Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, the target of neutralizing antibodies. Given its ...potential to escape vaccine-induced humoral immunity, we measured the neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild-type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that received their primary series recently (<3 months), distantly (6–12 months), or an additional “booster” dose, while accounting for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinees. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron, only 4–6-fold lower than wild type, suggesting enhanced cross-reactivity of neutralizing antibody responses. In addition, we find that Omicron pseudovirus infects more efficiently than other variants tested. Overall, this study highlights the importance of additional mRNA doses to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants.
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•The SARS-CoV-2 Omicron variant harbors 34 mutations in the spike, more than other variants•Two doses of mRNA-based vaccines elicit poor neutralization of Omicron•Three mRNA vaccine doses elicit potent variant cross-neutralization, including Omicron•The Omicron pseudovirus infects cells more efficiently than other SARS-CoV-2 variants
SARS-CoV-2 Omicron variant pseudovirus exhibits escape from vaccine-induced humoral immunity. However, a third dose of COVID-19 mRNA vaccine elicited humoral immunity capable of cross-neutralizing this strain. In addition, pseudovirus produced with the Omicron spike exhibited more efficient transduction of ACE2-expressing target cells than other variants.
The systems often rely on gene families encoding surface antigens localized at subtelomeres; presumably because these genomic regions are prone to gene silencing and perhaps enhanced mutagenesis 7. ......the clusters of telomeres that are formed at the nuclear periphery during meiosis may favor ectopic recombinations, which can be responsible for the generation of new mosaic antigens 8. ...structure is similar to leucine zipper motifs that are known to be involved in nonspecific protein–protein interaction. ...Msgs have been demonstrated to be involved in adhesion to (i) constituents of the extracellular matrix present between lung epithelial cells (fibronectin, vibronectin, laminin) 20, (ii) lung surfactant protein D 21, and (iii) macrophage mannose receptors 22. Consistently, all Msgs, except those of Families IV and C, were predicted to be fungal adhesins using a bioinformatics tool based on signatures conserved among fungal adhesins 23, and all present sites of nitrogen-linked glycosylation that are known to be crucial in pathogen–host interactions. ...they fit the model of fungal adhesin structure with a serine and threonine-rich region at the C terminus responsible for stiffening of the molecule through O-glycosylation and a ligand-binding domain at the N terminus 24. ...the fact that the Msg sets of P. carinii and P. murina are similar, except the additional presence of Family C in P. murina, might reflect that they both infect rodents.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Decreased levels of most phenolics were detected in UV-B-treated fruit after 24 h.•Accumulation of phenolics was observed 36 h after UV-B irradiation.•Down-accumulation of carotenoids was detected ...regardless of UV-B dose.•Lipids decreased but their biosynthetic intermediates increased after UV-B exposure.•Pteridins increased and indole alkaloids decreased in 60 min UV-B-treated fruit.
The possibility to modify plant metabolic profile of plants and fruit to improve their healthy properties using eco-friendly tools, rather than transgenic approaches, gained interest in the last decades. Ultraviolet-B (UV-B) radiation, at low levels, thanks to its ability to influence plant secondary metabolism, could be successfully used to achieve this goal. However, few studies have been conducted so far on the effects of post-harvest UV-B treatments on fruit metabolomics. The present research, aimed to evaluate the impact of UV-B on peach metabolites profile through non-targeted metabolomics (UHPLC-ESI/QTOF-MS) coupled with multivariate chemometrics, provided evidence that 10 and 60 min of post-harvest UV-B irradiation influenced several classes of metabolites. Most phenolics were down-accumulated 24 h after both UV-B treatments, though, after 36 h, anthocyanins, flavones and dihydroflavonols increased (2.06−, 1.92−, 1.68-fold with 10 min UV-B; 6.65−, 2.53−, 2.05-fold with 60 min UV-B, respectively). UV-B reduced carotenoids and most lipids and increased some biosynthetic intermediates and degradation products, some of them known for their positive role in human health. Among alkaloids, some pteridines accumulated, likely derived from folates degradation, while indole alkaloids decreased. Despite the decrease of some bioprotective metabolites as carotenoids, the UV-B-induced up-accumulation of many antioxidant phenolics after 36 h from the exposure suggests an improvement of the healthy properties of peach fruit and reinforces the potential of UV-B controlled irradiation as a nutraceuticals-increasing tool in fruit.
Sociologists have long used educational expectations to understand the complex mental processes underlying individuals' educational decision making. Yet, little research evaluates how students ...actually formulate their educational expectations. Status attainment theory asserts that students adopt their educational expectations early based on family background and social influences, and that their educational expectations are driven by a static mental construct as a result. In contrast, recent research based on Bayesian learning theory hypothesizes that students mostly adapt their educational expectations in light of new information about their academic potential. Comparing models of expectations formation in adolescence, we find that students' expectations do not derive from a static mental construct. However, students adapt their educational expectations only modestly and only in response to very large changes in grade point averages. Thus, adolescent educational expectations stabilize early and are rather persistent over time.
