Proteomic profiling reveals the transglutaminase-2 externalization pathway in kidneys after unilateral ureteric obstruction

Increased export of transglutaminase-2 (TG2) by tubular epithelial cells (TECs) into the surrounding interstitium modifies the extracellular homeostatic balance, leading to fibrotic membrane expansion. Although silencing of extracellular TG2 ameliorates progressive kidney scarring in animal models of CKD, the pathway through which TG2 is secreted from TECs and contributes to disease progression has not been elucidated. In this study, we developed a global proteomic approach to identify binding partners of TG2 responsible for TG2 externalization in kidneys subjected to unilateral ureteric obstruction (UUO) using TG2 knockout kidneys as negative controls. We report a robust and unbiased analysis of the membrane interactome of TG2 in fibrotic kidneys relative to the entire proteome after UUO, detected by SWATH mass spectrometry. The data have been deposited to the ProteomeXchange with identifier PXD008173. Clusters of exosomal proteins in the TG2 interactome supported the hypothesis that TG2 is secreted by extracellular membrane vesicles during fibrosis progression. In established TEC lines, we found TG2 in vesicles of both endosomal (exosomes) and plasma membrane origin (microvesicles/ectosomes), and TGF-β1 stimulated TG2 secretion. Knockout of syndecan-4 (SDC4) greatly impaired TG2 exosomal secretion. TG2 coprecipitated with SDC4 from exosome lysate but not ectosome lysate. Ex vivo, EGFP-tagged TG2 accumulated in globular elements (blebs) protruding/retracting from the plasma membrane of primary cortical TECs, and SDC4 knockout impaired bleb formation, affecting TG2 release. Through this combined in vivo and in vitro approach, we have dissected the pathway through which TG2 is secreted from TECs in CKD

Predicting High Risk Of Exacerbations In Bronchiectasis: The E-faced Score

Although the FACED score has demonstrated a great prognostic capacity in bronchiectasis, it does not include the number or severity of exacerbations as a separate variable, which is important in the natural history of these patients. Objective: Construction and external validation of a new index, the E-FACED, to evaluate the predictive capacity of exacerbations and mortality. Methods: The new score was constructed on the basis of the complete cohort for the construction of the original FACED score, while the external validation was undertaken with six cohorts from three countries (Brazil, Argentina, and Chile). The main outcome was the number of annual exacerbations/hospitalizations, with all-cause and respiratory-related deaths as the secondary outcomes. A statistical evaluation comprised the relative weight and ideal cut-off point for the number or severity of the exacerbations and was incorporated into the FACED score (E-FACED). The results obtained after the application of FACED and E-FACED were compared in both the cohorts. Results: A total of 1,470 patients with bronchiectasis (819 from the construction cohorts and 651 from the external validation cohorts) were followed up for 5 years after diagnosis. The best cut-off point was at least two exacerbations in the previous year (two additional points), meaning that the E-FACED has nine points of growing severity. E-FACED presented an excellent prognostic capacity for exacerbations (areas under the receiver operating characteristic curve: 0.82 for at least two exacerbations in 1 year and 0.87 for at least one hospitalization in 1 year) that was statistically better than that of the FACED score (0.72 and 0.78, P < 0.05, respectively). The predictive capacities for all-cause and respiratory mortality were 0.87 and 0.86, respectively, with both being similar to those of the FACED. Conclusion: E-FACED score significantly increases the FACED capacity to predict future yearly exacerbations while maintaining the score's simplicity and prognostic capacity for death.1227528

