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Overlapping genes are widely prevalent; however, their expression and consequences are poorly understood. Here, we describe and functionally characterize a novel zyx-1 overlapping gene, azyx-1 , with distinct regulatory functions in Caenorhabditis elegans . We observed conservation of alternative open reading frames (ORFs) overlapping the 5′ region of zyxin family members in several animal species, and find shared sites of azyx-1 and zyxin proteoform expression in C . elegans . In line with a standard ribosome scanning model, our results support cis regulation of zyx-1 long isoform(s) by upstream initiating azyx-1a . Moreover, we report on a rare observation of trans regulation of zyx-1 by azyx-1 , with evidence of increased ZYX-1 upon azyx-1 overexpression. Our results suggest a dual role for azyx-1 in influencing zyx-1 proteoform heterogeneity and highlight its impact on C . elegans muscular integrity and locomotion.

Background The phylum Nematoda is incredibly diverse and includes many parasites of humans, livestock, and plants. Peptide-activated G protein-coupled receptors (GPCRs) are central to the regulation of physiology and numerous behaviors, and they represent appealing pharmacological targets for parasite control. Efforts are ongoing to characterize the functions and define the ligands of nematode GPCRs, with already most peptide GPCRs known or predicted in Caenorhabditis elegans . However, comparative analyses of peptide GPCR conservation between C. elegans and other nematode species are limited, and many nematode GPCRs remain orphan. A phylum-wide perspective on peptide GPCR profiles will benefit functional and applied studies of nematode peptide GPCRs. Results We constructed a pan-phylum resource of C. elegans peptide GPCR orthologs in 125 nematode species using a semi-automated pipeline for analysis of predicted proteome datasets. The peptide GPCR profile varies between nematode species of different phylogenetic clades and multiple C. elegans peptide GPCRs have orthologs across the phylum Nematoda. We identified peptide ligands for two highly conserved orphan receptors, NPR-9 and NPR-16, that belong to the bilaterian galanin/allatostatin A (Gal/AstA) and somatostatin/allatostatin C (SST/AstC) receptor families. The AstA-like NLP-1 peptides activate NPR-9 in cultured cells and are cognate ligands of this receptor in vivo. In addition, we discovered an AstC-type peptide, NLP-99, that activates the AstC-type receptor NPR-16. In our pan-phylum resource, the phylum-wide representation of NPR-9 and NPR-16 resembles that of their cognate ligands more than those of allatostatin-like peptides that do not activate these receptors. Conclusions The repertoire of C. elegans peptide GPCR orthologs varies across phylogenetic clades and several peptide GPCRs show broad conservation in the phylum Nematoda. Our work functionally characterizes the conserved receptors NPR-9 and NPR-16 as the respective GPCRs for the AstA-like NLP-1 peptides and the AstC-related peptide NLP-99. NLP-1 and NLP-99 are widely conserved in nematodes and their representation matches that of their receptor in most species. These findings demonstrate the conservation of a functional Gal/AstA and SST/AstC signaling system in nematodes. Our dataset of C. elegans peptide GPCR orthologs also lays a foundation for further functional studies of peptide GPCRs in the widely diverse nematode phylum.

The onset of sexual maturity involves dramatic changes in physiology and gene expression in many animals. These include abundant yolk protein production in egg-laying species, an energetically costly process under extensive transcriptional control. Here, we used the model organism Caenorhabditis elegans to provide evidence for the spatiotemporally defined interaction of two evolutionarily conserved transcription factors, CEH-60/PBX and UNC-62/MEIS, acting as a gateway to yolk protein production. Via proteomics, bimolecular fluorescence complementation (BiFC), and biochemical and functional readouts, we show that this interaction occurs in the intestine of animals at the onset of sexual maturity and suffices to support the reproductive program. Our electron micrographs and functional assays provide evidence that intestinal PBX/MEIS cooperation drives another process that depends on lipid mobilization: the formation of an impermeable epicuticle. Without this lipid-rich protective layer, mutant animals are hypersensitive to exogenous oxidative stress and are poor partners for mating. Dedicated communication between the hypodermis and intestine in C. elegans likely supports these physiological outcomes, and we propose a fundamental role for the conserved PBX/MEIS interaction in multicellular signaling networks that rely on lipid homeostasis.

Oviparous animals support reproduction via the incorporation of yolk as a nutrient source into the eggs. In Caenorhabditis elegans , however, yolk proteins seem dispensable for fecundity, despite constituting the vast majority of the embryonic protein pool and acting as carriers for nutrient-rich lipids. Here, we used yolk protein–deprived C. elegans mutants to gain insight into the traits that may yet be influenced by yolk rationing. We show that massive yolk provisioning confers a temporal advantage during embryogenesis, while also increasing early juvenile body size and promoting competitive fitness. Opposite to species that reduce egg production under yolk deprivation, our results indicate that C. elegans relies on yolk as a fail-safe to secure offspring survival, rather than to maintain offspring numbers.

Overlapping genes are widely prevalent, however, their expression and consequences are poorly understood. Here, we describe and functionally characterize a novel zyx-1 overlapping gene, azyx-1, with distinct regulatory functions in C. elegans. We observed conservation of alternative open reading frames overlapping the 5’ region of zyxin family members in several animal species, and find shared sites of azyx-1 and zyxin proteoform expression in C. elegans. In line with a standard ribosome scanning model, our results support cis regulation of zyx-1 long isoform(s) by upstream initiating azyx-1a. Moreover, we report on a rare observation of trans regulation of zyx-1 by azyx-1, with evidence of increased ZYX-1 upon azyx-1 overexpression. Our results suggest a dual role for azyx-1 in influencing zyx-1 proteoform heterogeneity and highlights its impact on C. elegans muscular integrity and locomotion.

Seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies, using dried blood spots, was determined in October–November 2020, among residents and staff randomly selected from 20 nursing homes (NH) geographically distributed in Flanders, Belgium. Sociodemographic and medical data [including coronavirus disease 2019 (COVID-19) symptoms and results of RT-PCR tests] were retrieved using questionnaires. The overall seroprevalence was 17.1% [95% confidence interval (CI) 14.9–19.5], with 18.9% (95% CI 15.9–22.2) of the residents and 14.9% (95% CI 11.9–18.4) of the staff having antibodies, which was higher than the seroprevalence in blood donors. The seroprevalence in the 20 NH varied between 0.0% and 45.0%. Fourteen per cent of the staff with antibodies, reported no typical COVID-19 symptoms, while in residents, 51.0% of those with antibodies had no symptoms. The generalised mixed effect model showed a positive association between COVID-19 symptoms and positive serology, but this relation was weaker in residents compared to staff. This study shows that NH are more affected by SARS-CoV-2 than the general population. The large variation between NH, suggests that some risk factors for the spread among residents and staff may be related to the NH. Further, the results suggest that infected people, without the typical COVID-19 symptoms, might play a role in outbreaks.