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https://www.readbyqxmd.com/read/28545305/clostridium-difficile-toxins-a-and-b-receptors-pores-and-translocation-into-cells
#1
Kathleen E Orrell, Zhifen Zhang, Seiji N Sugiman-Marangos, Roman A Melnyk
The most potent toxins secreted by pathogenic bacteria contain enzymatic moieties that must reach the cytosol of target cells to exert their full toxicity. Toxins such as anthrax, diphtheria, and botulinum toxin all use three well-defined functional domains to intoxicate cells: a receptor-binding moiety that triggers endocytosis into acidified vesicles by binding to a specific host-cell receptor, a translocation domain that forms pores across the endosomal membrane in response to acidic pH, and an enzyme that translocates through these pores to catalytically inactivate an essential host cytosolic substrate...
May 26, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28533492/anti-tumor-activity-of-anthrax-toxin-variants-that-form-a-functional-translocation-pore-by-intermolecular-complementation
#2
Shihui Liu, Qian Ma, Rasem Fattah, Thomas H Bugge, Stephen H Leppla
Anthrax lethal toxin is a typical A-B type protein toxin secreted by Bacillus anthracis. Lethal factor (LF) is the catalytic A-subunit, a metalloprotease having MEKs as targets. LF relies on the cell-binding B-subunit, protective antigen (PA), to gain entry into the cytosol of target cells. PA binds to cell surface toxin receptors and is activated by furin protease to form an LF-binding-competent oligomer-PA pre-pore, which converts to a functional protein-conductive pore in the acidic endocytic vesicles, allowing translocation of LF into the cytosol...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28509866/hdac8-prevents-anthrax-lethal-toxin-induced-cell-cycle-arrest-through-silencing-pten-in-human-monocytic-thp-1-cells
#3
Soon-Duck Ha, Woohyun Cho, Sung Ouk Kim
Anthrax lethal toxin (LeTx) is a cytotoxic virulence factor that causes cell cycle arrest and cell death in various cell types. However, susceptibility to the cytotoxic effects varies depending on cell types. In proliferating monocytes, LeTx has only transient cytotoxic effects due to activation of the phosphoinositide 3-kinase (PI3K)-AKT-mediated adaptive responses. To date, the mechanism of LeTx in activating PI3K-AKT signaling axis is unknown. This study shows that the histone deacetylase 8 (HDAC8) is involved in activating PI3K-AKT signaling axis through down-regulating the phosphatase and tensin homolog 1 (PTEN) in human monocytic THP-1 cells...
May 16, 2017: Toxins
https://www.readbyqxmd.com/read/28506101/evaluation-of-personal-inhalable-aerosol-samplers-with-different-filters-for-use-during-anthrax-responses
#4
Sergey A Grinshpun, Angela M Weber, Michael Yermakov, Reshmi Indugula, Yousef Elmashae, Tiina Reponen, Laura Rose
Risk of inhalation exposure to viable Bacillus anthracis (B. anthracis) spores has primarily been assessed using short-term, stationary sampling methods which may not accurately characterize the concentration of inhalable-sized spores reaching a person's breathing zone. While a variety of aerosol sampling methods have been utilized during previous anthrax responses, no consensus has yet been established for personal air sampling. The goal of this study was to determine the best sampler-filter combination(s) for the collection and extraction of B...
May 16, 2017: Journal of Occupational and Environmental Hygiene
https://www.readbyqxmd.com/read/28504191/lethal-factor-antibodies-contribute-to-lethal-toxin-neutralization-in-recipients-of-anthrax-vaccine-precipitated
#5
Eric K Dumas, Lori Garman, Hannah Cuthbertson, Sue Charlton, Bassam Hallis, Renata J M Engler, Shyamal Choudhari, William D Picking, Judith A James, A Darise Farris
A major difference between two currently licensed anthrax vaccines is presence (United Kingdom Anthrax Vaccine Precipitated, AVP) or absence (United States Anthrax Vaccine Adsorbed, AVA) of quantifiable amounts of the Lethal Toxin (LT) component Lethal Factor (LF). The primary immunogen in both vaccine formulations is Protective Antigen (PA), and LT-neutralizing antibodies directed to PA are an accepted correlate of vaccine efficacy; however, vaccination studies in animal models have demonstrated that LF antibodies can be protective...
