Early-life DNA methylation profiles are indicative of age-related transcriptome changes.

BACKGROUND: Alterations to cellular and molecular programs with brain aging result in cognitive impairment and susceptibility to neurodegenerative disease. Changes in DNA methylation patterns, an epigenetic modification required for various CNS functions are observed with brain aging and can be prevented by anti-aging interventions, but the relationship of altered methylation to gene expression is poorly understood. RESULTS: Paired analysis of the hippocampal methylome and transcriptome with aging of male and female mice demonstrates that age-related differences in methylation and gene expression are anti-correlated within gene bodies and enhancers. Altered promoter methylation with aging was found to be generally un-related to altered gene expression. A more striking relationship was found between methylation levels at young age and differential gene expression with aging. Highly methylated gene bodies and promoters in early life were associated with age-related increases in gene expression even in the absence of significant methylation changes with aging. As well, low levels of methylation in early life were correlated to decreased expression with aging. This relationship was also observed in genes altered in two mouse Alzheimer\u27s models. CONCLUSION: DNA methylation patterns established in youth, in combination with other epigenetic marks, were able to accurately predict changes in transcript trajectories with aging. These findings are consistent with the developmental origins of disease hypothesis and indicate that epigenetic variability in early life may explain differences in aging trajectories and age-related disease

Comments on worldsheet theories dual to free large N gauge theories

We continue to investigate properties of the worldsheet conformal field theories (CFTs) which are conjectured to be dual to free large N gauge theories, using the mapping of Feynman diagrams to the worldsheet suggested in hep-th/0504229. The modular invariance of these CFTs is shown to be built into the formalism. We show that correlation functions in these CFTs which are localized on subspaces of the moduli space may be interpreted as delta-function distributions, and that this can be consistent with a local worldsheet description given some constraints on the operator product expansion coefficients. We illustrate these features by a detailed analysis of a specific four-point function diagram. To reliably compute this correlator we use a novel perturbation scheme which involves an expansion in the large dimension of some operators.Comment: 43 pages, 16 figures, JHEP format. v2: added reference

The near-infrared luminosity function of cluster galaxies beyond redshift one

We determined the K band luminosity function (LF) of cluster galaxies at redshift z~1.2, using near-infrared images of three X-ray luminous clusters at z=1.11,1.24,1.27. The composite LF was derived down to M*+4, by means of statistical background subtraction, and is well described by a Schechter function with K*=20.5 AB mag and alpha=-1. From the K band composite LF we derived the stellar mass function of cluster galaxies. Using available X-ray mass profiles we determined the M/L ratios of these three clusters, which tend to be lower than those measured in the local universe. With these data, no significant difference can be seen between the shapes of the cluster galaxies LF and the LF of field galaxies at similar redshift. We also found no significant evolution out to z ~1.2 in the bright (<M*+4) part of the cluster galaxies LF probed in this study, apart from a brightening of ~1.3 mag of the characteristic magnitude of the high redshift LF. We confirm, and extend to higher redshift, the result from previous work that the redshift evolution of the characteristic magnitude M* is consistent with passive evolution of a stellar population formed at z>2. The results obtained in this work support and extend previous findings that most of the stars in bright galaxies were formed at high redshift, and that K-bright (M>10^11 Msun) galaxies were already in place at z ~ 1.2, at least in the central regions of X-ray luminous clusters. Together with recent results on the field galaxies stellar mass function, this implies that most of the stellar mass is already assembled in massive galaxies by z ~ 1, both in low and high density environments.Comment: 16 pages, 10 figures, to appear in A&

Chandra Detection of a TypeII Quasar at z=3.288

We report on observations of a TypeII quasar at redshift z=3.288, identified as a hard X-ray source in a 185 ks observation with the Chandra X-ray Observatory and as a high-redshift photometric candidate from deep, multiband optical imaging. CXOJ084837.9+445352 (hereinafter CXO52) shows an unusually hard X-ray spectrum from which we infer an absorbing column density N(H) = (4.8+/-2.1)e23 / cm2 (90% confidence) and an implied unabsorbed 2-10 keV rest-frame luminosity of L(2-10) = 3.3e44 ergs/s, well within the quasar regime. Hubble Space Telescope imaging shows CXO52 to be elongated with slight morphological differences between the WFPC2 F814W and NICMOS F160W bands. Optical and near-infrared spectroscopy of CXO52 show high-ionization emission lines with velocity widths ~1000 km/s and flux ratios similar to a Seyfert2 galaxy or radio galaxy. The latter are the only class of high-redshift TypeII luminous AGN which have been extensively studied to date. Unlike radio galaxies, however, CXO52 is radio quiet, remaining undetected at radio wavelengths to fairly deep limits, f(4.8GHz) < 40 microJy. High-redshift TypeII quasars, expected from unification models of active galaxies and long-thought necessary to explain the X-ray background, are poorly constrained observationally with few such systems known. We discuss recent observations of similar TypeII quasars and detail search techniques for such systems: namely (1) X-ray selection, (2) radio selection, (3) multi-color imaging selection, and (4) narrow-band imaging selection. Such studies are likely to begin identifying luminous, high-redshift TypeII systems in large numbers. We discuss the prospects for these studies and their implications to our understanding of the X-ray background.Comment: 28 pages, 5 figures; to appear in The Astrophysical Journa

