Electric Field Effects on Graphene Materials

Understanding the effect of electric fields on the physical and chemical properties of two-dimensional (2D) nanostructures is instrumental in the design of novel electronic and optoelectronic devices. Several of those properties are characterized in terms of the dielectric constant which play an important role on capacitance, conductivity, screening, dielectric losses and refractive index. Here we review our recent theoretical studies using density functional calculations including van der Waals interactions on two types of layered materials of similar two-dimensional molecular geometry but remarkably different electronic structures, that is, graphene and molybdenum disulphide (MoS$_2$). We focus on such two-dimensional crystals because of they complementary physical and chemical properties, and the appealing interest to incorporate them in the next generation of electronic and optoelectronic devices. We predict that the effective dielectric constant ($\varepsilon$) of few-layer graphene and MoS$_2$ is tunable by external electric fields ($E_{\rm ext}$). We show that at low fields ($E_{\rm ext}^{}<0.01$ V/\AA) $\varepsilon$ assumes a nearly constant value $\sim$4 for both materials, but increases at higher fields to values that depend on the layer thickness. The thicker the structure the stronger is the modulation of $\varepsilon$ with the electric field. Increasing of the external field perpendicular to the layer surface above a critical value can drive the systems to an unstable state where the layers are weakly coupled and can be easily separated. The observed dependence of $\varepsilon$ on the external field is due to charge polarization driven by the bias, which show several similar characteristics despite of the layer considered.Comment: Invited book chapter on Exotic Properties of Carbon Nanomatter: Advances in Physics and Chemistry, Springer Series on Carbon Materials. Editors: Mihai V. Putz and Ottorino Ori (11 pages, 4 figures, 30 references

γ-Glutamylcysteine detoxifies reactive oxygen species by acting as glutathione peroxidase-1 cofactor

Reactive oxygen species regulate redox-signaling processes, but in excess they can cause cell damage, hence underlying the aetiology of several neurological diseases. Through its ability to down modulate reactive oxygen species, glutathione is considered an essential thiol-antioxidant derivative, yet under certain circumstances it is dispensable for cell growth and redox control. Here we show, by directing the biosynthesis of γ-glutamylcysteine—the immediate glutathione precursor—to mitochondria, that it efficiently detoxifies hydrogen peroxide and superoxide anion, regardless of cellular glutathione concentrations. Knocking down glutathione peroxidase-1 drastically increases superoxide anion in cells synthesizing mitochondrial γ-glutamylcysteine. In vitro, γ-glutamylcysteine is as efficient as glutathione in disposing of hydrogen peroxide by glutathione peroxidase-1. In primary neurons, endogenously synthesized γ-glutamylcysteine fully prevents apoptotic death in several neurotoxic paradigms and, in an in vivo mouse model of neurodegeneration, γ-glutamylcysteine protects against neuronal loss and motor impairment. Thus, γ-glutamylcysteine takes over the antioxidant and neuroprotective functions of glutathione by acting as glutathione peroxidase-1 cofactor

Exclusion of PINK1 as candidate gene for the late-onset form of Parkinson's disease in two European populations

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Recently, mutations in the PINK1 (PARK6) gene were shown to rarely cause autosomal-recessively transmitted, early-onset parkinsonism. In order to evaluate whether PINK1 contributes to the risk of common late-onset PD we analysed PINK1 sequence variations. A German (85 patients) and a Norwegian cohort (90 patients) suffering from late-onset PD were screened for mutations and single nucleotide polymorphisms (SNPs) in the PINK1 gene. Both cohorts consist of well-characterized patients presenting a positive family history of PD in ~17%. Investigations were performed by single strand conformation polymorphism (SSCP), denaturating high performance liquid chromatography (DHPLC) and sequencing analyses. SNP frequencies were compared by the χ(2 )test RESULTS: Several common SNPs were identified in our cohorts, including a recently identified coding variant (Q115L) in exon 1. Genotyping of the Q115L variation did not reveal significant frequency differences between patients and controls. Pathogenic mutations in the PINK1 gene were not identified, neither in the German nor in the Norwegian cohort. CONCLUSION: Sequence variation in the PINK1 gene appears to play a marginal quantitative role in the pathogenesis of the late-onset form of PD, in German and Norwegian cohorts, if at all

