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showing 10 items of 13546 documents

The European regulatory environment of rna-based vaccines

2016

A variety of different mRNA-based drugs are currently in development. This became possible, since major breakthroughs in RNA research during the last decades allowed impressive improvements of translation, stability and delivery of mRNA. This article focuses on antigen-encoding RNA-based vaccines that are either directed against tumors or pathogens. mRNA-encoded vaccines are developed both for preventive or therapeutic purposes. Most mRNA-based vaccines are directly administered to patients. Alternatively, primary autologous cells from cancer patients are modified ex vivo by the use of mRNA and then are adoptively transferred to patients. In the EU no regulatory guidelines presently exist t…

0301 basic medicineAutologous cellMessenger RNAVaccinesAnticancer vaccinationGenetically modified medicinal productsbusiness.industryGenetic enhancementmRNARNAGenetic therapy03 medical and health sciences030104 developmental biology0302 clinical medicineAntigenPreventive and therapeutic approachesInfectious disease (medical specialty)030220 oncology & carcinogenesisAdvanced therapy medicinal products (ATMP)ImmunologyMedicineVaccination against infectious diseasebusinessRegulatory framework in the EUEx vivo
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Biostimulation proved to be the most efficient method in the comparison of in situ soil remediation treatments after a simulated oil spill accident

2016

The use of in situ techniques in soil remediation is still rare in Finland and most other European countries due to the uncertainty of the effectiveness of the techniques especially in cold regions and also due to their potential side effects on the environment. In this study, we compared the biostimulation, chemical oxidation, and natural attenuation treatments in natural conditions and pilot scale during a 16-month experiment. A real fuel spill accident was used as a model for experiment setup and soil contamination. We found that biostimulation significantly decreased the contaminant leachate into the water, including also the non-aqueous phase liquid (NAPL). The total NAPL leachate was …

0301 basic medicineBACTERIALHealth Toxicology and Mutagenesis010501 environmental sciencesBacterial growth01 natural sciencesENHANCED BIOREMEDIATIONBiostimulationSoilChemical oxidationSoil PollutantsPetroleum PollutionLeachateTEMPERATUREFinlandSoil MicrobiologyGeneral MedicineContaminationPollutionSoil contamination6. Clean waterBiodegradation EnvironmentalCREOSOTE-CONTAMINATED SOILBiodegradationResearch ArticleSTRATEGIESAmendmentcomplex mixtures03 medical and health sciencesMolecular monitoringEnvironmental ChemistryFIELD1172 Environmental sciences0105 earth and related environmental sciencesANTARCTIC SOILEnvironmental engineeringBiodegradationDEGRADATIONModels TheoreticalCarbonBiostimulation030104 developmental biology13. Climate actionSoil bioremediationHydrocarbon contaminationAccidentsEnvironmental scienceCOMMUNITIESGroundwaterWater Pollutants ChemicalEnvironmental Science and Pollution Research International
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Dynamics and predicted drug response of a gene network linking dedifferentiation with β-catenin dysfunction in hepatocellular carcinoma

2019

Background & Aims Alterations of individual genes variably affect the development of hepatocellular carcinoma (HCC). Thus, we aimed to characterize the function of tumor-promoting genes in the context of gene regulatory networks (GRNs). Methods Using data from The Cancer Genome Atlas, from the LIRI-JP (Liver Cancer – RIKEN, JP project), and from our transcriptomic, transfection and mouse transgenic experiments, we identify a GRN which functionally links LIN28B-dependent dedifferentiation with dysfunction of β-catenin (CTNNB1). We further generated and validated a quantitative mathematical model of the GRN using human cell lines and in vivo expression data. Results We found that LIN28B and C…

0301 basic medicineBeta-cateninCarcinoma HepatocellularHepatocellular carcinomaLIN28BCellGene regulatory networkPrincipal component analysisMice TransgenicBiologyTransfectionTranscriptomeCohort Studies03 medical and health sciencesMice0302 clinical medicineMathematical modelmicroRNAmedicineAnimalsHumansGene Regulatory NetworksCTNNB1Genebeta CateninHepatologySequence Analysis RNALiver NeoplasmsGene regulatory networkRNA-Binding ProteinsHGF/MET pathwayMicroRNAHep G2 CellsHCCSModels TheoreticalPrognosisPersonalized medicinedigestive system diseases030104 developmental biologymedicine.anatomical_structureCancer researchSMARCA4biology.protein030211 gastroenterology & hepatologyTranscriptome
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Stability of a Split Streptomycin Binding Aptamer

2016

Here we investigated the stability of an aptamer, which is formed by two RNA strands and binds the antibiotic streptomycin. Molecular dynamics simulations in aqueous solution confirmed the geometry and the pattern of hydrogen bond interactions that was derived from the crystal structure (1NTB). The result of umbrella sampling simulations indicated a favored streptomycin binding with a free energy of ΔGbind° = −101.7 kJ mol–1. Experimentally, the increase in oligonucleotide stability upon binding of streptomycin was probed by single-molecule force spectroscopy. Rate dependent force spectroscopy measurements revealed a decrease in the natural off-rate (koff-COMPLEX = 0.22 ± 0.16 s–1) for the …

