28 research outputs found

    A Powerful New Quantitative Genetics Platform, Combining Caenorhabditis elegans High-Throughput Fitness Assays with a Large Collection of Recombinant Strains.

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    The genetic variants underlying complex traits are often elusive even in powerful model organisms such as Caenorhabditis elegans with controlled genetic backgrounds and environmental conditions. Two major contributing factors are: (1) the lack of statistical power from measuring the phenotypes of small numbers of individuals, and (2) the use of phenotyping platforms that do not scale to hundreds of individuals and are prone to noisy measurements. Here, we generated a new resource of 359 recombinant inbred strains that augments the existing C. elegans N2xCB4856 recombinant inbred advanced intercross line population. This new strain collection removes variation in the neuropeptide receptor gene npr-1, known to have large physiological and behavioral effects on C. elegans and mitigates the hybrid strain incompatibility caused by zeel-1 and peel-1, allowing for identification of quantitative trait loci that otherwise would have been masked by those effects. Additionally, we optimized highly scalable and accurate high-throughput assays of fecundity and body size using the COPAS BIOSORT large particle nematode sorter. Using these assays, we identified quantitative trait loci involved in fecundity and growth under normal growth conditions and after exposure to the herbicide paraquat, including independent genetic loci that regulate different stages of larval growth. Our results offer a powerful platform for the discovery of the genetic variants that control differences in responses to drugs, other aqueous compounds, bacterial foods, and pathogenic stresses

    The DEEP2 Galaxy Redshift Survey: Design, Observations, Data Reduction, and Redshifts

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    We describe the design and data sample from the DEEP2 Galaxy Redshift Survey, the densest and largest precision-redshift survey of galaxies at z ~ 1 completed to date. The survey has conducted a comprehensive census of massive galaxies, their properties, environments, and large-scale structure down to absolute magnitude M_B = -20 at z ~ 1 via ~90 nights of observation on the DEIMOS spectrograph at Keck Observatory. DEEP2 covers an area of 2.8 deg^2 divided into four separate fields, observed to a limiting apparent magnitude of R_AB=24.1. Objects with z < 0.7 are rejected based on BRI photometry in three of the four DEEP2 fields, allowing galaxies with z > 0.7 to be targeted ~2.5 times more efficiently than in a purely magnitude-limited sample. Approximately sixty percent of eligible targets are chosen for spectroscopy, yielding nearly 53,000 spectra and more than 38,000 reliable redshift measurements. Most of the targets which fail to yield secure redshifts are blue objects that lie beyond z ~ 1.45. The DEIMOS 1200-line/mm grating used for the survey delivers high spectral resolution (R~6000), accurate and secure redshifts, and unique internal kinematic information. Extensive ancillary data are available in the DEEP2 fields, particularly in the Extended Groth Strip, which has evolved into one of the richest multiwavelength regions on the sky. DEEP2 surpasses other deep precision-redshift surveys at z ~ 1 in terms of galaxy numbers, redshift accuracy, sample number density, and amount of spectral information. We also provide an overview of the scientific highlights of the DEEP2 survey thus far. This paper is intended as a handbook for users of the DEEP2 Data Release 4, which includes all DEEP2 spectra and redshifts, as well as for the publicly-available DEEP2 DEIMOS data reduction pipelines. [Abridged]Comment: submitted to ApJS; data products available for download at http://deep.berkeley.edu/DR4

    The DEEP2 Galaxy Redshift Survey: Design, Observations, Data Reduction, and Redshifts

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    We describe the design and data analysis of the DEEP2 Galaxy Redshift Survey, the densest and largest high-precision redshift survey of galaxies at z approx. 1 completed to date. The survey was designed to conduct a comprehensive census of massive galaxies, their properties, environments, and large-scale structure down to absolute magnitude MB = 20 at z approx. 1 via approx.90 nights of observation on the Keck telescope. The survey covers an area of 2.8 Sq. deg divided into four separate fields observed to a limiting apparent magnitude of R(sub AB) = 24.1. Objects with z approx. 0.7 to be targeted approx. 2.5 times more efficiently than in a purely magnitude-limited sample. Approximately 60% of eligible targets are chosen for spectroscopy, yielding nearly 53,000 spectra and more than 38,000 reliable redshift measurements. Most of the targets that fail to yield secure redshifts are blue objects that lie beyond z approx. 1.45, where the [O ii] 3727 Ang. doublet lies in the infrared. The DEIMOS 1200 line mm(exp 1) grating used for the survey delivers high spectral resolution (R approx. 6000), accurate and secure redshifts, and unique internal kinematic information. Extensive ancillary data are available in the DEEP2 fields, particularly in the Extended Groth Strip, which has evolved into one of the richest multiwavelength regions on the sky. This paper is intended as a handbook for users of the DEEP2 Data Release 4, which includes all DEEP2 spectra and redshifts, as well as for the DEEP2 DEIMOS data reduction pipelines. Extensive details are provided on object selection, mask design, biases in target selection and redshift measurements, the spec2d two-dimensional data-reduction pipeline, the spec1d automated redshift pipeline, and the zspec visual redshift verification process, along with examples of instrumental signatures or other artifacts that in some cases remain after data reduction. Redshift errors and catastrophic failure rates are assessed through more than 2000 objects with duplicate observations. Sky subtraction is essentially photon-limited even under bright OH sky lines; we describe the strategies that permitted this, based on high image stability, accurate wavelength solutions, and powerful B-spline modeling methods. We also investigate the impact of targets that appear to be single objects in ground-based targeting imaging but prove to be composite in Hubble Space Telescope data; they constitute several percent of targets at z approx. 1, approaching approx. 5%-10% at z > 1.5. Summary data are given that demonstrate the superiority of DEEP2 over other deep high-precision redshift surveys at z approx. 1 in terms of redshift accuracy, sample number density, and amount of spectral information. We also provide an overview of the scientific highlights of the DEEP2 survey thus far

    Incipient Balancing Selection through Adaptive Loss of Aquaporins in Natural Saccharomyces cerevisiae Populations

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    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-thaw–tolerant 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 function—providing an advantage in freeze-thaw tolerance but a fitness defect for growth in high-sugar environments—contributes 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

    Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

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    It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations
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