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We present the first results for the sputtering of grain mantles and cores obtained with selfconsistent multifluid hydromagnetic models of oblique C-type shocks propagating through dusty media. The threshold shock speed for mantle sputtering is about 10 km s-1 and is independent of density. The mantles are completely vapourized in shocks with speeds of 20-25 km s-1. At such shock speeds, core sputtering commences and gas-phase SiO forms. Core destruction is not total in any C-type shock because grains are not completely destroyed in shocks with speeds near the minimum speeds at which J-type shocks appear. Due to the density dependence of the critical shock speed for this transition, higher gas-phase SiO fractional abundances are produced behind shocks propagating in lower density gas. For shock speeds near the threshold speeds for both core and mantle sputtering, sputtering is much greater for shock velocities at smaller angles relative to the upstream magnetic field. At higher shock speeds, the angular variation is still present but less pronounced. [ABSTRACT FROM AUTHOR]

We report on the results of four XMM–Newton observations separated by about ten days from each other of Cyg OB2 #8A [O6If + O5.5III(f)]. This massive colliding wind binary is a very bright X-ray emitter — one of the first X-ray emitting O-stars discovered by the Einstein satellite — as well as a confirmed non-thermal radio emitter whose binarity was discovered quite recently. The X-ray spectrum between 0.5 and 10.0 keV is essentially thermal, and is best fitted with a three-component model with temperatures of about 3, 9 and 20 MK. The X-ray luminosity corrected for the interstellar absorption is rather large, i.e. about 1034 erg s−1. Compared to the ‘canonical’ ratio of O-type stars, Cyg OB2 #8A was a factor of 19–28 overluminous in X-rays during our observations. The EPIC spectra did not reveal any evidence for the presence of a non-thermal contribution in X-rays. This is not unexpected considering that the simultaneous detections of non-thermal radiation in the radio and soft X-ray (below 10.0 keV) domains is unlikely. Our data reveal a significant decrease in the X-ray flux from apastron to periastron with an amplitude of about 20 per cent. Combining our XMM–Newton results with those from previous ROSAT-PSPC and ASCA-SIS observations, we obtain a light curve suggesting a phase-locked X-ray variability. The maximum emission level occurs around phase 0.75, and the minimum is probably seen shortly after the periastron passage. Using hydrodynamic simulations of the wind–wind collision, we find a high X-ray emission level close to phase 0.75, and a minimum at periastron as well. The high X-ray luminosity, the strong phase-locked variability and the spectral shape of the X-ray emission of Cyg OB2 #8A revealed by our investigation point undoubtedly to X-ray emission dominated by colliding winds. [ABSTRACT FROM AUTHOR]

Objective. Standard models for perfusion quantification in DCE-MRI produce a bias by treating voxels as isolated systems. Spatiotemporal models can remove this bias, but it is unknown whether they are fundamentally identifiable. The aim of this study is to investigate this question in silico using one-dimensional toy systems with a one-compartment blood flow model and a two-compartment perfusion model. Approach. For each of the two models, identifiability is explored theoretically and in-silico for three systems. Concentrations over space and time are simulated by forward propagation. Different levels of noise and temporal undersampling are added to investigate sensitivity to measurement error. Model parameters are fitted using a standard gradient descent algorithm, applied iteratively with a stepwise increasing time window. Model fitting is repeated with different initial values to probe uniqueness of the solution. Reconstruction accuracy is quantified for each parameter by comparison to the ground truth. Main results. Theoretical analysis shows that flows and volume fractions are only identifiable up to a constant, and that this degeneracy can be removed by proper choice of parameters. Simulations show that in all cases, the tissue concentrations can be reconstructed accurately. The one-compartment model shows accurate reconstruction of blood velocities and arterial input functions, independent of the initial values and robust to measurement error. The two-compartmental perfusion model was not fully identifiable, showing good reconstruction of arterial velocities and input functions, but multiple valid solutions for the perfusion parameters and venous velocities, and a strong sensitivity to measurement error in these parameters. Significance. These results support the use of one-compartment spatiotemporal flow models, but two-compartment perfusion models were not sufficiently identifiable. Future studies should investigate whether this degeneracy is resolved in more realistic 2D and 3D systems, by adding physically justified constraints, or by optimizing experimental parameters such as injection duration or temporal resolution., (Creative Commons Attribution license.)

