System-based proteomic and metabonomic analysis of the Df(16)A+/- mouse identifies potential miR-185 targets and molecular pathway alterations

Deletions on chromosome 22q11.2 are a strong genetic risk factor for development of schizophrenia and cognitive dysfunction. We employed shotgun liquid chromatography-mass spectrometry (LC-MS) proteomic and metabonomic profiling approaches on prefrontal cortex (PFC) and hippocampal (HPC) tissue from Df(16)A +/- mice, a model of the 22q11.2 deletion syndrome. Proteomic results were compared with previous transcriptomic profiling studies of the same brain regions. The aim was to investigate how the combined effect of the 22q11.2 deletion and the corresponding miRNA dysregulation affects the cell biology at the systems level. The proteomic brain profiling analysis revealed PFC and HPC changes in various molecular pathways associated with chromatin remodelling and RNA transcription, indicative of an epigenetic component of the 22q11.2DS. Further, alterations in glycolysis/gluconeogenesis, mitochondrial function and lipid biosynthesis were identified. Metabonomic profiling substantiated the proteomic findings by identifying changes in 22q11.2 deletion syndrome (22q11.2DS)-related pathways, such as changes in ceramide phosphoethanolamines, sphingomyelin, carnitines, tyrosine derivates and panthothenic acid. The proteomic findings were confirmed using selected reaction monitoring mass spectrometry, validating decreased levels of several proteins encoded on 22q11.2, increased levels of the computationally predicted putative miR-185 targets UDP-N-acetylglucosamine-peptide N-acetylglucosaminyltransferase 110 kDa subunit (OGT1) and kinesin heavy chain isoform 5A and alterations in the non-miR-185 targets serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform, neurofilament light chain and vesicular glutamate transporter 1. Furthermore, alterations in the proteins associated with mammalian target of rapamycin signalling were detected in the PFC and with glutamatergic signalling in the hippocampus. Based on the proteomic and metabonomic findings, we were able to develop a schematic model summarizing the most prominent molecular network findings in the Df(16)A +/- mouse. Interestingly, the implicated pathways can be linked to one of the most consistent and strongest proteomic candidates, (OGT1), which is a predicted miR-185 target. Our results provide novel insights into system-biological mechanisms associated with the 22q11DS, which may be linked to cognitive dysfunction and an increased risk to develop schizophrenia. Further investigation of these pathways could help to identify novel drug targets for the treatment of schizophrenia

Prevalence of face recognition deficits in middle childhood

Approximately 2-2.5% of the adult population is believed to show severe difficulties with face recognition, in the absence of any neurological injury – a condition known as developmental prosopagnosia (DP). However, to date no research has attempted to estimate the prevalence of face recognition deficits in children, possibly because there are very few child-friendly, well-validated tests of face recognition. In the current study, we examined face and object recognition in a group of primary school children (aged 5-11 years), to establish whether our tests were suitable for children; and to provide an estimate of face recognition difficulties in children. In Experiment 1 (n = 184), children completed a pre-existing test of child face memory, the CFMT-K, and a bicycle test with the same format. In Experiment 2 (n = 413), children completed three-alternative forced choice matching tasks with faces and bicycles. All tests showed good psychometric properties. The face and bicycle tests were well-matched for difficulty and showed a similar developmental trajectory. Neither the memory nor matching tests were suitable to detect impairments in the youngest groups of children, but both tests appear suitable to screen for face recognition problems in middle childhood. In the current sample, 1.2-5.2% of children showed difficulties with face recognition; 1.2-4% showed face-specific difficulties – that is, poor face recognition with typical object recognition abilities. This is somewhat higher than previous adult estimates: it is possible that face matching tests overestimate the prevalence of face recognition difficulties in children; alternatively, some children may “outgrow” face recognition difficulties

