1,641 research outputs found

    The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes.

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    Evenly spaced nucleosomes directly correlate with condensed chromatin and gene silencing. The ATP-dependent chromatin assembly factor (ACF) forms such structures in vitro and is required for silencing in vivo. ACF generates and maintains nucleosome spacing by constantly moving a nucleosome towards the longer flanking DNA faster than the shorter flanking DNA. How the enzyme rapidly moves back and forth between both sides of a nucleosome to accomplish bidirectional movement is unknown. Here we show that nucleosome movement depends cooperatively on two ACF molecules, indicating that ACF functions as a dimer of ATPases. Further, the nucleotide state determines whether the dimer closely engages one or both sides of the nucleosome. Three-dimensional reconstruction by single-particle electron microscopy of the ATPase-nucleosome complex in an activated ATP state reveals a dimer architecture in which the two ATPases face each other. Our results indicate a model in which the two ATPases work in a coordinated manner, taking turns to engage either side of a nucleosome, thereby allowing processive bidirectional movement. This novel dimeric motor mechanism differs from that of dimeric motors such as kinesin and dimeric helicases that processively translocate unidirectionally and reflects the unique challenges faced by motors that move nucleosomes

    Are there functional consequences of a reduction in selenium intake in UK subjects?

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    Dietary Se levels in the UK have fallen over the last 20 years and recent surveys indicate that average Se intakes are 30-40 microg/d, which is well below the current UK reference nutrient intake for adult men (75 microg/d) or women (60 microg/d). Functional consequences of this decline have not been recognised, although epidemiological data suggest it may contribute to increased risk of infections and incidence of some cancers. Previous data have indicated that biochemical changes in Se-dependent proteins occur in otherwise healthy UK subjects given small Se supplements. The current studies have focused on the effect of small Se supplements on the immune response since there is evidence of specific interactions between Se intake and viral replication, and since the potential anti-cancer effects of Se may be mediated by non-antioxidant effects of Se such as changes in immune function. Data indicate that subjects given small Se supplements (50 or 100 microg Se/d) have changes in the activity of Se-dependent enzymes and evidence of improved immune function and clearance of an administered live attenuated virus in the form of poliovirus vaccine. Responses of individual subjects to Se supplements are variable, and current work is evaluating potential explanations for this variability, including genetic variability and pre-existing Se status

    Single-charge detection by an atomic precision tunnel junction

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    We demonstrate sensitive detection of single charges using a planar tunnel junction 8.5 nm wide and 17.2 nm long defined by an atomically precise phosphorus doping profile in silicon. The conductance of the junction responds to a nearby gate potential and also to changes in the charge state of a quantum dot patterned 52 nm away. The response of this detector is monotonic across the entire working voltage range of the device, which will make it particularly useful for studying systems of multiple quantum dots. The charge sensitivity is maximized when the junction is most conductive, suggesting that more sensitive detection can be achieved by shortening the length of the junction to increase its conductance

    Aeroelasticity of a Generic Hypersonic Vehicle

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76282/1/AIAA-2002-1209-307.pd

    The Bridgwater Infant Welfare Centre, 1922-1939: from an authoritarian concern with 'welfare mothers' to a more inclusive community health project?

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    The infant welfare movement in Britain has received considerable scholarly attention but continues to generate controversy and debate. Many of the services began with nineteenth-century voluntary initiative but were later developed by local authorities. Critics have drawn attention to the limitations of such provision; arguing that it was predicated on unattractive assumptions about class and gender roles. Under this interpretation working-class mothers were viewed with suspicion and targeted for advice aimed at inculcating middle-class standards of childcare and housekeeping. This paper accepts that there was an authoritarian character to much of the early welfare work but suggests that over time this gave way to more inclusive approaches that sought to provide clients with the services that met their real rather than assumed needs. This paper reviews the recent historiography, develops an overview of national trends, and then takes a detailed look at the Bridgwater Infant Welfare Centre. The case study benefi ts from unusually comprehensive records and, by drawing on evidence from a small Somerset town, adds to our understanding of infant welfare work that has previously been developed from research on major urban centres.Wellcome Trust Fellowshi

    Developing Preservice Elementary Teachers' Pedagogical Design Capacity for Reform‐Based Curriculum Design

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    Teachers use curriculum materials as a guide in their planning, critiquing and adapting them to address reform‐based goals and practices and specific contextual needs. To become well‐started beginners in planning lessons, novice teachers need opportunities to develop their pedagogical design capacity—that is, their ability to use personal and curricular resources in designing instruction for students. This study investigated the use of reform‐based criteria in supporting 24 preservice teachers enrolled in an elementary science methods course. In learning about and applying criteria, the preservice teachers developed aspects of their pedagogical design capacity by expanding their analysis ideas and refining their knowledge and beliefs about curriculum design. However, many struggled with analyzing lesson plans in a reform‐oriented way during student teaching. This occurred, in part, because the preservice teachers navigated different settings that conveyed conflicting ideas about the reasons why teachers make modifications. The methods course emphasized the importance of modifying materials to promote reform‐based science teaching, but few preservice teachers observed their mentor teachers make adaptations for this reason. These findings have important implications for theoretical models on curriculum materials use and the design of science teacher education.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91354/1/j.1467-873X.2012.00599.x.pd

    Faster decline of pitch memory over time in congenital amusia

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    Congenital amusia (amusia, hereafter) is a developmental disorder that impacts negatively on the perception of music. Psychophysical testing suggests that individuals with amusia have above average thresholds for detection of pitch change and pitch direction discrimination; however, a low-level auditory perceptual problem cannot completely explain the disorder, since discrimination of melodies is also impaired when the constituent intervals are suprathreshold for perception. The aim of the present study was to test pitch memory as a function of (a) time and (b) tonal interference, in order to determine whether pitch traces are inherently weaker in amusic individuals. Memory for the pitch of single tones was compared using two versions of a paradigm developed by Deutsch (1970a). In both tasks, participants compared the pitch of a standard (S) versus a comparison (C) tone. In the time task, the S and C tones were presented, separated in time by 0, 1, 5, 10, and 15 s (blocked presentation). In the interference task, the S and C tones were presented with a fixed time interval (5 s) but with a variable number of irrelevant tones in between: 0, 2, 4, 6, and 8 tones (blocked presentation). In the time task, control performance remained high for all time in tervals, but amusics showed a performance decrement over time. In the interference task, controls and amusics showed a similar performance decrement with increasing number of irrelevant tones. Overall, the results suggest that the pitch representations of amusic individuals are less stable and more prone to decay than those of matched non-amusic individuals

    Aeroelastic and Aerothermoelastic Vehicle Behavior in Hypersonic Flow

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76797/1/AIAA-2005-3305-890.pd
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