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Klein Christoph

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https://www.readbyqxmd.com/read/29352161/the-action-of-a-negative-allosteric-modulator-at-the-dopamine-d2-receptor-is-dependent-upon-sodium-ions
#1
Christopher J Draper-Joyce, Ravi Kumar Verma, Mayako Michino, Jeremy Shonberg, Anitha Kopinathan, Carmen Klein Herenbrink, Peter J Scammells, Ben Capuano, Ara M Abramyan, David M Thal, Jonathan A Javitch, Arthur Christopoulos, Lei Shi, J Robert Lane
Sodium ions (Na+) allosterically modulate the binding of orthosteric agonists and antagonists to many class A G protein-coupled receptors, including the dopamine D2 receptor (D2R). Experimental and computational evidences have revealed that this effect is mediated by the binding of Na+ to a conserved site located beneath the orthosteric binding site (OBS). SB269652 acts as a negative allosteric modulator (NAM) of the D2R that adopts an extended bitopic pose, in which the tetrahydroisoquinoline moiety interacts with the OBS and the indole-2-carboxamide moiety occupies a secondary binding pocket (SBP)...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352082/clostridial-strain-specific-characteristics-associated-with-necrotizing-enterocolitis
#2
Sophia Schönherr-Hellec, Geraldine L Klein, Johanne Delannoy, Laurent Ferraris, Jean Christophe Rozé, Marie José Butel, Julio Aires
We aimed at identifying potential clostridial factors linking these bacteria with necrotizing enterocolitis (NEC). We compared the phenotypic traits, stress responses, cellular cytotoxicity and inflammatory capabilities of the largest collection of Clostridium butyricum and Clostridium neonatale strains isolated from fecal samples of NEC and control preterm neonates (PN). When strains characteristics were used as explanatory variables, a statistical discriminant analysis allowed the separation of NEC and control strains into separate groups...
January 19, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29348365/detection-and-localization-of-surgically-resectable-cancers-with-a-multi-analyte-blood-test
#3
Joshua D Cohen, Lu Li, Yuxuan Wang, Christopher Thoburn, Bahman Afsari, Ludmila Danilova, Christopher Douville, Ammar A Javed, Fay Wong, Austin Mattox, Ralph H Hruban, Christopher L Wolfgang, Michael G Goggins, Marco Dal Molin, Tian-Li Wang, Richard Roden, Alison P Klein, Janine Ptak, Lisa Dobbyn, Joy Schaefer, Natalie Silliman, Maria Popoli, Joshua T Vogelstein, James D Browne, Robert E Schoen, Randall E Brand, Jeanne Tie, Peter Gibbs, Hui-Li Wong, Aaron S Mansfield, Jin Jen, Samir M Hanash, Massimo Falconi, Peter J Allen, Shibin Zhou, Chetan Bettegowda, Luis Diaz, Cristian Tomasetti, Kenneth W Kinzler, Bert Vogelstein, Anne Marie Lennon, Nickolas Papadopoulos
Earlier detection is key to reducing cancer deaths. Here we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1,005 patients with non-metastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69% to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals...
January 18, 2018: Science
https://www.readbyqxmd.com/read/29327927/atom-dependent-edge-enhanced-second-harmonic-generation-on-mos2-monolayers
#4
Kuang-I Lin, Yen-Hung Ho, Shu-Bai Liu, Jian-Jhih Ciou, Bo-Ting Huang, Christopher Chen, Han-Ching Chang, Chien-Liang Tu, Chang-Hsiao Chen
Edge morphology and lattice orientation of single-crystal molybdenum disulfide (MoS2) monolayers, a transition metal dichalcogenide (TMD), possessing a triangular shape with different edges grown by chemical vapor deposition are characterized by atomic force microscopy and transmission electron microscopy. Multiphoton laser scanning microscopy is utilized to study one-dimensional atomic edges of MoS2 monolayers with localized mid-gap electronic states, which result in greatly enhanced optical second-harmonic generation (SHG)...
