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https://www.readbyqxmd.com/read/28412695/cell-scientist-to-watch-robert-ernst
#1
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After obtaining his diploma in human biology at the Philipps-University Marburg, Germany, Robert Ernst joined the laboratory of Lutz Schmitt and obtained his PhD (summa cum laude) at Heinrich-Heine-University Düsseldorf in 2007. For his postdoctoral work, Robert worked with Hidde Ploegh at the Whitehead Institute for Biomedical Research, USA, supported by an EMBO long-term fellowship. Afterwards, he returned to Germany, to the laboratory of Kai Simons at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden...
April 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28403145/the-phosphatidylinositol-3-phosphate-5-kinase-inhibitor-apilimod-blocks-filoviral-entry-and-infection
#2
Elizabeth A Nelson, Julie Dyall, Thomas Hoenen, Alyson B Barnes, Huanying Zhou, Janie Y Liang, Julia Michelotti, William H Dewey, Lisa Evans DeWald, Richard S Bennett, Patrick J Morris, Rajarshi Guha, Carleen Klumpp-Thomas, Crystal McKnight, Yu-Chi Chen, Xin Xu, Amy Wang, Emma Hughes, Scott Martin, Craig Thomas, Peter B Jahrling, Lisa E Hensley, Gene G Olinger, Judith M White
Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase involved in endosome maturation that emerged from a haploid genetic screen as being required for Ebola virus (EBOV) infection. Here we analyzed the effects of apilimod, a PIKfyve inhibitor that was reported to be well tolerated in humans in phase 2 clinical trials, for its effects on entry and infection of EBOV and Marburg virus (MARV). We first found that apilimod blocks infections by EBOV and MARV in Huh 7, Vero E6 and primary human macrophage cells, with notable potency in the macrophages (IC50, 10 nM)...
April 12, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28402024/marburg-virus-like-particles-produced-in-insect-cells-induce-neutralizing-antibodies-in-rhesus-macaques
#3
Weiwei Gai, Xuexing Zheng, Chong Wang, Yongkun Zhao, Qi Wang, Hualei Wang, Gary Wong, Ying Xie, Haijun Wang, Zengguo Cao, Na Feng, Hang Chi, Tiecheng Wang, Yuwei Gao, Junjie Shan, Songtao Yang, Xianzhu Xia
Marburg virus (MARV), which is one of the most virulent agents in the world, causes lethal haemorrhagic fever in humans and nonhuman primates (NHPs) with a mortality rate of up to 90%. Currently, there is no effective treatment or approved vaccine for MARV for human use to control disease outbreak and spread. Virus-like particles (VLPs), which are morphologically identical to the native infectious virus particle, are efficacious as vaccines against many viruses, including human papilloma virus (HPV), porcine circovirus (PCV) type 2 and hepatitis B virus (HBV)...
April 12, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28396467/offering-patients-more-how-the-west-africa-ebola-outbreak-can-shape-innovation-in-therapeutic-research-for-emerging-and-epidemic-infections
#4
REVIEW
Amanda M Rojek, Peter W Horby
Although, after an epidemic of over 28 000 cases, there are still no licensed treatments for Ebola virus disease (EVD), significant progress was made during the West Africa outbreak. The pace of pre-clinical development was exceptional and a number of therapeutic clinical trials were conducted in the face of considerable challenges. Given the on-going risk of emerging infectious disease outbreaks in an era of unprecedented population density, international travel and human impact on the environment it is pertinent to focus on improving the research and development landscape for treatments of emerging and epidemic-prone infections...
May 26, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28390814/meeting-report-of-the-pathogenesis-of-pemphigus-and-pemphigoid-meeting-in-munich-september-2016
#5
Enno Schmidt, Volker Spindler, Rüdiger Eming, Masayuki Amagai, Frank Antonicelli, John F Baines, Meriem Belheouane, Philippe Bernard, Luca Borradori, Marzia Caproni, Giovanni Di Zenzo, Sergei Grando, Karen Harman, Marcel F Jonkman, Hiroshi Koga, Ralf J Ludwig, Andrew P Kowalczyk, Eliane J Müller, Wataru Nishie, Hendri Pas, Aimee S Payne, Christian D Sadik, Allan Seppänen, Jane Setterfield, Hiroshi Shimizu, Animesh A Sinha, Eli Sprecher, Michael Sticherling, Hideyuki Ujiie, Detlef Zillikens, Michael Hertl, Jens Waschke
Autoimmune blistering diseases are a heterogeneous group of about a dozen complex disorders that are characterized by intraepidermal (pemphigus) and subepidermal blistering (pemphigoid diseases and dermatitis herpetiformis). The Pathogenesis of Pemphigus and Pemphigoid Meeting, organized by the Departments of Dermatology in Lübeck and Marburg and the Institute of Anatomy and Cell Biology, Munich, was held in September 2016 in Munich. The meeting brought together basic scientists and clinicians from all continents dedicating their work to autoimmune blistering diseases...
