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Laussmann MA Passante E Hellwig CT Tomiczek B Flanagan L Prehn JH Huber HJ Rehm M 《The Journal of biological chemistry》2012,287(18):14402-14411
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Stauber EJ Kuczka P van Ohlen M Vogt B Janowitz T Piotrowski M Beuerle T Wittstock U 《PloS one》2012,7(4):e35545
Plants have evolved a variety of mechanisms for dealing with insect herbivory among which chemical defense through secondary metabolites plays a prominent role. Physiological, behavioural and sensorical adaptations to these chemicals provide herbivores with selective advantages allowing them to diversify within the newly occupied ecological niche. In turn, this may influence the evolution of plant metabolism giving rise to e.g. new chemical defenses. The association of Pierid butterflies and plants of the Brassicales has been cited as an illustrative example of this adaptive process known as 'coevolutionary armsrace'. All plants of the Brassicales are defended by the glucosinolate-myrosinase system to which larvae of cabbage white butterflies and related species are biochemically adapted through a gut nitrile-specifier protein. Here, we provide evidence by metabolite profiling and enzyme assays that metabolism of benzylglucosinolate in Pieris rapae results in release of equimolar amounts of cyanide, a potent inhibitor of cellular respiration. We further demonstrate that P. rapae larvae develop on transgenic Arabidopsis plants with ectopic production of the cyanogenic glucoside dhurrin without ill effects. Metabolite analyses and fumigation experiments indicate that cyanide is detoxified by β-cyanoalanine synthase and rhodanese in the larvae. Based on these results as well as on the facts that benzylglucosinolate was one of the predominant glucosinolates in ancient Brassicales and that ancient Brassicales lack nitrilases involved in alternative pathways, we propose that the ability of Pierid species to safely handle cyanide contributed to the primary host shift from Fabales to Brassicales that occured about 75 million years ago and was followed by Pierid species diversification. 相似文献
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MY Zhang T Yuan J Li A Rosa Borges JD Watkins J Guenaga Z Yang Y Wang R Wilson Y Li VR Polonis SH Pincus RM Ruprecht DS Dimitrov 《PloS one》2012,7(9):e44241
Identification of broadly cross-reactive HIV-1-neutralizing antibodies (bnAbs) may assist vaccine immunogen design. Here we report a novel human monoclonal antibody (mAb), designated m43, which co-targets the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein (Env). M43 bound to recombinant gp140 s from various primary isolates, to membrane-associated Envs on transfected cells and HIV-1 infected cells, as well as to recombinant gp120 s and gp41 fusion intermediate structures containing N-trimer structure, but did not bind to denatured recombinant gp140 s and the CD4 binding site (CD4bs) mutant, gp120 D368R, suggesting that the m43 epitope is conformational and overlaps the CD4bs on gp120 and the N-trimer structure on gp41. M43 neutralized 34% of the HIV-1 primary isolates from different clades and all the SHIVs tested in assays based on infection of peripheral blood mononuclear cells (PBMCs) by replication-competent virus, but was less potent in cell line-based pseudovirus assays. In contrast to CD4, m43 did not induce Env conformational changes upon binding leading to exposure of the coreceptor binding site, enhanced binding of mAbs 2F5 and 4E10 specific for the membrane proximal external region (MPER) of gp41 Envs, or increased gp120 shedding. The overall modest neutralization activity of m43 is likely due to the limited binding of m43 to functional Envs which could be increased by antibody engineering if needed. M43 may represent a new class of bnAbs targeting conformational epitopes overlapping structures on both gp120 and gp41. Its novel epitope and possibly new mechanism(s) of neutralization could helpdesign improved vaccine immunogens and candidate therapeutics. 相似文献
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Zhang MY Vu BK Choudhary A Lu H Humbert M Ong H Alam M Ruprecht RM Quinnan G Jiang S Montefiori DC Mascola JR Broder CC Haynes BF Dimitrov DS 《Journal of virology》2008,82(14):6869-6879
Broadly cross-reactive human immunodeficiency virus (HIV)-neutralizing antibodies are infrequently elicited in infected humans. The two best-characterized gp41-specific cross-reactive neutralizing human monoclonal antibodies, 4E10 and 2F5, target linear epitopes in the membrane-proximal external region (MPER) and bind to cardiolipin and several other autoantigens. It has been hypothesized that, because of such reactivity to self-antigens, elicitation of 2F5 and 4E10 and similar antibodies by vaccine immunogens based on the MPER could be affected by tolerance mechanisms. Here, we report the identification and characterization of a novel anti-gp41 monoclonal antibody, designated m44, which neutralized most of the 22 HIV type 1 (HIV-1) primary isolates from different clades tested in assays based on infection of peripheral blood mononuclear cells by replication-competent virus but did not bind to cardiolipin and phosphatidylserine in an enzyme-linked immunosorbent assay and a Biacore assay nor to any protein or DNA autoantigens tested in Luminex assays. m44 bound to membrane-associated HIV-1 envelope glycoproteins (Envs), to recombinant Envs lacking the transmembrane domain and cytoplasmic tail (gp140s), and to gp41 structures containing five-helix bundles and six-helix bundles, but not to N-heptad repeat trimers, suggesting that the C-heptad repeat is involved in m44 binding. In contrast to 2F5, 4E10, and Z13, m44 did not bind to any significant degree to denatured gp140 and linear peptides derived from gp41, suggesting a conformational nature of the epitope. This is the first report of a gp41-specific cross-reactive HIV-1-neutralizing human antibody that does not have detectable reactivity to autoantigens. Its novel conserved conformational epitope on gp41 could be helpful in the design of vaccine immunogens and as a target for therapeutics. 相似文献
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Plachta-Danielzik S Landsberg B Bosy-Westphal A Johannsen M Lange D J Müller M 《Obesity (Silver Spring, Md.)》2008,16(4):777-783
Population-based prevention of overweight needs evidence-based goals consistent with our present knowledge about energy gap (i.e., daily imbalance between energy intake and energy expenditure resulting in overweight). Longitudinal data of normal-weight children (1,029 girls and 1,028 boys; Kiel Obesity Prevention Study, KOPS) were used to calculate energy gain (i.e., increase in fat mass (FM) and fat-free mass (FFM)) in normal-weight children staying normal weight (persistent children) or becoming overweight (incident children). Taking into account weight gain in proportion to height gain (normal development) energy gap was calculated from increases in FM and FFM exceeding normal development. Children were divided into two groups and were followed from age 6 to 10 (group A) and 10 to 14 years (group B). FM and FFM were measured. Medians of 4-year BMI- (kg/m(2))/weight changes (kg) were +1.8/+13.2 (A) and +3.0/+18.7 (B) in girls, and +1.6/+12.8 (A) and +2.6/21.7 (B) in boys. Corresponding data for FM/FFM (kg) were +3.1/+10.2 (A) and +5.1/12.7 (B) in girls, and +2.3/10.8 (A) and +3.0/18.6 (B) in boys. The 4-year-incidence of overweight (%) were 9.4 (A) and 5.4 (B) in girls, and 11.0 (A) and 3.8 (B) in boys, respectively. Mean energy gains (kcal/day) were 26.8 (A) and 46.4 (B) in girls, and 22.1 (A) and 32.5 (B) in boys. The 90th percentile of energy gap (kcal/day) in incident children were 58.1 (A) and 72.0 (B) in girls and 46.0 (A) and 53.2 (B) in boys. To prevent overweight in children energy gap should not exceed 46-72 kcal/day. 相似文献