Iron and bismuth bound human serum transferrin reveals a partially-opened conformation in the N-lobe

Human serum transferrin (hTF) binds Fe(III) tightly but reversibly, and delivers it to cells via a receptor-mediated endocytosis process. The metal-binding and release result in significant conformational changes of the protein. Here, we report the crystal structures of diferric-hTF (Fe N Fe C-hTF) and bismuth-bound hTF (Bi N Fe C-hTF) at 2.8 and 2.4 Å resolutions respectively. Notably, the N-lobes of both structures exhibit unique 'partially-opened' conformations between those of the apo-hTF and holo-hTF. Fe(III) and Bi(III) in the N-lobe coordinate to, besides anions, only two (Tyr95 and Tyr188) and one (Tyr188) tyrosine residues, respectively, in contrast to four residues in the holo-hTF. The C-lobe of both structures are fully closed with iron coordinating to four residues and a carbonate. The structures of hTF observed here represent key conformers captured in the dynamic nature of the transferrin family proteins and provide a structural basis for understanding the mechanism of metal uptake and release in transferrin families. © 2012 Macmillan Publishers Limited. All rights reserved.published_or_final_versio

Experimental Assessment of the Water Quality Influence on the Phosphorus Uptake of an Invasive Aquatic Plant: Biological Responses throughout Its Phenological Stage

International audienceUnderstanding how an invasive plant can colonize a large range of environments is still a great challenge in freshwater ecology. For the first time, we assessed the relative importance of four factors on the phosphorus uptake and growth of an invasive macrophyte Elodea nuttallii (Planch.) St. John. This study provided data on its phenotypic plasticity, which is frequently suggested as an important mechanism but remains poorly investigated. The phosphorus uptake of two Elodea nuttallii subpopulations was experimentally studied under contrasting environmental conditions. Plants were sampled in the Rhine floodplain and in the Northern Vosges mountains, and then maintained in aquaria in hard (Rhine) or soft (Vosges) water. Under these conditions, we tested the influence of two trophic states (eutrophic state, 100 mu g.l(-1) P-PO43- and hypertrophic state, 300 mu g.l(-1) P-PO43-) on the P metabolism of plant subpopulations collected at three seasons (winter, spring and summer). Elodea nuttallii was able to absorb high levels of phosphorus through its shoots and enhance its phosphorus uptake, continually, after an increase of the resource availability (hypertrophic > eutrophic). The lowest efficiency in nutrient use was observed in winter, whereas the highest was recorded in spring, what revealed thus a storage strategy which can be beneficial to new shoots. This experiment provided evidence that generally, the water trophic state is the main factor governing P uptake, and the mineral status (softwater > hardwater) of the stream water is the second main factor. The phenological stage appeared to be a confounding factor to P level in water. Nonetheless, phenology played a role in P turnover in the plant. Finally, phenotypic plasticity allows both subpopulations to adapt to a changing environment

11 Rate of Convergence for Parallel Subspace Correction Methods for nonlinear variational inequalities

Given a reflexive Banach ¡ space and a convex ¢¤£¥¡§ ¦ ¨� © functional, we shall consider the following nonlinear optimization problem ���� � ¢�������������¡§ � (1

Computing patient-specific hemodynamics in stented femoral artery models obtained from computed tomography using a validated 3D reconstruction method

Patients with peripheral artery disease who undergo endovascular treatment are often inflicted by in-stent restenosis. The relation between restenosis and abnormal hemodynamics may be analyzed using patient-specific computational fluid dynamics (CFD) simulations. In this work, first a three-dimensional (3D) reconstruction method, based on an in-house semi-automatic segmentation algorithm of a patient's computed tomography (CT) images with calcification and metallic artifacts, and thrombus removal is described. The reconstruction method was validated using 3D printed rigid phantoms of stented femoral arteries by comparing the reconstructed geometries with the reference computer-aided design (CAD) geometries employed for 3D printing. The mean reconstruction error resulting from the validation of the reconstruction method was ~6% in both stented and non-stented regions. Secondly, a patient-specific model of the stented femoral artery was created and CFD analyses were performed with emphasis on the selection of the boundary conditions. CFD results were compared in scenarios with and without common femoral artery bifurcation, employing flat or parabolic inlet velocity profiles. Similar helical flow structures were visible in all scenarios. Negligible differences in wall shear stress (<0.5%) were found in the stented region. In conclusion, a robust method, applicable to patient-specific cases of stented diseased femoral arteries, was developed and validated

A Multiscale Model of Atherosclerotic Plaque Development: Toward a Coupling Between an Agent-Based Model and CFD Simulations

Computational models have been widely used to predict the efficacy of surgical interventions in response to Peripheral Occlusive Diseases. However, most of them lack a multiscale description of the development of the disease, which, in our hypothesis, is the key to develop an effective predictive model. Accordingly, in this work we present a multiscale computational framework that simulates the generation of atherosclerotic arterial occlusions. Starting from a healthy artery in homeostatic conditions, the perturbation of specific cellular and extracellular dynamics led to the development of the pathology, with the final output being a diseased artery. The presented model was developed on an idealized portion of a Superficial Femoral Artery (SFA), where an Agent-Based Model (ABM), locally replicating the plaque development, was coupled to Computational Fluid Dynamics (CFD) simulations that define the Wall Shear Stress (WSS) profile at the lumen interface. The ABM was qualitatively validated on histological images and a preliminary analysis on the coupling method was conducted. Once optimized the coupling method, the presented model can serve as a predictive platform to improve the outcome of surgical interventions such as angioplasty and stent deployment

A parallel scientific software for heterogeneous hydrogeoloy

Numerical modelling is an important key for the management and remediation of groundwater resources. As opposed to surface water and to highly karstic geologies, groundwater does not flow in well-identified open streams but is like water flowing in the voids of a sponge. Several field experiments show that the natural geological formations are highly heterogeneous, leadin