Monographs: 40 Years Of Evaluating Carcinogenic Hazards To Humans, Neil E. Pearce, Aaron Blair, Paolo Vineis, Wolfgang Ahrens, Aage Andersom, Josep M. Anto, Bruce K. Armstrong, Andrea A. Baccarelli, Frederick A. Beland, Amy Berrington, Pier Alberto Bertazzi, Linda S. Birnbaum, Ross C. Brownson, John R. Bucher, Kenneth P. Cantor, Elisabeth Cardis, John W. Cherrie, David C. Christiani, Pierluigi Cocco, David Coggon, Pietro Comba, Paul A. Demers, John M. Dement, Jeroen Douwes, Ellen A. Eisen, Lawrence S. Engel, Richard A. Fenske, Lora E. Fleming, Tony Fletcher, Elizabeth Fontham, Francesco Forastiere, Rainer Frentzel-Beyme, Lin Fritschi, Michel Gerin, Marcel Goldberg, Philippe Grandjean, Tom K. Grimsrud, Per Gustavsson, Andy Haines, Patricia Hartge, Johnni Hansen, Michael Hauptmann, Dick Heederik, Kari Hemminki, Denis Hemon, Irva Hertz-Picciotto, Jane A. Hoppin, James Huff, Bengt Jarvholm, Daehee Kang, Margaret R. Karagas

Dartmouth Scholarship

Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.

Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process …

New Functions For Alpha-Catenins In Health And Disease: From Cancer To Heart Regeneration., Alexia Vite, Jifen Li, Glenn L. Radice

Center for Translational Medicine Faculty Papers

Strong cell-cell adhesion mediated by adherens junctions is dependent on anchoring the transmembrane cadherin molecule to the underlying actin cytoskeleton. To do this, the cadherin cytoplasmic domain interacts with catenin proteins, which include α-catenin that binds directly to filamentous actin. Originally thought to be a static structure, the connection between the cadherin/catenin adhesion complex and the actin cytoskeleton is now considered to be dynamic and responsive to both intercellular and intracellular signals. Alpha-catenins are mechanosensing proteins that undergo conformational change in response to cytoskeletal tension thus modifying the linkage between the cadherin and the actin cytoskeleton. There are three α-catenin …

Understanding Nucleus Pulposus Cell Phenotype: A Prerequisite For Stem Cell Based Therapies To Treat Intervertebral Disc Degeneration., Hyowon Choi, Zariel I. Johnson, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc (IVD) degeneration and associated low back pain (LBP) remains a major burden to our society without significant improvements in treatment strategies or patient's quality of life. While the recent cell-transplantation studies for treatment of degenerative disc disease have shown promising results, to better gauge the success and functional outcomes of these therapies, it is crucial to understand if transplanted cells give rise to healthy nucleus pulposus (NP) tissue. NP cell phenotype is unique and is defined by expression of a characteristic set of markers that reflect specialized physiology and function. This review summarizes phenotypic markers that mirror the …

Computational Modeling Analysis Of Mitochondrial Superoxide Production Under Varying Substrate Conditions And Upon Inhibition Of Different Segments Of The Electron Transport Chain., Nikolai I. Markevich, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A computational mechanistic model of superoxide (O2•-) formation in the mitochondrial electron transport chain (ETC) was developed to facilitate the quantitative analysis of factors controlling mitochondrial O2•- production and assist in the interpretation of experimental studies. The model takes into account all individual electron transfer reactions in Complexes I and III. The model accounts for multiple, often seemingly contradictory observations on the effects of ΔΨ and ΔpH, and for the effects of multiple substrate and inhibitor conditions, including differential effects of Complex III inhibitors antimycin A, myxothiazol and stigmatellin. Simulation results confirm that, in addition to O2•- formation in Complex …

Preclinical Characterization Of Duoc-01, A Cell Therapy Product Derived From Banked Umbilical Cord Blood For Use As An Adjuvant To Umbilical Cord Blood Transplantation For Treatment Of Inherited Metabolic Diseases., Joanne Kurtzberg, Susan Buntz, Tracy Gentry, Pamela Noeldner, April Ozamiz, Benjamin Rusche, Robert W. Storms, Amy Wollish, David A Wenger, Andrew E. Balber

Department of Neurology Faculty Papers

BACKGROUND AIMS: Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period.