January 12, 2018: Nano Letters
https://www.readbyqxmd.com/read/29325769/the-structural-determinants-of-the-bitopic-binding-mode-of-a-negative-allosteric-modulator-of-the-dopamine-d2-receptor
#5
Christopher J Draper-Joyce, Mayako Michino, Ravi Kumar Verma, Carmen Klein Herenbrink, Jeremy Shonberg, Anitha Kopinathan, Peter J Scammells, Ben Capuano, David M Thal, Jonathan A Javitch, Arthur Christopoulos, Lei Shi, J Robert Lane
SB269652 is a negative allosteric modulator of the dopamine D2 receptor (D2R) yet possesses structural similarity to ligands with a competitive mode of interaction. In this study, we aimed to understand the ligand-receptor interactions that confer its allosteric action. We combined site-directed mutagenesis with molecular dynamics simulations using both SB269652 and derivatives from our previous structure activity studies. We identify residues within the conserved orthosteric binding site (OBS) and a secondary binding pocket (SBP) that determine affinity and cooperativity...
January 8, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29318178/outcomes-after-dermal-allograft-reconstruction-of-chronic-or-subacute-pectoralis-major-tendon-ruptures
#6
Julie A Neumann, Christopher M Klein, Carola F van Eck, Hithem Rahmi, John M Itamura
Background: Avoiding delay in the surgical management of pectoralis major (PM) ruptures optimizes outcomes. However, this is not always possible, and when a tear becomes chronic or when a subacute tear has poor tissue quality, a graft can facilitate reconstruction. Purpose: The primary aim was to evaluate the clinical outcomes of PM reconstruction with dermal allograft augmentation for chronic tears or for subacute tears with poor tissue quality. A second aim was to determine patient and surgical factors affecting outcome...
January 2018: Orthopaedic Journal of Sports Medicine
https://www.readbyqxmd.com/read/29316475/the-sentinel-lymph-node-spread-determines-quantitatively-melanoma-seeding-to-non-sentinel-lymph-nodes-and-survival
#7
Anja Ulmer, Klaus Dietz, Melanie Werner-Klein, Hans-Martin Häfner, Claudia Schulz, Philipp Renner, Florian Weber, Helmut Breuninger, Martin Röcken, Claus Garbe, Gerhard Fierlbeck, Christoph A Klein
INTRODUCTION: Complete lymph node dissection (CLND) after a positive sentinel node (SN) biopsy provides important prognostic information in melanoma patients but has been questioned for therapeutic use recently. We explored whether quantification of the tumour spread to SNs may replace histopathology of non-sentinel nodes (NSNs) for staging purposes. PATIENTS AND METHODS: We quantified melanoma spread in SNs and NSNs in 128 patients undergoing CLND for a positive SN...
January 6, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29305304/sleeve-gastrectomy-surgery-when-2-alcoholic-drinks-are-converted-to-4
#8
María Belén Acevedo, J Christopher Eagon, Bruce D Bartholow, Samuel Klein, Kathleen K Bucholz, Marta Yanina Pepino
BACKGROUND: While it is well established that Roux-en-Y gastric bypass (RYGB) causes a rapid and heightened peak blood alcohol concentration (BAC), results from previous studies on the effects of sleeve gastrectomy (SG) on alcohol pharmacokinetics are conflicting. Data from 2 studies found SG did not affect BAC, whereas another study found SG caused a heightened peak BAC after alcohol ingestion. Moreover, these 3 studies estimated BAC from breathalyzers, which might not reliably estimate peak BAC...
