The histone H3K4 demethylase JARID1A directly interacts with haematopoietic transcription factor GATA1 in erythroid cells through its second PHD domain

Chromatin remodelling and transcription factors play important roles in lineage commitment and development through control of gene expression. Activation of selected lineage-specific genes and repression of alternative lineage-affiliated genes results in tightly regulated cell differentiation transcriptional programmes. However, the complex functional and physical interplay between transcription factors and chromatin modifying enzymes remains elusive. Recent evidence has implicated histone demethylases in normal haematopoietic differentiation as well as in malignant haematopoiesis. Here we report an interaction between H3K4 demethylase JARID1A and the haematopoietic-specific master transcription proteins SCL and GATA1 in red blood cells. Specifically, we observe a direct physical contact between GATA1 and the second PHD domain of JARID1A. This interaction has potential implications for normal and malignant haematopoiesis

Fast magnetization switching of Stoner particles: A nonlinear dynamics picture

The magnetization reversal of Stoner particles is investigated from the point of view of nonlinear dynamics within the Landau-Lifshitz-Gilbert formulation. The following results are obtained. 1) We clarify that the so-called Stoner-Wohlfarth (SW) limit becomes exact when damping constant is infinitely large. Under the limit, the magnetization moves along the steepest energy descent path. The minimal switching field is the one at which there is only one stable fixed point in the system. 2) For a given magnetic anisotropy, there is a critical value for the damping constant, above which the minimal switching field is the same as that of the SW-limit. 3) We illustrate how fixed points and their basins change under a field along different directions. This change explains well why a non-parallel field gives a smaller minimal switching field and a short switching time. 4) The field of a ballistic magnetization reversal should be along certain direction window in the presence of energy dissipation. The width of the window depends on both of the damping constant and the magnetic anisotropy. The upper and lower bounds of the direction window increase with the damping constant. The window width oscillates with the damping constant for a given magnetic anisotropy. It is zero for both zero and infinite damping. Thus, the perpendicular field configuration widely employed in the current experiments is not the best one since the damping constant in a real system is far from zero.Comment: 10 pages, 9 figures. submitted to PR

Accuracy Assessment of Recreational and Mapping Grade GPS Receivers

Since its development in the early 1970s, Global Positioning System (GPS) technology has become more accessible and affordable for consumers. GPS applications have become ubiquitous in society. With the increased use of GPS, the question of accuracy is of concern. This study assessed the accuracy of four Garmin recreational GPS receivers, eTrex® , eTrex Legend® , eTrex Vista® , GPSMAP® 76CS, and three Trimble® mapping GPS receivers JunoTM , GeoExplorer3TM and GeoXHTM. Thirty-three ground control points (GCPs) were established in three different landscapes using survey grade GPS (Trimble’s 4700) that were corrected using National Geodetic Survey’s Online Positioning User Service (OPUS). Eleven GCPs were established in a forest landscape, eleven near buildings to simulate an urban landscape, and eleven with a clear unobstructed sky. The GPS receivers were tested with the Wide Angle Augmentation System (WAAS) on and off. In addition, results from averaging 30 GPS positions were evaluated. This study showed the GeoXH was the most accurate receiver and that the accuracy of the recreational (Garmin) receivers was from 2.52 to 18.42 meters depending on the landscape. The accuracies of the Garmin GPS receivers were similar

Structures of monomeric and oligomeric forms of the Toxoplasma gondiiperforin-like protein 1

Toxoplasma and Plasmodium are the parasitic agents of toxoplasmosis and malaria, respectively, and use perforin-like proteins (PLPs) to invade host organisms and complete their life cycles. The Toxoplasma gondii PLP1 (TgPLP1) is required for efficient exit from parasitophorous vacuoles in which proliferation occurs. We report structures of the membrane attack complex/perforin (MACPF) and Apicomplexan PLP C-terminal β-pleated sheet (APCβ) domains of TgPLP1. The MACPF domain forms hexameric assemblies, with ring and helix geometries, and the APCβ domain has a novel β-prism fold joined to the MACPF domain by a short linker. Molecular dynamics simulations suggest that the helical MACPF oligomer preserves a biologically important interface, whereas the APCβ domain binds preferentially through a hydrophobic loop to membrane phosphatidylethanolamine, enhanced by the additional presence of inositol phosphate lipids. This mode of membrane binding is supported by site-directed mutagenesis data from a liposome-based assay. Together, these structural and biophysical findings provide insights into the molecular mechanism of membrane targeting by TgPLP1

Solid Freeform Fabrication of Transparent Fused Quartz using a Filament Fed Process

Glass is a critical material for many scientific and engineering applications including optics, communications, electronics, and hermetic seals. Despite this technological relevance, there has been minimal research toward Additive Manufacturing (AM) of glass, particularly optically transparent glass. Additive Manufacturing of transparent glass offers potential advantages for lower processing costs for small production volumes, increased design freedom, and the ability to locally vary the optical properties of the part. Compared to common soda lime glass, fused quartz is better for AM since it has lower thermal expansion and higher index homogeneity. This paper presents a study of additive manufacturing of transparent fused quartz by a filament fed process. A CW CO2 laser (10.6 µm) is used to melt glass filaments layer by layer. The laser couples to phononic modes in the glass and is well absorbed. The beam and melt pool are stationary while the work piece is scanned using a standard lab motion system. Representative parts are built to explore the effects of variable laser power on the properties of printed fused quartz. During printing the incandescent emission from the melt pool is measured using a spectrometer. This permits process monitoring and identifies potential chemical changes in the glass during printing. After deposition, the printed parts are polished and the transmission measured to calculate the absorption/scattering coefficient. Finally, a low-order thermal analysis is presented and correlated to experimental results, including an energy balance and finite volume analysis using Fluent. These results suggest that optical quality fused quartz parts with low absorption and high index of refraction uniformity may be printed using the filament-fed process

