Medical Molecular Biology Commons^™

On Statistical Modeling Of Sequencing Noise In High Depth Data To Assess Tumor Evolution, R. Rabadan, G. Bhanot, S. Marsilio, N. Chiorazzi, L. Pasqualucci, H. Khiabanian

Journal Articles

© 2017, Springer Science+Business Media, LLC, part of Springer Nature. One cause of cancer mortality is tumor evolution to therapy-resistant disease. First line therapy often targets the dominant clone, and drug resistance can emerge from preexisting clones that gain fitness through therapy-induced natural selection. Such mutations may be identified using targeted sequencing assays by analysis of noise in high-depth data. Here, we develop a comprehensive, unbiased model for sequencing error background. We find that noise in sufficiently deep DNA sequencing data can be approximated by aggregating negative binomial distributions. Mutations with frequencies above noise may have prognostic value. We evaluate …

Neuro-Immune Interactions In Inflammation And Host Defense: Implications For Transplantation, S. S. Chavan, P. Ma, I. M. Chiu

Journal Articles

© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons Sensory and autonomic neurons of the peripheral nervous system (PNS) play a critical role in regulating the immune system during tissue inflammation and host defense. Recent studies have identified the molecular mechanisms underlying the bidirectional communication between the nervous system and the immune system. Here, we highlight the studies that demonstrate the importance of the neuro-immune interactions in health and disease. Nociceptor sensory neurons detect immune mediators to produce pain, and release neuropeptides that act on the immune system to regulate inflammation. In parallel, neural reflex …

Design And Mechanism Of (S)-3-Amino-4-(Difluoromethylenyl)Cyclopent-1-Ene-1-Carboxylic Acid, A Highly Potent Γ-Aminobutyric Acid Aminotransferase Inactivator For The Treatment Of Addiction, J. I. Juncosa, K. Takaya, H. V. Le, M. J. Moschitto, P. M. Weerawarna, R. Mascarenhas, D. Liu, S. L. Dewey, R. B. Silverman

Journal Articles

© 2018 American Chemical Society. γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. Inhibition of GABA aminotransferase (GABA-AT), a pyridoxal 5′-phosphate (PLP)-dependent enzyme that degrades GABA, has been established as a possible strategy for the treatment of substance abuse. The raised GABA levels that occur as a consequence of this inhibition have been found to antagonize the rapid release of dopamine in the ventral striatum (nucleus accumbens) that follows an acute challenge by an addictive substance. In addition, increased GABA levels are also known to elicit an anticonvulsant effect in patients with epilepsy. We previously …

Glucocorticoid Use And Factors Associated With Variability In This Use In The Systemic Lupus International Collaborating Clinics Inception Cohort, J. Little, B. Parker, M. Lunt, J. G. Hanly, M. B. Urowitz, A. E. Clarke, J. Romero-Diaz, C. Aranow, M. Mackay, I. N. Bruce, +32 Additional Authors

Journal Articles

© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. Objectives. To describe glucocorticoid (GC) use in the SLICC inception cohort and to explore factors associated with GC use. In particular we aimed to assess temporal trends in GC use and to what extent physician-related factors may influence use. Methods. Patients were recruited within 15 months of diagnosis of SLE from 33 centres between 1999 and 2011 and continue to be reviewed annually. Descriptive statistics were used to detail oral and parenteral GC use. Cross sectional and longitudinal analyses were …

Global And Multi-Focal Changes In Cerebral Blood Flow During Subthalamic Nucleus Stimulation In Parkinson’S Disease, A. M. Mubeen, B. Ardekani, M. Tagliati, R. Alterman, V. Dhawan, D. Eidelberg, J. J. Sidtis

Journal Articles

© 2017, © The Author(s) 2017. Electrical stimulation of subthalamic nuclei (STN) is a widely used therapy in Parkinson’s disease (PD). While deep brain stimulation (DBS) of the STN alters the neurophysiological activity in basal ganglia, the therapeutic mechanism has not been established. A positron emission tomography (PET) study of cerebral blood flow (CBF) during speech production in PD subjects treated with STN-DBS found significant increases in global (whole-brain) CBF.1That study utilized a series of whole-slice regions of interest to obtain global CBF values. The present study examined this effect using a voxel-based principal component analysis (PCA) combined with Fisher’s …

Switching Language Modes: Complementary Brain Patterns For Formulaic And Propositional Language, J. J. Sidtis, D. Van Lancker Sidtis, V. Dhawan, D. Eidelberg

Journal Articles

© John J. Sidtis et al. 2018. Language has been modeled as a rule governed behavior for generating an unlimited number of novel utterances using phonological, syntactic, and lexical processes. This view of language as essentially propositional is expanding as a contributory role of formulaic expressions (e.g., you know, have a nice day, how are you?) is increasingly recognized. The basic features of the functional anatomy of this language system have been described by studies of brain damage: left lateralization for propositional language and greater right lateralization and basal ganglia involvement for formulaic expressions. Positron emission tomography (PET) studies of …

Editorial: Neuro-Immune Interactions In Inflammation And Autoimmunity, N. Terrando, V. A. Pavlov

Journal Articles

No abstract provided.

