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Genome Sequencing Of The Sweetpotato Whitefly Bemisia Tabaci Med/Q, Wen Xie, Chunhai Chen, Zezhong Yang, Litao Guo, Xin Yang, Dan Wang, Ming Chen, Jinqun Huang, Yanan Wen, Yang Zeng, Yating Liu, Jixing Xia, Lixia Tian, Hongying Cui, Qingjun Wu, Shaoli Wang, Baoyun Xu, Xianchun Li, Xinqiu Tan, Murad Ghanim, Baoli Qiu, Huipeng Pan, Dong Chu, Helene Delatte, M. N. Maruthi, Feng Ge, Xueping Zhou, Xiaowei Wang, Fanghao Wan, Yuzhou Du, Xuguo Joe Zhou

Entomology Faculty Publications

The sweetpotato whitefly Bemisia tabaci is a highly destructive agricultural and ornamental crop pest. It damages host plants through both phloem feeding and vectoring plant pathogens. Introductions of B. tabaci are difficult to quarantine and eradicate because of its high reproductive rates, broad host plant range, and insecticide resistance. A total of 791 Gb of raw DNA sequence from whole genome shotgun sequencing, and 13 BAC pooling libraries were generated by Illumina sequencing using different combinations of mate-pair and pair-end libraries. Assembly gave a final genome with a scaffold N50 of 437 kb, and a total length of 658 Mb. …

Polymer Micelle Formulation For The Proteasome Inhibitor Drug Carfilzomib: Anticancer Efficacy And Pharmacokinetic Studies In Mice, Ji Eun Park, Se-Eun Chun, Derek Alexander Reichel, Jee Sun Min, Su-Chan Lee, Songhee Han, Gongmi Ryoo, Yunseok Oh, Shin-Hyung Park, Heon-Min Ryu, Kyung Bo Kim, Ho-Young Lee, Soo Kyung Bae, Younsoo Bae, Wooin Lee

Pharmaceutical Sciences Faculty Publications

Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradable block copolymers poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) can improve the metabolic stability of CFZ in vitro. Here, we prepared the CFZ-loaded PM, PEG-PCL-deoxycholic …

Cpt1a Methylation Is Associated With Plasma Adiponectin, S. Aslibekyan, A. N. Do, H. Xu, S. Li, M. R. Irvin, D Zhi, H. K. Tiwari, D. M. Absher, A. R. Shuldiner, T. Zhang, W. Chen, K. Tanner, C. Hong, B. D. Mitchell, G. Berenson, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background and Aims—Adiponectin, an adipose-secreted protein that has been linked to insulin sensitivity, plasma lipids, and inflammatory patterns, is an established biomarker for metabolic health. Despite clinical relevance and high heritability, the determinants of plasma adiponectin levels remain poorly understood.

Methods and Results—We conducted the first epigenome-wide cross-sectional study of adiponectin levels using methylation data on 368,051 cytosine-phosphate-guanine (CpG) sites in CD4+ T-cells from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n= 991). We fit linear mixed models, adjusting for age, sex, study site, T-cell purity, and family. We have identified a positive association (regression …

Using A Respiratory Navigator Significantly Reduces Variability When Quantifying Left Ventricular Torsion With Cardiovascular Magnetic Resonance, Sean M. Hamlet, Christopher M. Haggerty, Jonathan D. Suever, Gregory J. Wehner, Kristin N. Andres, David K. Powell, Richard J. Charnigo, Brandon K. Fornwalt

Electrical and Computer Engineering Faculty Publications

Background: Left ventricular (LV) torsion is an important indicator of cardiac function that is limited by high inter-test variability (50% of the mean value). We hypothesized that this high inter-test variability is partly due to inconsistent breath-hold positions during serial image acquisitions, which could be significantly improved by using a respiratory navigator for cardiovascular magnetic resonance (CMR) based quantification of LV torsion.