METHODS: DUOC-01 cultures initiated from banked CB units were characterized by use of time-lapse photomicroscopy during the 21-day manufacturing process. Antigen expression was measured by means of flow cytometry and immunocytochemistry; transcripts for cytokines and enzymes by quantitative real-time polymerase chain reaction; activities of lysosomal enzymes by …

Is Autologous Or Heterologous Pericardium Better For Valvuloplasty? A Comparative Study Of Calcification Propensity, Arthur W Bracey

The Texas Heart Institute Journal

No abstract provided.

Identification Of Novel Genes That Regulate Androgen Receptor Signaling And Growth Of Androgen-Deprived Prostate Cancer Cells, Elina Levina, Hao Ji, Mengqiang Chen, Mirza Baig, David Oliver, Patrice Ohouo, Chang-Uk Lim, Garry Schools, Steven Carmack, Ye Ding, Eugenia Broude, Igor Roninson, Ralph Buttyan, Michael Shtutman

Faculty Publications

Prostate cancer progression to castration refractory disease is associated with anomalous transcriptional activity of the androgen receptor (AR) in an androgen-depleted milieu. To identify novel gene products whose downregulation transactivates AR in prostate cancer cells, we performed a screen of enzymatically-generated shRNA lenti-libraries selecting for transduced LNCaP cells with elevated expression of a fluorescent reporter gene under the control of an AR-responsive promoter. The shRNAs present in selected populations were analyzed using high-throughput sequencing to identify target genes. Highly enriched gene targets were then validated with siRNAs against selected genes, testing first for increased expression of luciferase from an AR-responsive …

Pseudomonas Aeruginosa Reduces Vx-809 Stimulated F508del-Cftr Chloride Secretion By Airway Epithelial Cells, Bruce A. Stanton, Bonita Coutermarsh, Roxanna Barnaby, Deborah Hogan

Dartmouth Scholarship

Background:

P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and …

Antibacterial Activity Of Native California Medicinal Plant Extracts Isolated From Rhamnus Californica And Umbellularia Californica., Maria G. Carranza, Mary B. Sevigny, Debashree Banerjee, Lacie Fox-Cubley

Natural Sciences and Mathematics | Faculty Scholarship

BACKGROUND: Antimicrobial resistance (AMR) is a major threat to global public health. Medicinal plants have long been used as remedies for infectious diseases by native cultures around the world and have the potential for providing effective treatments for antibiotic-resistant infections. Rhamnus californica (Rhamnaceae) and Umbellularia californica (Lauraceae) are two indigenous California plant species historically used by Native Americans to treat skin, respiratory and gastrointestinal infections. This study aimed to assess the in vitro antimicrobial activity of methanolic extracts of leaves and bark of R. and U. californica against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive and Gram-negative bacteria.

METHODS: Methanolic …

Human Dna Exonuclease Trex1 Is Also An Exoribonuclease That Acts On Single-Stranded Rna, Fenghua Yuan, Tanmay Dutta, Ling Wang, Lei Song, Liya Gu, Liangyue Qian, Anaid Benitez, Shunbin Ning, Arun Malhotra, Murray P. Deutscher, Yanbin Zhang

Toxicology and Cancer Biology Faculty Publications

3' repair exonuclease 1 (TREX1) is a known DNA exonuclease involved in autoimmune disorders and the antiviral response. In this work, we show that TREX1 is also a RNA exonuclease. Purified TREX1 displays robust exoribonuclease activity that degrades single-stranded, but not double-stranded, RNA. TREX1-D200N, an Aicardi-Goutieres syndrome disease-causing mutant, is defective in degrading RNA. TREX1 activity is strongly inhibited by a stretch of pyrimidine residues as is a bacterial homolog, RNase T. Kinetic measurements indicate that the apparent K_m of TREX1 for RNA is higher than that for DNA. Like RNase T, human TREX1 is active in degrading native …

