Passive immunotherapy against Aβ in aged APP-transgenic mice reverses cognitive deficits and depletes parenchymal amyloid deposits in spite of increased vascular amyloid and microhemorrhage

BACKGROUND: Anti-Aβ immunotherapy in transgenic mice reduces both diffuse and compact amyloid deposits, improves memory function and clears early-stage phospho-tau aggregates. As most Alzheimer disease cases occur well past midlife, the current study examined adoptive transfer of anti-Aβ antibodies to 19- and 23-month old APP-transgenic mice. METHODS: We investigated the effects of weekly anti-Aβ antibody treatment on radial-arm water-maze performance, parenchymal and vascular amyloid loads, and the presence of microhemorrhage in the brain. 19-month-old mice were treated for 1, 2 or 3 months while 23-month-old mice were treated for 5 months. Only the 23-month-old mice were subject to radial-arm water-maze testing. RESULTS: After 3 months of weekly injections, this passive immunization protocol completely reversed learning and memory deficits in these mice, a benefit that was undiminished after 5 months of treatment. Dramatic reductions of diffuse Aβ immunostaining and parenchymal Congophilic amyloid deposits were observed after five months, indicating that even well-established amyloid deposits are susceptible to immunotherapy. However, cerebral amyloid angiopathy increased substantially with immunotherapy, and some deposits were associated with microhemorrhage. Reanalysis of results collected from an earlier time-course study demonstrated that these increases in vascular deposits were dependent on the duration of immunotherapy. CONCLUSIONS: The cognitive benefits of passive immunotherapy persist in spite of the presence of vascular amyloid and small hemorrhages. These data suggest that clinical trials evaluating such treatments will require precautions to minimize potential adverse events associated with microhemorrhage

The Evolution of the Global Star Formation History as Measured from the Hubble Deep Field

The Hubble Deep Field (HDF) is the deepest set of multicolor optical photometric observations ever undertaken, and offers a valuable data set with which to study galaxy evolution. Combining the optical WFPC2 data with ground-based near-infrared photometry, we derive photometrically estimated redshifts for HDF galaxies with J<23.5. We demonstrate that incorporating the near-infrared data reduces the uncertainty in the estimated redshifts by approximately 40% and is required to remove systematic uncertainties within the redshift range 1<z<2. Utilizing these photometric redshifts, we determine the evolution of the comoving ultraviolet (2800 A) luminosity density (presumed to be proportional to the global star formation rate) from a redshift of z=0.5 to z=2. We find that the global star formation rate increases rapidly with redshift, rising by a factor of 12 from a redshift of zero to a peak at z~1.5. For redshifts beyond 1.5, it decreases monotonically. Our measures of the star formation rate are consistent with those found by Lilly et al. (1996) from the CFRS at z 2, and bridge the redshift gap between those two samples. The overall star formation or metal enrichment rate history is consistent with the predictions of Pei and Fall (1995) based on the evolving HI content of Lyman-alpha QSO absorption line systems.Comment: Latex format, 10 pages, 3 postscript figures. Accepted for publication in Ap J Letter

Early-type galaxies in the SDSS. II. Correlations between observables

A magnitude limited sample of nearly 9000 early-type galaxies, in the redshift range 0.01 < z < 0.3, was selected from the Sloan Digital Sky Survey using morphological and spectral criteria. The sample was used to study how early-type galaxy observables, including luminosity L, effective radius R_o, surface brightness I_o, color, and velocity dispersion sigma, are correlated with one another. Measurement biases are understood with mock catalogs which reproduce all of the observed scaling relations and their dependences on fitting technique. At any given redshift, the intrinsic distribution of luminosities, sizes and velocity dispersions in our sample are all approximately Gaussian. A maximum likelihood analysis shows that sigma ~ L^{0.25\pm 0.012}, R_o ~ L^{0.63\pm 0.025}, and R_o ~ I^{-0.75\pm 0.02} in the r* band. In addition, the mass-to-light ratio within the effective radius scales as M_o/L ~ L^{0.14\pm 0.02} or M_o/L ~ M_o^{0.22\pm 0.05}, and galaxies with larger effective masses have smaller effective densities: Delta_o ~ M_o^{-0.52\pm 0.03}. These relations are approximately the same in the g*, i* and z* bands. Relative to the population at the median redshift in the sample, galaxies at lower and higher redshifts have evolved only little, with more evolution in the bluer bands. The luminosity function is consistent with weak passive luminosity evolution and a formation time of about 9 Gyrs ago.Comment: 29 pages, 11 figures. Accepted by AJ (scheduled for April 2003). This paper is part II of a revised version of astro-ph/011034

SARS CoV subunit vaccine: Antibodymediated neutralisation and enhancement

1. A SARS vaccine was produced based on recombinant native full-length Spike-protein trimers (triSpike) and efficient establishment of a vaccination procedure in rodents. 2. Antibody-mediated enhancement of SARS-CoV infection with anti-SARS-CoV Spike immune-serum was observed in vitro. 3. Antibody-mediated infection of SARS-CoV triggers entry into human haematopoietic cells via an FcγR-dependent and ACE2-, pH-, cysteine-protease-independent pathways. 4. The antibody-mediated enhancement phenomenon is not a mandatory component of the humoral immune response elicited by SARS vaccines, as pure neutralising antibody only could be obtained. 5. Occurrence of immune-mediated enhancement of SARS-CoV infection raises safety concerns regarding the use of SARS-CoV vaccine in humans and enables new ways to investigate SARS pathogenesis (tropism and immune response deregulation)

