The maintenance of standing genetic variation: Gene flow vs. selective neutrality in Atlantic stickleback fish

Adaptation to derived habitats often occurs from standing genetic variation. The maintenance within ancestral populations of genetic variants favourable in derived habitats is commonly ascribed to long-term antagonism between purifying selection and gene flow resulting from hybridization across habitats. A largely unexplored alternative idea based on quantitative genetic models of polygenic adaptation is that variants favoured in derived habitats are neutral in ancestral populations when their frequency is relatively low. To explore the latter, we first identify genetic variants important to the adaptation of threespine stickleback fish (Gasterosteus aculeatus) to a rare derived habitat-nutrient-depleted acidic lakes-based on whole-genome sequence data. Sequencing marine stickleback from six locations across the Atlantic Ocean then allows us to infer that the frequency of these derived variants in the ancestral habitat is unrelated to the likely opportunity for gene flow of these variants from acidic-adapted populations. This result is consistent with the selective neutrality of derived variants within the ancestor. Our study thus supports an underappreciated explanation for the maintenance of standing genetic variation, and calls for a better understanding of the fitness consequences of adaptive variation across habitats and genomic backgrounds

Translation-dependent mRNA localization to Caenorhabditis elegans adherens junctions

mRNA localization is an evolutionarily widespread phenomenon that can facilitate subcellular protein targeting. Extensive work has focused on mRNA targeting through 'zip-codes' within untranslated regions (UTRs), whereas much less is known about translation-dependent cues. Here, we examine mRNA localization in Caenorhabditis elegans embryonic epithelia. From an smFISH-based survey, we identified mRNAs associated with the cell membrane or cortex, and with apical junctions in a stage- and cell type-specific manner. Mutational analyses for one of these transcripts, dlg-1/discs large, revealed that it relied on a translation-dependent process and did not require its 5' or 3' UTRs. We suggest a model in which dlg-1 transcripts are co-translationally localized with the nascent protein: first the translating complex goes to the cell membrane using sequences located at the C-terminal/3' end, and then apically using N-terminal/5' sequences. These studies identify a translation-based process for mRNA localization within developing epithelia and determine the necessary cis-acting sequences for dlg-1 mRNA targeting

Multiaxial experiments with radial loading paths on a polymeric foam

Cellular materials such as polymeric foams in particular have been widely studied under uniaxial loading conditions. Many experimental studies have been focusing recently, however, on the responses of these foams to multiaxial loads. In the present study, a novel experimental hexapod device was used to perform combined uniaxial compression and simple shear tests. Using a post-processing method of analysis which can be used to study elementary mechanical behavior, the authors show the occurrence of non-proportional stress paths in the material under investigation although proportional kinematic paths were imposed. A failure limit criterion is presented for use with the foam of interest. The results of the present analysis yield useful information for meeting our future objective, namely to develop a numerical model for simulating multiaxial loading conditions.FUI GENOSI

Spatial control of nucleoporin condensation by fragile X-related proteins

Nucleoporins (Nups) build highly organized nuclear pore complexes (NPCs) at the nuclear envelope (NE). Several Nups assemble into a sieve-like hydrogel within the central channel of the NPCs. In the cytoplasm, the soluble Nups exist, but how their assembly is restricted to the NE is currently unknown. Here, we show that fragile X-related protein 1 (FXR1) can interact with several Nups and facilitate their localization to the NE during interphase through a microtubule-dependent mechanism. Downregulation of FXR1 or closely related orthologs FXR2 and fragile X mental retardation protein (FMRP) leads to the accumulation of cytoplasmic Nup condensates. Likewise, models of fragile X syndrome (FXS), characterized by a loss of FMRP, accumulate Nup granules. The Nup granule-containing cells show defects in protein export, nuclear morphology and cell cycle progression. Our results reveal an unexpected role for the FXR protein family in the spatial regulation of nucleoporin condensation

Resuming Training in High-Level Athletes After Mild COVID-19 Infection: A Multicenter Prospective Study (ASCCOVID-19)

BACKGROUND: There is a paucity of data on cardiovascular sequelae of asymptomatic/mildly symptomatic SARS-Cov-2 infections (COVID). OBJECTIVES: The aim of this prospective study was to characterize the cardiovascular sequelae of asymptomatic/mildly symptomatic COVID-19 among high/elite-level athletes. METHODS: 950 athletes (779 professional French National Rugby League (F-NRL) players; 171 student athletes) were included. SARS-Cov-2 testing was performed at inclusion, and F-NRL athletes were intensely followed-up for incident COVID-19. Athletes underwent ECG and biomarker profiling (D-Dimer, troponin, C-reactive protein). COVID(+) athletes underwent additional exercise testing, echocardiography and cardiac magnetic resonance imaging (CMR). RESULTS: 285/950 athletes (30.0%) had mild/asymptomatic COVID-19 [79 (8.3%) at inclusion (COVID(+)(prevalent)); 206 (28.3%) during follow-up (COVID(+)(incident))]. 2.6% COVID(+) athletes had abnormal ECGs, while 0.4% had an abnormal echocardiogram. During stress testing (following 7-day rest), COVID(+) athletes had a functional capacity of 12.8 ± 2.7 METS with only stress-induced premature ventricular ectopy in 10 (4.3%). Prevalence of CMR scar was comparable between COVID(+) athletes and controls [COVID(+) vs. COVID(-); 1/102 (1.0%) vs 1/28 (3.6%)]. During 289 ± 56 days follow-up, one athlete had ventricular tachycardia, with no obvious link with a SARS-CoV-2 infection. The proportion with troponin I and CRP values above the upper-limit threshold was comparable between pre- and post-infection (5.9% vs 5.9%, and 5.6% vs 8.7%, respectively). The proportion with D-Dimer values above the upper-limit threshold increased when comparing pre- and post-infection (7.9% vs 17.3%, P = 0.01). CONCLUSION: The absence of cardiac sequelae in pauci/asymptomatic COVID(+) athletes is reassuring and argues against the need for systematic cardiac assessment prior to resumption of training (clinicaltrials.gov; NCT04936503).L'Institut de Rythmologie et modélisation Cardiaqu