April 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28381540/therapeutic-treatment-of-marburg-and-ravn-virus-infection-in-nonhuman-primates-with-a-human-monoclonal-antibody
#6
Chad E Mire, Joan B Geisbert, Viktoriya Borisevich, Karla A Fenton, Krystle N Agans, Andrew I Flyak, Daniel J Deer, Herta Steinkellner, Ognian Bohorov, Natasha Bohorova, Charles Goodman, Andrew Hiatt, Do H Kim, Michael H Pauly, Jesus Velasco, Kevin J Whaley, James E Crowe, Larry Zeitlin, Thomas W Geisbert
As observed during the 2013-2016 Ebola virus disease epidemic, containment of filovirus outbreaks is challenging and made more difficult by the lack of approved vaccine or therapeutic options. Marburg and Ravn viruses are highly virulent and cause severe and frequently lethal disease in humans. Monoclonal antibodies (mAbs) are a platform technology in wide use for autoimmune and oncology indications. Previously, we described human mAbs that can protect mice from lethal challenge with Marburg virus. We demonstrate that one of these mAbs, MR191-N, can confer a survival benefit of up to 100% to Marburg or Ravn virus-infected rhesus macaques when treatment is initiated up to 5 days post-inoculation...
April 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28356221/rapid-detection-of-all-known-ebolavirus-species-by-reverse-transcription-loop-mediated-isothermal-amplification-rt-lamp
#7
Olamide K Oloniniyi, Yohei Kurosaki, Hiroko Miyamoto, Ayato Takada, Jiro Yasuda
Ebola virus disease (EVD), a highly virulent infectious disease caused by ebolaviruses, has a fatality rate of 25-90%. Without a licensed chemotherapeutic agent or vaccine for the treatment and prevention of EVD, control of outbreaks requires accurate and rapid diagnosis of cases. In this study, five sets of six oligonucleotide primers targeting the nucleoprotein gene were designed for specific identification of each of the five ebolavirus species using reverse transcription-loop mediated isothermal amplification (RT-LAMP) assay...
March 26, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28324047/functional-imaging-in-the-follow-up-of-enteropancreatic-neuroendocrine-tumors-clinical-usefulness-and-indications
#8
Elettra Merola, Marianne E Pavel, Francesco Panzuto, Gabriele Capurso, Noemi Cicchese, Anja Rinke, Thomas M Gress, Elsa Iannicelli, Daniela Prosperi, Patrizia Pizzichini, Vikas Prasad, Patrizia Kump, Rainer Lipp, Stefano Partelli, Massimo Falconi, Bertram Wiedenmann, Gianfranco Delle Fave
Context: Functional imaging tests (FITs) detecting somatostatin receptors expression (i.e., Somatostatin Receptor Scintigraphy, 68Ga-DOTA-peptide positron emission tomography/computed tomography) have a pivotal role in the diagnosis of neuroendocrine tumors (NETs), while their indication during follow-up still needs to be clarified. Objective: Investigate the role of FITs after diagnosis of metastatic enteropancreatic NETs, identifying patients who might benefit from these exams...
January 13, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28287337/generation-and-characterization-of-protective-antibodies-to-marburg-virus
#9
Jeffrey W Froude, Thibaut Pelat, Sebastian Miethe, Samantha E Zak, Anna Z Wec, Kartik Chandran, Jennifer Mary Brannan, Russell R Bakken, Michael Hust, Philippe Thullier, John M Dye
Marburg virus (MARV) and Ebola virus (EBOV) have been a source of epidemics and outbreaks for several decades. We present here the generation and characterization of the first protective antibodies specific for wild-type MARV. Non-human primates (NHP), cynomolgus macaques, were immunized with viral-replicon particles expressing the glycoproteins (GP) of MARV (Ci67 isolate). An antibody fragment (single-chain variable fragment, scFv) phage display library was built after four immunogen injections, and screened against the GP1-649 of MARV...