Hubble Space Telescope Imaging of the CFRS and LDSS Redshift Surveys---III. Field elliptical galaxies at 0.2 < z < 1.0

Surface photometry has been performed on a sample of 46 field elliptical galaxies. These galaxies are described well by a deVaucouleurs R^{1/4} profile. The sample was selected from the combined Canada-France and LDSS redshift surveys and spans the range 0.20 < z < 1.00. The relationship between galaxy half-light radius and luminosity evolves such that a galaxy of a given size is more luminous by Delta M_B=-0.97 \pm 0.14 mag at z=0.92 and the mean rest-frame color shifts blueward by Delta (U-V) =-0.68 \pm 0.11 at z=0.92 relative to the local cluster relations. Approximately 1/3 of these elliptical galaxies exhibit [OII] 3727 emission lines with equivalent widths > 15 angstroms indicating ongoing star formation. Estimated star-formation rates imply that \le 5% of the stellar mass in the elliptical galaxy population has been formed since z=1. We see no evidence for a decline in the space density of early-type galaxies with look-back time. The statistics and a comparison with local luminosity functions are both consistent with the view that the population of massive early-type galaxies was largely in place by z~1. This implies that merging is not required since that time to produce the present-day space density of elliptical galaxies.Comment: 21 pages plus 8 figures plus 5 tables. Accepted by Astrophysical Journa

Volume 35, AMT-1 Cruise Report and Preliminary Results

This report documents the scientific activities on board the Royal Research Ship (RRS) 'James Clark Ross' during the irst Atlantic Meridional Transect (AMT-1), 21 September to 24 October 1995. The ship sailed from Grimsby (England) for Montevideo (Uruguay) and then continued on to Stanley (Falkland Islands). The primary objective of the AMT program is to investigate basic biological processes in the open Atlantic Ocean over very broad spatial scales. For AMT-1, the meridional range covered was approximately 50 deg N to 50 deg S or nearly 8,000 nmi. The measurements to be taken during the AMT cruises are fundamental for the calibration, validation, and continuing understanding of remotely sensed observations of biological oceanography. They are also important for understanding plankton community structure over latitudinal scales and the role of the world ocean in global carbon cycles. During AMT-1 a variety of instruments were used to map the physical, chemical, and biological structure of the upper 200 m of the water column. Ocean color measurements were made using state-of-the-art sensors, whose calibration was traceable to the highest international standards. New advances in fluorometry were used to measure photosynthetic activity, which was then used to further interpret primary productivity. A unique set of samples and data were collected for the planktonic assemblages that vary throughout the range of the transect. These data will yield new interpretations on community composition and their role in carbon cycling. While the various provinces of the Atlantic Ocean were being crossed, the partial pressure of CO2 was related to biological productivity. This comparison revealed the areas of drawdown of atmospheric CO2 and how these areas relate to the surrounding biological productivity. These data, plus the measurements of light attenuation and phytoplankton optical properties, will be used as a primary input for basin-scale biological productivity models to help develop ecosystem dynamics models which will be important for improving the forecasting abilities of modelers. The AMT program is also attempting to meet the needs of international agencies in their implementation of Sensor Intercomparison and Merger for Biological and Interdisciplinary Ocean Studies (SIMBIOS), a program to develop a methodology and operational capability to combine data products from the various ocean color satellite missions

InternationaL cross-sectIonAl and longItudinal assessment on aSthma cONtrol in European adult patients : the LIAISON study protocol

The study is funded by Chiesi Farmaceutici S.p.A., Parma, ItalyPeer reviewedPublisher PD

SeaWiFS technical report series. Volume 26: Results of the SeaWiFS Data Analysis Round-Robin, July 1994 (DARR-1994)

The accurate determination of upper ocean apparent optical properties (AOP's) is essential for the vicarious calibration of the sea-viewing wide field-of-view sensor (SeaWiFS) instrument and the validation of the derived data products. To evaluate the role that data analysis methods have upon values of derived AOP's, the first Data Analysis Round-Robin (DARR-94) workshop was sponsored by the SeaWiFS Project during 21-23 July, 1994. The focus of this intercomparison study was the estimation of the downwelling irradiance spectrum just beneath the sea surface, E(sub d)(0(sup -), lambda); the upwelling nadir radiance just beneath the sea surface, L(sub u)(0(sup -), lambda); and the vertical profile of the diffuse attenuation coefficient spectrum, K(sub d)(z, lambda). In the results reported here, different methodologies from four research groups were applied to an identical set of 10 spectroradiometry casts in order to evaluate the degree to which data analysis methods influence AOP estimation, and whether any general improvements can be made. The overall results of DARR-94 are presented in Chapter 1 and the individual methods of the four groups are presented in Chapters 2-5. The DARR-94 results do not show a clear winner among data analysis methods evaluated. It is apparent, however, that some degree of outlier rejection is required in order to accurately estimate L(sub u)(0(sup -), lambda) or E(sub d)(0(sup -), lambda). Furthermore, the calculation, evaluation and exploitation of confidence intervals for the AOP determinations needs to be explored. That is, the SeaWiFS calibration and validation problem should be recast in statistical terms where the in situ AOP values are statistical estimates with known confidence intervals