283 research outputs found

    Mathematically Gifted Adolescents Have Deficiencies in Social Valuation and Mentalization

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    Many mathematically gifted adolescents are characterized as being indolent, underachieving and unsuccessful despite their high cognitive ability. This is often due to difficulties with social and emotional development. However, research on social and emotional interactions in gifted adolescents has been limited. The purpose of this study was to observe differences in complex social strategic behaviors between gifted and average adolescents of the same age using the repeated Ultimatum Game. Twenty-two gifted adolescents and 24 average adolescents participated in the Ultimatum Game. Two adolescents participate in the game, one as a proposer and the other as a responder. Because of its simplicity, the Ultimatum Game is an apt tool for investigating complex human emotional and cognitive decision-making in an empirical setting. We observed strategic but socially impaired offers from gifted proposers and lower acceptance rates from gifted responders, resulting in lower total earnings in the Ultimatum Game. Thus, our results indicate that mathematically gifted adolescents have deficiencies in social valuation and mentalization

    The frontline antibiotic vancomycin induces a zinc starvation response in bacteria by binding to Zn(II).

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    Vancomycin is a front-line antibiotic used for the treatment of nosocomial infections, particularly those caused by methicillin-resistant Staphylococcus aureus. Despite its clinical importance the global effects of vancomycin exposure on bacterial physiology are poorly understood. In a previous transcriptomic analysis we identified a number of Zur regulon genes which were highly but transiently up-regulated by vancomycin in Streptomyces coelicolor. Here, we show that vancomycin also induces similar zinc homeostasis systems in a range of other bacteria and demonstrate that vancomycin binds to Zn(II) in vitro. This implies that vancomycin treatment sequesters zinc from bacterial cells thereby triggering a Zur-dependent zinc starvation response. The Kd value of the binding between vancomycin and Zn(II) was calculated using a novel fluorometric assay, and NMR was used to identify the binding site. These findings highlight a new biologically relevant aspect of the chemical property of vancomycin as a zinc chelator.This work was supported by funding from the Royal Society, UK (516002.K5877/ROG), the Medical Research Council, UK (G0700141). A.Z. was supported from the Said foundation and Cambridge Trust.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep1960

    Evidence for a narrow dip structure at 1.9 GeV/c2^2 in 3π+3π3\pi^+ 3\pi^- diffractive photoproduction

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    A narrow dip structure has been observed at 1.9 GeV/c2^2 in a study of diffractive photoproduction of the  3π+3π~3\pi^+3\pi^- final state performed by the Fermilab experiment E687.Comment: The data of Figure 6 can be obtained by downloading the raw data file e687_6pi.txt. v5 (2nov2018): added Fig. 7, the 6 pion energy distribution as requested by a reade

    A comprehensive analysis of the genetic diversity and environmental adaptability in worldwide Merino and Merino-derived sheep breeds

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    BACKGROUND: To enhance and extend the knowledge about the global historical and phylogenetic relationships between Merino and Merino-derived breeds, 19 populations were genotyped with the OvineSNP50 BeadChip specifically for this study, while an additional 23 populations from the publicly available genotypes were retrieved. Three complementary statistical tests, Rsb (extended haplotype homozygosity between-populations), XP-EHH (cross-population extended haplotype homozygosity), and runs of homozygosity (ROH) islands were applied to identify genomic variants with potential impact on the adaptability of Merino genetic type in two contrasting climate zones. RESULTS: The results indicate that a large part of the Merino's genetic relatedness and admixture patterns are explained by their genetic background and/or geographic origin, followed by local admixture. Multi-dimensional scaling, Neighbor-Net, Admixture, and TREEMIX analyses consistently provided evidence of the role of Australian, Rambouillet and German strains in the extensive gene introgression into the other Merino and Merino-derived breeds. The close relationship between Iberian Merinos and other South-western European breeds is consistent with the Iberian origin of the Merino genetic type, with traces from previous contributions of other Mediterranean stocks. Using Rsb and XP-EHH approaches, signatures of selection were detected spanning four genomic regions located on Ovis aries chromosomes (OAR) 1, 6 and 16, whereas two genomic regions on OAR6, that partially overlapped with the previous ones, were highlighted by ROH islands. Overall, the three approaches identified 106 candidate genes putatively under selection. Among them, genes related to immune response were identified via the gene interaction network. In addition, several candidate genes were found, such as LEKR1, LCORL, GHR, RBPJ, BMPR1B, PPARGC1A, and PRKAA1, related to morphological, growth and reproductive traits, adaptive thermogenesis, and hypoxia responses. CONCLUSIONS: To the best of our knowledge, this is the first comprehensive dataset that includes most of the Merino and Merino-derived sheep breeds raised in different regions of the world. The results provide an in-depth picture of the genetic makeup of the current Merino and Merino-derived breeds, highlighting the possible selection pressures associated with the combined effect of anthropic and environmental factors. The study underlines the importance of Merino genetic types as invaluable resources of possible adaptive diversity in the context of the occurring climate changes

    Interactions between Casein Kinase Iε (CKIε) and Two Substrates from Disparate Signaling Pathways Reveal Mechanisms for Substrate-Kinase Specificity

