Intercellular calcium communication regulates platelet aggregation and thrombus growth

The ability of platelets to form stable adhesion contacts with other activated platelets (platelet cohesion or aggregation) at sites of vascular injury is essential for hemostasis and thrombosis. In this study, we have examined the mechanisms regulating cytosolic calcium flux during the development of platelet–platelet adhesion contacts under the influence of flow. An examination of platelet calcium flux during platelet aggregate formation in vitro demonstrated a key role for intercellular calcium communication (ICC) in regulating the recruitment of translocating platelets into developing aggregates. We demonstrate that ICC is primarily mediated by a signaling mechanism operating between integrin αIIbβ3 and the recently cloned ADP purinergic receptor P2Y12. Furthermore, we demonstrate that the efficiency by which calcium signals are propagated within platelet aggregates plays an important role in dictating the rate and extent of thrombus growth

Erythrocyte hemolysis and hemoglobin oxidation promote ferric chloride-induced vascular injury,” The

Abstract The release of redox-active iron and heme into the blood-stream is toxic to the vasculature, contributing to the development of vascular diseases. How iron induces endothelial injury remains ill defined. To investigate this, we developed a novel ex vivo perfusion chamber that enables direct analysis of the effects of FeCl3 on the vasculature. We demonstrate that FeCl3 treatment of isolated mouse aorta, perfused with whole blood, was associated with endothelial denudation, collagen exposure, and occlusive thrombus formation. Strikingly exposing vessels to FeCl3 alone, in the absence of perfused blood, was associated with only minor vascular injury. Whole blood fractionation studies revealed that FeCl3-induced vascular injury was red blood cell (erythrocyte)-dependent, requiring erythrocyte hemolysis and hemoglobin oxidation for endothelial denudation

Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes

T lymphocytes utilize amoeboid migration to navigate effectively within complex microenvironments. The precise rearrangement of the actin cytoskeleton required for cellular forward propulsion is mediated by actin regulators, including the actin‐related protein 2/3 (Arp2/3) complex, a macromolecular machine that nucleates branched actin filaments at the leading edge. The consequences of modulating Arp2/3 activity on the biophysical properties of the actomyosin cortex and downstream T cell function are incompletely understood. We report that even a moderate decrease of Arp3 levels in T cells profoundly affects actin cortex integrity. Reduction in total F‐actin content leads to reduced cortical tension and disrupted lamellipodia formation. Instead, in Arp3‐knockdown cells, the motility mode is dominated by blebbing migration characterized by transient, balloon‐like protrusions at the leading edge. Although this migration mode seems to be compatible with interstitial migration in three‐dimensional environments, diminished locomotion kinetics and impaired cytotoxicity interfere with optimal T cell function. These findings define the importance of finely tuned, Arp2/3‐dependent mechanophysical membrane integrity in cytotoxic effector T lymphocyte activities

The 2dF galaxy redshift survey: clustering properties of radio galaxies

The clustering properties of local, S1.4 GHz≥ 1 mJy, radio sources are investigated for a sample of 820 objects drawn from the joint use of the Faint Images of the Radio Sky at 20 cm (FIRST) and 2dF Galaxy Redshift surveys. To this aim, we present 271 new bJ≤ 19.45 spectroscopic counterparts of FIRST radio sources to be added to those already introduced in our previous paper. The two-point correlation function for the local radio population is found to be entirely consistent with estimates obtained for the whole sample of 2dFGRS galaxies. From measurements of the redshift-space correlation function ξ(s) we derive a redshift-space clustering length s0 = 10.7+0.8 −0.7 Mpc, while from the projected correlation function Ξ(rT) we estimate the parameters of the real-space correlation function ξ(r) = (r/r0) −γ, r0 = 6.7+0.9 −1.1 Mpc and γ= 1.6 ± 0.1, where h = 0.7 is assumed. Different results are instead obtained if we only consider sources that present signatures of active galactic nucleus (AGN) activity in their spectra. These objects are shown to be very strongly correlated, with r0 = 10.9+1.0 −1.2 Mpc and γ= 2 ± 0.1, a steeper slope than has been claimed in other recent works. No difference is found in the clustering properties of radio-AGNs of different radio luminosity. Comparisons with models for ξ(r) show that AGN-fuelled sources reside in dark matter haloes more massive than ∼1013.4 M⊙, higher than the corresponding figure for radio-quiet quasi-stellar objects. This value can be converted into a minimum black hole mass associated with radio-loud, AGN-fuelled objects of MminBH∼ 109 M⊙. The above results then suggest - at least for relatively faint radio objects - the existence of a threshold black hole mass associated with the onset of significant radio activity such as that of radio-loud AGNs; however, once the activity is triggered, there appears to be no evidence for a connection between black hole mass and level of radio outpu

Galaxy groups in the 2dFGRS: the group-finding algorithm and the 2PIGG catalogue

The construction of a catalogue of galaxy groups from the Two-degree Field Galaxy Redshift Survey (2dFGRS) is described. Groups are identified by means of a friends-of-friends percolation algorithm which has been thoroughly tested on mock versions of the 2dFGRS generated from cosmological N-body simulations. The tests suggest that the algorithm groups all galaxies that it should be grouping, with an additional 40 per cent of interlopers. About 55 per cent of the ∼190 000 galaxies considered are placed into groups containing at least two members of which ∼29 000 are found. Of these, ∼7000 contain at least four galaxies, and these groups have a median redshift of 0.11 and a median velocity dispersion of 260 km s−1. This 2dFGRS Percolation-Inferred Galaxy Group (2PIGG) catalogue represents the largest available homogeneous sample of galaxy groups. It is publicly available on the World Wide We

The 2dF Galaxy Redshift Survey: stochastic relative biasing between galaxy populations

It is well known that the clustering of galaxies depends on galaxy type. Such relative bias complicates the inference of cosmological parameters from galaxy redshift surveys, and is a challenge to theories of galaxy formation and evolution. In this paper we perform a joint counts-in-cells analysis on galaxies in the 2dF Galaxy Redshift Survey, classified by both colour and spectral type, η, as early- or late-type galaxies. We fit three different models of relative bias to the joint probability distribution of the cell counts, assuming Poisson sampling of the galaxy density field. We investigate the non-linearity and stochasticity of the relative bias, with cubic cells of side 10 =L = 45 Mpc (h = 0.7). Exact linear bias is ruled out with high significance on all scales. Power-law bias gives a better fit, but likelihood ratios prefer a bivariate lognormal distribution, with a non-zero ‘stochasticity', i.e. scatter that may result from physical effects on galaxy formation other than those from the local density field. Using this model, we measure a correlation coefficient in log-density space (rLN) of 0.958 for cells of length L = 10 Mpc, increasing to 0.970 by L = 45 Mpc. This corresponds to a stochasticity of 0.44 ± 0.02 and 0.27 ± 0.05, respectively. For smaller cells, the Poisson-sampled lognormal distribution presents an increasingly poor fit to the data, especially with regard to the fraction of completely empty cells. We compare these trends with the predictions of semi-analytic galaxy formation models: these match the data well in terms of the overall level of stochasticity, variation with scale and the fraction of empty cell