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Coats, Karen. "Alone by Cyn Balog". Bulletin of the Center for Children's Books 71, nr 4 (2017): 149. http://dx.doi.org/10.1353/bcc.2017.0832.
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Coats, Karen. "Unnatural Deeds by Cyn Balog". Bulletin of the Center for Children's Books 70, nr 4 (2016): 164. http://dx.doi.org/10.1353/bcc.2016.0945.
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Coats, Karen. "That Night by Cyn Balog". Bulletin of the Center for Children's Books 72, nr 9 (2019): 379. http://dx.doi.org/10.1353/bcc.2019.0305.
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Chichova, Mariela, Oskan Tasinov, Milena Shkodrova, Milena Mishonova, Iliyana Sazdova, Bilyana Ilieva, Dilyana Doncheva-Stoimenova i in. "New Data on Cylindrospermopsin Toxicity". Toxins 13, nr 1 (8.01.2021): 41. http://dx.doi.org/10.3390/toxins13010041.
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Cylindrospermopsin (CYN) is a widely spread cyanotoxin that can occur in fresh water and food. This research aims to investigate CYN toxicity by studying the effects of drinking 0.25 nM of CYN-contaminated water from a natural source, and of the direct application of moderate concentrations of CYN on different animal targets. The chosen structures and activities are rat mitochondria inner membrane permeability, mitochondrial ATP synthase (ATPase) and rat liver diamine oxidase (DAO) activities (EC 1.4.3.22.), the force of the contraction of an excised frog heart preparation with functional innervation, and the viability of a human intestinal epithelial cell line (HIEC-6). The oral exposure to CYN decreased the reverse (hydrolase) activity of rat liver ATPase whereas its short-term, in vitro application was without significant effect on this organelle, DAO activity, heart contractions, and their neuronal regulation. The application of CYN reduced HIEC-6 cells’ viability dose dependently. It was concluded that CYN is moderately toxic for the human intestinal epithelial cells, where the regeneration of the epithelial layer can be suppressed by CYN. This result suggests that CYN may provoke pathological changes in the human gastrointestinal tract.
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Chichova, Mariela, Oskan Tasinov, Milena Shkodrova, Milena Mishonova, Iliyana Sazdova, Bilyana Ilieva, Dilyana Doncheva-Stoimenova i in. "New Data on Cylindrospermopsin Toxicity". Toxins 13, nr 1 (8.01.2021): 41. http://dx.doi.org/10.3390/toxins13010041.
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Cylindrospermopsin (CYN) is a widely spread cyanotoxin that can occur in fresh water and food. This research aims to investigate CYN toxicity by studying the effects of drinking 0.25 nM of CYN-contaminated water from a natural source, and of the direct application of moderate concentrations of CYN on different animal targets. The chosen structures and activities are rat mitochondria inner membrane permeability, mitochondrial ATP synthase (ATPase) and rat liver diamine oxidase (DAO) activities (EC 1.4.3.22.), the force of the contraction of an excised frog heart preparation with functional innervation, and the viability of a human intestinal epithelial cell line (HIEC-6). The oral exposure to CYN decreased the reverse (hydrolase) activity of rat liver ATPase whereas its short-term, in vitro application was without significant effect on this organelle, DAO activity, heart contractions, and their neuronal regulation. The application of CYN reduced HIEC-6 cells’ viability dose dependently. It was concluded that CYN is moderately toxic for the human intestinal epithelial cells, where the regeneration of the epithelial layer can be suppressed by CYN. This result suggests that CYN may provoke pathological changes in the human gastrointestinal tract.
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Díez-Quijada, Leticia, Klara Hercog, Martina Štampar, Metka Filipič, Ana M. Cameán, Ángeles Jos i Bojana Žegura. "Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line". Toxins 12, nr 12 (8.12.2020): 778. http://dx.doi.org/10.3390/toxins12120778.
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Simultaneous occurrence of cylindrospermopsin (CYN) and microcystin-LR (MCLR) has been reported in the aquatic environment and thus human exposure to such mixtures is possible. As data on the combined effects of CYN/MCLR are scarce, we aimed to investigate the adverse effects related to genotoxic activities induced by CYN (0.125, 0.25 and 0.5 µg/mL) and MCLR (1 µg/mL) as single compounds and their combinations in HepG2 cells after 24 and 72 h exposure. CYN and CYN/MCLR induced DNA double-strand breaks after 72 h exposure, while cell cycle analysis revealed that CYN and CYN/MCLR arrested HepG2 cells in G0/G1 phase. Moreover, CYN and the combination with MCLR upregulated CYP1A1 and target genes involved in DNA-damage response (CDKN1A, GADD45A). Altogether, the results showed that after 72 h exposure genotoxic activity of CYN/MCLR mixture was comparable to the one of pure CYN. On the contrary, MCLR (1 µg/mL) had no effect on the viability of cells and had no influence on cell division. It did not induce DNA damage and did not deregulate studied genes after prolonged exposure. The outcomes of the study confirm the importance of investigating the combined effects of several toxins as the effects can differ from those induced by single compounds.
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Llana-Ruiz-Cabello, Maria, Angeles Jos, Ana Cameán, Flavio Oliveira, Aldo Barreiro, Joana Machado, Joana Azevedo i in. "Analysis of the Use of Cylindrospermopsin and/or Microcystin-Contaminated Water in the Growth, Mineral Content, and Contamination of Spinacia oleracea and Lactuca sativa". Toxins 11, nr 11 (28.10.2019): 624. http://dx.doi.org/10.3390/toxins11110624.
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Cyanobacteria and cyanotoxins constitute a serious environmental and human health problem. Moreover, concerns are raised with the use of contaminated water in agriculture and vegetable production as this can lead to food contamination and human exposure to toxins as well as impairment in crop development and productivity. The objective of this work was to assess the susceptibility of two green vegetables, spinach and lettuce, to the cyanotoxins microcystin (MC) and cylindrospermopsin (CYN), individually and in mixture. The study consisted of growing both vegetables in hydroponics, under controlled conditions, for 21 days in nutrient medium doped with MC or CYN at 10 μg/L and 50 μg/L, or CYN/MC mixture at 5 + 5 μg/L and 25 + 25 μg/L. Extracts from M. aeruginosa and C. ovalisporum were used as sources of toxins. The study revealed growth inhibition of the aerial part (Leaves) in both species when treated with 50µg/L of MC, CYN and CYN/MC mixture. MC showed to be more harmful to plant growth than CYN. Moreover spinach leaves growth was inhibited by both 5 + 5 and 25 + 25 µg/L CYN/MC mixtures, whereas lettuce leaves growth was inhibited only by 25 + 25 µg/L CYN/MC mixture. Overall, growth data evidence increased sensitivity of spinach to cyanotoxins in comparison to lettuce. On the other hand, plants exposed to CYN/MC mixture showed differential accumulation of CYN and MC. In addition, CYN, but not MC, was translocated from the roots to the leaves. CYN and MC affected the levels of minerals particularly in plant roots. The elements most affected were Ca, K and Mg. However, in leaves K was the mineral that was affected by exposure to cyanotoxins.
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Flores-Rojas, Esterhuizen-Londt i Pflugmacher. "Uptake, Growth, and Pigment Changes in Lemna minor L. Exposed to Environmental Concentrations of Cylindrospermopsin". Toxins 11, nr 11 (7.11.2019): 650. http://dx.doi.org/10.3390/toxins11110650.
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Cylindrospermopsin (CYN)-producing cyanobacterial blooms such as Raphidiopsis, Aphanizomenon, Anabaena, Umezakia, and Lyngbya spp. are occurring more commonly and frequently worldwide. CYN is an environmentally stable extracellular toxin, which inhibits protein synthesis, and, therefore, can potentially affect a wide variety of aquatic biota. Submerged and floating macrophytes, as primary producers in oligotrophic habitats, are at risk of exposure and information on the effects of CYN exposure at environmentally relevant concentrations is limited. In the present study, we investigated CYN uptake in the floating macrophyte Lemna minor with exposure to reported environmental concentrations. The effects were evaluated in terms of bioaccumulation, relative plant growth, and number of fronds per day. Variations in the concentrations and ratios of the chlorophylls as stress markers and carotenoids as markers of oxidative stress defense were measured. With exposure to 25 μg/L, L. minor could remove 43% of CYN within 24 h but CYN was not bioaccumulated. Generally, the pigment concentrations were elevated with exposure to 0.025, 0.25, and 2.5 μg/L CYN after 24 h, but normalized quickly thereafter. Changes in relative plant growth were observed with exposure to 0.25 and 2.5 μg/L CYN. Adverse effects were seen with these environmentally realistic concentrations within 24 h; however, L. minor successfully recovered within the next 48–96 h.
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Pierangelini, Mattia, Rati Sinha, Anusuya Willis, Michele A. Burford, Philip T. Orr, John Beardall i Brett A. Neilan. "Constitutive Cylindrospermopsin Pool Size in Cylindrospermopsis raciborskii under Different Light and CO2Partial Pressure Conditions". Applied and Environmental Microbiology 81, nr 9 (27.02.2015): 3069–76. http://dx.doi.org/10.1128/aem.03556-14.
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ABSTRACTCylindrospermopsin (CYN) and 7-deoxy-cylindrospermopsin (dCYN) are potent hepatotoxic alkaloids produced by numerous species of cyanobacteria, including the freshwaterCylindrospermopsis raciborskii.C. raciborskiiis an invasive cyanobacterium, and the study of how environmental parameters drive CYN production has received significant interest from water managers and health authorities. Light and CO2affect cell growth and physiology in photoautotrophs, and these are potential regulators of cyanotoxin biosynthesis. In this study, we investigated how light and CO2affect CYN and dCYN pool size as well as the expression of the key genes,cyrAandcyrK, involved in CYN biosynthesis in a toxicC. raciborskiistrain. For cells growing at different light intensities (10 and 100 μmol photons m−2s−1), we observed that the rate of CYN pool size production (μCYN) was coupled to the cell division rate (μc) during batch culture. This indicated that CYN pool size under our experimental conditions is constant and cell quotas of CYN (QCYN) and dCYN (QdCYN) are fixed. Moreover, a lack of correlation between expression ofcyrAand total CYN cell quotas (QCYNs) suggests that the CYN biosynthesis is regulated posttranscriptionally. Under elevated CO2(1,300 ppm), we observed minor effects on QCYNand no effects on expression ofcyrAandcyrK. We conclude that the CYN pool size is constitutive and not affected by light and CO2conditions. Thus,C. raciborskiibloom toxicity is determined by the absolute abundance ofC. raciborskiicells within the water column and the relative abundance of toxic and nontoxic strains.