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    Members of the Casein Kinase I (CKI) family of serine/threonine kinases regulate diverse biological pathways. The seven mammalian CKI isoforms contain a highly conserved kinase domain and divergent amino- and carboxy-termini. Although they share a preferred target recognition sequence and have overlapping expression patterns, individual isoforms often have specific substrates. In an effort to determine how substrates recognize differences between CKI isoforms, we have examined the interaction between CKIepsilon and two substrates from different signaling pathways.CKIepsilon, but not CKIalpha, binds to and phosphorylates two proteins: Period, a transcriptional regulator of the circadian rhythms pathway, and Disheveled, an activator of the planar cell polarity pathway. We use GST-pull-down assays data to show that two key residues in CKIalpha's kinase domain prevent Disheveled and Period from binding. We also show that the unique C-terminus of CKIepsilon does not determine Dishevelled's and Period's preference for CKIepsilon nor is it essential for binding, but instead plays an auxillary role in stabilizing the interactions of CKIepsilon with its substrates. We demonstrate that autophosphorylation of CKIepsilon's C-terminal tail prevents substrate binding, and use mass spectrometry and chemical crosslinking to reveal how a phosphorylation-dependent interaction between the C-terminal tail and the kinase domain prevents substrate phosphorylation and binding.The biochemical interactions between CKIepsilon and Disheveled, Period, and its own C-terminus lead to models that explain CKIepsilon's specificity and regulation

    An Inducible and Reversible Mouse Genetic Rescue System

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    Inducible and reversible regulation of gene expression is a powerful approach for uncovering gene function. We have established a general method to efficiently produce reversible and inducible gene knockout and rescue in mice. In this system, which we named iKO, the target gene can be turned on and off at will by treating the mice with doxycycline. This method combines two genetically modified mouse lines: a) a KO line with a tetracycline-dependent transactivator replacing the endogenous target gene, and b) a line with a tetracycline-inducible cDNA of the target gene inserted into a tightly regulated (TIGRE) genomic locus, which provides for low basal expression and high inducibility. Such a locus occurs infrequently in the genome and we have developed a method to easily introduce genes into the TIGRE site of mouse embryonic stem (ES) cells by recombinase-mediated insertion. Both KO and TIGRE lines have been engineered for high-throughput, large-scale and cost-effective production of iKO mice. As a proof of concept, we have created iKO mice in the apolipoprotein E (ApoE) gene, which allows for sensitive and quantitative phenotypic analyses. The results demonstrated reversible switching of ApoE transcription, plasma cholesterol levels, and atherosclerosis progression and regression. The iKO system shows stringent regulation and is a versatile genetic system that can easily incorporate other techniques and adapt to a wide range of applications

    Notch Lineages and Activity in Intestinal Stem Cells Determined by a New Set of Knock-In Mice

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    The conserved role of Notch signaling in controlling intestinal cell fate specification and homeostasis has been extensively studied. Nevertheless, the precise identity of the cells in which Notch signaling is active and the role of different Notch receptor paralogues in the intestine remain ambiguous, due to the lack of reliable tools to investigate Notch expression and function in vivo. We generated a new series of transgenic mice that allowed us, by lineage analysis, to formally prove that Notch1 and Notch2 are specifically expressed in crypt stem cells. In addition, a novel Notch reporter mouse, Hes1-EmGFPSAT, demonstrated exclusive Notch activity in crypt stem cells and absorptive progenitors. This roster of knock-in and reporter mice represents a valuable resource to functionally explore the Notch pathway in vivo in virtually all tissues

    The Complete Genome Sequence of Thermoproteus tenax: A Physiologically Versatile Member of the Crenarchaeota

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    Here, we report on the complete genome sequence of the hyperthermophilic Crenarchaeum Thermoproteus tenax (strain Kra 1, DSM 2078(T)) a type strain of the crenarchaeotal order Thermoproteales. Its circular 1.84-megabase genome harbors no extrachromosomal elements and 2,051 open reading frames are identified, covering 90.6% of the complete sequence, which represents a high coding density. Derived from the gene content, T. tenax is a representative member of the Crenarchaeota. The organism is strictly anaerobic and sulfur-dependent with optimal growth at 86 degrees C and pH 5.6. One particular feature is the great metabolic versatility, which is not accompanied by a distinct increase of genome size or information density as compared to other Crenarchaeota. T. tenax is able to grow chemolithoautotrophically (CO2/H-2) as well as chemoorganoheterotrophically in presence of various organic substrates. All pathways for synthesizing the 20 proteinogenic amino acids are present. In addition, two presumably complete gene sets for NADH:quinone oxidoreductase (complex I) were identified in the genome and there is evidence that either NADH or reduced ferredoxin might serve as electron donor. Beside the typical archaeal A(0)A(1)-ATP synthase, a membrane-bound pyrophosphatase is found, which might contribute to energy conservation. Surprisingly, all genes required for dissimilatory sulfate reduction are present, which is confirmed by growth experiments. Mentionable is furthermore, the presence of two proteins (ParA family ATPase, actin-like protein) that might be involved in cell division in Thermoproteales, where the ESCRT system is absent, and of genes involved in genetic competence (DprA, ComF) that is so far unique within Archaea
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