May 11, 2017: Vaccine
https://www.readbyqxmd.com/read/28498841/awareness-and-attitudes-towards-anthrax-and-meat-consumption-practices-among-affected-communities-in-zambia-a-mixed-methods-approach
#6
Doreen Chilolo Sitali, Chisoni Mumba, Eystein Skjerve, Oliver Mweemba, Consolata Kabonesa, Mwinyi Omary Mwinyi, Luke Nyakarahuka, John Bwalya Muma
BACKGROUND: In Zambia, human anthrax cases often occur following cases of animal anthrax. Human behaviour has been implicated in this transmission. The objective of the study was to explore human behavioural patterns that may contribute to outbreaks of anthrax among affected communities. METHODS: A mixed methods study was conducted in four districts of Zambia from November 2015 to February 2016. A cross sectional survey involving 1,127 respondents, six focus group discussions and seven key informant interviews with professional staff were conducted...
May 12, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28495766/ten-genome-sequences-of-human-and-livestock-isolates-of-bacillus-anthracis-from-the-country-of-georgia
#7
Ekaterine Khmaladze, Giorgi Dzavashvili, Gvantsa Chanturia, Mikeljon P Nikolich, Patrick S G Chain, Shannon L Johnson, Paata Imnadze
Bacillus anthracis causes the acute fatal disease anthrax, is a proven biological weapon, and is endemic in Georgia, where human and animal cases are reported annually. Here, we present whole-genome sequences of 10 historical B. anthracis strains from Georgia.
May 11, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28452296/forensic-approaches-to-detect-possible-agents-of-bioterror
#8
Alfredo A González, Jessica I Rivera-Pérez, Gary A Toranzos
Many biological agents have been strategic pathogenic agents throughout history. Some have even changed history as a consequence of early discoveries of their use as weapons of war. Many of these bioagents can be easily isolated from the environment, and some have recently been genetically manipulated to become more pathogenic for biowarfare. However, it is difficult to determine accidental outbreaks of disease from intentional exposures. In this review, we examine how molecular tools have been used in combination with forensic research to resolve cases of unusual outbreaks and trace the source of the biocrime...
April 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28442608/unexpected-relations-of-historical-anthrax-strain
#9
M H Antwerpen, J W Sahl, D Birdsell, T Pearson, M J Pearce, C Redmond, H Meyer, P S Keim
In 1998, it was claimed that an 80-year-old glass tube intentionally filled with Bacillus anthracis and embedded in a sugar lump as a WWI biological weapon still contained viable spores. Today, genome sequencing of three colonies isolated in 1998 and subjected to phylogenetic analysis surprisingly identified a well-known B. anthracis reference strain isolated in the United States in 1981, pointing to accidental laboratory contamination.IMPORTANCE Next-generation sequencing and subsequent phylogenetic analyses are useful and reliable tools for the classification of recent and historical samples...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28438974/b-anthracis-edema-toxin-increases-fractional-free-water-and-sodium-reabsorption-in-an-isolated-perfused-rat-kidney-model
#10
Dharmvir S Jaswal, Xizhong Cui, Parizad Torabi-Parizi, Lernik Ohanjanian, Hannish Sampath-Kumar, Yvonne Fitz, Yan Li, Wanying Xu, Peter Q Eichacker
Introduction:B. anthracis edema toxin (ET) consists of protective antigen (PA), necessary for host cell toxin uptake, and edema factor (EF), the toxic moiety which increases host cell cAMP. Since vasopressin stimulates renal water and sodium reabsorption via increased tubular cell cAMP, we hypothesized ET would also. To test this hypothesis, we employed an isolated perfused rat kidney model. Methods and Results: Kidneys were isolated and perfused with modified Krebs-Henseleit. Perfusate and urine samples were obtained at baseline and every 10 minutes over 150 minutes following addition to the perfusate of challenges with or without treatments...
