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Barbara H Bardenheier, Jonathan Duffy, Susan K Duderstadt, Jay B Higgs, Michael P Keith, Patricia J Papadopoulos, William R Gilliland, Michael M McNeil
U.S. military personnel assigned to areas deemed to be at high risk for anthrax attack receive Anthrax Vaccine Adsorbed (AVA). Few cases of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have been reported in persons who received AVA. Using a matched case-control study design, we assessed the relationship of RA and SLE with AVA vaccination using the Defense Medical Surveillance System. We identified potential cases using International Classification of Diseases, 9th Revision, Clinical Modification codes and confirmed cases with medical record review and rheumatologist adjudication...
October 2016: Military Medicine
Elsa Perrody, Laurence Abrami, Michal Feldman, Beatrice Kunz, Sylvie Urbé, Gisou van der Goot
Many membrane proteins fold inefficiently and require the help of enzymes and chaperones. Here we reveal a novel folding assistance system that operates on membrane proteins from the cytosolic side of the endoplasmic reticulum (ER). We show that folding of the Wnt signaling coreceptor LRP6 is promoted by ubiquitination of a specific lysine, retaining it in the ER while avoiding degradation. Subsequent ER exit requires removal of ubiquitin from this lysine by the deubiquitinating enzyme USP19. This ubiquitination-deubiquitination is conceptually reminiscent of the glucosylation-deglucosylation occurring in the ER lumen during the calnexin/calreticulin folding cycle...
October 18, 2016: ELife
Yong Yang, Hua Gu, Xiaofeng Yu, Li Zhan, Jiancai Chen, Yun Luo, Yunyi Zhang, Yanjun Zhang, Yiyu Lu, Jianmin Jiang, Lingling Mei
Emetic toxin producing Bacillus cereus (emetic B. cereus) is the third member of B. cereus group whose toxins are encoded by megaplasmids, beside anthrax and insecticidal toxins of B. anthracis and B. thuringiensis respectively. 18 emetic isolates collected from food poisoning events, clinical and non-random food samples in Zhejiang province of China, were analyzed by plasmid screening, pulse field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), as well as toxic gene identification to investigate their genotypic diversity...
October 14, 2016: FEMS Microbiology Letters
Mucahit Emet, Fatma Tortum, Selahattin Karagoz, Ayca Calbay
No abstract text is available yet for this article.
October 11, 2016: Journal of Emergency Medicine
K Rajkumar, A Bhattacharya, S David, S Hari Balaji, R Hariharan, M Jayakumar, N Balaji
AIM: This study was conducted to assess the extent of knowledge, awareness, attitude, and risks of zoonotic diseases among livestock owners in Puducherry region. MATERIALS AND METHODS: A total of 250 livestock farmers were selected randomly from eight revenue villages. And each farmer was interviewed with a questionnaire containing both open- and close-ended questions on various aspects of zoonotic diseases, a total of 49 questionnaires were framed to assess the source and transmission of infection to the farmers and to test their knowledge and awareness about zoonotic diseases...
September 2016: Veterinary World
Jason Giacomel, Iris Zalaudek
No abstract text is available yet for this article.
October 1, 2016: JAMA Dermatology
Ziping Liu, Xingguang Su
Herein, high quality DNA-CuInS2 QDs are facilely synthesized through a one-pot hydrothermal method with fluorescence quantum yield as high as 23.4%, and the strongly fluorescent DNA-CuInS2 QDs have been utilized as a novel fluorescent biosensor for label-free and ultrasensitive detection of anthrax lethal factor DNA. L-Cysteine (L-Cys) and a specific-sequence DNA are used as co-ligands to stabilize the CuInS2 QDs. The specific-sequence DNA consists of two domains: phosphorothiolates domain (sulfur-containing variants of the usual phosphodiester backbone) controls the nanocrystal passivation and serves as a ligand, and the functional domain (non-phosphorothioates) controls the biorecognition...
October 26, 2016: Analytica Chimica Acta
Leeor Zilbermintz, William Leonardi, Sharon H Tran, Josue Zozaya, Alyssa Mathew-Joseph, Spencer Liem, Anastasia Levitin, Mikhail Martchenko
The major limitations of pathogen-directed therapies are the emergence of drug-resistance and their narrow spectrum of coverage. A recently applied approach directs therapies against host proteins exploited by pathogens in order to circumvent these limitations. However, host-oriented drugs leave the pathogens unaffected and may result in continued pathogen dissemination. In this study we aimed to discover drugs that could simultaneously cross-inhibit pathogenic agents, as well as the host proteins that mediate their lethality...
