982 resultados para MAMMALIAN TARGET


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Background: MicroRNAs (miRNAs), which are small, non-coding RNAs approximately 21-nucleotides in length, have become a major focus of research in molecular biology. Mammalian miRNAs are proposed to regulate approximately 30% of all protein-coding genes. P

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The origin of new exons is an important mechanism for proteome diversity. Here, we report the recurrent origination of new exons in mammalian chromodomain Y-like (CDYL) genes and the functional consequences associated with the acquisition of the new exons

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Cytosine DNA methylation protects eukaryotic genomes by silencing transposons and harmful DNAs, but also regulates gene expression during normal development. Loss of CG methylation in the Arabidopsis thaliana met1 and ddm1 mutants causes varied and stochastic developmental defects that are often inherited independently of the original met1 or ddm1 mutation. Loss of non-CG methylation in plants with combined mutations in the DRM and CMT3 genes also causes a suite of developmental defects. We show here that the pleiotropic developmental defects of drm1 drm2 cmt3 triple mutant plants are fully recessive, and unlike phenotypes caused by met1 and ddm1, are not inherited independently of the drm and cmt3 mutations. Developmental phenotypes are also reversed when drm1 drm2 cmt3 plants are transformed with DRM2 or CMT3, implying that non-CG DNA methylation is efficiently re-established by sequence-specific signals. We provide evidence that these signals include RNA silencing though the 24-nucleotide short interfering RNA (siRNA) pathway as well as histone H3K9 methylation, both of which converge on the putative chromatin-remodeling protein DRD1. These signals act in at least three partially intersecting pathways that control the locus-specific patterning of non-CG methylation by the DRM2 and CMT3 methyltransferases. Our results suggest that non-CG DNA methylation that is inherited via a network of persistent targeting signals has been co-opted to regulate developmentally important genes. © 2006 Chan et al.

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The diversity and evolution of bitter taste perception in mammals is not well understood. Recent discoveries of bitter taste receptor (T2R) genes provide an opportunity for a genetic approach to this question. We here report the identification of 10 and 30 putative T2R genes from the draft human and mouse genome sequences, respectively, in addition to the 23 and 6 previously known T2R genes from the two species. A phylogenetic analysis of the T2R genes suggests that they can be classified into three main groups, which are designated A, B, and C. Interestingly, while the one-to-one gene orthology between the human and mouse is common to group B and C genes, group A genes show a pattern of species- or lineage-specific duplication. It is possible that group B and C genes are necessary for detecting bitter tastants common to both humans and mice, whereas group A genes are used for species-specific bitter tastants. The analysis also reveals that phylogenetically closely related T2R genes are close in their chromosomal locations, demonstrating tandem gene duplication as the primary source of new T2Rs. For closely related paralogous genes, a rate of nonsynonymous nucleotide substitution significantly higher than the rate of synonymous substitution was observed in the extracellular regions of T2Rs, which are presumably involved in tastant-binding. This suggests the role of positive selection in the diversification of newly duplicated T2R genes. Because many natural poisonous substances are bitter, we conjecture that the mammalian T2R genes are under diversifying selection for the ability to recognize a diverse array of poisons that the organisms may encounter in exploring new habitats and diets.

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Phylogenetic relationships among 37 living species of order Carnivora spanning a relatively broad range of divergence times and taxonomic levels were examined using nuclear sequence data from exon1 of the IRBP gene (approximate to1.3 kb) and first intron

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Background: Despite the small number of ursid species, bear phylogeny has long been a focus of study due to their conservation value, as all bear genera have been classified as endangered at either the species or subspecies level. The Ursidae family repre

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Background: Hair is unique to mammals. Keratin associated proteins (KRTAPs), which contain two major groups: high/ultrahigh cysteine and high glycine-tyrosine, are one of the major components of hair and play essential roles in the formation of rigid and

