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  • 1
    Online Resource
    Online Resource
    Massive Phytoplankton Blooms Under Arctic Sea Ice
    American Association for the Advancement of Science (AAAS) ; 2012
    In:  Science Vol. 336, No. 6087 ( 2012-06-15), p. 1408-1408
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 336, No. 6087 ( 2012-06-15), p. 1408-1408
    Abstract: Phytoplankton blooms over Arctic Ocean continental shelves are thought to be restricted to waters free of sea ice. Here, we document a massive phytoplankton bloom beneath fully consolidated pack ice far from the ice edge in the Chukchi Sea, where light transmission has increased in recent decades because of thinning ice cover and proliferation of melt ponds. The bloom was characterized by high diatom biomass and rates of growth and primary production. Evidence suggests that under-ice phytoplankton blooms may be more widespread over nutrient-rich Arctic continental shelves and that satellite-based estimates of annual primary production in these waters may be underestimated by up to 10-fold.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1215065
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2012
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  • 2
    Online Resource
    Online Resource
    Demographic history and rare allele sharing among human populations
    Proceedings of the National Academy of Sciences ; 2011
    In:  Proceedings of the National Academy of Sciences Vol. 108, No. 29 ( 2011-07-19), p. 11983-11988
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 108, No. 29 ( 2011-07-19), p. 11983-11988
    Abstract: High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2–4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1019276108
    RVK:
    TA 1000
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2011
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  • 3
    Online Resource
    Online Resource
    Characterization of HPV and host genome interactions in primary head and neck cancers
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 43 ( 2014-10-28), p. 15544-15549
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 43 ( 2014-10-28), p. 15544-15549
    Abstract: Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1416074111
    RVK:
    TA 1000
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
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  • 4
    Online Resource
    Online Resource
    Transformation of social networks in the late pre-Hispanic US Southwest
    Proceedings of the National Academy of Sciences ; 2013
    In:  Proceedings of the National Academy of Sciences Vol. 110, No. 15 ( 2013-04-09), p. 5785-5790
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 15 ( 2013-04-09), p. 5785-5790
    Abstract: The late pre-Hispanic period in the US Southwest (A.D. 1200–1450) was characterized by large-scale demographic changes, including long-distance migration and population aggregation. To reconstruct how these processes reshaped social networks, we compiled a comprehensive artifact database from major sites dating to this interval in the western Southwest. We combine social network analysis with geographic information systems approaches to reconstruct network dynamics over 250 y. We show how social networks were transformed across the region at previously undocumented spatial, temporal, and social scales. Using well-dated decorated ceramics, we track changes in network topology at 50-y intervals to show a dramatic shift in network density and settlement centrality from the northern to the southern Southwest after A.D. 1300. Both obsidian sourcing and ceramic data demonstrate that long-distance network relationships also shifted from north to south after migration. Surprisingly, social distance does not always correlate with spatial distance because of the presence of network relationships spanning long geographic distances. Our research shows how a large network in the southern Southwest grew and then collapsed, whereas networks became more fragmented in the northern Southwest but persisted. The study also illustrates how formal social network analysis may be applied to large-scale databases of material culture to illustrate multigenerational changes in network structure.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1219966110
    RVK:
    TA 1000
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
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  • 5
    Online Resource
    Online Resource
    Large-scale topology and the default mode network in the mouse connectome
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 52 ( 2014-12-30), p. 18745-18750
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 52 ( 2014-12-30), p. 18745-18750
    Abstract: Noninvasive functional imaging holds great promise for serving as a translational bridge between human and animal models of various neurological and psychiatric disorders. However, despite a depth of knowledge of the cellular and molecular underpinnings of atypical processes in mouse models, little is known about the large-scale functional architecture measured by functional brain imaging, limiting translation to human conditions. Here, we provide a robust processing pipeline to generate high-resolution, whole-brain resting-state functional connectivity MRI (rs-fcMRI) images in the mouse. Using a mesoscale structural connectome (i.e., an anterograde tracer mapping of axonal projections across the mouse CNS), we show that rs-fcMRI in the mouse has strong structural underpinnings, validating our procedures. We next directly show that large-scale network properties previously identified in primates are present in rodents, although they differ in several ways. Last, we examine the existence of the so-called default mode network (DMN)—a distributed functional brain system identified in primates as being highly important for social cognition and overall brain function and atypically functionally connected across a multitude of disorders. We show the presence of a potential DMN in the mouse brain both structurally and functionally. Together, these studies confirm the presence of basic network properties and functional networks of high translational importance in structural and functional systems in the mouse brain. This work clears the way for an important bridge measurement between human and rodent models, enabling us to make stronger conclusions about how regionally specific cellular and molecular manipulations in mice relate back to humans.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1404346111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
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    detail.hit.zdb_id: 1461794-8
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    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Genetic and functional analyses implicate the NUDT11 , HNF1B , and SLC22A3 genes in prostate cancer pathogenesis
    Proceedings of the National Academy of Sciences ; 2012
    In:  Proceedings of the National Academy of Sciences Vol. 109, No. 28 ( 2012-07-10), p. 11252-11257
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 109, No. 28 ( 2012-07-10), p. 11252-11257
    Abstract: One of the central goals of human genetics is to discover the genes and pathways driving human traits. To date, most of the common risk alleles discovered through genome-wide association studies (GWAS) map to nonprotein-coding regions. Because of our relatively poorer understanding of this part of the genome, the functional consequences of trait-associated variants pose a considerable challenge. To identify the genes through which risk loci act, we hypothesized that the risk variants are regulatory elements. For each of 12 known risk polymorphisms, we evaluated the correlation between risk allele status and transcript abundance for all annotated protein-coding transcripts within a 1-Mb interval. A total of 103 transcripts were evaluated in 662 prostate tissue samples [normal ( n = 407) and tumor ( n = 255)] from 483 individuals [European Americans ( n = 233), Japanese ( n = 127), and African Americans ( n = 123)]. In a pooled analysis, 4 of the 12 risk variants were strongly associated with five transcripts ( NUDT11 , MSMB , NCOA4 , SLC22A3 , and HNF1B ) in histologically normal tissue ( P ≤ 0.001). Although associations were also observed in tumor tissue, they tended to be more attenuated. Previously, we showed that MSMB and NCOA4 participate in prostate cancer pathogenesis. Suppressing the expression of NUDT11 , SLC22A3 , and HNF1B influences cellular phenotypes associated with tumor-related properties in prostate cancer cells. Taken together, the data suggest that these transcripts contribute to prostate cancer pathogenesis.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1200853109
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2012
    detail.hit.zdb_id: 209104-5
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    SSG: 11
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