Proceedings of the Natural Academy of Sciences

Proceedings of the National Academy of Sciences RSS feed -- current issue
  • Structural basis of a virus-host arms race [Plant Biology]
    [Aug 2014]

    The tomato mosaic virus (ToMV) resistance gene Tm-1 encodes a protein that shows no sequence homology to functionally characterized proteins. Tm-1 binds ToMV replication proteins and thereby inhibits replication complex formation. ToMV mutants that overcome this resistance have amino acid substitutions in the helicase domain of the replication proteins (ToMV-Hel)....
    Categories: Journal Articles
  • Cleaning up the record on MIC and equitability [Physical Sciences]
    [Aug 2014]

    Although we appreciate Kinney and Atwal’s interest in equitability and maximal information coefficient (MIC), we believe they misrepresent our work. We highlight a few of our main objections below. Fig. 1. Equitability of MIC and mutual information under a range of noise models. The equitability of MIC and mutual information...
    Categories: Journal Articles
  • Falsifiability or bust [Physical Sciences]
    [Aug 2014]

    The term “equitability” was introduced by Reshef et al. in ref. 1 to describe measures of statistical dependence that “give similar scores to equally noisy relationships of different types.” Their paper also introduced a new statistic, the “maximal information coefficient” (MIC), that was said to satisfy this equitability criterion. There...
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  • Getting "function" right [Letters (Online Only)]
    [Aug 2014]

    Addressing critiques (1, 2) of the Encyclopedia of DNA Elements’ (ENCODE) claims to have dispelled the notion of “junk DNA,” Kellis et al. (3) “review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments.” The authors consider that “both scientists and nonscientists have an...
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  • Both SE and CR elements can impact human disease [Biological Sciences]
    [Aug 2014]

    We agree with Brunet and Doolittle (1) on the utility of distinguishing the evolutionarily selected effects (SE) of some genomic elements from the causal roles (CR) of other elements that lack signatures of selection (1–4). DNA sequences identified by biochemical approaches include both SE and CR elements, and genetic variation...
    Categories: Journal Articles
  • Robust excitons inhabit soft supramolecular tubes [Physics]
    [Aug 2014]

    Nature's highly efficient light-harvesting antennae, such as those found in green sulfur bacteria, consist of supramolecular building blocks that self-assemble into a hierarchy of close-packed structures. In an effort to mimic the fundamental processes that govern nature’s efficient systems, it is important to elucidate the role of each level of...
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  • Spliceostatin biosynthesis [Biochemistry]
    [Aug 2014]

    Spliceostatins are potent spliceosome inhibitors biosynthesized by a hybrid nonribosomal peptide synthetase−polyketide synthase (NRPS−PKS) system of the trans-acyl transferase (AT) type. Burkholderia sp. FERM BP-3421 produces hemiketal spliceostatins, such as FR901464, as well as analogs containing a terminal carboxylic acid. We provide genetic and biochemical evidence for hemiketal biosynthesis by...
    Categories: Journal Articles
  • Free-energy inference from partial work [Biophysics and Computational Biology]
    [Aug 2014]

    Fluctuation relations (FRs) are among the few existing general results in nonequilibrium systems. Their verification requires the measurement of the total work performed on a system. Nevertheless in many cases only a partial measurement of the work is possible. Here we consider FRs in dual-trap optical tweezers where two different...
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  • Hinge opening in a model insulin-receptor complex [Biophysics and Computational Biology]
    [Aug 2014]

    Insulin provides a classical model of a globular protein, yet how the hormone changes conformation to engage its receptor has long been enigmatic. Interest has focused on the C-terminal B-chain segment, critical for protective self-assembly in β cells and receptor binding at target tissues. Insight may be obtained from truncated...
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  • Cyclin D3 role in {beta}-cell fitness and viability [Cell Biology]
    [Aug 2014]

    Type 1 diabetes is an autoimmune condition caused by the lymphocyte-mediated destruction of the insulin-producing β cells in pancreatic islets. We aimed to identify final molecular entities targeted by the autoimmune assault on pancreatic β cells that are causally related to β cell viability. Here, we show that cyclin D3...
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  • Sequence determinants of Polycomb recruitment [Genetics]
    [Aug 2014]

