ESAM supports neutrophil extravasation, activation of Rho, and VEGF-induced vascular permeability

Endothelial cell–selective adhesion molecule (ESAM) is specifically expressed at endothelial tight junctions and on platelets. To test whether ESAM is involved in leukocyte extravasation, we have generated mice carrying a disrupted ESAM gene and analyzed them in three different inflammation models. We found that recruitment of lymphocytes into inflamed skin was unaffected by the gene disruption. However, the migration of neutrophils into chemically inflamed peritoneum was inhibited by 70% at 2 h after stimulation, recovering at later time points. Analyzing neutrophil extravasation directly by intravital microscopy in the cremaster muscle revealed that leukocyte extravasation was reduced (50%) in ESAM−/− mice without affecting leukocyte rolling and adhesion. Depletion of >98% of circulating platelets did not abolish the ESAM deficiency–related inhibitory effect on neutrophil extravasation, indicating that it is only ESAM at endothelial tight junctions that is relevant for the extravasation process. Knocking down ESAM expression in endothelial cells resulted in reduced levels of activated Rho, a GTPase implicated in the destabilization of tight junctions. Indeed, vascular permeability stimulated by vascular endothelial growth factor was reduced in ESAM−/− mice. Collectively, ESAM at endothelial tight junctions participates in the migration of neutrophils through the vessel wall, possibly by influencing endothelial cell contacts

Shipborne measurements of XCO2_{2}, XCH4_{4}, and XCO above the Pacific Ocean and comparison to CAMS atmospheric analyses and S5P/TROPOMI

Measurements of atmospheric column-averaged dry-air mole fractions of carbon dioxide (XCO2), methane (XCH4), and carbon monoxide (XCO) have been collected across the Pacific Ocean during the Measuring Ocean REferences 2 (MORE-2) campaign in June 2019. We deployed a shipborne variant of the EM27/SUN Fourier transform spectrometer (FTS) on board the German RN Sonne which, during MORE-2, crossed the Pacific Ocean from Vancouver, Canada, to Singapore. Equipped with a specially manufactured fast solar tracker, the FTS operated in direct-sun viewing geometry during the ship cruise reliably delivering solar absorption spectra in the shortwave infrared spectral range (4000 to 11000 cm(-1)). After filtering and bias correcting the dataset, we report on XCO2, XCH4, and XCO measurements for 22 d along a trajectory that largely aligns with 30 degrees N of latitude between 140 degrees W and 120 degrees E of longitude. The dataset has been scaled to the Total Carbon Column Observing Network (TCCON) station in Karlsruhe, Germany, before and after the MORE-2 campaign through side-by-side measurements. The la repeatability of hourly means of XCO2, XCH4, and XCO is found to be 0.24 ppm, 1.1 ppb, and 0.75 ppb, respectively. The Copernicus Atmosphere Monitoring Service (CAMS) models gridded concentration fields of the atmospheric composition using assimilated satellite observations, which show excellent agreement of 0.52 +/- 0.31 ppm for XCO2, 0.9 +/- 4.1 ppb for XCH4, and 3.2 +/- 3.4 ppb for XCO (mean difference +/- SD, standard deviation, of differences for entire record) with our observations. Likewise, we find excellent agreement to within 2.2 +/- 6.6 ppb with the XCO observations of the TROPOspheric MOnitoring Instrument (TROPOMI) on the Sentinel-5 Precursor satellite (S5P). The shipborne measurements are accessible at https://doi.org/10.1594/PANGAEA.917240 (Knapp et al., 2020)

Functionally specialized junctions between endothelial cells of lymphatic vessels

Recirculation of fluid and cells through lymphatic vessels plays a key role in normal tissue homeostasis, inflammatory diseases, and cancer. Despite recent advances in understanding lymphatic function (Alitalo, K., T. Tammela, and T.V. Petrova. 2005. Nature. 438:946–953), the cellular features responsible for entry of fluid and cells into lymphatics are incompletely understood. We report the presence of novel junctions between endothelial cells of initial lymphatics at likely sites of fluid entry. Overlapping flaps at borders of oak leaf–shaped endothelial cells of initial lymphatics lacked junctions at the tip but were anchored on the sides by discontinuous button-like junctions (buttons) that differed from conventional, continuous, zipper-like junctions (zippers) in collecting lymphatics and blood vessels. However, both buttons and zippers were composed of vascular endothelial cadherin (VE-cadherin) and tight junction–associated proteins, including occludin, claudin-5, zonula occludens–1, junctional adhesion molecule–A, and endothelial cell–selective adhesion molecule. In C57BL/6 mice, VE-cadherin was required for maintenance of junctional integrity, but platelet/endothelial cell adhesion molecule–1 was not. Growing tips of lymphatic sprouts had zippers, not buttons, suggesting that buttons are specialized junctions rather than immature ones. Our findings suggest that fluid enters throughout initial lymphatics via openings between buttons, which open and close without disrupting junctional integrity, but most leukocytes enter the proximal half of initial lymphatics

