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Joshua C Eby, Mary C Gray, Jason M Warfel, Tod J Merkel, Erik L Hewlett
ACT is an essential virulence factor of Bordetella pertussis and antibodies to ACT protect against B. pertussis infection in mice. The toxin is, therefore, a strong candidate antigen for addition to future acellular pertussis vaccines. In order to characterize the functionality of the immunologic response to ACT after infection, we have developed an assay for testing the ability of serum samples from subjects infected with B. pertussis to neutralize ACT-induced cytotoxicity in J774 macrophage cells. Baboons develop neutralizing anti-ACT antibodies following infection with B...
October 19, 2016: Clinical and Vaccine Immunology: CVI
Marcella Araújo Manfredi, Alyne Alexandrino Antunes, Larissa de Oliveira Passos Jesus, Maria Aparecida Juliano, Luiz Juliano, Wagner Alves de Souza Judice
Kex2 is a Ca(2+)-dependent serine protease from S. cerevisiae. Characterization of the substrate specificity of Kex2 is of particular interest because this protease serves as the prototype of a large family of eukaryotic subtilisin-related proprotein-processing proteases that cleave sites consisting of pairs or clusters of basic residues. Our goal was to study the prime region subsite S' of Kex2 because previous studies have only taken into account non-prime sites using AMC substrates but not the specificity of prime sites identified through structural modeling or predicted cleavage sites...
October 5, 2016: Biochimie
Spencer C Alford, Connor O'Sullivan, Perry L Howard
Protein toxin splicing mediated by split inteins can be used as a strategy for conditional cell ablation. The approach requires artificial fragmentation of a potent protein toxin and tethering each toxin fragment to a split intein fragment. The toxin-intein fragments are, in turn, fused to dimerization domains, such that addition of a dimerizing agent reconstitutes the split intein. These chimeric toxin-intein fusions remain nontoxic until the dimerizer is added, resulting in activation of intein splicing and ligation of toxin fragments to form an active toxin...
2017: Methods in Molecular Biology
Wilbur H Chen, Marcela F Pasetti, Rajan P Adhikari, Holly Baughman, Robin Douglas, Jill El-Khorazaty, Nancy Greenberg, Frederick W Holtsberg, Grant C Liao, Mardi K Reymann, Xiaolin Wang, Kelly L Warfield, M Javad Aman
: Staphylococcus aureus produces several enterotoxins and superantigens, exposure to which can elicit profound toxic shock. A recombinant staphylococcal enterotoxin B (rSEB), containing 3 distinct mutations in the MHCII binding site, was combined with Alhydrogel as a potential parenteral vaccine named STEBVax.Consenting healthy adult volunteers, age 23-38 years, participated in a first-in-human open label dose-escalation study of parenteral doses of STEBVax ranging from 0.01 μg up to 20 μg...
October 5, 2016: Clinical and Vaccine Immunology: CVI
Michihiro Hashimoto, Azusa Asai, Hiroyuki Kawagishi, Ryuta Mikawa, Yuji Iwashita, Kazuki Kanayama, Kazushi Sugimoto, Tadashi Sato, Mitsuo Maruyama, Masataka Sugimoto
Senescent cells accumulate in many tissues as animals age and are considered to underlie several aging-associated pathologies. The tumor suppressors p19(ARF) and p16(INK4a), both of which are encoded in the CDKN2A locus, play critical roles in inducing and maintaining permanent cell cycle arrest during cellular senescence. Although the elimination of p16(INK4a)-expressing cells extends the life span of the mouse, it is unclear whether tissue function is restored by the elimination of senescent cells in aged animals and whether and how p19(ARF) contributes to tissue aging...
August 4, 2016: JCI Insight
Marta H Taniwaki, Jens C Frisvad, Larissa S Ferranti, Aline de Souza Lopes, Thomas O Larsen, Maria Helena P Fungaro, Beatriz T Iamanaka
A total of 172 Brazil nut samples (114 in shell and 58 shelled) from the Amazon rainforest region and São Paulo state, Brazil was collected at different stages of the Brazil nut production chain: rainforest, street markets, processing plants and supermarkets. The mycobiota of the Brazil nut samples were evaluated and also compared in relation to water activity. A huge diversity of Aspergillus and Penicillium species were found, besides Eurotium spp., Zygomycetes and dematiaceous fungi. A polyphasic approach using morphological and physiological characteristics, as well as molecular and extrolite profiles, were studied to distinguish species among the more important toxigenic ones in Aspergillus section Flavi and A...
