Conserved spatiotemporal expression landscape of dominant tRNA genes in human and mouse.

Transfer RNAs are integral for protein synthesis and the interpretation of the information contained in DNA. To date, a few methods, including custom microarrays and custom targeted sequencing, have been used to quantify tRNA. However, methods using available RNA-sequencing data have not yet been reported. We created a bioinformatics pipeline to quantify the highly expressed tRNAs in RNA-Seq effectively, demonstrated by the preserved ratio of the expression levels of two massively duplicated tRNAAla genes in mouse. Using this quantification, we examined the tRNA expression with relation to tissue type and developmental stage in both human and mouse. Heart exhibited the highest overall tRNA expression for both human and mouse. Furthermore, tRNA expression grew to a peak before decreasing steadily with developmental stage, a trend that was conserved in both human and mouse. The two mitochondrial tRNA genes, tRNASer(TCA)(m) and tRNALeu(TTA)(m), which partly contribute to these trends, have been attributed to various human diseases. The tissue-specific high expression of tRNAGln(CAG) and tRNAGln(CAA) in human brains, especially in hindbrain and cerebellum, suggests their important roles in neurological disorders. In summary, our approach revealed conserved spatiotemporal expression of highly expressed tRNAs in both human and mouse. Our method can be applied to other RNA-Seq data to examine the roles of these tRNAs in different human diseases or scientific studies.

Corrigendum: COVID-19 pandemic's disproportionate impact on childhood bereavement for youth of color: reflections and recommendations.

[This corrects the article DOI: 10.3389/fped.2023.1063449.].

COVID-19 pandemic's disproportionate impact on childhood bereavement for youth of color: Reflections and recommendations.

The COVID-19 pandemic devastated public welfare worldwide, bringing excess deaths connected to causes such as homicide, substance abuse, and heart disease. In the U.S., these mortality increases disproportionally impacted communities of color and contributed to a rise in bereavement among adults and children. The death of an important person is one of the most frequently reported disruptive childhood experiences. According to 2023 Childhood Bereavement Estimation Model (CBEM) results, one in 14 U.S. children will experience the death of a parent by age 18. The current study analyzes the impact of the pandemic on childhood bereavement due to parent death by comparing CBEM results for 2021 and 2020 to the average of annual results for 2016 through 2019 for combined U.S. Census race and Hispanic origin categories. Analyses demonstrate that more than 700,000 U.S. children were newly bereaved due to a parent's death in 2020 and 2021. 2020 increases were observed for each race and Hispanic origin population, ranging from 14.9% to 72.4% compared to the 2016-2019 annual average. Hispanic Asian Pacific Islander and Hispanic Black youth experienced the largest percentage increases, while non-Hispanic white youth experienced the smallest. The results contribute to the growing evidence documenting longstanding and enduring disparities in critical U.S. health outcomes based on race and Hispanic origin. Recommendations for the scale and focus of efforts to understand and address bereavement in a way that accommodates the rising need for support in diverse populations to help all bereaved children find hope and healing are offered.

Efficacy Testing of Personal Protective Filters on Biosafety Level 4 Positive Pressure Suits.

Introduction: Positive pressure breathing air-fed protective suits from three vendors are commonly used in biosafety level 4 (BSL-4) laboratories: they are Dover Chemturion suits (ILC Dover, DE), Delta suits (Honeywell Safety, NC), and HVO suits (HVO-ISSI-Deutschland GmbH, Germany). To address the potential risk of infectious agents being introduced through the supplied breathing air stream, some suit manufacturers incorporate protective filters on the suits themselves. However, these integrated filters are not amenable to in situ testing for efficacy verification. We have been using external filters from Matheson USA on the positive pressure suits since our BSL-4 laboratories were commissioned two decades ago. As part of our BSL-4 protective suit management program, we test these filters before them being put into use, and annually thereafter. In the past few years, we have observed these filters failing at a higher rate, as high as two out of three of the new filters tested at one point. Objective: The purpose of this study was to procure personal protective filters from other sources and validate their efficacy long-term. Methods: Filters from Respirex, HVO, and Honeywell were validated for filter integrity and filter loading. Results: Respirex filters performed well during the initial testing and periodic testing thereafter. Regular testing of the Respirex filters has now been ongoing for 30 months with continued successful performance. Conclusion: Filters from Respirex are a suitable option to protect personnel wearing positive pressure suits in BSL-4 laboratories.

Activation of p53-regulated pro-apoptotic signaling pathways in PrP-mediated myopathy.

BACKGROUND: We have reported that doxycycline-induced over-expression of wild type prion protein (PrP) in skeletal muscles of Tg(HQK) mice is sufficient to cause a primary myopathy with no signs of peripheral neuropathy. The preferential accumulation of the truncated PrP C1 fragment was closely correlated with these myopathic changes. In this study we use gene expression profiling to explore the temporal program of molecular changes underlying the PrP-mediated myopathy. RESULTS: We used DNA microarrays, and confirmatory real-time PCR and Western blot analysis to demonstrate deregulation of a large number of genes in the course of the progressive myopathy in the skeletal muscles of doxycycline-treated Tg(HQK) mice. These include the down-regulation of genes coding for the myofibrillar proteins and transcription factor MEF2c, and up-regulation of genes for lysosomal proteins that is concomitant with increased lysosomal activity in the skeletal muscles. Significantly, there was prominent up-regulation of p53 and p53-regulated genes involved in cell cycle arrest and promotion of apoptosis that paralleled the initiation and progression of the muscle pathology. CONCLUSION: The data provides the first in vivo evidence that directly links p53 to a wild type PrP-mediated disease. It is evident that several mechanistic features contribute to the myopathy observed in PrP over-expressing mice and that p53-related apoptotic pathways appear to play a major role.

Generation to generation: discrimination and harassment experiences of physician mothers and their physician daughters.

OBJECTIVE: To examine bias and sexual harassment experiences of physician mothers and their physician daughters; correlations of these experiences with career satisfaction, stress at work, stress at home, and percentage of women in specialty; and influences of the mother on her daughter's experiences. METHODS: A convenience sample of 214 families with mother and daughter physicians was sent a 56-item survey that included questions on bias and sexual harassment experiences. Statistical comparisons were made within 136 dyads where both mother and daughter returned the questionnaire. RESULTS: Eighty-four percent of mothers and 87% of daughters responded. Mothers and daughters reported similarly high rates and severity of sexual harassment before medical school, while in residency/fellowship, while in practice/work setting, and by teachers and supervisors. Daughters reported higher rates of harassment during medical school and by patients, mothers by colleagues. Gender and racial/ethnic discrimination was lower for daughters compared with their mothers, but gender discrimination was still substantial. Compared with other daughters, daughters who experienced discrimination or sexual harassment reported lower career satisfaction and more stress at work and at home and worked in specialties with fewer women. CONCLUSIONS: Gender discrimination and sexual harassment remain entrenched in medical education and professional workplaces. Maternal role models and mentors were not as protective as anticipated. Leadership of medical institutions and professional associations must deal more effectively with persistent discrimination and harassment or risk the loss of future leaders.