The three lipocalins of egg-white: only Ex-FABP inhibits siderophore-dependent iron sequestration by Salmonella Enteritidis

Salmonella Enteritidis is the most prevalent food-borne pathogen associated with egg-related outbreaks in the European Union. During egg colonization, S. Enteritidis must resist the powerful anti-bacterial activities of egg white (EW) and overcome ovotransferrin-imposed iron-restriction (the most important anti-bacterial mechanism of EW). Many pathogens respond to iron restriction by secreting iron-chelating chemicals called siderophores but EW contains a siderophore-sequestering “lipocalin” protein (Ex-FABP) that is predicted to limit the usefulness of siderophores in EW. S. Enteritidis produces two siderophores: enterobactin, which is strongly bound by Ex-FABP; and the di-glucosylated enterobactin-derivative, salmochelin (a so-called “stealth” siderophore), which is not recognized by Ex-FABP. Thus, production of salmochelin may allow S. Enteritidis to escape Ex-FABP-mediated growth inhibition under iron restriction although it is unclear whether its EW concentration is sufficient to inhibit pathogens. Further, two other lipocalins (Cal-γ and α-1-ovoglycoprotein) are found in EW but their siderophore sequestration potential remains unexplored. In addition, the effect of EW lipocalins on the major EW pathogen, S. Enteritidis, has yet to be reported. We overexpressed and purified the three lipocalins of EW and investigated their ability to interact with the siderophores of S. Enteritidis, as well as their EW concentrations. The results show that Ex-FABP is present in EW at concentrations (5.1 μM) sufficient to inhibit growth of a salmochelin-deficient S. Enteritidis mutant under iron restriction but has little impact on the salmochelin-producing wildtype. Neither Cal-γ nor α-1-ovoglycoprotein bind salmochelin or enterobactin, nor do they inhibit iron-restricted growth of S. Enteritidis. However, both are present in EW at significant concentrations (5.6 and 233 μM, respectively) indicating that α-1-ovoglycoprotein is the 4th most abundant protein in EW, with Cal-γ and Ex-FABP at 11th and 12th most abundant. Further, we confirm the preference (16-fold) of Ex-FABP for the ferrated form (Kd of 5.3 nM) of enterobactin over the iron-free form (Kd of 86.2 nM), and its lack of affinity for salmochelin. In conclusion, our findings show that salmochelin production by S. Enteritidis enables this key egg-associated pathogen to overcome the enterobactin-sequestration activity of Ex-FABP when this lipocalin is provided at levels found in EW

A method to derive satellite PAR albedo time series over first-year sea ice in the Arctic Ocean

Deriving sea ice albedo from spaceborne platforms is of interest to model the propagation of the photosynthetically available radiation (PAR) through Arctic sea ice. We show here that use of the Moderate Resolution Imaging Spectroradiometer (MODIS) operational surface reflectance satellite product to derive albedo in the PAR spectral range is possible. To retrieve PAR albedo from the remote sensing surface reflectance, we trained a predictive model based on a principal component analysis with in situ and simulated data. The predictive model can be applied to first-year sea ice surfaces such as dry snow, melting snow, bare ice and melt ponds. Based on in situ measurements and the prescribed atmospheric correction uncertainty, the estimated PAR albedo had a mean absolute error of 0.057, a root mean square error of 0.074 and an R2 value of 0.91. As a demonstration, we retrieved PAR albedo on a 9-km2 area over late spring and early summer 2015 and 2016 at a coastal location in Baffin Bay, Canada. On-site measurements of PAR albedo, melt pond fraction and types of precipitation were used to examine the estimated PAR albedo time series. The results show a dynamic and realistic PAR albedo time series, although clouds remained the major obstacle to the method. This easy-to-implement model may be used for the partitioning of PAR in the Arctic Ocean and ultimately to better understand the dynamics of marine primary producers.publishedVersio

Preventing Corrosion of Aluminum Metal with Nanometer-Thick Films of Al2O3 Capped with TiO2 for Ultraviolet Plasmonics

