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showing 10 items of 5435 documents

Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.

2019

Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of…

0301 basic medicineMaleCancer ResearchBiopsyL-amp GB EGFR-low amplified glioblastomamedicine.disease_causewt wildtypeMYBPC3 myosin-binding protein C0302 clinical medicineHIC1 hypermethylated in cancer 1Gene duplicationIn Situ Hybridization FluorescenceIDH2 isocitrate dehydrogenase 2MutationRB-pat RB signaling pathwayEGFRvIII epidermal growth factor receptor variant number IIIPAH phenylalanine hydroxylaseGBM glioblastoma IDH-wildtype (glioblastoma multiforme primary glioblastoma).ANOVA ANalysis Of VArianceN-amp GB EGFR-no amplified glioblastomaMiddle AgedCDKN2A cyclin-dependent kinase inhibitor 2Alcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogensPrognosisPrimary tumorImmunohistochemistryH-amp GB EGFR-high amplified glioblastomaErbB ReceptorsTKR-pat tyrosine-kinase receptors signaling pathway030220 oncology & carcinogenesisDisease ProgressionCDK6 cyclin-dependent kinase 6CDH1 Cadherin 1FemaleCREM cAMP response element modulatorIHC immunohistochemistryAdultOriginal articleDNA Copy Number VariationsCDKN1B cyclin-dependent kinase inhibitor 1BBiologyRARB retinoic acid receptor betaCNS central nervous systemlcsh:RC254-282IDH1 isocitrate dehydrogenase 1BCL2 B-cell cll/ lymphoma 2CNAs copy number algerationsWHO World Health Organization03 medical and health sciencesYoung Adultp53-pat p53 signaling pathwaymedicineBiomarkers TumorTMA tissue microarrayPTENHumansProtein kinase BPI3K/AKT/mTOR pathwaySurvival analysisAgedGenetic heterogeneityGene AmplificationGFAP glial fibrillary acidic proteinMLPA multiplex ligation-dependent probe amplificationmedicine.diseaseFISH fluorescence in situ hibridizationSurvival AnalysisCDKN2B cyclin-dependent kinase inhibitor 2BPTEN phosphatase and tensin homologEGFR epidermal growth factor receptorCNV-load load of copy number variations030104 developmental biologyMutationPARK2 parkinCancer researchbiology.proteinTCGA The Cancer Genome AtlasLARGE1 acetylglucosaminyltransferase-like protein 1GlioblastomaCHD7 Chromodomain Helicase DNA Binding Protein 7DAPI 4′6-diamidino-2-phenylindoleNeoplasia (New York, N.Y.)
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Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia

2019

Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562–3468). We observed a genome-wide significant effect (p < 1 × 10…

0301 basic medicineMaleCandidate geneMultifactorial InheritanceImaging geneticsQH301 BiologyLANGUAGEGenome-wide association study3124 Neurology and psychiatryCANDIDATE GENESDyslexiaCohort StudiesREADING-DISABILITYMOLECULAR-GENETICS0302 clinical medicineCognitionAUTOMATIZED NAMING RANChildSUSCEPTIBILITY LOCUSRapid automatized namingR2CSHORT-TERM-MEMORY~DC~IMAGING-GENETICSRJ Pediatrics[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive SciencesPsychiatry and Mental healthDyslexia/geneticsAnxietyFemalemedicine.symptomBDCRC0321 Neuroscience. Biological psychiatry. NeuropsychiatryClinical psychologyNeuroinformaticsAdultReading disabilityAdolescentGenotypeRJPolymorphism Single NucleotideArticlelcsh:RC321-571ENVIRONMENTAL-INFLUENCES03 medical and health sciencesCellular and Molecular NeuroscienceQH301Young AdultmedicinedysleksiaHumansGenetic Predisposition to Diseaselcsh:Neurosciences. Biological psychiatry. NeuropsychiatryBiological Psychiatrygeenitbusiness.industryDyslexiaDASmedicine.diseaseComorbiditypredictors030104 developmental biology[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human geneticsRC0321DEVELOPMENTAL DYSLEXIAbusiness030217 neurology & neurosurgeryGenome-Wide Association Study
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Heterozygous deletion of the LRFN2 gene is associated with working memory deficits