Mutational Spectrum In A Worldwide Study Of 29,700 Families With Brca1 Or Brca2 Mutations, T. R. Rebbeck, T. M. Friebel, E. Friedman, U. Hamann, D. Huo, A. Kwong, E. Olah, O. I. Olopade, A. Lee, K. L. Nathanson, +231 Additional Authors

Journal Articles

No abstract provided.

Molecular And Functional Neuroscience In Immunity, V. A. Pavlov, S. S. Chavan, K. J. Tracey

Journal Articles

No abstract provided.

Limited Reliability Of The Spot Urine Protein/Creatinine Ratio In The Longitudinal Evaluation Of Patients With Lupus Nephritis, G. Shidham, I. Ayoub, D. Birmingham, P. Hebert, B. Rovin, B. Diamond, D. Wofsy, L. Hebert

Journal Articles

© 2018 International Society of Nephrology Introduction: Cross-sectional studies document that the spot protein/creatinine ratio (PCR) is often an inaccurate estimate of proteinuria magnitude compared with the 24-hour PCR, which is the gold standard. However, the extent to which the inaccuracy of the spot PCR varies over time and between individuals has not previously been reported. We address these crucial questions using a unique database, an National Institutes of Health trial in which lupus nephritis (LN) patients (N = 103) provided spot PCR testing each month and 24-hour PCR testing every 3 months for up to 15 months after induction …

Comparison Of Therapeutic Triiodothyronine Versus Metoprolol In The Treatment Of Myocardial Infarction In Rats, K. Zhang, Y. D. Tang, Y. Zhang, K. Ojamaa, Y. Li, A. S. Saini, M. A. Carrillo-Sepulveda, V. Rajagopalan, A. M. Gerdes

Journal Articles

© 2018 Mary Ann Liebert, Inc. Background: Beta blockers are standard therapy for myocardial infarction (MI). Preclinical studies have shown efficacy and safety of thyroid hormone (TH) treatment of cardiovascular disorders. Since THs interact with the sympathoadrenergic system, this study aimed to compare triiodothyronine (T3) and metoprolol (Met) in the treatment of rats with MI on pathophysiology and TH-adrenergic signaling. Methods: Female Sprague-Dawley rats aged 12 weeks underwent left anterior descending coronary artery ligation (MI) or sham surgeries. T3 (5 μg/kg/day) or Met (100 mg/kg/day) was given in drinking water immediately after surgery for eight weeks. At the terminal of …

Altered Leukocyte Gene Expression After Traumatic Spinal Cord Injury: Clinical Implications, P. E. Herman, O. Bloom

Journal Articles

No abstract provided.

Fine-Mapping And Functional Studies Highlight Potential Causal Variants For Rheumatoid Arthritis And Type 1 Diabetes, H. J. Westra, M. Martínez-Bonet, S. Onengut-Gumuscu, A. Lee, Y. Luo, N. Teslovich, J. Worthington, J. Martin, P. K. Gregersen, S. Raychaudhuri, +9 Additional Authors

Journal Articles

© 2018, The Author(s), under exclusive licence to Springer Nature America, Inc. To define potentially causal variants for autoimmune disease, we fine-mapped1,276 rheumatoid arthritis (11,475 cases, 15,870 controls)3and type 1 diabetes loci (9,334 cases, 11,111 controls)4. After sequencing 799 1-kilobase regulatory (H3K4me3) regions within these loci in 568 individuals, we observed accurate imputation for 89% of common variants. We defined credible sets of ≤5 causal variants at 5 rheumatoid arthritis and 10 type 1 diabetes loci. We identified potentially causal missense variants at DNASE1L3, PTPN22, SH2B3, and TYK2, and noncoding variants at MEG3, CD28–CTLA4, and IL2RA. We also identified potential …

Anticancer And Differentiation Properties Of The Nitric Oxide Derivative Of Lopinavir In Human Glioblastoma Cells, M. S. Basile, E. Mazzon, T. Krajnovic, D. Draca, E. Cavalli, Y. Al-Abed, P. Bramanti, F. Nicoletti, S. Mijatovic, D. Maksimovic-Ivanic

Journal Articles

© 2018 by the authors. Glioblastoma (GBM) is the most frequent and deadly form of primary malignant brain tumor among adults. A promising emerging approach for GBM treatment may be offered from HIV protease inhibitors (HIV-PIs). In fact, in addition to their primary pharmacological activity in the treatment of HIV infection, they possess important anti-neoplastic effects. According to previous studies, the addition of a nitric oxide (NO) donating group to parental compounds can reduce their toxicity and enhance the anticancer action of various compounds, including HIV-PIs. In this study we compared the effects of the HIV-PI Lopinavir (Lopi) and of …