Extending plasmonics into the ultraviolet range imposes the use of aluminum to achieve the best optical performance. However, water corrosion is a major limiting issue for UV aluminum plasmonics, as this phenomenon occurs significantly faster in presence of UV light, even at low laser powers of a few microwatts. Here we assess the performance of nanometer-thick layers of various metal oxides deposited by atomic layer deposition (ALD) and plasma-enhanced chemical vapor deposition (PECVD) on top of aluminum nanoapertures to protect the metal against UV photocorrosion. The combination of a 5 nm Al2O3 layer covered by a 5 nm TiO2 capping provides the best resistance performance, while a single 10 nm layer of SiO2 or HfO2 is a good alternative. We also report the influence of the laser wavelength, the laser operation mode and the pH of the solution. Properly choosing these conditions significantly extends the range of optical powers for which the aluminum nanostructures can be used. As application, we demonstrate the label-free detection of streptavidin proteins with improved signal to noise ratio. Our approach is also beneficial to promote the long-term stability of the aluminum nanostructures. Finding the appropriate nanoscale protection against aluminum corrosion is the key to enable the development of UV plasmonic applications in chemistry and biology

Design and Evaluation of a Novel Haptic Interface for Horse-Drawn Carriage Simulation

Animal welfare has become an increasingly important concern in the sports field. Learning horse-drawn carriage driving requires much time and effort for both the drivers and the horses because the associated gestures to avoid harming the horses are difficult to acquire. This raises the need to develop realistic simulation environments for future drivers. To this end, two haptic interface prototypes were designed, coupled with dedicated simulation software. The first was developed based on a SPIDAR haptic device and implemented simple behaviors of the carriage. A user study demonstrated interest in such a simulator, which led to the design of a second prototype, on a different architecture than the first prototype, for integrating more precise laws of horse behavior such as mood and allowing a more subtle control of forces. An evaluation with driving learners revealed that the simulator was capable of not only producing sensations close to reality but also improving the interaction between the trainer and the learner.This work was supported by the Ifce and SAHn under grant no. 2016-17-007

Accelerating metabolic models evaluation with statistical metamodels: application to Salmonella infection models

Mathematical and numerical models are increasingly used in microbial ecology to model the fate of microbial communities in their ecosystem. These models allow to connect in a mechanistic framework species-level informations, such as the microbial genomes, with macro-scale features, such as species spatial distributions or metabolite gradients. Numerous models are built upon species-level metabolic models that predict the metabolic behaviour of a microbe by solving an optimization problem knowing its genome and its nutritional environment. However, screening the community dynamics with these metabolic models implies to solve such an optimization problem by species at each time step, leading to a significant computational load further increased by several orders of magnitude when spatial dimensions are added. In this paper, we propose a statistical framework based on Reproducing Kernel Hilbert Space (RKHS) metamodels that are used to provide fast approximations of the original metabolic model. The metamodel can replace the optimization step in the system dynamics, providing comparable outputs at a much lower computational cost. We will first build a system dynamics model of a simplified gut microbiota composed of a unique commensal bacterial strain in interaction with the host and challenged by a Salmonella infection. Then, the machine learning method will be introduced, and particularly the ANOVA-RKHS that will be exploited to achieve variable selection and model parsimony. A training dataset will be constructed with the original system dynamics model and hyper-parameters will be carefully chosen to provide fast and accurate approximations of the original model. Finally, the accuracy of the trained metamodels will be assessed, in particular by comparing the system dynamics outputs when the original model is replaced by its metamodel. The metamodel allows an overall relative error of 4.71% but reducing the computational load by a speed-up factor higher than 45, while correctly reproducing the complex behaviour occurring during Salmonella infection. These results provide a proof-of-concept of the potentiality of machine learning methods to give fast approximations of metabolic model outputs and pave the way towards PDE-based spatio-temporal models of microbial communities including microbial metabolism and host-microbiota-pathogen interactions

Molecular mechanisms underlying physical exercise-induced brain BDNF overproduction

