1,511 research outputs found

    The effect of goalkeepers adopting Muller-Lyer postures

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    Poster 5 - Motor Control: Neural Correlates/Sensorimotor/Motor Practice and Observation: no. 57The posture that a goalkeeper assumes can influence perceptions of his or her size and the motor behavior of an opponent. Van der Kamp & Masters (2008) showed that postures that mimicked an amputated Muller-Lyer illusion in a wings-out/arms-up configuration resulted in larger estimates of goalkeeper height than a wings-in/arms-down configuration. Furthermore, when participants threw to score in a handball goal, the shots were placed further from the arms-up goalkeeper, presumably because he was thought capable of covering a greater area of the goal. We aimed to verify that throwing behaviour was related to (mis-)perceptions of goalkeeper height and, by association, goalkeeper reach. A 1.9 m animated representation of a goalkeeper was projected onto a blank screen. The goalkeeper was shown in an arms-up (45 degrees above horizontal), arms-out (horizontal), or arms-down (45 degrees below horizontal) posture. The 3 postures were each shown 10 times in a random order. For each presentation 34 participants made two estimates of the goalkeeper’s maximum static reach, which was defined as the position of middle finger of the goalkeeper in the arms-out posture. Estimates were made by aiming a laser pointer and throwing a ball. The horizontal displacements of the aiming and throwing estimates from the actual position of middle finger (75 cm from the midline of the body) were measured. For the horizontal displacement measure, there was no significant difference between aiming and throwing estimates (p > .05), but a significant effect of posture, F(2, 66) = 10.1, p <.01. Participants perceived the hand closer to the midline of the body in the arms-down posture (67.4 cm) than the arms-up posture (75.2 cm). The findings corroborate previous work in suggesting that the goalkeeper can influence perceptions of his maximum reach and the motor behaviour of an opponent by adopting illusory postures. Further investigations need to address whether the effects are also mediated by hand position or perceptions of arm length rather than body height.published_or_final_versionThe 2010 Conference of the North American Society for the Psychology of Sport and Physical Activity (NASPSPA 2010), Tucson, AZ., 10-12 June 2010. In Journal of Sport and Exercise Psychology, 2010, v. 32 suppl., p. S12

    Randomized phase I trial HIV-CORE 003: Depletion of serum amyloid P component and immunogenicity of DNA vaccination against HIV-1

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    BACKGROUND: The failure of DNA vaccination in humans, in contrast to its efficacy in some species, is unexplained. Observational and interventional experimental evidence suggests that DNA immunogenicity may be prevented by binding of human serum amyloid P component (SAP). SAP is the single normal DNA binding protein in human plasma. The drug (R)-1-[6-[(R)-2-carboxypyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, miridesap), developed for treatment of systemic amyloidosis and Alzheimer’s disease, depletes circulating SAP by 95–99%. The proof-of-concept HIV-CORE 003 clinical trial tested whether SAP depletion by CPHPC would enhance the immune response in human volunteers to DNA vaccination delivering the HIVconsv immunogen derived from conserved sub-protein regions of HIV-1. METHODS: Human volunteers received 3 intramuscular immunizations with an experimental DNA vaccine (DDD) expressing HIV-1-derived immunogen HIVconsv, with or without prior depletion of SAP by CPHPC. All subjects were subsequently boosted by simian (chimpanzee) adenovirus (C)- and poxvirus MVA (M)-vectored vaccines delivering the same immunogen. After administration of each vaccine modality, the peak total magnitudes, kinetics, functionality and memory subsets of the T-cell responses to HIVconsv were thoroughly characterized. RESULTS: No differences were observed between the CPHPC treated and control groups in any of the multiple quantitative and qualitative parameters of the T-cell responses to HIVconsv, except that after SAP depletion, there was a statistically significantly greater breadth of T-cell specificities, that is the number of recognized epitopes, following the DDDC vaccination. CONCLUSIONS: The protocol used here for SAP depletion by CPHPC prior to DNA vaccination produced only a very modest suggestion of enhanced immunogenicity. Further studies will be required to determine whether SAP depletion might have a practical value in DNA vaccination for other plasmid backbones and/or immunogens. TRIAL REGISTRATION: Clinicaltrials.gov NCT02425241

