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https://www.readbyqxmd.com/read/27926929/functional-and-evolutionary-analyses-identify-proteolysis-as-a-general-mechanism-for-nlrp1-inflammasome-activation
#1
Joseph Chavarría-Smith, Patrick S Mitchell, Alvin M Ho, Matthew D Daugherty, Russell E Vance
Inflammasomes are cytosolic multi-protein complexes that initiate immune responses to infection by recruiting and activating the Caspase-1 protease. Human NLRP1 was the first protein shown to form an inflammasome, but its physiological mechanism of activation remains unknown. Recently, specific variants of mouse and rat NLRP1 were found to be activated upon N-terminal cleavage by the anthrax lethal factor protease. However, agonists for other NLRP1 variants, including human NLRP1, are not known, and it remains unclear if they are also activated by proteolysis...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27925405/animal-to-human-dose-translation-of-obiltoxaximab-for-treatment-of-inhalational-anthrax-under-the-us-fda-animal-rule
#2
C F Nagy, J Mondick, N Serbina, L S Casey, S E Carpenter, J French, R Guttendorf
Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax under the US Food and Drug Administration's (FDA) Animal Rule. The human dose was selected and justified by comparing observed obiltoxaximab exposures in healthy and infected New Zealand White rabbits and cynomolgus macaques to observed exposures in healthy humans, to simulated exposures in healthy and infected humans, and to serum PA levels in infected animals. In humans, at 16 mg/kg intravenous, obiltoxaximab AUC was >2 times that in animals, while maximum serum concentrations were comparable to those in animals and were maintained in excess of the concentration required for PA neutralization in infected animals for 2-3 weeks...
December 7, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27915984/structure-function-and-evolution-of-clostridium-botulinum-c2-and-c3-toxins-insight-to-poultry-and-veterinary-vaccines
#3
P Chellapandi, A Prisilla
Clostridium botulinum group III strains are able to produce cytotoxins, C2 toxin and C3 exotoxin, along with botulinum neurotoxin types C and D. C2 toxin and C3 exotoxin produced from this organism are the most important members of bacterial ADP-ribosyltransferase superfamily. Both toxins have distinct pathophysiological functions in the avian and mammalian hosts. The members of this superfamily transfer an ADP-ribose moiety of NAD+ to specific eukaryotic target proteins. The present review describes the structure, function and evolution aspects of these toxins with a special emphasis to the development of veterinary vaccines...
December 1, 2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27909054/identification-of-a-substrate-selective-exosite-within-the-metalloproteinase-anthrax-lethal-factor
#4
Allison B Goldberg, Eunice Cho, Chad J Miller, Hua Jane Lou, Benjamin E Turk
The metalloproteinase anthrax lethal factor (LF) is secreted by Bacillus anthracis to promote disease virulence through disruption of host signaling pathways. LF is a highly specific protease, exclusively cleaving mitogen-activated protein kinase kinases (MKKs) and rodent NACHT leucine-rich repeat and pyrin domain containing protein 1B (NLRP1B). How LF achieves such restricted substrate specificity is not understood. Previous studies have suggested the existence of an exosite interaction between LF and MKKs that promotes cleavage efficiency and specificity...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27905935/development-of-a-filter-to-prevent-infections-with-spore-forming-bacteria-in-injecting-drug-users
#5
Nour Alhusein, Jenny Scott, Barbara Kasprzyk-Hordern, Albert Bolhuis
BACKGROUND: In heroin injectors, there have been a number of outbreaks caused by spore-forming bacteria, causing serious infections such as anthrax or botulism. These are, most likely, caused by injecting contaminated heroin, and our aim was to develop a filter that efficiently removes these bacteria and is also likely to be acceptable for use by people who inject drugs (i.e. quick, simple and not spoil the hit). METHODS: A prototype filter was designed and different filter membranes were tested to assess the volume of liquid retained, filtration time and efficiency of the filter at removing bacterial spores...
