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Emerging evidence indicates a fundamental role for the epigenome in immunity. Here, we mapped the epigenomic and transcriptional landscape of immunity to influenza vaccination in humans at the single-cell level. Vaccination against seasonal influenza induced persistently diminished H3K27ac in monocytes and myeloid dendritic cells (mDCs), which was associated with impaired cytokine responses to Toll-like receptor stimulation. Single-cell ATAC-seq analysis revealed an epigenomically distinct subcluster of monocytes with reduced chromatin accessibility at AP-1-targeted loci after vaccination. Similar effects were observed in response to vaccination with the AS03-adjuvanted H5N1 pandemic influenza vaccine. However, this vaccine also stimulated persistently increased chromatin accessibility at interferon response factor (IRF) loci in monocytes and mDCs. This was associated with elevated expression of antiviral genes and heightened resistance to the unrelated Zika and Dengue viruses. These results demonstrate that vaccination stimulates persistent epigenomic remodeling of the innate immune system and reveal AS03's potential as an epigenetic adjuvant.RelA-SpoT Homolog (RSH) enzymes control bacterial physiology through synthesis and degradation of the nucleotide alarmone (p)ppGpp. We recently discovered multiple families of small alarmone synthetase (SAS) RSH acting as toxins of toxin-antitoxin (TA) modules, with the FaRel subfamily of toxSAS abrogating bacterial growth by producing an analog of (p)ppGpp, (pp)pApp. Here we probe the mechanism of growth arrest used by four experimentally unexplored subfamilies of toxSAS FaRel2, PhRel, PhRel2, and CapRel. Surprisingly, all these toxins specifically inhibit protein synthesis. To do so, they transfer a pyrophosphate moiety from ATP to the tRNA 3' CCA. The modification inhibits both tRNA aminoacylation and the sensing of cellular amino acid starvation by the ribosome-associated RSH RelA. Conversely, we show that some small alarmone hydrolase (SAH) RSH enzymes can reverse the pyrophosphorylation of tRNA to counter the growth inhibition by toxSAS. Collectively, we establish RSHs as RNA-modifying enzymes.COVID-19 can cause severe neurological symptoms, but the underlying pathophysiological mechanisms are unclear. Here, we interrogated the brain stems and olfactory bulbs in postmortem patients who had COVID-19 using imaging mass cytometry to understand the local immune response at a spatially resolved, high-dimensional, single-cell level and compared their immune map to non-COVID respiratory failure, multiple sclerosis, and control patients. We observed substantial immune activation in the central nervous system with pronounced neuropathology (astrocytosis, axonal damage, and blood-brain-barrier leakage) and detected viral antigen in ACE2-receptor-positive cells enriched in the vascular compartment. Microglial nodules and the perivascular compartment represented COVID-19-specific, microanatomic-immune niches with context-specific cellular interactions enriched for activated CD8+ T cells. Altered brain T-cell-microglial interactions were linked to clinical measures of systemic inflammation and disturbed hemostasis. This study identifies profound neuroinflammation with activation of innate and adaptive immune cells as correlates of COVID-19 neuropathology, with implications for potential therapeutic strategies. There are few population-based studies concerning the bowel habits of adult Nigerians. Only one of these was published about a decade ago in the Northcentral region, the others were published over four decades ago. This study was conducted to determine the bowel habits and the frequencies of bowel movement disorders among adults in a Southwestern Nigerian population. The study was a community-based cross-sectional survey of a cohort of Nigerian adults aged 18 to 70 years. The data collection instrument consisted of demographic information, lifestyle factors, abdominal circumference, bowel habits, and the Rome IV bowel disorder questionnaire questions regarding bowel movement disorders. A copy of the Bristol Stool Scale was shown to each respondent to allow easy evaluation of stool form. Summary statistics included Means, frequencies and percentages. Associations between categorical variables were tested by Chi-square test or Fisher exact test as required. The statistical significance cut-off was set at P-w in the study population and this may be related to the consumption of the African diet that is rich in fibre content. The burden of birth defects is disproportionately higher in developing countries. This study assessed the knowledge of risk factors and prevention of birth defects among ante-natal clinic attendees at the University College Hospital, Ibadan, Oyo State, Nigeria. This was a cross-sectional study among 415 mothers who presented at the antenatal clinic. A semi-structured questionnaire was used to obtain information on respondents' socio-demographic profile, pregnancy, birth history, knowledge on prevention and risk factors for birth defects. Descriptive statistics was used to present results, independent t-test and ANOVA were used to determine the factors associated with mean of overall knowledge of birth defects. Test statistics was done at a 5% level of statistical significance. The mean age of the women was 31.7 ± 4.8 years. Overall, 93 (22.4%) of the women were above 35 years, 118 (29.9%) were skilled workers and 343 (84.9%) had tertiary education. More than half (219, 52.8%) of the respondents had good knowledge of birth defects (56.4% had good knowledge of prevention and 66.0% had good knowledge of risk factors). Antenatal clinic attendees in their first trimester had higher mean overall knowledge score (8.3 ± 4.9) compared to those in second (7.9 ± 4.5) and third (7.9 ± 4.9) trimesters but this was not statistically significant (p=0.873). However, respondents in skilled/ semi-skilled occupation (8.62) had a significantly higher mean knowledge score compared with those in unskilled occupation/ unemployed (7.33) (p=0.005). Knowledge of birth defects is relatively low among women. To reduce the occurrence and severity of birth defects, there is a need to educate mothers on the knowledge, prevention and importance of screening for birth defects.Knowledge of birth defects is relatively low among women. Selleckchem AEBSF To reduce the occurrence and severity of birth defects, there is a need to educate mothers on the knowledge, prevention and importance of screening for birth defects.