169,905 research outputs found

    S -Nitrosoglutathione Reductase Plays Opposite Roles in SH-SY5Y Models of Parkinson's Disease and Amyotrophic Lateral Sclerosis

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    Oxidative and nitrosative stresses have been reported as detrimental phenomena concurring to the onset of several neurodegenerative diseases. Here we reported that the ectopic modulation of the denitrosylating enzyme S-nitrosoglutathione reductase (GSNOR) differently impinges on the phenotype of two SH-SY5Y-based in vitro models of neurodegeneration, namely, Parkinson's disease (PD) and familial amyotrophic lateral sclerosis (fALS). In particular, we provide evidence that GSNOR-knocking down protects SH-SY5Y against PD toxins, while, by contrast, its upregulation is required for G93A-SOD1 expressing cells resistance to NO-releasing drugs. Although completely opposite, both conditions are characterized by Nrf2 localization in the nuclear compartment: in the first case induced by GSNOR silencing, while in the second one underlying the antinitrosative response. Overall, our results demonstrate that GSNOR expression has different effect on neuronal viability in dependence on the stimulus applied and suggest that GSNOR could be a responsive gene downstream of Nrf2 activation. © 2015 Salvatore Rizza et al

    «[C]ome li grammatici latini» L’ingombrante eredità della tradizione grammaticale latina nella grammaticografia italiana

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    In tutta la storia delle grammatiche italiane il peso della tradizione grammaticale latina è grande e ancora visibile ai nostri giorni. Il saggio indaga, in un corpus di grammatiche prodotte dal ’400 al ’900, gli elementi di continuità che rivelano lo stretto legame tra la grammaticografia italiana e quella del mondo antico

    Aspetti della paratassi nella predicazione quattrocentesca, in Le forme e i luoghi della predicazione: atti del Seminario internazionale di studi, Macerata, 21-23 novembre 2006, a cura di C. Micaelli, G. Frenguelli, Macerata: Eum, 2009, pp. 233-253. ISBN: 978-88-605-6234-0. Scritto assieme a C. Giovanardi con esatta divisione delle parti.

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    Prendendo in esame un corpus di prediche di Bernardino da Siena e di Girolamo Savonala, lo studio si sofferma su alcuni tipi di collegamento sintattico realizzati, nel campo della paratassi, mediante la congiunzione prototipica "e". Evidenzia, in particolare, la produttività del collegamento interfrasale forte (in cui la e collega due frasi con soggetto diverso) e di alcune sue configurazioni (come la presenza, dopo "e", del gerundio e del participio, la paraipotassi, l’espressione di rapporti di causalità), spesso legate alla caratterizzazione funzionale delle parti di cui la predica si compone. Sottolinea, infine, le linee di continuità e le divergenze in questa tipologia di collegamenti frasali rispetto alla prosa media delle cronache trecentesche. Il lavoro è stato condotto dai due autori con esatta divisione delle parti

    50-Hz MF does not affect global DNA methylation of SH-SY5Y cells treated with the neurotoxin MPP+

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    Exposure to extremely low frequency magnetic fields (ELF-MFs) has been associated with an increased risk of neurodegenerative disorders. The underlying mechanisms, however, are still debated. Since epigenetics play a key role in the neurodegenerative process, we investigated whether exposure to ELF-MF (50 Hz, 1 mT) might affect global DNA methylation of SH-SY5Y dopaminergic-like neuroblastoma cells. We assessed the percentage of 5-methylcytosine (5-mC) of three repetitive interspersed sequences (ALU, LINE-1, or SATα), through pyrosequencing analysis. We demonstrated that ELF exposure (up to 72 h) does not induce any change in the methylation pattern of ALU, LINE-1, and SATα in both proliferating and differentiated SH-SY5Y cells. Furthermore, when administered in combination with 1-methyl-4-phenylpyridinium (MPP+), a neurotoxin mimicking the Parkinson's Disease (PD) phenotype, ELF-MF exposure does not trigger any modulation in the percentage of 5-mC of the repetitive elements. Our findings demonstrate that exposure to 50-Hz MF does not affect global DNA methylation in proliferating and dopaminergic differentiated SH-SY5Y cells, either under basal culture conditions or under neurotoxic stress. Bioelectromagnetics. 40:33–41, 2019. © 2018 Bioelectromagnetics Society. © 2018 Bioelectromagnetics Societ

    Indices of methylation in sperm DNA from fertile men differ between distinct geographical regions