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Flores-Rojas, Nelida Cecilia, i Maranda Esterhuizen. "Uptake and Effects of Cylindrospermopsin: Biochemical, Physiological and Biometric Responses in The Submerged Macrophyte Egeria densa Planch". Water 12, nr 11 (26.10.2020): 2997. http://dx.doi.org/10.3390/w12112997.
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Cylindrospermopsin (CYN) is being detected in surface waters more commonly and frequently worldwide. This stable, extracellular cyanotoxin causes protein synthesis inhibition, thus posing a risk to aquatic biota, including macrophytes, which serve as primary producers. Nevertheless, data regarding the effects caused by environmental concentrations of CYN is still limited. In the presented study, the uptake of CYN at environmental concentrations by the submerged macrophyte Egeria densa was investigated. Bioaccumulation, changes in the plant biomass, as well as shoot-length were assessed as responses. Variations in the cellular H2O2 levels, antioxidative enzyme activities, as well as concentrations and ratios of the photosynthetic pigments were also measured. E. densa removed 54% of CYN within 24 h and up to 68% after 336 h; however, CYN was not bioaccumulated. The antioxidative enzyme system was activated by CYN exposure. Pigment concentrations decreased with exposure but normalized after 168 h. The chlorophyll a to b ratio increased but normalized quickly thereafter. Carotenoids and the ratio of carotenoids to total chlorophylls increased after 96 h suggesting participation in the antioxidative system. Growth stimulation was observed. The ability to remove CYN and resistance to CYN toxicity within 14 days proved E. densa as suitable for phytoremediation; nonetheless, prolonged exposure (32 days) resulted in adverse effects related to CYN uptake, which needs to be studied further.
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Rotondo, Rossella, Maria Antonietta Oliva i Antonietta Arcella. "The Sesquiterpene Lactone Cynaropicrin Manifests Strong Cytotoxicity in Glioblastoma Cells U-87 MG by Induction of Oxidative Stress". Biomedicines 10, nr 7 (2.07.2022): 1583. http://dx.doi.org/10.3390/biomedicines10071583.
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Cynaropicrin has shown a wide range of pharmacological properties, such as antitumor action. Here, we showed the inhibitory effect of Cyn on human glioblastoma cell U-87 MG growth. According to the IC50 values, Cyn 4, 8 and 10 µM displayed a significant cytotoxicity, as confirmed by the cell count and MTT assay. Furthermore, Cyn completely abolished the ability of U-87 MG to form colonies and induced drastic morphological changes. Interestingly, pretreatment with ROS scavenger N-acetylcysteine 3 mM reversed the cytotoxicity induced by Cyn 25 µM and preserved the cells by morphological changes. Therefore, oxidative stress induction was evaluated at low 8- and high 25-µM concentrations in U-87 MG, as demonstrated by the quantitative and qualitative analysis of ROS. A prolonged increase in ROS generation under Cyn 25 µM exposure was followed by the loss of the mitochondrial membrane potential in treated U-87 MG cells. An acute treatment with Cyn 25 µM induced Cyt c release, as revealed by immunofluorescence staining and the activation of cell death pathways, apoptosis and autophagy. On the other hand, chronic treatment with Cyn 8 µM induced senescence, as revealed by the increase in SA-β-Gal activity. Moreover, at this concentration, Cyn led to ERK dephosphorylation accompanied by a relevant reduction of the NF-κB p65 subunit. Finally, the combined effect of TMZ and Cyn resulted in synergistic cytotoxicity, as evaluated by the Bliss additivity model. The strong cytotoxicity of Cyn was also confirmed on IDH1 mutant U-87 MG cells and patient-derived IDH wild-type glioblastoma cell lines NULU and ZAR. In conclusion, given the high toxicity at minimal concentrations, the high inhibition of tumor cell growth and synergy with the standard drug for glioblastoma TMZ, Cyn could be proposed as a potential adjuvant for the treatment of glioblastoma.
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Abbas, Feras, Cristina Porojan, Maxine A. D. Mowe, Mary Lehane, Simon M. Mitrovic, Richard P. Lim, Darren C. J. Yeo i Ambrose Furey. "Sample extraction and liquid chromatography–tandem mass spectrometry (LC-MS/MS) method development and validation for the quantitative detection of cyanobacterial hepatotoxins and neurotoxins in Singapore's reservoirs". Marine and Freshwater Research 71, nr 5 (2020): 673. http://dx.doi.org/10.1071/mf19157.
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Cyanobacterial blue–green algal toxins are produced by harmful algal blooms (HABs). Most species of phytoplankton are not harmful, but excessive amounts of certain HAB taxa can cause harm to human and animal health, aquatic ecosystems and local economies. To investigate the prevalence of cylindrospermopsin (CYN) and anatoxin-a (ANA) in Singapore’s reservoirs, a hazard analysis was initiated to profile the CYN and ANA levels present. Water samples from 17 reservoirs were monitored monthly over a 12-month period (November 2012–October 2013). Analyses were conducted by liquid chromatography–tandem mass spectrometry (LC-MS/MS) using a triple-stage quadrupole mass spectrometer with a turbo-assisted ion spray source. CYN was more prevalent than ANA. Intracellular CYN concentrations exceeded 0.4μgL–1 in 6 of 17 man-made reservoirs surveyed, and slightly exceeded the provisional CYN drinking water guidelines of 1μgL–1 (National Health and Medical Research Council and National Resource Management Ministerial Council 2011) on one occasion (1.1μgL–1, July 2013) in one reservoir. The dominant cyanobacteria genera during that period were Cylindrospermopsis, Planktolyngbya, Pseudanabaena and Microcystis. For ANA, all 17 reservoirs had concentrations below 0.1μgL–1. Based on random forest analysis, the most important environmental factors affecting CYN concentrations were total nitrogen (most important), nitrate, total phosphorus and Cylindrospermopsis counts (least important). The findings of this study indicate that reducing total nitrogen concentrations may be useful in minimising CYN concentrations in tropical reservoirs.
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Ziesemer, Sabine, Susann Meyer, Julia Edelmann, Janita Vennmann, Celine Gudra, Denise Arndt, Marcus Effenberg i in. "Target Mechanisms of the Cyanotoxin Cylindrospermopsin in Immortalized Human Airway Epithelial Cells". Toxins 14, nr 11 (11.11.2022): 785. http://dx.doi.org/10.3390/toxins14110785.
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Cylindrospermopsin (CYN) is a cyanobacterial toxin that occurs in aquatic environments worldwide. It is known for its delayed effects in animals and humans such as inhibition of protein synthesis or genotoxicity. The molecular targets and the cell physiological mechanisms of CYN, however, are not well studied. As inhalation of CYN-containing aerosols has been identified as a relevant route of CYN uptake, we analyzed the effects of CYN on protein expression in cultures of immortalized human bronchial epithelial cells (16HBE14o−) using a proteomic approach. Proteins whose expression levels were affected by CYN belonged to several functional clusters, mainly regulation of protein stability, cellular adhesion and integration in the extracellular matrix, cell proliferation, cell cycle regulation, and completion of cytokinesis. With a few exceptions of upregulated proteins (e.g., ITI inhibitor of serine endopeptidases and mRNA stabilizer PABPC1), CYN mediated the downregulation of many proteins. Among these, centrosomal protein 55 (CEP55) and osteonectin (SPARC) were significantly reduced in their abundance. Results of the detailed semi-quantitative Western blot analyses of SPARC, claudin-6, and CEP55 supported the findings from the proteomic study that epithelial cell adhesion, attenuation of cell proliferation, delayed completion of mitosis, as well as induction of genomic instability are major effects of CYN in eukaryotic cells.
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CENGIZ, S., L. CAVAS i K. YURDAKOC. "Alpha-amylase inhibition kinetics by caulerpenyne". Mediterranean Marine Science 11, nr 1 (30.03.2010): 93. http://dx.doi.org/10.12681/mms.93.
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Many algae have important secretions which are generally used for defensive purposes. These secretions take attentions of a lot of researchers who are wondering if these metabolites can be used for medical researches or not. Among these metabolites, caulerpenyne (CYN) which is the main metabolite of Caulerpa species, have had an important place in Caulerpa researches since the results related to its determined properties such as cytotoxic, antiviral, antiproliferative and apoptotic effects have been proven by many scientific reports. In the present study, the inhibitory effect of CYN isolated from C. prolifera on alpha-amylase was investigated. The inhibition experiments were done with CYN by spectrophotometric determination method. In order to evaluate the type of inhibition Lineweaver–Burk plot was produced. The results obtained from enzyme kinetic studies exhibited an un-competitive type of inhibition, which is characterized by the difference of Vmax and KM from those of the free enzyme, of alpha-amylase in the presence of CYN. The present study showed that Caulerpa species can be a potential target for producing diabetic drugs in the light of the results obtained for CYN.
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Quealy-Gainer, Kate. "Dead River by Cyn Balog (review)". Bulletin of the Center for Children's Books 66, nr 9 (2013): 411–12. http://dx.doi.org/10.1353/bcc.2013.0325.
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BITTENCOURT-OLIVEIRA, MARIA DO CARMO, VIVIANE PICCIN-SANTOS, ARIADNE N. MOURA, NÍSIA K. C. ARAGÃO-TAVARES i MICHELINE K. CORDEIRO-ARAÚJO. "Cyanobacteria, microcystins and cylindrospermopsin in public drinking supply reservoirs of Brazil". Anais da Academia Brasileira de Ciências 86, nr 1 (marzec 2014): 297–310. http://dx.doi.org/10.1590/0001-3765201302512.
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Brazil has a history of blooms and contamination of freshwater systems by cyanobacterial toxins. The monitoring relevance of toxins from cyanobacteria in reservoirs for public supply is notorious given its high toxicity to mammals, included humans beings. The most recurrent toxins in Brazilian water bodies are microcystins (MC). However, the recent record of cylindrospermopsin (CYN) in northeastern Brazil, Pernambuco state, alerts us to the possibility that this could be escalating. This study reports occurrence of MC and CYN, quantified with ELISA, in 10 reservoirs, devoted to public drinking supply in northeastern Brazil. The composition and quantification of the cyanobacteria community associated with these water bodies is also presented. From 23 samples investigated for the presence of MC, and CYN, 22 and 8 out were positive, respectively. Considering the similarity of the cyanobacteria communities found in reservoirs from Pernambuco, including toxin-producing species associated to MC and CYN, we suggest that geographic spreading can be favored by these factors. These issues emphasize the need for increased monitoring of MC and CYN in drinking supply reservoirs in Brazil.
