Comparison of 20nm silver nanoparticles synthesized with and without a gold core: Structure, dissolution in cell culture media, and biological impact on macrophages

Widespread use of silver nanoparticles raises questions of environmental and biological impact. Many synthesis approaches are used to produce pure silver and silver-shell gold-core particles optimized for specific applications. Since both nanoparticles and silver dissolved from the particles may impact the biological response, it is important to understand the physicochemical characteristics along with the biological impact of nanoparticles produced by different processes. The authors have examined the structure, dissolution, and impact of particle exposure to macrophage cells of two 20 nm silver particles synthesized in different ways, which have different internal structures. The structures were examined by electron microscopy and dissolution measured in Rosewell Park Memorial Institute media with 10% fetal bovine serum. Cytotoxicity and oxidative stress were used to measure biological impact on RAW 264.7 macrophage cells. The particles were polycrystalline, but 20 nm particles grown on gold seed particles had smaller crystallite size with many high-energy grain boundaries and defects, and an apparent higher solubility than 20 nm pure silver particles. Greater oxidative stress and cytotoxicity were observed for 20 nm particles containing the Au core than for 20 nm pure silver particles. A simple dissolution model described the time variation of particle size and dissolved silver for particle loadings larger than 9 μg/ml for the 24-h period characteristic of many in-vitro studies

Transcriptome Analysis of Targeted Mouse Mutations Reveals the Topography of Local Changes in Gene Expression.

The unintended consequences of gene targeting in mouse models have not been thoroughly studied and a more systematic analysis is needed to understand the frequency and characteristics of off-target effects. Using RNA-seq, we evaluated targeted and neighboring gene expression in tissues from 44 homozygous mutants compared with C57BL/6N control mice. Two allele types were evaluated: 15 targeted trap mutations (TRAP); and 29 deletion alleles (DEL), usually a deletion between the translational start and the 3' UTR. Both targeting strategies insert a bacterial beta-galactosidase reporter (LacZ) and a neomycin resistance selection cassette. Evaluating transcription of genes in +/- 500 kb of flanking DNA around the targeted gene, we found up-regulated genes more frequently around DEL compared with TRAP alleles, however the frequency of alleles with local down-regulated genes flanking DEL and TRAP targets was similar. Down-regulated genes around both DEL and TRAP targets were found at a higher frequency than expected from a genome-wide survey. However, only around DEL targets were up-regulated genes found with a significantly higher frequency compared with genome-wide sampling. Transcriptome analysis confirms targeting in 97% of DEL alleles, but in only 47% of TRAP alleles probably due to non-functional splice variants, and some splicing around the gene trap. Local effects on gene expression are likely due to a number of factors including compensatory regulation, loss or disruption of intragenic regulatory elements, the exogenous promoter in the neo selection cassette, removal of insulating DNA in the DEL mutants, and local silencing due to disruption of normal chromatin organization or presence of exogenous DNA. An understanding of local position effects is important for understanding and interpreting any phenotype attributed to targeted gene mutations, or to spontaneous indels

An analysis of prognostic factors associated with recurrence in the treatment of atypical meningiomas

AbstractBackgroundThere has been increased reporting of atypical meningioma (grade II) since the World Health Organization reclassification in 2000, and the use of postoperative radiation therapy (RT) in the treatment of these tumors is controversial. We evaluated patients treated at our institution to identify patient subgroups with increased risk of recurrence that may benefit from adjuvant RT.Methods and materialsWe retrospectively assessed 50 patients treated for World Health Organization grade II meningiomas between March 2000 and February 2013. Sex, race, age of diagnosis, tumor location, performance status, size of tumor, MIB-1 index, resection status, and RT were recorded. Patient follow-up, recurrence, and vital status were measured to assess 3-year overall survival (OS) and recurrence free survival (RFS).ResultsThe median follow-up was 37 months (range, 1-148). Female sex was associated with decreased RFS compared with male sex (86.1% vs 100%, P = .047). Subtotal resection demonstrated both inferior RFS (67.5% vs 96.6%, P = .025) and OS compared with gross total resection (70.0% vs 100%, P < .001). Tumors >4.5 cm had worse RFS than tumors ≤4.5 cm (85.4% vs 100%, P = .025). Patient OS was lower in tumors with an MIB-1 index >5% than ≤5% (89.7% vs 100%, P = .008). Eastern Cooperative Oncology Group 2-4 negatively impacted OS relative to patients with an Eastern Cooperative Oncology Group 0-1 (66.7% vs 100%, P < .001).ConclusionsSignificantly higher rates of recurrence occurred in female sex, subtotal resection, and tumors larger than 4.5 cm. Further studies are needed to confirm these findings and determine whether patients without any of these risk factors can undergo surgical resection without adjuvant radiation therapy

Corrigendum to: “Conceptual fear generalization gradients and their relationship with anxious traits: Results from a Registered Report” [Int. J. Psychophysiol. 170 (2021) 43–50]

The authors regret to inform that an error was made in the data analysis syntax for the analyses reported in the referenced article. Particularly, we included the “Behavioral Inhibition Scale” (BIS) in this study and correlated the scores on this questionnaire to generalization gradients in a fear generalization paradigm. Accidentally, we used items from the Intolerance of Uncertainty Scale (IUS), rather than the BIS, to calculate the BIS total scores. As a result of this error, the average BIS total score and the correlations that we report in Table 1 of the original article with this scale are incorrect. We report the correct BIS total score, standard deviation, and correlations with this scale in the updated table below (Table 1). Please note that, using the correct BIS scores, the correlation between the Generalization Index (GI) for fear potentiated startle (FPS) and BIS (r = −0.19; p = .037) now reached the conventional alpha cut-off level for statistical significance (0.05). However, this correlation was not significant according to our adjusted alpha level (0.017) that we had pre-specified for our study. As such, all the main conclusions of the original article remain unchanged. The authors would like to apologise for any inconvenience caused