The COVID-19 pandemic has profoundly affected healthcare workers, increasing vulnerability to neuropsychiatric disorders, such as anxiety and depression. Psychological distress may be shaped by resili Show more
The COVID-19 pandemic has profoundly affected healthcare workers, increasing vulnerability to neuropsychiatric disorders, such as anxiety and depression. Psychological distress may be shaped by resilience, coping behaviours, and immune dysregulation. We investigated psychological distress symptoms, resilience, alcohol use, and cytokine profiles in 1440 workers from four hospitals in Fortaleza, Brazil. Participants were classified as frontline or second-line workers and assessed with the SRQ-20, CD-RISC, and AUDIT. Blood samples were analysed for SARS-CoV-2 antibodies and cytokines. Data were collected at two time points (August-October 2021; March-April 2022). Frontline workers reported higher distress, with decreased vital energy and somatic symptoms most prominent. Lower resilience scores correlated with all SRQ-20 domains, while higher alcohol use was linked to decreased energy and depressive thoughts. Reduced anti-spike antibody levels were also associated with greater distress. COVID-19 infection and symptom severity were associated with more persistent mental distress symptoms. Sex-specific immune signatures emerged: in women, lower interleukin (IL)-7 and C-X-C motif chemokine ligand 9 (CXCL-9) and higher IL-27 correlated with depressive-anxious mood and energy depletion; in men, IL-18, IL-9, and tumour necrosis factor beta (TNF-β) were positively associated with distress. This study demonstrates that psychological distress among healthcare workers during COVID-19 was shaped by resilience, alcohol use, infection severity, and sex-dependent immune alterations. Strengthening resilience and targeting inflammatory pathways may help mitigate the long-term mental health burden in this workforce during future public health crises. Show less
Carbamoyl phosphate synthetase-I (CPS1) is a key enzyme in the urea cycle and patients with defects in the function or expression of CPS1 suffer from hyperammonemia. CPS1 is expressed in the liver at Show more
Carbamoyl phosphate synthetase-I (CPS1) is a key enzyme in the urea cycle and patients with defects in the function or expression of CPS1 suffer from hyperammonemia. CPS1 is expressed in the liver at neonatal and adult stages in a CCAAT enhancer-binding protein-alpha (C/EBPalpha)-dependent manner. Despite expression of C/EBPalpha, CPS1 is not expressed in fetal liver, indicating an additional factor is involved in the regulation of CPS1 expression. The aim of this study was to elucidate the mechanism of CPS1 expression. Microarray was performed to find Y-box binding protein-1 (YB-1) that was expressed in mouse fetal liver. The role of YB-1 in CPS1 expression was investigated by overexpression of YB-1 in mouse fetal liver culture and luciferase reporter assays using the CPS1 promoter. Chromatin immunoprecipitation assay was used to examine recruitment of YB-1 to the CPS1 promoter in vivo. Expression of YB-1 and CPS1 was inversely correlated in vivo, and YB-1 inhibited CPS1 expression and ammonia clearance in fetal liver culture. Although YB-1 was not expressed in adult liver, acute liver injury up-regulated YB-1 and down-regulated CPS1, accompanying an increase of the serum ammonia level. YB-1 inhibited C/EBPalpha-induced transcription from the CPS1 promoter via the Y-box near the C/EBPalpha-binding site. Chromatin immunoprecipitation assays demonstrated that YB-1 was recruited to the CPS1 promoter in fetal and injured adult liver, but not in normal adult liver. YB-1 is a key regulator of ammonia detoxification by negatively regulating CPS1 expression via suppression of C/EBPalpha function. Show less
The GPA1 gene of S. cerevisiae encodes a G alpha subunit that plays a positive role in the transduction of signals stimulating recovery from pheromone-induced cell cycle arrest. The GPA1Val50 mutation Show more
The GPA1 gene of S. cerevisiae encodes a G alpha subunit that plays a positive role in the transduction of signals stimulating recovery from pheromone-induced cell cycle arrest. The GPA1Val50 mutation, in which Gly-50 is replaced by valine, causes hyperadaptation to pheromone. However, GPA1Val50 cells do not recover from division arrest in the absence of both CLN1 and CLN3, which encode G1 cyclins, indicating that the recovery-promoting activity of GPA1Val50 requires the function of G1 cyclins. An sgv1 mutation suppresses the hyperadaptive response caused by GPA1Val50 and also confers cold- and temperature-sensitive growth. The SGV1 gene encodes an apparent protein kinase homologous to CDC28/cdc2 kinase: SGV1 is 42% identical to CDC28. The activated mutation, CLN3-2, partially suppresses the growth defect of sgv1, suggesting that the SGV1 and CLN3 proteins may act in the same growth control pathway. Show less