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Changqing Lu, Lihua Dong, Hui Zhou, Qianmei Li, Guojiao Huang, Shu Jun Bai, Linchuan Liao
Oligodendrocytes are the myelin-producing cells of the central nervous system (CNS). A variety of brain disorders from "classical" demyelinating diseases, such as multiple sclerosis, stroke, schizophrenia, depression, Down syndrome and autism, are shown myelination defects. Oligodendrocyte myelination is regulated by a complex interplay of intrinsic, epigenetic and extrinsic factors. Gpr17 (G protein-coupled receptor 17) is a G protein-coupled receptor, and has been identified to be a regulator for oligodendrocyte development...
March 14, 2018: Scientific Reports
Ben A Wagstaff, Edward S Hems, Martin Rejzek, Jennifer Pratscher, Elliot Brooks, Sakonwan Kuhaudomlarp, Ellis C O'Neill, Matthew I Donaldson, Steven Lane, John Currie, Andrew M Hindes, Gill Malin, J Colin Murrell, Robert A Field
Prymnesium parvum is a toxin-producing microalga that causes harmful algal blooms globally, which often result in large-scale fish kills that have severe ecological and economic implications. Although many toxins have previously been isolated from P. parvum , ambiguity still surrounds the responsible ichthyotoxins in P. parvum blooms and the biotic and abiotic factors that promote bloom toxicity. A major fish kill attributed to P. parvum occurred in Spring 2015 on the Norfolk Broads, a low-lying set of channels and lakes (Broads) found on the East of England...
March 14, 2018: Biochemical Society Transactions
Tomoya Maeda, Yuya Tanaka, Masayuki Inui
The Corynebacterium glutamicum R grtA (cgR_2936), grtB (cgR_2934), and grtC (cgR_2933) genes were identified as paralogs encoding glutamine-rich toxic proteins. We also identified a new antisense small RNA AsgR (antisense sRNA for grtA) that overlaps the 3' end of the grtA gene. Single over-expressions of grtA, grtB, and grtC resulted in complete inhibition of Escherichia coli cell growth. This growth was rescued by co-expression of AsgR. Similar effects were observed in C. glutamicum, although the toxicities of these proteins were moderate...
March 14, 2018: Molecular Microbiology
Aleksandra Małachowska, Paweł Olszewski
BACKGROUND: Transcriptional control of gene expression is a widely utilized regulatory mechanism in synthetic biology, biotechnology and recombinant protein production. It is achieved by utilization of naturally occurring promoters responding to nutrients or chemicals. Despite their regulatory properties, these promoters often possess features which diminish their utility for biotechnology. High basal expression level and low induction ratio can be removed using genetic engineering techniques, although this process is often laborious and time-consuming...
March 13, 2018: Microbial Cell Factories
Yun-Mi Kang, Kyung-Sook Chung, In-Hoon Kook, Yoon-Bum Kook, Hyunsu Bae, Minho Lee, Hyo-Jin An
Although bee venom (BV) is a toxin that causes bee stings to be painful, it has been widely used clinically for the treatment of certain immune‑associated diseases. BV has been used traditionally for the treatment of chronic inflammatory diseases. In this regard, the present study analyzed the effect of BV on the regulation of inflammatory mediator production by mast cells and their allergic inflammatory responses in an animal model. HMC‑1 cells were treated with BV prior to stimulation with phorbol‑12‑myristate 13‑acetate plus calcium ionophore A23187 (PMACI)...
March 12, 2018: International Journal of Molecular Medicine
Hannah G Hampton, Simon A Jackson, Robert D Fagerlund, Anne I M Vogel, Ron L Dy, Tim R Blower, Peter C Fineran
Bacteria resist phage infection using multiple strategies, including CRISPR-Cas and abortive infection (Abi) systems. Abi systems provide population-level protection from phage predation, via "altruistic" cell suicide. It has recently been shown that some Abi systems function via a toxin-antitoxin (TA) mechanism, such as the widespread AbiE family. The Streptococcus agalactiae AbiE system consists of a bicistronic operon encoding the AbiEi antitoxin and AbiEii toxin, which function as a Type IV TA system...
March 5, 2018: Journal of Molecular Biology
Wiebke Schmidt, David Raymond, David Parish, Ian G C Ashton, Peter I Miller, Carlos J A Campos, Jamie D Shutler
The need to ensure future food security and issues of varying estuarine water quality is driving the expansion of aquaculture into near-shore coastal waters. It is prudent to fully evaluate new or proposed aquaculture sites, prior to any substantial financial investment in infrastructure and staffing. Measurements of water temperature, salinity and dissolved oxygen can be used to gain insight into the physical, chemical and biological water quality conditions within a farm site, towards identifying its suitability for farming, both for the stock species of interest and for assessing the potential risk from harmful or toxic algae...
