Activity

BACKGROUND Lead (Pb) exposure and prenatal stress (PS) during development are co-occurring risk factors with shared biological substrates. PS has been associated with transgenerational passage of altered behavioral phenotypes, whereas the transgenerational behavioral or biochemical consequences of Pb exposure, and modification of any such effects by PS, is unknown. OBJECTIVES The present study sought to determine whether Pb, PS, or combined Pb and PS exposures produced adverse transgenerational consequences on brain and behavior. METHODS Maternal Pb and PS exposures were carried out in F0 mice. Outside breeders were used at each subsequent breeding, producing four F1-F2 lineages [F1 female-F2 female (FF), FM (male), MF, and MM]. F3 offspring were generated from each of these lineages and examined for outcomes previously found to be altered by Pb, PS, or combined Pb and PS in F1 offspring behavioral performance [fixed-interval (FI) schedule of food reward, locomotor activity, and anxiety-like behavior], dopamishowing multiple changes through Pb-exposed lineages. Lineage effects may occur through maternal responses to pregnancy, altered maternal behavior, epigenetic modifications, or a combination of mechanisms, but they have significant public health ramifications regardless of mechanism. https//doi.org/10.1289/EHP4977.Ferrets are an attractive mammalian model for several diseases especially those affecting the lungs, liver and kidneys. Many chronic human diseases have been difficult to model in rodents due to differences in size and cellular anatomy. This is particularly the case for the lung where ferrets provide an attractive mammalian model of both acute and chronic lung diseases such as influenza, cystic fibrosis, A1A emphysema and obliterative bronchiolitis, closely recapitulating disease pathogenesis as it occurs in humans. As such, ferrets have the potential to be a valuable pre-clinical model for the evaluation of cell-based therapies for lung regeneration and, likely, for other tissues. Induced pluripotent stem cells (iPSCs) provide a great option for provision of enough autologous cells to make patient-specific cell therapies a reality. Unfortunately, they have not been successfully created from ferrets. In this study, we demonstrate the generation of ferret iPSCs that reflect the primed pluripotent state of human iPSCs. Ferret fetal fibroblasts were reprogrammed and acquired core features of pluripotency, having the capacity for self-renewal, multi-lineage differentiation and a high-level expression of the core pluripotency genes and pathways at both the transcriptional and protein level. In conclusion, we have generated ferret pluripotent stem cells that provide an opportunity for advancing our capacity to evaluate autologous cell engraftment in ferrets.Ultra-processed food (UPF) consumption is increasing globally at an unprecedented rate. We investigated UPF consumption among Canadian adults and associated socio-demographic and health-related factors. This study was a secondary analysis of the Foodbook study (2014-2015), which collected self-reported data on foods consumed by Canadians during a seven-day period. UPF diversity was assessed by summing the different types of UPFs consumed in the previous week to produce a diversity score. Descriptive statistics summarized UPF diversity among subgroups in Canada. Regression models identified significant associations between UPF diversity, body mass index (BMI), and socio-demographic variables. 6,062 participants, aged 18 years and older, were included, representing 24.7 million Canadian adults. Almost all Canadian adults (99.0%) consumed UPFs at least once weekly. The most common UPFs consumed were chocolate, chips/pretzels, cold breakfast cereal and fast foods. UPF diversity was greatest among men, young respondents, those with high income, and those with obesity. When controlling for potential confounders, UPF diversity for men and women was significantly associated with younger age and higher BMI; it was also associated with region for women. This study suggests UPF consumption in Canada varies across socio-demographic subgroups, but ultimately is pervasive. Further research examining potential health risks associated with UPF consumption is encouraged to inform Canadian interventions. Novelty • Almost all Canadians consume at least one type of ultra-processed food weekly • Nearly half or more Canadians consume chocolate, chips/pretzels, cold breakfast cereal or fast food at least once weekly • Gender, age, and BMI are consistently associated with ultra-processed food diversity.Emerging evidence suggests that extracellular vesicle (EV) -associated microRNAs (miRNAs) are potential diagnostic tools for human diseases. However, the experimental procedure for detection of EV-associated miRNAs (EV-miRNAs) from body fluids is relatively complex and not cost-effective. Due to limited amount of EVs /EV-RNAs, column-based RNA purification, which is an expensive approach, is often used to detect EV-miRNAs via reverse transcription-quantitative real-time PCR (RT-qPCR). We developed and validated a simple and cost-effective method (single-step RT-qPCR), in which we directly detect EV-miRNAs without EV-RNA purification. We validated this protocol using the EVs isolated from mouse broncho-alveolar lavage fluid (BALF) and serum. The obtained EVs were lysed in EV-lysis buffer, followed by RT-qPCR without isolation / purification of RNAs. We successfully detected the designated miRNAs from lysed EVs. 106 – 107 EVs were optimal to detect the EV-miRNAs using the single-step RT-qPCR. In our published work, using conventional RT-qPCR method, we have reported that miR-142 and 223 are dramatically upregulated in both BALF- and serum-EVs after lung infection. learn more Hence, we re-assessed and confirmed the level of EV-miR-142/223 using the newly developed single-step RT-qPCR. Notably, inhibition of RNase activity in the lysed EVs remains crucial for the detection of EV-miRNAs. Moreover, repeated freeze-thaw cycling significantly interferes the EV-miRNA quantification. Collectively, the single-step RT-qPCR for the detection of EV-miRNAs in vivo will potentially provide a fast, accurate and convenient way to quantify circulating and/or body fluid-derived EV-miRNAs. This method may potentially be applied to the diagnostic blood testing used in the medical centers or research laboratories.