The predominant approach for antibody generation remains animal immunization, which can yield exceptionally selective and potent antibody clones owing to the powerful evolutionary process of somatic ...hypermutation. However, animal immunization is inherently slow, not always accessible and poorly compatible with many antigens. Here, we describe ‘autonomous hypermutation yeast surface display’ (AHEAD), a synthetic recombinant antibody generation technology that imitates somatic hypermutation inside engineered yeast. By encoding antibody fragments on an error-prone orthogonal DNA replication system, surface-displayed antibody repertoires continuously mutate through simple cycles of yeast culturing and enrichment for antigen binding to produce high-affinity clones in as little as two weeks. We applied AHEAD to generate potent nanobodies against the SARS-CoV-2 S glycoprotein, a G-protein-coupled receptor and other targets, offering a template for streamlined antibody generation at large.Autonomous hypermutation yeast surface display (AHEAD) mimics the process of somatic hypermutation in animals to enable the rapid in vitro evolution of antibodies, including nanobodies targeting the RBD of SARS-CoV-2.
About the Authors: Philippe M. Hauser * E-mail: Philippe.Hauser@chuv.ch Affiliation: Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland ORCID logo ...http://orcid.org/0000-0003-2834-7922 Melanie T. Cushion Affiliations Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America, Veterans Administration Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America ORCID logo http://orcid.org/0000-0001-6621-2784 Citation: Hauser PM, Cushion MT (2018) Is sex necessary for the proliferation and transmission of Pneumocystis? Whatever the reason, trophic forms seem to have remained in a latent state during the echinocandin treatment because withdrawal of the drug led to repopulation of asci within a week. ...trophic forms may have subtle roles within the life cycle such as ensuring survival of the fungus rather than proliferation. Targeted staining of a glycoprotein specific to the surface of P. murina ascospores recently provided direct evidence that asci do release these forms during infection and that the latter are then widely present within the population (Fig 2L, green label) 23. ...dehiscence, i.e., the release of the ascospores, does occur frequently within the lungs where the asci have been produced, demonstrating that sex contributes significantly to the proliferation of Pneumocystis (Fig 1). Cushion MT, Ashbaugh A, Hendrix K, Linke MJ, Tisdale N, Sayson SG, Porollo A (2018) Gene expression of Pneumocystis murina after treatment with anidulafungin results in strong signals for sexual reproduction, cell wall integrity, and cell cycle arrest, indicating a requirement for ascus formation for proliferation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Emulators of Earth System Models (ESMs) are complementary to ESMs by providing climate information at lower computational costs. Thus far, the emulation of spatially resolved climate extremes has ...only received limited attention, even though extreme events are one of the most impactful aspects of climate change. Here, we propose a method for the emulation of local annual maximum temperatures, with a focus on reproducing essential statistical properties such as correlations in space and time. We test different emulator configurations and find that driving the emulations with global mean surface temperature offers an optimal compromise between model complexity and performance. We show that the emulations can mimic the temporal evolution and spatial patterns of the underlying climate model simulations and are able to reproduce their natural variability. The general design and the good performance for annual maximum temperatures suggest that the proposed methodology can be applied to other climate extremes.
Plain Language Summary
Climate models are invaluable tools for studying climate change but take a very long time to run, even on modern supercomputers. Emulators of climate models are statistical tools that can be calibrated to mimic the behavior of complex climate models with a much lower computational demand. However, they are typically not designed to reproduce climate extremes, despite the fact that extreme climate events belong to the most impactful aspects of climate change. In this study, we propose a method for the emulation of annual maximum temperature in time and space. This method also reproduces the natural variability of climate models, even though it is driven only by global mean surface temperature. We show that the resulting emulations are very similar to the data created by climate models. In an example application, we use the emulator to examine the extreme temperatures for different climate scenarios.
Key Points
We present a method for the emulation of spatially resolved annual maximum temperatures from Earth System Models
The emulator reproduces statistical properties and correlations in space and time and can be extended to other extreme indicators
The method exhibits good performance for annual maximum temperatures
Table 1 Haemodynamically significant congenital anomalies of the coronary arteries Isolated/primary-without CHD * Anomalous origin of accessory coronary arteries from the pulmonary artery (ALCAPA, ...ARCAPA) * Ectopic origin of the coronary arteries from aortic sinus * Absence of a coronary artery * Congenital coronary artery fistula Secondary-with CHD * PA + IVS * AA + MS AA, aortic atresia; ALCAPA, anomalous origin of the left coronary artery from the pulmonary artery; ARCAPA, anomalous origin of the right coronary artery from the pulmonary artery; CHD, congenital heart disease; IVS, interventricular septum; MS, mitral stenosis; PA, pulmonary atresia. In such cases symptoms appear within a few days of birth, and death follows within two weeks; it is compatible with life only if associated with pulmonary hypertension. Since Edwards' fundamental contribution, 8 it has been known that dramatic changes occur in the coronary circulation in all children with ALCAPA within the first weeks of life.
This article addresses a potentially serious problem with the widely used self-rated health (SRH) survey item: that different groups have systematically different ways of using the item's response ...categories. Analyses based on unadjusted SRH may thus yield misleading results. The authors evaluate anchoring vignettes as a possible solution to this problem. Using vignettes specifically designed to calibrate the SRH item and data from the Wisconsin Longitudinal Study (WLS; N = 2,625), the authors show how demographic and health-related factors, including sex and education, predict differences in rating styles. Such differences, when not adjusted for statistically, may be sufficiently large to lead to mistakes in rank orderings of groups. In the present sample, unadjusted models show that women have better SRH than men, but this difference disappears in models adjusting for women's greater health-optimism. Anchoring vignettes appear a promising tool for improving intergroup comparability of SRH.
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