8,171 research outputs found

    Automatic correction of hand pointing in stereoscopic depth

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    In order to examine whether stereoscopic depth information could drive fast automatic correction of hand pointing, an experiment was designed in a 3D visual environment in which participants were asked to point to a target at different stereoscopic depths as quickly and accurately as possible within a limited time window (≤300 ms). The experiment consisted of two tasks: "depthGO" in which participants were asked to point to the new target position if the target jumped, and "depthSTOP" in which participants were instructed to abort their ongoing movements after the target jumped. The depth jump was designed to occur in 20% of the trials in both tasks. Results showed that fast automatic correction of hand movements could be driven by stereoscopic depth to occur in as early as 190 ms.This work was supported by the Grants from the National Natural Science Foundation of China (60970062 and 61173116) and the Doctoral Fund of Ministry of Education of China (20110072110014)

    Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients

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    Background Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. Methods We report on visuospatial cognition in two individuals with contrasting partial deletions in the WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. Results Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB’s atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. Conclusions Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed

    A thyroid hormone regulated asymmetric responsive centre is correlated with eye migration during flatfish metamorphosis

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    Flatfish metamorphosis is a unique post-embryonic developmental event in which thyroid hormones (THs) drive the development of symmetric pelagic larva into asymmetric benthic juveniles. One of the eyes migrates to join the other eye on the opposite side of the head. Developmental mechanisms at the basis of the acquisition of flatfish anatomical asymmetry remain an open question. Here we demonstrate that an TH responsive asymmetric centre, determined by deiodinase 2 expression, ventrally juxtaposed to the migrating eye in sole (Solea senegalensis) correlates with asymmetric cranial ossification that in turn drives eye migration. Besides skin pigmentation that is asymmetric between dorsal and ventral sides, only the most anterior head region delimited by the eyes becomes asymmetric whereas the remainder of the head and organs therein stay symmetric. Sub-ocular ossification is common to all flatfish analysed to date, so we propose that this newly discovered mechanism is universal and is associated with eye migration in all flatfish.Fundacao para a Ciencia e Tecnologia (FCT) [SFRH/BPD/66808/2009, IF/01274/2014]; FCT [SFRH/BPD/79105/2011, SFRH/BPD/89889/2012, PTDC/MAR/115005/2009, PEst-C/MAR/LA0015/2011, UID/Multi/04326/2013, Pest-OE/EQB/LA0023/2013, UID/BIM/04773/2013]; European Regional Development Fund through COMPETE; INIA; EU [RTA2013-00023-C02-01

    Cover to Volume 3

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    The fibroblast mitogen platelet-derived growth factor -BB (PDGF-BB) induces a transient expression of the orphan nuclear receptor NR4A1 (also named Nur77, TR3 or NGFIB). The aim of the present study was to investigate the pathways through which NR4A1 is induced by PDGF-BB and its functional role. We demonstrate that in PDGF-BB stimulated NIH3T3 cells, the MEK1/2 inhibitor CI-1040 strongly represses NR4A1 expression, whereas Erk5 downregulation delays the expression, but does not block it. Moreover, we report that treatment with the NF-κB inhibitor BAY11-7082 suppresses NR4A1 mRNA and protein expression. The majority of NR4A1 in NIH3T3 was found to be localized in the cytoplasm and only a fraction was translocated to the nucleus after continued PDGF-BB treatment. Silencing NR4A1 slightly increased the proliferation rate of NIH3T3 cells; however, it did not affect the chemotactic or survival abilities conferred by PDGF-BB. Moreover, overexpression of NR4A1 promoted anchorage-independent growth of NIH3T3 cells and the glioblastoma cell lines U-105MG and U-251MG. Thus, whereas NR4A1, induced by PDGF-BB, suppresses cell growth on a solid surface, it increases anchorage-independent growth

    Phylogeography of Japanese encephalitis virus:genotype is associated with climate

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    The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate

    DNA replication stress mediates APOBEC3 family mutagenesis in breast cancer

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    BACKGROUND: The APOBEC3 family of cytidine deaminases mutate the cancer genome in a range of cancer types. Although many studies have documented the downstream effects of APOBEC3 activity through next-generation sequencing, less is known about their upstream regulation. In this study, we sought to identify a molecular basis for APOBEC3 expression and activation. RESULTS: HER2 amplification and PTEN loss promote DNA replication stress and APOBEC3B activity in vitro and correlate with APOBEC3 mutagenesis in vivo. HER2-enriched breast carcinomas display evidence of elevated levels of replication stress-associated DNA damage in vivo. Chemical and cytotoxic induction of replication stress, through aphidicolin, gemcitabine, camptothecin or hydroxyurea exposure, activates transcription of APOBEC3B via an ATR/Chk1-dependent pathway in vitro. APOBEC3B activation can be attenuated through repression of oncogenic signalling, small molecule inhibition of receptor tyrosine kinase signalling and alleviation of replication stress through nucleoside supplementation. CONCLUSION: These data link oncogene, loss of tumour suppressor gene and drug-induced replication stress with APOBEC3B activity, providing new insights into how cytidine deaminase-induced mutagenesis might be activated in tumourigenesis and limited therapeutically

    Do residents’ perceptions of being well-placed and objective presence of local amenities match? A case study in West Central Scotland, UK

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    Background:<p></p> Recently there has been growing interest in how neighbourhood features, such as the provision of local facilities and amenities, influence residents’ health and well-being. Prior research has measured amenity provision through subjective measures (surveying residents’ perceptions) or objective (GIS mapping of distance) methods. The latter may provide a more accurate measure of physical access, but residents may not use local amenities if they do not perceive them as ‘local’. We believe both subjective and objective measures should be explored, and use West Central Scotland data to investigate correspondence between residents’ subjective assessments of how well-placed they are for everyday amenities (food stores, primary and secondary schools, libraries, pharmacies, public recreation), and objective GIS-modelled measures, and examine correspondence by various sub-groups.<p></p> Methods:<p></p> ArcMap was used to map the postal locations of ‘Transport, Health and Well-being 2010 Study’ respondents (n = 1760), and the six amenities, and the presence/absence of each of them within various straight-line and network buffers around respondents’ homes was recorded. SPSS was used to investigate whether objective presence of an amenity within a specified buffer was perceived by a respondent as being well-placed for that amenity. Kappa statistics were used to test agreement between measures for all respondents, and by sex, age, social class, area deprivation, car ownership, dog ownership, walking in the local area, and years lived in current home.<p></p> Results:<p></p> In general, there was poor agreement (Kappa <0.20) between perceptions of being well-placed for each facility and objective presence, within 800 m and 1000 m straight-line and network buffers, with the exception of pharmacies (at 1000 m straight-line) (Kappa: 0.21). Results varied between respondent sub-groups, with some showing better agreement than others. Amongst sub-groups, at 800 m straight-line buffers, the highest correspondence between subjective and objective measures was for pharmacies and primary schools, and at 1000 m, for pharmacies, primary schools and libraries. For road network buffers under 1000 m, agreement was generally poor.<p></p> Conclusion:<p></p> Respondents did not necessarily regard themselves as well-placed for specific amenities when these amenities were present within specified boundaries around their homes, with some exceptions; the picture is not clear-cut with varying findings between different amenities, buffers, and sub-groups
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