Accumulating evidence supports that physical exercise (EX) is the most effective non-pharmacological strategy to improve brain health. EX prevents cognitive decline associated with age and decreases the risk of developing neurodegenerative diseases and psychiatric disorders. These positive effects of EX can be attributed to an increase in neurogenesis and neuroplastic processes, leading to learning and memory improvement. At the molecular level, there is a solid consensus to involve the neurotrophin brain-derived neurotrophic factor (BDNF) as the crucial molecule for positive EX effects on the brain. However, even though EX incontestably leads to beneficial processes through BDNF expression, cellular sources and molecular mechanisms underlying EX-induced cerebral BDNF overproduction are still being elucidated. In this context, the present review offers a summary of the different molecular mechanisms involved in brain’s response to EX, with a specific focus on BDNF. It aims to provide a cohesive overview of the three main mechanisms leading to EX-induced brain BDNF production: the neuronal-dependent overexpression, the elevation of cerebral blood flow (hemodynamic hypothesis), and the exerkine signaling emanating from peripheral tissues (humoral response). By shedding light on these intricate pathways, this review seeks to contribute to the ongoing elucidation of the relationship between EX and cerebral BDNF expression, offering valuable insights into the potential therapeutic implications for brain health enhancement

Diffusion‐weighted MR spectroscopy: Consensus, recommendations, and resources from acquisition to modeling

Brain cell structure and function reflect neurodevelopment, plasticity, and aging; and changes can help flag pathological processes such as neurodegeneration and neuroinflammation. Accurate and quantitative methods to noninvasively disentangle cellular structural features are needed and are a substantial focus of brain research. Diffusion‐weighted MRS (dMRS) gives access to diffusion properties of endogenous intracellular brain metabolites that are preferentially located inside specific brain cell populations. Despite its great potential, dMRS remains a challenging technique on all levels: from the data acquisition to the analysis, quantification, modeling, and interpretation of results. These challenges were the motivation behind the organization of the Lorentz Center workshop on “Best Practices & Tools for Diffusion MR Spectroscopy” held in Leiden, the Netherlands, in September 2021. During the workshop, the dMRS community established a set of recommendations to execute robust dMRS studies. This paper provides a description of the steps needed for acquiring, processing, fitting, and modeling dMRS data, and provides links to useful resources

Severe ACTA1-related nemaline myopathy: intranuclear rods, cytoplasmic bodies, and enlarged perinuclear space as characteristic pathological features on muscle biopsies.

peer reviewedNemaline myopathy (NM) is a muscle disorder with broad clinical and genetic heterogeneity. The clinical presentation of affected individuals ranges from severe perinatal muscle weakness to milder childhood-onset forms, and the disease course and prognosis depends on the gene and mutation type. To date, 14 causative genes have been identified, and ACTA1 accounts for more than half of the severe NM cases. ACTA1 encodes α-actin, one of the principal components of the contractile units in skeletal muscle. We established a homogenous cohort of ten unreported families with severe NM, and we provide clinical, genetic, histological, and ultrastructural data. The patients manifested antenatal or neonatal muscle weakness requiring permanent respiratory assistance, and most deceased within the first months of life. DNA sequencing identified known or novel ACTA1 mutations in all. Morphological analyses of the muscle biopsy specimens showed characteristic features of NM histopathology including cytoplasmic and intranuclear rods, cytoplasmic bodies, and major myofibrillar disorganization. We also detected structural anomalies of the perinuclear space, emphasizing a physiological contribution of skeletal muscle α-actin to nuclear shape. In-depth investigations of the nuclei confirmed an abnormal localization of lamin A/C, Nesprin-1, and Nesprin-2, forming the main constituents of the nuclear lamina and the LINC complex and ensuring nuclear envelope integrity. To validate the relevance of our findings, we examined muscle samples from three previously reported ACTA1 cases, and we identified the same set of structural aberrations. Moreover, we measured an increased expression of cardiac α-actin in the muscle samples from the patients with longer lifespan, indicating a potential compensatory effect. Overall, this study expands the genetic and morphological spectrum of severe ACTA1-related nemaline myopathy, improves molecular diagnosis, highlights the enlargement of the perinuclear space as an ultrastructural hallmark, and indicates a potential genotype/phenotype correlation

Astrometric accelerations as dynamical beacons : discovery and characterization of HIP 21152 B, the First T-dwarf companion in the Hyades * * Based in part on data collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan.