Methods: We assessed respiratory-related variability in measured LV torsion with two distinct experimental protocols. First, 17 volunteers were recruited for CMR with cine displacement encoding with stimulated echoes (DENSE) in which a respiratory navigator was used to measure …

Cytomegalovirus Serostatus, Inflammation, And Antibody Response To Influenza Vaccination In Older Adults: The Moderating Effect Of Beta Blockade, Rebecca G. Reed, Richard N. Greenberg, Suzanne C. Segerstrom

Psychology Faculty Publications

Cytomegalovirus (CMV) has been implicated as a factor in immunosenescence, including poor antibody response to vaccination and higher immune activation and inflammation. Some people may be more or less vulnerable to the negative effects of CMV. The present investigation tested the effects of beta-blocker use and chronological age on the associations between CMV and immunity in adults aged 60–91 (N=98; 69% CMV seropositive) who were administered the trivalent influenza vaccine for up to 5 years. Peak antibody response, corrected for baseline, and spring (persistent) antibody response, corrected for peak, were assessed, as well as beta-2 microglobulin (β2μ) and interleukin-6 (IL-6). …

Relb Expression Determines The Differential Effects Of Ascorbic Acid In Normal And Cancer Cells, Xiaowei Wei, Yong Xu, Fang Fang Xu, Luksana Chaiswing, David M. Schnell, Teresa Noel, Chi Wang, Jinfei Chen, Daret K. St. Clair, William H. St. Clair

Toxicology and Cancer Biology Faculty Publications

Cancer cells typically experience higher oxidative stress than normal cells, such that elevating pro-oxidant levels can trigger cancer cell death. Although pre-exposure to mild oxidative agents will sensitize cancer cells to radiation, this pre-exposure may also activate the adaptive stress defense system in normal cells. Ascorbic acid is a prototype redox modulator that when infused intravenously appears to kill cancers without injury to normal tissues; however, the mechanisms involved remain elusive. In this study, we show how ascorbic acid kills cancer cells and sensitizes prostate cancer to radiation therapy while also conferring protection upon normal prostate epithelial cells against radiation-induced …

Faster Self-Paced Rate Of Drinking For Alcohol Mixed With Energy Drinks Versus Alcohol Alone, Cecile A. Marczinski, Mark T. Fillmore, Sarah F. Maloney, Amy L. Stamates

Psychology Faculty Publications

The consumption of alcohol mixed with energy drinks (AmED) has been associated with higher rates of binge drinking and impaired driving when compared with alcohol alone. However, it remains unclear why the risks of use of AmED are heightened compared with alcohol alone even when the doses of alcohol consumed are similar. Therefore, the purpose of this laboratory study was to investigate if the rate of self-paced beverage consumption was faster for a dose of AmED versus alcohol alone using a double-blind, within-subjects, placebo-controlled study design. Participants (n = 16) of equal gender who were social drinkers attended 4 separate …

Otolith Dysfunction In Persons With Both Diabetes And Benign Paroxysmal Positional Vertigo., Linda J. DʼSilva, Hinrich Staecker, James Lin, Christy Maddux, John Ferraro, Hongying Dai, Patricia M. Kluding

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Vestibular dysfunction is a well-recognized complication of type 2 diabetes (DM) that may contribute to increased fall risk. The prevalence of benign paroxysmal positional vertigo (BPPV) is higher in people with DM. The impact of DM on the otolith organs of the vestibular system in people with BPPV is unknown. The purpose of this study was to analyze otolith function using vestibular-evoked myogenic potential (VEMP) tests in people with DM and concurrent BPPV (BPPV + DM), and to examine the relationships between VEMP variables and diabetes-related variables.

STUDY DESIGN: Prospective, cross-sectional study.

SETTING: Tertiary academic medical center.

SUBJECTS AND …

Reduced Skeletal Muscle Satellite Cell Number Alters Muscle Morphology After Chronic Stretch But Allows Limited Serial Sarcomere Addition, Matthew C. Kinney, Sudarshan Dayanidhi, Peter B. Dykstra, John J. Mccarthy, Charlotte A. Peterson, Richard L. Lieber

Physiology Faculty Publications

Introduction: Muscles add sarcomeres in response to stretch, presumably to maintain optimal sarcomere length. Clinical evidence from patients with cerebral palsy, who have both decreased serial sarcomere number and reduced satellite cells (SCs), suggests a hypothesis that SCs may be involved in sarcomere addition. Methods: A transgenic Pax7‐DTA mouse model underwent conditional SC depletion, and their soleii were then stretch‐immobilized to assess the capacity for sarcomere addition. Muscle architecture, morphology, and extracellular matrix (ECM) changes were also evaluated. Results: Mice in the SC‐reduced group achieved normal serial sarcomere addition in response to stretch. However, muscle fiber cross‐sectional …