0301 basic medicineBinding SitesAqueous solutionChemistryHydrogen bondAptamerForce spectroscopyWaterHydrogen BondingAptamers NucleotideMolecular Dynamics SimulationSurfaces Coatings and FilmsGibbs free energy03 medical and health sciencessymbols.namesakeMolecular dynamicsCrystallography030104 developmental biologyStreptomycinMaterials ChemistrysymbolsThermodynamicsPhysical and Theoretical ChemistryUmbrella samplingBinding siteThe Journal of Physical Chemistry B
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Dual Function Molecules and Processes in Cell Fate Decision: A Preface to the Special Issue

2020

A lot of water has passed under the bridge since 1999, when C.J. Jeffery stated in a pioneering review that “the idea of one gene-one protein-one function has become too simple” [...]

0301 basic medicineBiologyCatalysisInorganic Chemistrylcsh:Chemistry03 medical and health sciences0302 clinical medicineSettore BIO/10 - BiochimicaAnimalsHumanscell fate decisionPhysical and Theoretical ChemistryMolecular Biologylcsh:QH301-705.5SpectroscopyDual functiondouble-faced molecules and processesOrganic ChemistryGene Expression Regulation DevelopmentalCell DifferentiationGeneral MedicineComputer Science Applications030104 developmental biologyEditorialn/alcsh:Biology (General)lcsh:QD1-999030220 oncology & carcinogenesisNeuroscienceSignal TransductionInternational Journal of Molecular Sciences
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A sensitive real-time RT-PCR reveals a high incidence of Southern tomato virus (STV) in Spanish tomato crops

2018

[EN] Southern tomato virus (STV) is a double-stranded RNA (dsRNA) virus belonging to genus Amalgavirus (family Amalgamaviridae). STV has been detected in tomato plants showing different symptoms although it has not been demonstrated that STV is the causal agent. To study the STV incidence and its pathogenic role, a sensitive and quantitative real-time reverse transcription-polymerase chain reaction assay (RT-qPCR) was developed. The standard curve perfonned with viral RNA transcripts allowed a wide dynamic range for STV quantitation from 10(4) to 10(11) copies/ng of total RNA. STV detection by RT-qPCR was 10(2)-fold more sensitive than conventional RT-PCR or RT-LAMP and 10(4)-fold more sens…

0301 basic medicineBiologySolanum lycopersicum; Amalgaviridae; Amalgavirus; persistent viruses; RT-qPCRViruslcsh:Agriculture03 medical and health sciencesSolanum lycopersicumTranscription (biology)Plant virusGene expressionPRODUCCION VEGETALGenePersistent virusesfungiRT-qPCRlcsh:SRNAfood and beveragesMICROBIOLOGIAagriculture; plant protectionAmalgaviridaeVirologyRNA silencingAmalgavirusGENETICA030104 developmental biologyReal-time polymerase chain reactionAgronomy and Crop Science
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Dry selection and wet evaluation for the rational discovery of new anthelmintics

2017

Helminths infections remain a major problem in medical and public health. In this report, atom-based 2D bilinear indices, a TOMOCOMD-CARDD (QuBiLs-MAS module) molecular descriptor family and linear discriminant analysis (LDA) were used to find models that differentiate among anthelmintic and non-anthelmintic compounds. Two classification models obtained by using non-stochastic and stochastic 2D bilinear indices, classified correctly 86.64% and 84.66%, respectively, in the training set. Equation 1(2) correctly classified 141(135) out of 165 [85.45%(81.82%)] compounds in external validation set. Another LDA models were performed in order to get the most likely mechanism of action of anthelmin…

0301 basic medicineBiophysicsNon-stochastic and stochastic atom-based bilinear indicesBilinear interpolationLDA-based QSAR modelQuBiLs-MAS module01 natural sciencesSet (abstract data type)03 medical and health sciencesMolecular descriptorStatisticsPhysical and Theoretical ChemistryMolecular BiologySelection (genetic algorithm)MathematicsFree and open source softwareTraining setTOMOCOMD-CARDD softwareExternal validationAnthelmintic activityAtom (order theory)Computational creeningCondensed Matter PhysicsLinear discriminant analysis0104 chemical sciencesIndazole010404 medicinal & biomolecular chemistry030104 developmental biologyLead generationMolecular Physics
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Angiotensin II type 1 receptor antagonists in animal models of vascular, cardiac, metabolic and renal disease

