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https://www.readbyqxmd.com/read/29149596/rational-design-of-evolutionarily-stable-microbial-kill-switches
#1
Finn Stirling, Lisa Bitzan, Samuel O'Keefe, Elizabeth Redfield, John W K Oliver, Jeffrey Way, Pamela A Silver
The evolutionary stability of synthetic genetic circuits is key to both the understanding and application of genetic control elements. One useful but challenging situation is a switch between life and death depending on environment. Here are presented "essentializer" and "cryodeath" circuits, which act as kill switches in Escherichia coli. The essentializer element induces cell death upon the loss of a bi-stable cI/Cro memory switch. Cryodeath makes use of a cold-inducible promoter to express a toxin. We employ rational design and a toxin/antitoxin titering approach to produce and screen a small library of potential constructs, in order to select for constructs that are evolutionarily stable...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29140753/a-mutated-recombinant-subunit-vaccine-protects-mice-and-guinea-pigs-against-botulinum-type-a-intoxication
#2
Chi Ho Yu, Dong Hyun Song, Jun Young Choi, Hae Eun Joe, Woo Hyeon Jeong, Gyeung Haeng Hur, Young Kee Shin, Seong Tae Jeong
Botulinum neurotoxins (BoNTs) are the most potent toxins to mammals. A toxoid vaccine was previously used for prevention of botulinum intoxication; however, this vaccine is no longer available. Currently, no approved botulinum vaccines are available from the Food and Drug Administration (FDA). Recently, a recombinant host cell receptor-binding subunit created for use as a potential vaccine completed phase 2 clinical trials. The current study designed a vaccine candidate against BoNT type A (BoNT/A) using a structural design...
November 15, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29133618/therapeutic-impact-of-nanoparticle-therapy-targeting-tumor-associate-macrophages
#3
Courtney Penn, Kun Yang, Hong Zong, Jae-Young Lim, Alex Cole, Dongli Yang, James Baker, Sascha N Goonewardena, Ronald J Buckanovich
Antiangiogenic therapies, despite initial encouragement, have demonstrated a limited benefit in ovarian cancer. Laboratory studies suggest anti-angiogenic therapy induced hypoxia can induce tumor "stemness' as resistance to antiangiogenic therapy develops and limits the therapeutic benefit. Resistance to antiangiogenic therapy and an induction of tumor stemness may be mediated by proangiogenic tumor associated macrophages (TAMs). As such TAMs have been proposed as a therapeutic target. We demonstrate here that ovarian TAMs express high levels of the folate receptor-2 (FOLR2) and can be selectively targeted using G5-dendrimer nanoparticles using methotrexate as both a ligand and a toxin...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29118540/total-endoscopic-and-anal-irrigation-management-approach-to-noncompliant-neuropathic-bladder-and-bowel-in-children-a-long-term-follow-up
#4
Naif Alqarni, Hamdan Alhazmi, Ossamah Alsowayan, Tamer Eweda, Khalid Fouda Neel
Purpose: To evaluate the long-term efficacy and durability of combined intradetrusor botulinum-A toxin (BTX-A), endoscopic treatment of vesicouerteral reflux and anal irrigation for stool incontinence (SI) via a total endoscopic and anal irrigation management (TEAM(®)) approach in patients with myelomeningocele and neuropathic bladder and bowel who did not respond to conservative measures. Materials and Methods: Fourteen myelomeningocele patients with at least 3 years follow-up were included in the study...
October 2017: Urology Annals
https://www.readbyqxmd.com/read/29107209/phkv-a-toxin-isolated-from-the-spider-venom-induces-antinociception-by-inhibition-of-cholinesterase-activating-cholinergic-system
#5
Flavia Karine Rigo, Mateus Fortes Rossato, Gabriela Trevisan, Samira Dal-Toé De Prá, Rafael Porto Ineu, Mariane Bernardo Duarte, Célio José de Castro Junior, Juliano Ferreira, Marcus Vinicius Gomez
BACKGROUND AND AIMS: Cholinergic agents cause antinociception by mimicking the release of acetylcholine (ACh) from spinal cholinergic nerves. PhKv is a peptide isolated from the venom of the armed spider Phoneutria nigriventer. It has an antiarrythmogenic activity that involves the enhanced release of acetylcholine. The aim of this study was to investigate whether PhKv had an antinociceptive action in mice. METHODS: Male albino Swiss mice (25-35g) were used in this study...
