RESUMEN
BACKGROUND: Unique among cnidarians, jellyfish have remarkable morphological and biochemical innovations that allow them to actively hunt in the water column and were some of the first animals to become free-swimming. The class Scyphozoa, or true jellyfish, are characterized by a predominant medusa life-stage consisting of a bell and venomous tentacles used for hunting and defense, as well as using pulsed jet propulsion for mobility. Here, we present the genome of the giant Nomura's jellyfish (Nemopilema nomurai) to understand the genetic basis of these key innovations. RESULTS: We sequenced the genome and transcriptomes of the bell and tentacles of the giant Nomura's jellyfish as well as transcriptomes across tissues and developmental stages of the Sanderia malayensis jellyfish. Analyses of the Nemopilema and other cnidarian genomes revealed adaptations associated with swimming, marked by codon bias in muscle contraction and expansion of neurotransmitter genes, along with expanded Myosin type II family and venom domains, possibly contributing to jellyfish mobility and active predation. We also identified gene family expansions of Wnt and posterior Hox genes and discovered the important role of retinoic acid signaling in this ancient lineage of metazoans, which together may be related to the unique jellyfish body plan (medusa formation). CONCLUSIONS: Taken together, the Nemopilema jellyfish genome and transcriptomes genetically confirm their unique morphological and physiological traits, which may have contributed to the success of jellyfish as early multi-cellular predators.
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Evolución Molecular , Genoma/fisiología , Conducta Predatoria , Escifozoos/fisiología , Animales , Evolución Biológica , Filogenia , Escifozoos/genéticaRESUMEN
Novel chalcones were found as potent inhibitors of interleukin (IL)-5. 1-(2-Benzyloxy-6-hydroxyphenyl)-3-(4-hydroxyphenyl)-2-propen-1-one (2b, 78.8% inhibition at 50microM, IC(50)=25.3microM) was initially identified as a potent inhibitor of IL-5. This shows the compatible activity with budesonide or sophoricoside. To identify structural requirements, 26 chalcones were prepared and their inhibitory activities were tested against IL-5. Among them, compound 4-[(E)-3-(2-cyclohexylmethoxy-6-hydroxyphenyl)-3-oxoprop-1-enyl]benzenesulfonamide (2w, 99.5% inhibition at 50microM, IC(50)=1.8microM) shows the most potent activity. The important structural requirements of these chalcone analogs exhibiting the inhibitory activity against IL-5 were recognized as the following. (1) The hydrophobic group such as benzyloxy or cyclohexylmethoxy at 6-position of A ring is necessary. (2) The existence of phenolic hydroxyl at 6-position of A ring is critical. (3) Propenone unit as alpha,beta-unsaturated ketone is essential. (4) Electron withdrawing groups with hydrogen acceptor property at 4-position of B ring enhance the activity and quantitative structure-activity relationship of 2 regarding these substituents was determined.
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Chalconas/farmacología , Interleucina-5/antagonistas & inhibidores , Animales , Linfocitos B/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Chalconas/síntesis química , Chalconas/química , Evaluación Preclínica de Medicamentos , Ratones , Estructura Molecular , Relación Estructura-ActividadRESUMEN
A simple and reliable method for the determination of polychlorinated biphenyls (PCBs) from mono- to octachlorobiphenyls in fish oil for dietary supplement is described. The method combines Florisil clean up and headspace solid-phase microextraction on 65 microm polydimethylsiloxane-divinylbenzene (PDMS-DVB). Analyte detection was carried out using GC-time-of-flight mass spectrometry (GC-TOF-MS). Fifty three PCB congeners including the seven indicator PCBs (IUPAC Nos. 28, 52, 101, 118, 138, 153 and 180) were analyzed. Under optimal conditions, the method detection limit (MDL) of each congener in the range from 0.8 to 31 ng/g was found. A certified reference material (BCR-349) was analyzed and it showed good agreement with the certified data.
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Aceites de Pescado/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Silicatos de Magnesio/química , Bifenilos Policlorados/análisis , Adsorción , Bifenilos Policlorados/química , Bifenilos Policlorados/aislamiento & purificación , Reproducibilidad de los ResultadosRESUMEN
Methylmercury (MeHg) is well known as a neurotoxic chemical. However, little is mentioned about its neurotoxic mechanism or molecular target in human neuronal cells in particular. We show in this study that exposure of human neuronal cell line, SH-SY5Y, to MeHg dose- and time-dependently impairs viability and mRNA expression of selenoprotein W (SeW) with a significant difference, unlike other selenoenzymes such as, SeP, GPX4, 5DI, and 5'DI. Using real-time RT PCR, the influence of selenium (Se) and glutathione (GSH) on SeW expression was also investigated. While Se depletion caused a weakly reduced SeW mRNA levels, additional Se caused an increase of SeW mRNA levels. Although 2 mM GSH had induced a weak shift on SeW level, the expression of SeW mRNA was down-regulated in SH-SY5Y cells treated with 25 microM BSO, an inhibitor of GSH synthesis. To understand the relationship between a decrease of SeW expression and intracellular GSH and ROS, we measured the concentration of intracellular GSH and ROS in cells treated to 1.4 microM MeHg using fluorescence based assays. A positive correlation was found between SeW mRNA level and intracellular GSH but no significant correlation was observed between intracellular ROS and SeW mRNA level or intracellular GSH contents. Therefore, we suggest that SeW is the novel molecular target of MeHg in human neuronal cells and down-regulation of this selenoenzyme by MeHg is dependent not on generation of ROS but on depletion of GSH.
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Contaminantes Ambientales/toxicidad , Glutatión/metabolismo , Compuestos de Metilmercurio/toxicidad , Neuronas/efectos de los fármacos , Proteínas/metabolismo , Selenio , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo , Glutatión/farmacología , Humanos , Neuronas/metabolismo , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Selenio/farmacología , Selenoproteína W , SelenoproteínasRESUMEN
The analytical method of antispasmodic agent tiropramide ((+/-)alpha-(benzoylamino)-4-[2-(diethylamino)ethoxy]-N,N-dipropylbenzenepropanamide hydrochloride) was developed by gas chromatography/nitrogen-phosphorus detector (GC/NPD) in human plasma. Two kinds of tiropramide tablets were orally administered to volunteers by Latin square crossover design, and blood was withdrawn as designed schedule. The plasma of 1 mL was loaded on Sep-pak C18 cartridge and eluted with methanol after washing with 30% methanol. The residue dissolved in 100 microL of methanol after evaporation was analyzed by GC/NPD. Precision (CV%) of intra-day was located within 2.6% and accuracy was less than 9.7%. Inter-day precision was below 8.7% and accuracy was relatively good as less than 14%. Plasma samples obtained from human volunteers were analyzed for the determination of tiropramide concentration by using this method. The method was sensitive, rapid and suitable enough to be applied for pharmacokinetic and bioequivalence studies of tiropramide in human volunteers.