Macrophages support pathological erythropoiesis in polycythemia vera and beta-thalassemia

Regulation of erythropoiesis is achieved by integration of distinct signals. Among these, macrophages are emerging as erythropoietin-complementary regulators of erythroid development, particularly under stress conditions. We investigated the contribution of macrophages for physiological and pathological conditions of enhanced erythropoiesis. We utilized mouse models of induced anemia, Polycythemia vera and β-thalassemia in which macrophages were chemically depleted. Our data indicate that macrophages contribute decisively for recovery from induced anemia as well as the pathological progression of Polycythemia vera and β-thalassemia by modulating erythroid proliferation and differentiation. We validated these observations in primary human cultures, showing a critical direct impact of macrophages on proliferation and enucleation of erythroblasts from healthy individuals and Polycythemia vera or β-thalassemic patients. In summary, we identify a new mechanism that we named “Stress Erythropoiesis Macrophage-supporting Activity” (SEMA) that contributes to the pathophysiology of these disorders and will have critical scientific and therapeutic implications in the near future

Shear band patterns in metallic glasses under static indentation, dynamic indentation, and scratch processes

The deformation structure in terms of shear band patterns in bulk metallic glasses (BMGs) under static indentation, dynamic indentation, and dynamic scratch tests has been investigated. The evolved shear band patterns appear to be a strong function of loading rate, although the plastic regions beneath the loading surface have similarities in shape irrespective of loading type. Comparison of currently available modeling estimates with experimental measurements has revealed that these models predict the plastic zone size reasonably well at low loads but deviate considerably at higher loads. The variation in spacing of shear bands is rationalized on the basis of the shear displacement accommodated by the shear bands formed under different loading rates, which results from a proposed shear-band formation mechanism based on the momentum diffusion model. © The Minerals, Metals & Materials Society and ASM International 2007

The D-CIXS X-ray spectrometer on the SMART-1 mission to the Moon - First Results

The SMART-1 mission has recently arrived at the Moon. Its payload includes D-CIXS, a compact X-ray spectrometer. SMART-1 is a technology evaluation mission, and D-CIXS is the first of a new generation of planetary X-ray spectrometers. Novel technologies enable new capabilities for measuring the fluorescent yield of a planetary surface or atmosphere which is illuminated by solar X-rays. During the extended SMART-1 cruise phase, observations of the Earth showed strong argon emission, providing a good source for calibration and demonstrating the potential of the technique. At the Moon, our initial observations over Mare Crisium show a first unambiguous remote sensing of calcium in the lunar regolith. Data obtained are broadly consistent with current understanding of mare and highland composition. Ground truth is provided by the returned Luna 20 and 24 sample sets

Characterization of Human Alpha-Dystrobrevin Isoforms in HL-60 Human Promyelocytic Leukemia Cells Undergoing Granulocytic Differentiation

The biochemical properties and spatial localization of the protein alpha-dystrobrevin and other isoforms were investigated in cells of the human promyelocytic leukemia line HL-60 granulocytic differentiation as induced by retinoic acid (RA). Alpha-dystrobrevin was detected both in the cytosol and the nuclei of these cells, and a short isoform (gamma-dystrobrevin) was modified by tyrosine phosphorylation soon after the onset of the RA-triggered differentiation. Varying patterns of distribution of alpha-dystrobrevin and its isoforms could be discerned in HL-60 promyelocytes, RA-differentiated mature granulocytes, and human neutrophils. Moreover, the gamma-dystrobrevin isoform was found in association with actin and myosin light chain. The results provide new information about potential involvement of alpha-dystrobrevin and its splice isoforms in signal transduction in myeloid cells during induction of granulocytic differentiation and/or at the commitment stage of differentiation or phagocytic cells

Utrophin Binds Laterally along Actin Filaments and Can Couple Costameric Actin with Sarcolemma When Overexpressed in Dystrophin-deficient Muscle

Dystrophin is widely thought to mechanically link the cortical cytoskeleton with the muscle sarcolemma. Although the dystrophin homolog utrophin can functionally compensate for dystrophin in mice, recent studies question whether utrophin can bind laterally along actin filaments and anchor filaments to the sarcolemma. Herein, we have expressed full-length recombinant utrophin and show that the purified protein is fully soluble with a native molecular weight and molecular dimensions indicative of monomers. We demonstrate that like dystrophin, utrophin can form an extensive lateral association with actin filaments and protect actin filaments from depolymerization in vitro. However, utrophin binds laterally along actin filaments through contribution of acidic spectrin-like repeats rather than the cluster of basic repeats used by dystrophin. We also show that the defective linkage between costameric actin filaments and the sarcolemma in dystrophin-deficient mdx muscle is rescued by overexpression of utrophin. Our results demonstrate that utrophin and dystrophin are functionally interchangeable actin binding proteins, but that the molecular epitopes important for filament binding differ between the two proteins. More generally, our results raise the possibility that spectrin-like repeats may enable some members of the plakin family of cytolinkers to laterally bind and stabilize actin filaments