1,714 research outputs found

    SWI/SNF-like chromatin remodeling factor Fun30 supports point centromere function in S. cerevisiae

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    Budding yeast centromeres are sequence-defined point centromeres and are, unlike in many other organisms, not embedded in heterochromatin. Here we show that Fun30, a poorly understood SWI/SNF-like chromatin remodeling factor conserved in humans, promotes point centromere function through the formation of correct chromatin architecture at centromeres. Our determination of the genome-wide binding and nucleosome positioning properties of Fun30 shows that this enzyme is consistently enriched over centromeres and that a majority of CENs show Fun30-dependent changes in flanking nucleosome position and/or CEN core micrococcal nuclease accessibility. Fun30 deletion leads to defects in histone variant Htz1 occupancy genome-wide, including at and around most centromeres. FUN30 genetically interacts with CSE4, coding for the centromere-specific variant of histone H3, and counteracts the detrimental effect of transcription through centromeres on chromosome segregation and suppresses transcriptional noise over centromere CEN3. Previous work has shown a requirement for fission yeast and mammalian homologs of Fun30 in heterochromatin assembly. As centromeres in budding yeast are not embedded in heterochromatin, our findings indicate a direct role of Fun30 in centromere chromatin by promoting correct chromatin architecture

    Genome-wide chromatin mapping with size resolution reveals a dynamic sub-nucleosomal landscape in Arabidopsis

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    All eukaryotic genomes are packaged as chromatin, with DNA interlaced with both regularly patterned nucleosomes and sub-nucleosomal-sized protein structures such as mobile and labile transcription factors (TF) and initiation complexes, together forming a dynamic chromatin landscape. Whilst details of nucleosome position in Arabidopsis have been previously analysed, there is less understanding of their relationship to more dynamic sub-nucleosomal particles (subNSPs) defined as protected regions shorter than the ~150bp typical of nucleosomes. The genome-wide profile of these subNSPs has not been previously analysed in plants and this study investigates the relationship of dynamic bound particles with transcriptional control. Here we combine differential micrococcal nuclease (MNase) digestion and a modified paired-end sequencing protocol to reveal the chromatin structure landscape of Arabidopsis cells across a wide particle size range. Linking this data to RNAseq expression analysis provides detailed insight into the relationship of identified DNA-bound particles with transcriptional activity. The use of differential digestion reveals sensitive positions, including a labile -1 nucleosome positioned upstream of the transcription start site (TSS) of active genes. We investigated the response of the chromatin landscape to changes in environmental conditions using light and dark growth, given the large transcriptional changes resulting from this simple alteration. The resulting shifts in the suites of expressed and repressed genes show little correspondence to changes in nucleosome positioning, but led to significant alterations in the profile of subNSPs upstream of TSS both globally and locally. We examined previously mapped positions for the TFs PIF3, PIF4 and CCA1, which regulate light responses, and found that changes in subNSPs co-localized with these binding sites. This small particle structure is detected only under low levels of MNase digestion and is lost on more complete digestion of chromatin to nucleosomes. We conclude that wide-spectrum analysis of the Arabidopsis genome by differential MNase digestion allows detection of sensitive features hereto obscured, and the comparisons between genome-wide subNSP profiles reveals dynamic changes in their distribution, particularly at distinct genomic locations (i.e. 5’UTRs). The method here employed allows insight into the complex influence of genetic and extrinsic factors in modifying the sub-nucleosomal landscape in association with transcriptional changes

    The Atacama Cosmology Telescope: the stellar content of galaxy clusters selected using the Sunyaev-Zel'dovich effect

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    We present a first measurement of the stellar mass component of galaxy clusters selected via the Sunyaev-Zel'dovich (SZ) effect, using 3.6 um and 4.5 um photometry from the Spitzer Space Telescope. Our sample consists of 14 clusters detected by the Atacama Cosmology Telescope (ACT), which span the redshift range 0.27 < z < 1.07 (median z = 0.50), and have dynamical mass measurements, accurate to about 30 per cent, with median M500 = 6.9 x 10^{14} MSun. We measure the 3.6 um and 4.5 um galaxy luminosity functions, finding the characteristic magnitude (m*) and faint-end slope (alpha) to be similar to those for IR-selected cluster samples. We perform the first measurements of the scaling of SZ-observables (Y500 and y0) with both brightest cluster galaxy (BCG) stellar mass and total cluster stellar mass (M500star). We find a significant correlation between BCG stellar mass and Y500 (E(z)^{-2/3} DA^2 Y500 ~ M*^{1.2 +/- 0.6}), although we are not able to obtain a strong constraint on the slope of the relation due to the small sample size. Additionally, we obtain E(z)^{-2/3} DA^2 Y500 ~ M500star^{1.0 +/- 0.6} for the scaling with total stellar mass. The mass fraction in stars spans the range 0.006-0.034, with the second ranked cluster in terms of dynamical mass (ACT-CL J0237-4939) having an unusually low total stellar mass and the lowest stellar mass fraction. For the five clusters with gas mass measurements available in the literature, we see no evidence for a shortfall of baryons relative to the cosmic mean value.Comment: Accepted for publication in MNRAS; 12 pages, 10 figure

    Effect of Tilted Magnetic Field on the Anomalous H=0 Conducting Phase in High-Mobility Si MOSFETs