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    STUDY QUESTION Which are the main determinants, if any, of sperm DNA methylation levels? SUMMARY ANSWER Geographical region resulted associated with the sperm methylation status assessed on genome-wide repetitive sequences. WHAT IS KNOWN ALREADY DNA methylation level, assessed on repetitive sequences from peripheral blood lymphocyte, can vary with age, gender, alcohol consumption and white blood cell counts. STUDY DESIGN, SIZE, DURATION A cross-sectional study. Individual data were collected from 269 young healthy men of proven fertility living in three geographical regions: Inuits from Greenland, Caucasians from Warsaw (Poland) and Kharkiv (Ukraine). Semen samples were collected between May 2002 and February 2004 and aliquots were immediately frozen. PARTICIPANTS/MATERIALS, SETTING, METHODS We estimated sperm DNA global methylation level (DGML) in two ways. First DNA methylation in repetitive DNA sequences (LINE-1, Satα and Alu) was quantified by PCR pyrosequencing after bisulfite conversion and second by flow cytometry (FCM) using fluorescently labeled monoclonal antibodies anti-5-methylcytosine. We analyzed whether personal characteristics and habits, body mass index, semen quality parameters, sperm chromatin integrity, biomarkers of accessory gland function and the plasma concentration of reproductive hormones were associated with sperm DNA methylation levels in men. Associations were evaluated by analysis of variance and linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE The geographical location emerged as the main determinant when using the methylation level in repetitive sequences. FCM DGML results were not associated with those from repetitive sequence analysis. No other consistent associations between methylation markers and the assessed variables were identified across countries. LIMITATIONS, REASONS FOR CAUTION The methods used are only surrogates of the actual sperm methylome and the methylation levels at individual specific loci were not explored. WIDER IMPLICATIONS OF THE FINDINGS Sperm DGML is relatively independent from semen quality parameters and is a new candidate biomarker for epidemiological studies of the impact of environmental contaminants on male fertility. STUDY FUNDING/COMPETING INTEREST(S) The study is part of the project CLEAR (Climate change, Environmental contaminants and Reproductive health) supported by the European Commission 7th framework program, contract no: FP7-ENV-2008-1-226217. No competing interest is declared. © 2014 The Author

    Exposure to perfluoroalkyl substances and sperm DNA global methylation in arctic and European populations

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    Perfluoroalkyl substances (PFASs) are widely used in a variety of industrial processes and products, and have been detected globally in humans and wildlife. PFASs are suspected to interfere with endocrine signaling and to adversely affect human reproductive health. The aim of the present study was to investigate the associations between exposure to PFASs and sperm global methylation levels in a population of non-occupationally exposed fertile men. Measurements of PFASs in serum from 262 partners of pregnant women from Greenland, Poland and Ukraine, were also carried out by liquid chromatography tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) were detected in 97% of the blood samples. Two surrogate markers were used to assess DNA global methylation levels in semen samples from the same men: (a) average DNA methylation level in repetitive DNA sequences (Alu, LINE-1, Satα) quantified by PCR-pyrosequencing after bisulfite conversion; (b) flow cytometric immunodetection of 5-methyl-cytosines. After multivariate linear regression analysis, no major consistent associations between PFASs exposure and sperm DNA global methylation endpoints could be detected. However, since weak but statistically significant associations of different PFASs with DNA hypo- and hyper-methylation were found in some of the studied populations, effects of PFASs on sperm epigenetic processes cannot be completely excluded, and this issue warrants further investigation. © 2014 Wiley Periodicals, Inc

    A proposed integrated systems approach to the radiation biology of cosmic interest: Biophysics and molecular characterization of tissues irradiated with 14 MeV neutrons

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    Low-dose exposure of ionizing radiation triggers cell-to-cell communications and tissue interplay alterations. These alterations may play a fundamental role in non-cancer effects, overwhelming the theory of the DNA centric approach. Neither the mechanisms of these effects are fully understood nor is it possible to dissect the real incidence of quality and quantity of incident radiation during in vivo exposure, overall for particulate high-linear energy transfer (LET) radiation. Moreover, the knowledge of particulate high-LET radiation is mandatory for the human deep space exploration and to gain efficiency in the dose/effect ratio for radiotherapy. The aim of this minireview was to describe an integrated system approach to the radiation biology of cosmic interest which could be set up in the framework of a future Sino-Italy cooperation among participating laboratories. We propose, in particular, to deliver X-rays and neutron irradiation at ENEAFNG (Frascati, Italy) and heavy ion irradiation at IMPCAS (Lanzhou, China) to in vivo models. The integrated system approach will focus on the correlation between the quality and quantity of radiation exposure and its in vivo biological effects. Wide range molecular profiling will analyze mainly cell and DNA damages and cell-to-cell and tissues interplay, meanwhile biochemical and chemical specific composition will be detected by infrared spectroscopy. The recently characterized alteration of leptin metabolism is discussed in more detail to present a successful example of systemic approach to cosmic radiation biology. ᄅ Accademia Nazionale dei Lincei 2013
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