Benchmark brown dwarf companions with well-determined ages and model-independent masses are powerful tools to test substellar evolutionary models and probe the formation of giant planets and brown dwarfs. Here, we report the independent discovery of HIP 21152 B, the first imaged brown dwarf companion in the Hyades, and conduct a comprehensive orbital and atmospheric characterization of the system. HIP 21152 was targeted in an ongoing high-contrast imaging campaign of stars exhibiting proper-motion changes between Hipparcos and Gaia, and was also recently identified by Bonavita et al. (2022) and Kuzuhara et al. (2022). Our Keck/NIRC2 and SCExAO/CHARIS imaging of HIP 21152 revealed a comoving companion at a separation of 0.″37 (16 au). We perform a joint orbit fit of all available relative astrometry and radial velocities together with the Hipparcos-Gaia proper motions, yielding a dynamical mass of 24−4+6MJup , which is 1–2σ lower than evolutionary model predictions. Hybrid grids that include the evolution of cloud properties best reproduce the dynamical mass. We also identify a comoving wide-separation (1837″ or 7.9 × 104 au) early-L dwarf with an inferred mass near the hydrogen-burning limit. Finally, we analyze the spectra and photometry of HIP 21152 B using the Saumon & Marley (2008) atmospheric models and a suite of retrievals. The best-fit grid-based models have f sed = 2, indicating the presence of clouds, T eff = 1400 K, and logg=4.5dex . These results are consistent with the object’s spectral type of T0 ± 1. As the first benchmark brown dwarf companion in the Hyades, HIP 21152 B joins the small but growing number of substellar companions with well-determined ages and dynamical masses

Astrometric Accelerations as Dynamical Beacons: Discovery and Characterization of HIP 21152 B, the First T-dwarf Companion in the Hyades*

Benchmark brown dwarf companions with well-determined ages and model-independent masses are powerful tools to test substellar evolutionary models and probe the formation of giant planets and brown dwarfs. Here, we report the independent discovery of HIP 21152 B, the first imaged brown dwarf companion in the Hyades, and conduct a comprehensive orbital and atmospheric characterization of the system. HIP 21152 was targeted in an ongoing high-contrast imaging campaign of stars exhibiting proper-motion changes between Hipparcos and Gaia, and was also recently identified by Bonavita et al. (2022) and Kuzuhara et al. (2022). Our Keck/NIRC2 and SCExAO/CHARIS imaging of HIP 21152 revealed a comoving companion at a separation of 0.″37 (16 au). We perform a joint orbit fit of all available relative astrometry and radial velocities together with the Hipparcos-Gaia proper motions, yielding a dynamical mass of $24^{+6}_{-4}M_{Jup}$, which is 1–2σ lower than evolutionary model predictions. Hybrid grids that include the evolution of cloud properties best reproduce the dynamical mass. We also identify a comoving wide-separation (1837″ or $7.9 {\times} 10^4 au$) early-L dwarf with an inferred mass near the hydrogen-burning limit. Finally, we analyze the spectra and photometry of HIP 21152 B using the Saumon & Marley (2008) atmospheric models and a suite of retrievals. The best-fit grid-based models have $f_{sed} = 2$, indicating the presence of clouds, $T_{eff} = 1400 K$, and $log\, g=4.5dex$ . These results are consistent with the object’s spectral type of T0 ± 1. As the first benchmark brown dwarf companion in the Hyades, HIP 21152 B joins the small but growing number of substellar companions with well-determined ages and dynamical masses. * Based in part on data collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan