Midkine drives cardiac inflammation by promoting neutrophil trafficking and NETosis in myocarditis

Heart failure due to dilated cardiomyopathy is frequently caused by myocarditis. However, the pathogenesis of myocarditis remains incompletely understood. Here, we report the presence of neutrophil extracellular traps (NETs) in cardiac tissue of patients and mice with myocarditis. Inhibition of NET formation in experimental autoimmune myocarditis (EAM) of mice substantially reduces inflammation in the acute phase of the disease. Targeting the cytokine midkine (MK), which mediates NET formation in vitro, not only attenuates NET formation in vivo and the infiltration of polymorphonuclear neutrophils (PMNs) but also reduces fibrosis and preserves systolic function during EAM. Low-density lipoprotein receptor-related protein 1 (LRP1) acts as the functionally relevant receptor for MK-induced PMN recruitment as well as NET formation. In summary, NETosis substantially contributes to the pathogenesis of myocarditis and drives cardiac inflammation, probably via MK, which promotes PMN trafficking and NETosis. Thus, MK as well as NETs may represent novel therapeutic targets for the treatment of cardiac inflammation

TanDEM-X elevation model data for canopy height and aboveground biomass retrieval in a tropical peat swamp forest

It was demonstrated in the past that radar data is useful to estimate aboveground biomass due to their interferometric capability. Therefore, the potential of a globally available TanDEM-X digital elevation model (DEM) was investigated for aboveground biomass estimation via canopy height models (CHMs) in a tropical peat swamp forest. However, CHMs based on X-band interferometers usually require external terrain models. High accurate terrain models are not available on global scale. Therefore, an approach exclusively based on TanDEM-X and the decrease of accuracy compared to an approach utilizing a high accurate terrain model is assessed. In addition, the potential of X-band interferometric heights in tropical forests needs to be evaluated. Therefore, two CHMs were derived from an intermediate TanDEM-X DEM (iDEM; as a precursor for WorldDEMTM) alone and in combination with lidar measurements used as terrain model. The analysis showed high accuracies (root mean square error [RMSE] = 5 m) for CHMs based on iDEM and reliable estimation of aboveground biomass. The iDEM CHM, exclusively based on TanDEM-X, achieved a poor R2 of 0.2, nonetheless resulted in a cross-validated RMSE of 54 t ha−1 (16%). The low R2 suggested that the X-band height alone was not sufficient to estimate an accurate CHM, and thus the need for external terrain models was confirmed. A CHM retrieved from the difference of iDEM and an accurate lidar terrain model achieved a considerably higher correlation with aboveground biomass (R2 = 0.68) and low cross-validated RMSE of 24.5 t ha−1 (7.5%). This was higher or comparable to other aboveground biomass estimations in tropical peat swamp forests. The potential of X-band interferometric heights for CHM and biomass estimation was thus confirmed in tropical forest in addition to existing knowledge in boreal forests.</p

Blocking LFA-1 Aggravates Cardiac Inflammation in Experimental Autoimmune Myocarditis

The lymphocyte function-associated antigen 1 (LFA-1) is a member of the beta2-integrin family and plays a pivotal role for T cell activation and leukocyte trafficking under inflammatory conditions. Blocking LFA-1 has reduced or aggravated inflammation depending on the inflammation model. To investigate the effect of LFA-1 in myocarditis, mice with experimental autoimmune myocarditis (EAM) were treated with a function blocking anti-LFA-1 antibody from day 1 of disease until day 21, the peak of inflammation. Cardiac inflammation was evaluated by measuring infiltration of leukocytes into the inflamed cardiac tissue using histology and flow cytometry and was assessed by analysis of the heart weight/body weight ratio. LFA-1 antibody treatment severely enhanced leukocyte infiltration, in particular infiltration of CD11b+ monocytes, F4/80+ macrophages, CD4+ T cells, Ly6G+ neutrophils, and CD133+ progenitor cells at peak of inflammation which was accompanied by an increased heart weight/body weight ratio. Thus, blocking LFA-1 starting at the time of immunization severely aggravated acute cardiac inflammation in the EAM model

