Deamidation drives molecular aging of the SARS-CoV-2 spike protein receptor-binding motif

The spike protein is the main protein component of the SARS-CoV-2 virion surface. The spike receptor-binding motif mediates recognition of the human angiotensin-converting enzyme 2 receptor, a critical step in infection, and is the preferential target for spike-neutralizing antibodies. Posttranslational modifications of the spike receptor-binding motif have been shown to modulate viral infectivity and host immune response, but these modifications are still being explored. Here we studied asparagine deamidation of the spike protein, a spontaneous event that leads to the appearance of aspartic and isoaspartic residues, which affect both the protein backbone and its charge. We used computational prediction and biochemical experiments to identify five deamidation hotspots in the SARS-CoV-2 spike protein. Asparagine residues 481 and 501 in the receptor-binding motif deamidate with a half-life of 16.5 and 123 days at 37 °C, respectively. Deamidation is significantly slowed at 4 °C, indicating a strong dependence of spike protein molecular aging on environmental conditions. Deamidation of the spike receptor-binding motif decreases the equilibrium constant for binding to the human angiotensin-converting enzyme 2 receptor more than 3.5-fold, yet its high conservation pattern suggests some positive effect on viral fitness. We propose a model for deamidation of the full SARS-CoV-2 virion illustrating how deamidation of the spike receptor-binding motif could lead to the accumulation on the virion surface of a nonnegligible chemically diverse spike population in a timescale of days. Our findings provide a potential mechanism for molecular aging of the spike protein with significant consequences for understanding virus infectivity and vaccine development.     

Factors driving adaptive radiation in plants of oceanic islands: a case study from the Juan Fernández Archipelago

Adaptive radiation is a common evolutionary phenomenon in oceanic islands. From one successful immigrant population, dispersal into different island environments and directional selection can rapidly yield a series of morphologically distinct species, each adapted to its own particular environment. Not all island immigrants, however, follow this evolutionary pathway. Others successfully arrive and establish viable populations, but they remain in the same ecological zone and only slowly diverge over millions of years. This transformational speciation, or anagenesis, is also common in oceanic archipelagos. The critical question is why do some groups radiate adaptively and others not? The Juan Fernández Islands contain 105 endemic taxa of angiosperms, 49% of which have originated by adaptive radiation (cladogenesis) and 51% by anagenesis, hence providing an opportunity to examine characteristics of taxa that have undergone both types of speciation in the same general island environment. Life form, dispersal mode, and total number of species in progenitors (genera) of endemic angiosperms in the archipelago were investigated from literature sources and compared with modes of speciation (cladogenesis vs. anagenesis). It is suggested that immigrants tending to undergo adaptive radiation are herbaceous perennial herbs, with leaky self-incompatible breeding systems, good intra-island dispersal capabilities, and flexible structural and physiological systems. Perhaps more importantly, the progenitors of adaptively radiated groups in islands are those that have already been successful in adaptations to different environments in source areas, and which have also undergone eco-geographic speciation. Evolutionary success via adaptive radiation in oceanic islands, therefore, is less a novel feature of island lineages but rather a continuation of tendency for successful adaptive speciation in lineages of continental source regions.     

Demography and fishery of the sea urchin Loxechinus albus (Echinodermata: Echinidae) in south-austral Chile region

In the Magellan Region of southern Chile (52 degrees 20'S - 55 degrees 30'S), the edible urchin Loxechinus albus is collected by 1200 artisanal fishermen, of whom 450 are divers. About 360 small fishing boats and 54 transport vessels carry the fresh product to 16 processing plants. Landings of about 27 000 tons were recorded between January and December 1995. Test diameters of urchins harvested monthly were measured for a total of 119 239 specimens, and 36 406 specimens were individually weighed; sex determination was carried out on 2 314 specimens. Field data indicate that the harvest was about 6.6 x 106 dozen urchins (this is a measuring method employed by fishermen in the region), with an extractive effort of 14 753 diver/days. The fisheries yield ranged from an annual minimum of 235 DUDD (dozen urchins per diver/day) to a maximum of 660 DUDD. In overall terms, the lowest average yields were between January and April (415-427 DUDD), and the highest yields between May and December (456-510 DUDD). Mean sizes increased from June to November and decreased from December to June. Size frequency of males and females were polymodal, with the most relevant modes at 72-84 mm in males, and at 79-88 mm in the females. The percentage of individuals below the minimum legal size (70 mm) did not exceed 4.9% for males and 3.6% for females. The size-weight records fit a power model which suggested that this species has a negative allometric growth (b = 2.007). Regarding weight, urchins in the size range from 80.0 to 84.9 mm were those with the maximum contribution to the regional landings. The highest values recorded for the utilized condition factor were: Average Condition Factor (ACF) = May to July, and November; Isometric (or Cubic) Condition Factor (ICF) = July; and Allometric Condition Factor (ACF) = June. Spawning occurred mainly between August and September, and ended by the end of October. Exploitation of this species represents one of the main sources of employment for the artisanal fisheries sector in the Magellan Region. The main difficulty observed in this fishery was obtaining a sufficient supply of urchins with a yellow-gold colored gonadic material, which forms the basis for demand of this urchin by the international market.     

