667 research outputs found
The histone deacetylase Rpd3p is required for transient changes in genomic expression in response to stress
BACKGROUND: Yeast responding to stress activate a large gene expression program called the Environmental Stress Response that consists of approximately 600 repressed genes and approximately 300 induced genes. Numerous factors are implicated in regulating subsets of Environmental Stress Response genes; however, a complete picture of Environmental Stress Response regulation remains unclear. We investigated the role of the histone deacetylase Rpd3p, previously linked to the upstream regions of many Environmental Stress Response genes, in producing Environmental Stress Response gene expression changes in response to stress. RESULTS: We found that the Rpd3-Large complex is required for proper expression of both induced and repressed Environmental Stress Response genes under multiple stress conditions. Cells lacking RPD3 or the Rpd3-Large subunit PHO23 had a major defect in Environmental Stress Response initiation, particularly during the transient phase of expression immediately after stress exposure. Chromatin-immunoprecipitation showed a direct role for Rpd3-Large at representative genes; however, there were different effects on nucleosome occupancy and histone deacetylation at different promoters. Computational analysis implicated regulators that may act with Rpd3p at Environmental Stress Response genes. We provide genetic and biochemical evidence that Rpd3p is required for binding and action of the stress-activated transcription factor Msn2p, although the contribution of these factors differs for different genes. CONCLUSIONS: Our results implicate Rpd3p as an important co-factor in the Environmental Stress Response regulatory network, and suggest the importance of histone modification in producing transient changes in gene expression triggered by stress
Bile acids targeted metabolomics and medication classification data in the ADNI1 and ADNIGO/2 cohorts
Alzheimerâs disease (AD) is the most common cause of dementia. The mechanism of disease development and progression is not well understood, but increasing evidence suggests multifactorial etiology, with a number of genetic, environmental, and aging-related factors. There is a growing body of evidence that metabolic defects may contribute to this complex disease. To interrogate the relationship between system level metabolites and disease susceptibility and progression, the AD Metabolomics Consortium (ADMC) in partnership with AD Neuroimaging Initiative (ADNI) is creating a comprehensive biochemical database for patients in the ADNI1 cohort. We used the Biocrates Bile Acids platform to evaluate the association of metabolic levels with disease risk and progression. We detail the quantitative metabolomics data generated on the baseline samples from ADNI1 and ADNIGO/2 (370 cognitively normal, 887 mild cognitive impairment, and 305 AD). Similar to our previous reports on ADNI1, we present the tools for data quality control and initial analysis. This data descriptor represents the third in a series of comprehensive metabolomics datasets from the ADMC on the ADNI
Author Correction: Discovery of 42 genome-wide significant loci associated with dyslexia
Correction to: Nature Genetics https://doi.org/10.1038/s41588-022-01192-y. Published online 20 October 2022.
In the version of this article originally published, a paragraph was omitted in the Methods section, reading âGenomic control. Top SNPs are reported from the more conservative GWAS results adjusted for genomic control (Fig. 1, Extended Data Figs. 1â4, and Supplementary Tables 1, 2, 9 and 10), whereas downstream analyses (including gene-set analysis, enrichment and heritability partitioning, genetic correlations, polygenic prediction, candidate gene replication) are based on GWAS results without genomic control.â The paragraph has now been included in the HTML and PDF versions of the article
The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey
The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic
data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data
release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median
z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar
spectra, along with the data presented in previous data releases. These spectra
were obtained with the new BOSS spectrograph and were taken between 2009
December and 2011 July. In addition, the stellar parameters pipeline, which
determines radial velocities, surface temperatures, surface gravities, and
metallicities of stars, has been updated and refined with improvements in
temperature estimates for stars with T_eff<5000 K and in metallicity estimates
for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars
presented in DR8, including stars from SDSS-I and II, as well as those observed
as part of the SDSS-III Sloan Extension for Galactic Understanding and
Exploration-2 (SEGUE-2).
