With aging, significant changes in circadian rhythms occur, including a shift in phase toward a “morning” chronotype and a loss of rhythmicity in circulating hormones. However, the effects of aging on molecular rhythms in the human brain have remained elusive. Here, we used a previously described time-of-death analysis to identify transcripts throughout the genome that have a significant circadian rhythm in expression in the human prefrontal cortex [Brodmann’s area 11 (BA11) and BA47]. Expression levels were determined by microarray analysis in 146 individuals. Rhythmicity in expression was found in ∼10% of detected transcripts (P < 0.05). Using a metaanalysis across the two brain areas, we identified a core set of 235 genes (q < 0.05) with significant circadian rhythms of expression. These 235 genes showed 92% concordance in the phase of expression between the two areas. In addition to the canonical core circadian genes, a number of other genes were found to exhibit rhythmic expression in the brain. Notably, we identified more than 1,000 genes (1,186 in BA11; 1,591 in BA47) that exhibited age-dependent rhythmicity or alterations in rhythmicity patterns with aging. Interestingly, a set of transcripts gained rhythmicity in older individuals, which may represent a compensatory mechanism due to a loss of canonical clock function. Thus, we confirm that rhythmic gene expression can be reliably measured in human brain and identified for the first time (to our knowledge) significant changes in molecular rhythms with aging that may contribute to altered cognition, sleep, and mood in later life.
Background: Fusion transcripts are formed by either fusion genes (DNA level) or trans-splicing events (RNA level). They have been recognized as a promising tool for diagnosing, subtyping and treating cancers. RNA-seq has become a precise and efficient standard for genome-wide screening of such aberration events. Many fusion transcript detection algorithms have been developed for paired-end RNA-seq data but their performance has not been comprehensively evaluated to guide practitioners. In this paper, we evaluated 15 popular algorithms by their precision and recall trade-off, accuracy of supporting reads and computational cost. We further combine top-performing methods for improved ensemble detection.Results: Fifteen fusion transcript detection tools were compared using three synthetic data sets under different coverage, read length, insert size and background noise, and three real data sets with selected experimental validations. No single method dominantly performed the best but SOAPfuse generally performed well, followed by FusionCatcher and JAFFA. We further demonstrated the potential of a meta-caller algorithm by combining top performing methods to re-prioritize candidate fusion transcripts with high confidence that can be followed by experimental validation.Conclusion: Our result provides insightful recommendations when applying individual tool or combining top performers to identify fusion transcript candidates.
Background SARS-CoV-2 epidemiology implicates airborne transmission; aerosol infectiousness and impacts of masks and variants on aerosol shedding are not well understood. Methods We recruited COVID-19 cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute breath samples while vocalizing into a Gesundheit-II, with and without masks at up to two visits two days apart. We quantified and sequenced viral RNA, cultured virus, and assayed sera for anti-spike and anti-receptor binding domain antibodies. Results We enrolled 49 seronegative cases (mean days post onset 3.8 ±2.1), May 2020 through April 2021. We detected SARS-CoV-2 RNA in 45% of fine (≤5 µm), 31% of coarse (>5 µm) aerosols, and 65% of fomite samples overall and in all samples from four alpha-variant cases. Masks reduced viral RNA by 48% (95% confidence interval [CI], 3 to 72%) in fine and by 77% (95% CI, 51 to 89%) in coarse aerosols; cloth and surgical masks were not significantly different. The alpha variant was associated with a 43-fold (95% CI, 6.6 to 280-fold) increase in fine aerosol viral RNA, compared with earlier viruses, that remained a significant 18-fold (95% CI, 3.4 to 92-fold) increase adjusting for viral RNA in saliva, swabs, and other potential confounders. Two fine aerosol samples, collected while participants wore masks, were culture-positive. Conclusion SARS-CoV-2 is evolving toward more efficient aerosol generation and loose-fitting masks provide significant but only modest source control. Therefore, until vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.
Background: SARS-CoV-2 epidemiology implicates airborne transmission; mask source-control efficacy for, variant impact on, and infectiousness of aerosols are not well understood. Methods: We recruited COVID-19 cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute breath samples while vocalizing into a Gesundheit-II, with and without masks at up to two visits two days apart. We quantified and sequenced viral RNA, cultured virus, and assayed sera for anti-spike and anti-receptor binding domain antibodies. Results: We enrolled 61 participants with active infection, May 2020 through April 2021. Among 49 seronegative cases (mean days post onset 3.8 ±2.1), we detected SARS-CoV-2 RNA in 45% of fine (≥5 μm), 31% of coarse (>5 μm) aerosols, and 65% of fomite samples overall and in all samples from four alpha variant cases. Masks reduced viral RNA by 48% (95% confidence interval [CI], 3 to 72%) in fine and by 77% (95% CI, 51 to 89%) in coarse aerosols. The alpha variant was associated with a 43-fold (95% CI, 6.6 to 280-fold) increase in fine aerosol viral RNA that remained a significant 18-fold (95% CI, 3.4 to 92-fold) increase adjusting for viral RNA in saliva, in mid-turbinate swabs, and other potential confounders. Two fine aerosol samples, collected days 2-3 post illness onset, while participants wore masks, were culture-positive. Conclusion: SARS-CoV-2 is evolving toward more efficient airborne transmission and loose-fitting masks provide significant but only modest source control. Therefore, until vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.
Collectively, the results provide evidence for persistent MDD effects across current episodes or remission, in the absence of detectable progressive neuropathology.
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