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951.
952.
Guergnon J Godet AN Galioot A Falanga PB Colle JH Cayla X Garcia A 《Biochimica et biophysica acta》2011,1812(11):1498-1507
Protein phosphatase 2A (PP2A) is a large family of holoenzymes that comprises 1% of total cellular proteins and accounts for the majority of Ser/Thr phosphatase activity in eukaryotic cells. Although initially viewed as constitutive housekeeping enzymes, it is now well established that PP2A proteins represent a family of highly and sophistically regulated phosphatases. The past decade, multiple complementary studies have improved our knowledge about structural and functional regulation of PP2A holoenzymes. In this regard, after summarizing major cellular regulation, this review will mainly focus on discussing a particulate biological strategy, used by various viruses, which is based on the targeting of PP2A enzymes by viral proteins in order to specifically deregulate, for their own benefit, cellular pathways of their hosts. The impact of such PP2A targeting for research in human diseases, and in further therapeutic developments, is also discussed. 相似文献
953.
Pamela M. Prentice Thomas M. Houslay Julien G. A. Martin Alastair J. Wilson 《Journal of evolutionary biology》2020,33(5):642-652
Genetic factors underpinning phenotypic variation are required if natural selection is to result in adaptive evolution. However, evolutionary and behavioural ecologists typically focus on variation among individuals in their average trait values and seek to characterize genetic contributions to this. As a result, less attention has been paid to if and how genes could contribute towards within‐individual variance or trait ‘predictability’. In fact, phenotypic ‘predictability’ can vary among individuals, and emerging evidence from livestock genetics suggests this can be due to genetic factors. Here, we test this empirically using repeated measures of a behavioural stress response trait in a pedigreed population of wild‐type guppies. We ask (a) whether individuals differ in behavioural predictability and (b) whether this variation is heritable and so evolvable under selection. Using statistical methodology from the field of quantitative genetics, we find support for both hypotheses and also show evidence of a genetic correlation structure between the behavioural trait mean and individual predictability. We show that investigating sources of variability in trait predictability is statistically tractable and can yield useful biological interpretation. We conclude that, if widespread, genetic variance for ‘predictability’ will have major implications for the evolutionary causes and consequences of phenotypic variation. 相似文献
954.
Felix Riede Astolfo G.M. Araujo Michael C. Barton Knut Andreas Bergsvik Huw S. Groucutt Shumon T. Hussain Javier Fernandez‐Lopez de Pablo Andreas Maier Ben Marwick Lydia Pyne Kathryn Ranhorn Natasha Reynolds Julien Riel‐Salvatore Florian Sauer Kamil Serwatka Annabell Zander 《Evolutionary anthropology》2020,29(2):49-52
955.
Libor Zvorka Rmy Lassus John Robert Britton Julien Cucherousset 《Global Change Biology》2020,26(10):5693-5704
Reducing the abundances of invasive species by removals aims to minimize their ecological impacts and enable ecosystem recovery. Removal methods are usually selective, modifying phenotypic traits in the managed populations. However, there is little empirical evidence of how removal‐driven changes in multiple phenotypic traits of surviving individuals of invasive species can affect ecosystem functioning and recovery. Overcoming this knowledge gap is highly relevant because individuals are the elemental units of ecological processes and so integrating individual‐level responses into the management of biological invasions could improve their efficiency. Here we provide novel demonstration that removals by trapping, angling and biocontrol from lakes of the globally invasive crayfish Procambarus clarkii induced substantial changes in multiple phenotypic traits. A mesocosm experiment then revealed that these changes in phenotypic traits constrain recovery of basic ecosystem functions (decomposition of organic matter, benthic primary production) by acting in the opposite direction than the effects of reduced invader abundance. However, only minor ecological impacts of invader abundance and phenotypic traits variation remained a year after its complete eradication. Our study provides quantitative evidence to an original idea that removal‐driven trait changes can dampen recovery of invaded ecosystems even when the abundance of invasive species is substantially reduced. We suggest that the phenotypic responses of invaders to the removal programme have strong effects on ecosystem recovery and should be considered within the management of biological invasions, particularly when complete eradication is not achievable. 相似文献
956.
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958.
