Upregulated IL-32 expression and reduced gut short chain fatty acid caproic acid in people living with HIV with subclinical atherosclerosis

Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) are still at higher risk for cardiovascular diseases (CVDs) that are mediated by chronic inflammation. Identification of novel inflammatory mediators with the inherent potential to be used as CVD biomarkers and also as therapeutic targets is critically needed for better risk stratification and disease management in PLWH. Here, we investigated the expression and potential role of the multi-isoform proinflammatory cytokine IL-32 in subclinical atherosclerosis in PLWH (n=49 with subclinical atherosclerosis and n=30 without) and HIV- controls (n=25 with subclinical atherosclerosis and n=24 without). While expression of all tested IL-32 isoforms (α, β, γ, D, ϵ, and θ) was significantly higher in peripheral blood from PLWH compared to HIV- controls, IL-32D and IL-32θ isoforms were further upregulated in HIV+ individuals with coronary artery atherosclerosis compared to their counterparts without. Upregulation of these two isoforms was associated with increased plasma levels of IL-18 and IL-1β and downregulation of the atheroprotective protein TRAIL, which together composed a unique atherosclerotic inflammatory signature specific for PLWH compared to HIV- controls. Logistic regression analysis demonstrated that modulation of these inflammatory variables was independent of age, smoking, and statin treatment. Furthermore, our in vitro functional data linked IL-32 to macrophage activation and production of IL-18 and downregulation of TRAIL, a mechanism previously shown to be associated with impaired cholesterol metabolism and atherosclerosis. Finally, increased expression of IL-32 isoforms in PLWH with subclinical atherosclerosis was associated with altered gut microbiome (increased pathogenic bacteria; Rothia and Eggerthella species) and lower abundance of the gut metabolite short-chain fatty acid (SCFA) caproic acid, measured in fecal samples from the study participants. Importantly, caproic acid diminished the production of IL-32, IL-18, and IL-1β in human PBMCs in response to bacterial LPS stimulation. In conclusion, our studies identified an HIV-specific atherosclerotic inflammatory signature including specific IL-32 isoforms, which is regulated by the SCFA caproic acid and that may lead to new potential therapies to prevent CVD in ART-treated PLWH

Acute toxicity of a commercial glyphosate formulation on European sea bass juveniles (Dicentrarchus labrax L.): gene expressions of heme oxygenase-1 (ho-1), acetylcholinesterase (AChE) and aromatases (cyp19a and cyp19b).

International audienceAcute toxicity of Roundup, a commercial glyphosate--based herbicide, was evaluated in a teleost marine fish, the European sea bass, after 96 h of exposure. The LC50 96-h value of Roundup was 529 mg/L. Juveniles (Dicentrarchus labrax L.) were exposed to a sublethal concentration (35% of the LC50, i.e. 193 mg/L) of Roundup for 96-h. The study of heme oxygenase-1 (ho-1) gene expression was performed in four tissues (liver, gills, brain and gonads) and highlighted the disruption of antioxidant defence system. Results showed that ho-1 mRNA levels in liver and gills significantly decreased (p<0.001 and p<0.01 respectively) in fish exposed to 193 mg/L of Roundup, whereas in brain and gonads, ho-1 mRNA level was not altered. The analysis of acetylcholinesterase expression was used to evaluate the overall neurotoxicity of the herbicide and aromatase genes to assess the alteration of the endocrine system. Results showed that AChE and cyp19b gene transcriptions significantly increased (p<0.01) in brain of sea bass, whereas aromatase gene expression (cyp19a) in gonads was not significantly altered. Our results showed complex tissue-specific transcriptional responses after 96 h of exposure to a sublethal concentration. All these disruptions confirmed the deleterious effects of this glyphosate-based herbicide in a marine species

Beyond Democracy in Cambodia: political reconstruction in a post-conflict society - Edited by Joakim Ojendal and Mona Lilja

The genome sequence of Streptomyces ambofaciens, a species known to produce the congocidine and spiramycin antibiotics, has revealed the presence of numerous gene clusters predicted to be involved in the biosynthesis of secondary metabolites. Among them, the type II polyketide synthase-encoding alp cluster was shown to be responsible for the biosynthesis of a compound with antibacterial activity. Here, by means of a deregulation approach, we gained access to workable amounts of the antibiotics for structure elucidation. These compounds, previously designated as alpomycin, were shown to be known members of kinamycin family of antibiotics. Indeed, a mutant lacking AlpW, a member of the TetR regulator family, was shown to constitutively produce kinamycins. Comparative transcriptional analyses showed that expression of alpV, the essential regulator gene required for activation of the biosynthetic genes, is strongly maintained during the stationary growth phase in the alpW mutant, a stage at which alpV transcripts and thereby transcripts of the biosynthetic genes normally drop off. Recombinant AlpW displayed DNA binding activity toward specific motifs in the promoter region of its own gene and that of alpV and alpZ. These recognition sequences are also targets for AlpZ, the γ-butyrolactone-like receptor involved in the regulation of the alp cluster. However, unlike that of AlpZ, the AlpW DNA-binding ability seemed to be insensitive to the signaling molecules controlling antibiotic biosynthesis. Together, the results presented in this study reveal S. ambofaciens to be a new producer of kinamycins and AlpW to be a key late repressor of the cellular control of kinamycin biosynthesis

