Biogenic propane production by a marine Photobacterium strain isolated from the Western English Channel

Propane is a major component of liquefied petroleum gas, a major energy source for off-grid communities and industry. The replacement of fossil fuel-derived propane with more sustainably derived propane is of industrial interest. One potential production route is through microbial fermentation. Here we report, for the first time, the isolation of a marine bacterium from sediment capable of natural propane biosynthesis. Propane production, both in mixed microbial cultures generated from marine sediment and in bacterial monocultures was detected and quantified by gas chromatography–flame ionization detection. Using DNA sequencing of multiple reference genes, the bacterium was shown to belong to the genus Photobacterium. We postulate that propane biosynthesis is achieved through inorganic carbonate assimilation systems. The discovery of this strain may facilitate synthetic biology routes for industrial scale production of propane via microbial fermentation

The ribosomal P-stalk couples amino acid starvation to GCN2 activation in mammalian cells

The eukaryotic translation initiation factor 2α (eIF2α) kinase GCN2 is activated by amino acid starvation to elicit a rectifying physiological program known as the Integrated Stress Response (ISR). A role for uncharged tRNAs as activating ligands of yeast GCN2 is supported experimentally. However, mouse GCN2 activation has recently been observed in circumstances associated with ribosome stalling with no global increase in uncharged tRNAs. We report on a mammalian CHO cell-based CRISPR-Cas9 mutagenesis screen for genes that contribute to ISR activation by amino acid starvation. Disruption of genes encoding components of the ribosome P-stalk, uL10 and P1, selectively attenuated GCN2-mediated ISR activation by amino acid starvation or interference with tRNA charging without affecting the endoplasmic reticulum unfolded protein stress-induced ISR, mediated by the related eIF2α kinase PERK. Wildtype ribosomes isolated from CHO cells, but not those with P-stalk lesions, stimulated GCN2-dependent eIF2α phosphorylation in vitro. These observations support a model whereby lack of a cognate charged tRNA exposes a latent capacity of the ribosome P-stalk to activate GCN2 in cells and help explain the emerging link between ribosome stalling and ISR activation

Evidence that Fetal Death is Associated with Placental Aging

Background: The risk of unexplained fetal death or stillbirth increases late in pregnancy, suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA, and lipids. We hypothesized that placentas at >41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. Objective: We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging. We also aimed to develop an in vitro term placental explant culture model to test the aging pathways. Study Design: We collected placentas from women at 37-39 weeks’ gestation (early-term and term), late-term, and with unexplained stillbirth. We used immunohistochemistry to compare the 3 groups for: DNA/RNA oxidation (8-hydroxy-deoxyguanosine), lysosomal distribution (lysosome-associated membrane protein 2), lipid oxidation (4-hydroxynonenal), and autophagosome size (microtubule-associated proteins 1A/1B light chain 3B, LC3B). The expression of aldehyde oxidase 1 was measured by real-time polymerase chain reaction. Using a placental explant culture model, we tested the hypothesis that aldehyde oxidase 1 mediates oxidative damage to lipids in the placenta. Results: Placentas from late-term pregnancies show increased aldehyde oxidase 1 expression, oxidation of DNA/RNA and lipid, perinuclear location of lysosomes, and larger autophagosomes compared to placentas from women delivered at 37-39 weeks. Stillbirth-associated placentas showed similar changes in oxidation of DNA/RNA and lipid, lysosomal location, and autophagosome size to placentas from late-term. Placental explants from term deliveries cultured in serum-free medium also showed evidence of oxidation of lipid, perinuclear lysosomes, and larger autophagosomes, changes that were blocked by the G-protein-coupled estrogen receptor 1 agonist G1, while the oxidation of lipid was blocked by the aldehyde oxidase 1 inhibitor raloxifene. Conclusion: Our data are consistent with a role for aldehyde oxidase 1 and G-protein-coupled estrogen receptor 1 in mediating aging of the placenta that may contribute to stillbirth. The placenta is a tractable model of aging in human tissue

The helminth T2 RNase v1 promotes metabolic homeostasis in an IL-33– and group 2 innate lymphoid cell–dependent mechanism

