Editors Highlight: Subvisible Aggregates of Immunogenic Proteins Promote a Th1-Type Response
Protein aggregation is associated with enhanced immunogenicity of biotherapeutics. As a result, regulatory guidelines recommend screening for aggregation during bioprocessing. However, the mechanisms underlying the enhanced immunogenicity of aggregates are poorly understood. In the investigations described herein, the immunogenicity in mice of a humanized single chain variable antibody fragment (scFv) purified after expression in Escherichia coli has been examined. Reproducible scFv aggregates were obtained within the subvisible particle size range (mean diameter 2 µm) using thermal and mechanical stresses. Intraperi...
Source: Toxicological Sciences - September 25, 2016 Category: Toxicology Authors: Ratanji, K. D., Dearman, R. J., Kimber, I., Thorpe, R., Wadhwa, M., Derrick, J. P. Tags: T Helper 1-Type Response Induced by Subvisible Aggregates of Immunogenic Proteins Source Type: research
Editors Highlight: Transplacental and Lactational Transfer of Firemaster(R) 550 Components in Dosed Wistar Rats
This study is the first to confirm ip-PPP as a urinary metabolite of ITPs and establish a pharmacokinetic profile of FM 550 in a mammalian model.
Key words: Firemaster 550; lactational transfer; gestational transfer; metabolites; rodent. (Source: Toxicological Sciences)
Source: Toxicological Sciences - September 25, 2016 Category: Toxicology Authors: Phillips, A. L., Chen, A., Rock, K. D., Horman, B., Patisaul, H. B., Stapleton, H. M. Tags: Analysis of Placental and Lactational Transfer of Flame-Retardant Constituents Source Type: research
Editors Highlight: Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS): A Web-Based Tool for Addressing the Challenges of Cross-Species Extrapolation of Chemical Toxicity
Conservation of a molecular target across species can be used as a line-of-evidence to predict the likelihood of chemical susceptibility. The web-based Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS; https://seqapass.epa.gov/seqapass/) application was developed to simplify, streamline, and quantitatively assess protein sequence/structural similarity across taxonomic groups as a means to predict relative intrinsic susceptibility. The intent of the tool is to allow for evaluation of any potential protein target while remaining amenable to variable degrees of protein characterization, in the context of ...
Source: Toxicological Sciences - September 25, 2016 Category: Toxicology Authors: LaLone, C. A., Villeneuve, D. L., Lyons, D., Helgen, H. W., Robinson, S. L., Swintek, J. A., Saari, T. W., Ankley, G. T. Tags: Web-Based Tool for Cross-Species Extrapolation of Chemical Toxicity Source Type: research
Dryad in the UK and USA--Prospective and Retrospective Data Publication
(Source: Toxicological Sciences)
Source: Toxicological Sciences - September 25, 2016 Category: Toxicology Authors: Khan, K., Weeks, A. Tags: Perspective: Data Sharing with the Dryad Digital Repository Source Type: research
Mechanisms of Action Point Towards Combined PBDE/NDL-PCB Risk Assessment
At present, human risk assessment of the structurally similar non-dioxin-like (NDL) PCBs and polybrominated diphenylethers (PBDEs) is done independently for both groups of compounds. There are however obvious similarities between NDL-PCBs and PBDEs with regard to modulation of the intracellular calcium homeostasis (basal calcium levels, voltage-gated calcium channels, calcium uptake, ryanodine receptor) and thyroid hormone (TH) homeostasis (TH levels and transport). which are mechanisms of action related to neurobehavioral effects (spontaneous activity, habituation and learning ability). There also similarities in agonisti...