2016

International audience; Learning disabilities (LDs) are a clinically and genetically heterogeneous group of diseases. Array-CGH and high-throughput sequencing have dramatically expanded the number of genes implicated in isolated intellectual disabilities and LDs, highlighting the implication of neuron-specific post-mitotic transcription factors and synaptic proteins as candidate genes. We report a unique family diagnosed with autosomal dominant learning disability and a 6p21 microdeletion segregating in three patients. The 870 kb microdeletion encompassed the brain-expressed gene LRFN2, which encodes for a synaptic cell adhesion molecule. Neuropsychological assessment identified selective w…

0301 basic medicineMaleCandidate genefamilyspeechHippocampal formationRats Sprague-Dawley0302 clinical medicineBorderline intellectual functioningNeuropsychological assessmentChilddisordersGenetics (clinical)Cells Culturedadhesion-like moleculesMembrane Glycoproteinsmedicine.diagnostic_testLearning DisabilitiesBrainMagnetic Resonance Imaging3. Good healthPedigreeMemory Short-TermBrain sizeFemaleAdultHeterozygotenmda receptorautismNerve Tissue ProteinsBiologyReceptors N-Methyl-D-AspartateArticle03 medical and health sciencesFluorodeoxyglucose F18[ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathologyexpressionGeneticsmedicineAnimalsHumansMemory DisorderslanguageGenetic heterogeneityWorking memoryMembrane Proteinsdown-syndromeRats030104 developmental biologyEndophenotypePositron-Emission TomographySynapsesshort-termRadiopharmaceuticalsNeuroscience030217 neurology & neurosurgeryGene Deletion[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
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Synergistic action of CB1 and 5-HT2B receptors in preventing pilocarpine-induced status epilepticus in rats

2019

Abstract Endocannabinoids (eCBs) and serotonin (5-HT) play a neuromodulatory role in the central nervous system. Both eCBs and 5-HT regulate neuronal excitability and their pharmacological potentiation has been shown to control seizures in pre-clinical and human studies. Compelling evidence indicates that eCB and 5-HT systems interact to modulate several physiological and pathological brain functions, such as food intake, pain, drug addiction, depression, and anxiety. Nevertheless, there is no evidence of an eCB/5-HT interaction in experimental and human epilepsies, including status epilepticus (SE). Here, we performed video-EEG recording in behaving rats treated with the pro-convulsant age…

0301 basic medicineMaleCannabinoid receptormedicine.medical_treatmentPharmacologySettore BIO/09 - Fisiologia0302 clinical medicineStatus Epilepticus5-HT2BEEGStatus epilepticuPilocarpineCalcium Channel BlockersEndocannabinoid systemCB1Clinical applicationNeurologyPilocarpinemedicine.symptommedicine.drugReceptorAM251AgonistSerotoninEndocannabinoid systemmedicine.drug_classMorpholinesCannabinoid receptors; Clinical applications; EEG; Endocannabinoid system; Serotonin; Status epilepticus; Synergistic interactions; Animals; Benzoxazines; Calcium Channel Blockers; Male; Morpholines; Muscarinic Agonists; Naphthalenes; Pilocarpine; Rats; Rats Sprague-Dawley; Receptor Cannabinoid CB1; Receptor Serotonin 5-HT2B; Serotonin 5-HT2 Receptor Agonists; Status EpilepticusStatus epilepticusClinical applicationsMuscarinic AgonistsNaphthaleneslcsh:RC321-57103 medical and health sciencesmedicineAnimalsCannabinoid receptorslcsh:Neurosciences. Biological psychiatry. NeuropsychiatryCannabinoidbusiness.industryAntagonistSynergistic interactionsBenzoxazinesRats030104 developmental biologySerotoninCannabinoidSprague-Dawleybusiness030217 neurology & neurosurgerySerotonin 5-HT2 Receptor Agonists
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Activation of Corticothalamic Layer 6 Cells Decreases Angular Tuning in Mouse Barrel Cortex.

2019

In the mouse whisker system, the contribution of L6 corticothalamic cells (L6 CT) to cortical and thalamic processing of the whisker deflection direction was investigated. A genetically defined population of L6 CT cells project to infragranular GABAergic interneurons that hyperpolarize neurons in somatosensory barrel cortex (BC). Optogenetic activation of these neurons switched BC to an adapted mode in which excitatory cells lost their angular tuning. In contrast, however, this was not the case with a general activation of inhibitory interneurons via optogenetic activation of Gad2-expressing cells. The decrease in angular tuning, when L6 CT cells were activated, was due to changes in cortic…