    Sprouty2 mediated tuning of signalling is essential for somite myogenesis

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    Background: Negative regulators of signal transduction cascades play critical roles in controlling different aspects of normal embryonic development. Sprouty2 (Spry2) negatively regulates receptor tyrosine kinases (RTK) and FGF signalling and is important in differentiation, cell migration and proliferation. In vertebrate embryos, Spry2 is expressed in paraxial mesoderm and in forming somites. Expression is maintained in the myotome until late stages of somite differentiation. However, its role and mode of action during somite myogenesis is still unclear. Results: Here, we analysed chick Spry2 expression and showed that it overlaps with that of myogenic regulatory factors MyoD and Mgn. Targeted mis-expression of Spry2 led to inhibition of myogenesis, whilst its C-terminal domain led to an increased number of myogenic cells by stimulating cell proliferation. Conclusions: Spry2 is expressed in somite myotomes and its expression overlaps with myogenic regulatory factors. Overexpression and dominant-negative interference showed that Spry2 plays a crucial role in regulating chick myogenesis by fine tuning of FGF signaling through a negative feedback loop. We also propose that mir-23, mir-27 and mir-128 could be part of the negative feedback loop mechanism. Our analysis is the first to shed some light on in vivo Spry2 function during chick somite myogenesis

    Experimental and theoretical investigation of ligand effects on the synthesis of ZnO nanoparticles

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    ZnO nanoparticles with highly controllable particle sizes(less than 10 nm) were synthesized using organic capping ligands in Zn(Ac)2 ethanolic solution. The molecular structure of the ligands was found to have significant influence on the particle size. The multi-functional molecule tris(hydroxymethyl)-aminomethane (THMA) favoured smaller particle distributions compared with ligands possessing long hydrocarbon chains that are more frequently employed. The adsorption of capping ligands on ZnnOn crystal nuclei (where n = 4 or 18 molecular clusters of(0001) ZnO surfaces) was modelled by ab initio methods at the density functional theory (DFT) level. For the molecules examined, chemisorption proceeded via the formation of Zn...O, Zn...N, or Zn...S chemical bonds between the ligands and active Zn2+ sites on ZnO surfaces. The DFT results indicated that THMA binds more strongly to the ZnO surface than other ligands, suggesting that this molecule is very effective at stabilizing ZnO nanoparticle surfaces. This study, therefore, provides new insight into the correlation between the molecular structure of capping ligands and the morphology of metal oxide nanostructures formed in their presence

    Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background

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    The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability

    Self-activated ultrahigh chemosensitivity of oxide thin film nanostructures for transparent sensors

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    One of the top design priorities for semiconductor chemical sensors is developing simple, low-cost, sensitive and reliable sensors to be built in handheld devices. However, the need to implement heating elements in sensor devices, and the resulting high power consumption, remains a major obstacle for the realization of miniaturized and integrated chemoresistive thin film sensors based on metal oxides. Here we demonstrate structurally simple but extremely efficient all oxide chemoresistive sensors with similar to 90% transmittance at visible wavelengths. Highly effective self-activation in anisotropically self-assembled nanocolumnar tungsten oxide thin films on glass substrate with indium-tin oxide electrodes enables ultrahigh response to nitrogen dioxide and volatile organic compounds with detection limits down to parts per trillion levels and power consumption less than 0.2 microwatts. Beyond the sensing performance, high transparency at visible wavelengths creates opportunities for their use in transparent electronic circuitry and optoelectronic devices with avenues for further functional convergence.open181

    Use of Motor Abundance in Young and Older Adults during Dual-Task Treadmill Walking

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    Contains fulltext : 110120.pdf (publisher's version ) (Open Access)Motor abundance allows individuals to perform any task reliably while being variable in movement's particulars. The study investigated age-related differences in this feature when young adults (YA) and older adults (OA) performed challenging tasks, namely treadmill walking alone and while performing a cognitive task. A goal function for treadmill walking was first defined, i.e., maintain constant speed at each step, which led to a goal equivalent manifold (GEM) containing all combinations of step time and step length that equally satisfied the function. Given the GEM, amounts of goal-equivalent and non-goal-equivalent variability were afterwards determined and used to define an index providing information about the set of effective motor solutions relative to the GEM. The set was limited in OA compared to YA in treadmill walking alone, indicating that OA made less flexible use of motor abundance than YA. However, this differentiation between YA and OA disappeared when concurrently performing the cognitive task. It is proposed that OA might have benefited from cognitive compensation

