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151.
Benjamin H. Conlon Adriana Aurori Alexandru‐Ioan Giurgiu John Kefuss Daniel S. Dezmirean Robin F. A. Moritz Jarkko Routtu 《Molecular ecology》2019,28(12):2958-2966
Social insect colonies possess a range of defences which protect them against highly virulent parasites and colony collapse. The host–parasite interaction between honey bees (Apis mellifera) and the mite Varroa destructor is unusual, as honey bee colonies are relatively poorly defended against this parasite. The interaction has existed since the mid‐20th Century, when Varroa switched host to parasitize A. mellifera. The combination of a virulent parasite and relatively naïve host means that, without acaricides, honey bee colonies typically die within 3 years of Varroa infestation. A consequence of acaricide use has been a reduced selective pressure for the evolution of Varroa resistance in honey bee colonies. However, in the past 20 years, several natural‐selection‐based breeding programmes have resulted in the evolution of Varroa‐resistant populations. In these populations, the inhibition of Varroa's reproduction is a common trait. Using a high‐density genome‐wide association analysis in a Varroa‐resistant honey bee population, we identify an ecdysone‐induced gene significantly linked to resistance. Ecdysone both initiates metamorphosis in insects and reproduction in Varroa. Previously, using a less dense genetic map and a quantitative trait loci analysis, we have identified Ecdysone‐related genes at resistance loci in an independently evolved resistant population. Varroa cannot biosynthesize ecdysone but can acquire it from its diet. Using qPCR, we are able to link the expression of ecdysone‐linked resistance genes to Varroa's meals and reproduction. If Varroa co‐opts pupal compounds to initiate and time its own reproduction, mutations in the host's ecdysone pathway may represent a key selection tool for honey bee resistance and breeding. 相似文献
152.
Garcin ED Arvai AS Rosenfeld RJ Kroeger MD Crane BR Andersson G Andrews G Hamley PJ Mallinder PR Nicholls DJ St-Gallay SA Tinker AC Gensmantel NP Mete A Cheshire DR Connolly S Stuehr DJ Aberg A Wallace AV Tainer JA Getzoff ED 《Nature chemical biology》2008,4(11):700-707
Nitric oxide synthase (NOS) enzymes synthesize nitric oxide, a signal for vasodilatation and neurotransmission at low concentrations and a defensive cytotoxin at higher concentrations. The high active site conservation among all three NOS isozymes hinders the design of selective NOS inhibitors to treat inflammation, arthritis, stroke, septic shock and cancer. Our crystal structures and mutagenesis results identified an isozyme-specific induced-fit binding mode linking a cascade of conformational changes to a new specificity pocket. Plasticity of an isozyme-specific triad of distant second- and third-shell residues modulates conformational changes of invariant first-shell residues to determine inhibitor selectivity. To design potent and selective NOS inhibitors, we developed the anchored plasticity approach: anchor an inhibitor core in a conserved binding pocket, then extend rigid bulky substituents toward remote specificity pockets, which become accessible upon conformational changes of flexible residues. This approach exemplifies general principles for the design of selective enzyme inhibitors that overcome strong active site conservation. 相似文献
153.
154.