In perfusion MRI, image voxels form a spatially organized network of systems, all exchanging indicator with their immediate neighbors. Yet the current paradigm for perfusion MRI analysis treats all voxels or regions-of-interest as isolated systems supplied by a single global source. This simplification not only leads to long-recognized systematic errors but also fails to leverage the embedded spatial structure within the data. Since the early 2000s, a variety of models and implementations have been proposed to analyze systems with between-voxel interactions. In general, this leads to large and connected numerical inverse problems that are intractible with conventional computational methods. With recent advances in machine learning, however, these approaches are becoming practically feasible, opening up the way for a paradigm shift in the approach to perfusion MRI. This paper seeks to review the work in spatiotemporal modelling of perfusion MRI using a coherent, harmonized nomenclature and notation, with clear physical definitions and assumptions. The aim is to introduce clarity in the state-of-the-art of this promising new approach to perfusion MRI, and help to identify gaps of knowledge and priorities for future research., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Common variable immunodeficiency (CVID) associated liver disease is an underrecognized and poorly studied non-infectious complication that lacks an established treatment. We describe a CVID patient with severe multiorgan complications, including non-cirrhotic portal hypertension secondary to nodular regenerative hyperplasia leading to diuretic-refractory ascites. Remarkably, treatment with rituximab, administered for concomitant immune thrombocytopenia, resulted in the complete and sustained resolution of portal hypertension and ascites. Our case, complemented with a literature review, suggests a beneficial effect of rituximab that warrants further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Roosens, Staels, Van Loo, Humblet-Baron, Meyts, De Samblanx, Verslype, van Malenstein, van der Merwe, Laleman and Schrijvers.)

NFKB1 haploinsufficiengcy was first described in 2015 in three families with common variable immunodeficiency (CVID), presenting heterogeneously with symptoms of increased infectious susceptibility, skin lesions, malignant lymphoproliferation and autoimmunity. The described mutations all led to a rapid degradation of the mutant protein, resulting in a p50 haploinsufficient state. Since then, more than 50 other mutations have been reported, located throughout different domains of NFKB1 with the majority situated in the N-terminal Rel homology domain (RHD). The clinical spectrum has also expanded with possible disease manifestations in almost any organ system. In silico prediction tools are often used to estimate the pathogenicity of NFKB1 variants but to prove causality between disease and genetic findings, further downstream functional validation is required. In this report, we studied 2 families with CVID and two novel variants in NFKB1 (c.1638-2A>G and c.787G>C). Both mutations affected mRNA and/or protein expression of NFKB1 and resulted in excessive NLRP3 inflammasome activation in patient macrophages and upregulated interferon stimulated gene expression. Protein-protein interaction analysis demonstrated a loss of interaction with NFKB1 interaction partners for the p.V263L mutation. In conclusion, we proved pathogenicity of two novel variants in NFKB1 in two families with CVID characterized by variable and incomplete penetrance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Staels, De Keukeleere, Kinnunen, Keskitalo, Lorenzetti, Vanmeert, Prezzemolo, Pasciuto, Lescrinier, Bossuyt, Gerbaux, Willemsen, Neumann, Van Loo, Corveleyn, Willekens, Stalmans, Meyts, Liston, Humblet-Baron, Seppänen, Varjosalo and Schrijvers.)

Background: In vitro maturation of immature testicular tissue (ITT) cryopreserved for fertility preservation is a promising fertility restoration strategy. Organotypic tissue culture proved successful in mice, leading to live births. In larger mammals, including humans, efficiently reproducing spermatogenesis ex vivo remains challenging. With advances in biomaterials technology, culture systems are becoming more complex to better mimic in vivo conditions. Along with improving culture media components, optimizing physical culture conditions (e.g., tissue perfusion, oxygen diffusion) also needs to be considered. Recent studies in mice showed that by using silicone-based hybrid culture systems, the efficiency of spermatogenesis can be improved. Such systems have not been reported for ITT of large mammals. Methods: Four different organotypic tissue culture systems were compared: static i.e., polytetrafluoroethylene membrane inserts (OT), agarose gel (AG) and agarose gel with polydimethylsiloxane chamber (AGPC), and dynamic i.e., microfluidic (MF). OT served as control. Porcine ITT fragments were cultured over a 30-day period using a single culture medium. Analyses were performed at days (d) 0, 5, 10, 20 and 30. Seminiferous tubule (ST) integrity, diameters, and tissue core integrity were evaluated on histology. Immunohistochemistry was used to identify germ cells (PGP9.5, VASA, SYCP3, CREM), somatic cells (SOX9, INSL3) and proliferating cells (Ki67), and to assess oxidative stress (MDA) and apoptosis (C-Caspase3). Testosterone was measured in supernatants using ELISA. Results: ITT fragments survived and grew in all systems. ST diameters, and Sertoli cell (SOX9) numbers increased, meiotic (SYCP3) and post-meiotic (CREM) germ cells were generated, and testosterone was secreted. When compared to control (OT), significantly larger STs (d10 through d30), better tissue core integrity (d5 through d20), higher numbers of undifferentiated spermatogonia (d30), meiotic and post-meiotic germ cells (SYCP3: d20 and 30, CREM: d20) were observed in the AGPC system. Apoptosis, lipid peroxidation (MDA), ST integrity, proliferating germ cell (Ki67/VASA) numbers, Leydig cell (INSL3) numbers and testosterone levels were not significantly different between systems. Conclusions: Using a modified culture system (AGPC), germ cell survival and the efficiency of porcine germ cell differentiation were moderately improved ex vivo . We assume that further optimization can be obtained with concomitant modifications in culture media components., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor JBS declared a past co-authorship with one of the authors CW, (Copyright © 2022 Kanbar, de Michele, Poels, Van Loo, Giudice, Gilet and Wyns.)

