Estimating the solar wind pressure at comet 67P from Rosetta magnetic field measurements

Aims: The solar wind pressure is an important parameter of space weather, which plays a crucial role in the interaction of the solar wind with the planetary plasma environment. Here we investigate the possibility of determining a solar wind pressure proxy from Rosetta magnetic field data, measured deep inside the induced magnetosphere of comet 67P/Churyumov-Gerasimenko. This pressure proxy would be useful not only for other Rosetta related studies but could also serve as a new, independent input database for space weather propagation to other locations in the Solar System. Method: For the induced magnetospheres of comets the magnetic pressure in the innermost part of the pile-up region is balanced by the solar wind dynamic pressure. Recent investigations of Rosetta data have revealed that the maximum magnetic field in the pile-up region can be approximated by magnetic field measurements performed in the inner regions of the cometary magnetosphere, close to the boundary of the diamagnetic cavity, from which the external solar wind pressure can be estimated. Results: We were able to determine a solar wind pressure proxy for the time interval when the Rosetta spacecraft was located near the diamagnetic cavity boundary, between late April 2015 and January 2016. We then compared our Rosetta pressure proxy to solar wind pressure extrapolated to comet 67P from near-Earth. After the exclusion of disturbances caused by transient events, we found a strong correlation between the two datasets

3D pressure-corrected ballistic extrapolation of solar wind speed in the inner heliosphere

Solar wind parameters at different locations in the inner heliosphere can be estimated using various solar wind extrapolation methods. The simple ballistic method extrapolates solar wind parameters from the point of measurement to a chosen heliospheric position by assuming that major solar wind structures are persistent and arrive relatively unaltered to the target position. The method considers the rotation period of the Sun while assuming a constant solar wind speed during radial propagation. We improve the simple ballistic model by considering the interaction between the slow and the fast solar wind with a pressure correction during the propagation. Instead of extrapolating from the position of a single spacecraft, we apply this pressure-corrected ballistic method to 2D speed maps of the solar source surface available from solar coronal models to determine the solar wind speed in the inner heliosphere in 3D, between latitudes of ±50°. We also take into account the effects of the solar differential rotation in our model. Our method is simple and fast, and it can be applied to different source surface datasets. The results of our model are validated with in situ data from the ACE spacecraft. We find that the pressure-corrected ballistic method can give accurate predictions of the solar wind in 3D

The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction-dependent manner

The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1) to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1-RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s) reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Understanding the structure of the fading magnetosphere around comet 67P/Churyumov-Gerasimenko using measurements from the last weeks of the Rosetta mission.

International audienceAfter accompanying comet 67P/Churyumov-Gerasimenko on its journey and observing the evolution of its induced magnetosphere throughout the comet's life-cycle, the Rosetta mission concluded at the end of September 2016 with a controlled impact on the cometary nucleus. At this time, the comet was located more than 3.8 AU from the Sun, but the data still show clear indications of a small induced magnetosphere. The observations of the nascent magnetosphere of the awakening low activity comet had to be performed under constantly changing conditions, because the orbit was varied to satisfy operational requirements. This made it difficult to examine the structure of the magnetosphere of the low activity comet at that time. In contrast, near the conclusion of the Rosetta mission the spacecraft observed the fading cometary magnetosphere through multiple similar elliptical orbits, which allow us to obtain a more precise picture of its structure. We examined the measured plasma properties through these consecutive orbits, from which we were able to determine the structure of the fading magnetosphere using a simple, latitude dependant model

Understanding the structure of the fading magnetosphere around comet 67P/Churyumov-Gerasimenko using measurements from the last weeks of the Rosetta mission.