Genetic Heterogeneity Of Pseudoxanthoma Elasticum: The Chinese Signature Profile Of Abcc6 And Enpp1 Mutations., Liang Jin, Qiujie Jiang, Zhengsheng Wu, Changxia Shao, Yong Zhou, Luting Yang, Jouni Uitto, Gang Wang

Department of Dermatology and Cutaneous Biology Faculty Papers

Pseudoxanthoma elasticum (PXE), an autosomal recessive disorder characterized by ectopic mineralization, is caused by mutations in the ABCC6 gene. We examined clinically 29 Chinese PXE patients from unrelated families, so far the largest cohort of Asian PXE patients. In a subset of 22 patients, we sequenced ABCC6 and another candidate gene, ENPP1, and conducted pathogenicity analyses for each variant. We identified a total of 17 distinct mutations in ABCC6, 15 of them being, to our knowledge, previously unreported, including 5 frameshift and 10 missense variants. In addition, a missense mutation in combination with a recurrent nonsense mutation in ENPP1 was …

Optimization Of Image Reconstruction For Magnetic Resonance Imaging–Guided Near-Infrared Diffuse Optical Spectroscopy In Breast, Yan Zhao, Michael A. Mastanduno, Shudong Jiang, Fadi Ei-Ghussein, Jiang Gui, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

An optimized approach to nonlinear iterative reconstruction of magnetic resonance imaging (MRI)–guided near-infrared spectral tomography (NIRST) images was developed using an L-curve-based algorithm for the choice of regularization parameter. This approach was applied to clinical exam data to maximize the reconstructed values differentiating malignant and benign lesions. MRI/NIRST data from 25 patients with abnormal breast readings (BI-RADS category 4-5) were analyzed using this optimal regularization methodology, and the results showed enhanced p values and area under the curve (AUC) for the task of differentiating malignant from benign lesions. Of the four absorption parameters and two scatter parameters, the most significant …

Regulators Associated With Clinical Outcomes Revealed By Dna Methylation Data In Breast Cancer, Matthew H. Ung, Frederick S. Varn, Shaoke Lou, Chao Cheng

Dartmouth Scholarship

The regulatory architecture of breast cancer is extraordinarily complex and gene misregulation can occur at many levels, with transcriptional malfunction being a major cause. This dysfunctional process typically involves additional regulatory modulators including DNA methylation. Thus, the interplay between transcription factor (TF) binding and DNA methylation are two components of a cancer regulatory interactome presumed to display correlated signals. As proof of concept, we performed a systematic motif-based in silico analysis to infer all potential TFs that are involved in breast cancer prognosis through an association with DNA methylation changes. Using breast cancer DNA methylation and clinical data derived from …

Haemophilus Influenzae Responds To Glucocorticoids Used In Asthma Therapy By Modulation Of Biofilm Formation And Antibiotic Resistance, Chris S. Earl, Tee Wooi Keong, Shi-Qi An, Sarah Murdoch, Yvonne Mccarthy, Junkal Garmendia, Joseph Ward, J Maxwell Dow, Liang Yang, George A. O'Toole, Robert P. Ryan

Dartmouth Scholarship

Glucocorticosteroids are used as a main treatment to reduce airway inflammation in people with asthma who suffer from neutrophilic airway inflammation, a condition frequently associ- ated with Haemophilus influenzae colonization. Here we show that glucocorticosteroids have a direct influence on the behavior of H. influenzae that may account for associated difficulties with therapy. Using a mouse model of infection, we show that cortico- steroid treatment promotes H. influenzae persistence. Transcrip- tomic analysis of bacteria either isolated from infected mouse airway or grown in laboratory medium identified a number of genes encoding regulatory factors whose expression responded to the presence of …

Ferritin Levels In The Cerebrospinal Fluid Predict Alzheimer's Disease Outcomes And Are Regulated By Apoe, Scott Ayton, Noel G. Faux, Ashley I. Bush, Charles D. Smith, Greg A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Alzheimer's Disease Neuroimaging Initiative