Heavy Metal and Disinfectant Resistance of Listeria monocytogenes from Foods and Food Processing Plants 总被引:1,自引:0,他引:1
SS Ratani RM Siletzky V Dutta S Yildirim JA Osborne W Lin AD Hitchins TJ Ward S Kathariou 《Applied and environmental microbiology》2012,78(19):6938-6945
The persistence of Listeria monocytogenes in food processing plants and other ecosystems reflects its ability to adapt to numerous stresses. In this study, we investigated 138 isolates from foods and food processing plants for resistance to the quaternary ammonium disinfectant benzalkonium chloride (BC) and to heavy metals (cadmium and arsenic). We also determined the prevalence of distinct cadmium resistance determinants (cadA1, cadA2, and cadA3) among cadmium-resistant isolates. Most BC-resistant isolates were resistant to cadmium as well. Arsenic resistance was encountered primarily in serotype 4b and was an attribute of most isolates of the serotype 4b epidemic clonal group ECIa. Prevalence of the known cadmium resistance determinants was serotype associated: cadA1 was more common in isolates of serotypes 1/2a and 1/2b than 4b, while cadA2 was more common in those of serotype 4b. A subset (15/77 [19%]) of the cadmium-resistant isolates lacked the known cadmium resistance determinants. Most of these isolates were of serotype 4b and were also resistant to arsenic, suggesting novel determinants that may confer resistance to both cadmium and arsenic in these serotype 4b strains. The findings may reflect previously unrecognized components of the ecological history of different serotypes and clonal groups of L. monocytogenes, including exposures to heavy metals and disinfectants. 相似文献
155.
Jorge Nino Flavius Mitrache Peter Cosyn Robin De Keyser 《仿生工程学报(英文版)》2007,4(4):227-236
This paper is focused on the model identification of a Micro Air Vehicle (MAV) in straight steady flight condition. The identification is based on input-output data collected from flight tests using both frequency and time dorrtain techniques. The vehicle is an in-house 40 cm wingspan airplane. Because of the complex coupled, multivariable and nonlinear dynamics of the aircraft, linear SISO structures for both the lateral and longitudinal models around a reference state were derived. The aim of the identification is to provide models that can be used in future development of control techniques for the MAV. 相似文献
156.
Memories compete for retrieval when they are related to a common retrieval cue. Previous research has shown that retrieval of a target memory may lead to subsequent retrieval-induced forgetting (RIF) of currently irrelevant competing memories. In the present study, we investigated the time course of competitive semantic retrieval and examined the neurocognitive mechanisms underlying RIF. We contrasted two theoretical accounts of RIF by examining a critical aspect of this memory phenomenon, namely the extent to which it depends on successful retrieval of the target memory. Participants first studied category-exemplar word-pairs (e.g. Fruit—Apple). Next, we recorded electrophysiological measures of brain activity while the participants performed a competitive semantic cued-recall task. In this task, the participants were provided with the studied categories but they were instructed to retrieve other unstudied exemplars (e.g. Fruit—Ma__?). We investigated the event-related potential (ERP) correlates of retrieval success by comparing ERPs from successful and failed retrieval trials. To isolate the ERP correlates of continuous retrieval attempts from the ERP correlates of retrieval success, we included an impossible retrieval condition, with incompletable word-stem cues (Drinks—Wy__) and compared it with a non-retrieval presentation baseline condition (Occupation—Dentist). The participants’ memory for all the studied exemplars was tested in the final phase of the experiment. Taken together, the behavioural results suggest that RIF is independent of target retrieval. Beyond investigating the mechanisms underlying RIF, the present study also elucidates the temporal dynamics of semantic cued-recall by isolating the ERP correlates of retrieval attempt and retrieval success. The ERP results revealed that retrieval attempt is reflected in a late posterior negativity, possibly indicating construction of candidates for completing the word-stem cue and retrieval monitoring whereas retrieval success was reflected in an anterior positive slow wave. 相似文献
157.
S. Samoudi D. Latour J. Robin M. Sabart B. Misson H. Ait Hammou Kh. Mouhri M. Loudiki 《Contemporary Problems of Ecology》2016,9(5):554-562
The first results of the horizontal distribution of the cell abundance and toxicity of Microcystis in the hypereutrophic Moroccan reservoir Lalla Takerkoust are reported. An unexpected spatio-temporal heterogeneity has been shown between Microcystis abundance and microcystins concentrations. The principal determining factors were analyzed in order to identify the most likely sites for the proliferation and/or accumulation of Microcystis in this reservoir. The horizontal heterogeneity seems to be mainly influenced by the wind direction and inflows. The results can serve as reference data for monitoring cyanobacterial water blooms and associated cyanotoxins in the lake. 相似文献
158.