VE-PTP maintains the endothelial barrier via plakoglobin and becomes dissociated from VE-cadherin by leukocytes and by VEGF

We have shown recently that vascular endothelial protein tyrosine phosphatase (VE-PTP), an endothelial-specific membrane protein, associates with vascular endothelial (VE)–cadherin and enhances VE-cadherin function in transfected cells (Nawroth, R., G. Poell, A. Ranft, U. Samulowitz, G. Fachinger, M. Golding, D.T. Shima, U. Deutsch, and D. Vestweber. 2002. EMBO J. 21:4885–4895). We show that VE-PTP is indeed required for endothelial cell contact integrity, because down-regulation of its expression enhanced endothelial cell permeability, augmented leukocyte transmigration, and inhibited VE-cadherin–mediated adhesion. Binding of neutrophils as well as lymphocytes to endothelial cells triggered rapid (5 min) dissociation of VE-PTP from VE-cadherin. This dissociation was only seen with tumor necrosis factor α–activated, but not resting, endothelial cells. Besides leukocytes, vascular endothelial growth factor also rapidly dissociated VE-PTP from VE-cadherin, indicative of a more general role of VE-PTP in the regulation of endothelial cell contacts. Dissociation of VE-PTP and VE-cadherin in endothelial cells was accompanied by tyrosine phoshorylation of VE-cadherin, β-catenin, and plakoglobin. Surprisingly, only plakoglobin but not β-catenin was necessary for VE-PTP to support VE-cadherin adhesion in endothelial cells. In addition, inhibiting the expression of VE-PTP preferentially increased tyrosine phosphorylation of plakoglobin but not β-catenin. In conclusion, leukocytes interacting with endothelial cells rapidly dissociate VE-PTP from VE-cadherin, weakening endothelial cell contacts via a mechanism that requires plakoglobin but not β-catenin

Effects of rubber hand illusion and excitatory theta burst stimulation on tactile sensation: A pilot study

Synchronous visuotactile stimulation on the own hidden hand and a visible fake limb can alter bodily self-perception and influence spontaneous neuroplasticity. The rubber hand illusion (RHI) paradigm experimentally produces an illusion of rubber hand ownership and arm shift by simultaneously stroking a rubber hand in view and a participant's visually occluded hand. The aim of this cross-over, placebo-controlled, single-blind study was to assess whether RHI, in combination with high-frequency repetitive transcranial magnetic stimulation (rTMS) given as intermittent (excitatory) theta burst stimulation (iTBS) applied over the hand area of the primary sensory region (S1) can enhance tactile sensation in a group of 21 healthy subjects and one patient with cervical spinal cord injury. Four sessions covered all combinations of real and sham stimulations of the RHI and the TBS: Real TBS and real RHI, real TBS and sham RHI, sham TBS and real RHI, and both conditions sham. The condition sham TBS and real RHI shows the greatest effect on the proprioceptive drift (median 2.3 cm, IQR 2) and on the score of RHI questionnaires (median 3, IQR 2) in the control group as well as in the real-real condition (median 2, IQR 2). The sham TBS and real RHI condition also shows the best results in the electrical perception test of the patient (median 1.9 mA). Conversely, the upregulation of the cortical excitability of S1 via TBS seems to impair the effect of the RHI. This might be due to a strengthening of the top-down connection between the central nervous system and the periphery, diminishing the RHI. This finding helps in understanding the mechanisms of top-down and bottom-up mechanisms in healthy subjects and patients with spinal cord injury. The RHI paradigm could represent an interesting therapeutic approach in improving tactile sensation and rTMS techniques could modulate these effects. Yet, further studies are needed, to examine the direction of the interaction effect of TMS and RH.Spinal Cord Injury and Tissue Regeneration Center SalzburgPeer Reviewe

ChromID identifies the protein interactome at chromatin marks

ISSN:1546-1696ISSN:1087-015