Measurement of the SOC State Specific Heat in ^4He

When a heat flux Q is applied downward through a sample of liquid 4He near the lambda transition, the helium self organizes such that the gradient in temperature matches the gravity induced gradient in Tlambda. All the helium in the sample is then at the same reduced temperature tSOC = ((T[sub SOC] - T[sub lambda])/T[sub lambda]) and the helium is said to be in the Self-Organized Critical (SOC) state. We have made preliminary measurements of the 4He SOC state specific heat, C[del]T(T(Q)). Despite having a cell height of 2.54 cm, our results show no difference between C[del]T and the zero-gravity 4He specific heat results of the Lambda Point Experiment (LPE) [J.A. Lipa et al., Phys. Rev. B, 68, 174518 (2003)] over the range 250 to 450 nK below the transition. There is no gravity rounding because the entire sample is at the same reduced temperature tSOC(Q). Closer to Tlambda the SOC specific heat falls slightly below LPE, reaching a maximum at approximately 50 nK below Tlambda, in agreement with theoretical predictions [R. Haussmann, Phys. Rev. B, 60, 12349 (1999)]

Gate induced enhancement of spin-orbit coupling in dilute fluorinated graphene

We analyze the origin of spin-orbit coupling (SOC) in fluorinated graphene using Density Functional Theory (DFT) and a tight-binding model for the relevant orbitals. As it turns out, the dominant source of SOC is the atomic spin-orbit of fluorine adatoms and not the impurity induced SOC based on the distortion of the graphene plane as in hydrogenated graphene. More interestingly, our DFT calculations show that SOC is strongly affected by both the type and concentrations of the graphene's carriers, being enhanced by electron doping and reduced by hole doping. This effect is due to the charge transfer to the fluorine adatom and the consequent change in the fluorine-carbon bonding. Our simple tight-binding model, that includes the SOC of the $2p$ orbitals of F and effective parameters based on maximally localized Wannier functions, is able to account for the effect. The strong enhancement of the SOC induced by graphene doping opens the possibility to tune the spin relaxation in this material.Comment: 9 pages, 8 figure

Short-term effects of deep ploughing on soil C stocks following renewal of a dairy pasture in New Zealand

In New Zealand’s high producing permanent pastures the topsoil constitutes a large reservoir of soil organic carbon (SOC), which shows a marked stratification with depth. As consequence, sub-surface layers can contain 10 times less carbon than the surface soil. In permanent pastures with high carbon inputs, the formation and decomposition of these surface SOC stocks are often at equilibrium and C storage shows little change over time. Pastoral based dairy systems utilising ryegrass plus clover cultivars require renewal every 7-10 years to avoid reversion to less productive grasses. This may involve spring cultivation (either no-till, shallow till or full cultivation), summer forage cropping and autumn re-grassing. It has been hypothesised that SOC stocks can be increased by inverting the soil profile at pasture renewal through infrequent (once in 25-30 years) deep mouldboard ploughing (up to 30 cm depth). Increased C sequestration occurs when the new grass quickly rebuilds SOC stocks in the new topsoil (exposed low C sub-soil) at a rate faster than the decomposition of SOC in the rich former topsoil transferred to depth (now below 15 cm). However, benefits form accelerated C storage may be offset if crop and pasture production is adversely affected by the ploughing event (e.g., as result of compaction or excessive drainage). Hence, the aim of this work was to assess the short-term effects of infrequent inversion tillage of long-term New Zealand pastoral-based dairy soils under summer crop management and autumn re-grassing. An imperfectly drained Typic Fragiaqualf under dairy grazing was deep ploughed (approx. 25 cm) and re-sown with turnip in October 2016; other treatments included were shallow (< 10 cm) cultivation and no-till. The site was core sampled (0-40 cm) before cultivation and after 5 months of turnip growth to assess changes in SOC. Plant growth, herbage quality, and nutrient leaching were monitored during the 5-month period; root growth was assessed at the end of the crop rotation. Full cultivation transferred SOC below 10 cm depth, as expected. Soil bulk density decreased whereas root mass increased (10-20 cm depth; P < 0.05) under deep cultivation only. Besides, losses of mineral N were attenuated under deep tillage, resulting in a relative increase in crop yield. The potential for infrequent inversion tillage increasing soil C sequestration as a greenhouse gas (GHG) mitigation tool is currently being tested at other sites in New Zealand

