Secretory phospholipase A2 in SARS-CoV-2 infection and multisystem inflammatory syndrome in children (MIS-C)

Secretory phospholipase 2 (sPLA2) acts as a mediator between proximal and distal events of the inflammatory cascade. Its role in SARS-CoV-2 infection is unknown, but could contribute to COVID-19 inflammasome activation and cellular damage. We present the first report of plasma sPLA2 levels in adults and children with COVID-19 compared with controls. Currently asymptomatic adults with a history of recent COVID-19 infection (≥4 weeks before) identified by SARS-CoV-2 IgG antibodies had sPLA2 levels similar to those who were seronegative (9 ± 6 vs.17 ± 28 ng/mL, P = 0.26). In contrast, children hospitalized with severe COVID-19 had significantly elevated sPLA2 compared with those with mild or asymptomatic SARS-CoV-2 infection (269 ± 137 vs. 2 ± 3 ng/mL, P = 0.01). Among children hospitalized with multisystem inflammatory syndrome in children (MIS-C), all had severe disease requiring pediatric intensive care unit (PICU) admission. sPLA2 levels were significantly higher in those with acute illness <10 days versus convalescent disease ≥10 days (540 ± 510 vs. 2 ± 1, P = 0.04). Thus, sPLA2 levels correlated with COVID-19 severity and acute MIS-C in children, implicating a role in inflammasome activation and disease pathogenesis. sPLA2 may be a useful biomarker to stratify risk and guide patient management for children with acute COVID-19 and MIS-C. Therapeutic compounds targeting sPLA2 and inflammasome activation warrant consideration.     

B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV

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Constraints on Salt Marsh Development Following Managed Coastal Realignment: Dispersal Limitation or Environmental Tolerance?

Salt marshes restored through managed coastal realignment (MR) often develop slowly and show persistent differences in vegetation from natural marshes. Development might be constrained by the availability of propagules or poor suitability of the abiotic environment for their establishment. To distinguish between these factors, we compared vegetation colonization and environmental conditions at a salt marsh created by MR at Brancaster, Norfolk, UK, with five reference marshes, varying in age from 30 to circa 6,000 years. After 5 years, plant communities of the MR site remained different from those in mature reference marshes. In contrast, the communities of the youngest reference marsh were not significantly different from mature reference marshes. At the MR site, abundance of perennial and later‐successional species was low and large areas remained unvegetated. These differences are unlikely to be due to dispersal limitation, because 76% of the species from the local species pool colonized the site within 5 years. Although the annuals Salicornia europaea and Suaeda maritima were abundant by year 2, they were not ubiquitous until the end of the study. Tidal elevations of the MR site were suitable for vegetation development, but soil redox potentials were lower than that at the reference sites. Reducing conditions in the MR site appear to be the major cause of vegetation differences from the reference marshes, as they are associated with an abundance of bare ground and a small range of vegetation clusters. Measures to avoid low sediment redox potentials may have a great benefit in some salt marsh restoration projects.     

Divergent diving behavior during short and long trips of a bimodal forager,the little auk Alle alle

The purpose of this study was to characterize for the first time seabird diving behavior during bimodal foraging. Little auks Alle alle, small zooplanktivorous Alcids of the High Arctic, have recently been shown to make foraging trips of short and long duration. Because short (ST) and long trips (LT) are thought to occur in different locations and serve different purposes (chick‐ and self‐feeding, respectively) we hypothesized that foraging differences would be apparent, both in terms of water temperature and diving characteristics. Using Time Depth Recorders (TDRs), we tested this hypothesis at three colonies along the Greenland Sea with contrasting oceanographic conditions. We found that diving behavior generally differed between ST and LT. However, the magnitude of the disparity in diving characteristics depended on local foraging conditions. At the study site where conditions were favorable, diving behavior differed only to a small degree between LT and ST. Together with a lack of difference in diving depth and ocean temperature, this indicates that these birds did not increase their foraging effort during ST nor did they travel long distances to seek out more profitable prey. In contrast, where local foraging conditions were poor, birds increased their diving effort substantially to collect a chick meal during ST as indicated by longer, more U‐shaped dives with slower ascent rates and shorter resting times (post‐dive intervals and extended surface pauses). In addition, large differences in diving depth and ocean temperature indicate that birds forage on different prey species and utilize different foraging areas during LT, which may be up to 200 km away from the colony. Continued warming and deteriorating near‐colony foraging conditions may have energetic consequences for little auks breeding in the eastern Greenland Sea.     