Genetic Drivers Of Kidney Defects In The Digeorge Syndrome., Esther Lopez-Rivera, Yangfan P. Liu, Miguel Verbitsky, Blair R. Anderson, Valentina P. Capone, Edgar A. Otto, Zhonghai Yan, Adele Mitrotti, Jeremiah Martino, Nicholas J. Steers, David A. Fasel, Katarina Vukojevic, Rong Deng, Silvia E. Racedo, Qingxue Liu, Max Werth, Rik Westland, Asaf Vivante, Gabriel S. Makar, Monica Bodria, Matthew G. Sampson, Christopher E. Gillies, Virginia Vega-Warner, Mariarosa Maiorana, Donald S. Petrey, Barry Honig, Vladimir J. Lozanovski, Rémi Salomon, Laurence Heidet, Wassila Carpentier, Dominique Gaillard, Alba Carrea, Loreto Gesualdo, Daniele Cusi, Claudia Izzi, Francesco Scolari, Joanna A E Van Wijk, Adela Arapovic, Mirna Saraga-Babic, Marijan Saraga, Nenad Kunac, Ali Samii, Donna M. Mcdonald-Mcginn, Terrence B. Crowley, Elaine H. Zackai, Dorota Drozdz, Monika Miklaszewska, Marcin Tkaczyk, Przemyslaw Sikora, Maria Szczepanska, Malgorzata Mizerska-Wasiak, Grazyna Krzemien, Agnieszka Szmigielska, Marcin Zaniew, John M. Darlow, Prem Puri, David Barton, Emilio Casolari, Susan L. Furth, Bradley A. Warady, Zoran Gucev, Hakon Hakonarson, Hana Flogelova, Velibor Tasic, Anna Latos-Bielenska, Anna Materna-Kiryluk, Landino Allegri, Craig S. Wong, Iain A Drummond, Vivette D'Agati, Akira Imamoto, Jonathan M. Barasch, Friedhelm Hildebrandt, Krzysztof Kiryluk, Richard P. Lifton, Bernice E. Morrow, Cecile Jeanpierre, Virginia E. Papaioannou, Gian Marco Ghiggeri, Ali G. Gharavi, Nicholas Katsanis, Simone Sanna-Cherchi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown.

METHODS: We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice.

RESULTS: We identified heterozygous deletions of 22q11.2 in 1.1% …

Mechanisms Of Therapeutic Resistance In Prostate Cancer, Mary Nakazawa, Channing Paller, Natasha Kyprianou

Urology Faculty Publications

Prostate cancer is the second leading cause of cancer deaths in the USA. The challenge in managing castration-resistant prostate cancer (CRPC) stems not from the lack of therapeutic options but from the limited duration of clinical and survival benefit offered by treatments in this setting due to primary and acquired resistance. The remarkable molecular heterogeneity and tumor adaptability in advanced prostate cancer necessitate optimization of such treatment strategies. While the future of CRPC management will involve newer targeted therapies in deliberately biomarker-selected patients, interventions using current approaches may exhibit improved clinical benefit if employed in the context of optimal sequencing …

Secondary Release Of Exosomes From Astrocytes Contributes To The Increase In Neural Plasticity And Improvement Of Functional Recovery After Stroke In Rats Treated With Exosomes Harvested From Microrna 133b-Overexpressing Multipotent Mesenchymal Stromal Cells., Hongqi Xin, Fengjie Wang, Yanfeng Li, Qing-E Lu, Wing L. Cheung, Yi Zhang, Zhenggang Zhang, Michael Chopp

Emergency Medicine Articles

We previously demonstrated that multipotent mesenchymal stromal cells (MSCs) that overexpress microRNA 133b (miR-133b) significantly improve functional recovery in rats subjected to middle cerebral artery occlusion (MCAO) compared with naive MSCs and that exosomes generated from naive MSCs mediate the therapeutic benefits of MSC therapy for stroke. Here we investigated whether exosomes isolated from miR-133b-overexpressing MSCs (Ex-miR-133b+) exert amplified therapeutic effects. Rats subjected to 2 h of MCAO were intra-arterially injected with Ex-miR-133b+, exosomes from MSCs infected by blank vector (Ex-Con), or phosphate-buffered saline (PBS) and were sacrificed 28 days after MCAO. Compared with the PBS treatment, both exosome treatment …

