A novel ACVR1 mutation in the glycine/serine-rich domain found in the most benign case of a fibrodysplasia ossificans progressiva variant reported to date

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, autosomal dominant condition, classically characterised by heterotopic ossification beginning in childhood and congenital great toe malformations; occurring in response to a c.617 G>A ACVR1 mutation in the functionally important glycine/serine-rich domain of exon 6. Here we describe a novel c.587 T>C mutation in the glycine/serine-rich domain of ACVR1, associated with delayed onset of heterotopic ossification and an exceptionally mild clinical course. Absence of great toe malformations, the presence of early ossification of the cervical spine facets joints, plus mild bilateral camptodactyly of the 5th fingers, together with a novel ACVR1 mutation, are consistent with the 'FOP-variant' syndrome. The c.587 T>C mutation replaces a conserved leucine with proline at residue 196. Modelling of the mutant protein reveals a steric clash with the kinase domain that will weaken interactions with FKBP12 and induce exposure of the glycine/serine-rich repeat. The mutant receptor is predicted to be hypersensitive to ligand stimulation rather than being constitutively active, consistent with the mild clinical phenotype. This case extends our understanding of the 'FOP-variant' syndrome.

Gender effects in orientation on primary students’ performance on items rich in graphics

This study investigated the longitudinal performance of 378 students who completed mathematics items rich in graphics. Specifically, this study explored student performance across axis (e.g., numbers lines), opposed-position (e.g., line and column graphs) and circular (e.g., pie charts) items over a three-year period (ages 9-11 years). The results of the study revealed significant performance differences in the favour of boys on graphics items that were represented in horizontal and vertical displays. There were no gender differences on items that were represented in a circular manner.

Darjeeling, a feature-rich VM for the resource poor

The programming and retasking of sensor nodes could benefit greatly from the use of a virtual machine (VM) since byte code is compact, can be loaded on demand, and interpreted on a heterogeneous set of devices. The challenge is to ensure good programming tools and a small footprint for the virtual machine to meet the memory constraints of typical WSN platforms. To this end we propose Darjeeling, a virtual machine modelled after the Java VM and capable of executing a substantial subset of the Java language, but designed specifically to run on 8- and 16-bit microcontrollers with 2 - 10 KB of RAM. The Darjeeling VM uses a 16- rather than a 32-bit architecture, which is more efficient on the targeted platforms. Darjeeling features a novel memory organisation with strict separation of reference from non-reference types which eliminates the need for run-time type inspection in the underlying compacting garbage collector. Darjeeling uses a linked stack model that provides light-weight threads, and supports synchronisation. The VM has been implemented on three different platforms and was evaluated with micro benchmarks and a real-world application. The latter includes a pure Java implementation of the collection tree routing protocol conveniently programmed as a set of cooperating threads, and a reimplementation of an existing environmental monitoring application. The results show that Darjeeling is a viable solution for deploying large-scale heterogeneous sensor networks. Copyright 2009 ACM.

Rich probabilistic representations for bearing only decentralised data fusion

The aim of this paper is to demonstrate the validity of using Gaussian mixture models (GMM) for representing probabilistic distributions in a decentralised data fusion (DDF) framework. GMMs are a powerful and compact stochastic representation allowing efficient communication of feature properties in large scale decentralised sensor networks. It will be shown that GMMs provide a basis for analytical solutions to the update and prediction operations for general Bayesian filtering. Furthermore, a variant on the Covariance Intersect algorithm for Gaussian mixtures will be presented ensuring a conservative update for the fusion of correlated information between two nodes in the network. In addition, purely visual sensory data will be used to show that decentralised data fusion and tracking of non-Gaussian states observed by multiple autonomous vehicles is feasible.

Cytokine secretion via cholesterol-rich lipid raft-associated SNAREs at the phagocytic cup

