Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered

Investigating the use of a hybrid plasmonic–photonic nanoresonator for optical trapping using finite-difference time-domain method

We investigate the use of a hybrid nanoresonator comprising a photonic crystal (PhC) cavity coupled to a plasmonic bowtie nanoantenna (BNA) for the optical trapping of nanoparticles in water. Using finite difference time-domain simulations, we show that this structure can confine light to an extremely small volume of ~30,000 nm3 (~30 zl) in the BNA gap whilst maintaining a high quality factor (5400–7700). The optical intensity inside the BNA gap is enhanced by a factor larger than 40 compared to when the BNA is not present above the PhC cavity. Such a device has potential applications in optical manipulation, creating high precision optical traps with an intensity gradient over a distance much smaller than the diffraction limit, potentially allowing objects to be confined to much smaller volumes and making it ideal for optical trapping of Rayleigh particles (particles much smaller than the wavelength of light)

Predicting calvarial morphology in sagittal craniosynostosis

Early fusion of the sagittal suture is a clinical condition called, sagittal craniosynostosis. Calvarial reconstruction is the most common treatment option for this condition with a range of techniques being developed by different groups. Computer simulations have a huge potential to predict the calvarial growth and optimise the management of this condition. However, these models need to be validated. The aim of this study was to develop a validated patient-specific finite element model of a sagittal craniosynostosis. Here, the finite element method was used to predict the calvarial morphology of a patient based on its preoperative morphology and the planned surgical techniques. A series of sensitivity tests and hypothetical models were carried out and developed to understand the effect of various input parameters on the result. Sensitivity tests highlighted that the models are sensitive to the choice of input parameter. The hypothetical models highlighted the potential of the approach in testing different reconstruction techniques. The patient-specific model highlighted that a comparable pattern of calvarial morphology to the follow up CT data could be obtained. This study forms the foundation for further studies to use the approach described here to optimise the management of sagittal craniosynostosis

Copy number variation in bipolar disorder.

Large (>100 kb), rare (500 kb) CNVs in BD compared with SZ, most notably for deletions >1 Mb (P=9 × 10(-4))

A model of online protection to reduce children's online risk exposure: empirical evidence from Asia

Children are surrounded by a variety of digital media and are exposed to potential risks that come with such easy accessibility. Learning how to be safe online is an important consideration for both children and their caregivers. The present study proposes an integrated model of online safety based on constructs from protection motivation theory and the health belief model, namely perceived severity of (and susceptibility to) risk, online self-efficacy, online privacy concern, and digital literacy. The study comprised a survey conducted among 420 schoolchildren aged 9–16 years. Using partial least squares-structural equation modelling, the results illustrated the presence of a negative effect of ‘perceived severity of online risk’ toward online risks, whereas the effect of ‘digital literacy’ was found to be positive. Children whose perception of online risks was more severe were less exposed to online risks if they had higher ‘online privacy concerns’ than the children with higher ‘digital literacy’ who are more exposed to online risk. Results of the study show that engaging in safe online behaviour requires children to have a high perception regarding severity of online risks as well as knowledge of online privacy concerns. Online risks and opportunities occur in parallel. Consequently, the factors that increase or decrease risk may also increase or decrease the benefits

A systematic review of protocol studies on conceptual design cognition

This paper reports the first systematic review and synthesis of protocol studies on conceptual design cognition. 47 protocol studies from the domains of architectural design, engineering design, and product de-sign engineering were reviewed towards answering the following re-search question: What is our current understanding of the cognitive processes involved in conceptual design tasks carried out by individual designers? Studies were found to reflect three viewpoints on the cognitive nature of designing, namely: design as search; design as ex-ploration; and design activities. Synthesising the findings of individual studies yielded a classification of cognitive processes involved in con-ceptual design tasks, described in different terms across different viewpoints. Towards a common terminology, these processes are posi-tioned within the cognitive psychology literature, revealing seven basic types of process that appear to be fundamental to designing across all viewpoints: memory (working and long term); visual perception; men-tal imagery; attention; semantic association; cognitive control; and higher-order processes, e.g. analysis and reasoning. The development of common cognitive models of conceptual design, grounded in a sci-entifically rigorous understanding of design cognition, is identified as an avenue for future research

How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins?