April 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28437008/effects-from-metal-ion-in-tumor-endothelial-marker-8-and-anthrax-protective-antigen-biolayer-interferometry-experiment-and-molecular-dynamics-simulation-study
#11
Zhe Jia, Christine Ackroyd, Tingting Han, Vibhor Agrawal, Yinling Liu, Kenneth Christensen, Brian Dominy
One of the anthrax receptors, tumor endothelial marker 8 (TEM8), is reported to be a potential anticancer target due to its over-expression during tumor angiogenesis. To extend our BioLayer Interferometry study in PA-TEM8 binding, we present a computational approach to reveal the role of an integral metal ion on receptor structure and binding thermodynamics. We estimated the interaction energy between PA and TEM8 using computer simulation. Consistent with experimental study, computational results indicate the metal ion in TEM8 contributes significantly to the binding affinity, and PA-TEM8 binding is more favorable in the presence of Mg(2+) than Ca(2+) ...
June 5, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28428293/draft-genome-sequence-of-bacillus-cereus-la2007-a-human-pathogenic-isolate-harboring-anthrax-like-plasmids
#12
Angela Pena-Gonzalez, Chung K Marston, Luis M Rodriguez-R, Cari B Kolton, Julia Garcia-Diaz, Amanda Theppote, Michael Frace, Konstantinos T Konstantinidis, Alex R Hoffmaster
We present the genome sequence of Bacillus cereus LA2007, a strain isolated in 2007 from a fatal pneumonia case in Louisiana. Sequence-based genome analysis revealed that LA2007 carries a plasmid highly similar to Bacillus anthracis pXO1, including the genes responsible for the production and regulation of anthrax toxin.
April 20, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28418302/anthrax-cases-associated-with-animal-hair-shaving-brushes
#13
Christine M Szablewski, Kate Hendricks, William A Bower, Sean V Shadomy, Nathaniel Hupert
During the First World War, anthrax cases in the United States and England increased greatly and seemed to be associated with use of new shaving brushes. Further investigation revealed that the source material and origin of shaving brushes had changed during the war. Cheap brushes of imported horsehair were being made to look like the preferred badger-hair brushes. Unfortunately, some of these brushes were not effectively disinfected and brought with them a nasty stowaway: Bacillus anthracis. A review of outbreak summaries, surveillance data, and case reports indicated that these cases originated from the use of ineffectively disinfected animal-hair shaving brushes...
May 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28400473/tlr-sensing-of-bacterial-spore-associated-rna-triggers-host-immune-responses-with-detrimental-effects
#14
Min-Kyung Choo, Yasuyo Sano, Changhoon Kim, Kei Yasuda, Xiao-Dong Li, Xin Lin, Mary Stenzel-Poore, Lena Alexopoulou, Sankar Ghosh, Eicke Latz, Ian R Rifkin, Zhijian J Chen, George C Stewart, Hyonyong Chong, Jin Mo Park
The spores of pathogenic bacteria are involved in host entry and the initial encounter with the host immune system. How bacterial spores interact with host immunity, however, remains poorly understood. Here, we show that the spores of Bacillus anthracis (BA), the etiologic agent of anthrax, possess an intrinsic ability to induce host immune responses. This immunostimulatory activity is attributable to high amounts of RNA present in the spore surface layer. RNA-sensing TLRs, TLR7, and TLR13 in mice and their human counterparts, are responsible for detecting and triggering the host cell response to BA spores, whereas TLR2 mediates the sensing of vegetative BA...
May 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28398711/major-birth-defects-after-vaccination-reported-to-the-vaccine-adverse-event-reporting-system-vaers-1990-to-2014
#15
Pedro L Moro, Janet Cragan, Paige Lewis, Lakshmi Sukumaran
BACKGROUND: Major birth defects are important infant outcomes that have not been well studied in the postmarketing surveillance of vaccines given to pregnant women. We assessed the presence of major birth defects following vaccination in the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system used to monitor the safety of vaccines in the United States. METHODS: We searched VAERS for reports of major birth defects during January 1, 1990, through December 31, 2014...