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    The suppression by a magnetic field of the anomalous H=0 conducting phase in high-mobility silicon MOSFETs is independent of the angle between the field and the plane of the 2D electron system. In the presence of a parallel field large enough to fully quench the anomalous conducting phase, the behavior is similar to that of disordered GaAs/AlGaAs heterostructures: the system is insulating in zero (perpendicular) field and exhibits reentrant insulator-quantum Hall effect-insulator transitions as a function of perpendicular field. The results demonstrate that the suppression of the low-T phase is related only to the electrons' spin.Comment: 4 pages, including 3 figures. We corrected several typos in the figures and caption

    Step activity and stride-to-stride fluctuations are negatively correlated in individuals with transtibial amputation

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    Background Variability occurs naturally from stride to stride in healthy gait. It has been shown that individuals with lower limb loss have significantly increased stride-to-stride fluctuations during walking. This is considered indicative of movement disorganization and is associated with less healthy movement. Given that lower limb prosthesis users perform on average less physical activity than able bodied individuals, the purpose of this study was to determine whether increased fluctuations also correspond to a reduced level of activity in daily life. Methods Twenty-two transtibial amputees wore an activity monitor (Actigraph, Pensacola, FL, USA) for 3 weeks. Lower limb kinematics during treadmill walking were measured using a 12-camera motion capture system. The largest Lyapunov exponent (λ) was calculated bilaterally at the ankle, knee and hip to quantify the stride-to-stride fluctuations of the lower limb joints. Pearson correlations were used to identify the relationships between the average daily step count over the 3 week collection period and λ. Findings Significant, moderate negative correlations between daily step count and λ were found at the intact ankle (r = 0.57, P = 0.005), and the knee on the affected side (r = 0.44, P = 0.038). No such correlation was found at any other lower limb joint. Interpretation The negative correlation evident at these two joints demonstrates that increased stride-to-stride fluctuations are related to decreased activity levels, however it remains unclear whether these changes in the stride-to-stride fluctuations promote decreased activity or whether less active individuals do not gain sufficient motor learning experience to achieve a skilled movement

    Human Movement Variability and Aging

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    An optimal level of variability enables us to interact adaptively and safely to a continuously changing environment, where often our movements must be adjusted in a matter of milliseconds. A large body of research exists that demonstrates natural variability in healthy gait (along with variability in other, healthy biological signals such as heart rate) and a loss of this variability in aging and injury, as well as in a variety of neurodegenerative and physiological disorders. We submit that this field of research is now in pressing need of an innovative “next step” that goes beyond the many descriptive studies that characterize levels of variability in various patient populations. We need to devise novel therapies that will harness the existing knowledge on biological variability and create new possibilities for those in the grip of disease. We also propose that the nature of the specific physiological limitation present in the neuromuscular apparatus may be less important in the physiological complexity framework than the control mechanisms adopted by the older individual in the coordination of the available degrees of freedom. The theoretical underpinnings of this framework suggest that interventions designed to restore healthy system dynamics may optimize functional improvements in older adults. We submit that interventions based on the restoration of optimal variability and movement complexity could potentially be applied across a range of diseases or dysfunctions as it addresses the adaptability and coordination of available degrees of freedom, regardless of the internal constraints of the individual

    The Atacama Cosmology Telescope: Sunyaev-Zel'dovich Selected Galaxy Clusters at 148 GHz from Three Seasons of Data

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    [Abridged] We present a catalog of 68 galaxy clusters, of which 19 are new discoveries, detected via the Sunyaev-Zel'dovich effect (SZ) at 148 GHz in the Atacama Cosmology Telescope (ACT) survey of 504 square degrees on the celestial equator. A subsample of 48 clusters within the 270 square degree region overlapping SDSS Stripe 82 is estimated to be 90% complete for M_500c > 4.5e14 Msun and 0.15 < z < 0.8. While matched filters are used to detect the clusters, the sample is studied further through a "Profile Based Amplitude Analysis" using a single filter at a fixed \theta_500 = 5.9' angular scale. This new approach takes advantage of the "Universal Pressure Profile" (UPP) to fix the relationship between the cluster characteristic size (R_500) and the integrated Compton parameter (Y_500). The UPP scalings are found to be nearly identical to an adiabatic model, while a model incorporating non-thermal pressure better matches dynamical mass measurements and masses from the South Pole Telescope. A high signal to noise ratio subsample of 15 ACT clusters is used to obtain cosmological constraints. We first confirm that constraints from SZ data are limited by uncertainty in the scaling relation parameters rather than sample size or measurement uncertainty. We next add in seven clusters from the ACT Southern survey, including their dynamical mass measurements based on galaxy velocity dispersions. In combination with WMAP7 these data simultaneously constrain the scaling relation and cosmological parameters, yielding \sigma_8 = 0.829 \pm 0.024 and \Omega_m = 0.292 \pm 0.025. The results include marginalization over a 15% bias in dynamical mass relative to the true halo mass. In an extension to LCDM that incorporates non-zero neutrino mass density, we combine our data with WMAP7+BAO+Hubble constant measurements to constrain \Sigma m_\nu < 0.29 eV (95% C. L.).Comment: 32 pages, 21 figures To appear in J. Cosmology and Astroparticle Physic
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