Virtual Prototyping for validation of functional architectures

International audienceThis paper will present a new approach how to use virtual prototyping to validate functional architectures. The approach points out how functional architecture can be set up and tested in order to get highly validated data before making final architectural/design decisions. The introduction will speak about the current facts, the constrains and the tendencies to create a common and understandable picture in which the proposed solution may be implemented. Then we will give a description and definition of MiLMiL / SiLSiL / HiL, rapid prototyping and virtual prototyping to avoid confusion. The main part will discuss functional and logical architecture, the mapping of both as well a the variants that have to be considered. It will be shown how validation by virtual prototyping can help to define and proof architectural decision. Finally we will give a short outlook on how to migrate from virtual prototyping systems via rapid prototyping via fullpass and bypass to HiL applications. The conclusion summarizes the advantages compared to the current situation

Binding of coatomer by the PEX11 C-terminus is not required for function

AbstractMicrobodies are single membrane-bound organelles found in eukaryotes from trypanosomes to man. Although they have diverse roles in metabolism, the mechanisms and molecules involved in membrane biogenesis and matrix protein import are conserved. Similarly, the basic mechanisms and structures involved in vesicular transport are similar throughout eukaryotic evolution. The PEX11 proteins are required for the division of microbodies in trypanosomes, yeast and mammals, and a role of coatomer in this process has been suggested. We show here that the binding of trypanosome, yeast and bovine coatomers to selected peptides is identical. Coatomer binds to the C-termini of trypanosome PEX11 and rat Pex11α, but not yeast Pex11p or human Pex11β. Mutations of the C-terminus of trypanosome PEX11 that eliminated coatomer binding did not affect function in yeast or trypanosomes. Thus binding of coatomer to the C-terminus of PEX11 is not required for PEX11 function

Teamwork in an honours group writing assignment

Scientific practice is essentially collaborative. Most research publications list multiple authors making collaborative writing a key skill for scientists. This paper reports the student experience of a collaborative writing task for honours students in experimental science. Students were asked to work in groups of five to research and construct a scientific review suitable for publication in a peer-reviewed journal. Students submitted a piece of individual writing as well as the final group review and where also asked to assess the contribution of group members. Students found group work demanding and this appeared to overshadow the experience of collaborative writing. However, at the same time, students strongly agreed that teamwork skills and collaboration were essential for successful research. This dichotomy between the need for collaborative skills and the difficulty of putting this into practice argues for greater development of teamwork skills in the undergraduate curriculum in preparation for research training

Invasion by P. falciparum Merozoites Suggests a Hierarchy of Molecular Interactions

Central to the pathology of malaria disease are the repeated cycles of parasite invasion and destruction of human erythrocytes. In Plasmodium falciparum, the most virulent species causing malaria, erythrocyte invasion involves several specific receptor–ligand interactions that direct the pathway used to invade the host cell, with parasites varying in their dependency on these different pathways. Gene disruption of a key invasion ligand in the 3D7 parasite strain, the P. falciparum reticulocyte binding-like homolog 2b (PfRh2b), resulted in the parasite invading via a novel pathway. Here, we show results that suggest the molecular basis for this novel pathway is not due to a molecular switch but is instead mediated by the redeployment of machinery already present in the parent parasite but masked by the dominant role of PfRh2b. This would suggest that interactions directing invasion are organized hierarchically, where silencing of dominant invasion ligands reveal underlying alternative pathways. This provides wild parasites with the ability to adapt to immune-mediated selection or polymorphism in erythrocyte receptors and has implications for the use of invasion-related molecules in candidate vaccines

Structure, localization and histone binding properties of nuclear-associated nucleosome assembly protein from Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>Nucleosome assembly proteins (NAPs) are histone chaperones that are crucial for the shuttling and incorporation of histones into nucleosomes. NAPs participate in the assembly and disassembly of nucleosomes thus contributing to chromatin structure organization. The human malaria parasite <it>Plasmodium falciparum </it>contains two nucleosome assembly proteins termed PfNapL and PfNapS.</p> <p>Methods</p> <p>Three-dimensional crystal structure of PfNapS has been determined and analysed. Gene knockout and localization studies were also performed on PfNapS using transfection studies. Fluorescence spectroscopy was performed to identify histone-binding sites on PfNapS. Extensive sequence and structural comparisons were done with the crystal structures available for NAP/SET family of proteins.</p> <p>Results</p> <p>Crystal structure of PfNapS shares structural similarity with previous structures from NAP/SET family. Failed attempts to knock-out the gene for PfNapS from malaria parasite suggest essentiality in the parasite. GFP-fused PfNapS fusion protein targeting indicates cellular localization of PfNapS in the parasite nucleus. Fluorescence spectroscopy data suggest that PfNapS interacts with core histones (tetramer, octamer, H3, H4, H2A and H2B) at a different site from its interaction with linker histone H1. This analysis illustrates two regions on the PfNapS dimer as the possible sites for histone recognition.</p> <p>Conclusions</p> <p>This work presents a thorough analysis of the structural, functional and regulatory attributes of PfNapS from <it>P. falciparum </it>with respect to previously studied histone chaperones.</p