Variations in the alginate content and composition of Durvillaea antarctica and D. willana from southern New Zealand

The brown seaweeds Durvillaea antarctica andD. willana are dominant components of the lowerlittoral and upper sublittoral of exposed rocky shoresin southern New Zealand. Tissue samples of bothspecies, harvested from a site on the south-east coastof South Island over a period of 2 years, wereanalysed for alginate content and composition.Individuals of both species were further separatedinto different blade (lamina and palm) and stipe(cortex and medulla) fractions to assess variationwithin the thallus. On average the alginate contentand frequency of mannuronic acid (F_m) was higherin D. antarctica than in D. willana. Blades contained more alginate than stipes, laminaeand stipes were rich in mannuronic acid whereasholdfasts were rich in guluronic acid. Variations incomposition are considered to reflect the functionaldifferences of the tissue, giving flexibility to bladeand stipe and rigidity to the holdfast. Despitefluctuations in content and composition betweencollection times no seasonal trends in eithercomponent were apparent.     

Mitochondrial DNA control region diversity in the endangered blue chaffinch, Fringilla teydea

The blue chaffinch (Fringilla teydea) is found only on the two central Canary Islands of Gran Canaria and Tenerife, where it is restricted to pine forest habitat. It is reasonably abundant on the latter island but endangered on the former. Here, sequence variation was studied in a fragment spanning domains I and II of the mitochondrial DNA (mtDNA) control region. Phylogenetic analysis of all haplotypes with a F. coelebs outgroup indicated the two island populations were reciprocally monophyletic, supporting their individual conservation. Unlike in other species, most within-island haplotype diversity was due to mutations in the domain II region. Surprisingly, genetic diversity was greater in the smaller Gran Canarian population. We suggest that this is unlikely to be maintained under current population sizes although it may be mitigated by incorporating genetic information into the captive breeding programme.     

The heat shock protein Ssa2p is required for import of fructose-1, 6-bisphosphatase into Vid vesicles

Fructose-1,6-bisphosphatase (FBPase) is targeted to the vacuole for degradation when Saccharomyces cerevisiae are shifted from low to high glucose. Before vacuolar import, however, FBPase is sequestered inside a novel type of vesicle, the vacuole import and degradation (Vid) vesicles. Here, we reconstitute import of FBPase into isolated Vid vesicles. FBPase sequestration into Vid vesicles required ATP and cytosol, but was inhibited if ATP binding proteins were depleted from the cytosol. The heat shock protein Ssa2p was identified as one of the ATP binding proteins involved in FBPase import. A Deltassa2 strain exhibited a significant decrease in the rate of FBPase degradation in vivo as compared with Deltassa1, Deltassa3, or Deltassa4 strains. Likewise, in vitro import was impaired for the Deltassa2 strain, but not for the other Deltassa strains. The cytosol was identified as the site of the Deltassa2 defect; Deltassa2 cytosol did not stimulate FBPase import into import competent Vid vesicles, but wild-type cytosol supported FBPase import into competent Deltassa2 vesicles. The addition of purified recombinant Ssa2p stimulated FBPase import into Deltassa2 Vid vesicles, providing Deltassa2 cytosol was present. Thus, Ssa2p, as well as other undefined cytosolic proteins are required for the import of FBPase into vesicles.     

Elongation arrest is a physiologically important function of signal recognition particle

Signal recognition particle (SRP) targets proteins for co-translational insertion through or into the endoplasmic reticulum membrane. Mammalian SRP slows nascent chain elongation by the ribosome during targeting in vitro. This 'elongation arrest' activity requires the SRP9/14 subunit of the particle and interactions of the C-terminus of SRP14. We have purified SRP from Saccharomyces cerevisiae and demonstrated that it too has elongation arrest activity. A yeast SRP containing Srp14p truncated at its C-terminus (delta C29) did not maintain elongation arrest, was substantially deficient in promoting translocation and interfered with targeting by wild-type SRP. In vivo, this mutation conferred a constitutive defect in the coupling of protein translation and translocation and temperature-sensitive growth, but only a slight defect in protein translocation. In combination, these data indicate that the primary defect in SRP delta C29 is in elongation arrest, and that this is a physiologically important and conserved function of eukaryotic SRP.     

pH-controlled quaternary states of hexameric DnaB helicase

DnaB is the major helicase in the Escherichia coli replisome. It is a homohexameric enzyme that interacts with many other replisomal proteins and cofactors. It is usually loaded onto a single strand of DNA at origins of replication from its complex with its loading partner DnaC, then translocates in the 5' to 3' direction, unwinding duplex DNA in an NTP-driven process. Quaternary polymorphism has been described for the DnaB oligomer, a feature it has in common with some other hexameric helicases. In the present work, electron microscopy and in- depth rotational analysis studies of negatively stained specimens has allowed the establishment of conditions that govern the transition between the two different rotational symmetry states (C(3) and C(6)) of DnaB. It is shown: (a) that the pH value of the sample buffer, within the physiological range, dictates the quaternary organisation of the DnaB oligomer; (b) that the pH-induced transition is fully reversible; (c) that the type of adenine nucleotide complexed to DnaB, whether hydrolysable or not, does not affect its quaternary architecture; (d) that the DnaB.DnaC complex exists only as particles with C(3) symmetry; and (e) that DnaC interacts only with DnaB particles that have C(3) symmetry. Structural consequences of this quaternary polymorphism, as well as its functional implications for helicase activity, are discussed.