March 13, 2017: MAbs
https://www.readbyqxmd.com/read/28284781/diagnosis-course-and-management-of-angioedema-in-patients-with-acquired-c1-inhibitor-deficiency
#10
Andrea Zanichelli, Giulia Maria Azin, Maddalena Alessandra Wu, Chiara Suffritti, Lorena Maggioni, Sonia Caccia, Francesca Perego, Romualdo Vacchini, Marco Cicardi
BACKGROUND: Acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) is a rare disease with no prevalence data or approved therapies. OBJECTIVE: To report data on patients with C1-INH-AAE followed at Angioedema Center, Milan (from 1976 to 2015). METHODS: Diagnostic criteria included history of recurrent angioedema without wheals; decreased C1-INH antigen levels and/or functional activity of C1-INH and C4 antigen less than 50% of normal; late symptom onset (>40 years); no family history of angioedema and C1-INH deficiency...
March 8, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28246168/role-of-glycine-221-in-catalytic-activity-of-hyaluronan-binding-protein-2
#11
Fabian Stavenuiter, Eduard H T M Ebberink, Koen Mertens, Alexander B Meijer
HABP2 (hyaluronan-binding protein 2) is a Ca(2+)-dependent serine protease with putative roles in blood coagulation and fibrinolysis. A G221E substitution, known as the Marburg I polymorphism, reportedly affects HABP2 function and has been associated with increased risk for cardiovascular disease. However, the importance of Gly-221 for HABP2 activity is unclear. Here, we used G221E, G221A, and G221S mutants to assess the role of Gly-221 in HABP2 catalysis. The G221E variant failed to activate the single-chain urokinase-type plasminogen activator, and the G221A and G221S variants displayed moderately reduced single-chain urokinase-type plasminogen activator activation...
April 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28197304/ester-prodrugs-of-ihvr-19029-with-enhanced-oral-exposure-and-prevention-of-gastrointestinal-glucosidase-interaction
#12
Julia Ma, Shuo Wu, Xuexiang Zhang, Fang Guo, Katherine Yang, Jia Guo, Qing Su, Huagang Lu, Patrick Lam, Yuhuan Li, Zhengyin Yan, William Kinney, Ju-Tao Guo, Timothy M Block, Jinhong Chang, Yanming Du
IHVR-19029 (6) is a lead endoplasmic reticulum α-glucosidases I and II inhibitor, which efficiently protected mice from lethal Ebola and Marburg virus infections via injection route, but suffered from low bioavailability and off-target interactions with gut glucosidases when administered orally. In an effort to improve efficacious exposure levels and avoid side effects, we designed and synthesized ester prodrugs. Not only were the prodrugs stable in simulated gastric and intestinal fluids and were inactive against glucosidases but they also exhibited antiviral activities against dengue virus infection in a cell based assay...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28194016/modelling-filovirus-maintenance-in-nature-by-experimental-transmission-of-marburg-virus-between-egyptian-rousette-bats
#13
Amy J Schuh, Brian R Amman, Megan E B Jones, Tara K Sealy, Luke S Uebelhoer, Jessica R Spengler, Brock E Martin, Jo Ann D Coleman-McCray, Stuart T Nichol, Jonathan S Towner
The Egyptian rousette bat (ERB) is a natural reservoir host for Marburg virus (MARV); however, the mechanisms by which MARV is transmitted bat-to-bat and to other animals are unclear. Here we co-house MARV-inoculated donor ERBs with naive contact ERBs. MARV shedding is detected in oral, rectal and urine specimens from inoculated bats from 5-19 days post infection. Simultaneously, MARV is detected in oral specimens from contact bats, indicating oral exposure to the virus. In the late study phase, we provide evidence that MARV can be horizontally transmitted from inoculated to contact ERBs by finding MARV RNA in blood and oral specimens from contact bats, followed by MARV IgG antibodies in these same bats...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28179007/global-research-trends-of-world-health-organization-s-top-eight-emerging-pathogens
#14
Waleed M Sweileh
BACKGROUND: On December 8(th), 2015, World Health Organization published a priority list of eight pathogens expected to cause severe outbreaks in the near future. To better understand global research trends and characteristics of publications on these emerging pathogens, we carried out this bibliometric study hoping to contribute to global awareness and preparedness toward this topic. METHOD: Scopus database was searched for the following pathogens/infectious diseases: Ebola, Marburg, Lassa, Rift valley, Crimean-Congo, Nipah, Middle Eastern Respiratory Syndrome (MERS), and Severe Respiratory Acute Syndrome (SARS)...