Julien Dine Irina A. Ionescu Jens Stepan Yi-Chun Yen Florian Holsboer Rainer Landgraf Matthias Eder Ulrike Schmidt 《PloS one》2013,8(3)
Neuropeptide S (NPS) increasingly emerges as a potential novel treatment option for anxiety diseases like panic and posttraumatic stress disorder. However, the neural underpinnings of its anxiolytic action are still not clearly understood. Recently, we reported that neurons of the ventral hippocampus (VH) take up intranasally administered fluorophore-conjugated NPS and, moreover, that application of NPS to mouse brain slices affects neurotransmission and plasticity at hippocampal CA3-CA1 synapses. Although these previous findings define the VH as a novel NPS target structure, they leave open whether this brain region is directly involved in NPS-mediated anxiolysis and how NPS impacts on neuronal activity propagation in the VH. Here, we fill this knowledge gap by demonstrating, first, that microinjections of NPS into the ventral CA1 region are sufficient to reduce anxiety-like behavior of C57BL/6N mice and, second, that NPS, via the NPS receptor, rapidly weakens evoked neuronal activity flow from the dentate gyrus to area CA1 in vitro. Additionally, we show that intranasally applied NPS alters neurotransmission and plasticity at CA3-CA1 synapses in the same way as NPS administered to hippocampal slices. Thus, our study provides, for the first time, strong experimental evidence for a direct involvement of the VH in NPS-induced anxiolysis and furthermore presents a novel mechanism of NPS action. 相似文献
959.
Emilie Pasche Patrick Ruch Douglas Teodoro Angela Huttner Stephan Harbarth Julien Gobeill Rolf Wipfli Christian Lovis 《PloS one》2013,8(4)
Background
Improving antibiotic prescribing practices is an important public-health priority given the widespread antimicrobial resistance. Establishing clinical practice guidelines is crucial to this effort, but their development is a complex task and their quality is directly related to the methodology and source of knowledge used.Objective
We present the design and the evaluation of a tool (KART) that aims to facilitate the creation and maintenance of clinical practice guidelines based on information retrieval techniques.Methods
KART consists of three main modules 1) a literature-based medical knowledge extraction module, which is built upon a specialized question-answering engine; 2) a module to normalize clinical recommendations based on automatic text categorizers; and 3) a module to manage clinical knowledge, which formalizes and stores clinical recommendations for further use. The evaluation of the usability and utility of KART followed the methodology of the cognitive walkthrough.Results
KART was designed and implemented as a standalone web application. The quantitative evaluation of the medical knowledge extraction module showed that 53% of the clinical recommendations generated by KART are consistent with existing clinical guidelines. The user-based evaluation confirmed this result by showing that KART was able to find a relevant antibiotic for half of the clinical scenarios tested. The automatic normalization of the recommendation produced mixed results among end-users.Conclusions
We have developed an innovative approach for the process of clinical guidelines development and maintenance in a context where available knowledge is increasing at a rate that cannot be sustained by humans. In contrast to existing knowledge authoring tools, KART not only provides assistance to normalize, formalize and store clinical recommendations, but also aims to facilitate knowledge building. 相似文献960.
Jakub Gruszczyk Vanesa Olivares-Illana Julien Nourikyan Aurore Fleurie Emmanuelle Béchet Virginie Gueguen-Chaignon Céline Freton Magali Aumont-Nicaise Solange Moréra Christophe Grangeasse Sylvie Nessler 《PloS one》2013,8(10)
A particular class of tyrosine-kinases sharing no structural similarity with eukaryotic tyrosine-kinases has been evidenced in a large array of bacterial species. These bacterial tyrosine-kinases are able to autophosphorylate on a C-terminal tyrosine-rich motif. Their autophosphorylation has been shown to play a crucial role in the biosynthesis or export of capsular polysaccharide. The analysis of the first crystal structure of the staphylococcal tyrosine kinase CapB2 associated with the activating domain of the transmembrane modulator CapA1 had brought conclusive explanation for both the autophosphorylation and activation processes. In order to explain why CapA1 activates CapB2 more efficiently than its cognate transmembrane modulator CapA2, we solved the crystal structure of CapA2B2 and compared it with the previously published structure of CapA1B2. This structural analysis did not provide the expected clues about the activation discrepancy observed between the two modulators. Staphylococcus aureus also encodes for a CapB2 homologue named CapB1 displaying more than 70% sequence similarity and being surprisingly nearly unable to autophosphorylate. We solved the crystal structure of CapA1B1 and carefully compare it with the structure of CapA1B2. The active sites of both proteins are highly conserved and the biochemical characterization of mutant proteins engineered to test the importance of small structural discrepancies identified between the two structures did not explain the inactivity of CapB1. We thus tested if CapB1 could phosphorylate other protein substrates or hydrolyze ATP. However, no activity could be detected in our in vitro assays. Taken together, these data question about the biological role of the homologous protein pairs CapA1/CapB1 and CapA2/CapB2 and we discuss about several possible interpretations. 相似文献