A Quantitative Lc-Ms/Ms Method For Simultaneous Determination Of Cocaine And Its Metabolites In Whole Blood, Xiabin Chen, Xirong Zheng, Kai Ding, Ziyuan Zhou, Chang-Guo Zhan, Fang Zheng

Molecular Modeling and Biopharmaceutical Center Faculty Publications

As new metabolic pathways of cocaine were recently identified, a high performance liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed to simultaneously determine cocaine and nine cocaine-related metabolites in whole blood samples. One-step solid phase extraction was used to extract all of the ten compounds and corresponding internal standards from blood samples. All compounds and internal standards extracted were separated on an Atlantis T3 (100 Å, 3 μm, 2.1 mm × 150 mm I.D) column and detected in positive ion and high sensitivity mode with multiple reaction monitoring. This method was validated for its sensitivity, linearity, specificity, accuracy, precision, …

Adolescent Cannabinoid Exposure Induces A Persistent Sub-Cortical Hyper-Dopaminergic State And Associated Molecular Adaptations In The Prefrontal Cortex., Justine Renard, Laura G Rosen, Michael Loureiro, Cleusa De Oliveira, Susanne Schmid, Walter J Rushlow, Steven R Laviolette

Brain and Mind Institute Researchers' Publications

Considerable evidence suggests that adolescent exposure to delta-9-tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the risk of developing schizophrenia-related symptoms in early adulthood. In the present study, we used a combination of behavioral and molecular analyses with in vivo neuronal electrophysiology to compare the long-term effects of adolescent versus adulthood THC exposure in rats. We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations. Thus, adolescent THC exposure induced behavioral abnormalities resembling positive and negative schizophrenia-related endophenotypes and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA) pathway. …

The Effect Of Sazetidine-A And Other Nicotinic Ligands On Nicotine Controlled Goal-Tracking In Female And Male Rats, S. Charntikov, A. M. Falco, K. Fink, Linda P. Dwoskin, R. A. Bevins

Pharmaceutical Sciences Faculty Publications

Nicotine is the primary addictive component of tobacco products and its complex stimulus effects are readily discriminated by humans and non-human animals. Previous preclinical research investigating directly the nature of the nicotine stimulus has been limited to male rodents. The current study began to address this significant gap in the literature by training female and male rats to discriminate 0.4 mg/kg nicotine from saline in the discriminated goal-tracking task. In this task, access to sucrose was intermittently available on nicotine session. On saline session, intermixed with nicotine sessions on separate days, sucrose was not available. Both sexes acquired the discrimination …

Nephrotoxicity During Vancomycin Therapy In Combination With Piperacillin-Tazobactam Or Cefepime, Wilbur Cliff Rutter, Jessica N. Cox, Craig A. Martin, Donna R. Burgess, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a retrospective, matched cohort study that was conducted at an academic medical center between September 2010 and September 2014 and that included adult patients without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h. The primary outcome was the difference in …

Cystatin C And Cardiac Measures In Children And Adolescents With Ckd., Tammy M. Brady, Kelly Townsend, Michael F. Schneider, Christopher Cox, Thomas Kimball, Peace Madueme, Bradley A. Warady, Susan Furth, Mark Mitsnefes

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Cardiovascular disease (CVD) is highly prevalent among children with chronic kidney disease (CKD). Cystatin C is an established marker of kidney function and an emerging biomarker for CVD events. We quantified the relationship between cystatin C level and cardiac structure and function over time among children with CKD and assessed whether cystatin C level and diastolic function retained an association after accounting for kidney function.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: 678 children and adolescents with mild to moderate CKD enrolled in the CKD in Children (CKiD) Study with 1,228 echocardiographically obtained cardiac structure and function measurements. …

Myocardial Relaxation Is Accelerated By Fast Stretch, Not Reduced Afterload, Charles S. Chung, Charles W. Hoopes, Kenneth S. Campbell

