Podocytes Produce and Secrete Functional Complement C3 and Complement Factor H

Podocytes are an important part of the glomerular filtration barrier and the key player in the development of proteinuria, which is an early feature of complement mediated renal diseases. Complement factors are mainly liver-born and present in circulation. Nevertheless, there is a growing body of evidence for additional sites of complement protein synthesis, including various cell types in the kidney. We hypothesized that podocytes are able to produce complement components and contribute to the local balance of complement activation and regulation. To investigate the relevant balance between inhibiting and activating sides, our studies focused on complement factor H (CFH), an important complement regulator, and on C3, the early key component for complement activation. We characterized human cultured podocytes for the expression and secretion of activating and regulating complement factors, and analyzed the secretion pathway and functional activity. We studied glomerular CFH and C3 expression in puromycin aminonucleoside (PAN) -treated rats, a model for proteinuria, and the physiological mRNA-expression of both factors in murine kidneys. We found, that C3 and CFH were expressed in cultured podocytes and expression levels differed from those in cultivated glomerular endothelial cells. The process of secretion in podocytes was stimulated with interferon gamma and located in the Golgi apparatus. Cultured podocytes could initiate the complement cascade by the splitting of C3, which can be shown by the generation of C3a, a functional C3 split product. C3 contributed to external complement activation. Podocyte-secreted CFH, in conjunction with factor I, was able to split C3b. Podocytes derived from a patient with a CFH mutation displayed impaired cell surface complement regulation. CFH and C3 were synthesized in podocytes of healthy C57Bl/6-mice and were upregulated in podocytes of PAN treated rats. These data show that podocytes produce functionally active complement components, and could therefore influence the local glomerular complement activation and regulation. This modulating effect should therefore be considered in all diseases where glomerular complement activation occurs. Furthermore, our data indicate a potential novel role of podocytes in the innate immune system

Adapting agricultural water use to climate change in a post-Soviet context: challenges and opportunities in southeast Kazakhstan

The convergence of climate change and post-Soviet socio-economic and institutional transformations has been underexplored so far, as have the consequences of such convergence on crop agriculture in Central Asia. This paper provides a place-based analysis of constraints and opportunities for adaptation to climate change, with a specific focus on water use, in two districts in southeast Kazakhstan. Data were collected by 2 multi-stakeholder participatory workshops, 21 semi-structured in-depth interviews, and secondary statistical data. The present-day agricultural system is characterised by enduring Soviet-era management structures, but without state inputs that previously sustained agricultural productivity. Low margins of profitability on many privatised farms mean that attempts to implement integrated water management have produced water users associations unable to maintain and upgrade a deteriorating irrigation infrastructure. Although actors engage in tactical adaptation measures, necessary structural adaptation of the irrigation system remains difficult without significant public or private investments. Market-based water management models have been translated ambiguously to this region, which fails to encourage efficient water use and hinders adaptation to water stress. In addition, a mutual interdependence of informal networks and formal institutions characterises both state governance and everyday life in Kazakhstan. Such interdependence simultaneously facilitates operational and tactical adaptation, but hinders structural adaptation, as informal networks exist as a parallel system that achieves substantive outcomes while perpetuating the inertia and incapacity of the state bureaucracy. This article has relevance for critical understanding of integrated water management in practice and adaptation to climate change in post-Soviet institutional settings more broadly

Oligo-Miocene extensional tectonics and fluid flow across the Northern Snake Range detachment system, Nevada