International audienceAfter accompanying comet 67P/Churyumov-Gerasimenko on its journey and observing the evolution of its induced magnetosphere throughout the comet's life-cycle, the Rosetta mission concluded at the end of September 2016 with a controlled impact on the cometary nucleus. At this time, the comet was located more than 3.8 AU from the Sun, but the data still show clear indications of a small induced magnetosphere. The observations of the nascent magnetosphere of the awakening low activity comet had to be performed under constantly changing conditions, because the orbit was varied to satisfy operational requirements. This made it difficult to examine the structure of the magnetosphere of the low activity comet at that time. In contrast, near the conclusion of the Rosetta mission the spacecraft observed the fading cometary magnetosphere through multiple similar elliptical orbits, which allow us to obtain a more precise picture of its structure. We examined the measured plasma properties through these consecutive orbits, from which we were able to determine the structure of the fading magnetosphere using a simple, latitude dependant model

Estimating the solar wind pressure at comet 67P from Rosetta magnetic field measurements

Aims: The solar wind pressure is an important parameter of space weather, which plays a crucial role in the interaction of the solar wind with the planetary plasma environment. Here we investigate the possibility of determining a solar wind pressure proxy from Rosetta magnetic field data, measured deep inside the induced magnetosphere of comet 67P/Churyumov-Gerasimenko. This pressure proxy would be useful not only for other Rosetta related studies but could also serve as a new, independent input database for space weather propagation to other locations in the Solar System. Method: For the induced magnetospheres of comets the magnetic pressure in the innermost part of the pile-up region is balanced by the solar wind dynamic pressure. Recent investigations of Rosetta data have revealed that the maximum magnetic field in the pile-up region can be approximated by magnetic field measurements performed in the inner regions of the cometary magnetosphere, close to the boundary of the diamagnetic cavity, from which the external solar wind pressure can be estimated. Results: We were able to determine a solar wind pressure proxy for the time interval when the Rosetta spacecraft was located near the diamagnetic cavity boundary, between late April 2015 and January 2016. We then compared our Rosetta pressure proxy to solar wind pressure extrapolated to comet 67P from near-Earth. After the exclusion of disturbances caused by transient events, we found a strong correlation between the two datasets

The activity of Rac1 is modulated by SDC4.

<p>(A) The level of active Rac1-GTP was monitored in MCF-7 cells expressing different SDC4 constructs by pull-down assay employing CRIB domain of Pak1. The Ser179Glu cells contained the least Rac1-GTP among the cell lines. Administration of non-hydrolysable GTP-γS equalized the amount of pulled-down Rac1, while the high access of GDP eliminated it. Rac1 and GFP were used as loading control. Bar diagrams represent the quantification of the ratio of Rac1-GTP and the endogenous Rac1 normalized to MCF-7 cells. According to this the Rac1 activity of the control cells was reduced 3-fold in the Ser179Glu cells and was increased by 15% in the ΔPDZ cells. In the 4th slab SDC4 was probed on the CRIB-based Rac1 assay. In the 5th panel Rac1 was tested in GFP co-IPs. The pattern is similar to that of Rac1 received in the Rac-assay. MCF-7 line served as a negative control. The results of panel A are representatives of at least 5 independent experiments; data are reported as mean ± SEM (n = 5). (B) Pak1 kinase was probed in the SDC4 co-IPs. The most abundant Pak1 was detected in the Ser179Glu mutant cells. Pak1 was used as loading control.</p

Schematic representation of the assumed mechanism of the regulation of Rac1 activity by SDC4.

<p>The activation cycle of Rac1 is regulated by several factors. GEFs catalyze the exchange of GDP for GTP. The intrinsic GTPase activity can be accelerated by GAPs. The GDIs can extract Rac1 from the membrane keeping it mostly in GDP-bound form in the cytosol. The red arrows show the potential regulatory sites of the phosphomimetic SDC4, 1) inhibiting Tiam1 a Rac1-GEF and 2) inducing the accumulation of the cytosolic Rac1-RhoGDI1 complex.</p

Schematic representation of the assumed mechanism of the inhibition of Tiam1 by phosphomimetic SDC4.

<p>(A) The only connection of SDC4 to Tiam1 via PDZ binding site or Glu¹⁷⁹ does not interfere with Tiam1 activity; however the simultaneous interactions block the enzyme activity. (B) Structure of Tiam1 contains two pleckstrin homology domains (PHn and PHc). Rac1 binding site is located between the PHn and PHc domains. In pull down experiment PH domain was identified as interaction site, and PHn was shown to regulate binding of GTPases [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0187094#pone.0187094.ref010" target="_blank">10</a>] thus we suppose that phosphomimetic SDC4 can interact with the PDZ and PHn domains simultaneously to exclude Rac1.</p