Passerine Exposure to Primarily PCDFs and PCDDs in the River Floodplains Near Midland, Michigan, USA

House wren (Troglodytes aedon), tree swallow (Tachycineta bicolor), and eastern bluebird (Sialia sialis) tissues collected in study areas (SAs) downstream of Midland, Michigan (USA) contained concentrations of polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzo-p-dioxins (PCDDs) greater than in upstream reference areas (RAs) in the region. The sum of concentrations of PCDD/DFs (ΣPCDD/DFs) in eggs of house wrens and eastern bluebirds from SAs were 4- to 22-fold greater compared to those from RAs, whereas concentrations in tree swallow eggs were similar among areas. Mean concentrations of ΣPCDD/DFs and sum 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (ΣTEQsWHO-Avian), based on 1998 WHO avian toxic equivalency factors, in house wren and eastern bluebird eggs ranged from 860 (430) to 1500 (910) ng/kg wet weight (ww) and 470 (150) to 1100 (510) ng/kg ww, respectively, at the most contaminated study areas along the Tittabawassee River, whereas mean concentrations in tree swallow eggs ranged from 280 (100) to 760 (280) ng/kg ww among all locations. Concentrations of ΣPCDD/DFs in nestlings of all studied species at SAs were 3- to 50-fold greater compared to RAs. Mean house wren, tree swallow, and eastern bluebird nestling concentrations of ΣPCDD/DFs and ΣTEQsWHO-Avian ranged from 350 (140) to 610 (300) ng/kg ww, 360 (240) to 1100 (860) ng/kg ww, and 330 (100) to 1200 (690) ng/kg ww, respectively, at SAs along the Tittabawassee River. Concentrations of ΣTEQsWHO-Avian were positively correlated with ΣPCDD/DF concentrations in both eggs and nestlings of all species studied. Profiles of relative concentrations of individual congeners were dominated by furan congeners (69–84%), primarily 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,7,8-pentachlorodibenzofuran, for all species at SAs on the Tittabawassee and Saginaw rivers but were dominated by dioxin congeners at upstream RAs

Clinical trial simulation to evaluate power to compare the antiviral effectiveness of two hepatitis C protease inhibitors using nonlinear mixed effect models: a viral kinetic approach.

International audienceBACKGROUND: Models of hepatitis C virus (HCV) kinetics are increasingly used to estimate and to compare in vivo drug's antiviral effectiveness of new potent anti-HCV agents. Viral kinetic parameters can be estimated using non-linear mixed effect models (NLMEM). Here we aimed to evaluate the performance of this approach to precisely estimate the parameters and to evaluate the type I errors and the power of the Wald test to compare the antiviral effectiveness between two treatment groups when data are sparse and/or a large proportion of viral load (VL) are below the limit of detection (BLD). METHODS: We performed a clinical trial simulation assuming two treatment groups with different levels of antiviral effectiveness. We evaluated the precision and the accuracy of parameter estimates obtained on 500 replication of this trial using the stochastic approximation expectation-approximation algorithm which appropriately handles BLD data. Next we evaluated the type I error and the power of the Wald test to assess a difference of antiviral effectiveness between the two groups. Standard error of the parameters and Wald test property were evaluated according to the number of patients, the number of samples per patient and the expected difference in antiviral effectiveness. RESULTS: NLMEM provided precise and accurate estimates for both the fixed effects and the inter-individual variance parameters even with sparse data and large proportion of BLD data. However Wald test with small number of patients and lack of information due to BLD resulted in an inflation of the type I error as compared to the results obtained when no limit of detection of VL was considered. The corrected power of the test was very high and largely outperformed what can be obtained with empirical comparison of the mean VL decline using Wilcoxon test. CONCLUSION: This simulation study shows the benefit of viral kinetic models analyzed with NLMEM over empirical approaches used in most clinical studies. When designing a viral kinetic study, our results indicate that the enrollment of a large number of patients is to be preferred to small population sample with frequent assessments of VL

Estrogen protects neuronal cells from amyloid beta-induced apoptosis via regulation of mitochondrial proteins and function

