The impact of ocean acidification (OA) on coral calcification, a subject of intense current interest, is poorly understood in part because of the presence of symbionts in adult corals. Early life ...history stages of Acropora spp. provide an opportunity to study the effects of elevated CO2 on coral calcification without the complication of symbiont metabolism. Therefore, we used the Illumina RNAseq approach to study the effects of acute exposure to elevated CO2 on gene expression in primary polyps of Acropora millepora, using as reference a novel comprehensive transcriptome assembly developed for this study. Gene ontology analysis of this whole transcriptome data set indicated that CO2‐driven acidification strongly suppressed metabolism but enhanced extracellular organic matrix synthesis, whereas targeted analyses revealed complex effects on genes implicated in calcification. Unexpectedly, expression of most ion transport proteins was unaffected, while many membrane‐associated or secreted carbonic anhydrases were expressed at lower levels. The most dramatic effect of CO2‐driven acidification, however, was on genes encoding candidate and known components of the skeletal organic matrix that controls CaCO3 deposition. The skeletal organic matrix effects included elevated expression of adult‐type galaxins and some secreted acidic proteins, but down‐regulation of other galaxins, secreted acidic proteins, SCRiPs and other coral‐specific genes, suggesting specialized roles for the members of these protein families and complex impacts of OA on mineral deposition. This study is the first exhaustive exploration of the transcriptomic response of a scleractinian coral to acidification and provides an unbiased perspective on its effects during the early stages of calcification.
Corals play a key role in ocean ecosystems and carbonate balance, but their molecular response to ocean acidification remains unclear. The only previous whole‐transcriptome study (Moya et al. ...Molecular Ecology, 2012; 21, 2440) documented extensive disruption of gene expression, particularly of genes encoding skeletal organic matrix proteins, in juvenile corals (Acropora millepora) after short‐term (3 d) exposure to elevated pCO2. In this study, whole‐transcriptome analysis was used to compare the effects of such ‘acute’ (3 d) exposure to elevated pCO2 with a longer (‘prolonged’; 9 d) period of exposure beginning immediately post‐fertilization. Far fewer genes were differentially expressed under the 9‐d treatment, and although the transcriptome data implied wholesale disruption of metabolism and calcification genes in the acute treatment experiment, expression of most genes was at control levels after prolonged treatment. There was little overlap between the genes responding to the acute and prolonged treatments, but heat shock proteins (HSPs) and heat shock factors (HSFs) were over‐represented amongst the genes responding to both treatments. Amongst these was an HSP70 gene previously shown to be involved in acclimation to thermal stress in a field population of another acroporid coral. The most obvious feature of the molecular response in the 9‐d treatment experiment was the upregulation of five distinct Bcl‐2 family members, the majority predicted to be anti‐apoptotic. This suggests that an important component of the longer term response to elevated CO2 is suppression of apoptosis. It therefore appears that juvenile A. millepora have the capacity to rapidly acclimate to elevated pCO2, a process mediated by upregulation of specific HSPs and a suite of Bcl‐2 family members.
We use asteroseismic data obtained by the NASA Kepler mission to estimate the fundamental properties of more than 500 main-sequence and sub-giant stars. Data obtained during the first 10 months of ...Kepler science operations were used for this work, when these solar-type targets were observed for one month each in survey mode. Stellar properties have been estimated using two global asteroseismic parameters and complementary photometric and spectroscopic data. Homogeneous sets of effective temperatures, Tsubeff , were available for the entire ensemble from complementary photometry; spectroscopic estimates of Tsubeff and Fe/H were available from a homogeneous analysis of ground-based data on a subset of 87 stars. We adopt a grid-based analysis, coupling six pipeline codes to 11 stellar evolutionary grids. Future analyses using individual oscillation frequencies will offer significant improvements on up to 150 stars, in particular for estimates of the ages, where having the individual frequency data is most important.
Preterm birth is a leading cause of cognitive impairment in childhood and is associated with cerebral gray and white matter abnormalities. Using multimodal image analysis, we tested the hypothesis ...that altered thalamic development is an important component of preterm brain injury and is associated with other macro- and microstructural alterations. T(1)- and T(2)-weighted magnetic resonance images and 15-direction diffusion tensor images were acquired from 71 preterm infants at term-equivalent age. Deformation-based morphometry, Tract-Based Spatial Statistics, and tissue segmentation were combined for a nonsubjective whole-brain survey of the effect of prematurity on regional tissue volume and microstructure. Increasing prematurity was related to volume reduction in the thalamus, hippocampus, orbitofrontal lobe, posterior cingulate cortex, and centrum semiovale. After controlling for prematurity, reduced thalamic volume predicted: lower cortical volume; decreased volume in frontal and temporal lobes, including hippocampus, and to a lesser extent, parietal and occipital lobes; and reduced fractional anisotropy in the corticospinal tracts and corpus callosum. In the thalamus, reduced volume was associated with increased diffusivity. This demonstrates a significant effect of prematurity on thalamic development that is related to abnormalities in allied brain structures. This suggests that preterm delivery disrupts specific aspects of cerebral development, such as the thalamocortical system.