February 2017: Food Microbiology
Antonio Varriale, Karine Bonnot, Sergio Peransi, Andrea Scala, Sabato D'Auria
A fast and reliable detection of biological agents in air is of a crucial importance to respond to terrorist attacks. With the aim to efficiently react to such hazards there is the need to develop highly sensitive and specific detection analytical devices for selective and quantitative detection of biological threats such as the presence of Bacillus anthracis spores and/or the presence of Ricin A toxins. In this study we explored how to achieve an oriented immobilization of antibody molecules on silicon nitride surfaces to improve their efficiency to bind to specific target molecules...
August 30, 2016: Colloids and Surfaces. B, Biointerfaces
Nathalie Goeders, Ray Chai, Bihe Chen, Andrew Day, George P C Salmond
Toxin-antitoxin (TA) systems are small genetic modules that encode a toxin (that targets an essential cellular process) and an antitoxin that neutralises or suppresses the deleterious effect of the toxin. Based on the molecular nature of the toxin and antitoxin components, TA systems are categorised into different types. Type III TA systems, the focus of this review, are composed of a toxic endoribonuclease neutralised by a non-coding RNA antitoxin in a pseudoknotted configuration. Bioinformatic analysis shows that the Type III systems can be classified into subtypes...
2016: Toxins
Kit-Ling Fan, Yan-Li Wang, Gary Chu, Ling-Pong Leung
BACKGROUND: Injection of botulinum toxin type A for cosmetic purposes is common. It is believed to be safe, but adverse reactions have been reported, including dysphagia, generalized paralysis, respiratory depression, and death caused by focal injection of the toxin. Early administration of antitoxin in patients with adverse reactions is the mainstay of management, but the time window for its clinical efficacy is not well defined. CASE REPORTS: Two female adult patients with clinical botulism after botulinum toxin type A injection are described...
September 26, 2016: Journal of Emergency Medicine
Samira Lahrabli, Herman Azanmasso, Fatima Lmidmani, Abdellatif El Fatimi
OBJECTIVE: Spasticity of the upper limb is a disabling symptom in patients with vascular hemiplegia, both functionally and orthopedic evolution of these patients. Many treatments exist for spasticity, and botulinum toxin may be an attractive therapeutic alternative, to fight against the often deleterious spasticity. MATERIAL/PATIENTS AND METHODS: We report a retrospective work of 10 spastic patients treated with ultrasound-guided injection of botulinum toxin into the MPR Casablanca service...
September 2016: Annals of Physical and Rehabilitation Medicine
Victoria I Verhoeve, Krit Jirakanwisal, Tadanobu Utsuki, Kevin R Macaluso
Crucial factors influencing the epidemiology of Rickettsia felis rickettsiosis include pathogenesis and transmission. Detection of R. felis DNA in a number of arthropod species has been reported, with characterized isolates, R. felis strain LSU and strain LSU-Lb, generated from the cat flea, Ctenocephalides felis, and the non-hematophagous booklouse, Liposcelis bostrychophila, respectively. While it is realized that strain influence on host biology varies, the rickettsial response to these distinct host environments remained undefined...
2016: PloS One
R Garreta-Figuera, A Torrequebrada-Gimenez, En Representacion Del Grupo de Estudio 5e En Representacion Del Grupo de Estudio 5e
INTRODUCTION: Although spasticity is a disabling complication of high incidence, there is a lack of either regional or national epidemiological studies in Spain evaluating its management. AIM: To evaluate the management of spasticity in Spain. PATIENTS AND METHODS: An epidemiological, observational, multicenter, and retrospective study involving 49 rehabilitation services of public and private hospitals was designed. RESULTS: Two hundred and thirty-five patients from 49 centers, with evidence of upper (UL) or lower limb (LL) spasticity with one valid baseline visit and at least one follow-up visit, were included...
October 1, 2016: Revista de Neurologia
Zdzisław A Bogucki, Mariola Kownacka
The purpose of this work is to present a new, still experimental method of treating temporomandibular disorders (TMD) by injecting botulinum toxin Type A (TBX-A), using its effects not as a toxin but as a medication. The mechanism of TBX-A, indications and contraindications for its use, as well as possible side effects, are discussed. Temporomandibular disorders are of concern to approximately 70-80% of the population. The effect of botulinum toxin depends on blocking the release of acetylcholine from a presynaptic neuromuscular synapse and, in the autonomous system, blocking its release from post-ganglionic cholinergic neurons...
May 2016: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Rebecca A Flaherty, Shaun W Lee
Many bacterial pathogens secrete potent toxins to aid in the destruction of host tissue, to initiate signaling changes in host cells or to manipulate immune system responses during the course of infection. Though methods have been developed to successfully purify and produce many of these important virulence factors, there are still many bacterial toxins whose unique structure or extensive post-translational modifications make them difficult to purify and study in in vitro systems. Furthermore, even when pure toxin can be obtained, there are many challenges associated with studying the specific effects of a toxin under relevant physiological conditions...
2016: Journal of Visualized Experiments: JoVE
Kevin T Huguet, Mathieu Gonnet, Benoît Doublet, Axel Cloeckaert
The multidrug resistance Salmonella Genomic Island 1 (SGI1) is an integrative mobilizable element identified in several enterobacterial pathogens. This chromosomal island requires a conjugative IncA/C plasmid to be excised as a circular extrachromosomal form and conjugally mobilized in trans. Preliminary observations suggest stable maintenance of SGI1 in the host chromosome but paradoxically also incompatibility between SGI1 and IncA/C plasmids. Here, using a Salmonella enterica serovar Agona clonal bacterial population as model, we demonstrate that a Toxin-Antitoxin (TA) system encoded by SGI1 plays a critical role in its stable host maintenance when an IncA/C plasmid is concomitantly present...
2016: Scientific Reports
Kim Vriens, Steve Peigneur, Barbara De Coninck, Jan Tytgat, Bruno P A Cammue, Karin Thevissen
Scorpion toxins that block potassium channels and antimicrobial plant defensins share a common structural CSαβ-motif. These toxins contain a toxin signature (K-C4-X-N) in their amino acid sequence, and based on in silico analysis of 18 plant defensin sequences, we noted the presence of a toxin signature (K-C5-R-G) in the amino acid sequence of the Arabidopsis thaliana defensin AtPDF2.3. We found that recombinant (r)AtPDF2.3 blocks Kv1.2 and Kv1.6 potassium channels, akin to the interaction between scorpion toxins and potassium channels...
2016: Scientific Reports
Clare L Kirkpatrick, Daniel Martins, Peter Redder, Antonio Frandi, Johann Mignolet, Julien Bortoli Chapalay, Marc Chambon, Gerardo Turcatti, Patrick H Viollier
Bacterial toxin-antitoxin systems (TASs) are thought to respond to various stresses, often inducing growth-arrested (persistent) sub-populations of cells whose housekeeping functions are inhibited. Many such TASs induce this effect through the translation-dependent RNA cleavage (RNase) activity of their toxins, which are held in check by their cognate antitoxins in the absence of stress. However, it is not always clear whether specific mRNA targets of orthologous RNase toxins are responsible for their phenotypic effect, which has made it difficult to accurately place the multitude of TASs within cellular and adaptive regulatory networks...
2016: Nature Microbiology
Adam Perczak, Krzysztof Juś, Katarzyna Marchwińska, Daniela Gwiazdowska, Agnieszka Waśkiewicz, Piotr Goliński
Essential oils are volatile compounds, extracted from plants, which have a strong odor. These compounds are known for their antibacterial and antifungal properties. However, data concerning degradation of mycotoxins by these metabolites are very limited. The aim of the present study was to investigate the effect of essential oils (cedarwood, cinnamon leaf, cinnamon bark, white grapefruit, pink grapefruit, lemon, eucalyptus, palmarosa, mint, thymic, and rosemary) on zearalenone (ZEA) reduction under various in vitro conditions, including the influence of temperature, pH, incubation time and mycotoxin and essential oil concentrations...
2016: Frontiers in Microbiology
Lei Lv, Donghao Li, Chengbi Cui, Yangyang Zhao, Zhijun Guo
Ochratoxin A (OTA), a toxin produced by Aspergillus ochraceus and Penicillium verrucosum, is one of the most abundant food-contaminating mycotoxins worldwide. OTA mainly exerts nephrotoxicity, immunotoxicity, mutagenicity, carcinogenicity, teratogenicity, and neurotoxicity. This paper describes a simple and sensitive aptamer/single-walled carbon nanohorn (SWCNH)-based assay for OTA detection. SWCNHs can protect DNA from DNase I cleavage. However, aptamers can be detached from the surface of SWCNHs through specific target binding, exposing them to enzymatic cleavage and releases the target for a new cycle...
August 10, 2016: Biosensors & Bioelectronics
Ines Rodriguez, Maria Fraga, Amparo Alfonso, Delphine Guillebault, Linda Medlin, Julia Baudart, Pauline Jacob, Karim Helmi, Thomas Meyer, Ulrich Breitenbach, Nicholas M Holden, Bas Boots, Roberto Spurio, Lucia Cimarelli, Laura Mancini, Stefania Marcheggiani, Meric Albay, Reyhan Akcaalan, Latife Köker, Luis M Botana
Monitoring the quality of freshwater is an important issue for public health. In the context of the European project μAqua, 150 samples were collected from several waters in France, Germany, Ireland, Italy, and Turkey for 2 yr. These samples were analyzed using 2 multitoxin detection methods previously developed: a microsphere-based method coupled to flow-cytometry, and an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The presence of microcystins, nodularin, domoic acid, cylindrospermopsin, and several analogues of anatoxin-a (ATX-a) was monitored...
August 9, 2016: Environmental Toxicology and Chemistry
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