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Diez-Quijada, Leticia, Antonio Casas-Rodriguez, Remedios Guzmán-Guillén, Verónica Molina-Hernández, Rafael G. Albaladejo, Ana María Cameán i Angeles Jos. "Immunomodulatory Effects of Pure Cylindrospermopsin in Rats Orally Exposed for 28 Days". Toxins 14, nr 2 (15.02.2022): 144. http://dx.doi.org/10.3390/toxins14020144.
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Cylindrospermopsin (CYN) is a ubiquitous cyanotoxin showing increasing incidence worldwide. CYN has been classified as a cytotoxin and, among its toxic effects, its immunotoxicity is scarcely studied. This work investigates for the first time the influence of oral CYN exposure (18.75; 37.5 and 75 µg/kg b.w./day, for 28 days) on the mRNA expression of selected interleukin (IL) genes (IL-1β, IL-2, IL-6, Tumor Necrosis Factor alpha (TNF-α), Interferon gamma (IFN-γ)) in the thymus and the spleen of male and female rats, by quantitative real-time polymerase chain reaction (RT-qPCR). Moreover, their serum levels were also measured by a multiplex-bead-based immunoassay, and a histopathological study was performed. CYN produced immunomodulation mainly in the thymus of rats exposed to 75 μg CYN/kg b.w./day in both sexes. However, in the spleen only IL-1β and IL-2 (males), and TNF-α and IFN-γ (females) expression was modified after CYN exposure. Only female rats exposed to 18.75 μg CYN/kg b.w./day showed a significant decrease in TNF-α serum levels. There were no significant differences in the weight or histopathology in the organs studied. Further research is needed to obtain a deeper view of the molecular mechanisms involved in CYN immunotoxicity and its consequences on long-term exposures.
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Nustede, Rainer, Inna Kuznetsova, Karl Welte i Julia Skokowa. "Mechanism of the Elevated UPR in CN Patients but Not in CyN Patients Carrying Same ELANE Mutations". Blood 118, nr 21 (18.11.2011): 14. http://dx.doi.org/10.1182/blood.v118.21.14.14.
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Abstract Abstract 14 Several studies found that in patients with severe congenital neutropenia (CN) harboring mutations in the ELANE gene mutated NE protein induced unfolded protein response (UPR) leading to elevated apoptosis and diminished differentiation of myeloid cells. However, it is unclear, why UPR was not detected in patients with cyclic neutropenia (CyN) carrying the same ELANE mutations, which have been found in CN patients. Several UPR components have been identified in mammalian cells, which include three transducers (IRE1, PERK, and activating transcription factor 6 (ATF-6) as well as one master regulator (BiP/GRP78). BiP is known to be regulated by ATF6. The activation of ATF6 and its target genes (GADD34, CHOP and BiP) in CN patients has not been studied yet. We were able to detect significantly elevated levels of ATF6 and BiP in myeloid cells of CN patients with ELANE mutations, in comparison to CyN patients and to healthy individuals. Therefore, we investigated the mechanism of UPR and activation of ATF6 and ATF6 target genes in CN patients in comparison to CyN patients. We transduced the myeloid cell lines HL60 and NB4 with lentiviral constructs contained either wild type (WT) ELANE cDNA, or mutated (MUT) ELANE cDNA and measured mRNA and protein expression of ATF6 as well as mRNA expression of ATF6 target genes. We compared the effects of three ELANE mutations: C42R, V145-C152del (both mutations presented in CN patients, but not in CyN patients) and S97L (typical for CN and CyN patients) with WT ELANE. We found that in both cell lines only C42R ELANE MUT, but not V145-C152del ELANE MUT or S97L ELANE MUT induced expression of ATF6, GADD34, CHOP and BiP, as compared to control transduced cells. Furthermore, we hypothesize that degradation of mutated NE protein by Secretory Leukocyte Protease Inhibitor (SLPI) might be involved in UPR induction. However, we detected only very low levels of SLPI mRNA in CD33+ myeloid cells and in PMNs of patients with severe congenital neutropenia (CN), as compared to patients with cyclic neutropenia (CyN) and to healthy individuals. The lack of the NE inhibitor, SLPI in CN patients may further contribute to elevated UPR triggered by ELANE MUT and normal levels of SLPI in CyN patients might protect from ELANE MUT-induced UPR. Indeed, inhibition of SLPI using SLPI-specific shRNA led to a significantly elevated expression levels of ATF6, GADD34 and BIP, as compared to ctrl shRNA transduced cells. More importantly, co-transduction of NB4 cells with SLPI shRNA in combination with ELANE S97L MUT (which is common for both CN and CyN patients), but not with WT ELANE led to elevated levels of ATF6, GADD34 and BIP. In summary, different ELANE mutations have different effects on UPR as judged by ATF6 activation and the level of ELANE-triggered UPR is regulated by SLPI. Disclosures: No relevant conflicts of interest to declare.
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Okolo, Onyemaechi N., Emmanuel Katsanis, Seongseok Yun, Candace Y. Reveles i Faiz Anwer. "Allogeneic Transplant in ELANE and MEFV Mutation Positive Severe Cyclic Neutropenia: Review of Prognostic Factors for Secondary Severe Events". Case Reports in Hematology 2017 (2017): 1–7. http://dx.doi.org/10.1155/2017/5375793.
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Objective and Importance.Cyclic neutropenia (CyN) is a rare autosomal dominant inherited disorder due to the mutation ELANE primarily affecting bone marrow stem cells and is characterized by recurrent neutropenia every 2 to 4 weeks. Symptoms vary from benign to severe, including death. Postulations on the cause of wide spectrum in symptom presentation include the possibility of other genetic mutations, such as MEFV. Recommended treatment for CyN is G-CSF to keep ANC higher to minimize risk of infection.Case.A 25-year-old male diagnosed with CyN, on G-CSF but worsening quality of life. Pretransplant investigations revealed ELANE mutation positive severe CyN along with familial Mediterranean fever (MEFV) mutation.Intervention.Bone marrow transplantation as treatment for dual mutation (ELANE and MEFV mutation) positive severe CyN.Conclusion.BMT may be considered as an alternative treatment for severe CyN in patients who are refractory to G-CSF. It is postulated that in our patient the combined mutations (CyN and MEFV) may have contributed to the severity of this individual’s symptoms. We suggest CyN patients who present with severe symptoms have evaluation with ELANE mutation testing, Periodic Fever Syndromes Panel, and routine marrow assessment with FISH, conventional cytogenetics, and morphological evaluation for MDS/AML.
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Orlando Caicedo, Willan, Juan Carlos Moyano, Segundo Benedicto Valle, Luis Antonio Díaz i María Eduarda Caicedo. "Calidad fermentativa de ensilajes líquidos de chontaduro (Bactris gasipaes) tratados con yogur natural, suero de leche y melaza". Revista de Investigaciones Veterinarias del Perú 30, nr 1 (4.03.2019): 167–77. http://dx.doi.org/10.15381/rivep.v30i1.15672.
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El estudio tuvo como objetivo evaluar los efectos de la adición de yogur natural, suero de leche y melaza en ensilajes líquidos de chontaduro (Bactris gasipaes) sobre indicadores físicoquímicos, biológicos y organolépticos para su uso en la alimentación animal. Se trabajó con tres ensilados utilizando la drupa madura de la planta: chontaduro con yogur natural (CYN), chontaduro con suero de leche (CSL), y chontaduro con suero de leche y melaza (CSLM). Se preparon 30 microsilos por tratamiento de un 1 kg cada uno que se evaluaron los días 1, 4, 8, 15, 30 y 60 de iniciado el proceso de conservación (cinco por tratamiento). Las variables estudiadas fueron temperatura, pH, presencia de bacterias (E. coli, Clostridium spp, Salmonella spp), olor, color y consistencia. Temperaturas más altas se encontraron en CYN (22.56 ºC) y CSLM (22.52 ºC) en el día 1, CYN (22.48 ºC) y CSL (22.42 ºC) en el día 15, CYN (22.50 ºC) en el día 30, y CYN (22.46 ºC) y CSL (22.34 ºC) en el día 60 (p<0.05). Los valores más altos de pH se observaron en CYN (4.82) en el día 1 y día 4 (4.49) con relación a los otros tratamientos (p<0.05). CSLM presentó el menor pH entre los días 8 y 60 (4.19-4.17) (p<0.05). No hubo presencia de las bacterias en estudio en ninguno de los tratamientos. Los ensilados presentaron olor dulce fermentado, color café amarillento y consistencia semidura en todas las evaluaciones. Los tres ensilados líquidos de drupa de chontaduro presentaron un comportamiento adecuado de los indicadores físicoquímicos, microbiológicos y organolépticos hasta el día 60, todos aptos para el consumo de animales.
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Fonseca, A. L., J. Da Silva, E. A. Nunes, S. M. F. O. Azevedo i R. M. Soares. "In vivo genotoxicity of treated water containing the cylindrospermopsin-producer Cylindrospermopsis raciborskii". Journal of Water and Health 12, nr 3 (19.03.2014): 474–83. http://dx.doi.org/10.2166/wh.2014.087.
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Cylindrospermopsin (CYN) is an alkaloid commonly produced by some cyanobacteria that has been implicated in outbreaks of human illness. The aim of this study was to investigate the genotoxicity of Cylindrospermopsis raciborskii cellular content (including CYN) and its byproducts resulting from chlorination during water treatment. DNA damage in blood and liver cells was analysed by the comet assay and micronucleus test (MN). Mice were injected intraperitoneally with the following treatments: (a) physiological saline, (b) treated water, (c) treated water plus C. raciborskii extract (CYN producer strain, CYPO-011 K), (d) C. raciborskii extract (CYN producer strain, CYPO-011 K), (e) C. raciborskii extract (CYN non producer strain), and (f) treated water plus C. raciborskii extract (CYN non producer strain) extract. After 48 h, samples were taken to perform tests (blood and liver cells to the comet assay and bone marrow to MN test). The CYPO-011 K had a genotoxic and mutagenic effects on liver and bone marrow cells. The group that received chlorine-treated water plus CYPO-011 K also exhibited genotoxic effects in the liver, as well as in the blood, and a mutagenic effect in blood marrow cells. The results emphasise the need of improving CYN monitoring in waters bodies in order to reduce the risk of human exposure.
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Diez-Quijada, Leticia, María Puerto, Daniel Gutiérrez-Praena, Maria V. Turkina, Alexandre Campos, Vitor Vasconcelos, Ana M. Cameán i Ángeles Jos. "In Vitro Toxicity Evaluation of Cyanotoxins Cylindrospermopsin and Microcystin-LR on Human Kidney HEK293 Cells". Toxins 14, nr 7 (23.06.2022): 429. http://dx.doi.org/10.3390/toxins14070429.