0301 basic medicineMaleCognitive NeurosciencePopulationNeuroscience (miscellaneous)OptogeneticsSomatosensory systemInhibitory postsynaptic potentiallcsh:RC321-57103 medical and health sciencesCellular and Molecular NeuroscienceMice0302 clinical medicineThalamusexcitation inhibition balancedirection selectivitymedicineAnimalsGABAergic Neuronseducationlcsh:Neurosciences. Biological psychiatry. NeuropsychiatryOriginal ResearchNeuronseducation.field_of_studyAfferent PathwaysNeocortexGAD2NTSR1ChemistryNeural InhibitionSomatosensory CortexBarrel cortexSensory Systemslayer 6030104 developmental biologymedicine.anatomical_structurenervous systemTouch PerceptionVibrissaeExcitatory postsynaptic potentialGABAergicFemaleNeuroscience030217 neurology & neurosurgeryNeuroscienceFrontiers in neural circuits
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Sugar-sweetened and artificially-sweetened beverages and changes in cognitive function in the SUN project.

2019

Background: Sugar-sweetened beverages (SSB) and artificially-sweetened beverages (ASB) have been inconsistently associated with declines in cognitive function. Because of their low caloric content ...

0301 basic medicineMaleMedicine (miscellaneous)Neuropsychological Tests03 medical and health sciences0302 clinical medicineCognitionmedicineDementiaHumansCognitive DysfunctionFood scienceLongitudinal StudiesProspective StudiesSugarAgedSugar-Sweetened Beverages030109 nutrition & dieteticsNutrition and Dieteticsbusiness.industryGeneral Neurosciencedigestive oral and skin physiologyArtificially Sweetened Beveragesnutritional and metabolic diseasesfood and beveragesCaloric theoryCognitionGeneral MedicineMiddle Agedmedicine.diseasestomatognathic diseasesSpainbusinesshuman activities030217 neurology & neurosurgeryNutritional neuroscience
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Selection of the Optimal Algorithm for Real-Time Estimation of Beta Band Power during DBS Surgeries in Patients with Parkinson's Disease

2017

Deep Brain Stimulation (DBS) is a surgical procedure for the treatment of motor disorders in patients with Parkinson’s Disease (PD). DBS involves the application of controlled electrical stimuli to a given brain structure. The implantation of the electrodes for DBS is performed by a minimally invasive stereotactic surgery where neuroimaging and microelectrode recordings (MER) are used to locate the target brain structure. The Subthalamic Nucleus (STN) is often chosen for the implantation of stimulation electrodes in DBS therapy. During the surgery, an intraoperative validation is performed to locate the dorsolateral region of STN. Patients with PD reveal a high power in the β band (frequenc…

0301 basic medicineMaleParkinson's diseaseDeep brain stimulationStereotactic surgeryTime FactorsGeneral Computer ScienceArticle SubjectGeneral Mathematicsmedicine.medical_treatmentDeep Brain StimulationElectroencephalographylcsh:Computer applications to medicine. Medical informaticsSignalNeurosurgical ProceduresStatistics Nonparametriclcsh:RC321-57103 medical and health sciences0302 clinical medicineNeuroimagingSubthalamic NucleusmedicineHumansPerioperative Periodlcsh:Neurosciences. Biological psychiatry. Neuropsychiatrymedicine.diagnostic_testFourier Analysisbusiness.industryGeneral NeuroscienceSpectral density estimationElectroencephalographyParkinson DiseaseGeneral Medicinemedicine.diseasenervous system diseasesSubthalamic nucleus030104 developmental biologysurgical procedures operativenervous systemlcsh:R858-859.7FemalebusinessBeta RhythmMicroelectrodes030217 neurology & neurosurgeryAlgorithmsBiomedical engineeringResearch ArticleComputational Intelligence and Neuroscience
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Combined effects of the PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7 rs641738 variants on NAFLD severity: a multicenter biopsy-based study.

2016

The PNPLA3 p.I148M, TM6SF2 p.E167K, and MBOAT7 rs641738 variants represent genetic risk factors for nonalcoholic fatty liver disease (NAFLD). Here we investigate if these polymorphisms modulate both steatosis and fibrosis in patients with NAFLD. We recruited 515 patients with NAFLD (age 16–88 years, 280 female patients). Liver biopsies were performed in 320 patients. PCR-based assays were used to genotype the PNPLA3, TM6SF2, and MBOAT7 variants. Carriers of the PNPLA3 and TM6SF2 risk alleles showed increased serum aspartate aminotransferase and alanine transaminase activities (P 0.05). The MBOAT7 variant was solely associated with increased fibrosis (P = 0.046). In the multivariate model, v…

