10 research outputs found

    Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course

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    The “isomorphic subtype of diffuse astrocytoma” was identified histologically in 2004 as a supratentorial, highly differentiated glioma with low cellularity, low proliferation and focal diffuse brain infiltration. Patients typically had seizures since childhood and all were operated on as adults. To define the position of these lesions among brain tumours, we histologically, molecularly and clinically analysed 26 histologically prototypical isomorphic diffuse gliomas. Immunohistochemically, they were GFAP-positive, MAP2-, OLIG2- and CD34-negative, nuclear ATRX-expression was retained and proliferation was low. All 24 cases sequenced were IDH-wildtype. In cluster analyses of DNA methylation data, isomorphic diffuse gliomas formed a group clearly distinct from other glial/glio-neuronal brain tumours and normal hemispheric tissue, most closely related to paediatric MYB/MYBL1-altered diffuse astrocytomas and angiocentric gliomas. Half of the isomorphic diffuse gliomas had copy number alterations of MYBL1 or MYB (13/25, 52%). Gene fusions of MYBL1 or MYB with various gene partners were identified in 11/22 (50%) and were associated with an increased RNA-expression of the respective MYB-family gene. Integrating copy number alterations and available RNA sequencing data, 20/26 (77%) of isomorphic diffuse gliomas demonstrated MYBL1 (54%) or MYB (23%) alterations. Clinically, 89% of patients were seizure-free after surgery and all had a good outcome. In summary, we here define a distinct benign tumour class belonging to the family of MYB/MYBL1-altered gliomas. Isomorphic diffuse glioma occurs both in children and adults, has a concise morphology, frequent MYBL1 and MYB alterations and a specific DNA methylation profile. As an exclusively histological diagnosis may be very challenging and as paediatric MYB/MYBL1-altered diffuse astrocytomas may have the same gene fusions, we consider DNA methylation profiling very helpful for their identification

    Biological control of Alphitobius diaperinus with Steinernema rarum CUL and Heterorhabditis bacteriophora SMC and feasibility of application in rice hull

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    Chemical insecticides often are not efficient in reducing Alphitobius diaperinus populations in poultry farms and have induced insect resistance. Entomopathogenic nematodes (EPNs) appear as an alternative to pest biocontrol agents; however, their efficiency on rice hull litter is still unknown. The aim of this study was to evaluate the potential of Steinernema rarum (CUL isolate), Heterorhabditis bacteriophora (SMC isolate) and their symbiotic bacteria as biocontrol agents of A. diaperinus larvae and adults in rice hull litter. Mortality of insect adults and fifth- and seventh-instar larvae was determined in Petri dishes containing filter paper or rice hull. The effect of Xenorhabdus szentirmaii and Photorhabdus luminescens on L7 and adults in rice hull substrate was also evaluated. Moreover, the effectiveness of the EPNs was assessed in bags in an environment simulating the prevailing conditions in a broiler chicken farm. Under laboratory conditions, insect mortality was significantly affected by EPN species, substrate, insect stage and time after application. Mortality of L5 and L7 caused by EPNs in rice hulls reached a peak of 64 and 57.3 %, respectively, whereas symbiotic bacteria applied on rice hull showed low mortality rate at both insect stages. In the simulated poultry farm conditions, S. rarum and H. bacteriophora caused up to 40.8 and 50.4 % mortality of A. diaperinus larvae, respectively, but with adult mortality being low for both species. We conclude that infective juveniles from S. rarum CUL and H. bacteriophora SMC isolates can be used as biological control agents of A. diaperinus larvae in chicken litter containing rice hulls.Fil: del Valle, Eleodoro Eduardo. Universidad Nacional del Litoral. Facultad de Ciencias Agrarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Frizzo, Laureano Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Malmierca, Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Zbrun, María Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Lax, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Zoología Aplicada; ArgentinaFil: Doucet, Marcelo Edmundo. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Zoología Aplicada; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; Argentin

    Novel therapeutic targets for the treatment of heart failure

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