October 26, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29099294/introducing-the-new-bacterial-branch-of-the-rnase-a-superfamily
#6
Bonnie J Cuthbert, Kalistyn H Burley, Celia W Goulding
Bovine pancreatic ribonuclease (RNase A) is the founding member of the RNase A superfamily. Members of this superfamily of ribonucleases have high sequence diversity, but possess a similar structural fold, together with a conserved His-Lys-His catalytic triad and structural disulfide bonds. Until recently, RNase A proteins had exclusively been identified in eukaryotes within vertebrae. Here, we discuss the discovery by Batot et al. of a bacterial RNase A superfamily member, CdiA-CT(Ykris): a toxin that belongs to an inter-bacterial competition system from Yersinia kristensenii...
November 3, 2017: RNA Biology
https://www.readbyqxmd.com/read/29093459/nigritoxin-is-a-bacterial-toxin-for-crustaceans-and-insects
#7
Yannick Labreuche, Sabine Chenivesse, Alexandra Jeudy, Sophie Le Panse, Viviane Boulo, Dominique Ansquer, Sylvie Pagès, Alain Givaudan, Mirjam Czjzek, Frédérique Le Roux
The Tetraconata (Pancrustacea) concept proposes that insects are more closely related to aquatic crustaceans than to terrestrial centipedes or millipedes. The question therefore arises whether insects have kept crustacean-specific genetic traits that could be targeted by specific toxins. Here we show that a toxin (nigritoxin), originally identified in a bacterial pathogen of shrimp, is lethal for organisms within the Tetraconata and non-toxic to other animals. X-ray crystallography reveals that nigritoxin possesses a new protein fold of the α/β type...
November 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/29066337/clostridium-difficile-causing-pediatric-infections-new-findings-from-a-hospital-based-study-in-italy
#8
Patrizia Spigaglia, Fabrizio Barbanti, Elio Castagnola, Maria Cristina Diana, Luisa Pescetto, Roberto Bandettini
Recent studies support a change of Clostridium difficile infections (CDIs) epidemiology in pediatric patients. Since limited information is available about C. difficile in this population, we investigated the epidemiology of CDI in a large pediatric hospital that acts as reference centre in Italy and analyzed C. difficile isolates to identify the prevalent PCR-ribotypes (RTs), the binary toxin (CDT)-positive strains and the antibiotic susceptibility patterns. The CDI incidence was 6.6 cases/1000 admissions and the majority (92%) of CDI were healthcare-associated (47% occurred in the Hematology-Oncology and in the Gastroenterology units)...
October 21, 2017: Anaerobe
https://www.readbyqxmd.com/read/29033912/the-infectious-basis-of-acpa-positive-rheumatoid-arthritis
#9
REVIEW
Lazaros I Sakkas, Dimitrios Daoussis, Stamatis-Nick Liossis, Dimitrios P Bogdanos
Rheumatoid arthritis (RA) is associated with HLA-DRB1 shared epitope (HLA-DRB1SE) and anti-citrullinated protein autoantibodies (ACPAs). ACPAs precedes the onset of clinical and subclinical RA. There are strong data for three infectious agents as autoimmunity triggers in RA, namely Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans causes of periodontal disease (PD), and Epstein-Barr virus (EBV). P. gingivalis expresses arginine gingipains, that cleave proteins at the arginine residues, and peptidyl arginine deiminase (PPAD), which citrullinates arginine residues of proteins, thus forming neoantigens that lead to ACPA production...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29018235/phosphine-inhibits-transcription-of-the-catalase-gene-through-the-dre-dref-system-in-drosophila-melanogaster
#10
Tao Liu, Li Li, Baishu Li, Guoping Zhan
Phosphine (PH3) is a toxin commonly used for pest control. Its toxicity is attributed primarily to its ability to induce oxidative damage. Our previous work showed that phosphine could disrupt the cell antioxidant defence system by inhibiting expression of the catalase gene in Drosophila melanogaster (DmCAT). However, the exact mechanism of this inhibition remains unclear. Here, we implemented a luciferase reporter assay driven by the DmCAT promoter in D. melanogaster S2 cells and showed that this reporter could be inhibited by phosphine treatment...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28993610/evolution-of-host-adaptation-in-the-salmonella-typhoid-toxin
#11
Xiang Gao, Lingquan Deng, Gabrielle Stack, Hai Yu, Xi Chen, Yuko Naito-Matsui, Ajit Varki, Jorge E Galán
The evolution of virulence traits is central for the emergence or re-emergence of microbial pathogens and for their adaptation to a specific host (1-5) . Typhoid toxin is an essential virulence factor of the human-adapted bacterial pathogen Salmonella Typhi (6,7) , the cause of typhoid fever in humans (8-12) . Typhoid toxin has a unique A2B5 architecture with two covalently linked enzymatic 'A' subunits, PltA and CdtB, associated with a homopentameric 'B' subunit made up of PltB, which has binding specificity for the N-acetylneuraminic acid (Neu5Ac) sialoglycans (6,13) prominently present in humans (14) ...