October 5, 2016: Scientific Reports
Elisa Biondi, Joshua D Lane, Debasis Das, Saurja Dasgupta, Joseph A Piccirilli, Shuichi Hoshika, Kevin M Bradley, Bryan A Krantz, Steven A Benner
Reported here is a laboratory in vitro evolution (LIVE) experiment based on an artificially expanded genetic information system (AEGIS). This experiment delivers the first example of an AEGIS aptamer that binds to an isolated protein target, the first whose structural contact with its target has been outlined and the first to inhibit biologically important activities of its target, the protective antigen from Bacillus anthracis We show how rational design based on secondary structure predictions can also direct the use of AEGIS to improve the stability and binding of the aptamer to its target...
October 3, 2016: Nucleic Acids Research
William Leonardi, Leeor Zilbermintz, Luisa W Cheng, Josue Zozaya, Sharon H Tran, Jeffrey H Elliott, Kseniya Polukhina, Robert Manasherob, Amy Li, Xiaoli Chi, Dima Gharaibeh, Tara Kenny, Rouzbeh Zamani, Veronica Soloveva, Andrew D Haddow, Farooq Nasar, Sina Bavari, Michael C Bassik, Stanley N Cohen, Anastasia Levitin, Mikhail Martchenko
Diverse pathogenic agents often utilize overlapping host networks, and hub proteins within these networks represent attractive targets for broad-spectrum drugs. Using bacterial toxins, we describe a new approach for discovering broad-spectrum therapies capable of inhibiting host proteins that mediate multiple pathogenic pathways. This approach can be widely used, as it combines genetic-based target identification with cell survival-based and protein function-based multiplex drug screens, and concurrently discovers therapeutic compounds and their protein targets...
September 30, 2016: Scientific Reports
Jason W Sahl, Talima Pearson, Richard Okinaka, James M Schupp, John D Gillece, Hannah Heaton, Dawn Birdsell, Crystal Hepp, Viacheslav Fofanov, Ramón Noseda, Antonio Fasanella, Alex Hoffmaster, David M Wagner, Paul Keim
: Anthrax is a zoonotic disease that occurs naturally in wild and domestic animals but has been used by both state-sponsored programs and terrorists as a biological weapon. A Soviet industrial production facility in Sverdlovsk, USSR, proved deficient in 1979 when a plume of spores was accidentally released and resulted in one of the largest known human anthrax outbreaks. In order to understand this outbreak and others, we generated a Bacillus anthracis population genetic database based upon whole-genome analysis to identify all single-nucleotide polymorphisms (SNPs) across a reference genome...
2016: MBio
Madushini N Dharmasena, Catherine M Feuille, Carly Elizabeth C Starke, Arvind A Bhagwat, Scott Stibitz, Dennis J Kopecko
The licensed oral, live-attenuated bacterial vaccine for typhoid fever, Salmonella enterica serovar Typhi strain Ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. However, Ty21a is acid-labile and, for effective oral immunization, stomach acidity has to be either neutralized with buffer or by-passed with Ty21a in an enteric-coated capsule (ECC). Several studies have shown that efficacy is reduced when Ty21a is administered in an ECC versus as a buffered liquid formulation, the former limiting exposure to GI tract lymphoid tissues...
2016: PloS One
Lucien Fabre, Eugenio Santelli, Driss Mountassif, Annemarie Donoghue, Aviroop Biswas, Rikard Blunck, Dorit Hanein, Niels Volkmann, Robert Liddington, Isabelle Rouiller
Anthrax toxin comprises three soluble proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA must be cleaved by host proteases before it oligomerizes and forms a prepore, to which LF and EF bind. After endocytosis of this tripartite complex, the prepore transforms into a narrow transmembrane pore that delivers unfolded LF and EF into the host cytosol. Here, we find that translocation of multiple 90-kD LF molecules is rapid and efficient. To probe the molecular basis of this translocation, we calculated a three-dimensional map of the fully loaded (PA63)7-(LF)3 prepore complex by cryo-electron microscopy (cryo-EM)...
October 2016: Journal of General Physiology
Bryan A Krantz
No abstract text is available yet for this article.