First record of human trichinosis in Chile associated with consumption of wild boar (Sus scrofa)

The first South American case of human trichinosis, resulting from the consumption of roast wild boar (Sus scrofa) is reported in Chile. The patient presented fever, diarrhea, myalgias, facial edema, sub-conjunctival reddening, photophobia, eosinophilia, and elevated glutamic oxalacetic transaminase. The diagnosis was confirmed by two immunoenzymatic tests (ELISA) using somatic and excretion-secretion antigens.     

The thankless task of playing genetics with mammalian mitochondrial DNA: a 30-year review

The advances obtained through the genetic tools available in yeast for studying the oxidative phosphorylation (OXPHOS) biogenesis and in particular the role of the mtDNA encoded genes, strongly contrast with the very limited benefits that similar approaches have generated for the study of mammalian mtDNA. Here we review the use of the genetic manipulation in mammalian mtDNA, its difficulty and the main types of mutants accumulated in the past 30 years and the information derived from them. We also point out the need for a substantial improvement in this field in order to obtain new tools for functional genetic studies and for the generation of animal models of mtDNA-linked diseases.     

A tRNA(Glu) that uncouples protein and tetrapyrrole biosynthesis

Glu-tRNA is either bound to elongation factor Tu to enter protein synthesis or is reduced by glutamyl-tRNA reductase (GluTR) in the first step of tetrapyrrole biosynthesis in most bacteria, archaea and in chloroplasts. Acidithiobacillus ferrooxidans, a bacterium that synthesizes a vast amount of heme, contains three genes encoding tRNA(Glu). All tRNA(Glu) species are substrates in vitro of GluRS1 from A. ferrooxidans.Glu-tRNA(3)(Glu), that fulfills the requirements for protein synthesis, is not substrate of GluTR. Therefore, aminoacylation of tRNA(3)(Glu) might contribute to ensure protein synthesis upon high heme demand by an uncoupling of protein and heme biosynthesis.     

Insect growth inhibition by tocotrienols and hydroquinones from Roldana barba-johannis

The methanol extract from the aerial parts of Roldana barba-johannis (Asteraceae) afforded sargachromenol, sargahydroquinoic acid, and sargaquinoic acid. These natural products and their corresponding acetylated and methylated derivatives showed insecticidal and insect growth regulatory activities against the Fall Armyworm [Spodoptera frugiperda J.E. Smith, (Lepidoptera: Noctuidae)], an important insect pest of corn. The most active compounds were sargachromenol and its acetylated derivative; sargahydroquinoic acid and its acetylated derivative; and a mixture of sargachromenol, sargahydroquinoic acid, and sargaquinoic acid (6:3:1) and the acetylated form of this mixture. All these compounds and mixtures had significant inhibitory effects between 5.0 and 20.0 ppm in diets. Most compounds were insecticidal to larvae, with lethal doses between 20 and 35 ppm. In addition, these substances also demonstrated scavenging properties toward 2,2-diphenyl-1-picrylhydrazyl radical in TLC autographic and spectrophotometric assays. These compounds appear to have selective effects on the pre-emergence metabolism of the insect. The results from these compounds were fully comparable in activity to those known natural insect growth inhibitors such as gedunin and methanol extracts of Cedrela salvadorensis and Yucca periculosa. These substances may be useful as natural insecticidal agents.     

Distinct physiological and metabolic reprogramming by highbush blueberry (Vaccinium corymbosum) cultivars revealed during long‐term UV‐B radiation

Despite the Montreal protocol and the eventual recovery of the ozone layer over Antarctica, there are still concerns about increased levels of ultraviolet‐B (UV‐B) radiation in the Southern Hemisphere. UV‐B induces physiological, biochemical and morphological stress responses in plants, which are species‐specific and different even for closely related cultivars. In woody plant species, understanding of long‐term mechanisms to cope with UV‐B‐induced stress is limited. Therefore, a greenhouse UV‐B daily course simulation was performed for 21 days with two blueberry cultivars (Legacy and Bluegold) under UV‐B_BE irradiance doses of 0, 0.07 and 0.19 W m^?2. Morphological changes, photosynthetic performance, antioxidants, lipid peroxidation and metabolic features were evaluated. We found that both cultivars behaved differently under UV‐B exposure, with Legacy being a UV‐B‐resistant cultivar. Interestingly, Legacy used a combined strategy: initially, in the first week of exposure its photoprotective compounds increased, coping with the intake of UV‐B radiation (avoidance strategy), and then, increasing its antioxidant capacity. These strategies proved to be UV‐B radiation dose dependent. The avoidance strategy is triggered early under high UV‐B radiation in Legacy. Moreover, the rapid metabolic reprogramming capacity of this cultivar, in contrast to Bluegold, seems to be the most relevant contribution to its UV‐B stress‐coping strategy.