The safety of bivalirudin during elective percutaneous coronary interventions in heart transplant patients

Background: Bivalirudin has been shown to be safe and effective during percutaneous coronary interventions (PCI) of native coronary arteries in the REPLACE 2 trial. The safety of bivalirudin during PCIs in heart transplant patients is not known. Methods: Heart transplant patients who had undergone PCI of de novo lesions and received bivalirudin during the procedure were included in the study. Medical records were reviewed for the occurrence of death, myocardial infarction, target vessel revascularization or major bleeding up to 30 days after discharge. The results were compared with the REPLACE 2 trial and with a control group of heart transplant recipients who received heparin during their procedures. Results: There were 51 separate PCIs performed in 30 patients in the study group. The mean age was 56 ± 12 years and 6 (20%) were women. The control group consisted of 24 patients who had undergone 35 PCIs. There were no deaths, myocardial infarctions or target vessel revascularization during the follow-up period in the study group. The combined endpoint of death, myocardial infarctions, target vessel revascularization and major bleeding requiring two or more units of packed red blood cells occurred in 2 (3.9%) patients compared to 275 (9.2%) patients in the REPLACE 2 trial (p = 0.195) and 5 (14.3%) in the control group (p = 0.115). Conclusion: Bivalirudin is a safe antithrombotic medication to use during elective PCI in heart transplant patients with cardiac allograft vasculopathy. (Cardiol J 2007; 14: 458-462

Structural and molecular basis of ZNRF3/RNF43 transmembrane ubiquitin ligase inhibition by the Wnt agonist R-spondin

The four R-spondin (Rspo) proteins are secreted agonists of Wnt signalling in vertebrates, functioning in embryogenesis and adult stem cell biology. Through ubiquitination and degradation of Wnt receptors, the transmembrane E3 ubiquitin ligase ZNRF3 and related RNF43 antagonize Wnt signalling. Rspo ligands have been reported to inhibit the ligase activity through direct interaction with ZNRF3 and RNF43. Here we report multiple crystal structures of the ZNRF3 ectodomain (ZNRF3ecto), a signalling-competent Furin1–Furin2 (Fu1–Fu2) fragment of Rspo2 (Rspo2Fu1–Fu2), and Rspo2Fu1–Fu2 in complex with ZNRF3ecto, or RNF43ecto. A prominent loop in Fu1 clamps into equivalent grooves in the ZNRF3ecto and RNF43ecto surface. Rspo binding enhances dimerization of ZNRF3ecto but not of RNF43ecto. Comparison of the four Rspo proteins, mutants and chimeras in biophysical and cellular assays shows that their signalling potency depends on their ability to recruit ZNRF3 or RNF43 via Fu1 into a complex with LGR receptors, which interact with Rspo via Fu2

Did Ebola emerge in West Africa by a policy-driven phase change in agroecology? Ebola's social context

SCOPUS: no.jinfo:eu-repo/semantics/publishe

A reduced-order strategy for 4D-Var data assimilation

This paper presents a reduced-order approach for four-dimensional variational data assimilation, based on a prior EO F analysis of a model trajectory. This method implies two main advantages: a natural model-based definition of a mul tivariate background error covariance matrix $\textbf{B}_r$, and an important decrease of the computational burden o f the method, due to the drastic reduction of the dimension of the control space. % An illustration of the feasibility and the effectiveness of this method is given in the academic framework of twin experiments for a model of the equatorial Pacific ocean. It is shown that the multivariate aspect of $\textbf{B}_r$ brings additional information which substantially improves the identification procedure. Moreover the computational cost can be decreased by one order of magnitude with regard to the full-space 4D-Var method

Hedgehog-Interacting Protein is a multimodal antagonist of Hedgehog signalling

Hedgehog (HH) morphogen signalling, crucial for cell growth and tissue patterning in animals, is initiated by the binding of dually lipidated HH ligands to cell surface receptors. Hedgehog-Interacting Protein (HHIP), the only reported secreted inhibitor of Sonic Hedgehog (SHH) signalling, binds directly to SHH with high nanomolar affinity, sequestering SHH. Here, we report the structure of the HHIP N-terminal domain (HHIP-N) in complex with a glycosaminoglycan (GAG). HHIP-N displays a unique bipartite fold with a GAG-binding domain alongside a Cysteine Rich Domain (CRD). We show that HHIP-N is required to convey full HHIP inhibitory function, likely by interacting with the cholesterol moiety covalently linked to HH ligands, thereby preventing this SHH-attached cholesterol from binding to the HH receptor Patched (PTCH1). We also present the structure of the HHIP C-terminal domain in complex with the GAG heparin. Heparin can bind to both HHIP-N and HHIP-C, thereby inducing clustering at the cell surface and generating a high-avidity platform for SHH sequestration and inhibition. Our data suggest a multimodal mechanism, in which HHIP can bind two specific sites on the SHH morphogen, alongside multiple GAG interactions, to inhibit SHH signalling