Emerging SARS-CoV-2 variants are creating major challenges in the ongoing COVID-19 pandemic. Being able to predict mutations that could arise in SARS-CoV-2 leading to increased transmissibility or ...immune evasion would be extremely valuable in development of broad-acting therapeutics and vaccines, and prioritising viral monitoring and containment. Here we use in vitro evolution to seek mutations in SARS-CoV-2 receptor binding domain (RBD) that would substantially increase binding to ACE2. We find a double mutation, S477N and Q498H, that increases affinity of RBD for ACE2 by 6.5-fold. This affinity gain is largely driven by the Q498H mutation. We determine the structure of the mutant-RBD:ACE2 complex by cryo-electron microscopy to reveal the mechanism for increased affinity. Addition of Q498H to SARS-CoV-2 RBD variants is found to boost binding affinity of the variants for human ACE2 and confer a new ability to bind rat ACE2 with high affinity. Surprisingly however, in the presence of the common N501Y mutation, Q498H inhibits binding, due to a clash between H498 and Y501 side chains. To achieve an intermolecular bonding network, affinity gain and cross-species binding similar to Q498H alone, RBD variants with the N501Y mutation must acquire instead the related Q498R mutation. Thus, SARS-CoV-2 RBD can access large affinity gains and cross-species binding via two alternative mutational routes involving Q498, with route selection determined by whether a variant already has the N501Y mutation. These mutations are now appearing in emerging SARS-CoV-2 variants where they have the potential to influence human-to-human and cross-species transmission.
Since the late 1980s, with the first identification of individuals who were exposed to human immunodeficiency virus type 1 (HIV-1) yet remained uninfected, or “HIV-1—resistant” individuals, a large ...number of cohorts that include HIV-exposed seronegative (HESN) subjects have been identified globally for the purpose of investigating the genetic, immunologic, and environmental factors that may help alter susceptibility to HIV-1. In this article, in light of the recent International Symposium on Natural Immunity to HIV, we review the characteristics of different groups with respect to their relative risks and briefly summarize the known cohorts that include exposed uninfected subjects worldwide.
ABSTRACT
Asteroseismology is a powerful tool to infer fundamental stellar properties. The use of these asteroseismic-inferred properties in a growing number of astrophysical contexts makes it vital ...to understand their accuracy. Consequently, we performed a hare-and-hounds exercise where the hares simulated data for six artificial main-sequence stars and the hounds inferred their properties based on different inference procedures. To mimic a pipeline such as that planned for the PLATO mission, all hounds used the same model grid. Some stars were simulated using the physics adopted in the grid, others a different one. The maximum relative differences found (in absolute value) between the inferred and true values of the mass, radius, and age were 4.32, 1.33, and 11.25 per cent, respectively. The largest systematic differences in radius and age were found for a star simulated assuming gravitational settling, not accounted for in the model grid, with biases of −0.88 per cent (radius) and 8.66 per cent (age). For the mass, the most significant bias (−3.16 per cent) was found for a star with a helium enrichment ratio outside the grid range. Moreover, an ∼7 per cent dispersion in age was found when adopting different prescriptions for the surface corrections or shifting the classical observations by ±1σ. The choice of the relative weight given to the classical and seismic constraints also impacted significantly the accuracy and precision of the results. Interestingly, only a few frequencies were required to achieve accurate results on the mass and radius. For the age the same was true when at least one l = 2 mode was considered.
Abstract
The impact of ocean acidification (OA) on coral calcification, a subject of intense current interest, is poorly understood in part because of the presence of symbionts in adult corals. Early ...life history stages of
Acropora
spp. provide an opportunity to study the effects of elevated CO
2
on coral calcification without the complication of symbiont metabolism. Therefore, we used the Illumina RNAseq approach to study the effects of acute exposure to elevated CO
2
on gene expression in primary polyps of
Acropora millepora
, using as reference a novel comprehensive transcriptome assembly developed for this study. Gene ontology analysis of this whole transcriptome data set indicated that CO
2
‐driven acidification strongly suppressed metabolism but enhanced extracellular organic matrix synthesis, whereas targeted analyses revealed complex effects on genes implicated in calcification. Unexpectedly, expression of most ion transport proteins was unaffected, while many membrane‐associated or secreted carbonic anhydrases were expressed at lower levels. The most dramatic effect of CO
2
‐driven acidification, however, was on genes encoding candidate and known components of the skeletal organic matrix that controls CaCO
3
deposition. The skeletal organic matrix effects included elevated expression of adult‐type galaxins and some secreted acidic proteins, but down‐regulation of other galaxins, secreted acidic proteins, SCRiPs and other coral‐specific genes, suggesting specialized roles for the members of these protein families and complex impacts of OA on mineral deposition. This study is the first exhaustive exploration of the transcriptomic response of a scleractinian coral to acidification and provides an unbiased perspective on its effects during the early stages of calcification.
"There is a dual purpose in developing a mechanical heart and lung apparatus. The first is to maintain a part of the cardiorespiratory functions temporarily in patients with a failing heart or lung, ...or both, in the hope that, with such direct aid for a short time, these organs may be able to resume their entire function. The second purpose is of surgical interest."Bernard J. Miller, John H. Gibbon Jr and Mary H. Gibbon, 19511.While the early pioneers of cardiopulmonary bypass (CPB) hoped the technology could be used as a form of temporary life support for patients with acute cardiac or respiratory failure, initial attempts at prolonged "partial perfusion", using rotating disc oxygenators (in which blood was directly exposed to oxygen) proved disappointing2-4. These "direct contact" oxygenators caused considerable trauma to the blood, resulting in haemolysis and protein denaturation, and could rarely be used for more than a few hours before serious complications occurred5.
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