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Purpose: Advocates and critics of target-setting in the workplace seem unable to reach beyond their own well-entrenched battle lines. While the advocates of goal-directed behaviour point to what they see as demonstrable advantages, the critics of target-setting highlight equally demonstrable disadvantages. Indeed, the academic literature on this topic is currently mired in controversy, with neither side seemingly capable of envisaging a better way forward. This paper seeks to break the current deadlock and move thinking forward in this important aspect of performance measurement and management by outlining a new, more fruitful approach, based on both theory and practical experience. Design/methodology/approach: The topic was approached in three phases: assembling and reading key academic and other literature on the subject of target-setting and goal-directed behaviour, with a view to understanding, in depth, the arguments advanced by the advocates and critics of target-setting; comparing these published arguments with one's own experiential findings, in order to bring the essence of disagreement into much sharper focus; and then bringing to bear the academic and practical experience to identify the essential elements of a new, more fruitful approach offering all the benefits of goal-directed behaviour with none of the typical disadvantages of target-setting. Findings: The research led to three key findings: the advocates of goal-directed behaviour and critics of target-setting each make valid points, as seen from their own current perspectives; the likelihood of these two communities, left to themselves, ever reaching a new synthesis, seems vanishingly small (with leading thinkers in the goal-directed behaviour community already acknowledging this); and, between the three authors, it was discovered that their unusual combination of academic study and practical experience enabled them to see things differently. Hence, they would like to share their new thinking more widely. Research limitations/implications: The authors fully accept that their paper is informed by extensive practical experience and, as yet, there have been no opportunities to test their findings, conclusions and recommendations through rigorous academic research. However, they hope that the paper will move thinking forward in this arena, thereby informing future academic research. Practical implications: The authors hope that the practical implications of the paper will be significant, as it outlines a novel way for organisations to capture the benefits of goal-directed behaviour with none of the disadvantages typically associated with target-setting. Social implications: Given that increased efficiency and effectiveness in the management of organisations would be good for society, the authors think the paper has interesting social implications. Originality/value: Leading thinkers in the field of goal-directed behaviour, such as Locke and Latham, and leading critics of target-setting, such as Ordóñez et al. continue to argue with one another - much like, at the turn of the nineteenth century, proponents of the "wave theory of light" and proponents of the "particle theory of light" were similarly at loggerheads. Just as this furious scientific debate was ultimately resolved by Taylor's experiment, showing that light could behave both as a particle and wave at the same time, the authors believe that the paper demonstrates that goal-directed behaviour and target-setting can successfully co-exist. © Emerald Group Publishing Limited.

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Background: The regular mammalian X and Y chromosomes diverged from each other at least 166 to 148 million years ago, leaving few traces of their early evolution, including degeneration of the Y chromosome and evolution of dosage compensation. Results: We

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Acid-sensing ion channels (ASICs) are emerging as fundamental players in the regulation of neural plasticity and in pathological conditions. Here we showed that lead (Pb2+), a well known neurotoxic metal ion, reversibly and concentration-dependently inhib

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The genes encoding triosephosphate isomerase (TIM) in three species of Microcystis (M. aeruginosa, M. viridis and M. wesenbergii) were investigated. Reverse transcriptase-polymerase chain reaction indicated that they were transcribed in the cells. Analyses showed that their DNA and deduced amino acid sequences were highly conserved between all the three species, only a single nonsynonymous substitution was seen at position 31, from an Asp in M. aeruginosa and M. viridis to Glu in M. wesenbergii. Sequence alignment of these with 12 other known cyanobacterial TIM sequences showed that all the cyanobacterial TIMs had a very high level of amino acid identity (over 50% between each two). Comparison of the cyanobacterial TIMs with other reported TIMs (from diverse lineages of the three Domains) showed that they possessed common active-site residues and sequence motifs. All cyanobacterial TIMs have two common cysteine residues (Cys127 and Cys176), and the Cys176 is almost cyanobacteria-specific with only one exception in Streptomyces coelicolor. Both secondary structure alignment and comparative modelling of Synechocystis sp. TIM showed that Cys176 was located at the hinge region of the flexible loop-6 and might therefore be critical to the movement of TIM's loop-6, which is important to the function of the enzyme. Thus, the cyanobacterial TIM-specific Cys176 may be a potential site for the discovery of suitable drugs against cyanobacteria, and such drugs may have utility in controlling water blooms due to cyanobacteria.

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OVERVIEW: Kodak European Research (KER) developed a strategy for technology intelligence based on a theoretical model developed by Kerr et al. (2006). KER scouts designed and implemented a four-step approach to identify relevant technologies and research centers across Europe, Africa and the Middle East. The approach provides clear guidance for integrating web searches, scouting trips, networking and interactions with intermediaries. KER's example illustrates how companies can organize themselves to look outside corporate boundaries in search of technologies relevant for their business. The approach may be useful to those in other companies who have been asked to start a technology intelligence activity. © 2010 Industrial Research Institute, Inc.

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In this paper, we present an expectation-maximisation (EM) algorithm for maximum likelihood estimation in multiple target models (MTT) with Gaussian linear state-space dynamics. We show that estimation of sufficient statistics for EM in a single Gaussian linear state-space model can be extended to the MTT case along with a Monte Carlo approximation for inference of unknown associations of targets. The stochastic approximation EM algorithm that we present here can be used along with any Monte Carlo method which has been developed for tracking in MTT models, such as Markov chain Monte Carlo and sequential Monte Carlo methods. We demonstrate the performance of the algorithm with a simulation. © 2012 ISIF (Intl Society of Information Fusi).