Economic Evaluation Of Lupus Nephritis In The Systemic Lupus International Collaborating Clinics Inception Cohort Using A Multistate Model Approach., M. R.W. Barber, J. G. Hanly, L. Su, M. B. Urowitz, Y. St Pierre, J. Romero-Diaz, C. Gordon, C. Aranow, M. Mackay, A. E. Clarke, +30 Additional Authors

Journal Articles

OBJECTIVE: Little is known about the long-term costs of lupus nephritis (LN). The costs were compared between patients with and without LN using multistate modeling.

METHODS: Patients from 32 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using the estimated glomerular filtration rate (GFR) or estimated proteinuria. A multistate model was used to predict 10-year cumulative …

Correction: The Cop9 Signalosome Interacts With And Regulates Interferon Regulatory Factor 5 Protein Stability [Mol Cell Biol, 38, (2013) (E00493-17)] Doi: 10.1128/Mcb.00493-17, J. Korczeniewska, B. J. Barnes

Journal Articles

© 2018 American Society for Microbiology. The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial functions in the regulation of host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and macrophage polarization. Tight regulation of IRF5 is thus warranted for an efficient response to extracellular stressors and for limiting autoimmune and inflammatory responses. Here we report that the COP9 signalosome (CSN), a general modulator of diverse cellular and developmental processes, associates constitutively with IRF5 and promotes its protein stability. The constitutive CSN/IRF5 interaction was identified using proteomics and confirmed by endogenous immunoprecipitations. The CSN/IRF5 interaction occurred on …

Corrected And Republished From: The Cop9 Signalosome Interacts With And Regulates Interferon Regulatory Factor 5 Protein Stability., J. Korczeniewska, B. J. Barnes

Journal Articles

© 2018 American Society for Microbiology. The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial functions in the regulation of host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and macrophage polarization. Tight regulation of IRF5 is thus warranted for an efficient response to extracellular stressors and for limiting autoimmune and inflammatory responses. Here we report that the COP9 signalosome (CSN), a general modulator of diverse cellular and developmental processes, associates constitutively with IRF5 and promotes its protein stability. The constitutive CSN/IRF5 interaction was identified using proteomics and confirmed by endogenous immunoprecipitations. The CSN/IRF5 interaction occurred on …

Lupus Community Panel Proposals For Optimising Clinical Trials: 2018, J. T. Merrill, S. Manzi, C. Aranow, A. Askenase, I. Bruce, E. Chakravarty, B. Chong, K. Costenbader, M. Dall'era, V. P. Werth, +7 Additional Authors

Journal Articles

© 2018 Article author(s). Formidable impediments stand in the way of treatment development for lupus. These include the unwieldy size of current trials, international competition for scarce patients, complex outcome measures and a poor understanding of these outcomes in the world at large. The heterogeneity of the disease itself coupled to superimposition of variegated background polypharmacy has created enough immunological noise to virtually ensure the failure of lupus treatment trials, leaving an understandable suspicion that at least some of the results in testing failed drugs over the years may not have been negative, but merely uninterpretable. The authors have consulted …

Persistent Stress-Induced Neuroplastic Changes In The Locus Coeruleus/Norepinephrine System, Olga Borodovitsyna, Neal Joshi, Daniel Chandler

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Neural plasticity plays a critical role in mediating short- and long-term brain responses to environmental stimuli. A major effector of plasticity throughout many regions of the brain is stress. Activation of the locus coeruleus (LC) is a critical step in mediating the neuroendocrine and behavioral limbs of the stress response. During stressor exposure, activation of the hypothalamic-pituitary-adrenal axis promotes release of corticotropin-releasing factor in LC, where its signaling promotes a number of physiological and cellular changes. While the acute effects of stress on LC physiology have been described, its long-term effects are less clear. This review will describe how stress …

Exploring The Regulatory Mechanism Of The Notch Ligand Receptor Jagged1 Via The Aryl Hydrocarbon Receptor In Breast Cancer, Sean Alan Piwarski

Theses, Dissertations and Capstones

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that binds pollutants, therapeutic drugs and endogenous ligands. AHR is of particular interest in cancer and has been shown to play roles in both tumor progression and tumor suppression. As a result, it has received growing attention as a possible chemotherapeutic target. AHR is expressed in all breast cancer subtypes and can promote or inhibit breast cancer depending on the ligand it binds. The Notch signaling pathway is a highly conserved evolutionary pathway that plays extremely vital roles during development by regulating cell fate and differentiation. Notch signaling has increasingly …