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71.
Glioblastoma is the most aggressive tumor in the CNS and is characterized by having a cancer stem cell (CSC) subpopulation
essential for tumor survival. The purinergic system plays an important role in glioma growth, since adenosine triphosphate
(ATP) can induce proliferation of glioma cells, and alteration in extracellular ATP degradation by the use of exogenous nucleotidases
dramatically alters the size of gliomas in rats. The aim of this work was to characterize the effect of the purinergic system
on glioma CSCs. Human U87 glioma cultures presented tumor spheres that express the markers of glioma cancer stem cells CD133,
Oct-4, and Nanog. Messenger RNA of several purinergic receptors were differently expressed in spheres when compared to a cell
monolayer not containing spheres. Treatment of human gliomas U87 or U343 as well as rat C6 gliomas with 100 μM of ATP reduced
the number of tumor spheres when grown in neural stem cell medium supplemented with epidermal growth factor and basic fibroblast
growth factor. Moreover, ATP caused a decline in the number of spheres observed in culture in a dose-dependent manner. ATP
also reduces the expression of Nanog, as determined by flow cytometry, as well as CD133 and Oct-4, as analyzed by flow cytometry
and RT-PCR in U87 cells. The differential expression of purinergic receptor in tumor spheres when compared to adherent cells
and the effect of ATP in reducing tumor spheres suggest that the purinergic system affects CSC biology and that ATP may be
a potential agonist for differentiation therapy. 相似文献
72.
73.
Polynucleotide kinase–phosphatase enables neurogenesis via multiple DNA repair pathways to maintain genome stability 下载免费PDF全文
Mikio Shimada Lavinia C Dumitrache Helen R Russell Peter J McKinnon 《The EMBO journal》2015,34(19):2465-2480
Polynucleotide kinase–phosphatase (PNKP) is a DNA repair factor possessing both 5′-kinase and 3′-phosphatase activities to modify ends of a DNA break prior to ligation. Recently, decreased PNKP levels were identified as the cause of severe neuropathology present in the human microcephaly with seizures (MCSZ) syndrome. Utilizing novel murine Pnkp alleles that attenuate expression and a T424GfsX48 frame-shift allele identified in MCSZ individuals, we determined how PNKP inactivation impacts neurogenesis. Mice with PNKP inactivation in neural progenitors manifest neurodevelopmental abnormalities and postnatal death. This severe phenotype involved defective base excision repair and non-homologous end-joining, pathways required for repair of both DNA single- and double-strand breaks. Although mice homozygous for the T424GfsX48 allele were lethal embryonically, attenuated PNKP levels (akin to MCSZ) showed general neurodevelopmental defects, including microcephaly, indicating a critical developmental PNKP threshold. Directed postnatal neural inactivation of PNKP affected specific subpopulations including oligodendrocytes, indicating a broad requirement for genome maintenance, both during and after neurogenesis. These data illuminate the basis for selective neural vulnerability in DNA repair deficiency disease. 相似文献
74.
Tan L 《Behavioural processes》2008,78(2):279-284
The retention interval (RI) between the sample and production phase in a numerical reproduction task was varied to determine whether a "produce-small" effect would be obtained with increased delays. Four pigeons were trained with a retention interval of 2s, and then tested with intervals of 0.5s and 8s. Results showed a number-dependent, "produce-large" effect-response number increased when RI was increased-analyses of average response number and accuracy suggested RI affected responding most on the 2-flash trials with an 8-s RI. Additionally, discrimination between trial types decreased as RI increased. Existing explanations for the "choose-short/small" effect appear unable to account for these results; however the "produce-large" effect may be attributed to a disruption in stimulus control over responding. 相似文献
75.
76.
