Quantum corrections to slow-roll inflation: scalar and tensor modes

Inflation is often described through the dynamics of a scalar field, slow-rolling in a suitable potential. Ultimately, this inflaton must be identified with the expectation value of a quantum field, evolving in a quantum effective potential. The shape of this potential is determined by the underlying tree-level potential, dressed by quantum corrections from the scalar field itself and the metric perturbations. Following [1], we compute the effective scalar field equations and the corrected Friedmann equations to quadratic order in both scalar field, scalar metric and tensor perturbations. We identify the quantum corrections from different sources at leading order in slow-roll, and estimate their magnitude in benchmark models of inflation. We comment on the implications of non-minimal coupling to gravity in this context.

Endothelial Barrier Function and Leukocyte Transmigration in Atherosclerosis

The vascular endothelium is a highly specialized barrier that controls passage of fluids and migration of cells from the lumen into the vessel wall. Endothelial cells assist leukocytes to extravasate and despite the variety in the specific mechanisms utilized by different leukocytes to cross different vascular beds, there is a general principle of capture, rolling, slow rolling, arrest, crawling, and ultimately diapedesis via a paracellular or transcellular route. In atherosclerosis, the barrier function of the endothelium is impaired leading to uncontrolled leukocyte extravasation and vascular leakage. This is also observed in the neovessels that grow into the atherosclerotic plaque leading to intraplaque hemorrhage and plaque destabilization. This review focuses on the vascular endothelial barrier function and the interaction between endothelial cells and leukocytes during transmigration. We will discuss the role of endothelial dysfunction, transendothelial migration of leukocytes and plaque angiogenesis in atherosclerosis.

Neutrophils lacking ERM proteins polarize and crawl directionally but have decreased adhesion strength

Ezrin/radixin/moesin (ERM) proteins are adaptors that link the actin cytoskeleton to the cytoplasmic domains of membrane proteins. Leukocytes express mostly moesin with lower levels of ezrin but no radixin. When leukocytes are activated, ERMs are postulated to redistribute membrane proteins from microvilli into uropods during polarization and to transduce signals that influence adhesion and other responses. However, these functions have not been tested in leukocytes lacking all ERMs. We used knockout (KO) mice with neutrophils lacking ezrin, moesin, or both proteins (double knockout [DKO]) to probe how ERMs modulate cell shape, adhesion, and signaling in vitro and in vivo. Surprisingly, chemokine-stimulated DKO neutrophils still polarized and redistributed ERM-binding proteins such as PSGL-1 and CD44 to the uropods. Selectin binding to PSGL-1 on moesin KO or DKO neutrophils activated kinases that enable integrin-dependent slow rolling but not those that generate neutrophil extracellular traps. Flowing neutrophils of all genotypes rolled normally on selectins and, upon chemokine stimulation, arrested on integrin ligands. However, moesin KO and DKO neutrophils exhibited defective integrin outside-in signaling and reduced adhesion strength. In vivo, DKO neutrophils displayed normal directional crawling toward a chemotactic gradient, but premature detachment markedly reduced migration from venules into inflamed tissues. Our results demonstrate that stimulated neutrophils do not require ERMs to polarize or to move membrane proteins into uropods. They also reveal an unexpected contribution of moesin to integrin outside-in signaling and adhesion strengthening.

Molecular and Pathophysiological Mechanisms of Diabetic Retinopathy in Relation to Adhesion Molecules

Diabetic Retinopathy (DR) is considered as a most common microvascular complication of diabetes affected by one in three people who are suffered for diabetes. Several pathophysiological mechanisms and adhesion molecules may play an etiologic role in the development of diabetes and its complications. The adhesion molecules located on both leucocytes and endothelial cells and considered as important molecules which can assessed the endothelial function. The functions of adhesion molecules involved in the cellular margination, slow rolling and transmigration of leukocytes. Hyperglycemia and its immediate biochemical sequelae or the low-grade inflammation directly alter endothelial function or influence endothelial cell functioning indirectly by induce oxidative stress and activates leukocytosis and leukocyte-endothelial cell interactions by the increased expression of adhesion molecules, growth factors, inflammatory factors, chemokines etc. and results DR. This review summarized the several pathophysiological mechanisms and role of adhesion molecules in disruption of homeostasis of vasculature by leukocytes in the development of diabetic retinopathy.

A possible analogy between the dynamics of a skydiver and a scalar field: Cosmological consequences

The cosmological consequences of a slow-rolling scalar field with constant kinetic term in analogy to the vertical movement of a skydiver after reaching terminal velocity are investigated. In this approach, the scalar field potential is given by a quadratic function of the field. This model provides solutions in which the universe was dominated in the past by a mixture of baryons and dark matter, is currently accelerating (as indicated by type Ia supernovae data), but will be followed by a contraction phase. The theoretical predictions of this model are consistent with current observations, therefore, a terminal scalar field is a viable candidate to dark energy.

Endothelial cell-derived CD95 ligand serves as a chemokine in induction of neutrophil slow rolling and adhesion

Integrin activation is crucial for the regulation of leukocyte rolling, adhesion and trans-vessel migration during inflammation and occurs by engagement of myeloid cells through factors presented by inflamed vessels. However, endothelial-dependent mechanisms of myeloid cell recruitment are not fully understood. Here we show using an autoperfused flow chamber assay of whole blood neutrophils and intravital microscopy of the inflamed cremaster muscle that CD95 mediates leukocyte slow rolling, adhesion and transmigration upon binding of CD95-ligand (CD95L) that is presented by endothelial cells. In myeloid cells, CD95 triggers activation of Syk-Btk/PLCγ2/Rap1 signaling that ultimately leads to integrin activation. Excitingly, CD95-deficient myeloid cells exhibit impaired bacterial clearance in an animal model of sepsis induced by cecal ligation and puncture (CLP). Our data identify the cellular and molecular mechanisms underlying the chemoattractant effect of endothelial cell-derived CD95L in induction of neutrophil recruitment and support the use of therapeutic inhibition of CD95’s activity in inflammatory diseases.