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911.
Lucian Farcal Fernando Torres Andón Luisana Di Cristo Bianca Maria Rotoli Ovidio Bussolati Enrico Bergamaschi Agnieszka Mech Nanna B. Hartmann Kirsten Rasmussen Juan Riego-Sintes Jessica Ponti Agnieszka Kinsner-Ovaskainen Fran?ois Rossi Agnes Oomen Peter Bos Rui Chen Ru Bai Chunying Chen Louise Rocks Norma Fulton Bryony Ross Gary Hutchison Lang Tran Sarah Mues Rainer Ossig Jürgen Schnekenburger Luisa Campagnolo Lucia Vecchione Antonio Pietroiusti Bengt Fadeel 《PloS one》2015,10(5)
Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with the objective to identify and evaluate in vitro test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS). Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues). The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO2 NMs with different surface chemistry – hydrophilic (NM-103) and hydrophobic (NM-104), two forms of ZnO – uncoated (NM-110) and coated with triethoxycapryl silane (NM-111) and two SiO2 NMs produced by two different manufacturing techniques – precipitated (NM-200) and pyrogenic (NM-203). Cell specific toxicity effects of all NMs were observed; macrophages were the most sensitive cell type after short-term exposures (24-72h) (ZnO>SiO2>TiO2). Longer term exposure (7 to 21 days) significantly affected the cell barrier integrity in the presence of ZnO, but not TiO2 and SiO2, while the embryonic stem cell test (EST) classified the TiO2 NMs as potentially ‘weak-embryotoxic’ and ZnO and SiO2 NMs as ‘non-embryotoxic’. A hazard ranking could be established for the representative NMs tested (ZnO NM-110 > ZnO NM-111 > SiO2 NM-203 > SiO2 NM-200 > TiO2 NM-104 > TiO2 NM-103). This ranking was different in the case of embryonic tissues, for which TiO2 displayed higher toxicity compared with ZnO and SiO2. Importantly, the in vitro methodology applied could identify cell- and NM-specific responses, with a low variability observed between different test assays. Overall, this testing approach, based on a battery of cellular systems and test assays, complemented by an exhaustive physico-chemical characterization of NMs, could be deployed for the development of an ITS suitable for risk assessment of NMs. This study also provides a rich source of data for modeling of NM effects. 相似文献
912.
Manish S. Dalwani Mary Agnes McMahon Susan K. Mikulich-Gilbertson Susan E. Young Michael F. Regner Kristen M. Raymond Shannon K. McWilliams Marie T. Banich Jody L. Tanabe Thomas J Crowley Joseph T. Sakai 《PloS one》2015,10(5)
ObjectiveStructural neuroimaging studies have demonstrated lower regional gray matter volume in adolescents with severe substance and conduct problems. These research studies, including ours, have generally focused on male-only or mixed-sex samples of adolescents with conduct and/or substance problems. Here we compare gray matter volume between female adolescents with severe substance and conduct problems and female healthy controls of similar ages. Hypotheses: Female adolescents with severe substance and conduct problems will show significantly less gray matter volume in frontal regions critical to inhibition (i.e. dorsolateral prefrontal cortex and ventrolateral prefrontal cortex), conflict processing (i.e., anterior cingulate), valuation of expected outcomes (i.e., medial orbitofrontal cortex) and the dopamine reward system (i.e. striatum).MethodsWe conducted whole-brain voxel-based morphometric comparison of structural MR images of 22 patients (14-18 years) with severe substance and conduct problems and 21 controls of similar age using statistical parametric mapping (SPM) and voxel-based morphometric (VBM8) toolbox. We tested group differences in regional gray matter volume with analyses of covariance, adjusting for age and IQ at p<0.05, corrected for multiple comparisons at whole-brain cluster-level threshold.ResultsFemale adolescents with severe substance and conduct problems compared to controls showed significantly less gray matter volume in right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, medial orbitofrontal cortex, anterior cingulate, bilateral somatosensory cortex, left supramarginal gyrus, and bilateral angular gyrus. Considering the entire brain, patients had 9.5% less overall gray matter volume compared to controls.ConclusionsFemale adolescents with severe substance and conduct problems in comparison to similarly aged female healthy controls showed substantially lower gray matter volume in brain regions involved in inhibition, conflict processing, valuation of outcomes, decision-making, reward, risk-taking, and rule-breaking antisocial behavior. 相似文献
913.