Induction of a type 2 cellular response in the white adipose tissue leads to weight loss and improves glucose homeostasis in obese animals. Injection of obese mice with recombinant helminth-derived Schistosoma mansoni egg-derived v1 (v1), a potent inducer of type 2 activation, improves metabolic status involving a mechanism reliant upon release of the type 2 initiator cytokine IL-33. IL-33 initiates the accumulation of group 2 innate lymphoid cells (ILC2s), eosinophils, and alternatively activated macrophages in the adipose tissue. IL-33 release from cells in the adipose tissue is mediated by the RNase activity of v1; however, the ability of v1 to improve metabolic status is reliant upon effective binding of v1 to CD206. We demonstrate a novel mechanism for RNasemediated release of IL-33 inducing ILC2-dependent improvements in the metabolic status of obese animals.— Hams, E., Bermingham, R., Wurlod, F. A., Hogan, A. E., O’Shea, D., Preston, R. J., Rodewald, H.-R., McKenzie, A. N. J., Fallon, P. G. The helminth T2 RNase v1 promotes metabolic homeostasis in an IL-33– and group 2 innate lymphoid cell–dependent mechanism

The ribosomal P-stalk couples amino acid starvation to GCN2 activation in mammalian cells.

The eukaryotic translation initiation factor 2a (eIF2a) kinase GCN2 is activated by amino acid starvation to elicit a rectifying physiological program known as the Integrated Stress Response (ISR). A role for uncharged tRNAs as activating ligands of yeast GCN2 is supported experimentally. However, mouse GCN2 activation has recently been observed in circumstances associated with ribosome stalling with no global increase in uncharged tRNAs. We report on a mammalian CHO cell-based CRISPR-Cas9 mutagenesis screen for genes that contribute to ISR activation by amino acid starvation. Disruption of genes encoding components of the ribosome P-stalk, uL10 and P1, selectively attenuated GCN2-mediated ISR activation by amino acid starvation or interference with tRNA charging without affecting the endoplasmic reticulum unfolded protein stress-induced ISR, mediated by the related eIF2a kinase PERK. Wildtype ribosomes isolated from CHO cells, but not those with P-stalk lesions, stimulated GCN2-dependent eIF2a phosphorylation in vitro. These observations support a model whereby lack of a cognate charged tRNA exposes a latent capacity of the ribosome P-stalk to activate GCN2 in cells and help explain the emerging link between ribosome stalling and ISR activation

Biosafety standards for working with Crimean-Congo haemorrhagic fever virus

In countries from which Crimean-Congo haemorrhagic fever (CCHF) is absent, the causative virus CCHF virus (CCHFV) is classified as a hazard group 4 agent and handled in containment level 4. In contrast, most endemic countries out of necessity have had to perform diagnostic tests under biosafety level (BSL) -2 or -3 conditions. In particular, Turkey and several of the Balkan countries have safely processed more than 100000 samples over many years in BSL-2 laboratories. It is therefore advocated that biosafety requirements for CCHF diagnostic procedures should be revised, to allow the required tests to be performed under enhanced BSL-2 conditions with appropriate biosafety laboratory equipment and personal protective equipment used according to standardized protocols in the affected countries. Downgrading of CCHFV research work from Cl-4, BSL-4 to Cl-3, BSL-3 should also be considered.Additional co-authors: Gülay Korukluoglu, Pieter Lyssen, Ali Mirazimi, Johan Neyts, Matthias Niedrig, Aykut Ozkul, Anna Papa, Janusz Paweska, Amadou A Sall, Connie S Schmaljohn, Robert Swanepoel, Yavuz Uyar, Friedemann Weber, Herve Zelle

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

How do recorded mental health recovery narratives create connection and improve hopefulness?

Background: Mental health recovery narratives are an active ingredient of recovery-oriented interventions such as peer support. Recovery narratives can create connection and hope, but there is limited evidence on the predictors of impact. Aims: The aim of this study was to identify characteristics of the narrator, narrative content and participant which predict the short-term impact of recovery narratives on participants. Method: Independent studies were conducted in an experimental (n = 40) and a clinical setting (n = 13). In both studies, participants with mental health problems received recorded recovery narratives and rated impact on hopefulness and connection. Predictive characteristics were identified using multi-level modelling. Results: The experimental study found that narratives portraying a narrator as living well with mental health problems that is intermediate between no and full recovery, generated higher self-rated levels of hopefulness. Participants from ethnic minority backgrounds had lower levels of connection with narrators compared to participants from a white background, potentially due to reduced visibility of a narrator’s diversity characteristics. Conclusions: Narratives describing partial but not complete recovery and matching on ethnicity may lead to a higher impact. Having access to narratives portraying a range of narrator characteristics to maximise the possibility of a beneficial impact on connection and hopefulness