April 11, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28398677/preparing-for-biological-threats-addressing-the-needs-of-pregnant-women
#16
REVIEW
Amelia K Watson, Sascha Ellington, Christina Nelson, Tracee Treadwell, Denise J Jamieson, Dana M Meaney-Delman
Intentional release of infectious agents and biological weapons to cause illness and death has the potential to greatly impact pregnant women and their fetuses. We review what is known about the maternal and fetal effects of seven biological threats: Bacillus anthracis (anthrax); variola virus (smallpox); Clostridium botulinum toxin (botulism); Burkholderia mallei (glanders) and Burkholderia pseudomallei (melioidosis); Yersinia pestis (plague); Francisella tularensis (tularemia); and Rickettsia prowazekii (typhus)...
March 15, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28388223/public-understanding-of-medical-countermeasures
#17
Brooke Fisher Liu, Sandra C Quinn, Michael Egnoto, Vicki Freimuth, Natalie Boonchaisri
Medical countermeasures, including new drugs and vaccines, are necessary to protect the public's health from novel diseases and terrorist threats. Experience with the 2001 anthrax attack and the 2009 H1N1 pandemic suggest that there is limited willingness to accept such drugs and that minority groups may respond differently from others. We conducted 148 intercept interviews in the metropolitan Washington, DC, area, examining 2 hypothetical scenarios: a new respiratory virus and public exposure to high levels of radiation...
March 2017: Health Security
https://www.readbyqxmd.com/read/28374254/bacteriophage-t4-as-a-nanoparticle-platform-to-display-and-deliver-pathogen-antigens-construction-of-an-effective-anthrax-vaccine
#18
Pan Tao, Qin Li, Sathish B Shivachandra, Venigalla B Rao
Protein-based subunit vaccines represent a safer alternative to the whole pathogen in vaccine development. However, limitations of physiological instability and low immunogenicity of such vaccines demand an efficient delivery system to stimulate robust immune responses. The bacteriophage T4 capsid-based antigen delivery system can robustly elicit both humoral and cellular immune responses without any adjuvant. Therefore, it offers a strong promise as a novel antigen delivery system. Currently Bacillus anthracis, the causative agent of anthrax, is a serious biothreat agent and no FDA-approved anthrax vaccine is available for mass vaccination...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28348035/what-is-the-predictive-value-of-animal-models-for-vaccine-efficacy-in-humans-the-importance-of-bridging-studies-and-species-independent-correlates-of-protection
#19
Hana Golding, Surender Khurana, Marina Zaitseva
Animal models have played a pivotal role in all stages of vaccine development. Their predictive value for vaccine effectiveness depends on the pathogen, the robustness of the animal challenge model, and the correlates of protection (if known). This article will cover key questions regarding bridging animal studies to efficacy trials in humans. Examples include human papillomavirus (HPV) vaccine in which animal protection after vaccination with heterologous prototype virus-like particles (VLPs) predicted successful efficacy trials in humans, and a recent approval of anthrax vaccine in accordance with the "Animal Rule...
March 27, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28343781/sublingual-targeting-of-sting-with-3-3-cgamp-promotes-systemic-and-mucosal-immunity-against-anthrax-toxins
#20
Tara L Martin, Junbae Jee, Eunsoo Kim, Haley E Steiner, Estelle Cormet-Boyaka, Prosper N Boyaka
Anthrax is caused by Bacillus anthracis, a zoonotic bacterial pathogen affecting humans and livestock worldwide. The current human anthrax vaccine, anthrax vaccine adsorbed (AVA), is an injected vaccine with a cumbersome administration schedule and fails to promote mucosal immunity. Bacterial enterotoxins, which stimulate production of the cyclic nucleotide cAMP are effective experimental mucosal vaccine adjuvants, but their inherent toxicity has precluded their use in humans. We investigated whether cyclic dinucleotides that target Stimulator of Interferon Gamma Genes (STING) in mammalian cells could represent an alternative to bacterial enterotoxins as adjuvant for sublingual immunization and promotion of mucosal immunity and secretory IgA responses in addition to systemic immunity...
April 25, 2017: Vaccine
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