Variations on the statement "the variant surface glycoprotein (VSG) coat that covers the external face of the mammalian bloodstream form of Trypanosoma brucei acts a physical barrier" appear regularly in research articles and reviews. The concept of the impenetrable VSG coat is an attractive one, as it provides a clear model for understanding how a trypanosome population persists; each successive VSG protects the plasma membrane and is immunologically distinct from previous VSGs. What is the evidence that the VSG coat is an impenetrable barrier, and how do antibodies and other extracellular proteins interact with it? In this review, the nature of the extracellular surface of the bloodstream form trypanosome is described, and past experiments that investigated binding of antibodies and lectins to trypanosomes are analysed using knowledge of VSG sequence and structure that was unavailable when the experiments were performed. Epitopes for some VSG monoclonal antibodies are mapped as far as possible from previous experimental data, onto models of VSG structures. The binding of lectins to some, but not to other, VSGs is revisited with more recent knowledge of the location and nature of N-linked oligosaccharides. The conclusions are: (i) Much of the variation observed in earlier experiments can be explained by the identity of the individual VSGs. (ii) Much of an individual VSG is accessible to antibodies, and the barrier that prevents access to the cell surface is probably at the base of the VSG N-terminal domain, approximately 5 nm from the plasma membrane. This second conclusion highlights a gap in our understanding of how the VSG coat works, as several plasma membrane proteins with large extracellular domains are very unlikely to be hidden from host antibodies by VSG.The authors’ lab is funded by the Wellcome Trust (093008/Z10/Z) and the Medical Research Council (MR/L008246/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It was first available from PLOS via http://dx.doi.org/10.1371/journal.ppat.100525

Dystroglycan versatility in cell adhesion: a tale of multiple motifs

Dystroglycan is a ubiquitously expressed heterodimeric adhesion receptor. The extracellular a-subunit makes connections with a number of laminin G domain ligands including laminins, agrin and perlecan in the extracellular matrix and the transmembrane b-subunit makes connections to the actin filament network via cytoskeletal linkers including dystrophin, utrophin, ezrin and plectin, depending on context. Originally discovered as part of the dystrophin glycoprotein complex of skeletal muscle, dystroglycan is an important adhesion molecule and signalling scaffold in a multitude of cell types and tissues and is involved in several diseases. Dystroglycan has emerged as a multifunctional adhesion platform with many interacting partners associating with its short unstructured cytoplasmic domain. Two particular hotspots are the cytoplasmic juxtamembrane region and at the very carboxy terminus of dystroglycan. Regions which between them have several overlapping functions: in the juxtamembrane region; a nuclear localisation signal, ezrin/radixin/moesin protein, rapsyn and ERK MAP Kinase binding function, and at the C terminus a regulatory tyrosine governing WW, SH2 and SH3 domain interactions. We will discuss the binding partners for these motifs and how their interactions and regulation can modulate the involvement of dystroglycan in a range of different adhesion structures and functions depending on context. Thus dystroglycan presents as a multifunctional scaffold involved in adhesion and adhesion-mediated signalling with its functions under exquisite spatiotemporal regulation

Evidence for Shared Cognitive Processing of Pitch in Music and Language

Language and music epitomize the complex representational and computational capacities of the human mind. Strikingly similar in their structural and expressive features, a longstanding question is whether the perceptual and cognitive mechanisms underlying these abilities are shared or distinct – either from each other or from other mental processes. One prominent feature shared between language and music is signal encoding using pitch, conveying pragmatics and semantics in language and melody in music. We investigated how pitch processing is shared between language and music by measuring consistency in individual differences in pitch perception across language, music, and three control conditions intended to assess basic sensory and domain-general cognitive processes. Individuals’ pitch perception abilities in language and music were most strongly related, even after accounting for performance in all control conditions. These results provide behavioral evidence, based on patterns of individual differences, that is consistent with the hypothesis that cognitive mechanisms for pitch processing may be shared between language and music.National Science Foundation (U.S.). Graduate Research Fellowship ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Grant 5K99HD057522