Physiology Faculty Publications

Fast relaxation of cross-bridge generated force in the myocardium facilitates efficient diastolic function. Recently published research studying mechanisms that modulate the relaxation rate has focused on molecular factors. Mechanical factors have received less attention since the 1980s when seminal work established the theory that reducing afterload accelerates the relaxation rate. Clinical trials using afterload reducing drugs, partially based on this theory, have thus far failed to improve outcomes for patients with diastolic dysfunction. Therefore, we reevaluated the protocols that suggest reducing afterload accelerates the relaxation rate and identified that myocardial relengthening was a potential confounding factor. We hypothesized that the …

Safety And Improvement Of Movement Function After Stroke With Atomoxetine: A Pilot Randomized Trial, Andrea Ward, Cheryl Carrico, Elizabeth Powell, Philip M. Westgate, Laurie Nichols, Anne Fleischer, Lumy Sawaki

Physical Medicine and Rehabilitation Faculty Publications

Background: Intensive, task-oriented motor training has been associated with neuroplastic reorganization and improved upper extremity movement function after stroke. However, to optimize such training for people with moderate-to-severe movement impairment, pharmacological modulation of neuroplasticity may be needed as an adjuvant intervention.

Objective: Evaluate safety, as well as improvement in movement function, associated with motor training paired with a drug to upregulate neuroplasticity after stroke.

Methods: In this double-blind, randomized, placebo-controlled study, 12 subjects with chronic stroke received either atomoxetine or placebo paired with motor training. Safety was assessed using vital signs. Upper extremity movement function was assessed using Fugl-Meyer Assessment, …

Oviposition Traits Generate Extrinsic Postzygotic Isolation Between Two Pine Sawfly Species, Emily E. Bendall, Kim L. Vertacnik, Catherine R. Linnen

Biology Faculty Publications

Background: Although empirical data indicate that ecological speciation is prevalent in nature, the relative importance of different forms of reproductive isolation and the traits generating reproductive isolation remain unclear. To address these questions, we examined a pair of ecologically divergent pine-sawfly species: while Neodiprion pinetum specializes on a thin-needled pine (Pinus strobus), N. lecontei utilizes thicker-needled pines. We hypothesized that extrinsic postzygotic isolation is generated by oviposition traits. To test this hypothesis, we assayed ovipositor morphology, oviposition behavior, and host-dependent oviposition success in both species and in F1 and backcross females.

Results: Compared to N. lecontei, N. …

Reduced Microrna-503 Expression Augments Lung Fibroblast Vegf Production In Chronic Obstructive Pulmonary Disease, Jun Ikari, Amy J. Nelson, Jannah Obaid, Alvaro Giron-Martinez, Kumiko Ikari, Fumihiko Makino, Shunichiro Iwasawa, Yoko Gunji, Maha Farid, Xingqi Wang, Hesham Basma, Dawn Demeo, Carol Feghali-Bostwick, Olaf Holz, Klaus Rabe, Xiangde Liu, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Alterations in microRNA (miRNA) expression may contribute to COPD pathogenesis. In COPD, lung fibroblast repair functions are altered in multiple ways, including extracellular mediator release. Our prior study revealed miR-503 expression is decreased in COPD lung fibroblasts, although the exact role played by miR-503 is undetermined. The current study examined a role of miR-503 in cytokine, growth factor and fibronectin production by lung fibroblasts from patients with and without COPD. Primary adult lung fibroblasts were isolated from patients with or without COPD. MiR-503 expression and interleukin (IL)-6, -8, PGE2, HGF, KGF, VEGF and fibronectin release were examined with or without …

Cold Tolerance Of Third-Instar Drosophila Suzukii Larvae., Ruth Jakobs, Banafsheh Ahmadi, Sarah Houben, Tara D Gariepy, Brent J Sinclair

Biology Publications

Drosophila suzukii is an emerging global pest of soft fruit; although it likely overwinters as an adult, larval cold tolerance is important both for determining performance during spring and autumn, and for the development of temperature-based control methods aimed at larvae. We examined the low temperature biology of third instar feeding and wandering larvae in and out of food. We induced phenotypic plasticity of thermal biology by rearing under short days and fluctuating temperatures (5.5-19°C). Rearing under fluctuating temperatures led to much slower development (42.1days egg-adult) compared to control conditions (constant 21.5°C; 15.7days), and yielded larger adults of both sexes. …