December 1, 2016: Harm Reduction Journal
https://www.readbyqxmd.com/read/27898235/postexposure-prophylaxis-after-possible-anthrax-exposure-adherence-and-adverse-events
#6
Leisha D Nolen, Rita M Traxler, Grishma A Kharod, Pallavi A Kache, Stefan Katharios-Lanwermeyer, Katherine A Hendricks, Sean V Shadomy, William A Bower, Dana Meaney-Delman, Henry T Walke
Anthrax postexposure prophylaxis (PEP) was recommended to 42 people after a laboratory incident that involved potential aerosolization of Bacillus anthracis spores in 2 laboratories at the Centers for Disease Control and Prevention in 2014. At least 31 (74%) individuals who initiated PEP did not complete either the recommended 60 days of antimicrobial therapy or the 3-dose vaccine regimen. Among the 29 that discontinued the antimicrobial component of PEP, most (38%) individuals discontinued PEP because of their low perceived risk of infection; 9 (31%) individuals discontinued prophylaxis due to PEP-related minor adverse events, and 10% cited both low risk and adverse events as their reason for discontinuation...
November 29, 2016: Health Security
https://www.readbyqxmd.com/read/27893966/vaccination-via-chloroplast-genetics-affordable-protein-drugs-for-the-prevention-and-treatment-of-inherited-or-infectious-human-diseases
#7
Henry Daniell, Hui-Ting Chan, Elise K Pasoreck
Plastid-made biopharmaceuticals treat major metabolic or genetic disorders, including Alzheimer's, diabetes, hypertension, hemophilia, and retinopathy. Booster vaccines made in chloroplasts prevent global infectious diseases, such as tuberculosis, malaria, cholera, and polio, and biological threats, such as anthrax and plague. Recent advances in this field include commercial-scale production of human therapeutic proteins in FDA-approved cGMP facilities, development of tags to deliver protein drugs to targeted human cells or tissues, methods to deliver precise doses, and long-term stability of protein drugs at ambient temperature, maintaining their efficacy...
November 23, 2016: Annual Review of Genetics
https://www.readbyqxmd.com/read/27883989/recombinant-anthrax-protective-antigen-observation-of-aggregation-phenomena-by-tem-reveals-specific-effects-of-sterols
#8
J Robin Harris, Andrei Soliakov, Allan Watkinson, Jeremy H Lakey
Negatively stained transmission electron microscope images are presented that depict the aggregation of recombinant anthrax protective antigen (rPA83 monomer and the PA63 prepore oligomer) under varying in vitro biochemical conditions. Heat treatment (50°C) of rPA83 produced clumped fibrils, but following heating the PA63 prepore formed disordered aggregates. Freeze-thaw treatment of the PA63 prepore generated linear flexuous aggregates of the heptameric oligomers. Aqueous suspensions of cholesterol microcrystals were shown to bind small rPA83 aggregates at the edges of the planar bilayers...
November 15, 2016: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/27880744/notice-to-readers-final-2015-reports-of-nationally-notifiable-infectious-diseases-and-conditions
#9
(no author information available yet)
The table listed in this report on pages 1307-1321 presents finalized data, as of June 30, 2016, from the National Notifiable Diseases Surveillance System (NNDSS) for 2015. These data will be published in more detail in the Summary of Notifiable Infectious Diseases and Conditions - United States, 2015 (1). Because no cases were reported in the United States during 2015, the following diseases do not appear in this early release table: anthrax; dengue hemorrhagic fever; diphtheria; eastern equine encephalitis virus disease, nonneuroinvasive; poliomyelitis, paralytic; poliovirus infection, nonparalytic; severe acute respiratory syndrome-associated coronavirus disease (SARS-CoV); smallpox; western equine encephalitis virus disease, neuroinvasive and nonneuroinvasive; yellow fever; and viral hemorrhagic fevers...
November 25, 2016: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/27874231/stability-of-domain-4-of-the-anthrax-toxin-protective-antigen-and-the-effect-of-the-vwa-domain-of-cmg2-on-stability
#10
Sireesha Mamillapalli, Masaru Miyagi, James G Bann
The major immunogenic component of the current anthrax vaccine, anthrax vaccine adsorbed (AVA) is protective antigen (PA). We have shown recently that the thermodynamic stability of PA can be significantly improved by binding to the Von-Willebrand factor A (VWA) domain of capillary morphogenesis protein 2 (CMG2), and improvements in thermodynamic stability may improve storage and long-term stability of PA for use as a vaccine. In order to understand the origin of this increase in stability, we have isolated the receptor binding domain of PA, domain 4 (D4), and have studied the effect of the addition of CMG2 on thermodynamic stability...