BACKGROUND: Neurodegeneration in Alzheimer's disease is associated with increased apoptosis and parallels increased levels of amyloid beta, which can induce neuronal apoptosis. Estrogen exposure prior to neurotoxic insult of hippocampal neurons promotes neuronal defence and survival against neurodegenerative insults including amyloid beta. Although all underlying molecular mechanisms of amyloid beta neurotoxicity remain undetermined, mitochondrial dysfunction, including altered calcium homeostasis and Bcl-2 expression, are involved in neurodegenerative vulnerability. RESULTS: In this study, we investigated the mechanism of 17β-estradiol-induced prevention of amyloid beta-induced apoptosis of rat hippocampal neuronal cultures. Estradiol treatment prior to amyloid beta exposure significantly reduced the number of apoptotic neurons and the associated rise in resting intracellular calcium levels. Amyloid beta exposure provoked down regulation of a key antiapoptotic protein, Bcl-2, and resulted in mitochondrial translocation of Bax, a protein known to promote cell death, and subsequent release of cytochrome c. E(2 )pretreatment inhibited the amyloid beta-induced decrease in Bcl-2 expression, translocation of Bax to the mitochondria and subsequent release of cytochrome c. Further implicating the mitochondria as a target of estradiol action, in vivo estradiol treatment enhanced the respiratory function of whole brain mitochondria. In addition, estradiol pretreatment protected isolated mitochondria against calcium-induced loss of respiratory function. CONCLUSION: Therefore, we propose that estradiol pretreatment protects against amyloid beta neurotoxicity by limiting mitochondrial dysfunction via activation of antiapoptotic mechanisms

The Role of the Substantia Nigra Pars Compacta in Regulating Sleep Patterns in Rats

Background. As of late, dopaminergic neurotransmission has been recognized to be involved in the generation of sleep disturbances. Increasing evidence shows that sleep disturbances in Parkinson's disease (PD) patients are mostly related to the disease itself, rather than being a secondary phenomenon. Evidence contained in the literature lends support to the hypothesis that the dopaminergic nigrostriatal pathway is closely involved in the regulation of sleep patterns. Methodology/Principal Findings. To test this hypothesis we examined the electrophysiological activity along the sleep-wake cycle of rats submitted to a surgically induced lesion of the SNpc by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We demonstrated that a 50% lesion of the substantia nigra pars compacta (SNpc) suffices to produce disruptions of several parameters in the sleep-wake pattern of rats. A robust and constant decrease in the latency to the onset of slow wave sleep (SWS) was detected throughout the five days of recording in both light [F((22.16)) = 72.46, p<0.0001] and dark [F((22.16)) = 75.0, p<0.0001] periods. Also found was a pronounced increase in the percentage of sleep efficiency during the first four days of recording [F((21.15)) = 21.48, p<0.0001], in comparison to the sham group. Additionally, the reduction in the SNpc dopaminergic neurons provoked an ablation in the percentage of rapid eye movement sleep (REM) during three days of the sleep-wake recording period with a strong correlation (r = 0.91; p<0.0001) between the number of dopaminergic neurons lost and the percentage decrease of REM sleep on the first day of recording. On day 4, the percentage of REM sleep during the light and dark periods was increased, [F((22.16)) = 2.46, p<0.0007], a phenomenon consistent with REM rebound. Conclusions/Significance. We propose that dopaminergic neurons present in the SNpc possess a fundamental function in the regulation of sleep processes, particularly in promoting REM sleep.AFIPCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilUniv Fed Parana, Dept Farmacol, BR-80060000 Curitiba, Parana, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilFAPESP: 98/14.303-3Web of Scienc

Does Proximity to Retailers Influence Alcohol and Tobacco Use Among Latino Adolescents?

Despite decades of research surrounding determinants of alcohol and tobacco (A&T) use among adolescents, built environment influences have only recently been explored. This study used ordinal regression on 205 Latino adolescents to explore the influence of the built environment (proximity to A&T retailers) on A&T use, while controlling for recognized social predictors. The sample was 45% foreign-born. A&T use was associated with distance from respondents’ home to the nearest A&T retailer (−), acculturation (+), parents’ consistent use of contingency management (−), peer use of A&T (+), skipping school (+), attending school in immediate proximity to the US/Mexico border (+), and the interaction between the distance to the nearest retailer and parents’ consistent use of contingency management (+). The association between decreasing distance to the nearest A&T retailer and increased A&T use in Latino adolescents reveals an additional risk behavior determinant in the US–Mexico border region