Cooperative amyloid fibre binding and disassembly by the Hsp70 disaggregase

Although amyloid fibres are highly stable protein aggregates, a specific combination of human Hsp70 system chaperones can disassemble them, including fibres formed of α-synuclein, huntingtin, or Tau. Disaggregation requires the ATPase activity of the constitutively expressed Hsp70 family member, Hsc70, together with the J domain protein DNAJB1 and the nucleotide exchange factor Apg2. Clustering of Hsc70 on the fibrils appears to be necessary for disassembly. Here we use atomic force microscopy to show that segments of in vitro assembled α-synuclein fibrils are first coated with chaperones and then undergo bursts of rapid, unidirectional disassembly. Cryo-electron tomography and total internal reflection fluorescence microscopy reveal fibrils with regions of densely bound chaperones, preferentially at one end of the fibre. Sub-stoichiometric amounts of Apg2 relative to Hsc70 dramatically increase recruitment of Hsc70 to the fibres, creating localised active zones that then undergo rapid disassembly at a rate of ~ 4 subunits per second. The observed unidirectional bursts of Hsc70 loading and unravelling may be explained by differences between the two ends of the polar fibre structure

Observations and Theoretical Implications of the Large Separation Lensed Quasar SDSS J1004+4112

We study the recently discovered gravitational lens SDSS J1004+4112, the first quasar lensed by a cluster of galaxies. It consists of four images with a maximum separation of 14.62''. The system has been confirmed as a lensed quasar at z=1.734 on the basis of deep imaging and spectroscopic follow-up observations. We present color-magnitude relations for galaxies near the lens plus spectroscopy of three central cluster members, which unambiguously confirm that a cluster at z=0.68 is responsible for the large image separation. We find a wide range of lens models consistent with the data, but they suggest four general conclusions: (1) the brightest cluster galaxy and the center of the cluster potential well appear to be offset by several kpc; (2) the cluster mass distribution must be elongated in the North--South direction, which is consistent with the observed distribution of cluster galaxies; (3) the inference of a large tidal shear (~0.2) suggests significant substructure in the cluster; and (4) enormous uncertainty in the predicted time delays between the images means that measuring the delays would greatly improve constraints on the models. We also compute the probability of such large separation lensing in the SDSS quasar sample, on the basis of the CDM model. The lack of large separation lenses in previous surveys and the discovery of one in SDSS together imply a mass fluctuation normalization \sigma_8=1.0^{+0.4}_{-0.2} (95% CL), if cluster dark matter halos have an inner slope -1.5. Shallower profiles would require higher values of \sigma_8. Although the statistical conclusion might be somewhat dependent on the degree of the complexity of the lens potential, the discovery is consistent with the predictions of the abundance of cluster-scale halos in the CDM scenario. (Abridged)Comment: 21 pages, 24 figures, 5 tables, accepted for publication in Ap

Weak Lensing with SDSS Commissioning Data: The Galaxy-Mass Correlation Function To 1/h Mpc

(abridged) We present measurements of galaxy-galaxy lensing from early commissioning imaging data from the Sloan Digital Sky Survey (SDSS). We measure a mean tangential shear around a stacked sample of foreground galaxies in three bandpasses out to angular radii of 600'', detecting the shear signal at very high statistical significance. The shear profile is well described by a power-law. A variety of rigorous tests demonstrate the reality of the gravitational lensing signal and confirm the uncertainty estimates. We interpret our results by modeling the mass distributions of the foreground galaxies as approximately isothermal spheres characterized by a velocity dispersion and a truncation radius. The velocity dispersion is constrained to be 150-190 km/s at 95% confidence (145-195 km/s including systematic uncertainties), consistent with previous determinations but with smaller error bars. Our detection of shear at large angular radii sets a 95% confidence lower limit $s>140^{\prime\prime}$, corresponding to a physical radius of $260h^{-1}$ kpc, implying that galaxy halos extend to very large radii. However, it is likely that this is being biased high by diffuse matter in the halos of groups and clusters. We also present a preliminary determination of the galaxy-mass correlation function finding a correlation length similar to the galaxy autocorrelation function and consistency with a low matter density universe with modest bias. The full SDSS will cover an area 44 times larger and provide spectroscopic redshifts for the foreground galaxies, making it possible to greatly improve the precision of these constraints, measure additional parameters such as halo shape, and measure the properties of dark matter halos separately for many different classes of galaxies.Comment: 28 pages, 11 figures, submitted to A