2016

AbstractWe have reviewed the effects of angiotensin II type 1 receptor antagonists (ARBs) in various animal models of hypertension, atherosclerosis, cardiac function, hypertrophy and fibrosis, glucose and lipid metabolism, and renal function and morphology. Those of azilsartan and telmisartan have been included comprehensively whereas those of other ARBs have been included systematically but without intention of completeness. ARBs as a class lower blood pressure in established hypertension and prevent hypertension development in all applicable animal models except those with a markedly suppressed renin–angiotensin system; blood pressure lowering even persists for a considerable time after d…

0301 basic medicineBlood Pressure030204 cardiovascular system & hematologyKidneyurologic and male genital diseasesBenzoatesAnimals Genetically ModifiedRenin-Angiotensin SystemGene Knockout Techniques0302 clinical medicineAzilsartanPharmacology (medical)TelmisartanOxadiazolesKidneybiologyStrokemedicine.anatomical_structureCardiovascular DiseasesHypertensionDrug Therapy Combinationmedicine.drugmedicine.medical_specialty03 medical and health sciencesMetabolic DiseasesCulture TechniquesInternal medicineRenin–angiotensin systemmedicineAnimalsHumansAntihypertensive AgentsPharmacologyAngiotensin II receptor type 1business.industryAngiotensin-converting enzymeAtherosclerosisLipid Metabolismmedicine.diseaseDisease Models AnimalGlucose030104 developmental biologyBlood pressureEndocrinologyPathophysiology of hypertensionbiology.proteinBenzimidazolesEndothelium VascularTelmisartanbusinessAngiotensin II Type 1 Receptor BlockersPharmacology & Therapeutics
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Amorphous, Smart, and Bioinspired Polyphosphate Nano/Microparticles: A Biomaterial for Regeneration and Repair of Osteo-Articular Impairments In-Situ

2018

Using femur explants from mice as an in vitro model, we investigated the effect of the physiological polymer, inorganic polyphosphate (polyP), on differentiation of the cells of the bone marrow in their natural microenvironment into the osteogenic and chondrogenic lineages. In the form of amorphous Ca-polyP nano/microparticles, polyP retains its function to act as both an intra- and extracellular metabolic fuel and a stimulus eliciting morphogenetic signals. The method for synthesis of the nano/microparticles with the polyanionic polyP also allowed the fabrication of hybrid particles with the bisphosphonate zoledronic acid, a drug used in therapy of bone metastases in cancer patients. The r…

0301 basic medicineBone Regenerationlong bone defects; bone marrow cells; inorganic polyphosphate; microparticles; bisphosphonates; <i>Runx2</i>; <i>Sox9</i>; cathepsin-K; tumor metastases; human mesenchymal stem cellsmedicine.medical_treatmentBiocompatible MaterialsCore Binding Factor Alpha 1 SubunitZoledronic Acidlcsh:ChemistryMiceRunx2OsteogenesisPolyphosphatesFemurlcsh:QH301-705.5tumor metastasesSpectroscopymicroparticlescathepsin-KDiphosphonatesTissue ScaffoldsChemistryImidazolesBiomaterialSOX9 Transcription FactorGeneral MedicineUp-RegulationComputer Science ApplicationsCell biologyRUNX2medicine.anatomical_structureinorganic polyphosphateChondrogenesisSox9medicine.drugArticleCatalysisChondrocyteInorganic Chemistryhuman mesenchymal stem cells03 medical and health sciencesOsteoclastmedicineAnimalsHumansPhysical and Theoretical Chemistrybone marrow cellsbisphosphonatesMolecular BiologyOrganic ChemistryMesenchymal stem cellMesenchymal Stem CellsBisphosphonateRatslong bone defects030104 developmental biologyZoledronic acidlcsh:Biology (General)lcsh:QD1-999Gene Expression RegulationNanoparticlesBone marrowInternational Journal of Molecular Sciences
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Efficacy and Resistance Management Potential of a Modified Vip3C Protein for Control of Spodoptera frugiperda in Maize

2018

AbstractA modified Vip3C protein has been developed that has a spectrum of activity that has the potential to be commercially useful for pest control, and shows good efficacy against Spodoptera frugiperda in insect bioassays and field trials. For the first time Vip3A and Vip3C proteins have been compared to Cry1 and Cry2 proteins in a complete set of experiments from insect bioassays to competition binding assays to field trials, and the results of these complementary experiments are in agreement with each other. Binding assays with radiolabelled toxins and brush border membrane vesicles from S. frugiperda and Helicoverpa armigera show that the modified Vip3C protein shares binding sites wi…

0301 basic medicineBrush bordermedia_common.quotation_subject030106 microbiologyBacillus thuringiensislcsh:MedicineInsectBiologyHelicoverpa armigeraSpodopteraSpodopteraZea maysArticleInsecticide Resistance03 medical and health sciencesBacillus thuringiensisBioassayAnimalsBinding sitePest Control Biologicallcsh:Sciencemedia_commonMultidisciplinaryBinding Sitesbusiness.industryfungilcsh:RPest controlbiology.organism_classificationPlants Genetically ModifiedEndotoxinsBiochemistryLarvalcsh:QbusinessScientific Reports
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