Kalyani Mondal Karin Regnstrom Winse Morishige Robin BarbourGary Probst Ying-Zi XuDean R. Artis Nanhua YaoPaul Beroza Michael P. Bova 《Biochemical and biophysical research communications》2013
Alzheimer’s disease (AD) is a devastating neurodegenerative disease affecting millions of people. β-Secretase-1 (BACE-1), an enzyme involved in the processing of the amyloid precursor protein (APP) to form Aβ, is a well validated target for AD. Herein, the authors characterize 10 randomly selected hydroxyethylamine (HEA) BACE-1 inhibitors in terms of their association and dissociation rate constants and thermodynamics of binding using surface plasmon resonance (SPR). Rate constants of association (ka) measured at 25 °C ranged from a low of 2.42 × 104 M−1 s−1 to the highest value of 8.3 × 105 M−1 s−1. Rate constants of dissociation (kd) ranged from 1.09 × 10−4 s−1 (corresponding to a residence time of close to three hours), to the fastest of 0.028 s−1. Three compounds were selected for further thermodynamic analysis where it was shown that equilibrium binding was enthalpy driven while unfavorable entropy of binding was observed. Structural analysis revealed that upon ligand binding, the BACE-1flap folds down over the bound ligand causing an induced fit. The maximal difference between alpha carbon positions in the open and closed conformations of the flap was over 5 Å. Thus the negative entropy of binding determined using SPR analysis was consistent with an induced fit observed by structural analysis. 相似文献
159.
Liu Y Sainz IM Wu Y Pixley R Espinola RG Hassan S Khan MM Colman RW 《Experimental cell research》2008,314(4):774-788
Cleaved high molecular weight kininogen (HKa), as well as its domain 5 (D5), inhibits migration and proliferation induced by angiogenic factors and induces apoptosis in vitro. To study its effect on tube formation we utilized a collagen-fibrinogen, three-dimensional gel, an in vitro model of angiogenesis. HKa, GST-D5 and D5 had a similar inhibitory effect of tube length by 90+/-4.5%, 86+/-5.5% and 77+/-12.9%, respectively. D5-derived synthetic peptides: G440-H455 H475-H485 and G486-K502 inhibited tube length by 51+/-3.7%, 54+/-3.8% and 77+/-1.7%, respectively. By a comparison of its inhibitory potency and its sequences, a functional sequence of HKa was defined to G486-G496. PP2, a Src family kinase inhibitor, prevented tube formation in a dose-dependent manner (100-400 nM), but PP3 at 5 microM, an inactive analogue of PP2, did not. HKa and D5 inhibited Src 416 phosphorylation by 62+/-12.3% and 83+/-6.1%, respectively. The C-terminal Src kinase (Csk) inhibits Src kinase activity. Using a siRNA to Csk, expression of Csk was down-regulated by 86+/-7.0%, which significantly increased tube length by 27+/-5.8%. The addition of HKa and D5 completely blocked this effect. We further showed that HKa inhibited Src family kinase activity by disrupting the complex of uPAR, alphavbeta3 integrin and Src. Our results indicate that the anti-angiogenic effect of HKa and D5 is mediated at least in part through Src family kinases and identify a potential novel target for therapeutic inhibition of neovascularization in cancer and inflammatory arthritis. 相似文献
160.
Edward E. Ishiguro Teresa Ainsworth Robin E. Harkness William W. Kay Trevor J. Trust 《Current microbiology》1984,10(4):199-202
A temperate bacteriophage designated TP446 was isolated from culture supernatants ofAeromonas salmonicida strain A446. Phage TP446 adsorbed to all of the typical and atypical strains ofA. salmonicida tested that possessed A-layer, the surface protein array that represents the primary virulence factor of this fish pathogen. In contrast, TP446 failed to adsorb to mutants lacking A-layer. These results indicate that the A-layer is a component of the receptor for phage TP446. 相似文献