November 10, 2017: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/29299246/toward-a-methodical-framework-for-comprehensively-assessing-forest-multifunctionality
#9
Stefan Trogisch, Andreas Schuldt, Jürgen Bauhus, Juliet A Blum, Sabine Both, François Buscot, Nadia Castro-Izaguirre, Douglas Chesters, Walter Durka, David Eichenberg, Alexandra Erfmeier, Markus Fischer, Christian Geißler, Markus S Germany, Philipp Goebes, Jessica Gutknecht, Christoph Zacharias Hahn, Sylvia Haider, Werner Härdtle, Jin-Sheng He, Andy Hector, Lydia Hönig, Yuanyuan Huang, Alexandra-Maria Klein, Peter Kühn, Matthias Kunz, Katrin N Leppert, Ying Li, Xiaojuan Liu, Pascal A Niklaus, Zhiqin Pei, Katherina A Pietsch, Ricarda Prinz, Tobias Proß, Michael Scherer-Lorenzen, Karsten Schmidt, Thomas Scholten, Steffen Seitz, Zhengshan Song, Michael Staab, Goddert von Oheimb, Christina Weißbecker, Erik Welk, Christian Wirth, Tesfaye Wubet, Bo Yang, Xuefei Yang, Chao-Dong Zhu, Bernhard Schmid, Keping Ma, Helge Bruelheide
Biodiversity-ecosystem functioning (BEF) research has extended its scope from communities that are short-lived or reshape their structure annually to structurally complex forest ecosystems. The establishment of tree diversity experiments poses specific methodological challenges for assessing the multiple functions provided by forest ecosystems. In particular, methodological inconsistencies and nonstandardized protocols impede the analysis of multifunctionality within, and comparability across the increasing number of tree diversity experiments...
December 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/29295558/effects-of-sleeve-gastrectomy-vs-roux-en-y-gastric-bypass-on-eating-behavior-and-sweet-taste-perception-in-subjects-with-obesity
#10
Katie Nance, J Christopher Eagon, Samuel Klein, Marta Yanina Pepino
The goal of this study was to test the hypothesis that weight loss induced by Roux-en-Y gastric bypass (RYGB) has greater effects on taste perception and eating behavior than comparable weight loss induced by sleeve gastrectomy (SG). We evaluated the following outcomes in 31 subjects both before and after ~20% weight loss induced by RYGB (n = 23) or SG (n = 8): (1) sweet, savory, and salty taste sensitivity; (2) the most preferred concentrations of sucrose and monosodium glutamate; (3) sweetness palatability, by using validated sensory testing techniques; and (4) eating behavior, by using the Food Craving Inventory and the Dutch Eating Behavior Questionnaire...
December 24, 2017: Nutrients
https://www.readbyqxmd.com/read/29290613/the-antiviral-and-cancer-genomic-dna-deaminase-apobec3h-is-regulated-by-an-rna-mediated-dimerization-mechanism
#11
Nadine M Shaban, Ke Shi, Kate V Lauer, Michael A Carpenter, Christopher M Richards, Daniel Salamango, Jiayi Wang, Michael W Lopresti, Surajit Banerjee, Rena Levin-Klein, William L Brown, Hideki Aihara, Reuben S Harris
Human APOBEC3H and homologous single-stranded DNA cytosine deaminases are unique to mammals. These DNA-editing enzymes function in innate immunity by restricting the replication of viruses and transposons. APOBEC3H also contributes to cancer mutagenesis. Here, we address the fundamental nature of RNA in regulating human APOBEC3H activities. APOBEC3H co-purifies with RNA as an inactive protein, and RNase A treatment enables strong DNA deaminase activity. RNA-binding-defective mutants demonstrate clear separation of function by becoming DNA hypermutators...
January 4, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29283973/tenascin-c-promotes-chronic-pressure-overload-induced-cardiac-dysfunction-hypertrophy-and-myocardial-fibrosis
#12
Bruno K Podesser, Maximilian Kreibich, Elda Dzilic, David Santer, Lorenz Förster, Sandra Trojanek, Dietmar Abraham, Martin Krššák, Klaus U Klein, Eva V Tretter, Christoph Kaun, Johann Wojta, Barbara Kapeller, Inês Fonseca Gonçalves, Karola Trescher, Attila Kiss
AIMS: Left ventricular (LV) hypertrophy is characterized by cardiomyocyte hypertrophy and interstitial fibrosis ultimately leading to increased myocardial stiffness and reduced contractility. There is substantial evidence that the altered expression of matrix metalloproteinases (MMP) and Tenascin-C (TN-C) are associated with the progression of adverse LV remodeling. However, the role of TN-C in the development of LV hypertrophy because of chronic pressure overload as well as the regulatory role of TN-C on MMPs remains unknown...