November 22, 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27867766/reanalysis-of-the-anthrax-epidemic-in-rhodesia-1978-1984
#11
James M Wilson, Walter Brediger, Thomas P Albright, Julie Smith-Gagen
In the mid-1980s, the largest epidemic of anthrax of the last 200 years was documented in a little known series of studies by Davies in The Central African Journal of Medicine. This epidemic involved thousands of cattle and 10,738 human cases with 200 fatalities in Rhodesia during the Counterinsurgency. Grossly unusual epidemiological features were noted that, to this day, have not been definitively explained. This study performed a historical reanalysis of the data to reveal an estimated geographic involvement of 245,750 km(2), with 171,990 cattle and 17,199 human cases...
2016: PeerJ
https://www.readbyqxmd.com/read/27865796/bletilla-striata-medicinal-uses-phytochemistry-and-pharmacological-activities
#12
REVIEW
Xirui He, Jiacheng Fang, Xiaoxiao Wang, Zefeng Zhao, Yu Chang, Hao Guo, Linhong Huang
ETHNOPHARMACOLOGICAL RELEVANCE: Bletilla striata (Thunb.) Reichb. f. (Orchidaceae), also known as Hyacinth Orchid and Baiji (Simplified Chinese: ), not only has been widely used for the treatment of hematemesis, hemoptysis, and traumatic bleeding due to the efficacy of arresting bleeding with astringent action, but also has been applied topically to overcome ulcers, sores, swellings, and chapped skin due to the efficacy of dispersing swelling and promoting tissue regeneration. Additional medical applications include the treatment of tuberculosis, malignant ulcers, hemorrhoids, anthrax, eye diseases, and silicosis...
November 16, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27854272/impact-of-dendrimer-terminal-group-chemistry-on-blockage-of-the-anthrax-toxin-channel-a-single-molecule-study
#13
Goli Yamini, Nnanya Kalu, Ekaterina M Nestorovich
Nearly all the cationic molecules tested so far have been shown to reversibly block K⁺ current through the cation-selective PA63 channels of anthrax toxin in a wide nM-mM range of effective concentrations. A significant increase in channel-blocking activity of the cationic compounds was achieved when multiple copies of positively charged ligands were covalently linked to multivalent scaffolds, such as cyclodextrins and dendrimers. Even though multivalent binding can be strong when the individual bonds are relatively weak, for drug discovery purposes we often strive to design multivalent compounds with high individual functional group affinity toward the respective binding site on a multivalent target...
November 15, 2016: Toxins
https://www.readbyqxmd.com/read/27843420/historical-data-analysis-of-hospital-discharges-related-to-the-amerithrax-attack-in-florida
#14
Lauralyn K Burke, C Perry Brown, Tammie M Johnson
Interrupted time-series analysis (ITSA) can be used to identify, quantify, and evaluate the magnitude and direction of an event on the basis of time-series data. This study evaluates the impact of the bioterrorist anthrax attacks ("Amerithrax") on hospital inpatient discharges in the metropolitan statistical area of Palm Beach, Broward, and Miami-Dade counties in the fourth quarter of 2001. Three statistical methods-standardized incidence ratio (SIR), segmented regression, and an autoregressive integrated moving average (ARIMA)-were used to determine whether Amerithrax influenced inpatient utilization...