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Cyanotoxins are secondary metabolites produced by different types of cyanobacteria. Among them, Cylindrospermopsin (CYN) and Microcystins (MCs) stand out due to their wide geographical distribution and toxicity in various organs, including the kidney, which is involved in their distribution and elimination. However, the renal toxicity caused by CYN and MCs has hardly been studied. The aim of this work was to assess the cytotoxicity effects caused by CYN and MC-LR in the renal cell line HEK293, and for the first time, the influence of CYN on the gene expression of selected genes in these cells by quantitative real-time PCR (qRT-PCR). CYN caused an upregulation in the gene expression after exposure to the highest concentration (5 µg/mL) and the longest time of exposure (24 h). Moreover, shotgun proteomic analysis was used to assess the molecular responses of HEK293 cells after exposure to the individuals and combinations of CYN + MC-LR. The simultaneous exposure to both cyanotoxins caused a greater number of alterations in protein expression compared to single toxins, causing changes in the cellular, lipid and protein metabolism and in protein synthesis and transport. Further studies are needed to complete the toxicity molecular mechanisms of both CYN and MC-LR at the renal level.
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Hercog, Klara, Alja Štern, Sara Maisanaba, Metka Filipič i Bojana Žegura. "Plastics in Cyanobacterial Blooms—Genotoxic Effects of Binary Mixtures of Cylindrospermopsin and Bisphenols in HepG2 Cells". Toxins 12, nr 4 (31.03.2020): 219. http://dx.doi.org/10.3390/toxins12040219.
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Ever-expanding environmental pollution is causing a rise in cyanobacterial blooms and the accumulation of plastics in water bodies. Consequently, exposure to mixtures of cyanotoxins and plastic-related contaminants such as bisphenols (BPs) is of increasing concern. The present study describes genotoxic effects induced by co-exposure to one of the emerging cyanotoxins—cylindrospermopsin (CYN)—(0.5 µg/mL) and BPs (bisphenol A (BPA), S (BPS), and F (BPF); (10 µg/mL)) in HepG2 cells after 24 and 72 h of exposure. The cytotoxicity was evaluated with an MTS assay and genotoxicity was assessed through the measurement of the induction of DNA double strand breaks (DSB) with the γH2AX assay. The deregulation of selected genes (xenobiotic metabolic enzyme genes, DNA damage, and oxidative response genes) was assessed using qPCR. The results showed a moderate reduction of cell viability and induction of DSBs after 72 h of exposure to the CYN/BPs mixtures and CYN alone. None of the BPs alone reduced cell viability or induced DSBs. No significant difference was observed between CYN and CYN/BPs exposed cells, except with CYN/BPA, where the antagonistic activity of BPA against CYN was indicated. The deregulation of some of the tested genes (CYP1A1, CDKN1A, GADD45A, and GCLC) was more pronounced after exposure to the CYN/BPs mixtures compared to single compounds, suggesting additive or synergistic action. The present study confirms the importance of co-exposure studies, as our results show pollutant mixtures to induce effects different from those confirmed for single compounds.
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Sobieh, Shaimaa S., Rasha Abed El-Gammal, Wafaa S. Abu El-Kheir, Alia A. El-Sheimy, Alaa A. Said i Yassein M. El-Ayouty. "Heterologous Expression of Cyanobacterial Cyanase Gene (CYN) in Microalga Chlamydomonas reinhardtii for Bioremediation of Cyanide Pollution". Biology 11, nr 10 (29.09.2022): 1420. http://dx.doi.org/10.3390/biology11101420.
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Recombinant DNA technology offered the creation of new combinations of DNA segments that are not found together in nature. The present study aimed to produce an ecofriendly bioremediation model to remediate cyanide pollution from a polluted marine system. Cyanide is a known toxic compound produced through natural and anthropogenic activities. An Agrobacterium-tumefaciens-mediated genetic transformation technique was used to generate transformed Chlamydomonas reinhardtii using plant expression vector pTRA-K-cTp carries isolated coding sequence of the cyanobacterial cyanase gene (CYN) isolated from Synechococcus elongatus (PCC6803). qRT-PCR analysis showed the overexpression of CYN in transgenic C. reinhardtii, as compared with the respective wild type. Growth parameters and biochemical analyses were performed under cyanide stress conditions using transgenic and wild C. reinhardtii for evaluating the effect of the presence of the cyanobacterial cyanase gene in algae. The transgenic C. reinhardtii strain (TC. reinhardtii-2) showed promising results for cyanide bioremediation in polluted water samples. Cyanide depletion assays and algal growth showed a significant resistance in the transgenic type against cyanide stress, as compared to the wild type. Genetically modified alga showed the ability to phytoremediate a high level of potassium cyanide (up to150 mg/L), as compared to the wild type. The presence of the CYN gene has induced a protection response in TC. Reinhardtii-2, which was shown in the results of growth parameter analyses. Therefore, the present study affirms that transgenic C. reinhardtii by the CYN coding gene is a potential effective ecofriendly bioremediator model for the remediation of cyanide pollutants in fresh water.
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González-Blanco, Carlos, Felipe Augusto Dörr, Renata Albuquerque, Janice Onuki i Ernani Pinto. "Alternative Isolation Protocol for Desulfo and Zwitterionic Cylindrospermopsin Alkaloids and Comparison of Their Toxicity in HepG2 Cells". Molecules 25, nr 13 (2.07.2020): 3027. http://dx.doi.org/10.3390/molecules25133027.
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The term cylindrospermopsins (CYNs) refers to a structurally related class of cyanobacterial metabolites comprised of a tricyclic guanidine group and a hydroxymethyluracil moiety. Most reports in environmental aquatic samples refer to cylindrospermopsin (CYN), and reports on other CYN alkaloids are scarce, due, in part, to a lack of versatile isolation protocols. Thus, using commercially available solid phase extraction (SPE) cartridges, we optimized an isolation protocol for the complete recovery of CYN, 7-deoxy-cylindrospermopsin (7D-CYN) and 7-deoxy-desulfo-cylindrospermopsin (7D-desulfo-CYN) from the same aliquot. The isolation protocol was adaptable depending on the nature of the sample (solid biomass, culture broth or environmental water sample) and tolerates up to 4 L of dense culture broth or 400 mg of lyophilized biomass. To quantitate the CYN alkaloids, we validated an LC-DAD-MS2 method, which takes advantage of the UV absorption of the uracil group (λ 262 nm). Using electrospray ionization (ESI) in a positive ion mode, the high-resolution MS1 data confirms the presence of the protonated alkaloids, and the MS2 fragment assignment is reported as complementary proof of the molecular structure of the CYNs. We isolated three CYN alkaloids with different water solubility using the same lyophilized sample, with a purity that ranged from 95% to 99%. The biological activity of the purified CYNs, along with a synthetic degradation product of CYN (desulfo-cylindrospermopsin), was evaluated by assessing necrosis and apoptosis in vitro using flow cytometry. CYN’s lethal potency in HepG2 cells was greater than the other analogs, due to the presence of all four functional groups: guanidine, uracil, C-7 hydroxyl and the sulfate residue.
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Traina, Giovanna. "Caulerpenyne Affects Bradykinin-Induced Intracellular Calcium Kinetics in LoVo Cells". Applied Sciences 11, nr 6 (17.03.2021): 2697. http://dx.doi.org/10.3390/app11062697.
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Sesquiterpene caulerpenyne (CYN) is the major metabolite present in green macroalgae Caulerpa taxifolia. This metabolite has been shown to be cytotoxic in some cell lines and was found to be active in various assays of pharmacological interest. In addition, it exerts antibiotic, antiviral, phytotoxic, antidyslipidemic, and antiproliferative activities. In the present study, we report that pretreatment with CYN decreases the bradykinin-induced calcium peak in human colon LoVo cells. We hypothesize that CYN pretreatment may adversely affect bradykinin-induced intracellular calcium increases. The data suggest that CYN, by reducing the increase in intracellular calcium, exerts an inhibitory role on calcium homeostasis and, likely, intercellular transmission.
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Saito, Satoshi, Shiho Nishimura, Miyuki Tsumura, Yoko Mizoguchi, Sonoko Sakata, Aya Furue, Mizuka Miki i in. "A Comparison of Myelopoiesis from Induced Pluripotent Stem Cells with a Mutation in ELANE between Cyclic Neutropenia and Severe Congenital Neutropenia". Blood 126, nr 23 (3.12.2015): 2193. http://dx.doi.org/10.1182/blood.v126.23.2193.2193.
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Abstract The ELANE is known as the responsible gene for both cyclic neutropenia (CyN) and severe congenital neutropenia (SCN). However, relations between mutations in the ELANE gene and abnormal myelopoiesis in the different phenotype of these diseases still remain unclear. It has been reported that induced pluripotent stem cell (iPSC) from an individual patient with SCN (SCN-iPSC) demonstrated maturation arrest of myeloid progenitor cells and poor response to granulocyte-colony stimulating factor as similarly observed in patient's bone marrow cells. Thus, the study on myelopoiesis using disease specific iPSC seems to provide disease pathogenesis as a novel in vitro experimental model. In this study, we established iPSC line from an individual patient with CyN (CyN-iPSC) with heterozygous mutation in ELANE gene (Exon5, R191Q point mutation). Then we compared myelopoiesis among healthy Control-iPS (253G1), SCN-iPS (Exon5, C194X point mutation) , and CyN-iPSC. Undifferentiated colonies derived from CyN-iPSC were staind with pluripotency markers (OCT3/4 and NANOG). CyN-iPSC retained a normal karyotype and ELANE locus mutation of the original samples. In vitro myelopoiesis was examined by using a serum- and feeder-free monolayer hematopoietic culture system. iPSC colonies were cultured on growth factor-reduced Matrigel-coated cell culture dishes in modified Tenneille Serum Replacer 1 (mTeSR™1) medium (StemCell Technologies, Inc.), containing BSA, rh bFGF, rh TGFβ, Lithium Chloride, Pipecolic acid, GABA. Medium was replaced every four days. Then medium was changed to StemPro®-34 SMF Complete Medium plus nutrient supplement (Life technologies Corp.). The iPSC were cultured with BMP4 (80 ng/mL) for four days, and then replaced with VEGF165 (80 ng/mL), bFGF (25.7 ng/mL), and SCF (100 ng/mL) on Day 4. On Day 6, cytokines were replaced with a combination of SCF (50 ng/mL), IL-3 (50 ng/mL), and G-CSF (50 ng/mL). Medium was replaced every 3 - 4 days. No significant difference in the ratio of proliferating CD33+ cells were noted between CyN-iPSCs and Control-iPSCs. CyN-iPSCs showed less capability in the proliferation and maturation for CD15+ cells on days 20 to 40 than Control-iPSCs. The decreased number of CD15+ cells derived from CyN-iPSc implies the defect in mature neutrophil survival. In contrast, CD15+ / CD33+ cells derived from SCN-iPSCs were hardly observed in this culture condition, suggesting the defects of proliferation and maturation in SCN-iPSCs. We next examined the colony formation of CD34+ cells derived from CyN-iPSCs, Control-iPSCs, and SCN-iPSCs. CD34+ cells were obtainded at the day 12 of primary culture of iPSCs and purified by cell sorting using FACS-Aria®. No significant differences in the number of G-colony and GM-colony between CD34+ cells from CyN-iPSCs and Control-iPSCs. In contrast, CD34+ cells from SCN-iPSCs gave rise to the significantly decreased number of G-colony and GM-colony. The observations of myeloid proliferation/maturation and colony formation of CD34+ cells were almost compatible with those obtained from bone marrow cells in patients with SCN and CyN. Furthermore, neutrophils differentiated from CyN-iPSCs showed the excessive cell death, whereas SCN-iPSCs presented the defective myelopoiesis. These results suggest that the analyses using CyN-iPSCs and SCN-iPSCs may be useful tool for investigating the relation of gene mutation and pathophysiology in both diseases. Disclosures No relevant conflicts of interest to declare.