January 2018: Aquacultural Engineering
Anita Verma, Miriam M Ngundi, Gregory A Price, Kazuyo Takeda, James Yu, Drusilla L Burns
Toxin neutralizing antibodies represent the major mode of protective immunity against a number of toxin-mediated bacterial diseases, including anthrax; however, the cellular mechanisms that lead to optimal neutralizing antibody responses remain ill defined. Here we show that the cellular binding pathway of anthrax protective antigen (PA), the binding component of anthrax toxin, determines the toxin neutralizing antibody response to this antigen. PA, which binds cellular receptors and efficiently enters antigen-presenting cells by receptor-mediated endocytosis, was found to elicit robust anti-PA IgG and toxin neutralizing antibody responses...
February 27, 2018: MBio
Tânia C Gonçalves, Rachid Boukaiba, Jordi Molgó, Muriel Amar, Michel Partiseti, Denis Servent, Evelyne Benoit
The Chinese bird spider huwentoxin-IV (HwTx-IV) is well-known to be a highly potent blocker of NaV 1.7 subtype of voltage-gated sodium (NaV ) channels, a genetically validated analgesic target, and thus promising as a potential lead molecule for the development of novel pain therapeutics. In the present study, the interaction between HwTx-IV and NaV 1.6 channel subtype was investigated using multiscale (from in vivo to individual cell) functional approaches. HwTx-IV was approximatively 2 times more efficient than tetrodotoxin (TTX) to inhibit the compound muscle action potential recorded from the mouse skeletal neuromuscular system in vivo, and 30 times more effective to inhibit nerve-evoked than directly-elicited muscle contractile force of isolated mouse hemidiaphragms...
February 20, 2018: Neuropharmacology
Yijie Chen, Mengchun Chen, Yue Zhang, Joo Hee Lee, Tamara Escajadillo, Hua Gong, Ronnie H Fang, Weiwei Gao, Victor Nizet, Liangfang Zhang
Neutralization of bacterial toxins has become a compelling approach to treating bacterial infections as it may pose less selective pressure for the development of bacterial resistance. Currently, the majority of toxin neutralization platforms act by targeting the molecular structure of the toxin, which requires toxin identification and customized design for different diseases. Therefore, their development has been challenged by the enormous number and complexity of bacterial toxins. Herein, biomimetic toxin nanosponges are formulated by coating membranes of human red blood cells (hRBCs) onto polymeric nanoparticles, which act as a toxin decoy to absorb and neutralize a broad-spectrum of hemolytic toxins regardless of their molecular structure...
February 13, 2018: Advanced Healthcare Materials
Dejan Micic, Andres Yarur, Alex Gonsalves, Vijaya L Rao, Susan Broadaway, Russell Cohen, Sushila Dalal, John N Gaetano, Laura R Glick, Ayal Hirsch, Joel Pekow, Atsushi Sakuraba, Seth T Walk, David T Rubin
INTRODUCTION: Clostridium difficile is the most commonly isolated stool pathogen in inflammatory bowel disease (IBD). Traditional risk factors for C. difficile may not exist in patients with IBD, and no prior studies have assessed the risk factors for the isolation of C. difficile in both symptomatic and asymptomatic IBD outpatients. METHODS: We prospectively recruited consecutive IBD patients presenting to our outpatient clinic between April 2015 and February 2016...
February 8, 2018: Digestive Diseases and Sciences
M López, A Rueda, J P Florido, L Blasco, L Fernández-García, R Trastoy, F Fernández-Cuenca, L Martínez-Martínez, J Vila, A Pascual, G Bou, M Tomas
In this study, we compared eighteen clinical strains of A. baumannii belonging to the ST-2 clone and isolated from patients in the same intensive care unit (ICU) in 2000 (9 strains referred to collectively as Ab_GEIH-2000) and 2010 (9 strains referred to collectively as Ab_GEIH-2010), during the GEIH-REIPI project (Umbrella BioProject PRJNA422585). We observed two main molecular differences between the Ab_GEIH-2010 and the Ab_GEIH-2000 collections, acquired over the course of the decade long sampling interval and involving the mobilome: i) a plasmid harbouring genes for blaOXA 24/40 ß-lactamase and abKA/abkB proteins of a toxin-antitoxin system; and ii) two temperate bacteriophages, Ab105-1ϕ (63 proteins) and Ab105-2ϕ (93 proteins), containing important viral defence proteins...
February 6, 2018: Scientific Reports
Juan J Quereda, Christopher Andersson, Pascale Cossart, Jörgen Johansson, Javier Pizarro-Cerdá
Most human listeriosis outbreaks are caused by Listeria monocytogenes evolutionary lineage I strains which possess four exotoxins: a phosphatidylinositol-specific phospholipase C (PlcA), a broad-range phospholipase C (PlcB), listeriolysin O (LLO) and listeriolysin S (LLS). The simultaneous contribution of these molecules to virulence has never been explored. Here, the importance of these four exotoxins of an epidemic lineage I L. monocytogenes strain (F2365) in virulence was assessed in chicken embryos infected in the allantoic cavity...