    Trimethylation of histone H3 at lysine 27 (H3K27me3) is a chromatin mark associated with Polycomb-mediated gene repression. Despite its critical role in development, it remains largely unclear how this mark is targeted to defined loci in mammalian cells. Here, we use iterative genome editing to identify small DNA sequences capable...
    Categories: Journal Articles
  • Roles of IL-17 cytokines/CIKS in psoriasis [Immunology and Inflammation]
    [Aug 2014]

    Psoriasis is a chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and differentiation and by an influx of inflammatory cells. The mechanisms underlying psoriasis in humans and in mouse models are poorly understood, although evidence strongly points to crucial contributions of IL-17 cytokines, which signal via the obligatory adaptor...
    Categories: Journal Articles
  • atRA stabilizes nTregs in inflammatory conditions [Immunology and Inflammation]
    [Aug 2014]

    Recent studies have demonstrated that thymus-derived naturally occurring CD4+Foxp3+ regulatory T cells (Tregs) in human and mouse may be unstable and dysfunctional in the presence of proinflammatory cytokines. All-trans RA (atRA), the active derivative of vitamin A, has been shown to regulate Treg and T effector cell differentiation. We hypothesize...
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  • Cross-resistance against RSV entry inhibitors [Microbiology]
    [Aug 2014]

    Respiratory syncytial virus (RSV) is a leading pediatric pathogen that is responsible for a majority of infant hospitalizations due to viral disease. Despite its clinical importance, no vaccine prophylaxis against RSV disease or effective antiviral therapeutic is available. In this study, we established a robust high-throughput drug screening protocol by...
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  • Combination therapy of degradable HPMA conjugates [Medical Sciences]
    [Aug 2014]

    For rapid and effective clinical translation, polymer-based anticancer therapeutics need long circulating conjugates that produce a sustained concentration gradient between the vasculature and solid tumor. To this end, we designed second-generation backbone-degradable diblock N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carriers and evaluated sequential combination therapy of HPMA copolymer-paclitaxel and HPMA copolymer-gemcitabine conjugates against...
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  • Hepcidin and iron in HIV-1, HBV, and HCV [Medical Sciences]
    [Aug 2014]

    During HIV type-1 (HIV-1), hepatitis C virus (HCV), and hepatitis B virus (HBV) infections, altered iron balance correlates with morbidity. The liver-produced hormone hepcidin dictates systemic iron homeostasis. We measured hepcidin, iron parameters, cytokines, and inflammatory markers in three cohorts: plasma donors who developed acute HIV-1, HBV, or HCV viremia...
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  • HBV infection in MPCCs and iPS-derived hepatocytes [Microbiology]
    [Aug 2014]

    Hepatitis B virus (HBV) chronically infects 400 million people worldwide and is a leading driver of end-stage liver disease and liver cancer. Research into the biology and treatment of HBV requires an in vitro cell-culture system that supports the infection of human hepatocytes, and accurately recapitulates virus–host interactions. Here, we...
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  • Transient Darwinian selection in Paratyphi A [Microbiology]
    [Aug 2014]

    Multiple epidemic diseases have been designated as emerging or reemerging because the numbers of clinical cases have increased. Emerging diseases are often suspected to be driven by increased virulence or fitness, possibly associated with the gain of novel genes or mutations. However, the time period over which humans have been...
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  • Mycovirus is related to bornavirus and nyavirus [Microbiology]
    [Aug 2014]

    Mycoviruses are widespread in nature and often occur with dsRNA and positive-stranded RNA genomes. Recently, strong evidence from RNA sequencing analysis suggested that negative-stranded (−)ssRNA viruses could infect fungi. Here we describe a (−)ssRNA virus, Sclerotinia sclerotiorum negative-stranded RNA virus 1 (SsNSRV-1), isolated from a hypovirulent strain of Sclerotinia sclerotiorum....
    Categories: Journal Articles
  • ESCRT protein recruitment during budding of HIV-1 [Microbiology]
    [Aug 2014]

    HIV-1 virions assemble at the plasma membrane of mammalian cells and recruit the endosomal sorting complex required for transport (ESCRT) machinery to enable particle release. However, little is known about the temporal and spatial organization of ESCRT protein recruitment. Using multiple-color live-cell total internal reflection fluorescence microscopy, we observed that...
    Categories: Journal Articles