Sting Expression And Response To Treatment With Sting Ligands In Premalignant And Malignant Disease., Jason R Baird, Zipei Feng, Hong D Xiao, David Friedman, Ben Cottam, Bernard A Fox, Gwen Kramer, Rom S Leidner, Richard Bryan Bell, Kristina H Young, Marka R Crittenden, Michael J Gough

Articles, Abstracts, and Reports

Human papilloma virus positive (HPV+) tumors represent a large proportion of anal, vulvar, vaginal, cervical and head and neck squamous carcinomas (HNSCC) and late stage invasive disease is thought to originate from a premalignant state. Cyclic dinucleotides that activate STimulator of INterferon Genes (STING) have been shown to cause rapid regression of a range of advanced tumors. We aimed to investigate STING ligands as a novel treatment for papilloma. We tested therapies in a spontaneous mouse model of papilloma of the face and anogenital region that histologically resembles human HPV-associated papilloma. We demonstrate that STING ligands cause rapid regression of …

Post-Traumatic Stress Symptoms In Pathological Gambling: Potential Evidence Of Anti-Reward Processes, Cheryl L. Green, Ramzi W. Nahhas, Arielle A. Scoglio, Igor Elman

Population and Public Health Sciences Faculty Publications

Background: Excessive gambling is considered to be a part of the addiction spectrum. Stress-like emotional states are a key feature both of pathological gambling (PG) and of substance addiction. In substance addiction, stress symptomatology has been attributed in part to "anti-reward" allostatic neuroadaptations, while a potential involvement of anti-reward processes in the course of PG has not yet been investigated. Methods: To that end, individuals with PG (n = 22) and mentally healthy subjects (n = 13) were assessed for trauma exposure and post-traumatic stress symptomatology (PTSS) using the Life Events Checklist and the Civilian Mississippi Scale, respectively. Results: In …

The Distinct Metabolic Phenotype Of Lung Squamous Cell Carcinoma Defines Selective Vulnerability To Glycolytic Inhibition, Justin Goodwin, Michael L. Neugent, Shin Yup Lee, Joshua H. Choe, Hyunsung Choi, Dana M. R. Jenkins, Robin J. Ruthenborg, Maddox W. Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D. Minna, Kristi L. Helke, Pankaj K. Singh, David B. Shackelford, Jung-Whan Kim

Journal Articles: Eppley Institute

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, …

An Indicator Cell Assay For Blood-Based Diagnostics., Samuel A Danziger, Leslie R Miller, Karanbir Singh, G Adam Whitney, Elaine R Peskind, Ge Li, Robert J Lipshutz, John D Aitchison, Jennifer J Smith

Articles, Abstracts, and Reports

We have established proof of principle for the Indicator Cell Assay Platform™ (iCAP™), a broadly applicable tool for blood-based diagnostics that uses specifically-selected, standardized cells as biosensors, relying on their innate ability to integrate and respond to diverse signals present in patients' blood. To develop an assay, indicator cells are exposed in vitro to serum from case or control subjects and their global differential response patterns are used to train reliable, disease classifiers based on a small number of features. In a feasibility study, the iCAP detected pre-symptomatic disease in a murine model of amyotrophic lateral sclerosis (ALS) with 94% …

Safety And Feasibility Of Minimally Invasive Inguinal Lymph Node Dissection In Patients With Melanoma (Safe-Milnd): Report Of A Prospective Multi-Institutional Trial., James W Jakub, Alicia M Terando, Amod Sarnaik, Charlotte E Ariyan, Mark Faries, Sabino Zani, Heather B Neuman, Nabil Wasif, Jeffrey M Farma, Bruce J Averbook, Karl Y Bilimoria, Travis E Grotz, Jacob B Jake Allred, Vera J Suman, Mary Sue Brady, Douglas Tyler, Jeffrey D Wayne, Heidi Nelson

Articles, Abstracts, and Reports

BACKGROUND: Minimally invasive inguinal lymph node dissection (MILND) is a novel approach to inguinal lymphadenectomy. SAFE-MILND (NCT01500304) is a multicenter, phase I/II clinical trial evaluating the safety and feasibility of MILND for patients with melanoma in a group of surgeons newly adopting the procedure.