    NF90 Binds the Dengue Virus RNA 3′ Terminus and is a Positive Regulator of Dengue Virus Replication

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    Background Viral RNA translation and replication are regulated by sequence and structural elements in the 5′ and 3′ untranslated regions (UTR) and by host cell and/or viral proteins that bind them. Dengue virus has a single-stranded RNA genome with positive polarity, a 5′ m7GpppG cap, and a conserved 3′-terminal stem loop (SL) that is linked to proposed functions in viral RNA transcription and translation. Mechanisms explaining the contributions of host proteins to viral RNA translation and replication are poorly defined, yet understanding host protein-viral RNA interactions may identify new targets for therapeutic intervention. This study was directed at identifying functionally significant host proteins that bind the conserved dengue virus RNA 3′ terminus. Methodology/Principal Findings Proteins eluted from a dengue 3′ SL RNA affinity column at increasing ionic strength included two with double-strand RNA binding motifs (NF90/DRBP76 and DEAH box polypeptide 9/RNA helicase A (RHA)), in addition to NF45, which forms a heterodimer with NF90. Although detectable NF90 and RHA proteins localized to the nucleus of uninfected cells, immunofluorescence revealed cytoplasmic NF90 in dengue virus-infected cells, leading us to hypothesize that NF90 has a functional role(s) in dengue infections. Cells depleted of NF90 were used to quantify viral RNA transcript levels and production of infectious dengue virus. NF90 depletion was accompanied by a 50%-70% decrease in dengue RNA levels and in production of infectious viral progeny. Conclusions/Significance The results indicate that NF90 interacts with the 3′ SL structure of the dengue RNA and is a positive regulator of dengue virus replication. NF90 depletion diminished the production of infectious dengue virus by more than 50%, which may have important significance for identifying therapeutic targets to limit a virus that threatens more than a billion people worldwide.Ruth L. Kirschstein National Research Service Award (NIH-NRSA GM64985)UNCF-Merck Postdoctoral FellowshipNational Institute of Allergy and Infectious Diseases (U.S.)Ellison Medical Foundatio

    Biosynthesis of copper carbonate nanoparticles by ureolytic fungi

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    In this research, the ureolytic fungi Neurospora crassa, Pestalotiopsis sp. and Myrothecium gramineum were investigated for the preparation of nanoscale copper carbonate and the role of fungal extracellular protein in such mineral formation. After incubation in urea-modified media, carbonate-laden fungal supernatants were used for the precipitation of copper carbonate, with experimental results agreeing closely with those obtained using geochemical modelling (Geochemist's Workbench). Compared with commercial and chemically synthesized copper carbonate, the minerals obtained using fungal supernatants were nanoscale and showed varying morphologies. It was found that extracellular protein played an important role in determining the size and morphology of the carbonate minerals precipitated, and after mixture with CuCl2 and resultant copper carbonate precipitation, more than 80% protein was removed from the N. crassa supernatant. Moreover, with addition of extracellular protein extracted from different fungal supernatants or standard bovine serum albumin, more than 96% of protein was removed by carbonate mineral precipitation. These results provide direct experimental evidence for the preparation of copper carbonate nanoparticles utilizing fungal ureolytic activity and show that fungal extracellular protein plays an important role in the formation and size of specific nano metal carbonates. Such a process provides opportunities for production of specific and/or novel metal carbonate nanoparticles of applied relevance, and as precursors of other useful biomineral products such as oxides.</p

    Targeting cancer metabolism: a therapeutic window opens

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    Genetic events in cancer activate signalling pathways that alter cell metabolism. Clinical evidence has linked cell metabolism with cancer outcomes. Together, these observations have raised interest in targeting metabolic enzymes for cancer therapy, but they have also raised concerns that these therapies would have unacceptable effects on normal cells. However, some of the first cancer therapies that were developed target the specific metabolic needs of cancer cells and remain effective agents in the clinic today. Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy.Burroughs Wellcome FundSmith Family FoundationStarr Cancer ConsortiumDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.
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