Weak Lensing Measurements of 42 SDSS/RASS Galaxy Clusters

We present a lensing study of 42 galaxy clusters imaged in Sloan Digital Sky Survey (SDSS) commissioning data. Cluster candidates are selected optically from SDSS imaging data and confirmed for this study by matching to X-ray sources found independently in the ROSAT all sky survey (RASS). Five color SDSS photometry is used to make accurate photometric redshift estimates that are used to rescale and combine the lensing measurements. The mean shear from these clusters is detected to 2 h-1 Mpc at the 7-sigma level, corresponding to a mass within that radius of 4.2 +/- 0.6 x 10^14 h-1 M_sun. The shear profile is well fit by a power law with index -0.9 +/- 0.3, consistent with that of an isothermal density profile. This paper demonstrates our ability to measure ensemble cluster masses from SDSS imaging data.Comment: 14 pages, 7 figures, Accepted for publication in Ap

The Sloan Digital Sky Survey Quasar Lens Search. III. Constraints on Dark Energy from the Third Data Release Quasar Lens Catalog

We present cosmological results from the statistics of lensed quasars in the Sloan Digital Sky Survey (SDSS) Quasar Lens Search. By taking proper account of the selection function, we compute the expected number of quasars lensed by early-type galaxies and their image separation distribution assuming a flat universe, which is then compared with 7 lenses found in the SDSS Data Release 3 to derive constraints on dark energy under strictly controlled criteria. For a cosmological constant model (w=-1) we obtain \Omega_\Lambda=0.74^{+0.11}_{-0.15}(stat.)^{+0.13}_{-0.06}(syst.). Allowing w to be a free parameter we find \Omega_M=0.26^{+0.07}_{-0.06}(stat.)^{+0.03}_{-0.05}(syst.) and w=-1.1\pm0.6(stat.)^{+0.3}_{-0.5}(syst.) when combined with the constraint from the measurement of baryon acoustic oscillations in the SDSS luminous red galaxy sample. Our results are in good agreement with earlier lensing constraints obtained using radio lenses, and provide additional confirmation of the presence of dark energy consistent with a cosmological constant, derived independently of type Ia supernovae.Comment: 9 pages, 3 figures, 2 tables, accepted for publication in A

Comparative Analysis of Measures of Viral Reservoirs in HIV-1 Eradication Studies

HIV-1 reservoirs preclude virus eradication in patients receiving highly active antiretroviral therapy (HAART). The best characterized reservoir is a small, difficult-to-quantify pool of resting memory CD4+ T cells carrying latent but replication-competent viral genomes. Because strategies targeting this latent reservoir are now being tested in clinical trials, well-validated high-throughput assays that quantify this reservoir are urgently needed. Here we compare eleven different approaches for quantitating persistent HIV-1 in 30 patients on HAART, using the original viral outgrowth assay for resting CD4+ T cells carrying inducible, replication-competent viral genomes as a standard for comparison. PCR-based assays for cells containing HIV-1 DNA gave infected cell frequencies at least 2 logs higher than the viral outgrowth assay, even in subjects who started HAART during acute/early infection. This difference may reflect defective viral genomes. The ratio of infected cell frequencies determined by viral outgrowth and PCR-based assays varied dramatically between patients. Although strong correlations with the viral outgrowth assay could not be formally excluded for most assays, correlations achieved statistical significance only for integrated HIV-1 DNA in peripheral blood mononuclear cells and HIV-1 RNA/DNA ratio in rectal CD4+ T cells. Residual viremia was below the limit of detection in many subjects and did not correlate with the viral outgrowth assays. The dramatic differences in infected cell frequencies and the lack of a precise correlation between culture and PCR-based assays raise the possibility that the successful clearance of latently infected cells may be masked by a larger and variable pool of cells with defective proviruses. These defective proviruses are detected by PCR but may not be affected by reactivation strategies and may not require eradication to accomplish an effective cure. A molecular understanding of the discrepancy between infected cell frequencies measured by viral outgrowth versus PCR assays is an urgent priority in HIV-1 cure research