The Virtual Metabolic Human database: integrating human and gut microbiome metabolism with nutrition and disease

A multitude of factors contribute to complex diseases and can be measured with ‘omics’ methods. Databases facilitate data interpretation for underlying mechanisms. Here, we describe the Virtual Metabolic Human (VMH, www.vmh.life) database encapsulating current knowledge of human metabolism within five interlinked resources ‘Human metabolism’, ‘Gut microbiome’, ‘Disease’, ‘Nutrition’, and ‘ReconMaps’. The VMH captures 5180 unique metabolites, 17 730 unique reactions, 3695 human genes, 255 Mendelian diseases, 818 microbes, 632 685 microbial genes and 8790 food items. The VMH’s unique features are (i) the hosting of the metabolic reconstructions of human and gut microbes amenable for metabolic modeling; (ii) seven human metabolic maps for data visualization; (iii) a nutrition designer; (iv) a user-friendly webpage and application-programming interface to access its content; (v) user feedback option for community engagement and (vi) the connection of its entities to 57 other web resources. The VMH represents a novel, interdisciplinary database for data interpretation and hypothesis generation to the biomedical community

Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate

Current Research into Applications of Tomography for Fusion Diagnostics

Retrieving spatial distribution of plasma emissivity from line integrated measurements on tokamaks presents a challenging task due to ill-posedness of the tomography problem and limited number of the lines of sight. Modern methods of plasma tomography therefore implement a-priori information as well as constraints, in particular some form of penalisation of complexity. In this contribution, the current tomography methods under development (Tikhonov regularisation, Bayesian methods and neural networks) are briefly explained taking into account their potential for integration into the fusion reactor diagnostics. In particular, current development of the Minimum Fisher Regularisation method is exemplified with respect to real-time reconstruction capability, combination with spectral unfolding and other prospective tasks

Impact of fast ions on density peaking in JET: fluid and gyrokinetic modeling

The effect of fast ions on turbulent particle transport, driven by ion temperature gradient (ITG)/ trapped electron mode turbulence, is studied. Two neutral beam injection (NBI) heated JET discharges in different regimes are analyzed at the radial position ρ$_{t}$=0.6, one of them an L-mode and the other one an H-mode discharge. Results obtained from the computationally efficient fluid model EDWM and the gyro-fluid model TGLF are compared to linear and nonlinear gyrokinetic GENE simulations as well as the experimentally obtained density peaking. In these models, the fast ions are treated as a dynamic species with a Maxwellian background distribution. The dependence of the zero particle flux density gradient (peaking factor) on fast ion density, temperature and corresponding gradients, is investigated. The simulations show that the inclusion of a fast ion species has a stabilizing influence on the ITG mode and reduces the peaking of the main ion and electron density profiles in the absence of sources. The models mostly reproduce the experimentally obtained density peaking for the L-mode discharge whereas the H-mode density peaking is significantly underpredicted, indicating the importance of the NBI particle source for the H-mode density profile

The effect of beryllium oxide on retention in JET ITER-like wall tiles

Preliminary results investigating the microstructure, bonding and effect of beryllium oxide formation on retention in the JET ITER-like wall beryllium tiles, are presented. The tiles have been investigated by several techniques: Scanning Electron Microscopy (SEM) equipped with Energy Dispersive X-ray (EDX), Transmission Electron microscopy (TEM) equipped with EDX and Electron Energy Loss Spectroscopy (EELS), Raman Spectroscopy and Thermal Desorption Spectroscopy (TDS). This paper focuses on results from melted materials of the dump plate tiles in JET. From our results and the literature, it is concluded, beryllium can form micron deep oxide islands contrary to the nanometric oxides predicted under vacuum conditions. The deepest oxides analyzed were up to 2-micron thicknesses. The beryllium Deuteroxide (BeOxDy) bond was found with Raman Spectroscopy. Application of EELS confirmed the oxide presence and stoichiometry. Literature suggests these oxides form at temperatures greater than 700 °C where self-diffusion of beryllium ions through the surface oxide layer can occur. Further oxidation is made possible between oxygen plasma impurities and the beryllium ions now present at the wall surface. Under Ultra High Vacuum (UHV) nanometric Beryllium oxide layers are formed and passivate at room temperature. After continual cyclic heating (to the point of melt formation) in the presence of oxygen impurities from the plasma, oxide growth to the levels seen experimentally (approximately two microns) is proposed. This retention mechanism is not considered to contribute dramatically to overall retention in JET, due to low levels of melt formation. However, this mechanism, thought the result of operation environment and melt formation, could be of wider concern to ITER, dependent on wall temperatures