Lipopolysaccharide-activated macrophages rapidly synthesize and secrete tumor necrosis factor α (TNFα) to prime the immune system. Surface delivery of membrane carrying newly synthesized TNFα is controlled and limited by the level of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins syntaxin 4 and SNAP-23. Many functions in immune cells are coordinated from lipid rafts in the plasmamembrane, and we investigated a possible role for lipid rafts in TNFα trafficking and secretion. TNFα surface delivery and secretion were found to be cholesterol- dependent. Upon macrophage activation, syntaxin 4 was recruited to cholesterol-dependent lipid rafts, whereas its regulatory protein, Munc18c, was excluded from the rafts. Syntaxin 4 in activated macrophages localized to discrete cholesterol-dependent puncta on the plasmamembrane, particularly on filopodia. Imaging the early stages of TNFα surface distribution revealed these puncta to be the initial points of TNFα delivery. During the early stages of phagocytosis, syntaxin 4 was recruited to the phagocytic cup in a cholesterol dependent manner. Insertion of VAMP3-positive recycling endosome membrane is required for efficient ingestion of a pathogen. Without this recruitment of syntaxin 4, it is not incorporated into the plasma membrane, and phagocytosis is greatly reduced. Thus, relocation of syntaxin 4 into lipid rafts in macrophages is a critical and rate-limiting step in initiating an effective immune response.

Biomimetic tubular nanofiber mesh and platelet rich plasma-mediated delivery of BMP-7 for large bone defect regeneration.

There is a growing need for successful bone tissue engineering strategies and advanced biomaterials that mimic the structure and function of native tissues carry great promise. Successful bone repair approaches may include an osteoconductive scaffold, osteoinductive growth factors, cells with an osteogenic potential and capacity for graft vascularisation. To increase osteoinductivity of biomaterials, the local combination and delivery of growth factors has been developed. In the present study we investigated the osteogenic effects of calcium phosphate (CaP)-coated nanofiber mesh tube-mediated delivery of BMP-7 from a PRP matrix for the regeneration of critical sized segmental bone defects in a small animal model. Bilateral full-thickness diaphyseal segmental defects were created in twelve male Lewis rats and nanofiber mesh tubes were placed around the defect. Defects received either treatment with a CaP-coated nanofiber mesh tube (n = 6), an un-coated nanofiber mesh tube (n=6) a CaP-coated nanofiber mesh tube with PRP (n=6) or a CaP-coated nanofiber mesh tube in combination with 5 μg BMP-7 and PRP (n = 6). After 12 weeks, bone volume and biomechanical properties were evaluated using radiography, microCT, biomechanical testing and histology. The results demonstrated significantly higher biomechanical properties and bone volume for the BMP group compared to the control groups. These results were supported by the histological evaluations, where BMP group showed the highest rate of bone regeneration within the defect. In conclusion, BMP-7 delivery via PRP enhanced functional bone defect regeneration, and together these data support the use of BMP-7 in the treatment of critical sized defects.

The adenine-rich tract in the 5ʹ-end of the hepatitis C virus ORF encodes a peptide regulating the binding of the C protein to RNA

Hepatitis C virus (HCV ) core (C) protein is thought to bind to viral RNA before it undergoes oligomerization leading to RNA encapsidation. Details of these events are so far unknown. The 5ʹ-terminal C protein coding sequence that includes an adenine (A)-rich tract is a part of an internal ribosome entry site(IRES). This nucleotide sequence but not the corresponding protein sequence is needed for proper initiation of translation of viral RNA by an IRES-dependent mechanism. In this study, we examined the importance of this sequence for the ability of the C protein to bind to viral RNA. Serially truncated C proteins with deletions from 10 up to 45 N-terminal amino acids were expressed in Escherichia coli, purified and tested for binding to viral RNA by a gel shift assay. The results showed that truncation of the C protein from its N-terminus by more than 10 amino acids abolished almost completely its expression in E. coli. The latter could be restored by adding a tag to the N-terminus of the protein. The tagged proteins truncated by 15 or more amino acids showed an anomalous migration in SDS-PAGE. Truncation by more than 20 amino acids resulted in a complete loss of ability of tagged C protein to bind to viral RNA. These results provide clues to the early events in the C protein - RNA interactions leading to C protein oligomerization, RNA encapsidation and virion assembly.

The difference of thermal stability between Fe-substituted palygorskite and Al-rich palygorskite

Sedimentary palygorskite (SP) and hydrothermal palygorskite (HP) were characterized by XRF, TG/DSC, andXRD. The total iron and dissociative iron in palygorskite were detected using spectrophotometry. The results showed that about 3.57 wt% of Fe2O3 was detected in SP in contrast with 0.4 wt% in HP. SP was a Fe-substituted palygorskite, and HP was an Al-rich palygorskite. The occurrence of Fe substitution in SP resulted in two mass loss steps of coordinated water and resulted in a larger d spacing. The SP showed greater thermal stability than the HP. It was proposed the change of (200) diffraction peak and (240) diffraction peak reflect changes of tetrahedral and octahedral structures in palygorskite.