Mutations in myocyte enhancer factor 2C (MEF2C), an important transcription factor in neurodevelopment, are associated with a Rett-like syndrome. Structural variants (SVs) upstream of MEF2C, which do not disrupt the gene itself, have also been found in patients with a similar phenotype, suggesting that disruption of MEF2C regulatory elements can also cause a Rett-like phenotype. To characterize those elements that regulate MEF2C during neural development and that are affected by these SVs, we used genomic tools coupled with both in vitro and in vivo functional assays. Through circularized chromosome conformation capture sequencing (4C-seq) and the assay for transposase-accessible chromatin using sequencing (ATAC-seq), we revealed a complex interaction network in which the MEF2C promoter physically contacts several distal enhancers that are deleted or translocated by disease-associated SVs. A total of 16 selected candidate regulatory sequences were tested for enhancer activity in vitro, with 14 found to be functional enhancers. Further analyses of their in vivo activity in zebrafish showed that each of these enhancers has a distinct activity pattern during development, with eight enhancers displaying neuronal activity. In summary, our results disentangle a complex regulatory network governing neuronal MEF2C expression that involves multiple distal enhancers. In addition, the characterized neuronal enhancers pose as novel candidates to screen for mutations in neurodevelopmental disorders, such as Rett-like syndrome., (© The Author(s) 2018. Published by Oxford University Press.)

Agrobacterium tumefaciens is a Gram-negative soil bacterium that genetically transforms plants and, under laboratory conditions, also transforms non-plant organisms, such as fungi and yeasts. During the transformation process a piece of ssDNA (T-strand) is transferred into the host cells via a type IV secretion system. The VirD2 relaxase protein, which is covalently attached at the 5' end of the T-strand through Tyr29, mediates nuclear entry as it contains a nuclear localization sequence. How the T-strand reaches the chromatin and becomes integrated in the chromosomal DNA is still far from clear. Here, we investigated whether VirD2 binds to histone proteins in the yeast Saccharomyces cerevisiae. Using immobilized GFP-VirD2 and in vitro synthesized His6-tagged S. cerevisiae proteins, interactions between VirD2 and the histones H2A, H2B, H3 and H4 were revealed. In vivo, these interactions were confirmed by bimolecular fluorescence complementation experiments. After co-cultivation of Agrobacterium strains expressing VirD2 tagged with a fragment of the yellow fluorescent protein analogue Venus with yeast strains expressing histone H2A or H2B tagged with the complementary part of Venus, fluorescence was detected in dot-shaped structures in the recipient yeast cells. The results indicated that VirD2 was transferred from Agrobacterium to yeast cells and that it interacted with histones in the host cell, and thus may help direct the T-DNA (transferred DNA) to the chromatin as a prelude to integration into the host chromosomal DNA., (© 2015 The Authors.)

Generating new carbon-carbon (C-C) bonds in an enantioselective way is one of the big challenges in organic synthesis. Aldolases are a natural tool for stereoselective C-C bond formation in a green and sustainable way. This review will focus on thermophilic aldolases in general and on dihydroxyacetone phosphate-dependent aldolases in particular. Biochemical properties and applications for synthesis of rare sugars and carbohydrates will be discussed.

Background: The psychobiological model of personality developed by Cloninger includes four dimensions of temperament and three dimensions of character. Studies have indicated that the personality dimensions of patients with depression differ from those of control subjects without depression., Aim: To assess whether the personality traits of persons who have experienced one or more depressive episodes in the past and have made full recovery differ from the personality traits of persons who have never suffered from depression., Method: The personality dimensions for 40 persons in remission but with a previous history of depression and for 49 healthy controls were determined by means of a Dutch version of the Temperament and Character Inventory (tci) questionnaire. results Compared to the control subjects, patients in remission showed a significant increase on the temperament scale Harm Avoidance and a statistically significant decrease on the character scale Self-Directedness. The increase also applied to all subscales of Harm Avoidance and the decrease applied to four of the five subscales of Self-Directedness., Conclusion: Compared to healthy control subjects, patients in remission showed a distinctly different personality profile. None of these differences can therefore be regarded merely as a transient phenomenon during a depressive episode ('state effect'). However, it cannot be concluded from the current study whether the altered personality profile is a consequence of having had a depression or whether it is a 'scarring effect' of a pre-existing vulnerability factor.