A deep learning approach to photo–identification demonstrates high performance on two dozen cetacean species

We thank the countless individuals who collected and/or processed the nearly 85,000 images used in this study and those who assisted, particularly those who sorted these images from the millions that did not end up in the catalogues. Additionally, we thank the other Kaggle competitors who helped develop the ideas, models and data used here, particularly those who released their datasets to the public. The graduate assistantship for Philip T. Patton was funded by the NOAA Fisheries QUEST Fellowship. This paper represents HIMB and SOEST contribution numbers 1932 and 11679, respectively. The technical support and advanced computing resources from University of Hawaii Information Technology Services—Cyberinfrastructure, funded in part by the National Science Foundation CC* awards # 2201428 and # 2232862 are gratefully acknowledged. Every photo–identification image was collected under permits according to relevant national guidelines, regulation and legislation.Peer reviewedPublisher PD

The Fifth Data Release of the Sloan Digital Sky Survey

This paper describes the Fifth Data Release (DR5) of the Sloan Digital Sky Survey (SDSS). DR5 includes all survey quality data taken through June 2005 and represents the completion of the SDSS-I project (whose successor, SDSS-II will continue through mid-2008). It includes five-band photometric data for 217 million objects selected over 8000 square degrees, and 1,048,960 spectra of galaxies, quasars, and stars selected from 5713 square degrees of that imaging data. These numbers represent a roughly 20% increment over those of the Fourth Data Release; all the data from previous data releases are included in the present release. In addition to "standard" SDSS observations, DR5 includes repeat scans of the southern equatorial stripe, imaging scans across M31 and the core of the Perseus cluster of galaxies, and the first spectroscopic data from SEGUE, a survey to explore the kinematics and chemical evolution of the Galaxy. The catalog database incorporates several new features, including photometric redshifts of galaxies, tables of matched objects in overlap regions of the imaging survey, and tools that allow precise computations of survey geometry for statistical investigations.Comment: ApJ Supp, in press, October 2007. This paper describes DR5. The SDSS Sixth Data Release (DR6) is now public, available from http://www.sdss.or

Monitoring the EU protected Geomalacus maculosus (Kerry Slug): what are the factors affecting catch returns in open and forested habitats?

Geomalacus maculosus is a slug species protected under EU law with a distribution limited to the west of Ireland and north-west Iberia. The species, originally thought to be limited within Ireland to deciduous woodland and peatland, has been found in a number of commercial conifer plantations since 2010. While forest managers are now required to incorporate the protection of the species where it is present, no clear species monitoring protocols are currently available. This study examines the efficacy of De Sangosse refuge traps across three habitats frequently associated with commercial forest plantations in Ireland and compares them with hand searching, a commonly used method for slug monitoring. Catch data during different seasons and under different weather conditions are also presented. Results indicate that autumn is the optimal time for sampling G. maculosus but avoiding extremes of hot or cold weather. While refuge traps placed at 1.5 m on trees in mature conifer plantations and directly on exposed rock in blanket peatlands result in significantly greater catches, hand searching is the most successful approach for clear-fell areas. Hand searches in clear-fell preceded by rain are likely to result in greater numbers caught. The results of this study form, for the first time, the basis for G. maculosus monitoring guidelines for forestry managers. © 2016, The Ecological Society of Japa