C3aR-initiated signaling is a critical mechanism of podocyte injury in membranous nephropathy

: The deposition of anti-podocyte auto-antibodies in the glomerular subepithelial space induces primary membranous nephropathy (MN), the leading cause of nephrotic syndrome worldwide. Taking advantage of the glomerulus-on-a-chip system, we modeled human primary MN induced by anti-PLA2R antibodies. Here we show that exposure of primary human podocytes expressing PLA2R to MN serum results in IgG deposition and complement activation on their surface, leading to loss of the chip permselectivity to albumin. C3a receptor (C3aR) antagonists as well as C3AR gene silencing in podocytes reduced oxidative stress induced by MN serum and prevented albumin leakage. In contrast, inhibition of the formation of the membrane-attack-complex (MAC), previously thought to play a major role in MN pathogenesis, did not affect permselectivity to albumin. In addition, treatment with a C3aR antagonist effectively prevented proteinuria in a mouse model of MN, substantiating the chip findings. In conclusion, using a combination of pathophysiologically relevant in vitro and in vivo models, we established that C3a/C3aR signaling plays a critical role in complement-mediated MN pathogenesis, indicating an alternative therapeutic target for MN

MeerKAT-16 H I observation of the dIrr galaxy WLM

We present observations and models of the kinematics and the distribution of the neutral hydrogen (HI) in the isolated dwarf irregular galaxy, Wolf-Lundmark-Melotte (WLM). We observed WLM with the Green Bank Telescope (GBT) and as part of the MeerKAT Early Science Programme, where 16 dishes were available. The HI disc of WLM extends out to a major axis diameter of 30 arcmin (8.5 kpc), and a minor axis diameter of 20 arcmin (5.6 kpc) as measured by the GBT. We use the MeerKAT data to model WLM using the TiRiFiC software suite, allowing us to fit different tilted-ring models and select the one that best matches the observation. Our final best-fitting model is a flat disc with a vertical thickness, a constant inclination and dispersion, and a radially-varying surface brightness with harmonic distortions. To simulate bar-like motions, we include second-order harmonic distortions in velocity in the tangential and the vertical directions. We present a model with only circular motions included and a model with non-circular motions. The latter describes the data better. Overall, the models reproduce the global distribution and the kinematics of the gas, except for some faint emission at the 2-sigma level. We model the mass distribution of WLM with a pseudo-isothermal (ISO) and a Navarro-Frenk-White (NFW) dark matter halo models. The NFW and the ISO models fit the derived rotation curves within the formal errors, but with the ISO model giving better reduced chi-square values. The mass distribution in WLM is dominated by dark matter at all radii.Comment: Accepted for publication in MNRAS, 25 pages, 21 figures, 5 table

Protective effect of human amniotic fluid stem cells in an immunodeficient mouse model of acute tubular necrosis.

Acute Tubular Necrosis (ATN) causes severe damage to the kidney epithelial tubular cells and is often associated with severe renal dysfunction. Stem-cell based therapies may provide alternative approaches to treating of ATN. We have previously shown that clonal c-kit(pos) stem cells, derived from human amniotic fluid (hAFSC) can be induced to a renal fate in an ex-vivo system. Herein, we show for the first time the successful therapeutic application of hAFSC in a mouse model with glycerol-induced rhabdomyolysis and ATN. When injected into the damaged kidney, luciferase-labeled hAFSC can be tracked using bioluminescence. Moreover, we show that hAFSC provide a protective effect, ameliorating ATN in the acute injury phase as reflected by decreased creatinine and BUN blood levels and by a decrease in the number of damaged tubules and apoptosis therein, as well as by promoting proliferation of tubular epithelial cells. We show significant immunomodulatory effects of hAFSC, over the course of ATN. We therefore speculate that AFSC could represent a novel source of stem cells that may function to modulate the kidney immune milieu in renal failure caused by ATN

Winged men and the cast of dice: Anti-finalism and radical materialism in Guillaume Lamy

The controversy over teleology raged in the early modern period with particular intensity. In this paper, I will show that Guillaume Lamy represents a “radical” current of antifi nalism, devoid of weakness, and far from compromise with his adversaries. This antifi nalism makes of Lamy not so much a sincere supporter of the unknowability of God’s ends, as scholars have maintained — in other words, a proto– fi deist — but rather a radical Lucretian materialist, whose aim is to openly distance himself equally from the partial Cartesia

Convergence of gut microbiotas in the adaptive radiations of African cichlid fishes

Ecoevolutionary dynamics of the gut microbiota at the macroscale level, that is, in across-species comparisons, are largely driven by ecological variables and host genotype. The repeated explosive radiations of African cichlid fishes in distinct lakes, following a dietary diversification in a context of reduced genetic diversity, provide a natural setup to explore convergence, divergence and repeatability in patterns of microbiota dynamics as a function of the host diet, phylogeny and environment. Here we characterized by 16S rRNA amplicon sequencing the gut microbiota of 29 cichlid species from two distinct lakes/radiations (Tanganyika and Barombi Mbo) and across a broad dietary and phylogenetic range. Within each lake, a significant deviation between a carnivorous and herbivorous lifestyle was found. Herbivore species were characterized by an increased bacterial taxonomic and functional diversity and converged in key compositional and functional community aspects. Despite a significant lake effect on the microbiota structure, this process has occurred with remarkable parallels in the two lakes. A metabolic signature most likely explains this trend, as indicated by a significant enrichment in herbivores/omnivores of bacterial taxa and functions associated with fiber degradation and detoxification of plant chemical compounds. Overall, compositional and functional aspects of the gut microbiota individually and altogether validate and predict main cichlid dietary habits, suggesting a fundamental role of gut bacteria in cichlid niche expansion and adaptation