Andreas Holzinger Lavinia Di Piazza Cornelius Lütz Michael Y. Roleda 《Phycological Research》2011,59(4):221-235
Fertile Saccharina latissima sporophytes, collected in the Kongsfjorden, Ny‐Ålesund, Spitsbergen, Norway (78°56.87′ N, 11°51.64′ E) were investigated in relation to its sensitivity to experimentally enhanced ultraviolet radiation : photosynthetically active radiation (UVR : PAR) ratios. Irradiance of UVR were 4.30 W m?2 of UV‐A (320–400 nm) and 0.40 W m?2 of UV‐B (280–320 nm), and PAR (400–700 nm) was ~4.30 W m?2 (=20 µmol photons m?2 s?1). Excised soral (sporogenic) and non‐soral (vegetative) tissues were separately irradiated for 16 h at 7°C. Transmission electron microscopy showed abundant occurrence of physodes, electron dense particles (~300–600 nm) in the sorus. Paraphysis cells, with partly crystalline content, large mitochondria and abundant golgi bodies were towering over the sporangia. In soral tissue, cells were not visibly altered by the PAR + UVR irradiation. The chloroplasts, flagella and nucleus of unreleased meiospores inside the sporangial parent cells were visibly intact. Severe changes in the chloroplast structure of vegetative tissue occurred after PAR + UVR irradiation. These changes included wrinkling and dilatation of the thylakoid membranes, and appearance of electron translucent areas inside the chloroplasts. In vegetative cells exposed to PAR + UVR, the total amount of physodes, was slightly higher as in cells exposed to PAR only. Initial values of optimum quantum yield of photosystem II (Fv/Fm) were 0.743 ± 0.04 in non‐soral and 0.633 ± 0.04 in soral tissue. Vegetative tissue was observed to be more sensitive to radiant exposure of PAR and PAR + UVR compared to reproductive tissue. Under PAR, a 20% reduction in Fv/Fm was observed in non‐soral compared to no reduction in soral tissue, whereas under PAR + UVR, 60% and 33% reduction in Fv/Fm was observed in non‐soral and soral tissues, respectively. This can be attributed to the corresponding three times higher antiradical power (ARP) capacity in soral compared to non‐soral tissue. 相似文献
77.
78.
Marian Beekman Hélène Blanché Markus Perola Anti Hervonen Vladyslav Bezrukov Ewa Sikora Friederike Flachsbart Lene Christiansen Anton J. M. De Craen Tom B. L. Kirkwood Irene Maeve Rea Michel Poulain Jean‐Marie Robine Silvana Valensin Maria Antonietta Stazi Giuseppe Passarino Luca Deiana Efstathios S. Gonos Lavinia Paternoster Thorkild I. A. Sørensen Qihua Tan Quinta Helmer Erik B. van den Akker Joris Deelen Francesca Martella Heather J. Cordell Kristin L. Ayers James W. Vaupel Outi Törnwall Thomas E. Johnson Stefan Schreiber Mark Lathrop Axel Skytthe Rudi G. J. Westendorp Kaare Christensen Jutta Gampe Almut Nebel Jeanine J. Houwing‐Duistermaat Pieternella Eline Slagboom Claudio Franceschi the GEHA consortium 《Aging cell》2013,12(2):184-193
Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome‐wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12‐q22 (LOD = 2.95), chromosome 19p13.3‐p13.11 (LOD = 3.76), and chromosome 19q13.11‐q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed‐effect meta‐analysis approach, rs4420638 at the TOMM40/APOE/APOC1 gene locus showed significant association with longevity (P‐value = 9.6 × 10?8). By combined modeling of linkage and association, we showed that association of longevity with APOEε4 and APOEε2 alleles explain the linkage at 19q13.11‐q13.32 with P‐value = 0.02 and P‐value = 1.0 × 10?5, respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12‐q22, and 19p13.3‐p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity. 相似文献
79.
Manuela Basso Giuseppina Samengo Giovanni Nardo Tania Massignan Giuseppina D'Alessandro Silvia Tartari Lavinia Cantoni Marianna Marino Cristina Cheroni Silvia De Biasi Maria Teresa Giordana Michael J. Strong Alvaro G. Estevez Mario Salmona Caterina Bendotti Valentina Bonetto 《PloS one》2009,4(12)
Background
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease, and protein aggregation has been proposed as a possible pathogenetic mechanism. However, the aggregate protein constituents are poorly characterized so knowledge on the role of aggregation in pathogenesis is limited.Methodology/Principal Findings
We carried out a proteomic analysis of the protein composition of the insoluble fraction, as a model of protein aggregates, from familial ALS (fALS) mouse model at different disease stages. We identified several proteins enriched in the detergent-insoluble fraction already at a preclinical stage, including intermediate filaments, chaperones and mitochondrial proteins. Aconitase, HSC70 and cyclophilin A were also significantly enriched in the insoluble fraction of spinal cords of ALS patients. Moreover, we found that the majority of proteins in mice and HSP90 in patients were tyrosine-nitrated. We therefore investigated the role of nitrative stress in aggregate formation in fALS-like murine motor neuron-neuroblastoma (NSC-34) cell lines. By inhibiting nitric oxide synthesis the amount of insoluble proteins, particularly aconitase, HSC70, cyclophilin A and SOD1 can be substantially reduced.Conclusion/Significance
Analysis of the insoluble fractions from cellular/mouse models and human tissues revealed novel aggregation-prone proteins and suggests that nitrative stress contribute to protein aggregate formation in ALS. 相似文献80.
Laura von Schantz Fredrika Gullfot Sebastian Scheer Lada Filonova Lavinia Cicortas Gunnarsson James E Flint Geoffrey Daniel Eva Nordberg-Karlsson Harry Brumer Mats Ohlin 《BMC biotechnology》2009,9(1):92