cypress: an R/Bioconductor package for cell-type-specific differential expression analysis power assessment.

SUMMARY: Recent methodology advances in computational signal deconvolution have enabled bulk transcriptome data analysis at a finer cell-type level. Through deconvolution, identifying cell-type-specific differentially expressed (csDE) genes is drawing increasing attention in clinical applications. However, researchers still face a number of difficulties in adopting csDE detection methods in practice, especially in their experimental design. Here we present cypress, the first experimental design and statistical power analysis tool in csDE identification. This tool can reliably model purified cell-type-specific (CTS) profiles, cell-type compositions, biological and technical variations, offering a high-fidelity simulator for bulk RNA-seq convolution and deconvolution. cypress conducts simulation and evaluates the impact of multiple influencing factors, by various biostatistical metrics, to help researchers optimize experimental design and conduct power analysis. AVAILABILITY AND IMPLEMENTATION: cypress is an open-source R/Bioconductor package at https://bioconductor.org/packages/cypress/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Space-Like Irradiation Exacerbated Cognitive Deficits and Amyloid Pathology in CRND8 Mouse Model of Alzheimer's Disease.

Background: Space radiation was linked to neurological damage and behavioral deficits which raised concerns of increased degenerative risk on the brain and development of Alzheimer's disease following space travel. Objective: In this study, we investigated the effects of irradiation by 56Fe and 28Si in CRND8 mice, an Alzheimer's disease mouse model. Methods: Six-month-old CRND8 mice were exposed to whole body irradiation by 56Fe and 28Si at 0.5 Gy and 2 Gy doses. Behavior tests were administered 1-month to 3-months post-irradiation. Amyloid deposition and other pathological changes were analyzed 3-months and/or 6-months post-irradiation. Results: The Novel Object Recognition test showed some decline in 8-month-old mice compared to non-irradiated CRND8 mice. Male mice also showed a loss of freezing behavior in the fear conditioning contextual test following irradiation. Golgi staining revealed a loss of spines in hippocampal neurons after irradiation. Total amyloid immunohistochemistry showed a robust increase in 3-months post-irradiation 56Fe groups which became normalized to non-irradiated group by 6-months post-irradiation. However, 2 Gy 28Si caused a trend towards increased plaque load at 3-months post-irradiation which became significant at 6-months post irradiation only in male CRND8 mice. While 0.5 Gy Fe did not induce obvious changes in the total number of iba-1 positive microglia, more hippocampal microglia were found to express PCNA after 0.5 Gy Fe treatment, suggesting potential involvement of microglial dysfunction. Conclusions: Overall, our study provides new evidence of gender-specific and ion-dependent effects of space radiation on cognition and amyloid pathology in AD models.

Compensatory responses induced by oxidative stress in Alzheimer disease

Oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the pathologic hallmarks, neurofibrillary tangles and senile plaques. In the first stage of development of the disease, amyloid-â deposition and hyperphosphorylated tau function as compensatory responses and downstream adaptations to ensure that neuronal cells do not succumb to oxidative damage. These findings suggest that Alzheimer disease is associated with a novel balance in oxidant homeostasis.