Recruitment and Growth of the Fan Mussel Pinna nobilis in the Montenegrin Adriatic Coast and Comparison with the Western Mediterranean

In this study, the comparative results of the fan mussel Pinna nobilis larvae collection during 3 years (2016–2019) on the sites of the Montenegrin Adriatic coast and the Western Mediterranean, France are presented. In both countries, growth studies of collected fan mussel juveniles were carried out as well. After 1 year growth measurement of P. nobilis recruits in their natural habitat on the site Dobrota, Montenegro, mean shell length was 198.58 ± 17.77 mm for the recruits from Sv. Nedjelja and 206.73 ± 16.40 mm for the recruits collected from Ljuta. The growth study carried out in a laboratory tank in France indicated that the mean shell length of P. nobilis recruits after a 9 month period was 100.50 ± 7.59 mm for the recruits from Bomasse, 96.33 ± 11.06 mm from Basse Renette 1, and 95.75 ± 8.45 mm for recruits from Basse Renette 2, respectively. In spite of much larger mean shell lengths obtained in Montenegro, mean monthly growth rate of P. nobilis recruits bred in France was higher due to more stable conditions and access to food within the tank in contrast to variations of environmental parameters in their natural habitat. We have presented first data on P. nobilis recruitment and growth in Montenegro and showed higher growth rate in comparison with the other sites in the Adriatic Sea and Mediterranean. It was shown that the temperature is of high importance for the growth rate of P. nobilis juveniles in their natural habitat due to lower growth during winter. Anthropogenic pressure was the main obstacle for development of P. nobilis populations during the study period, while biological pollution as the main threat for P. nobilis survival will be the subject of further studies in the Montenegrin Adriatic coast

Genome-guided exploration of streptomyces ambofaciens secondary metabolism

International audienceMembers of the Streptomyces genus are among the most prolific microorganisms producing secondary metabolites with wide uses in medicine and in agriculture. Sequencing of the genome of the model Streptomyces, Streptomyces coelicolor, has highlighted an unexpected feature, i.e. that the potential of these organisms to synthesise secondary metabolites has been largely underestimated. They indeed possess many more gene clusters encoding natural product-like biosynthetic pathways than there are known natural products. Similar observations have since been made for other bacterial or fungal genomes. Thus, it became clear that microbial secondary metabolism had been seriously underestimated and that genome-based approaches were very promising for the search of new bioactive compounds. Here, we present an overview of the secondary metabolite biosynthetic potential of Streptomyces ambofaciens, a species known for decades as producer of the macrolide spiramycin and the pyrrolamide congocidine. Interestingly, genome analysis has revealed that despite of the close phylogenetic relatedness between S. coelicolor and S. ambofaciens, most of its secondary metabolite gene clusters are species-specific

Distinct extracytoplasmic siderophore binding proteins recognize ferrioxamines and ferricoelichelin in streptomyces coelicolor A3(2)

Under iron limitation, the Gram-positive bacterium Streptomyces coelicolor A3(2) excretes three siderophores of the hydroxamate type: desferrioxamine B, desferrioxamine E, and coelichelin. These sequester iron from insoluble ferric hydroxides, and the resulting ferric complexes are believed to be transported into the cell via siderophore-binding proteins (SBPs) associated with ATP-binding cassette (ABC) transporters. Previous studies indicated that some of the genes in the desferrioxamine (des) and coelichelin (cch) biosynthetic clusters encode ABC transporter components required for efficient uptake of ferrioxamine E and ferricoelichelin, respectively, and a third ABC transporter gene cluster (cdt), not associated with siderophore biosynthesis genes, was implicated in the import of ferrioxamine B. In this study, the putative SBPs associated with these three gene clusters, DesE, CchF, and CdtB, were recombinantly overproduced in Escherichia coli and purified to homogeneity, and their binding affinity for cognate siderophores and noncognate siderophores was examined using fluorescence and circular dichroism spectroscopy. DesE was found to bind all of the ferric-tris-hydroxamates tested except ferricoelichelin, while CchF was found to bind only ferricoelichelin efficiently, providing further evidence that the cch cluster is a complete siderophore biosynthesis export uptake gene cluster. The picture was more complicated for CdtB, because it was found to be unstable in solution but was found to bind both ferrioxamine B and ferricoelichelin with high affinity. This was surprising because the cch cluster was previously reported to be necessary for efficient ferricoelichelin uptake. The remarkable specificity of the DesE and CchF proteins for different ferric-tris-hydroxamates raises intriguing questions about the molecular basis of their substrate specificity