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Emanuele Lombardo Cristian Sabellico Jan Hájek Veronika Staňková Tomá? Filipsky Valentina Balducci Paolo De Vito Stefano Leone Eugenia I. Bavavea Ilaria Proietti Silvestri Giuliana Righi Paolo Luly Luciano Saso Paolo Bovicelli Jens Z. Pedersen Sandra Incerpi 《PloS one》2013,8(4)
Natural polyphenol compounds are often good antioxidants, but they also cause damage to cells through more or less specific interactions with proteins. To distinguish antioxidant activity from cytotoxic effects we have tested four structurally related hydroxyflavones (baicalein, mosloflavone, negletein, and 5,6-dihydroxyflavone) at very low and physiologically relevant levels, using two different cell lines, L-6 myoblasts and THP-1 monocytes. Measurements using intracellular fluorescent probes and electron paramagnetic resonance spectroscopy in combination with cytotoxicity assays showed strong antioxidant activities for baicalein and 5,6-dihydroxyflavone at picomolar concentrations, while 10 nM partially protected monocytes against the strong oxidative stress induced by 200 µM cumene hydroperoxide. Wide range dose-dependence curves were introduced to characterize and distinguish the mechanism and targets of different flavone antioxidants, and identify cytotoxic effects which only became detectable at micromolar concentrations. Analysis of these dose-dependence curves made it possible to exclude a protein-mediated antioxidant response, as well as a mechanism based on the simple stoichiometric scavenging of radicals. The results demonstrate that these flavones do not act on the same radicals as the flavonol quercetin. Considering the normal concentrations of all the endogenous antioxidants in cells, the addition of picomolar or nanomolar levels of these flavones should not be expected to produce any detectable increase in the total cellular antioxidant capacity. The significant intracellular antioxidant activity observed with 1 pM baicalein means that it must be scavenging radicals that for some reason are not eliminated by the endogenous antioxidants. The strong antioxidant effects found suggest these flavones, as well as quercetin and similar polyphenolic antioxidants, at physiologically relevant concentrations act as redox mediators to enable endogenous antioxidants to reach and scavenge different pools of otherwise inaccessible radicals. 相似文献
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Paolo Ruggeri Andrea Splendiani Cristina Di Muri Tatiana Fioravanti Alberto Santojanni Iole Leonori Andrea De Felice Ilaria Biagiotti Piera Carpi Enrico Arneri Paola Nisi Cerioni Massimo Giovannotti Vincenzo Caputo Barucchi 《PloS one》2016,11(3)
It is well known that temporal fluctuations in small populations deeply influence evolutionary potential. Less well known is whether fluctuations can influence the evolutionary potentials of species with large census sizes. Here, we estimated genetic population parameters from as survey of polymorphic microsatellite DNA loci in archived otoliths from Adriatic European anchovy (Engraulis encrasicolus), a fish with large census sizes that supports numerous local fisheries. Stocks have fluctuated greatly over the past few decades, and the Adriatic fishery collapsed in 1987. Our results show a significant reduction of mean genetic parameters as a consequence of the population collapse. In addition, estimates of effective population size (Ne) are much smaller than those expected in a fishes with large population census sizes (Nc). Estimates of Ne indicate low effective population sizes, even before the population collapse. The ratio Ne/Ne ranged between 10−6 and 10−8, indicating a large discrepancy between the anchovy gene pool and population census size. Therefore, anchovy populations may be more vulnerable to fishery effort and environmental change than previously thought. 相似文献
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Cristina Leonarduzzi Andrea Piotti Ilaria Spanu Giovanni Giuseppe Vendramin 《Tree Genetics & Genomes》2016,12(5):95
Fragmented populations at the edges of a species’ distribution can be highly exposed to the loss of genetic variation, unless sufficient gene flow maintains their genetic connectivity. Gene movements leading to successful establishment of external gametes (i.e. effective gene flow) into fragmented populations can solely be assessed by investigating the origin of natural regeneration. This study is focused on studying gene flow patterns in two silver fir stands in Central Apennines, where the species has a highly fragmented distribution. By using nuclear and chloroplast microsatellite markers, we investigated genetic variation, fine-scale spatial genetic structure, effective gene flow rates and large-scale connectivity characterizing both stands. Similar levels of genetic variation and low genetic differentiation between stands (F ST = 0.005) and across generations were found, coupled with low inbreeding and weak to absent SGS in the adult cohort (Sp < 0.003). On the other hand, substantial differences between the two stands in terms of gene flow rates were observed. Irrespective of the parentage approach used, higher gene flow rates were found in the stand located at the upper silver fir altitudinal limit, especially for seed-mediated gene flow (0.79 in the upper stand vs. 0.48 in the lower stand). Conversely, the lower stand was characterized by a higher reproductive dominance of local adults. Our findings suggest that, despite similar levels of genetic variation and generally high gene flow rates, different processes may be acting on the two stands, reflecting varying ecological conditions. 相似文献