Data from: Mechanism of anti-remodelling action of treprostinil in human pulmonary arterial smooth muscle cells

Treprostinil is applied for pulmonary arterial hypertension (PAH) therapy. However, the mechanism by which the drug achieves its beneficial effects in PAH vessels is not fully understood. This study investigated the effects of treprostinil on PDGF-BB induced remodelling parameters in isolated human pulmonary arterial smooth muscle cells (PASMC) of four PAH patients. The production of TGF-β1, CTGF, collagen type-I and -IV, and of fibronectin were determined by ELISA and PCR. The role of cAMP was determined by ELISA and di-deoxyadenosine treatment. Proliferation was determined by direct cell count. Treprostinil increased cAMP levels dose and time dependently, which was not affected by PDGF-BB. Treprostinil significantly reduced PDGF-BB induced secretion of TGF-β1 and CTGF, both was counteracted when cAMP generation was blocked. Similarly, the PDGF-BB induced proliferation of PASMC was dose dependently reduced by treprostinil through signalling via cAMP - C/EBP-α p42 - p21(WAf1/Cip1). In regard to extracellular matrix remodelling, treprostinil significantly reduced PDGF-BB - TGF-β1 - CTGF induced synthesis and deposition of collagen type I and fibronectin, in a cAMP sensitive manner. In contrast, the deposition of collagen IV was not affected. The data suggest that this action of treprostinil in vessel wall remodelling may benefit patients with PAH and may reduce arterial wall remodelling

The ICRF-3: Proposed Roadmap to the Next Generation International Celestial Reference Frame

International audienceWe propose a 3rd generation radio-based International Celestial Reference Frame (ICRF- 3) to improve upon the highly successful ICRF-2. Our goals are to improve the precision, spatial and frequency coverages relative to the ICRF-2 by 2018. This date is driven by the desire to create radio frames early enough to test the Gaia optical frame during its construction. Several specific actions are underway. A collaboration has been started to improve S/X-band precision of the 2000 VLBA Calibrator Survey sources which are typically 5 times less precise than the rest of the ICRF-2. S/X-band southern precision improvements are planned from observations with southern antennas such as the AuScope and HartRAO, S. Africa. We seek to improve radio frequency coverage with X/Ka and K- band work. An X/Ka frame of 631 sources now has full sky coverage from the addition of a 2nd southern station in Argentina which should strengthen the southern hemisphere in general. A K-band collaboration has formed with similar coverage and southern precision goals. On the analysis front, special attention will be given to combination techniques both of VLBI catalogs and of multiple data types (e.g. VLBI GPS). Finally, work is underway to identify and pinpoint sources bright enough in both radio and optical to allow for a robust frame tie between VLBI and Gaia optical frames

ICRF-3: Roadmap to the next generation ICRF

International audienceWe propose a 3rd generation radio-based International Celestial Reference Frame (ICRF- 3) to improve upon the highly successful ICRF-2. Our goals are to improve the precision as well as the spatial and frequency coverages relative to the ICRF-2 by 2018. This date is driven by the desire to create radio frames early enough to test the Gaia optical frame during its construction. Several specific actions are underway. A collaboration has been started to improve S/X-band precision of the 2200 VLBA Calibrator Survey sources which are typically 5 times less precise than the rest of the ICRF-2. S/X-band southern precision improvements are planned from observations with southern antennas such as the AuScope and HartRAO, S. Africa. We seek to improve radio frequency coverage with X/Ka and K-band work. An X/Ka frame of 631 sources now has full sky coverage from the addition of a 2nd southern station in Argentina which should strengthen the southern hemisphere in general. A K-band collaboration has formed with similar coverage and southern hemisphere precision goals. On the analysis front, special attention will be given to combination techniques both of VLBI catalogs and of multiple data types (e.g. VLBI GPS). Finally, work is underway to identify and pinpoint sources bright enough in both radio and optical to allow for a robust frame tie between VLBI and Gaia optical frames