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CAVAS, L., S. CENGIZ i Z. ABIDIN KARABAY. "Seasonal rubisco enzyme activities and caulerpenyne levels in invasive Caulerpa racemosa var. cylindracea and native Caulerpa prolifera". Mediterranean Marine Science 13, nr 1 (11.04.2012): 126. http://dx.doi.org/10.12681/mms.29.
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Caulerpa racemosa var.cylindracea (C.racemosa) is an invasive marine seaweed in the Mediterranean Sea. Since no valid eradication method has been existed in the scientific literature on this species, it has currently been continuing its invasion along the coastlines of 13 Mediterranean countries. One of the important factors responsible for its invasion is thought as its toxic secondary metabolite, caulerpenyne (CYN). The present paper investigates seasonal changes in the secondary metabolite CYN, and rubisco enzyme (EC 4.1.1.39) activities of the invasive C. racemosa and native C. prolifera. Inasmuch as no correlation between CYN level and rubisco enzymic activity was observed in these species, it is considered that the regulation of CYN synthesis caulerpenyne and rubisco enzymic activity might be controlled independently. In conclusion, the further analysis on the rubisco enzymic activity determinations with MEP and mevalonate pathway which are considered responsible for CYN bio-synthesis should be studied in great detail in invasive and native Caulerpa species in the Mediterranean Sea to get the overall picture.
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Stüken, Anke, i Kjetill S. Jakobsen. "The cylindrospermopsin gene cluster of Aphanizomenon sp. strain 10E6: organization and recombination". Microbiology 156, nr 8 (1.08.2010): 2438–51. http://dx.doi.org/10.1099/mic.0.036988-0.
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Cylindrospermopsin (CYN), a potent hepatoxin, occurs in freshwaters worldwide. Several cyanobacterial species produce the toxin, but the producing species vary between geographical regions. Aphanizomenon flos-aquae, a common algae species in temperate fresh and brackish waters, is one of the three well-documented CYN producers in European waters. So far, no genetic information on the CYN genes of this species has been available. Here, we describe the complete CYN gene cluster, including flanking regions from the German Aphanizomenon sp. strain 10E6 using a full genome sequencing approach by 454 pyrosequencing and bioinformatic identification of the gene cluster. In addition, we have sequenced a ∼7 kb fragment covering the genes cyrC (partially), cyrA and cyrB (partially) of the same gene cluster in the CYN-producing Aphanizomenon sp. strains 10E9 and 22D11. Comparisons with the orthologous gene clusters of the Australian Cylindrospermopsis raciborskii strains AWT205 and CS505 and the partial gene cluster of the Israeli Aphanizomenon ovalisporum strain ILC-146 revealed a high gene sequence similarity, but also extensive rearrangements of gene order. The high sequence similarity (generally higher than that of 16S rRNA gene fragments from the same strains), atypical GC-content and signs of transposase activities support the suggestion that the CYN genes have been horizontally transferred.
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Sung, Y. C., i J. A. Fuchs. "Characterization of the cyn operon in Escherichia coli K12." Journal of Biological Chemistry 263, nr 29 (październik 1988): 14769–75. http://dx.doi.org/10.1016/s0021-9258(18)68104-9.
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Jiang, Yongguang, Peng Xiao, Gongliang Yu, Tomoharu Sano, Qianqian Pan i Renhui Li. "Molecular Basis and Phylogenetic Implications of Deoxycylindrospermopsin Biosynthesis in the Cyanobacterium Raphidiopsis curvata". Applied and Environmental Microbiology 78, nr 7 (27.01.2012): 2256–63. http://dx.doi.org/10.1128/aem.07321-11.
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ABSTRACTNew insights into the distribution and biochemistry of the cyanotoxin cylindrospermopsin (CYN) have been provided by the recent determination of its biosynthesis gene cluster (cyr) in several cyanobacterial species.Raphidiopsis curvataCHAB1150 isolated from China was analyzed for CYN analogues. Only 7-deoxy-CYN was detected in the cell extracts. Thecyrgene cluster ofR. curvataCHAB1150 was sequenced, and thecyrgenes of this strain were found to have extremely high similarities (96% to 100%) to those from other nostocalean species. These species includeCylindrospermopsis raciborskiiAWT205,Aphanizomenonsp. strain 10E6, andAphanizomenon ovalisporumILC-146. Insertion mutation was identified within thecyrIgene, and transcripts ofcyrIand another functional genecyrJwere detected inR. curvataCHAB1150. General congruence between the phylogenetic trees based on bothcyrand 16Srrnwas displayed. Neutral evolution was found on the whole sequences of thecyrgenes, and 0 to 89 negative selected codons were detected in each gene. Therefore, the function of CyrI is to catalyze the oxygenation of 7-deoxy-CYN in CYN biosynthesis. The transcripts of the mutatedcyrIgene may result from polycistronic transcription. The high conservation of thecyrgenes may be ascribed to purifying selection and horizontal gene transfer.
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Murphy, Fionnuala, G. Devlin i K. McDonnell. "The Evaluation of Flash Point and Cold Filter Plugging Point with Blends of Diesel and Cyn-Diesel Pyrolysis Fuel for Automotive Engines". Open Fuels & Energy Science Journal 6, nr 1 (12.07.2013): 1–8. http://dx.doi.org/10.2174/1876973x01306010001.
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The production of synthetic fuels from alternative sources has increased in recent years as a cleaner, more sustainable source of transport fuel is now required. The European Commission has outlined renewable energy targets pertaining to transport fuel which must be met by 2020. In response to these targets Ireland has committed, through the Biofuels Obligation Scheme of 2008, to producing 3% of transport fuels from biofuels by 2010 and 10% by 2020. In order to be suitable for sale in Europe, diesel fuels and biodiesels must meet certain European fuel specifications outlined in the EN 590:2009 standard. The aim of this paper was to prepare blends of varying proportions of synthetic diesel (Cyn-diesel) fuel, produced from the pyrolysis of plastic, vs regular fossil diesel. The flash point (°C) and cold filter plugging point (°C) of these blends as well as of the conventional petroleum diesel fuel were analysed in relation to compliance with the European fuel standard EN 590. The results confirmed that blending of Cyn-diesel with conventional petroleum diesel has a highly significant effect on the properties of the resulting fuel blend. The results show that by increasing the Cyn-diesel content of the blend, the flash point of the blend decreases and the cold filter plugging point increases. Furthermore, comparing the fuel blends to EN 590 specifications has highlighted significant trends. The cold filter plugging points of all of the fuel blends are in compliance with EN 590 specifications. However, only blends of up to, and including, 40% Cyn-diesel are in compliance with EN 590 specifications for flash point. This analysis shows that a blend of 40% Cyndiesel is in compliance with all of the EN 590 specifications examined, and as such could be placed on the European fuel market (provided that the blend meets the requirements for the other properties in the EN 590 specification). This finding highlights the potential for Cyn-diesel blends to be incorporated into the European and national renewable energy targets.
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Munoz, Macarena, David Ortiz, Julia Nieto-Sandoval, Samuel Cirés, Zahara M. de Pedro, Antonio Quesada i Jose A. Casas. "Catalytic Wet Peroxide Oxidation of Cylindrospermopsin over Magnetite in a Continuous Fixed-Bed Reactor". Catalysts 10, nr 11 (29.10.2020): 1250. http://dx.doi.org/10.3390/catal10111250.
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The development of cost-efficient and environmentally friendly technologies for the removal of cyanotoxins from water is crucial, given the increasingly frequent appearance of toxic cyanobacterial blooms. In this work, the application of catalytic wet peroxide oxidation (CWPO) promoted by natural magnetite for the removal of the highly toxic cyanotoxin cylindrospermopsin (CYN) has been investigated. A fixed-bed reactor packed with magnetite powder and granules was used to treat a continuous flow of CYN-bearing water. Experiments were carried out under ambient conditions and circumneutral pH (pH0 = 5). The effect of the main variables of the process, viz. magnetite load (8–14 g), feed flow rate (0.1–0.25 mL min−1), H2O2 dose (0.5–8 mg L−1) and initial CYN concentration (25–100 μg L−1), were systematically analyzed. CYN conversion values and kinetic constants were calculated to evaluate the feasibility of the catalytic system. The process was highly effective in the removal of the cyanotoxin, achieving up to 80% CYN conversion under optimized conditions (flow rate = 0.2 mL min−1, [H2O2]0 = 5 mg L−1, WFe3O4 = 14 g, pH0 = 5, T = 25 °C). It also showed reasonable activity (~55% CYN conversion) in two real samples (pond and river water). The decay on CYN conversion in these cases was mainly due to the scavenging of hydroxyl radicals by the co-existing species present in the matrices. Remarkably, the catalytic system showed high stability with limited iron leaching (the iron leached at the end of the experiments represented less than 0.2 wt.% of the catalyst’s initial iron content) in all cases. Its stability was further confirmed in a long-term continuous experiment (60 h time on stream). Furthermore, the magnetite granules at the top layer of the packed bed avoided the loss of magnetite powder from the reactor, confirming the suitability of the system for continuous long-term application.
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Ballot, Andreas, Jutta Fastner i Claudia Wiedner. "Paralytic Shellfish Poisoning Toxin-Producing Cyanobacterium Aphanizomenon gracile in Northeast Germany". Applied and Environmental Microbiology 76, nr 4 (4.01.2010): 1173–80. http://dx.doi.org/10.1128/aem.02285-09.