0301 basic medicineMalePathologyBiopsyBiochemistryGastroenterologySeverity of Illness Index0302 clinical medicineEndocrinologyFibrosisNon-alcoholic Fatty Liver DiseaseGenotypeNonalcoholic fatty liver diseaseAged 80 and overeducation.field_of_studybiologyFatty liverMiddle AgedLiver030211 gastroenterology & hepatologyFemaleAdultmedicine.medical_specialtyAdolescentGenotypePolymorphism Single Nucleotide03 medical and health sciencesYoung AdultInternal medicinemedicineHumansAdiponutrinGenetic Predisposition to DiseaseeducationAllelesGenetic Association StudiesAgedbusiness.industryMembrane ProteinsCell BiologyLipasemedicine.diseaseFibrosisFatty Liver030104 developmental biologyAlanine transaminasebiology.proteinSteatosisbusinessPatient-Oriented and Epidemiological ResearchAcyltransferasesTM6SF2Journal of lipid research
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Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium

2017

AbstractBarrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4α. A new organ culture system for adult murine oesophagus is described. Using this, Cdx2 and HNF4α were ectopically expressed by adenoviral infe…

0301 basic medicineMalePathologyCancer ResearchEsophageal NeoplasmsBiopsyEpitheliumMice0302 clinical medicineMetaplasiaCDX2 Transcription FactorCDX2CàncerOesophageal cancerAnatomyNeoplasm ProteinsBarrett's oesophagusGene Expression Regulation Neoplasticmedicine.anatomical_structureHepatocyte Nuclear Factor 4Loricrin/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being030211 gastroenterology & hepatologymedicine.symptomVillinHepatocyte nuclear factor 4-alphaAdultmedicine.medical_specialtyStratified squamous epitheliumBiologyAdenocarcinomaOrgan cultureArticle03 medical and health sciencesBarrett EsophagusEsophagusOrgan Culture TechniquesSDG 3 - Good Health and Well-beingmedicineAnimalsHumansMolecular BiologyHNF4αMetaplasiaHistologiaCell BiologyEpitheliumdigestive system diseases030104 developmental biologybiology.proteinEctopic expressionDevelopmental Biology
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Early miR-223 Upregulation in Gastroesophageal Carcinogenesis

2017

Objectives: To test miR-223 upregulation during gastric (intestinal-type) and Barrett esophageal carcinogenesis. Methods: miR-223 expression was assessed by quantitative reverse transcription polymerase chain reaction in a series of 280 gastroesophageal biopsy samples representative of the whole spectrum of phenotypic changes involved in both carcinogenetic cascades. The results were further validated by in situ hybridization on multiple tissue specimens obtained from six surgically treated gastroesophageal adenocarcinomas. miR-223 expression was also assessed in plasma samples from 30 patients with early stage (ie, stages I and II) gastroesophageal adenocarcinoma and relative controls. Res…

0301 basic medicineMalePathologyEsophageal NeoplasmsAtrophic gastritisCarcinogenesisPreneoplastic lesionsBarrett carcinogenesisGastroenterology0302 clinical medicineEarly Detection of CancerIn Situ HybridizationBarrett carcinogenesis; Gastric adenocarcinoma; Preneoplastic lesions; microRNA; Adenocarcinoma; Aged; Barrett Esophagus; Biomarkers Tumor; Carcinogenesis; Early Detection of Cancer; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; In Situ Hybridization; Male; MicroRNAs; Middle Aged; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms; Up-RegulationTumormedicine.diagnostic_testmicroRNAReverse Transcriptase Polymerase Chain ReactionBarrett carcinogenesiIntestinal metaplasiaGeneral MedicineMiddle AgedUp-RegulationReverse transcription polymerase chain reactionmedicine.anatomical_structure030220 oncology & carcinogenesisAdenocarcinomaBiomarker (medicine)FemaleEsophagogastric Junctionmedicine.medical_specialty2734BiologyAdenocarcinoma03 medical and health sciencesBarrett EsophagusStomach NeoplasmsInternal medicineBiopsyBiomarkers TumormedicineHumansEsophagusAgedRetrospective StudiesGastric adenocarcinomaCancermedicine.diseasedigestive system diseasesBarrett carcinogenesis; Gastric adenocarcinoma; microRNA; Preneoplastic lesions; Adenocarcinoma; Aged; Barrett Esophagus; Biomarkers Tumor; Carcinogenesis; Early Detection of Cancer; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; In Situ Hybridization; Male; MicroRNAs; Middle Aged; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms; Up-Regulation; 2734MicroRNAs030104 developmental biologyBiomarkers
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