The astrometry error introduced in the DR8 imaging catalogs has been
corrected in the DR9 data products. The next data release for SDSS-III will be
in Summer 2013, which will present the first data from the Apache Point
Observatory Galactic Evolution Experiment (APOGEE) along with another year of
data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at
http://www.sdss3.org/dr
Incipient Balancing Selection through Adaptive Loss of Aquaporins in Natural Saccharomyces cerevisiae Populations
A major goal in evolutionary biology is to understand how adaptive evolution has influenced natural variation, but identifying loci subject to positive selection has been a challenge. Here we present the adaptive loss of a pair of paralogous genes in specific Saccharomyces cerevisiae subpopulations. We mapped natural variation in freeze-thaw tolerance to two water transporters, AQY1 and AQY2, previously implicated in freeze-thaw survival. However, whereas freeze-thawâtolerant strains harbor functional aquaporin genes, the set of sensitive strains lost aquaporin function at least 6 independent times. Several genomic signatures at AQY1 and/or AQY2 reveal low variation surrounding these loci within strains of the same haplotype, but high variation between strain groups. This is consistent with recent adaptive loss of aquaporins in subgroups of strains, leading to incipient balancing selection. We show that, although aquaporins are critical for surviving freeze-thaw stress, loss of both genes provides a major fitness advantage on high-sugar substrates common to many strains' natural niche. Strikingly, strains with non-functional alleles have also lost the ancestral requirement for aquaporins during spore formation. Thus, the antagonistic effect of aquaporin functionâproviding an advantage in freeze-thaw tolerance but a fitness defect for growth in high-sugar environmentsâcontributes to the maintenance of both functional and nonfunctional alleles in S. cerevisiae. This work also shows that gene loss through multiple missense and nonsense mutations, hallmarks of pseudogenization presumed to emerge after loss of constraint, can arise through positive selection
Detecting and Characterizing Mg II absorption in DESI Survey Validation Quasar Spectra
In this paper we will present findings on the detection of Magnesium II
(MgII, lambda = 2796 {\AA}, 2803 {\AA}) absorption systems observed in data
from the Early Data Release (EDR) of the Dark Energy Spectroscopic Instrument
(DESI). DESI is projected to obtain spectroscopy of approximately 3 million
quasars (QSOs), of which over 99% are anticipated to be found at redshifts
greater than z < 0.3, such that DESI would be able to observe an associated or
intervening Mg II absorber illuminated by the background QSO. We have developed
an autonomous supplementary spectral pipeline that detects such systems through
an initial line-fitting process and then confirms line properties using a
Markov Chain Monte Carlo (MCMC) sampler. Based upon both a visual inspection
and the reanalysis of coadded observations, we estimate this sample of
absorption systems to have a completeness of 82.56% and purity of 99.08%. As
the spectra in which Mg II systems are detected are the result of coadding
multiple observations, we can determine the sensitivity, and therefore
completeness, of the sample by searching for known Mg II systems in coadded
data with fewer observations (and therefore lower signal-to-noise). From a
parent catalog containing 83,207 quasars, we detect a total of 23,921 Mg II
absorption systems following a series of quality cuts. Extrapolating from this
occurrence rate of 28.75% implies a catalog at the completion of the five-year
DESI survey that contains over eight hundred thousand Mg II absorbers. The
cataloging of these systems will enable significant further research as they
carry information regarding circumgalactic medium (CGM) environments, the
distribution of intervening galaxies, and the growth of metallicity across the
redshift range 0.3 < z < 2.5.Comment: 12 pages, 7 figure
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Preference for biological motion is reduced in ASD: implications for clinical trials and the search for biomarkers.
BACKGROUND: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology. METHODS: Eye-tracking data were collected from 486 6-to-30-year-old autistic (Nâ=â282) and non-autistic control (Nâ=â204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL). RESULTS: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline. LIMITATIONS: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons. CONCLUSIONS: Biological motion preference elicits small-to-medium-sized case-control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear
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