2016: Perspectives in Health Information Management
https://www.readbyqxmd.com/read/27837532/a-dock-and-lock-approach-to-preparation-of-targeted-liposomes
#15
Marina V Backer, Joseph M Backer
We developed a strategy for covalent coupling of targeting proteins to liposomes decorated with a standard adapter protein. This strategy is based on "dock and lock" interactions between two mutated fragments of human RNase I, a 1-15 aa fragment with the R4C amino acid substitution (Cys-tag), and a 21-127-aa fragment with the V118C substitution, (Ad-C). Upon binding to each other, Cys-tag and Ad-C spontaneously form a disulfide bond between the complementary 4C and 118C residues. Therefore, any targeting protein expressed with Cys-tag can be easily coupled to liposomes decorated with Ad-C...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27822867/rapid-snp-detection-and-genotyping-of-bacterial-pathogens-by-pyrosequencing
#16
Kingsley K Amoako, Matthew C Thomas, Timothy W Janzen, Noriko Goji
Bacterial identification and typing are fixtures of microbiology laboratories and are vital aspects of our response mechanisms in the event of foodborne outbreaks and bioterrorist events. Whole genome sequencing (WGS) is leading the way in terms of expanding our ability to identify and characterize bacteria through the identification of subtle differences between genomes (e.g. single nucleotide polymorphisms (SNPs) and insertions/deletions). Modern high-throughput technologies such as pyrosequencing can facilitate the typing of bacteria by generating short-read sequence data of informative regions identified by WGS analyses, at a fraction of the cost of WGS...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27814939/validation-of-high-throughput-screening-of-human-sera-for-detection-of-anti-pa-igg-by-enzyme-linked-immunosorbent-assay-elisa-as-an-emergency-response-to-an-anthrax-incident
#17
Vera A Semenova, Evelene Steward-Clark, Panagiotis Maniatis, Monica Epperson, Amit Sabnis, Jarad Schiffer
To improve surge testing capability for a response to a release of Bacillus anthracis, the CDC anti-Protective Antigen (PA) IgG Enzyme-Linked Immunosorbent Assay (ELISA) was re-designed into a high throughput screening format. The following assay performance parameters were evaluated: goodness of fit (measured as the mean reference standard r(2)), accuracy (measured as percent error), precision (measured as coefficient of variance (CV)), lower limit of detection (LLOD), lower limit of quantification (LLOQ), dilutional linearity, diagnostic sensitivity (DSN) and diagnostic specificity (DSP)...
November 1, 2016: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/27809794/alternative-pre-approved-and-novel-therapies-for-the-treatment-of-anthrax
#18
REVIEW
Breanne M Head, Ethan Rubinstein, Adrienne F A Meyers
BACKGROUND: Bacillus anthracis, the causative agent of anthrax, is a spore forming and toxin producing rod-shaped bacterium that is classified as a category A bioterror agent. This pathogenic microbe can be transmitted to both animals and humans. Clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosolization) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis, and death...
November 3, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27803944/optimization-of-physiochemical-parameters-during-bioremediation-of-synthetic-dye-by-marasmius-cladophyllus-umas-ms8-using-statistical-approach
#19
Fatin Nur Sufinas Shuib, Ahmad Husaini, Azham Zulkharnain, Hairul Azman Roslan, Tay Meng Guan
In many industrial areas such as in food, pharmaceutical, cosmetic, printing, and textile, the use of synthetic dyes has been integral with products such as azo dye, anthrax, and dyestuffs. As such, these industries produce a lot of waste by-products that could contaminate the environment. Bioremediation, therefore, has become an important emerging technology due to its cost-sustainable, effective, natural approach to cleaning up contaminated groundwater and soil via the use of microorganisms. The use of microorganisms in bioremediation requires the optimisation of parameters used in cultivating the organism...
2016: TheScientificWorldJournal
https://www.readbyqxmd.com/read/27797486/palladium-triggered-chemical-rescue-of-intracellular-proteins-via-genetically-encoded-allene-caged-tyrosine
#20
Jie Wang, Siqi Zheng, Yanjun Liu, Zhaoyue Zhang, Zhi Lin, Jiaofeng Li, Gong Zhang, Xin Wang, Jie Li, Peng R Chen
Chemical decaging has emerged as an attractive strategy for gain-of-function study of proteins via small molecule reagents. The previously reported chemical decaging reactions have been largely centered on liberating the side-chain of lysine on a given protein. Herein, we developed an allene-based caging moiety and the corresponding palladium decaging reagents for chemical rescue of tyrosine (Tyr) activity on intracellular proteins. This bioorthogonal decaging pair has been successfully applied to unmask enzymatic Tyr sites (eg...
October 31, 2016: Journal of the American Chemical Society
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