Large-Scale Structure at z~2.5

We have made a statistically complete, unbiased survey of C IV systems toward a region of high QSO density near the South Galactic Pole using 25 lines of sight spanning $1.5<z<2.8$. Such a survey makes an excellent probe of large-scale structure at early epochs. We find evidence for structure on the $15-35h^{-1}$ proper Mpc scale ($H_0 \equiv 100$ km $s^{-1}$ Mpc${-1}$) as determined by the two point C IV - C IV absorber correlation function, and reject the null hypothesis that C IV systems are distributed randomly on such scales at the $\sim 3.5\sigma$ level. The structure likely reflects the distance between two groups of absorbers subtending $\sim~ 13 \times 5 \times 21h^{-3}$ and $\sim 7 \times 1 \times 15h^{-3}$ Mpc$^3$ at $z\sim 2.3$ and $z \sim 2.5$ respectively. There is also a marginal trend for the association of high rest equivalent width C IV absorbers and QSOs at similar redshifts but along different lines of sight. The total number of C IV systems detected is consistent with that which would be expected based on a survey using many widely separated lines of sight. Using the same data, we also find 11 Mg II absorbers in a complete survey toward 24 lines of sight; there is no evidence for Mg II - Mg II or Mg II - QSO clustering, though the sample size is likely still small to detect such structure if it exists.Comment: 56 pages including 32 of figures, in gzip-ed uuencoded postscript format, 1 long table not included, aastex4 package. Accepted for publication in ApJ Supplement

The Near-Infrared Number Counts and Luminosity Functions of Local Galaxies

This study presents a wide-field near-infrared (K-band) survey in two fields; SA 68 and Lynx 2. The survey covers an area of 0.6 deg.$^2$, complete to K=16.5. A total of 867 galaxies are detected in this survey of which 175 have available redshifts. The near-infrared number counts to K=16.5 mag. are estimated from the complete photometric survey and are found to be in close agreement with other available studies. The sample is corrected for incompleteness in redshift space, using selection function in the form of a Fermi-Dirac distribution. This is then used to estimate the local near-infrared luminosity function of galaxies. A Schechter fit to the infrared data gives: M$^\ast_K = -25.1 \pm 0.3$, $\alpha = -1.3\pm 0.2$ and $\phi^\ast =(1.5\pm 0.5)\times 10^{-3}$ Mpc$^{-3}$ (for H$_0=50$ Km/sec/Mpc and q$_0=0.5$). When reduced to $\alpha=-1$, this agrees with other available estimates of the local IRLF. We find a steeper slope for the faint-end of the infrared luminosity function when compared to previous studies. This is interpreted as due to the presence of a population of faint but evolved (metal rich) galaxies in the local Universe. However, it is not from the same population as the faint blue galaxies found in the optical surveys. The characteristic magnitude ($M^\ast_K$) of the local IRLF indicates that the bright red galaxies ($M_K\sim -27$ mag.) have a space density of $\le 5\times 10^{-5}$ Mpc$^{-3}$ and hence, are not likely to be local objects.Comment: 24 pages, 8 figures, AASTEX 4.0, published in ApJ 492, 45

Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation

Funding: JW and NARG thank the Wellcome Trust (080088, 086827, 075470), The Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377) and the European Union ALLFUN (FP7/2007 2013, HEALTH-2010-260338) for funding. MGN was supported by a Vici grant of the Netherlands Organisation for Scientific Research. AJPB and DMM were funded by STRIFE, ERC-2009-AdG-249793 and AJPB additionally by FINSysB, PITN-GA-2008-214004 and the BBSRC [BB/F00513X/1]. MDL was supported by the MRC (MR/J008230/1). GDB and SV were funded by the Wellcome Trust (086558) and TB and MK were funded by the Deutsche Forschungsgemeinschaft (Bi 696/3-1; Bi 696/5-2; Bi 696/10-1). MS was supported by the Deutsche Forschungsgemeinschaft (Sch 897/1-3) and the National Institute of Dental and Craniofacial Research (R01 DE017514-01). TDK and RKSM were funded by the National Institute of Health (AR056296, AI101935) and the American Lebanese Syrian Associated Charities (ALSAC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

The Sloan Digital Sky Survey: The Cosmic Spectrum and Star-Formation History

We present a determination of the `Cosmic Optical Spectrum' of the Universe, i.e. the ensemble emission from galaxies, as determined from the red-selected Sloan Digital Sky Survey main galaxy sample and compare with previous results of the blue-selected 2dF Galaxy Redshift Survey. Broadly we find good agreement in both the spectrum and the derived star-formation histories. If we use a power-law star-formation history model where star-formation rate $\propto (1+z)^\beta$ out to z=1, then we find that $\beta$ of 2 to 3 is still the most likely model and there is no evidence for current surveys missing large amounts of star formation at high redshift. In particular `Fossil Cosmology' of the local universe gives measures of star-formation history which are consistent with direct observations at high redshift. Using the photometry of SDSS we are able to derive the cosmic spectrum in absolute units (i.e.$W \AA$^{-1}$Mpc$^{-3}$) at 2--5\AA resolution and find good agreement with published broad-band luminosity densities. For a Salpeter IMF the best fit stellar mass/light ratio is 3.7--7.5$\Msun/\Lsun$in the r-band (corresponding to$\omstars h = 0.0025$--0.0055) and from both the stellar emission history and the H$\alpha$luminosity density independently we find a cosmological star-formation rate of 0.03--0.04 h$\Msun$yr$^{-1}$Mpc$^{-3}$ today.Comment: 17 pages, 11 figures, ApJ in press (April 10th 2003