February 8, 2017: Globalization and Health
https://www.readbyqxmd.com/read/28167534/detection-of-lipid-induced-structural-changes-of-the-marburg-virus-matrix-protein-vp40-using-hydrogen-deuterium-exchange-mass-spectrometry
#15
Kaveesha J Wijesinghe, Sarah Urata, Nisha Bhattarai, Edgar E Kooijman, Bernard S Gerstman, Prem P Chapagain, Sheng Li, Robert V Stahelin
Marburg virus (MARV) is a lipid-enveloped virus from the Filoviridae family containing a negative sense RNA genome. One of the seven MARV genes encodes the matrix protein VP40, which forms a matrix layer beneath the plasma membrane inner leaflet to facilitate budding from the host cell. MARV VP40 (mVP40) has been shown to be a dimeric peripheral protein with a broad and flat basic surface that can associate with anionic phospholipids such as phosphatidylserine. Although a number of mVP40 cationic residues have been shown to facilitate binding to membranes containing anionic lipids, much less is known on how mVP40 assembles to form the matrix layer following membrane binding...
April 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28155588/friedrich-august-genth-aus-w%C3%A3-chersbach-und-die-entdeckung-der-ersten-nio-kristalle-am-marburger-chemischen-institut-unter-robert-wilhelm-bunsen
#16
https://www.readbyqxmd.com/read/28135118/ebola-virus-and-marburg-virus-in-human-milk-are-inactivated-by-holder-pasteurization
#17
Erin Hamilton Spence, Monica Huff, Karen Shattuck, Amy Vickers, Nadezda Yun, Slobodan Paessler
BACKGROUND: Potential donors of human milk are screened for Ebola virus (EBOV) using standard questions, but testing for EBOV and Marburg virus (MARV) is not part of routine serological testing performed by milk banks. Research aim: This study tested the hypothesis that EBOV would be inactivated in donor human milk (DHM) by standard pasteurization techniques (Holder) used in all North American nonprofit milk banks. METHODS: Milk samples were obtained from a nonprofit milk bank...
May 2017: Journal of Human Lactation: Official Journal of International Lactation Consultant Association
https://www.readbyqxmd.com/read/28130780/membrane-insertion-of-fusion-peptides-from-ebola-and-marburg-viruses-studied-by-replica-exchange-molecular-dynamics-simulations
#18
Mark A Olson, Michael S Lee, In-Chul Yeh
This work presents replica-exchange molecular dynamics simulations of inserting a 16-residue Ebola virus fusion peptide into a membrane bilayer. A computational approach is applied for modeling the peptide at the explicit all-atom level and the membrane-aqueous bilayer by a generalized Born continuum model with a smoothed switching function (GBSW). We provide an assessment of the model calculations in terms of three metrics: (1) the ability to reproduce the NMR structure of the peptide determined in the presence of SDS micelles and comparable structural data on other fusion peptides; (2) determination of the effects of the mutation Trp-8 to Ala and sequence discrimination of the homologous Marburg virus; and (3) calculation of potentials of mean force for estimating the partitioning free energy and their comparison to predictions from the Wimley-White interfacial hydrophobicity scale...
January 28, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28122983/innate-immune-responses-of-bat-and-human-cells-to-filoviruses-commonalities-and-distinctions
#19
Ivan V Kuzmin, Toni M Schwarz, Philipp A Ilinykh, Ingo Jordan, Thomas G Ksiazek, Ravi Sachidanandam, Christopher F Basler, Alexander Bukreyev
Marburg (MARV) and Ebola (EBOV) viruses are zoonotic pathogens that cause severe hemorrhagic fever in humans. The natural reservoir of MARV is the Egyptian rousette bat (Rousettus aegyptiacus); that of EBOV is unknown but believed to be another bat species. The Egyptian rousette develops subclinical productive infection with MARV but is refractory to EBOV. Interaction of filoviruses with hosts is greatly affected by the viral interferon (IFN)-inhibiting domains (IID). Our study was aimed at characterization of innate immune responses to filoviruses and the role of filovirus IID in bat and human cells...
April 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28109709/the-effect-of-gamma-irradiation-conditions-on-the-immunogenicity-of-whole-inactivated-influenza-a-virus-vaccine
#20
Shannon C David, Josyane Lau, Eve V Singleton, Rachelle Babb, Justin Davies, Timothy R Hirst, Shaun R McColl, James C Paton, Mohammed Alsharifi
Gamma-irradiation, particularly an irradiation dose of 50kGy, has been utilised widely to sterilise highly pathogenic agents such as Ebola, Marburg Virus, and Avian Influenza H5N1. We have reported previously that intranasal vaccination with a gamma-irradiated Influenza A virus vaccine (γ-Flu) results in cross-protective immunity. Considering the possible inclusion of highly pathogenic Influenza strains in future clinical development of γ-Flu, an irradiation dose of 50kGy may be used to enhance vaccine safety beyond the internationally accepted Sterility Assurance Level (SAL)...
January 18, 2017: Vaccine
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