Jose L. Rapanan Agnes S. Pascual Chandana K. Uppalapati Kimbal E. Cooper Kathryn J. Leyva Elizabeth E. Hull 《Journal of visualized experiments : JoVE》2015,(96)
Due to their unique motile properties, fish keratocytes dissociated from explant cultures have long been used to study the mechanisms of single cell migration. However, when explants are established, these cells also move collectively, maintaining many of the features which make individual keratocytes an attractive model to study migration: rapid rates of motility, extensive actin-rich lamellae with a perpendicular actin cable, and relatively constant speed and direction of migration. In early explants, the rapid interconversion of cells migrating individually with those migrating collectively allows the study of the role of cell-cell adhesions in determining the mode of migration, and emphasizes the molecular links between the two modes of migration. Cells in later explants lose their ability to migrate rapidly and collectively as an epithelial to mesenchymal transition occurs and genes associated with wound healing and inflammation are differentially expressed. Thus, keratocyte explants can serve as an in vitro model for the reepithelialization that occurs during cutaneous wound healing and can represent a unique system to study mechanisms of collective cell migration in the context of a defined program of gene expression changes. A variety of mutant and transgenic zebrafish lines are available, which allows explants to be established from fish with different genetic backgrounds. This allows the role of different proteins within these processes to be uniquely addressed. The protocols outlined here describe an easy and effective method for establishing these explant cultures for use in a variety of assays related to collective cell migration. 相似文献
914.
Grace Y. Sun Zihong Chen Kimberly J. Jasmer Dennis Y. Chuang Zezong Gu Mark Hannink Agnes Simonyi 《PloS one》2015,10(10)
A large group of flavonoids found in fruits and vegetables have been suggested to elicit health benefits due mainly to their anti-oxidative and anti-inflammatory properties. Recent studies with immune cells have demonstrated inhibition of these inflammatory responses through down-regulation of the pro-inflammatory pathway involving NF-κB and up-regulation of the anti-oxidative pathway involving Nrf2. In the present study, the murine BV-2 microglial cells were used to compare anti-inflammatory activity of quercetin and cyanidin, two flavonoids differing by their alpha, beta keto carbonyl group. Quercetin was 10 folds more potent than cyanidin in inhibition of lipopolysaccharide (LPS)-induced NO production as well as stimulation of Nrf2-induced heme-oxygenase-1 (HO-1) protein expression. In addition, quercetin demonstrated enhanced ability to stimulate HO-1 protein expression when cells were treated with LPS. In an attempt to unveil mechanism(s) for quercetin to enhance Nrf2/HO-1 activity under endotoxic stress, results pointed to an increase in phospho-p38MAPK expression upon addition of quercetin to LPS. In addition, pharmacological inhibitors for phospho-p38MAPK and MEK1/2 for ERK1/2 further showed that these MAPKs target different sites of the Nrf2 pathway that regulates HO-1 expression. However, inhibition of LPS-induced NO by quercetin was not fully reversed by TinPPIX, a specific inhibitor for HO-1 activity. Taken together, results suggest an important role of quercetin to regulate inflammatory responses in microglial cells and its ability to upregulate HO-1 against endotoxic stress through involvement of MAPKs. 相似文献
915.
Natalia E. Bernardes Agnes A. S. Takeda Thiago R. Dreyer Fernanda Z. Freitas Maria Célia Bertolini Marcos R. M. Fontes 《PloS one》2015,10(6)
Neurospora crassa is a filamentous fungus that has been extensively studied as a model organism for eukaryotic biology, providing fundamental insights into cellular processes such as cell signaling, growth and differentiation. To advance in the study of this multicellular organism, an understanding of the specific mechanisms for protein transport into the cell nucleus is essential. Importin-α (Imp-α) is the receptor for cargo proteins that contain specific nuclear localization signals (NLSs) that play a key role in the classical nuclear import pathway. Structures of Imp-α from different organisms (yeast, rice, mouse, and human) have been determined, revealing that this receptor possesses a conserved structural scaffold. However, recent studies have demonstrated that the Impα mechanism of action may vary significantly for different organisms or for different isoforms from the same organism. Therefore, structural, functional, and biophysical characterization of different Impα proteins is necessary to understand the selectivity of nuclear transport. Here, we determined the first crystal structure of an Impα from a filamentous fungus which is also the highest resolution Impα structure already solved to date (1.75 Å). In addition, we performed calorimetric analysis to determine the affinity and thermodynamic parameters of the interaction between Imp-α and the classical SV40 NLS peptide. The comparison of these data with previous studies on Impα proteins led us to demonstrate that N. crassa Imp-α possess specific features that are distinct from mammalian Imp-α but exhibit important similarities to rice Imp-α, particularly at the minor NLS binding site. 相似文献
916.