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ABSTRACT Neurotoxic paralytic shellfish poisoning (PSP) toxins, anatoxin-a (ATX), and hepatotoxic cylindrospermopsin (CYN) have been detected in several lakes in northeast Germany during the last 2 decades. They are produced worldwide by members of the nostocalean genera Anabaena, Cylindrospermopsis, and Aphanizomenon. Although no additional sources of PSP toxins and ATX have been identified in German water bodies to date, the observed CYN concentrations cannot be produced solely by Aphanizomenon flos-aquae, the only known CYN producer in Germany. Therefore, we attempted to identify PSP toxin, ATX, and CYN producers by isolating and characterizing 92 Anabaena, Aphanizomenon, and Anabaenopsis strains from five lakes in northeast Germany. In a polyphasic approach, all strains were morphologically and phylogenetically classified and then tested for PSP toxins, ATX, and CYN by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and enzyme-linked immunosorbent assay (ELISA) and screened for the presence of PSP toxin- and CYN-encoding gene fragments. As demonstrated by ELISA and LC-MS, 14 Aphanizomenon gracile strains from Lakes Melang and Scharmützel produced four PSP toxin variants (gonyautoxin 5 [GTX5], decarbamoylsaxitoxin [dcSTX], saxitoxin [STX], and neosaxitoxin [NEO]). GTX5 was the most prevalent PSP toxin variant among the seven strains from Lake Scharmützel, and NEO was the most prevalent among the seven strains from Lake Melang. The sxtA gene, which is part of the saxitoxin gene cluster, was found in the 14 PSP toxin-producing A. gracile strains and in 11 non-PSP toxin-producing Aphanizomenon issatschenkoi, A. flos-aquae, Anabaena planktonica, and Anabaenopsis elenkinii strains. ATX and CYN were not detected in any of the isolated strains. This study is the first confirming the role of A. gracile as a PSP toxin producer in German water bodies.
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Ferreira, Matheus Almeida, Cristina Celia Silveira Brandão i Yovanka Pérez Ginoris. "Oxidation of Cylindrospermopsin by Fenton Process: A Bench-Scale Study of the Effects of Dose and Ratio of H2O2 and Fe(II) and Kinetics". Toxins 13, nr 9 (29.08.2021): 604. http://dx.doi.org/10.3390/toxins13090604.
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The cyanotoxin cylindrospermopsin (CYN) has become a significant environmental and human health concern due to its high toxicological potential and widespread distribution. High concentrations of cyanotoxins may be produced during cyanobacterial blooms. Special attention is required when these blooms occur in sources of water intended for human consumption since extracellular cyanotoxins are not effectively removed by conventional water treatments, leading to the need for advanced water treatment technologies such as the Fenton process to produce safe water. Thus, the present study aimed to investigate the application of the Fenton process for the degradation of CYN at bench-scale. The oxidation of CYN was evaluated by Fenton reaction at H2O2/Fe(II) molar ratio in a range of 0.4 to 4.0, with the highest degradation of about 81% at molar ratio of 0.4. Doubling the concentrations of reactants for the optimized H2O2/Fe(II) molar ratio, the CYN degradation efficiency reached 91%. Under the conditions studied, CYN degradation by the Fenton process followed a pseudo-first-order kinetic model with an apparent constant rate ranging from 0.813 × 10−3 to 1.879 × 10−3 s−1.
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Wang, Shulian, Yongmei Chen, Yiying Jiao i Zhu Li. "Detoxification of Cylindrospermopsin by Pyrite in Water". Catalysts 9, nr 9 (21.08.2019): 699. http://dx.doi.org/10.3390/catal9090699.
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Cylindrospermopsin (CYN) is a cyanobacterial toxin released from eutrophic water. It persistently remains in the environment because its degradation under solar light is extremely low. In this study, pyrite, an abundant mineral, was investigated as a catalyst for decomposing and detoxifying CYN in water. A detailed examination of intermediates provided insights into the degradation pathway. Electron spin resonance spectra revealed that H2O2 and hydroxyl radicals (•OH) were generated at the pyrite surface while promoting the recycling of Fe(III) into Fe(II) during the degradation process. This degradation system could be uniquely efficient in the presence of relatively high levels of natural organic matter because the structure of the uracil ring is decomposed to detoxify CYN. This work confirms a new approach to selectively and effectively detoxifying CYN in water using an inexpensive, environmentally friendly, and bio-compatible mineral.
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Antonieti, Caio César, i Yovanka Pérez Ginoris. "Removal of Cylindrospermopsin by Adsorption on Granular Activated Carbon, Selection of Carbons and Estimated Fixed-Bed Breakthrough". Water 14, nr 10 (19.05.2022): 1630. http://dx.doi.org/10.3390/w14101630.
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Climate change and the increase in the availability of nutrients in aquatic environments have increased the occurrence of cyanobacterial blooms which can produce cyanotoxins such as cylindrospermopsin (CYN). Activated carbon adsorption have been proved to be efficient for CYN removal. In the present study, a carbon with high CYN adsorption capacity was identified between two granular activated carbons. For this carbon was estimated the operating time of a full-scale granular activated carbon column under different empty bed contact times (EBCT). The fixed-bed breakthrough was estimated using the Homogeneous Surface Diffusion Model (HSDM). Wood carbon showed greater capacity to remove CYN. The experimental equilibrium data best fitted Langmuir isotherm model, in which wood carbon had a maximum adsorption capacity of 3.67 μg/mg and Langmuir adsorption constant of 0.2791 L/μg. The methodology produced satisfactory results where the HSDM simulated the fixed-bed breakthrough with a coefficient of determination of 0.89, to the film diffusion coefficient (Kf) of 9 × 10−6 m/s and surface diffusion coefficient (Ds) of 3 × 10−16 m2/s. It was observed that the increase in EBCT promotes a reduction in the carbon use rate. The best carbon use rate found was 0.43 kg/m3 for a EBCT of 10 min and breakthrough time of 183.6 h.
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Yun, Hee Young, Eun-Ji Won, Jisoo Choi, Yusang Cho, Da-Jung Lim, In-Seon Kim i Kyung-Hoon Shin. "Stable Isotope Analysis of Residual Pesticides via High Performance Liquid Chromatography and Elemental Analyzer–Isotope Ratio Mass Spectrometry". Molecules 27, nr 23 (6.12.2022): 8587. http://dx.doi.org/10.3390/molecules27238587.
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To broaden the range of measurable pesticides for stable isotope analysis (SIA), we tested whether SIA of the anthranilic diamides cyantraniliprole (CYN) and chlorantraniliprole (CHL) can be achieved under elemental analyzer/isotope ratio mass spectrometry with compound purification in high-performance liquid chromatography (HPLC). Using this method, carbon isotope compositions were measured in pesticide residues extracted from plants (lettuce) grown indoors in potting soil that were treated with 500 mg/kg CHL and 250 mg/kg CYN and were followed up for 45 days. Our results show that the CYN and CHL standard materials did not have significant isotope differences before and after clean-up processing in HPLC. Further, when applied to the CYN product and CHL product in soil, stable isotope differences between the soil and plant were observed at <1.0‰ throughout the incubation period. There was a slight increase in the variability of pesticide isotope ratio detected with longer-term incubation (CHL, on average 1.5‰). Overall, we measured the carbon isotope ratio of target pesticides from HPLC fraction as the purification and pre-concentration step for environmental and biological samples. Such negligible isotopic differences in pesticide residues in soils and plants 45 days after application confirmed the potential of CSIA to quantify pesticide behavior in environments.
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Dale, David C., Audrey Anna Bolyard, Merideth L. Kelley, Vahagn Makaryan, Mary Ann Bonilla, Laurence A. Boxer, Sabine Mellor-Heineke, Karl H. Welte, Peter E. Newburger i Cornelia Zeidler. "Long Term Outcomes for Patients with Cyclic Neutropenia Treated with Granulocyte Colony-Stimulating Factor (G-CSF)". Blood 126, nr 23 (3.12.2015): 996. http://dx.doi.org/10.1182/blood.v126.23.996.996.
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Cyclic neutropenia (CyN) is a rare hematological condition with neutrophil counts decreasing to <0.2 x 109/L, usually at 21 day intervals, accompanied by fever, mouth ulcers and the risk of severe sepsis during the neutropenic periods. Twenty-six years ago we reported results of treating six patients with CyN on G-CSF (N Engl J Med. 1989;320: 1306-1311). We have now followed these patients and many other CyN on G-CSF for up to 28 years through the Severe Chronic Neutropenia International Registry (SCNIR). The original six patients (2 male, 4 female, ages 8.8 to 65) are all living, now ages 36 to 92 years. All of the original six had documented fever and recurring infections prior to treatment (i.e. mouth ulcers, gingivitis, lymphadenopathy, cellulitis, abscesses, pharyngitis, otitis, and pneumonia). Five were found to have mutations in ELANE after the discovery of mutations in this gene as the cause for CyN. The sixth patient, in retrospect, probably more appropriately should have be given the diagnosis of severe idiopathic neutropenia, is now age 92, off G-CSF and residing at home with skilled nursing care. The other five have maintained good health on G-CSF treatment and are now employed as teachers, working in a business, or retired. None have developed notable infections, hematological or other sequelae except for one patient with decreased bone density and one patient with idiopathic thrombocytopenia purpura (ITP) responding to splenectomy. In aggregate these six patients have received approximately 6.6 grams of G-CSF over 143 patient-years (median dose of G-CSF per patient per year is 0.035 gm, range 0.018 to 0.075 gm, treatment period: 7-28 years). Our broader experience with 308 patients with the diagnosis of CyN based on serial blood counts and/or genotyping and treated with G-CSF is similar to these original six patients. However, we are aware of at least 40 cases of severe sepsis and 17 deaths in patients with CyN not on G-CSF. We are not aware of any such severe infections in CyN patients consistently receiving G-CSF (i.e. at least two or three times per week). We have recorded one case on chronic myeloid leukemia in a CyN patient never on G-CSF. For patients receiving G-CSF we have recorded one case of non-Hodgkin's lymphoma, one case of AML in patient with probable CyN having 2 ELANE mutations and a secondary CSF3R mutation, and one case of AML after chronic immunosuppressive therapy with cyclophosphamide. Conclusion: Observations in 308 patients for 2993 years demonstrate that G-CSF is a very beneficial treatment for patients with CyN. There is good evidence that this treatment prevents severe infections and death from infections and there is a very low risk myeloid malignancies, and specifically conversion to MDS or AML. Disclosures Dale: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Boxer:Amgen: Equity Ownership.
