The oldest unvaccinated Covid-19 survivors in South America.

BACKGROUND: Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated. RESULTS: Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN. CONCLUSION: These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.

Quantitative Proteome Analysis of Jatropha curcas L. Genotypes with Contrasting Levels of Phorbol Esters.

The phorbol esters in the seeds of Jatropha curcas are a major hindrance to the full exploitation of the potential of this oil crop as a source of raw material for the production of biodiesel. Here, various quantitative proteomic strategies are used to establish the proteomes of roots, leaves, and endosperm of two genotypes of J. curcas with contrasting levels of phorbol esters in the seeds. In total 4532, 1775, and 503 proteins are identified respectively in roots, leaves, and endosperm, comprising 5068 unique proteins; of this total, 185 are differentially abundant in roots, 72 in leaves, and 20 in the endosperm. The biosynthetic pathways for flavonoids and terpenoids are well represented in roots, including the complete set of proteins for the mevalonate and non-mevalonate/Deoxyxylulose 5-Phosphate pathways, and proteins involved in the branches which lead to the synthesis tricyclic diterpenoids and gibberellins. Also, casbene synthase which catalyzes the first committed step in the biosynthesis of tigliane-type diterpenes is identified in roots of both genotypes, but not in leaves and endosperm. This dataset will be a valuable resource to explore the biochemical basis of the low toxicity of Jatropha genotypes with low concentration of phorbol esters in the seeds.

1 H NMR metabolomics reveals increased glutaminolysis upon overexpression of NSD3s or Pdp3 in Saccharomyces cerevisiae.

NSD3s, the proline-tryptophan-tryptophan-proline (PWWP) domain-containing, short isoform of the human oncoprotein NSD3, displays high transforming properties. Overexpression of human NSD3s or the yeast protein Pdp3 in Saccharomyces cerevisiae induces similar metabolic changes, including increased growth rate and sensitivity to oxidative stress, accompanied by decreased oxygen consumption. Here, we set out to elucidate the biochemical pathways leading to the observed metabolic phenotype by analyzing the alterations in yeast metabolome in response to NSD3s or Pdp3 overexpression using 1 H nuclear magnetic resonance (NMR) metabolomics. We observed an increase in aspartate and alanine, together with a decrease in arginine levels, on overexpression of NSD3s or Pdp3, suggesting an increase in the rate of glutaminolysis. In addition, certain metabolites, including glutamate, valine, and phosphocholine were either NSD3s or Pdp3 specific, indicating that additional metabolic pathways are adapted in a protein-dependent manner. The observation that certain metabolic pathways are differentially regulated by NSD3s and Pdp3 suggests that, despite the structural similarity between their PWWP domains, the two proteins act by unique mechanisms and may recruit different downstream signaling complexes. This study establishes for the first time a functional link between the human oncoprotein NSD3s and cancer metabolic reprogramming.