Neurology Faculty Publications

Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. …

The Endogenous Cell-Fate Factor Dachshund Restrains Prostate Epithelial Cell Migration Via Repression Of Cytokine Secretion Via A Cxcl Signaling Module., Ke Chen, Kongming Wu, Xuanmao Jiao, Liping Wang, Xiaoming Ju, Min Wang, Gabriele Disante, Shaohua Xu, Qiong Wang, Kevin Li, Xin Sun, Chongwen Xu, Zhiping Li, Mathew C. Casimiro, Adam Ertel, Sankar Addya, Peter Mccue, Michael P. Lisanti, Chenguang Wang, Richard J. Davis, Graeme Mardon, Richard Pestell

Department of Cancer Biology Faculty Papers

Prostate cancer is the second leading form of cancer-related death in men. In a subset of prostate cancer patients, increased chemokine signaling IL8 and IL6 correlates with castrate-resistant prostate cancer (CRPC). IL8 and IL6 are produced by prostate epithelial cells and promote prostate cancer cell invasion; however, the mechanisms restraining prostate epithelial cell cytokine secretion are poorly understood. Herein, the cell-fate determinant factor DACH1 inhibited CRPC tumor growth in mice. Using Dach1(fl/fl)/Probasin-Cre bitransgenic mice, we show IL8 and IL6 secretion was altered by approximately 1,000-fold by endogenous Dach1. Endogenous Dach1 is shown to serve as a key endogenous restraint to …

Preventing Farnesylation Of The Dynein Adaptor Spindly Contributes To The Mitotic Defects Caused By Farnesyltransferase Inhibitors, Andrew J. Holland, Rita M. Reis, Sherry Niessen, Cláudia Pereira, Douglas A. Andres, H. Peter Spielmann, Don W. Cleveland, Arshad Desai, Reto Gassmann

Molecular and Cellular Biochemistry Faculty Publications

The clinical interest in farnesyltransferase inhibitors (FTIs) makes it important to understand how these compounds affect cellular processes involving farnesylated proteins. Mitotic abnormalities observed after treatment with FTIs have so far been attributed to defects in the farnesylation of the outer kinetochore proteins CENP-E and CENP-F, which are involved in chromosome congression and spindle assembly checkpoint signaling. Here we identify the cytoplasmic dynein adaptor Spindly as an additional component of the outer kinetochore that is modified by farnesyltransferase (FTase). We show that farnesylation of Spindly is essential for its localization, and thus for the proper localization of dynein and its …

Xiap And Ciap1 Amplifications Induce Beclin 1-Dependent Autophagy Through Nfκb Activation., Fang Lin, Ghita Ghislat, Shouqing Luo, Maurizio Renna, Farah Siddiqi, David C. Rubinsztein

Peninsula Medical School

Perturbations in autophagy and apoptosis are associated with cancer development. XIAP and cIAP1 are two members of the inhibitors of apoptosis protein family whose expression is elevated in different cancers. Here we report that XIAP and cIAP1 induce autophagy by upregulating the transcription of Beclin 1, an essential autophagy gene. The E3 ubiquitin ligase activity of both proteins activates NFκB signalling, leading to the direct binding of p65 to the promoter of Beclin 1 and to its transcriptional activation. This mechanism may be relevant in cancer cells, since we found increased levels of autophagy in different B-cell lymphoma-derived cell lines …

Cytoskeletal Dynamics: A View From The Membrane, Magdalena Bezanilla, Amy S. Gladfelter, David R. Kovar, Wei-Lih Lee

Dartmouth Scholarship

Many aspects of cytoskeletal assembly and dynamics can be recapitulated in vitro; yet, how the cytoskeleton integrates signals in vivo across cellular membranes is far less understood. Recent work has demonstrated that the membrane alone, or through membrane-associated proteins, can effect dynamic changes to the cytoskeleton, thereby impacting cell physiology. Having identified mechanistic links between membranes and the actin, microtubule, and septin cytoskeletons, these studies highlight the membrane’s central role in coordinating these cytoskeletal systems to carry out essential processes, such as endocytosis, spindle positioning, and cellular compartmentalization.