The Northern Snake Range (Nevada) represents a spectacular example of a metamorphic core complex and exposes a complete section from the mylonitic footwall into the hanging wall of a fossil detachment system. Paired geochronological and stable isotopic data of mylonitic quartzite within the detachment footwall reveal that ductile deformation and infiltration of meteoric fluids occurred between 27 and 23 Ma. 40Ar/39Ar ages display complex recrystallization-cooling relationships but decrease systematically from 26.9 ± 0.2 Ma at the top to 21.3 ± 0.2 Ma at the bottom of footwall mylonite. Hydrogen isotope (δD) values in white mica are very low (-150 to-145 ‰) within the top 80-90 m of detachment footwall, in contrast to values obtained from the deeper part of the section where values range from-77 to-64 ‰, suggesting that time-integrated interaction between rock and meteoric fluid was restricted to the uppermost part of the mylonitic footwall. Pervasive mica-water hydrogen isotope exchange is difficult to reconcile with models of 40Ar loss during mylonitization solely by volume diffusion. Rather, we interpret the 40Ar/ 39Ar ages of white mica with low-δD values to date syn-mylonitic hydrogen and argon isotope exchange, and we conclude that the hydrothermal system of the Northern Snake Range was active during late Oligocene (27-23 Ma) and has been exhumed by the combined effects of ductile strain, extensional detachment faulting, and erosion. Copyright 2011 by the American Geophysical Union

Diffraction techniques and vibrational spectroscopy opportunities to characterise bones

From a histological point of view, bones that allow body mobility and protection of internal organs consist not only of different organic and inorganic tissues but include vascular and nervous elements as well. Moreover, due to its ability to host different ions and cations, its mineral part represents an important reservoir, playing a key role in the metabolic activity of the organism. From a structural point of view, bones can be considered as a composite material displaying a hierarchical structure at different scales. At the nanometre scale, an organic part, i.e. collagen fibrils and an inorganic part, i.e. calcium phosphate nanocrystals are intimately mixed to assure particular mechanical properties

Tests of light-lepton universality in angular asymmetries of B0→D∗−ℓνB^0 \to D^{*-} \ell \nu decays

We present the first comprehensive tests of light-lepton universality in the angular distributions of semileptonic \Bz-meson decays to charged spin-1 charmed mesons. We measure five angular-asymmetry observables as functions of the decay recoil that are sensitive to lepton-universality-violating contributions. We use events where one neutral \B is fully reconstructed in \PUpsilonFourS{} \to\B\overline{B} decays in data corresponding to \lumion integrated luminosity from electron-positron collisions collected with the \belletwo detector. We find no significant deviation from the standard model expectations

Measurement of branching fractions and direct CPCP asymmetries for B→KπB \to K\pi and B→ππB\to\pi\pi decays at Belle II

We report measurements of the branching fractions and direct $\it{CP}$ asymmetries of the decays $B^0 \to K^+ \pi^-$, $B^+ \to K^+ \pi^0$, $B^+ \to K^0 \pi^+$, and $B^0 \to K^0 \pi^0$, and use these for testing the standard model through an isospin-based sum rule. In addition, we measure the branching fraction and direct $\it{CP}$ asymmetry of the decay $B^+ \to \pi^+\pi^0$ and the branching fraction of the decay $B^0 \to \pi^+\pi^-$. The data are collected with the Belle II detector from $e^+e^-$ collisions at the $\Upsilon(4S)$ resonance produced by the SuperKEKB asymmetric-energy collider and contain $387\times 10^6$ bottom-antibottom meson pairs. Signal yields are determined in two-dimensional fits to background-discriminating variables, and range from 500 to 3900 decays, depending on the channel. We obtain $-0.03 \pm 0.13 \pm 0.04$ for the sum rule, in agreement with the standard model expectation of zero and with a precision comparable to the best existing determinations

First measurement of R(Xτ/ℓ)R(X_{\tau/\ell}) as an inclusive test of the b→cτνb \to c \tau \nu anomaly

We measure the tau-to-light-lepton ratio of inclusive $B$-meson branching fractions $R(X_{\tau/\ell}) \equiv \mathcal{B}(B\to X \tau \nu)/\mathcal{B}(B \to X \ell \nu)$, where $\ell$ indicates an electron or muon, and thereby test the universality of charged-current weak interactions. We select events that have one fully reconstructed $B$ meson and a charged lepton candidate from $189~\mathrm{fb}^{-1}$ of electron-positron collision data collected with the Belle II detector. We find $R(X_{\tau/\ell}) = 0.228 \pm 0.016~(\mathrm{stat}) \pm 0.036~(\mathrm{syst})$, in agreement with standard-model expectations. This is the first direct measurement of $R(X_{\tau/\ell})$