Agnes Juhasz Yun Ge Susan Markel Alice Chiu Linda Matsumoto Josephus van Balgooy 《Free radical research》2013,47(6):523-532
The family of NADPH oxidase (NOX) genes produces reactive oxygen species (ROS) pivotal for both cell signalling and host defense. To investigate whether NOX and NOX accessory gene expression might be a factor common to specific human tumour types, this study measured the expression levels of NOX genes 1–5, dual oxidase 1 and 2, as well as those of NOX accessory genes NoxO1, NoxA1, p47phox, p67phox and p22phox in human cancer cell lines and in tumour and adjacent normal tissue pairs by quantitative, real-time RT-PCR. The results demonstrate tumour-specific patterns of NOX gene expression that will inform further studies of the role of NOX activity in tumour cell invasion, growth factor response and proliferative potential. 相似文献
917.
Patricia Vollú Silva Raquel Souza Cruz Luiz Sérgio Keim Geraldo Renato de Paula Bernadete Teixeira Ferreira Carvalho Leonardo Rocchetto Coelho Maria Cícera da Silva Carvalho Joel Mauricio Corrêa da Rosa Agnes Marie Sá Figueiredo Lenise Arneiro Teixeira 《Memórias do Instituto Oswaldo Cruz》2013,108(6):812-813
We analysed the antimicrobial susceptibility, biofilm formation and genotypic
profiles of 27 isolates of Staphylococcus haemolyticus obtained
from the blood of 19 patients admitted to a hospital in Rio de Janeiro, Brazil.
Our analysis revealed a clinical significance of 36.8% and a multi-resistance
rate of 92.6% among these isolates. All but one isolate carried the
mecA gene. The staphylococcal cassette chromosome
mec type I was the most prevalent mec
element detected (67%). Nevertheless, the isolates showed clonal diversity based
on pulsed-field gel electrophoresis analysis. The ability to form biofilms was
detected in 66% of the isolates studied. Surprisingly, no icaAD
genes were found among the biofilm-producing isolates. 相似文献
918.
Coupling of Mitochondrial Import and Export Translocases by Receptor-Mediated Supercomplex Formation
Jian Qiu Lena-Sophie Wenz Ralf M. Zerbes Silke Oeljeklaus Maria Bohnert David A. Stroud Christophe Wirth Lars Ellenrieder Nicolas Thornton Stephan Kutik Sebastian Wiese Agnes Schulze-Specking Nicole Zufall Agnieszka Chacinska Bernard Guiard Carola Hunte Bettina Warscheid Martin van der Laan Nikolaus Pfanner Nils Wiedemann Thomas Becker 《Cell》2013
919.
Agnes Mira Szabo Valeria Endresz Ferenc Somogyvari Andras Miczak Ildiko Faludi 《Molecular biology reports》2013,40(8):4721-4725
We studied the role of isocitrate lyase in the interaction between Mycobacterium bovis BCG and mice. ApoB100-only LDLR?/? (B6;129S-ApoBtm2SgyLdlrtm1Her/J) mice were inoculated with M. bovis BCG harbouring plasmids carrying the gene for isocitrate lyase. The presence of ~29 times more copies of this gene resulted in a higher bacterial yield in the spleens and lungs of the infected mice. The spleen was 3–4 times heavier, and in the spleen the bacteria survived over 10 days longer than did the bacteria with the control plasmid. Propionate was less toxic for bacteria carrying icl plasmids in vitro. This recombinant BCG can be a possible vaccine candidate. 相似文献
920.
Remo Sanges Yavor Hadzhiev Marion Gueroult-Bellone Agnes Roure Marco Ferg Nicola Meola Gabriele Amore Swaraj Basu Euan R. Brown Marco De Simone Francesca Petrera Danilo Licastro Uwe Str?hle Sandro Banfi Patrick Lemaire Ewan Birney Ferenc Müller Elia Stupka 《Nucleic acids research》2013,41(6):3600-3618