Towards Activity Context using Software Sensors

Service-Oriented Computing delivers the promise of configuring and reconfiguring software systems to address user's needs in a dynamic way. Context-aware computing promises to capture the user's needs and hence the requirements they have on systems. The marriage of both can deliver ad-hoc software solutions relevant to the user in the most current fashion. However, here it is a key to gather information on the users' activity (that is what they are doing). Traditionally any context sensing was conducted with hardware sensors. However, software can also play the same role and in some situations will be more useful to sense the activity of the user. Furthermore they can make use of the fact that Service-oriented systems exchange information through standard protocols. In this paper we discuss our proposed approach to sense the activity of the user making use of software

Development of a novel UPLC-MS/MS-based platform to quantify amines, amino acids and methylarginines for applications in human disease phenotyping

Amine quantification is an important strategy in patient stratification and personalised medicine. This is because amines, including amino acids and methylarginines impact on many homeostatic processes. One important pathway regulated by amine levels is nitric oxide synthase (NOS). NOS is regulated by levels of (i) the substrate, arginine, (ii) amino acids which cycle with arginine and (iii) methylarginine inhibitors of NOS. However, biomarker research in this area is hindered by the lack of a unified analytical platform. Thus, the development of a common metabolomics platform, where a wide range of amino acids and methylarginines can be measured constitutes an important unmet need. Here we report a novel high-throughput ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) platform where ≈40 amine analytes, including arginine and methylarginines can be detected and quantified on a molar basis, in a single sample of human plasma. To validate the platform and to generate biomarkers, human plasma from a well-defined cohort of patients before and after coronary artery bypass surgery, who developed systemic inflammatory response syndrome (SIRS), were analysed. Bypass surgery with SIRS significantly altered 26 amine analytes, including arginine and ADMA. Consequently, pathway analysis revealed significant changes in a range of pathways including those associated with NOS

Context-Aware User Authentication – Supporting Proximity-Based Login in Pervasive Computing

Abstract. This paper explores computer security in pervasive computing with focus on user authentication. We present the concept of Proximity-Based User Authentication, as a usability-wise ideal for UbiComp systems. We present a context-aware user authentication protocol, which (1) uses a JavaCard for identi-fication and cryptographic calculations, (2) uses a context-awareness system for verifying the user’s location, and (3) implements a security fall-back strategy. We analyze the security of this protocol and discuss the tradeoff between usabil-ity and security. We also present our current implementation of the protocol and discuss future work.

Interacting mindreaders

Could interacting mindreaders be in a position to know things which they would be unable to know if they were manifestly passive observers? This paper argues that they could. Mindreading is sometimes reciprocal: the mindreader's target reciprocates by taking the mindreader as a target for mindreading. The paper explains how such reciprocity can significantly narrow the range of possible interpretations of behaviour where mindreaders are, or appear to be, in a position to interact. A consequence is that revisions and extensions are needed to standard theories of the evidential basis of mindreading. The view also has consequences for understanding how abilities to interact combined with comparatively simple forms of mindreading may explain the emergence, in evolution or development, of sophisticated forms of social cognition

Futures in the making: Practices to anticipate 'ubiquitous computing'

This paper addresses the discourse for a proactive thinking of futurity, intimately concerned with technology, which comes to an influential fruition in the discussion and representation of 'ubiquitous computing'. The imagination, proposal, or playing out of ubiquitous computing environments are bound up with particular ways of constructing futurity. This paper charts the techniques used in ubiquitous computing development to negotiate that futurity. In so doing, it engages with recent geographical debates around anticipation and futurity. The discussion accordingly proceeds in four parts. First, the spatial imagination engendered by the development of ubiquitous computing is explored. Second, particular techniques in ubiquitous computing research and development for anticipating future technology use, and their limits, are discussed through empirical findings. Third, anticipatory knowledge is explored as the basis for stable means of future orientation, which both generates and derives from the techniques for anticipating futures. Fourth, the importance of studying future orientation is situated in relation to the somewhat contradictory nature of anticipatory knowledges of ubicomp and related forms of spatial imagination. © 2012 Pion and its Licensors