October 2016: Journal of General Physiology
Somya Aggarwal, Vikas Kumar Somani, Vatika Gupta, Jaspreet Kaur, Damini Singh, Abhinav Grover, Rakesh Bhatnagar
BACKGROUND: Recent report on importance of phosphate starvation (PS) in Bacillus anthracis (BA) pathogenesis warrants further investigation of the underlying regulatory mechanism. Potential role of PhoPR two component system (TCS) in phosphate homeostasis and virulence of several pathogens necessitates the study of annotated PhoPR in BA. METHODS: Expression of phoP and phoR was analyzed using qRT-PCR. PhoPR was characterized biochemically. DNA-protein interaction was analyzed by EMSA...
September 23, 2016: Biochimica et Biophysica Acta
Jason G Ramage, Kristin W Prentice, Lindsay DePalma, Kodumudi S Venkateswaran, Sruti Chivukula, Carol Chapman, Melissa Bell, Shomik Datta, Ajay Singh, Alex Hoffmaster, Jawad Sarwar, Nishanth Parameswaran, Mrinmayi Joshi, Nagarajan Thirunavkkarasu, Viswanathan Krishnan, Stephen Morse, Julie R Avila, Shashi Sharma, Peter L Estacio, Larry Stanker, David R Hodge, Segaran P Pillai
We conducted a comprehensive, multiphase laboratory evaluation of the Anthrax BioThreat Alert(®) test strip, a lateral flow immunoassay (LFA) for the rapid detection of Bacillus anthracis spores. The study, conducted at 2 sites, evaluated this assay for the detection of spores from the Ames and Sterne strains of B. anthracis, as well as those from an additional 22 strains. Phylogenetic near neighbors, environmental background organisms, white powders, and environmental samples were also tested. The Anthrax LFA demonstrated a limit of detection of about 10(6) spores/mL (ca...
September 2016: Health Security
Miriam A Balderas, Chinh Nguyen, Austen Terwilliger, Wendy A Keitel, Angelina Iniguez, Rodrigo Torres, Frederico Palacios, Celia W Goulding, Anthony W Maresso
Bacillus anthracis is a sporulating Gram-positive bacterium that is the causative agent of anthrax and a potential weapon of bioterrorism. The U.S. licensed anthrax vaccine is made from an incompletely characterized culture supernatant of a nonencapsulated, toxigenic strain (anthrax vaccine absorbed - AVA) whose primary protective component is thought to be protective antigen (PA). AVA is effective in protecting animals and elicits toxin-neutralizing antibodies in humans, but enthusiasm is dampened by its undefined composition, multi-shot regimen, recommended boosters, and potential for adverse reactions...
September 19, 2016: Infection and Immunity
Taissia G Popova, Allison Teunis, Virginia Espina, Lance A Liotta, Serguei G Popov
In this study the hydrogel microparticles (MPs) were used to enhance migration of neutrophils in order to improve outcome of anthrax infection in a mouse model. Two MP formulations were tested. In the first one the polyacrylamide gel MPs were chemically coupled with Cibacron Blue (CB) affinity bait. In the second one the bait molecules within the MPs were additionally loaded with neutrophil-attracting chemokines (CKs), human CXCL8 and mouse CCL3. A non-covalent interaction of the bait with the CKs provided their gradual release after administration of the MPs to the host...
2016: PloS One
Ermias Mergia, Workineh Shibeshi, Getachew Terefe, Tilahun Teklehaymanot
BACKGROUND: African Trypanosomiasis is a neglected tropical disease with a large impact on the livelihood of the rural poor in Sub-Saharan Africa. The available drugs for managing this disease are old, expensive and are facing the problem of drug resistance. Thus, the aim of this study was to evaluate in vivo antitrypanosomal efficacy of aqueous and absolute methanol leaf extracts of Verbascum sinaiticum Benth. against Trypanosoma congolense field isolate. METHODS: Verbascum sinaiticum (Local name 'qetetina') is a biennial plant, and 60-150 cm tall...
2016: BMC Complementary and Alternative Medicine
Sabine Fenner, Zoe E Wilson, Steven V Ley
Herein, we describe our full investigations into the synthesis of the peptide-derived natural product plantazolicin A, a compound that demonstrates promising selective activity against the causative agent of anthrax toxicity, and its biosynthetic precursor plantazolicin B. This report particularly focuses on the challenging preparation of the arginine containing thiazole fragment, including the development of a robust, high yielding procedure that avoids the use of sulfurating agents. Extensive studies on the design of a coherent protecting group strategy and the establishment of a step-efficient dicyclization/oxidation approach allowed high levels of convergence for the construction of the oxazole fragments...
September 13, 2016: Chemistry: a European Journal
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