Mineralogical variations in the Earth's mantle and the relative proportions of peridotitic versus enriched and potentially crustally-derived pyroxenitic domains within the mantle have important ...implications for mantle dynamics, magma generation, and the recycling of surface material back into the mantle. Here we present iron (Fe) stable isotope data (δ57Fe, deviation in 57Fe/54Fe from the IRMM-014 standard in parts per thousand) for peridotite and garnet–pyroxenite xenoliths from Oahu, Hawaii and explore Fe isotopes as tracer of both peridotitic and pyroxenitic components in the source regions of oceanic basalts. The pyroxenites have δ57Fe values that are heavy (0.10 to 0.27‰) relative to values for mid-ocean ridge and ocean island basalts (MORB; OIB; δFe57∼0.16‰) and the primitive mantle (PM; δFe57∼0.04‰). Pyroxenite δ57Fe values are positively correlated with bulk pyroxenite titanium and heavy rare earth element (REE) abundances, which can be interpreted in terms of stable isotope fractionation during magmatic differentiation and pyroxene cumulate formation. In contrast, the peridotites have light δ57Fe values (−0.34 to 0.14‰) that correlate negatively with degree of melt depletion and radiogenic hafnium isotopes, with the most depleted samples possessing the most radiogenic Hf isotope compositions and lightest δ57Fe values. While these correlations are broadly consistent with a scenario of Fe isotope fractionation during partial melting, where isotopically heavy Fe is extracted into the melt phase, leaving behind low-δ57Fe peridotite residues, the extent of isotopic variation is far greater than predicted by partial melting models. One possibility is derivation of the samples from a heterogeneous source containing both light-δ57Fe (relative to PM) and heavy-δ57Fe components. While pyroxenite is a viable explanation for the heavy-δ57Fe component, the origin of the depleted light-δ57Fe component is more difficult to explain, as melting models predict that even large (>30%) degrees of melt extraction do not generate strongly fractionated residues. Multiple phases of melt extraction or other processes, such as metasomatism, melt percolation or the assimilation of xenocrystic olivine with light δ57Fe values may need to be invoked to explain these light δ57Fe values; a caveat to this is that these processes must either preserve, or generate correlations between δ57Fe and Hf isotopes. Published variations in δ57Fe in mantle melting products, such as MORB and OIB, are also greater than predicted by melting models assuming derivation from δ57Fe-homogeneous mantle. For example, OIB from the Society and Cook-Austral islands, which have radiogenic Pb and Sr isotope compositions indicative of recycled components such as subduction modified, low-Pb oceanic crust and terrigenous sediments have heavy mean δ57Fe values (∼0.21‰) significantly distinct to those of other OIB and MORB, which could explained by the presence of heavy-δ57Fe pyroxenite cumulate or pyroxenitic melt components, whereas large degree partial melts, such as komatiites and boninites, display light Fe-isotopic compositions which may reflect sampling of refractory, light-δ57Fe mantle components. Iron stable isotopes may therefore provide a powerful new means of fingerprinting mineralogical variations within the Earth's mantle and identifying the mineralogy of depleted and enriched components within the source regions of volcanic rocks.
•Refractory peridotite and cumulate pyroxenite display systematic differences in Fe isotope composition.•Fe isotopes provide evidence for cumulate pyroxenite in OIB source regions.•Fe isotopes record the melt depletion and enrichment history of the upper mantle.•The Fe isotope composition of the Earth's upper mantle is heterogeneous.
Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1, and BA.2. BA.2 RBD has slightly higher ACE2 affinity than ...BA.1 and slightly reduced neutralization by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the ACE2 binding site; however, more distant mutations S371F (BA.2) and R346K (BA.1.1) markedly reduce neutralization by therapeutic antibody Vir-S309. In-depth structure-and-function analyses of 27 potent RBD-binding mAbs isolated from vaccinated volunteers following breakthrough Omicron-BA.1 infection reveals that they are focused in two main clusters within the RBD, with potent right-shoulder antibodies showing increased prevalence. Selection and somatic maturation have optimized antibody potency in less-mutated epitopes and recovered potency in highly mutated epitopes. All 27 mAbs potently neutralize early pandemic strains, and many show broad reactivity with variants of concern.
Display omitted
•Potent RBD antibodies from Omicron breakthrough vaccinees broadly neutralize VoC•These, possible recall antibodies, are focused in two main clusters•Somatic maturation adapts public antibodies to recover potency•BA.2 > BA.1 ACE2 affinity. BA.2 < BA.1 neutralization by vaccine serum and Vir-S309
Analysis of antibodies from SARS-CoV-2 Omicron breakthrough infections reveals their structural and functional properties as well as ability to neutralize different pandemic strains.
Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains ...have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations. We explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.
Display omitted
•Despite similar RBD mutations, P.1 is easier to neutralize than B.1.351•P.1, B.1.351, and B.1.1.7 partially or fully escape most VH3-53 antibodies•mAb 222 (VH3-53) retains neutralization against all three variants•Neutralization is restored in VH3-53 chimeric antibodies with mAb 222 LC
Structural and functional analysis of the P.1 variant of SARS-CoV-2 from Brazil reveals less resistance to antibodies generated from natural infection or vaccination compared to another similar variant, B.1.351. A monoclonal antibody, mAb 222, is able to neutralize all three variants (P.1, B.1.351, and B.1.1.7), with its light chain able to restore neutralization potency to a broad group of antibodies.
The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early ...stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled ‘Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies’. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation–health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation–health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims.
Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape ...from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta-infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor-binding domain (RBD). Two of these RBD-binding mAbs recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y, including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.
Display omitted
•Generated 674 antibodies from patients infected with SARS-CoV-2 Beta variant•18 of 27 most potent mAbs target the 3 mutations in Beta RBD•A major response to N501Y includes a public IgVH4-39 sequence•Two antibodies recognize a neutralizing epitope conserved between SARS-CoV-1 and -2
Liu et al. generated 674 antibodies from patients infected with the SARS-CoV-2 Beta variant. 18 out of 27 most potent neutralizing antibodies isolated target the 3 mutations present in the receptor-binding domain of this variant. This underscores the poor neutralization by Beta serum of early pandemic and Delta viruses.
Using a sample of U.K. wire makers (
N
= 282), the authors tested a model in which personality and work environment antecedents affect proactive work behavior via cognitive-motivational mechanisms. ...Self-reported proactive work behaviors (proactive idea implementation and proactive problem solving) were validated against rater assessments for a subsample (
n
= 60) of wire makers. With the exception of supportive supervision, each antecedent was important, albeit through different processes. Proactive personality was significantly associated with proactive work behavior via role breadth self-efficacy and flexible role orientation, job autonomy was also linked to proactive behavior via these processes, as well as directly; and coworker trust was associated with proactive behavior via flexible role orientation. In further support of the model, the cognitive-motivational processes for proactive work behavior differed from those for the more passive outcome of generalized compliance.
Broad-scale studies of climate change effects on freshwater species have focused mainly on temperature, ignoring critical drivers such as flow regime and biotic interactions. We use downscaled ...outputs from general circulation models coupled with a hydrologic model to forecast the effects of altered flows and increased temperatures on four interacting species of trout across the interior western United States (1.01 million km2), based on empirical statistical models built from fish surveys at 9,890 sites. Projections under the 2080s A1B emissions scenario forecast a mean 47% decline in total suitable habitat for all trout, a group of fishes of major socioeconomic and ecological significance. We project that native cutthroat trout Oncorhynchus clarkii, already excluded from much of its potential range by nonnative species, will lose a further 58% of habitat due to an increase in temperatures beyond the species’ physiological optima and continued negative biotic interactions. Habitat for nonnative brook trout Salvelinus fontinalis and brown trout Salmo trutta is predicted to decline by 77% and 48%, respectively, driven by increases in temperature and winter flood frequency caused by warmer, rainier winters. Habitat for rainbow trout, Oncorhynchus mykiss, is projected to decline the least (35%) because negative temperature effects are partly offset by flow regime shifts that benefit the species. These results illustrate how drivers other than temperature influence species response to climate change. Despite some uncertainty, large declines in trout habitat are likely, but our findings point to opportunities for strategic targeting of mitigation efforts to appropriate stressors and locations.
The Omicron lineage of SARS-CoV-2, first described in November 2021, spread rapidly to become globally dominant and has split into a number of sub-lineages. BA.1 dominated the initial wave but has ...been replaced by BA.2 in many countries. Recent sequencing from South Africa’s Gauteng region uncovered two new sub-lineages, BA.4 and BA.5 which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences and, although closely related to BA.2, contain further mutations in the receptor binding domain of spike. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by serum from triple AstraZeneca or Pfizer vaccinated individuals compared to BA.1 and BA.2. Furthermore, using serum from BA.1 vaccine breakthrough infections there are likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.
Display omitted
1.BA.4/5 resist neutralization by triple-dosed vaccinee serum more than BA.1/2.2.BA.1 vaccine breakthrough serum shows reduced neutralization of BA.4/5.3.Activity of SARS-CoV-2 therapeutic antibodies against BA.4/5 is reduced.4.L452R and F486V mutations both make major contributions to BA.4/5 escape.
SARS-CoV-2 Omicron BA.4 and BA.5 sublineages bear mutations that lead to their reduced neutralization by sera from triple vaccinated individuals when compared to the more recent BA.1 and BA.2. Importantly, sera from individuals with breakthrough BA.1 infections also show reduced neutralization, suggesting that repeat Omicron infections are likely in the population.
Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused successive global waves of infection. These variants, with multiple mutations in the spike protein, are thought to ...facilitate escape from natural and vaccine-induced immunity and often increase in affinity for ACE2. The latest variant to cause concern is BA.2.75, identified in India where it is now the dominant strain, with evidence of wider dissemination. BA.2.75 is derived from BA.2 and contains four additional mutations in the receptor-binding domain (RBD). Here, we perform an antigenic and biophysical characterization of BA.2.75, revealing an interesting balance between humoral evasion and ACE2 receptor affinity. ACE2 affinity for BA.2.75 is increased 9-fold compared with BA.2; there is also evidence of escape of BA.2.75 from immune serum, particularly that induced by Delta infection, which may explain the rapid spread in India, where where there is a high background of Delta infection. ACE2 affinity appears to be prioritized over greater escape.
Display omitted
•BA.2.75 affinity for ACE2 is increased 9-fold compared with BA.2•N460K increases neutralization escape and likely increases ACE2 affinity•The revertant R493Q decreases neutralization escape but increases ACE2 affinity•Affinity to ACE2 appears to be prioritized over neutralization escape
Huo et al. characterize the SARS-CoV-2 variant BA.2.75 (originally identified in India). Its affinity for ACE2 is increased 9-fold over BA.2, and there is evidence of escape of BA.2.75 from immune serum, particularly from Delta infection. ACE2 affinity appears to be prioritized over greater escape via the R493Q reversion mutation.
PDF