December 27, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29273820/effects-of-caffeine-on-reaction-time-are-mediated-by-attentional-rather-than-motor-processes
#13
Christopher W N Saville, H M de Morree, Neil M Dundon, S M Marcora, C Klein
BACKGROUND: Caffeine has a well-established effect on reaction times (RTs) but the neurocognitive mechanisms underlying this are unclear. METHODS: In the present study, 15 female participants performed an oddball task after ingesting caffeine or a placebo, and electroencephalographic data were obtained. Single-trial P3b latencies locked to the stimulus and to the response were extracted and mediation models were fitted to the data to test whether caffeine's effect on RTs was mediated by its effect on either type of P3b latencies...
December 23, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/29260047/bilateral-acute-simultaneous-onset-anterior-uveitis-presumed-secondary-to-erlotinib-a-report-of-two-cases
#14
Kendra A Klein, Christopher G Azzoli, Lana M Rifkin
Purpose: To report two new cases of presumed erlotinib-associated bilateral acute simultaneous-onset anterior uveitis effectively treated with topical steroids. Observations: Two patients were referred to the uveitis clinic with bilateral acute simultaneous onset, anterior uveitis six weeks after starting the chemotherapeutic agent erlotinib. Frequent topical steroid were started and the inflammation responded swiftly and completely. Conclusions and importance: Bilateral acute simultaneous onset anterior uveitis is a potential side effect associated with erlotinib use that has not been well described...
June 2017: American Journal of Ophthalmology Case Reports
https://www.readbyqxmd.com/read/29247482/commonalities-in-epileptogenic-processes-from-different-acute-brain-insults-do-they-translate
#15
REVIEW
Pavel Klein, Raymond Dingledine, Eleonora Aronica, Christophe Bernard, Ingmar Blümcke, Detlev Boison, Martin J Brodie, Amy R Brooks-Kayal, Jerome Engel, Patrick A Forcelli, Lawrence J Hirsch, Rafal M Kaminski, Henrik Klitgaard, Katja Kobow, Daniel H Lowenstein, Phillip L Pearl, Asla Pitkänen, Noora Puhakka, Michael A Rogawski, Dieter Schmidt, Matti Sillanpää, Robert S Sloviter, Christian Steinhäuser, Annamaria Vezzani, Matthew C Walker, Wolfgang Löscher
The most common forms of acquired epilepsies arise following acute brain insults such as traumatic brain injury, stroke, or central nervous system infections. Treatment is effective for only 60%-70% of patients and remains symptomatic despite decades of effort to develop epilepsy prevention therapies. Recent preclinical efforts are focused on likely primary drivers of epileptogenesis, namely inflammation, neuron loss, plasticity, and circuit reorganization. This review suggests a path to identify neuronal and molecular targets for clinical testing of specific hypotheses about epileptogenesis and its prevention or modification...
December 15, 2017: Epilepsia
https://www.readbyqxmd.com/read/29236689/corrigendum-mechanism-of-early-dissemination-and-metastasis-in-her2-mammary-cancer
#16
Kathryn L Harper, Maria Soledad Sosa, David Entenberg, Hedayatollah Hosseini, Julie F Cheung, Rita Nobre, Alvaro Avivar-Valderas, Chandandaneep Nagi, Nomeda Girnius, Roger J Davis, Eduardo F Farias, John Condeelis, Christoph A Klein, Julio A Aguirre-Ghiso
This corrects the article DOI: 10.1038/nature20609.
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29236593/role-of-genetic-testing-for-inherited-prostate-cancer-risk-philadelphia-prostate-cancer-consensus-conference-2017
#17
Veda N Giri, Karen E Knudsen, William K Kelly, Wassim Abida, Gerald L Andriole, Chris H Bangma, Justin E Bekelman, Mitchell C Benson, Amie Blanco, Arthur Burnett, William J Catalona, Kathleen A Cooney, Matthew Cooperberg, David E Crawford, Robert B Den, Adam P Dicker, Scott Eggener, Neil Fleshner, Matthew L Freedman, Freddie C Hamdy, Jean Hoffman-Censits, Mark D Hurwitz, Colette Hyatt, William B Isaacs, Christopher J Kane, Philip Kantoff, R Jeffrey Karnes, Lawrence I Karsh, Eric A Klein, Daniel W Lin, Kevin R Loughlin, Grace Lu-Yao, S Bruce Malkowicz, Mark J Mann, James R Mark, Peter A McCue, Martin M Miner, Todd Morgan, Judd W Moul, Ronald E Myers, Sarah M Nielsen, Elias Obeid, Christian P Pavlovich, Stephen C Peiper, David F Penson, Daniel Petrylak, Curtis A Pettaway, Robert Pilarski, Peter A Pinto, Wendy Poage, Ganesh V Raj, Timothy R Rebbeck, Mark E Robson, Matt T Rosenberg, Howard Sandler, Oliver Sartor, Edward Schaeffer, Gordon F Schwartz, Mark S Shahin, Neal D Shore, Brian Shuch, Howard R Soule, Scott A Tomlins, Edouard J Trabulsi, Robert Uzzo, Donald J Vander Griend, Patrick C Walsh, Carol J Weil, Richard Wender, Leonard G Gomella
Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing...