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Cinthya Covessi Thom, de Souza, Filho Nelson Augusto Rosario, Taketomi Ernesto Akio, Miranda Juliana Silva i Godoi Ricardo Henrique Moreton. "Cyn d 1 airborne allergen in a Southern Brazilian city". Archives of Asthma, Allergy and Immunology 5, nr 1 (26.02.2021): 014–16. http://dx.doi.org/10.29328/journal.aaai.1001024.
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Zeidler, Cornelia, Sabine Mellor-Heineke, Maksim Klimiankou, Julia Skokowa i Karl Welte. "First Case of Leukemia in a Child Suffering from Cyclic Neutropenia with ELANE Mutation". Blood 126, nr 23 (3.12.2015): 997. http://dx.doi.org/10.1182/blood.v126.23.997.997.
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Congenital neutropenia (CN) and Cyclic neutropenia (CyN) are rare hematological conditions in which ELANE mutations have been found. The discrimination of Cyn from CN is based on the cycling neutrophil counts which decrease to <0.2 x 109/L, usually at 21 day intervals. Infectious episodes are typically less severe in CyN compared to infections in CN patients. While in patients suffering from ELANE-CN an increased risk of leukemic transformation of more than 10 percent is well documented, no AML has been reported in the European SCNIR cohort of 38 patients with ELANE -CYN so far. Here we report the first case of AML secondary to ELANE -CyN in a 17 year old girl. Severe neutropenia was first diagnosed at the age of four weeks during a septicemia with pseudomonas, but no serial blood counts were collected. G-CSF treatment was initiated at an age of 2 years after recurrent otitis media, pneumonia and skin abscesses. Infectious events occurred infrequently under G-CSF treatment. At an age of 14 years she was referred to us after a severe infectious event (liver abscess) and an unexplained high range of ANCs (0 to more than 10x109/µl) under G-CSF treatment with varying doses. Sequential blood counts confirmed the diagnosis of CyN. Molecular genetic testing revealed a heterozygous ELANE mutation, both parents are ELANE negative. Previous bone marrows varied between a maturation arrest on the promyelocyte stage with absence of neutrophils and up to 16 percent segmented neutrophils. No cytogenetic aberrations were detected prior to AML. AML was diagnosed recently when she presented with decreasing platelets and hemoglobin. Bone marrow at this time showed 14% blasts and presence of monosomy 7 plus trisomy 21 in the cytogenetic evaluation. Molecular genetic evaluation of the bone marrow revealed presence of a CSFR3 and RUNX1 mutations in the leukemic cells. Conclusion Our patient presented with a secondary AML after ELANE positive cyclic neutropenia. Cytogenetics, CSFR3 and RUNX1 mutations in the bone marrow at the time of leukemia diagnosis have been described in the pathway of leukemogenesis in Congenital neutropenia with ELANE, HAX1 or other underlying mutation. Our patient is the first case of leukemia in ELANE -CyN and proofs that ELANE -CyN is another pre-leukemic condition. However, the risk of myeloid transformation is very low. Disclosures No relevant conflicts of interest to declare.
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Barik, Sailen. "Dual-Family Peptidylprolyl Isomerases (Immunophilins) of Select Monocellular Organisms". Biomolecules 8, nr 4 (15.11.2018): 148. http://dx.doi.org/10.3390/biom8040148.
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The dual-family peptidylprolyl cis-trans isomerases (immunophilins) represent a naturally occurring chimera of the classical FK506-binding protein (FKBP) and cyclophilin (CYN), connected by a flexible linker. They are found exclusively in monocellular organisms. The modular builds of these molecules represent two distinct types: CYN-(linker)-FKBP and FKBP-3TPR (tetratricopeptide repeat)-CYN. Abbreviated respectively as CFBP and FCBP, the two classes also exhibit distinct organism preference, the CFBP being found in prokaryotes, and the FCBP in eukaryotes. This review summarizes the mystery of these unique class of prolyl isomerases, focusing on their host organisms, potential physiological role, and likely routes of evolution.
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Klimenkova, Olga, Maksim Klimiankou, Lothar Kanz, Cornelia Zeidler, Karl Welte i Julia Skokowa. "Differential Expression of Neutrophil Granule Protein Genes in Bone Marrow Myeloid Cells at the Peak and Nadir of Neutrophil Counts in Cyclic Neutropenia". Blood 126, nr 23 (3.12.2015): 2194. http://dx.doi.org/10.1182/blood.v126.23.2194.2194.
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Abstract Cyclic neutropenia (CyN) is a hematologic disorder in which peripheral-blood neutrophil counts show cycles at approx. 21-days intervals. The majority of CyN patients (ca. 90 %) harbor inherited mutations in the ELANE gene. The mechanism of cycling hematopoiesis downstream of ELANE mutations is unclear. In the present study we aimed to identify if there is a geterogeniety of bone marrow (BM) myeloid progenitors and granulocytic cells at the peak and nadir of the cycle of neutrophil counts. We performed FACS analysis of BM populations in CyN patient at the peak and nadir of the cycle and revealed reduced number of CD33high promyelocytes at the peak, as compared to the nadir neutrophil counts (6% vs 47%). Morphological examination of BM smears confirmed this observation. These data suggest differences in myeloid differentiation potential of hematopoietic cells of CyN patient during cycle. To compare the myeloid differentiation of BM cells at the peak and nadir, we performed CFU assay using BM cells isolated at these two different time points. Indeed, we found diminished capacity to produce CFU-G colonies at the peak of cycle, in comparison to the nadir (50 vs 68). This difference might be explained by the presence of different sub-populations of myeloid cells during the cycle. It was shown that the neutrophil populations can be distinguished by membrane expression of CD177, which is GPI-linked neutrophil antigen, localized primarily to the membrane of specific granules and to the plasma membrane. The proportion of CD177+ cells increased during neutrophil maturation in BM. Interestingly, in healthy individuals the fraction of CD177+ cells appeared to be constant in each individual. We evaluated the differences of CD177+ cell populations in CyN patients at the peak and nadir of cycle by FACS. We found that numbers of CD33+ CD177+ and CD16+ CD177+ populations were different during the cycle. At the peak we measured 7,1% of CD33+ CD177+ cells and 83% of CD16+ CD177+ cells. At the nadir 3,78% of cells were CD33+ CD177+ and 69% were CD16+ CD177+. We further performed mRNA expression analysis of CD33+ BM cells isolated from CyN patient at the peak and nadir of cycle and compared it to healthy individuals. We found lower mRNA expression (more than 10-fold) of CRISP3, ELANE, OLFM4, CEACAM6, MMP8, DEFA4 and LCN2 in CD33+ cellsat the peak of the cycle comparing to the nadir. These genes encode for neutrophil granule proteins, playing an important role in the developement and function of mature neutrophils. We further confirmed differential expression of these factors in CFU colonies using BM of CyN patient isolated at the peak and nadir of the cycle: CFU-G colonies grown from cells taken at the peak of the cycle expressed less mRNA levels of granula proteins than CFU-G colonies grown from cells taken at the nadir of the cycle. In summary, we hypothesize that the differential expression of the granule proteins is involved in the regulation of the cycle in myeloid cells in CyN. At the peak and nadir of neutrophil counts different populations (based on CD177 expression) of myeloid progenitors and neutrophils are present in the CyN BM. Disclosures No relevant conflicts of interest to declare.
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Díez-Quijada, Leticia, Ana I. Prieto, María Puerto, Ángeles Jos i Ana M. Cameán. "In Vitro Mutagenic and Genotoxic Assessment of a Mixture of the Cyanotoxins Microcystin-LR and Cylindrospermopsin". Toxins 11, nr 6 (4.06.2019): 318. http://dx.doi.org/10.3390/toxins11060318.
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The co-occurrence of various cyanobacterial toxins can potentially induce toxic effects different than those observed for single cyanotoxins, as interaction phenomena cannot be discarded. Moreover, mixtures are a more probable exposure scenario. However, toxicological information on the topic is still scarce. Taking into account the important role of mutagenicity and genotoxicity in the risk evaluation framework, the objective of this study was to assess the mutagenic and genotoxic potential of mixtures of two of the most relevant cyanotoxins, Microcystin-LR (MC-LR) and Cylindrospermopsin (CYN), using the battery of in vitro tests recommended by the European Food Safety Authority (EFSA) for food contaminants. Mixtures of 1:10 CYN/MC-LR (CYN concentration in the range 0.04–2.5 µg/mL) were used to perform the bacterial reverse-mutation assay (Ames test) in Salmonella typhimurium, the mammalian cell micronucleus (MN) test and the mouse lymphoma thymidine-kinase assay (MLA) on L5178YTk± cells, while Caco-2 cells were used for the standard and enzyme-modified comet assays. The exposure periods ranged between 4 and 72 h depending on the assay. The genotoxicity of the mixture was observed only in the MN test with S9 metabolic fraction, similar to the results previously reported for CYN individually. These results indicate that cyanobacterial mixtures require a specific (geno)toxicity evaluation as their effects cannot be extrapolated from those of the individual cyanotoxins.
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Sánchez, Jorge, Andres Sánchez i Jorge Sánchez. "Differences in the Nasal Inflammatory Response to Cynodon dactylon From Rural and Urban Areas in Patients With Allergic Rhinitis". Allergy & Rhinology 9 (styczeń 2018): 215265671881587. http://dx.doi.org/10.1177/2152656718815870.
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Background Epidemiological and experimental studies suggest that air pollution has a negative impact on human health and modifies the environment. However, the clinical implications of changes in environmental allergens secondary to air pollution have been little studied. Objectives To explore if the growth conditions of the Cynodon dactylon (rural vs urban area) modify the inflammatory response among patients with allergic rhinitis. Methodology: Two extracts were prepared for diagnostic test with Cyn d proteins obtained from rural and urban environment. Skin prick test (SPT), nasal challenge test (NCT), and eosinophil count in nasal mucus were performed in 3 groups: healthy subjects without rhinitis, rhinitis with (+) Cyn d, and rhinitis with (−) Cyn d. Results There was a 97% concordance in the positive and negative results of the SPT with the 2 extracts. However, Cyn d-urban extract generated larger wheals ( P = .03) and a higher number of patients with rhinitis presented a positive NCT to this extract (n = 7 vs 14, P = .04). Patients with positive NCT had a significant increase in eosinophils in mucus, but there was no difference between the extracts. The healthy controls did not react to the extracts tested in the skin or nasal test. Conclusion The findings suggest that the growth conditions in urban area of Cynodon dactylon can generate changes in the protein extract and have clinical implications in patients with allergic rhinitis.