Cell Signaling Events Differentiate Er-Negative Subtypes From Er-Positive Breast Cancer, Maria Worsham, Dhananjay A. Chitale, Kang-Mei Chen, Indrani Datta, George Divine

Otolaryngology Articles

Currently available markers routinely used in clinical practice are of limited value to patients with estrogen receptor-negative (ER(-)) breast cancer [basal-like and HER2neu-positive (HER(+))], an aggressive subtype. Our aim was to uncover molecular pathways and signaling networks exposed by differentially methylated genes informative of the biology of ER(-) breast cancer (BC) subtypes versus ER-positive (ER(+)). Whole-genome methylation array analysis was carried out using the Illumina Infinium HumanMethylation27 BeadChip on 14 primary BC: five ER(+), four triple-negative (TNBC), and five ER(-)HER2(+). Degree of methylation was calculated as a β-value (ranging from 0 to 1), and M-values [log (β/(1 - β)] were …

Sex-Specific Parental Effects On Offspring Lipid Levels, Irene M. Predazzi, Rafal S. Sobota, Serena Sanna, William S. Bush, Jacquelaine Bartlett, Jessica S. Lilley, Macrae F. Linton, David Schlessinger, Francesco Cucca, Sergio Fazio, Scott M. Williams

Dartmouth Scholarship

Background:

Plasma lipid levels are highly heritable traits, but known genetic loci can only explain a small portion of their heritability.

Methods and Results:

In this study, we analyzed the role of parental levels of total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and triglycerides (TGs) in explaining the values of the corresponding traits in adult offspring. We also evaluated the contribution of nongenetic factors that influence lipid traits (age, body mass index, smoking, medications, and menopause) alone and in combination with variability at the genetic loci known to associate with TC, LDL‐C, HDL‐C, and TG levels. …

Alternating Magnetic Field-Induced Hyperthermia Increases Iron Oxide Nanoparticle Cell Association/Uptake And Flux In Blood-Brain Barrier Models, Mo Dan, Younsoo Bae, Thomas A. Pittman, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

PURPOSE: Superparamagnetic iron oxide nanoparticles (IONPs) are being investigated for brain cancer therapy because alternating magnetic field (AMF) activates them to produce hyperthermia. For central nervous system applications, brain entry of diagnostic and therapeutic agents is usually essential. We hypothesized that AMF-induced hyperthermia significantly increases IONP blood-brain barrier (BBB) association/uptake and flux.

METHODS: Cross-linked nanoassemblies loaded with IONPs (CNA-IONPs) and conventional citrate-coated IONPs (citrate-IONPs) were synthesized and characterized in house. CNA-IONP and citrate-IONP BBB cell association/uptake and flux were studied using two BBB Transwell^® models (bEnd.3 and MDCKII cells) after conventional and AMF-induced hyperthermia exposure.

RESULTS: …

Comparison Of Survival In Patients With T Cell Lymphoma After Autologous And Allogeneic Stem Cell Transplantation As A Frontline Strategy Or In Relapsed Disease., Amer Beitinjaneh, Rima M. Saliba, L. Jeffrey Medeiros, Francesco Turturro, Gabriela Rondon, Martin Korbling, Luis Fayad, Michelle A. Fanale, Amin M. Alousi, Paolo Anderlini, Oran Betul, Uday R. Popat, Barbara Pro, Issa F. Khouri

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

We studied the roles of autologous (A) and allogeneic (allo) stem cell transplantation (SCT) in the treatment of 134 patients with T cell lymphoma (TCL) at our center. For frontline SCT, 58 patients were studied. The 4-year overall survival (OS) rates for ASCT (n = 47; median age, 49 years) and alloSCT (n = 11; median age, 55 years) groups were 76% and 54%, respectively (P > .05). The 4-year OS rates for first complete remission (CR1) patients were 84% and 83%, respectively. For SCT for relapsed disease, 76 patients were studied (41 with ASCT and 35 with alloSCT). The 4-year …

