Loss of ribosomal RNA modification causes developmental defects in zebrafish

Non-coding RNAs (ncRNAs) play key roles in diverse cellular activities, and efficient ncRNA function requires extensive posttranscriptional nucleotide modifications. Small nucleolar RNAs (snoRNAs) are a group of ncRNAs that guide the modification of specific nucleotides in ribosomal RNAs (rRNAs) and small nuclear RNAs. To investigate the physiological relevance of rRNA modification in vertebrates, we suppressed the expression of three snoRNAs (U26, U44 and U78), either by disrupting the host gene splicing or by inhibiting the snoRNA precursor processing, and analyzed the consequences of snoRNA loss-of-function in zebrafish. Using a highly sensitive mass spectrometric analysis, we found that decreased snoRNA expression reduces the snoRNA-guided methylation of the target nucleotides. Impaired rRNA modification, even at a single site, led to severe morphological defects and embryonic lethality in zebrafish, which suggests that rRNA modifications play an essential role in vertebrate development. This study highlights the importance of posttranscriptional modifications and their role in ncRNA function in higher eukaryotes

Activation of Sympathetic Signaling in Macrophages Blocks Systemic Inflammation and Protects against Renal Ischemia-Reperfusion Injury

Background: The sympathetic nervous system regulates immune cell dynamics. However, the detailed role of sympathetic signaling in inflammatory diseases is still unclear because it varies according to the disease situation and responsible cell types. This study focused on identifying the functions of sympathetic signaling in macrophages in LPS-induced sepsis and renal ischemia-reperfusion injury (IRI).Methods: We performed RNA sequencing of mouse macrophage cell lines to identify the critical gene that mediates the anti-inflammatory effect of β2-adrenergic receptor (Adrb2) signaling. We also examined the effects of salbutamol (a selective Adrb2 agonist) in LPS-induced systemic inflammation and renal IRI. Macrophage-specific Adrb2 conditional knockout (cKO) mice and the adoptive transfer of salbutamol-treated macrophages were used to assess the involvement of macrophage Adrb2 signaling.Results: In vitro, activation of Adrb2 signaling in macrophages induced the expression of T cell Ig and mucin domain 3 (Tim3), which contributes to anti-inflammatory phenotypic alterations. In vivo, salbutamol administration blocked LPS-induced systemic inflammation and protected against renal IRI; this protection was mitigated in macrophage-specific Adrb2 cKO mice. The adoptive transfer of salbutamol-treated macrophages also protected against renal IRI. Single-cell RNA sequencing revealed that this protection was associated with the accumulation of Tim3-expressing macrophages in the renal tissue.Conclusions: The activation of Adrb2 signaling in macrophages induces anti-inflammatory phenotypic alterations partially via the induction of Tim3 expression, which blocks LPS-induced systemic inflammation and protects against renal IRI

What Can Be Seen by 18F-FDG PET in Atherosclerosis Imaging? The Effect of Foam Cell Formation on 18F-FDG Uptake to Macrophages In Vitro

18F-FDG PET is a promising tool for detecting vulnerableplaques, depending on the extent of macrophage infiltration;however, it is still not clear which stage of the lesion can bedetected by 18F-FDG PET. Methods: In this study, we investigatedthe effect of foam cell formation on 18F-FDG uptake usingcultured mouse peritoneal macrophages. Results: 18F-FDGaccumulation was increased by foam cell formation, but theuptake was decreased to the control level after complete differentiationto foam cells. Changes in hexokinase activitytended to accompany changes in 18F-FDG uptake. In contrast,changes in glucose-6-phosphatase activity and glucose transporter1 expression did not parallel 18F-FDG uptake. Conclusion:Our results suggest that 18F-FDG PET detects the earlystage of foam cell formation in atherosclerosis

Evidence for Hypoxia-Induced Shift in ATP Production from Glycolysis to Mitochondrial Respiration in Pulmonary Artery Smooth Muscle Cells in Pulmonary Arterial Hypertension

Background: The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia. Methods: We investigated the enzymes involved in glycolysis and mitochondrial respiration, and studied the two major energy-yielding pathways (glycolysis and mitochondrial respiration) by measuring extracellular acidification rate (ECAR) and cellular oxygen consumption rate (OCR) using the Seahorse extracellular flux technology. Results: Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 and pyruvate dehydrogenase were increased in PAH-PASMCs compared with non-PAH-PASMCs. The mRNA and protein levels of lactate dehydrogenase, as well as the intracellular lactate concentration, were also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxia. However, these were not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxia. Under normoxia, ATP production was significantly lower in PAH-PASMCs (59 ± 5 pmol/min) than in non-PAH-PASMCs (70 ± 10 pmol/min). On the other hand, ATP production was significantly higher in PAH-PASMCs (31 ± 5 pmol/min) than in non-PAH-PASMCs (14 ± 3 pmol/min) under hypoxia. Conclusions: There is an underlying change in the metabolic strategy to generate ATP production under the challenge of hypoxia

Associations between Coparenting Relationships and Maternal Depressive Symptoms and Negative Bonding to Infant

Maternal mental illnesses during early postpartum may be caused by lack of the coparenting relationship parents share and cooperate regarding child-rearing. This study clarifies the association of the coparenting relationship and negative mental health of mothers at one and three months after childbirth. This study conducted a secondary analysis of data from an intervention study wherein 24 mothers rearing their first child with a cohabitant (husband/partner) participated. Maternal mental health was evaluated using the Edinburgh Postnatal Depression Scale to determine postpartum depressive symptoms and the Mother-to-Infant Bonding Scale to assess negative bonding. Mothers’ average age was 31.5 ± 4.2 years old. All mothers were not working during the research period. The prevalence of postpartum depression and bonding disorder were approximately 13% and 21%, respectively. A better coparenting relationship was associated with lower postpartum depressive symptoms at both one month (β = −0.617, p = 0.002) and three months (β = −0.709, p < 0.01) postpartum. In contrast, no association was found between a coparenting relationship and negative bonding. The results indicate that the coparenting relationship may possibly prevent maternal depression during the early postpartum period