MeerKAT-16 HI observation of the dIrr galaxy WLM

We present observations and models of the kinematics and the distribution of the neutral hydrogen (Hi) in the isolated dwarf irregular galaxy, Wolf-Lundmark-Melotte (WLM). We observed WLM with the Green Bank Telescope (GBT) and as part of the MeerKAT Early Science Programme, where 16 dishes were available. The Hi disc of WLM extends out to a major axis diameter of 300 (8.5 kpc), and a minor axis diameter of 200 (5.6 kpc) as measured by the GBT. We use the MeerKAT data to model WLM using the TiRiFiC software suite, allowing us to t di erent tilted-ring models and select the one that best matches the observation. Our nal best- tting model is a at disc with a vertical thickness, a constant inclination and dispersion, and a radially-varying surface brightness with harmonic distortions. To simulate bar- like motions, we include second-order harmonic distortions in velocity in the tangential and the vertical directions. We present a model with only circular motions included and a model with non-circular motions. The latter describes the data better. Overall, the models reproduce the global distribution and the kinematics of the gas, except for some faint emission at the 2 level. We model the mass distribution of WLM with a pseudo-isothermal (ISO) and a Navarro-Frenk-White (NFW) dark matter halo models. The NFW and the ISO models t the derived rotation curves within the formal errors, but with the ISO model giving better reduced chi-square values. The mass distribution in WLM is dominated by dark matter at all radii.The MeerKAT telescope is operated by the South African Radio Astronomy Observatory, which is a facility of the Na- tional Research Foundation, an agency of the Department of Science and Innovation. This work is based upon research supported by the South African Research Chairs Initiative of the Department of Sci- ence and Technology and National Research Foundation. The nancial assistance of the South African Radio Astron- omy Observatory (SARAO) towards this research is hereby acknowledged (www.sarao.ac.za). PK is partially supported by the BMBF project 05A17PC2 for D-MeerKAT. AS acknowledges the Russian Science Foundation grant 19-12-00281 and the Program of development of M.V.http://mnras.oxfordjournals.orgam2021Physic

The extended H i halo of NGC 4945 as seen by MeerKAT

The State Agency for Research of the Spanish Ministry of Science, Innovation and Universities through the ‘Center of Excellence Severo Ochoa’ awarded to the Instituto de Astrofísica de Andalucía; the Economic Transformation, Industry, Knowledge and Universities Council of the Regional Government of Andalusia and the European Regional Development Fund from the European Union; the South African Radio Astronomy Observatory (SARAO); BMBF Verbundforschung; DFG Sonderforschungsbereich and the European Research Council (ERC).http://mnras.oxfordjournals.orghj2022Physic

The extended H I halo of NGC 4945 as seen by MeerKAT

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Observations of the neutral atomic hydrogen (H I) in the nuclear starburst galaxy NGC 4945 with MeerKAT are presented. We find a large amount of halo gas, previously missed by H I observations, accounting for 6.8 per cent of the total H I mass. This is most likely gas blown into the halo by star formation. Our maps go down to a 3σ column density level of 5 × 1018 cm−2. We model the H I distribution using tilted-ring fitting techniques and find a warp on the galaxy’s approaching and receding sides. The H I in the northern side of the galaxy appears to be suppressed. This may be the result of ionization by the starburst activity in the galaxy, as suggested by a previous study. The origin of the warp is unclear but could be due to past interactions or ram pressure stripping. Broad, asymmetric H I absorption lines extending throughout the H I emission velocity channels are present towards the nuclear region of NGC 4945. Such broad lines suggest the existence of a nuclear ring moving at a high circular velocity. This is supported by the clear rotation patterns in the H I absorption velocity field. The asymmetry of the absorption spectra can be caused by outflows or inflows of gas in the nuclear region of NGC 4945. The continuum map shows small extensions on both sides of the galaxy’s major axis that might be signs of outflows resulting from the starburst activity. © The Author(s) 2022. Published by Oxford University Press on behalf of Royal Astronomical Society.RI acknowledges financial support from grant RTI2018-096228-B-C31 (MCIU/AEI/FEDER,UE) and from the State Agency for Research of the Spanish Ministry of Science, Innovation and Universities through the ‘Center of Excellence Severo Ochoa’ awarded to the Instituto de Astrofísica de Andalucía (SEV-2017-0709), from the grant IAA4SKA (Ref. R18-RT-3082) from the Economic Transformation, Industry, Knowledge and Universities Council of the Regional Government of Andalusia and the European Regional Development Fund from the European Union. The MeerKAT telescope is operated by the South African Radio Astronomy Observatory, which is a facility of the National Research Foundation, an agency of the Department of Science and Innovation. This work is based upon research supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation. The financial assistance of the South African Radio Astronomy Observatory (SARAO) towards this research is hereby acknowledged (www.sarao.ac.za). At Ruhr University Bochum, this research is supported by BMBF Verbundforschung grant 05A20PC4 and by DFG Sonderforschungsbereich SFB1491. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme grant agreement no. 882793, project name MeerGas. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no.679627; project name FORNAX).Peer reviewe