Increasing Adipocyte Lipoprotein Lipase Improves Glucose Metabolism In High Fat Diet-Induced Obesity, R. Grace Walton, Beibei Zhu, Resat Unal, Michael Spencer, Manjula Sunkara, Andrew J. Morris, Richard Charnigo, Wendy S. Katz, Alan Daugherty, Deborah A. Howatt, Philip A. Kern, Brian S. Finlin

Barnstable Brown Diabetes Center Faculty Publications

Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization …

Chemoselective Detection And Discrimination Of Carbonyl-Containing Compounds In Metabolite Mixtures By 1H-Detected 15N Nuclear Magnetic Resonance, Andrew N. Lane, Sengodagounder Arumugam, Pawel Lorkiewicz, Richard M. Higashi, Sébastien Laulhé, Michael H. Nantz, Hunter N. B. Moseley, Teresa W-M Fan

Toxicology and Cancer Biology Faculty Publications

NMR spectra of mixtures of metabolites extracted from cells or tissues are extremely complex, reflecting the large number of compounds that are present over a wide range of concentrations. Although multidimensional NMR can greatly improve resolution as well as improve reliability of compound assignments, lower abundance metabolites often remain hidden. We have developed a carbonyl-selective aminooxy probe that specifically reacts with free keto and aldehyde functions, but not carboxylates. By incorporating ¹⁵N in the aminooxy functional group, ¹⁵N-edited NMR was used to select exclusively those metabolites that contain a free carbonyl function while all other metabolites are rejected. …

Meta-Analysis On Zoonotic Infectious Diseases Between Humans And Non-Human Primates, Madalyn R. Page

Undergraduate Honors Capstone Projects

Due to genetic similarity, non-human primates are often the focus of zoonotic infectious disease research. The objective of zoonotic disease research can vary depending upon whether the study is focusing on human health or the health of wild non-human primate populations. Research with non-human primates is often associated with their use in medical laboratories for the benefit of human health. However, other studies focus on both the health of wild non-human primate populations and human interactions. This study reviews zoonotic disease research published in three main primatology journals: American Journal of Primatology, International Journal of Primatology, and Primates. …

Reverse Genetics Of Mononegavirales: How They Work, New Vaccines, And New Cancer Therapeutics., Christian K Pfaller, Roberto Cattaneo, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

The order Mononegavirales includes five families: Bornaviridae, Filoviridae, Nyamaviridae, Paramyxoviridae, and Rhabdoviridae. The genome of these viruses is one molecule of negative-sense single strand RNA coding for five to ten genes in a conserved order. The RNA is not infectious until packaged by the nucleocapsid protein and transcribed by the polymerase and co-factors. Reverse genetics approaches have answered fundamental questions about the biology of Mononegavirales. The lack of icosahedral symmetry and modular organization in the genome of these viruses has facilitated engineering of viruses expressing fluorescent proteins, and these fluorescent proteins have provided important insights about the molecular and cellular …

Transarterial Chemoembolization Is Ineffective For Neuroendocrine Tumors Metastatic To The Caudate Lobe: A Single Institution Review., Lawrence A Shirley, Megan Mcnally, Ravi Chokshi, Natalie Jones, Patrick Tassone, Gregory Guy, Hooman Khabiri, Carl Schmidt, Manisha Shah, Mark Bloomston

Oncology Articles

BACKGROUND: Caudate lobe liver metastases occur commonly in patients with neuroendocrine tumors. It is unknown, however, how these lesions respond to regional therapy and how their presence impacts outcomes. We reviewed our experience treating these lesions using transarterial chemoembolization (TACE).

METHODS: We reviewed radiographic response to TACE in 86 patients with metastatic neuroendocrine tumors to the liver. We determined the impact of caudate lesions on outcomes in comparison to the cohort of patients without caudate lesions, as well as response of caudate lesions to TACE versus lesions elsewhere in the liver.

RESULTS: Caudate lesions were identified in 45 (52%) patients. …