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Choi, Jae-won, Jae-heon Jang, Sun-hong Lee i Mi-ae Yoon. "Determination of Cylindrospermopsin in Surface and Treated Water using Liquid Chromatography-Tandem Mass Spectrometry". Journal of Environmental Analysis, Health and Toxicology 25, nr 2 (30.06.2022): 71–76. http://dx.doi.org/10.36278/jeaht.25.2.71.
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Cylindrospermopsin (CYN) is an emerging freshwater cyanobacterial toxin, and its reports on toxicity toward the human liver and kidney tissues has drawn a lot of attention. An appropriate analytical method is necessary to determine the presence of this emerging cyanobacterial toxin in water resources including drinking water; therefore, it is necessary to develop a sensitive analytical method for CYN detection. In this study, we developed a simple and sensitive analytical method for CYN detection using liquid chromatography-tandem mass spectrometry (LC-MS/MS) using direct injection. The method was validated for linearity of calibration, limit of detection, limit of quantitation, accuracy, and precision. The limit of detection and quantitation were in the range of 0.029 μg/L and 0.091 μg/L, respectively. Accuracy and precision were also obtained within an acceptable range. The optimized method was used to measure the concentrations of CYN in the surface water from each weir areas of the Geum River, Nakdong River. Additionally, this method was applied to samples of drinking water obtained from the treatment plants of the Geum River, Nakdong River for each process.
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Hinojosa, María G., Ana I. Prieto, Clara Muñoz-Castro, María V. Sánchez-Mico, Javier Vitorica, Ana M. Cameán i Ángeles Jos. "Cytotoxicity and Effects on the Synapsis Induced by Pure Cylindrospermopsin in an E17 Embryonic Murine Primary Neuronal Culture in a Concentration- and Time-Dependent Manner". Toxins 14, nr 3 (26.02.2022): 175. http://dx.doi.org/10.3390/toxins14030175.
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Cylindrospermopsin (CYN) is a cyanotoxin whose incidence has been increasing in the last decades. Due to its capacity to exert damage at different levels of the organism, it is considered a cytotoxin. Although the main target organ is the liver, recent studies indicate that CYN has potential toxic effects on the nervous system, both in vitro and in vivo. Thus, the aim of the present work was to study the effects of this cyanotoxin on neuronal viability and synaptic integrity in murine primary cultures of neurons exposed to environmentally relevant concentrations (0–1 µg/mL CYN) for 12, 24, and 48 h. The results demonstrate a concentration- and time-dependent decrease in cell viability; no cytotoxicity was detected after exposure to the cyanotoxin for 12 h, while all of the concentrations assayed decreased this parameter after 48 h. Furthermore, CYN was also demonstrated to exert damage at the synaptic level in a murine primary neuronal culture in a concentration- and time-dependent manner. These data highlight the importance of studying the neurotoxic properties of this cyanotoxin in different experimental models.
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Diez-Quijada, Leticia, Maria del Monte Benítez-González, María Puerto, Angeles Jos i Ana M. Cameán. "Immunotoxic Effects Induced by Microcystins and Cylindrospermopsin: A Review". Toxins 13, nr 10 (8.10.2021): 711. http://dx.doi.org/10.3390/toxins13100711.
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Cyanotoxin occurrence is gaining importance due to anthropogenic activities, climate change and eutrophication. Among them, Microcystins (MCs) and Cylindrospermopsin (CYN) are the most frequently studied due to their ubiquity and toxicity. Although MCs are primary classified as hepatotoxins and CYN as a cytotoxin, they have been shown to induce deleterious effects in a wide range of organs. However, their effects on the immune system are as yet scarcely investigated. Thus, to know the impact of cyanotoxins on the immune system, due to its importance in organisms’ homeostasis, is considered of interest. A review of the scientific literature dealing with the immunotoxicity of MCs and CYN has been performed, and both in vitro and in vivo studies have been considered. Results have confirmed the scarcity of reports on the topic, particularly for CYN. Decreased cell viability, apoptosis or altered functions of immune cells, and changed levels and mRNA expression of cytokines are among the most common effects reported. Underlying mechanisms, however, are still not yet fully elucidated. Further research is needed in order to have a full picture of cyanotoxin immunotoxicity.
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Cirés, Samuel, Lars Wörmer, Andreas Ballot, Ramsy Agha, Claudia Wiedner, David Velázquez, María Cristina Casero i Antonio Quesada. "Phylogeography of Cylindrospermopsin and Paralytic Shellfish Toxin-Producing Nostocales Cyanobacteria from Mediterranean Europe (Spain)". Applied and Environmental Microbiology 80, nr 4 (13.12.2013): 1359–70. http://dx.doi.org/10.1128/aem.03002-13.
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ABSTRACTPlanktonicNostocalescyanobacteria represent a challenge for microbiological research because of the wide range of cyanotoxins that they synthesize and their invasive behavior, which is presumably enhanced by global warming. To gain insight into the phylogeography of potentially toxicNostocalesfrom Mediterranean Europe, 31 strains ofAnabaena(Anabaena crassa,A. lemmermannii,A. mendotae, andA. planctonica),Aphanizomenon(Aphanizomenon gracile,A. ovalisporum), andCylindrospermopsis raciborskiiwere isolated from 14 freshwater bodies in Spain and polyphasically analyzed for their phylogeography, cyanotoxin production, and the presence of cyanotoxin biosynthesis genes. The potent cytotoxin cylindrospermopsin (CYN) was produced by all 6Aphanizomenon ovalisporumstrains at high levels (5.7 to 9.1 μg CYN mg−1[dry weight]) with low variation between strains (1.5 to 3.9-fold) and a marked extracellular release (19 to 41% dissolved CYN) during exponential growth. Paralytic shellfish poisoning (PSP) neurotoxins (saxitoxin, neosaxitoxin, and decarbamoylsaxitoxin) were detected in 2Aphanizomenon gracilestrains, both containing thesxtAgene. This gene was also amplified in non-PSP toxin-producingAphanizomenon gracileandAphanizomenon ovalisporum. Phylogenetic analyses supported the species identification and confirmed the high similarity of SpanishAnabaenaandAphanizomenonstrains with other European strains. In contrast,Cylindrospermopsis raciborskiifrom Spain grouped together with American strains and was clearly separate from the rest of the European strains, raising questions about the current assumptions of the phylogeography and spreading routes ofC. raciborskii. The present study confirms that the nostocalean genusAphanizomenonis a major source of CYN and PSP toxins in Europe and demonstrates the presence of thesxtAgene in CYN-producingAphanizomenon ovalisporum.
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Klimiankou, Maksim, Olga Klimenkova, Lothar Kanz, Cornelia Zeidler, Karl Welte i Julia Skokowa. "Time Course of Acquisition of a CSF3R Mutation and Subsequent Development of AML in a Patient with Cyclic Neutropenia". Blood 126, nr 23 (3.12.2015): 885. http://dx.doi.org/10.1182/blood.v126.23.885.885.
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Acquired CSF3R (colony stimulating factor 3 receptor, granulocyte) mutations have been detected with a high frequency (17-34%) in severe congenital neutropenia (CN) patients. Moreover, in CN patients who developed overt acute myeloid leukemia (AML) the frequency of CSF3R mutations in the intracellular critical region reaches more than 80%. Up to now there was no report on the detection of acquired mutations in CSF3R or development of AML/MDS in cyclic neutropenia patients (CyN). This group of patients reveals the same genotype with mutations in the ELANE gene as CN patients. In contrast, both groups of patients have a clearly distinct disease penetration. Using ultra-deep sequencing approach we screened 22 CyN patients for the presence of genetic abnormalities in the critical region of the CSF3R gene. Interestingly, we found only in one CyN patient a clone with acquired mutation in G-CSF receptor (NP_000751.3, p.Gln741X) at 3% of allele frequency. The cycling neutrophils and platelets were well documented and verified the diagnosis of CyN. Within two years after the first detection, the mutant clone harboring the CSF3R mutation expanded and was detected in 16% of patient's bone marrow (BM) MNCs. The sequencing of the ELANE gene in the CyN patient with CSF3R mutation revealed the presence of two mutations p.Ala233Pro and p.Val235TrpfsX (NP_001963.1). Intriguingly, both ELANE mutations were absent in DNA isolated from each of parents indicating their de novo origin. Additionally, the patient was found to be heterozygous for synonymous SNP rs17216649 (dbSNP build 138) on the same ELANE exon permitting determination of the parental origin of mutations. The sub-clone analysis in E.coli showed that both mutations were always found on the paternally-derived allele. The missense mutation p.Ala233Pro (NP_001963.1) is well known to be associated with CN phenotype, whereas the single-base deletion p.Val235TrpfsX (NP_001963.1) was reported as cause of CN only once. There are no reports about detection of these mutations in CyN patients. Three years after the first detection of the CSF3R mutation the patient presented with 14% blast cells in bone marrow acquiring monosomy 7 and trisomy 21. Based on results of cDNA sequencing all CSF3R expressing cells in the sample were positive for p.Gln741X (NP_000751.3) mutation. Recently, we demonstrated acquisition of cooperative of RUNX1 and CSF3R mutations in more than 60% of CN-AML/MDS patients. We also found RUNX1 mutation p.Asp171Asn (NP_001001890.1) at 10% allele frequency in BM MNCs of CyN-AML patient. To evaluate at which stage of hematopoietic differentiation acquisition of CSF3R mutations appeared leading to the leukemogenic transformation, we performed colony forming unit (CFU) assays using patients BM MNCs. We observed the appearance of abnormal «CFU-blast» colonies after cultivation of BM MNCs in MethoCult H4434 Enriched medium supplemented with rh SCF, rh G-CSF, rh IL-3, rh IL-6 and rh EPO (72,2% of CFU-blasts (n=232), 21,8% of CFU-G (n=70), 5% of CFU-GM (n=16) and 1% of BFU-E (n=3)). Interestingly, we found that all sequenced CFU-G (n=4), CFU-GM (n=6) and «CFU-blast» colonies (n=20) were positive for p.Q741X CSF3R mutation. At the same time, no CSF3R mutations were identified in BFU-E colonies. In summary, we report a first case of acquisition of CSF3R mutation and subsequent development of AML in a CyN patient underlying the complex nature of genotype:phenotype relations in CN and CyN patients. This case also represents an example of an extremely rare situation of double de novo ELANE mutations and provides a unique opportunity to investigate pathogenic molecular mechanisms of leukemia development in CyN patients. The ultra-deep next generation sequencing (NGS) for identification of CSF3R mutations is a useful tool to study the frequency of CSF3R mutations not only in CN but also in CyN patients and is clinically important for the identification of patients with the risk of progression to leukemia. Disclosures No relevant conflicts of interest to declare.