October 9, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28993337/whole-transcriptome-and-genomic-analysis-of-extensively-drug-resistant-mycobacterium-tuberculosis-clinical-isolates-identifies-downregulation-of-etha-as-a-mechanism-of-ethionamide-resistance
#12
Lynne de Welzen, Vegard Eldholm, Kashmeel Maharaj, Abigail L Manson, Ashlee M Earl, Alexander S Pym
Genetic based drug susceptibility testing has improved the diagnosis of drug-resistant tuberculosis, but is limited by our lack of knowledge of all resistance mechanisms. Next generation sequencing has assisted in identifying the principal genetic mechanisms of resistance for many drugs, but a significant proportion of phenotypic drug resistance is unexplained genetically. Few studies have formally compared the transcriptome of susceptible and resistant M. tuberculosis We carried out comparative whole genome transcriptomics on extensively drug-resistant (XDR) clinical isolates using RNA-sequencing (RNAseq) to find novel transcriptional mediated mechanisms of resistance...
October 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28990820/interleukin-2-secretion-by-t-cells-for-detection-of-biologically-active-staphylococcal-enterotoxin-type-e
#13
Reuven Rasooly, Paula Do, Bradley J Hernlem
Staphylococcus aureus is a significant worldwide source of clinical infections and foodborne illnesses; it acts through the synthesis of a group of enterotoxins (SEs) that cause gastroenteritis and also function as superantigens that activate T cells, resulting in massive cytokine production, yielding life-threatening toxicity. It is important that methods for detection and quantification of these toxins respond to their activity and not just the presence of the toxin molecule, which may be deactivated. Traditionally, live animals have been used to test for emesis following administration of the toxin-containing sample...
October 9, 2017: Journal of Food Protection
https://www.readbyqxmd.com/read/28979890/structure-based-prototype-peptides-targeting-the-pseudomonas-aeruginosa-type-vi-secretion-system-effector-as-a-novel-antibacterial-strategy
#14
Xiaopan Gao, Zhixia Mu, Bo Qin, Yicheng Sun, Sheng Cui
The type VI secretion system (T6SS) secretes numerous toxins for bacteria-bacteria competition. TplE is a newly identified trans-kingdom toxin secreted by the T6SS in Pseudomonas aeruginosa, while TplEi neutralizes the toxic effect of TplE to protect bacteria autointoxication. Blocking the interaction of TplE-TplEi could unleash the toxin, causing bacterial cell death. In this study, we applied a crystallographic approach to design a structural-based antimicrobial peptides targeting the interaction of TplE and TplEi...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28975486/sodium-fluoroacetate-toxicity-a-case-report-of-malicious-poisoning-in-dogs-across-a-phoenix-arizona-neighborhood
#15
Alexandra Brower, Jason Struthers, Jemima Schmidt
In May 2016, thirteen dogs housed in backyards within a single neighborhood were reported to have developed convulsions and died within a 24 h period. An investigation of the scene by law enforcement resulted in submission of eight dogs for postmortem examination. It was suspected that a rapid acting toxin was the cause of death. A gas chromatography-mass spectrophotometry (GC-MS) protocol combined with thin-layer chromatography that allows screening for common convulsants failed to identify a toxin in either pooled gastric content or liver samples from select cases...
October 3, 2017: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/28971540/integrated-activities-of-two-alternative-sigma-factors-coordinate-iron-acquisition-and-uptake-by-pseudomonas-aeruginosa
#16
Rebecca J Edgar, Georgina E Hampton, G Patricia Casas Garcia, Megan J Maher, Matthew A Perugini, David F Ackerley, Iain L Lamont
Alternative sigma (σ) factors govern expression of bacterial genes in response to diverse environmental signals. In Pseudomonas aeruginosa σ(PvdS) directs expression of genes for production of a siderophore, pyoverdine, as well as a toxin and a protease. σ(FpvI) directs expression of a receptor for ferripyoverdine import. Expression of the genes encoding σ(PvdS) and σ(FpvI) is iron-regulated and an antisigma protein, FpvR20 , post-translationally controls the activities of the sigma factors in response to the amount of ferripyoverdine present...