Beyond the disk: EUV coronagraphic observations of the Extreme Ultraviolet Imager on board Solar Orbiter

Most observations of the solar corona beyond 2 Rs consist of broadband visible light imagery from coronagraphs. The associated diagnostics mainly consist of kinematics and derivations of the electron number density. While the measurement of the properties of emission lines can provide crucial additional diagnostics of the coronal plasma (temperatures, velocities, abundances, etc.), these observations are comparatively rare. In visible wavelengths, observations at these heights are limited to total eclipses. In the VUV range, very few additional observations have been achieved since the pioneering results of UVCS. One of the objectives of the Full Sun Imager (FSI) channel of the EUI telescope on board the Solar Orbiter mission has been to provide very wide field-of-view EUV diagnostics of the morphology and dynamics of the solar atmosphere in temperature regimes that are typical of the lower transition region and of the corona. FSI carries out observations in two narrowbands of the EUV spectrum centered on 17.4 nm and 30.4 nm that are dominated, respectively, by lines of Fe IX/X (formed in the corona around 1 MK) and by the resonance line of He II (formed around 80 kK in the lower transition region). Unlike previous EUV imagers, FSI includes a moveable occulting disk that can be inserted in the optical path to reduce the amount of instrumental stray light to a minimum. FSI detects signals at 17.4 nm up to the edge of its FOV (7~Rs), which is about twice further than was previously possible. Comparisons with observations by the LASCO and Metis coronagraphs confirm the presence of morphological similarities and differences between the broadband visible light and EUV emissions, as documented on the basis of prior eclipse and space-based observations. The very-wide-field observations of FSI are paving the way for future dedicated instruments

Macroscopic control parameter for avalanche models for bursty transport

Similarity analysis is used to identify the control parameter RA for the subset of avalanching systems that can exhibit self-organized criticality (SOC). This parameter expresses the ratio of driving to dissipation. The transition to SOC, when the number of excited degrees of freedom is maximal, is found to occur when RA-->0. This is in the opposite sense to (Kolmogorov) turbulence, thus identifying a deep distinction between turbulence and SOC and suggesting an observable property that could distinguish them. A corollary of this similarity analysis is that SOC phenomenology, that is, power law scaling of avalanches, can persist for finite RA with the same RA-->0 exponent if the system supports a sufficiently large range of lengthscales, necessary for SOC to be a candidate for physical (RA finite) systems

Soil C Change Over 14 Years in Grasslands Sown Into a Highly Disturbed Soil

Perennial grasslands are thought to sequester C, so restoring them is touted as part of the solution for mitigating climate change. Moreover, there is growing interest among managed grassland stakeholders in selling C credits on nascent C markets. Former agricultural and municipal sites are often considered viable areas for conversion to grasslands, with types ranging from unmanaged prairies with diverse plant communities to monocultures in highly managed urban environments. We sowed five perennial plant communities into an area that had undergone massive soil disturbance five years previous during conversion from row crop agriculture to C3 turf. We found that soils lost an average of 461 g C m-2 over the initial 3-y period, irrespective of mowing, fertilizer addition, or plant community type, with a similar magnitude of soil C loss occurring in the adjacent undisturbed turf. However, by the fourth year of sampling, soil C had returned to pre-treatment levels for most treatments. When sampled 14 years after disturbance and sowing, many soils had gained SOC relative to 2004 (~300 g C m-2). Exceptions included control-prairie grasses, fertilized-Kentucky bluegrass, mowed-fine fescue and mowed-prairie forbs, which had gained enough SOC to return to 2004 levels, but not enough for SOC gain in 2018. Soil-disturbing renovation or restoration of non-irrigated grasslands in the upper Midwest results in a short-term, but highly significant loss of soil C, but after 14 years SOC can sometimes, but not always recover and exceed pre-establishment SOC