The ICRF-3: Proposed Roadmap to the Next Generation International Celestial Reference Frame

International audienceWe propose a 3rd generation radio-based International Celestial Reference Frame (ICRF- 3) to improve upon the highly successful ICRF-2. Our goals are to improve the precision, spatial and frequency coverages relative to the ICRF-2 by 2018. This date is driven by the desire to create radio frames early enough to test the Gaia optical frame during its construction. Several specific actions are underway. A collaboration has been started to improve S/X-band precision of the 2000 VLBA Calibrator Survey sources which are typically 5 times less precise than the rest of the ICRF-2. S/X-band southern precision improvements are planned from observations with southern antennas such as the AuScope and HartRAO, S. Africa. We seek to improve radio frequency coverage with X/Ka and K- band work. An X/Ka frame of 631 sources now has full sky coverage from the addition of a 2nd southern station in Argentina which should strengthen the southern hemisphere in general. A K-band collaboration has formed with similar coverage and southern precision goals. On the analysis front, special attention will be given to combination techniques both of VLBI catalogs and of multiple data types (e.g. VLBI GPS). Finally, work is underway to identify and pinpoint sources bright enough in both radio and optical to allow for a robust frame tie between VLBI and Gaia optical frames

The ICRF-3: Proposed Roadmap to the Next Generation International Celestial Reference Frame

International audienceWe propose a 3rd generation radio-based International Celestial Reference Frame (ICRF- 3) to improve upon the highly successful ICRF-2. Our goals are to improve the precision, spatial and frequency coverages relative to the ICRF-2 by 2018. This date is driven by the desire to create radio frames early enough to test the Gaia optical frame during its construction. Several specific actions are underway. A collaboration has been started to improve S/X-band precision of the 2000 VLBA Calibrator Survey sources which are typically 5 times less precise than the rest of the ICRF-2. S/X-band southern precision improvements are planned from observations with southern antennas such as the AuScope and HartRAO, S. Africa. We seek to improve radio frequency coverage with X/Ka and K- band work. An X/Ka frame of 631 sources now has full sky coverage from the addition of a 2nd southern station in Argentina which should strengthen the southern hemisphere in general. A K-band collaboration has formed with similar coverage and southern precision goals. On the analysis front, special attention will be given to combination techniques both of VLBI catalogs and of multiple data types (e.g. VLBI GPS). Finally, work is underway to identify and pinpoint sources bright enough in both radio and optical to allow for a robust frame tie between VLBI and Gaia optical frames

ICRF-3: Roadmap to the next generation ICRF

International audienceWe propose a 3rd generation radio-based International Celestial Reference Frame (ICRF- 3) to improve upon the highly successful ICRF-2. Our goals are to improve the precision as well as the spatial and frequency coverages relative to the ICRF-2 by 2018. This date is driven by the desire to create radio frames early enough to test the Gaia optical frame during its construction. Several specific actions are underway. A collaboration has been started to improve S/X-band precision of the 2200 VLBA Calibrator Survey sources which are typically 5 times less precise than the rest of the ICRF-2. S/X-band southern precision improvements are planned from observations with southern antennas such as the AuScope and HartRAO, S. Africa. We seek to improve radio frequency coverage with X/Ka and K-band work. An X/Ka frame of 631 sources now has full sky coverage from the addition of a 2nd southern station in Argentina which should strengthen the southern hemisphere in general. A K-band collaboration has formed with similar coverage and southern hemisphere precision goals. On the analysis front, special attention will be given to combination techniques both of VLBI catalogs and of multiple data types (e.g. VLBI GPS). Finally, work is underway to identify and pinpoint sources bright enough in both radio and optical to allow for a robust frame tie between VLBI and Gaia optical frames