October 3, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28970172/plasmid-pum505-encodes-a-toxin-antitoxin-system-conferring-plasmid-stability-and-increased-pseudomonas-aeruginosa-virulence
#17
K C Hernández-Ramírez, V M Chávez-Jacobo, M I Valle-Maldonado, J A Patiño-Medina, S P Díaz-Pérez, I E Jácome-Galarza, R Ortiz-Alvarado, V Meza-Carmen, M I Ramírez-Díaz
Pseudomonas aeruginosa plasmid pUM505 possesses a pathogenicity island that contains the pumAB genes that encode products with sequence similarity to Toxin-Antitoxin (TA) modules. RT-PCR assays on the overlapping regions of the pumAB genes generated a bicistronic messenger RNA, suggesting that they form an operon. When the pumAB genes were cloned into the pJET vector, recombinant plasmid pJET-pumAB was maintained under nonselective conditions in Escherichia coli cells after six daily subcultures, whereas pJET without pumAB genes was lost...
September 29, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28964275/detection-of-total-ergot-alkaloids-in-cereal-flour-and-in-bread-by-a-generic-enzyme-immunoassay-method
#18
Madeleine Gross, Valeriu Curtui, Ewald Usleber
Four sets of polyclonal antibodies against ergot alkaloids ergometrine, ergotamine, α-ergocryptine, and ergocornine were produced and characterized in a competitive direct or indirect enzyme immunoassay (EIA). Standard curve LODs were 0.03 ng/mL (ergometrine EIA) to 2.0 ng/mL (ergocornine EIA). Three EIAs were highly specific, whereas the ergometrine EIA had a broad specificity pattern and reacted, albeit weakly, with all seven major ergot alkaloids and their epimeric forms. Using the ergometrine EIA, a generic test system was established in which total ergot alkaloids are quantified by a standard curve for a toxin mixture composed of three alkaloids that matched the ergot alkaloid composition in naturally contaminated rye and wheat products...
October 2, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28962691/melatonin-prevents-preeclamptic-sera-and-antiphospholipid-antibodies-inducing-the-production-of-reactive-nitrogen-species-and-extrusion-of-toxic-trophoblastic-debris-from-first-trimester-placentae
#19
Mingzhi Zhao, Yanyun Li, Lance Xu, Anthony Hickey, Katie Groom, Peter R Stone, Lawrence W Chamley, Qi Chen
BACKGROUND: The exact cause of preeclampsia is unknown. However a "toxin" from the placenta triggers the condition via activation of the maternal endothelium. Extracellular vesicles (EVs) from the syncytiotrophoblast, may be an endothelial-activating toxin. Antiphospholipid antibodies (aPL) and preeclamptic sera both induce the production of endothelial cell-activating EVs by mechanisms which may produce excess free-radicals in the placenta. Melatonin is produced by the human placenta and has both direct and indirect anti-free-radical properties and may therefore counter the effects of aPL and preeclamptic sera...
October 2017: Placenta
https://www.readbyqxmd.com/read/28959656/qualitative-and-quantitative-assessment-of-the-presence-of-ciguatoxin-p-ctx-1b-in-spanish-mackerel-scomberomorus-commerson-from-waters-in-new-south-wales-australia
#20
Gurjeet S Kohli, Kristina Haslauer, Chowdhury Sarowar, Anna Liza Kretzschmar, Mark Boulter, D Tim Harwood, Olivier Laczka, Shauna A Murray
Ciguatera Fish Poisoning (CFP) is a tropical disease caused by the consumption of fish contaminated with ciguatoxins (CTXs). Currently, the only feasible prevention methods for CFP are to avoid the consumption of fish of certain species from some regions, avoid larger fish of certain species, or avoid all fish caught from specific regions. Here, we quantified levels of P-CTX-1B in Spanish Mackerel (Scomberomorus commerson), which is the main fish species that causes CFP in New South Wales and Queensland, Australia, using LC-MS detection against a toxin standard...
2017: Toxicology Reports
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