Source: Toxicological Sciences - September 25, 2016 Category: Toxicology Authors: Dingemans, M. M. L., Kock, M., van den Berg, M. Tags: Editorials, Look Inside ToxSci, & Special Content Contemporary Review: Combined Risk Assessment of PBDEs and PCBs Source Type: research
From the Editors Desk, Editors Highlights
(Source: Toxicological Sciences)
Source: Toxicological Sciences - September 25, 2016 Category: Toxicology Tags: Editorials, Look Inside ToxSci, & Special Content Source Type: research
Table of Contents
(Source: Toxicological Sciences)
Source: Toxicological Sciences - September 25, 2016 Category: Toxicology Tags: Standing Material Source Type: research
Subscriptions
(Source: Toxicological Sciences)
Source: Toxicological Sciences - September 25, 2016 Category: Toxicology Tags: Standing Material Source Type: research
Editorial Board
(Source: Toxicological Sciences)
Source: Toxicological Sciences - September 25, 2016 Category: Toxicology Tags: Standing Material Source Type: research
Cover
(Source: Toxicological Sciences)
Source: Toxicological Sciences - September 25, 2016 Category: Toxicology Tags: Cover Source Type: research
Toxicity Evaluation of Bisphenol A Administered by Gavage to Sprague Dawley Rats From Gestation Day 6 Through Postnatal Day 90
(Source: Toxicological Sciences)
Source: Toxicological Sciences - August 30, 2016 Category: Toxicology Authors: Delclos, K. B., Camacho, L., Lewis, S. M., Vanlandingham, M. M., Latendresse, J. R., Olson, G. R., Davis, K. J., Patton, R. E., Gamboa da Costa, G., Woodling, K. A., Bryant, M. S., Chidambaram, M., Trbojevich, R., Juliar, B. E., Felton, R. P., Thorn, B. T Tags: Corrigendum Source Type: research
Perfluorooctane Sulfonate Induces Autophagy-Dependent Apoptosis through Spinster 1-Mediated lysosomal-Mitochondrial Axis and Impaired Mitophagy
Lysosomal membrane permeabilization (LMP) and subsequently impaired autophagosome degradation was induced in HepG2 cells after treatment with perfluorooctane sulfonate (PFOS) for 24 h in our previous studies. We found that treatment of HepG2 cells with PFOS-induced autophagosome formation at earlier stage (6 h) of treatment in this study. The autophagosome formation inhibitor 3-methyladenine (3-MA) was able to relieve PFOS-induced LMP and release of cathepsin D in HepG2 cells. Knockdown of Spinster 1, a lysosomal membrane permease, attenuated PFOS-induced LMP in HepG2 cells. We proposed that Spinster 1 might work as a spec...
Source: Toxicological Sciences - August 30, 2016 Category: Toxicology Authors: Yao, X., Sha, S., Wang, Y., Sun, X., Cao, J., Kang, J., Jiang, L., Chen, M., Ma, Y. Tags: PFOS Effects on Autophagy and Mitophagy Source Type: research
Editors Highlight: Perfluorooctane Sulfonate-Choline Ion Pair Formation: A Potential Mechanism Modulating Hepatic Steatosis and Oxidative Stress in Mice
The mechanisms underlying perfluorooctane sulfonate (PFOS)-induced steatosis remain unclear. The hypothesis that PFOS causes steatosis and other hepatic effects by forming an ion pair with choline was examined. C57BL/6 mice were fed either a control diet or a marginal methionine/choline-deficient (mMCD) diet, with and without 0.003, 0.006, or 0.012% potassium PFOS. Dietary PFOS caused a dose-dependent decrease in body weight, and increases in the relative liver weight, hepatic triglyceride concentration and serum markers of liver toxicity and oxidative stress. Some of these effects were exacerbated in mice fed the mMCD die...
Source: Toxicological Sciences - August 30, 2016 Category: Toxicology Authors: Zhang, L., Krishnan, P., Ehresman, D. J., Smith, P. B., Dutta, M., Bagley, B. D., Chang, S.-C., Butenhoff, J. L., Patterson, A. D., Peters, J. M. Tags: Interaction of PFOS with Choline and Hepatic Steatosis Source Type: research
Methoxychlor and Vinclozolin Induce Rapid Changes in Intercellular and Intracellular Signaling in Liver Progenitor Cells
Methoxychlor (MXC) and vinclozolin (VIN) are well-recognized endocrine disrupting chemicals known to alter epigenetic regulations and transgenerational inheritance; however, non-endocrine disruption endpoints are also important. Thus, we determined the effects of MXC and VIN on the dysregulation of gap junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells. Both chemicals induced a rapid dysregulation of GJIC at non-cytotoxic doses, with 30 min EC50 values for GJIC inhibition being 10 µM for MXC and 126 µM for VIN. MXC inhi...
Source: Toxicological Sciences - August 30, 2016 Category: Toxicology Authors: Babica, P., Zurabian, R., Kumar, E. R., Chopra, R., Mianecki, M. J., Park, J.-S., Jasa, L., Trosko, J. E., Upham, B. L. Tags: Epigenetic Changes in Liver Progenitor Cells by Methoxychlor and Vinclozolin Source Type: research
Editors Highlight: Lower Fractional Anisotropy in the Globus Pallidus of Asymptomatic Welders, a Marker for Long-Term Welding Exposure
Conclusion: GP FA captured microstructural changes associated with chronic low-level Mn exposure, and may serve as a biomarker for neurotoxicity in asymptomatic welders. (Source: Toxicological Sciences)
Source: Toxicological Sciences - August 30, 2016 Category: Toxicology Authors: Lee, E.-Y., Flynn, M. R., Du, G., Lewis, M. M., Herring, A. H., Van Buren, E., Van Buren, S., Kong, L., Mailman, R. B., Huang, X. Tags: MRI Markers of Exposures in Welders Source Type: research