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Andrew Chay Ilaria Zamparo Andreas Koschinski Manuela Zaccolo Kim T. Blackwell 《PLoS computational biology》2016,12(2)
Norepinephrine, a neuromodulator that activates β-adrenergic receptors (βARs), facilitates learning and memory as well as the induction of synaptic plasticity in the hippocampus. Several forms of long-term potentiation (LTP) at the Schaffer collateral CA1 synapse require stimulation of both βARs and N-methyl-D-aspartate receptors (NMDARs). To understand the mechanisms mediating the interactions between βAR and NMDAR signaling pathways, we combined FRET imaging of cAMP in hippocampal neuron cultures with spatial mechanistic modeling of signaling pathways in the CA1 pyramidal neuron. Previous work implied that cAMP is synergistically produced in the presence of the βAR agonist isoproterenol and intracellular calcium. In contrast, we show that when application of isoproterenol precedes application of NMDA by several minutes, as is typical of βAR-facilitated LTP experiments, the average amplitude of the cAMP response to NMDA is attenuated compared with the response to NMDA alone. Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA), and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. Instead, attenuation of the cAMP response requires mechanisms upstream of adenylyl cyclase. Our model demonstrates that Gs-to-Gi switching due to PKA phosphorylation of βARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. This suggests that signaling by β-adrenergic receptors depends on temporal pattern of stimulation, and that switching may represent a novel mechanism for recruiting kinases involved in synaptic plasticity and memory. 相似文献
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Marina Padroni Andrea Bernardoni Carmine Tamborino Gloria Roversi Massimo Borrelli Andrea Saletti Alessandro De Vito Cristiano Azzini Luca Borgatti Onofrio Marcello Christopher d’Esterre Stefano Ceruti Ilaria Casetta Ting-Yim Lee Enrico Fainardi 《PloS one》2016,11(1)
Introduction
The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned.Methods
62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded.Results
Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS≤2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome.Conclusions
Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size. 相似文献29.
Ilaria Cova Francesca Clerici Annalia Rossi Valentina Cucumo Roberta Ghiretti Laura Maggiore Simone Pomati Daniela Galimberti Elio Scarpini Claudio Mariani Barbara Caracciolo 《PloS one》2016,11(3)
Background
Weight loss is common in people with Alzheimer’s disease (AD) and it could be a marker of impending AD in Mild Cognitive Impairment (MCI) and improve prognostic accuracy, if accelerated progression to AD would be shown.Aims
To assess weight loss as a predictor of dementia and AD in MCI.Methods
One hundred twenty-five subjects with MCI (age 73.8 ± 7.1 years) were followed for an average of 4 years. Two weight measurements were carried out at a minimum time interval of one year. Dementia was defined according to DSM-IV criteria and AD according to NINCDS-ADRDA criteria. Weight loss was defined as a ≥4% decrease in baseline weight.Results
Fifty-three (42.4%) MCI progressed to dementia, which was of the AD-type in half of the cases. Weight loss was associated with a 3.4-fold increased risk of dementia (95% CI = 1.5–6.9) and a 3.2-fold increased risk of AD (95% CI = 1.4–8.3). In terms of years lived without disease, weight loss was associated to a 2.3 and 2.5 years earlier onset of dementia and AD.Conclusions
Accelerated progression towards dementia and AD is expected when weight loss is observed in MCI patients. Weight should be closely monitored in elderly with mild cognitive impairment. 相似文献30.
Relief of hypoxia by angiogenesis promotes neural stem cell differentiation by targeting glycolysis 下载免费PDF全文
Christian Lange Miguel Turrero Garcia Ilaria Decimo Francesco Bifari Guy Eelen Annelies Quaegebeur Ruben Boon Hui Zhao Bram Boeckx Junlei Chang Christine Wu Ferdinand Le Noble Diether Lambrechts Mieke Dewerchin Calvin J Kuo Wieland B Huttner Peter Carmeliet 《The EMBO journal》2016,35(9):924-941
Blood vessels are part of the stem cell niche in the developing cerebral cortex, but their in vivo role in controlling the expansion and differentiation of neural stem cells (NSCs) in development has not been studied. Here, we report that relief of hypoxia in the developing cerebral cortex by ingrowth of blood vessels temporo‐spatially coincided with NSC differentiation. Selective perturbation of brain angiogenesis in vessel‐specific Gpr124 null embryos, which prevented the relief from hypoxia, increased NSC expansion at the expense of differentiation. Conversely, exposure to increased oxygen levels rescued NSC differentiation in Gpr124 null embryos and increased it further in WT embryos, suggesting that niche blood vessels regulate NSC differentiation at least in part by providing oxygen. Consistent herewith, hypoxia‐inducible factor (HIF)‐1α levels controlled the switch of NSC expansion to differentiation. Finally, we provide evidence that high glycolytic activity of NSCs is required to prevent their precocious differentiation in vivo. Thus, blood vessel function is required for efficient NSC differentiation in the developing cerebral cortex by providing oxygen and possibly regulating NSC metabolism. 相似文献