December 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29226302/international-union-of-immunological-societies-2017-primary-immunodeficiency-diseases-committee-report-on-inborn-errors-of-immunity
#18
Capucine Picard, H Bobby Gaspar, Waleed Al-Herz, Aziz Bousfiha, Jean-Laurent Casanova, Talal Chatila, Yanick J Crow, Charlotte Cunningham-Rundles, Amos Etzioni, Jose Luis Franco, Steven M Holland, Christoph Klein, Tomohiro Morio, Hans D Ochs, Eric Oksenhendler, Jennifer Puck, Mimi L K Tang, Stuart G Tangye, Troy R Torgerson, Kathleen E Sullivan
Beginning in 1970, a committee was constituted under the auspices of the World Health Organization (WHO) to catalog primary immunodeficiencies. Twenty years later, the International Union of Immunological Societies (IUIS) took the remit of this committee. The current report details the categorization and listing of 354 (as of February 2017) inborn errors of immunity. The growth and increasing complexity of the field have been impressive, encompassing an increasing variety of conditions, and the classification described here will serve as a critical reference for immunologists and researchers worldwide...
December 11, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29226301/the-2017-iuis-phenotypic-classification-for-primary-immunodeficiencies
#19
Aziz Bousfiha, Leïla Jeddane, Capucine Picard, Fatima Ailal, H Bobby Gaspar, Waleed Al-Herz, Talal Chatila, Yanick J Crow, Charlotte Cunningham-Rundles, Amos Etzioni, Jose Luis Franco, Steven M Holland, Christoph Klein, Tomohiro Morio, Hans D Ochs, Eric Oksenhendler, Jennifer Puck, Mimi L K Tang, Stuart G Tangye, Troy R Torgerson, Jean-Laurent Casanova, Kathleen E Sullivan
Since the 1990s, the International Union of Immunological Societies (IUIS) PID expert committee (EC), now called Inborn Errors of Immunity Committee, has published every other year a classification of the inborn errors of immunity. This complete catalog serves as a reference for immunologists and researchers worldwide. However, it was unadapted for clinicians at the bedside. For those, the IUIS PID EC is now publishing a phenotypical classification since 2013, which proved to be more user-friendly. There are now 320 single-gene inborn errors of immunity underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity, and auto-inflammation...
January 2018: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29222126/autoimmune-crmp5-neuropathy-phenotype-and-outcome-defined-from-105-cases
#20
Divyanshu Dubey, Vanda A Lennon, Avi Gadoth, Sean J Pittock, Eoin P Flanagan, John E Schmeling, Andrew McKeon, Christopher J Klein
OBJECTIVE: To establish the phenotype and clinical outcomes of collapsin response-mediator protein-5 (CRMP5) autoimmune neuropathy in comparison with anti-neuronal nuclear antibody type 1 (ANNA1)-immunoglobulin G (IgG) neuropathy. METHODS: Patients with CRMP5-IgG and/or ANNA1-IgGs were identified in our service-line testing, and medical records were reviewed. RESULTS: One hundred five patients with CRMP5-IgG neuropathy (88% smokers; 69% having cancer, most commonly small cell lung cancer [75%]) were identified and compared to 51 patients with ANNA1-IgG neuropathy, 27 with coexisting CRMP5-IgG...
December 8, 2017: Neurology
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