401 research outputs found

    When do children learn from unreliable speakers?

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    Children do not necessarily disbelieve a speaker with a history of inaccuracy; they take into account reasons for errors. Three- to 5 year-olds (N = 97) aimed to identify a hidden target in collaboration with a puppet. The puppet’s history of inaccuracy arose either from false beliefs, or occurred despite his being fully informed. On a subsequent test trial, children’s realistic expectation about the target was contradicted by the puppet who was fully informed. Children were more likely to revise their belief in line with the puppet’s assertion when his previous errors were due to false beliefs. Children who explained this puppet’s prior inaccuracy in terms of false belief were more likely to believe the puppet than those who did not. As children’s understanding of the mind advances, they increasingly balance the risk of learning falsehoods from unreliable speakers against that of rejecting truths from speakers who made excusable errors

    Crystal structure of a thermostable Bacillus DNA polymerase l large fragment at 2.1 Å resolution

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    AbstractBackground: The study of DNA polymerases in the Pol l family is central to the understanding of DNA replication and repair. DNA polymerases are used in many molecular biology techniques, including PCR, which require a thermostable polymerase. In order to learn about Pol l function and the basis of thermostability, we undertook structural studies of a new thermostable DNA polymerase.Results: A DNA polymerase large, Klenow-like, fragment from a recently identified thermostable strain of Bacillus stearothermophilus (BF) was cloned, sequenced, overexpressed and characterized. Its crystal structure was determined to 2.1 Å resolution by the method of multiple isomorphous replacement.Conclusions: This structure represents the highest resolution view of a Pol l enzyme obtained to date. Comparison of the three Pol l structures reveals no compelling evidence for many of the specific interactions that have been proposed to induce thermostability, but suggests that thermostability arises from innumerable small changes distributed throughout the protein structure. The polymerase domain is highly conserved in all three proteins. The N-terminal domains are highly divergent in sequence, but retain a common fold. When present, the 3′-5′ proofreading exonuclease activity is associated with this domain. Its absence is associated with changes in catalytic residues that coordinate the divalent ions required for activity and in loops connecting homologous secondary structural elements. In BF, these changes result in a blockage of the DNA-binding cleft

    Long-term trends in total inorganic nitrogen and sulfur deposition in the US from 1990 to 2010

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    Excess deposition (including both wet and dry deposition) of nitrogen and sulfur is detrimental to ecosystems. Recent studies have investigated the spatial patterns and temporal trends of nitrogen and sulfur wet deposition, but few studies have focused on dry deposition due to the scarcity of dry deposition measurements. Here, we use long-term model simulations from the coupled Weather Research and Forecasting and the Community Multiscale Air Quality (WRF-CMAQ) model covering the period from 1990 to 2010 to study changes in spatial distribution as well as temporal trends in total (TDEP), wet (WDEP), and dry deposition (DDEP) of total inorganic nitrogen (TIN) and sulfur (TS) in the United States (US). We first evaluate the model's performance in simulating WDEP over the US by comparing the model results with observational data from the US National Atmospheric Deposition Program. The coupled model generally underestimates the WDEP of both TIN (including both the oxidized nitrogen deposition, TNO3, and the reduced nitrogen deposition, NHx) and TS, with better performance in the eastern US than the western US. The underestimation of the wet deposition by the model is mainly caused by the coarse model grid resolution, missing lightning NOx emissions, and the poor temporal and spatial representation of NH3 emissions. TDEP of both TIN and TS shows significant decreases over the US, especially in the east, due to the large emission reductions that occurred in that region. The decreasing trends of TIN TDEP are caused by decreases in TNO3, and the increasing trends of TIN deposition over the Great Plains and Tropical Wet Forests (Southern Florida Coastal Plain) regions are caused by increases in NH3 emissions, although it should be noted that these increasing trends are not significant. TIN WDEP shows decreasing trends throughout the US, except for the Marine West Coast Forest region. TIN DDEP shows significant decreasing trends in the Eastern Temperate Forests, Northern Forests, Mediterranean California, and Marine West Coast Forest and significant increasing trends in the Tropical Wet Forests, Great Plains and Southern Semi-arid Highlands. For the other three regions (North American Deserts, Temperate Sierras, and Northwestern Forested Mountains), the decreasing or increasing trends are not significant. Both the WDEP and DDEP of TS have decreases across the US, with a larger decreasing trend in the DDEP than that in the WDEP. Across the US during the 1990–2010 period, DDEP of TIN accounts for 58–65 % of TDEP of TIN. TDEP of TIN over the US is dominated by deposition of TNO3 during the first decade, which then shifts to reduced nitrogen (NHx) dominance after 2003, resulting from a combination of NOx emission reductions and NH3 emission increases. The sulfur DDEP is usually higher than the sulfur WDEP until recent years, as the sulfur DDEP has a larger decreasing trend than WDEP

    Manifestación atípica de enfermedad de Still

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    La enfermedad de Still del adulto (ESA) es un proceso inflamatorio sistémico, de etiología desconocida, que se caracteriza por fiebre, artritis y eritema evanescente, además de valores elevados de ferritina sérica. Sin embargo, hasta la fecha, no hay una prueba definitiva de laboratorio o de imagen disponible para su diagnóstico, por lo tanto, la ESA es un diagnóstico de exclusión. Presentamos el caso de una mujer de 44 años con manifestación cutánea atípica de ESA y cuadro clínico de 1 año de evolución caracterizado por fiebre de 40°C, linfadenopatía, hiperferritinemia, y que en la sistemática de estudio presentó positividad para anti-CCP (anticuerpo antipéptido cíclico citrulinado)

    Engineered split in Pfu DNA polymerase fingers domain improves incorporation of nucleotide γ-phosphate derivative

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    Using compartmentalized self-replication (CSR), we evolved a version of Pyrococcus furiosus (Pfu) DNA polymerase that tolerates modification of the γ-phosphate of an incoming nucleotide. A Q484R mutation in α-helix P of the fingers domain, coupled with an unintended translational termination-reinitiation (split) near the finger tip, dramatically improve incorporation of a bulky γ-phosphate-O-linker-dabcyl substituent. Whether synthesized by coupled translation from a bicistronic (−1 frameshift) clone, or reconstituted from separately expressed and purified fragments, split Pfu mutant behaves identically to wild-type DNA polymerase with respect to chromatographic behavior, steady-state kinetic parameters (for dCTP), and PCR performance. Although naturally-occurring splits have been identified previously in the finger tip region of T4 gp43 variants, this is the first time a split (in combination with a point mutation) has been shown to broaden substrate utilization. Moreover, this latest example of a split hyperthermophilic archaeal DNA polymerase further illustrates the modular nature of the Family B DNA polymerase structure

    Herpes simplex virus type 2 antibody detection performance in Kisumu, Kenya, using the Herpeselect ELISA, Kalon ELISA, Western blot and inhibition testing

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    In certain parts of Africa, type-specific HSV type-2 ELISAs may have limited specificity. To date, no study has been conducted to validate HerpeSelect and Kalon type-specific HSV-2 ELISAs using both the Western blot (WB) and Recombinant gG ELISA inhibition testing as reference standards
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