February 6, 2018: Veterinary Research
Alexander Harms, Ditlev Egeskov Brodersen, Namiko Mitarai, Kenn Gerdes
Bacterial toxin-antitoxin (TA) modules are abundant genetic elements that encode a toxin protein capable of inhibiting cell growth and an antitoxin that counteracts the toxin. The majority of toxins are enzymes that interfere with translation or DNA replication, but a wide variety of molecular activities and cellular targets have been described. Antitoxins are proteins or RNAs that often control their cognate toxins through direct interactions and, in conjunction with other signaling elements, through transcriptional and translational regulation of TA module expression...
January 21, 2018: Molecular Cell
Katrin Grosser, Pathmanaban Ramasamy, Azim Dehghani Amirabad, Marcel H Schulz, Gilles Gasparoni, Martin Simon, Martina Schrallhammer
Endosymbiosis is a widespread phenomenon and hosts of bacterial endosymbionts can be found all-over the eukaryotic tree of life. Likely, this evolutionary success is connected to the altered phenotype arising from a symbiotic association. The potential variety of symbiont's contributions to new characteristics or abilities of host organisms are largely unstudied. Addressing this aspect, we focused on an obligate bacterial endosymbiont that confers an intraspecific killer phenotype to its host. The symbiosis between Paramecium tetraurelia and Caedibacter taeniospiralis, living in the host's cytoplasm, enables the infected paramecia to release Caedibacter symbionts, which can simultaneously produce a peculiar protein structure and a toxin...
January 30, 2018: Genome Biology and Evolution
S Yee, P J Blackall, C Turni
OBJECTIVE: To explore the diversity among isolates of the Actinobacillus pleuropneumoniae serovars most common in Australia (serovars 1, 5, 7 and 15) and to examine the Apx toxin profiles in selected representative isolates. DESIGN: A total of 250 isolates selected from different farms were examined for their genotypic profiles and a subset of 122 isolates for their toxin profiles. METHODS: The isolates of serovars 1, 5, 7 and 15 selected for this study came from different farms and different Australian states and were submitted for serotyping to the reference laboratory...
January 2018: Australian Veterinary Journal
Peyman Bemani, Mozafar Mohammadi, Ali Hakakian
Aim: Immunotoxins are proteins that consist of an antibody fragment linked to a toxin, used as agents for targeted therapy of cancers. Although the most potent immunotoxins are made from bacterial and plant toxins, obstacles which contribute to poor responses are immunogenicity in patients and rapid development of neutralizing antibodies. In the present study we proposed a new therapeutic immunotoxin for targeted cancer therapy of ROR1 expressing cancers: an anti ROR1 single chain fragment variable antibody (scFv)-endonuclease G (anti ROR1 scFv-EndoG)...
January 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Nassim Mahtal, Clémence Brewee, Sylvain Pichard, Orane Visvikis, Jean-Christophe Cintrat, Julien Barbier, Emmanuel Lemichez, Daniel Gillet
The Cytotoxic Necrotizing Factor 1 (CNF1) is a toxin produced by pathogenic strains of Escherichia coli responsible for extra-intestinal infections. CNF1 deamidates Rac1, thereby triggering its permanent activation, and worsening inflammatory reactions. Activated Rac1 is prone to proteasomal degradation. There is no targeted therapy against CNF1, despite its clinical relevance. In this work, we developed a fluorescent, cell-based immunoassay to screen for inhibitors of CNF1-induced Rac1 degradation among 1,120 mostly approved drugs...
January 23, 2018: ChemMedChem
Manon Bonneau, Celestine Atyame, Marwa Beji, Fabienne Justy, Martin Cohen-Gonsaud, Mathieu Sicard, Mylène Weill
Culex pipiens mosquitoes are infected with Wolbachia (wPip) that cause an important diversity of cytoplasmic incompatibilities (CIs). Functional transgenic studies have implicated the cidA-cidB operon from wPip and its homolog in wMel in CI between infected Drosophila males and uninfected females. However, the genetic basis of the CI diversity induced by different Wolbachia strains was unknown. We show here that the remarkable diversity of CI in the C. pipiens complex is due to the presence, in all tested wPip genomes, of several copies of the cidA-cidB operon, which undergoes diversification through recombination events...
January 22, 2018: Nature Communications
Pierre Adumeau, Delphine Vivier, Sai Kiran Sharma, Jessica Wang, Terry Zhang, Aimei Chen, Brian J Agnew, Brian M Zeglis
The conjugation of antibodies with cytotoxic drugs can alter their in vivo pharmacokinetics. As a result, the careful assessment of the in vivo behavior and specifically the tumor-targeting properties of antibody-drug conjugates represents a crucial step in their development. In order to facilitate this process, we have created a methodology that facilitates the dual labeling of an antibody with both a toxin and a radionuclide for positron emission tomography (PET). To minimize the impact of these modifications, this chemoenzymatic approach leverages strain-promoted azide-alkyne click chemistry to graft both cargoes to the heavy chain glycans of the immuoglobulin's Fc domain...
January 22, 2018: Molecular Pharmaceutics
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