METHODS: Twelve melanoma surgeons from 10 institutions without any previous MILND experience, enrolled patients into a prospective study after completing specialized training including didactic lectures, participating in a hands-on cadaveric laboratory, and being provided an instructional DVD of the procedure. Complications and adverse postoperative events were graded using the National Cancer Institute (NCI) Common Terminology Criteria …

Micrornas Regulating Cluster Of Differentiation 46 (Cd46) In Cardioembolic And Non-Cardioembolic Stroke, J.R. Tan, K.S. Tan, F.L. Yong, A. Armugam, C.W. Wang, K. Jeyaseelan, P.T.H. Wong

Research Publications (2016 to 2020)

Ischemic stroke is a major cause of mortality and morbidity globally. Among the ischemic stroke subtypes, cardioembolic stroke is with poor functional outcome (Modified Rankin score ≥ 2). Early diagnosis of cardioembolic stroke will prove beneficial. This study examined the microRNAs targeting cluster of differentiation 46 (CD46), a potential biomarker for cardioembolic stroke. CD46 mRNA level was shown to be differentially expressed (p < 0.001) between cardioembolic stroke (median = 1.32) and non-cardioembolic stroke subtypes (large artery stroke median = 5.05; small vessel stroke median = 6.45). Bioinformatic search showed that miR-19a, -20a, -185 and -374b were found to target CD46 mRNA and further verified by luciferase reporter assay. The levels of miRNAs targeting CD46 were significantly reduced (p < 0.05) in non-cardioembolic stroke patients (large artery stroke median: miR-19a = 0.63, miR-20a = 0.42, miR-185 = 0.32, miR-374b = 0.27; small artery stroke median: miR-19a = 0.07, miR-20a = 0.06, miR-185 = 0.07, miR-374b = 0.05) as compared to cardioembolic stroke patients (median: miR-19a = 2.69, miR-20a = 1.36, miR-185 = 1.05, miR-374b = 1.23). ROC curve showed that the miRNAs could distinguish cardioembolic stroke from non-cardioembolic stroke with better AUC value as compared to CD46. Endogenous expression of CD46 in Human Umbilical Vein Endothelial Cells (HUVECs) were found to be regulated by miR-19a and miR-20a. Thus implicating that miR-19a and -20a may play a role in pathogenesis of cardioembolic stroke, possibly via the endothelial cells.

Monitoring Butterflies Using Counts Of Puddling Males: A Case Study Of The Rajah Brooke's Birdwing (Trogonoptera Brookiana Albescens), C.K. Phon, L.G. Kirton, Y. Norma-Rashid

Research Publications (2016 to 2020)

The Rajah Brooke's Birdwing, Trogonoptera brookiana, is a large, iconic butterfly that is facing heavy commercial exploitation and habitat loss. Males of some subspecies exhibit puddling behavior. A method of conservation monitoring was developed for subspecies albescens in Ulu Geroh, Peninsular Malaysia, where the males consistently puddle in single-species aggregations at stable geothermal springs, reaching well over 300 individuals when the population is at its highest. Digital photography was used to conduct counts of numbers of males puddling. The numbers of birdwings puddling were significantly correlated with counts of birdwings in flight, but were much higher. The numbers puddling during …

Neglected Intestinal Parasites, Malnutrition And Associated Key Factors: A Population Based Cross-Sectional Study Among Indigenous Communities In Sarawak, Malaysia, Y. Rajoo, S. Ambu, Y.A.L. Lim, K. Rajoo, S.C. Tey, C.W. Lu, R. Ngui

Research Publications (2016 to 2020)

Intestinal parasitic infections (IPIs) have been recognized as one of the most significant causes of illness among disadvantaged communities. Many studies have been conducted on the prevalence of IPIs in Malaysia. However, these studies mostly focused on the indigenous groups in Peninsular Malaysia. The present study was conducted to provide the current baseline data on prevalence of IPIs, anaemia, malnutrition and associated risk factors among the indigenous communities in Sarawak, situation at northwest Borneo island of Malaysia. A cross sectional study was conducted among the longhouses communities. Stool samples were obtained and examined for the presence of IPIs using microscopy …