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Sequencing-based typing of MICA reveals 33 alleles: a study on linkage with classical HLA genes 总被引:1,自引:0,他引:1
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Donato Santovito Virginia Egea Kiril Bidzhekov Lucia Natarelli Andr Mouro Xavier Blanchet Kanin Wichapong Maria Aslani Coy Brunßen Michael Horckmans Michael Hristov Arie Geerlof Esther Lutgens Mat J. A. P. Daemen Tilman Hackeng Christian Ries Triantafyllos Chavakis Henning Morawietz Ronald Naumann Philipp Von Hundelshausen Sabine Steffens Johan Duchêne Remco T. A. Megens Michael Sattler Christian Weber 《Autophagy》2020,16(12):2294
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Parvinderdeep S. Kahlon Shallet Mindih Seta Gesche Zander Daniela Scheikl Ralph Hückelhoven Matthieu H. A. J. Joosten Remco Stam 《Proceedings. Biological sciences / The Royal Society》2020,287(1941)
Natural plant populations encounter strong pathogen pressure and defence-associated genes are known to be under selection dependent on the pressure by the pathogens. Here, we use populations of the wild tomato Solanum chilense to investigate natural resistance against Cladosporium fulvum, a well-known ascomycete pathogen of domesticated tomatoes. Host populations used are from distinct geographical origins and share a defined evolutionary history. We show that distinct populations of S. chilense differ in resistance against the pathogen. Screening for major resistance gene-mediated pathogen recognition throughout the whole species showed clear geographical differences between populations and complete loss of pathogen recognition in the south of the species range. In addition, we observed high complexity in a homologues of Cladosporium resistance (Hcr) locus, underlying the recognition of C. fulvum, in central and northern populations. Our findings show that major gene-mediated recognition specificity is diverse in a natural plant-pathosystem. We place major gene resistance in a geographical context that also defined the evolutionary history of that species. Data suggest that the underlying loci are more complex than previously anticipated, with small-scale gene recombination being possibly responsible for maintaining balanced polymorphisms in the populations that experience pathogen pressure. 相似文献
5.
Social interest reflects the motivation to approach a conspecific for the assessment of social cues and is measured in rats by the amount of time spent investigating conspecifics. Virgin female rats show lower social interest towards unfamiliar juvenile conspecifics than virgin male rats. We hypothesized that the neuropeptide oxytocin (OT) may modulate sex differences in social interest because of the involvement of OT in pro-social behaviors. We determined whether there are sex differences in OT system parameters in the brain and whether these parameters would correlate with social interest. We also determined whether estrus phase or maternal experience would alter low social interest and whether this would correlate with changes in OT system parameters. Our results show that regardless of estrus phase, females have significantly lower OT receptor (OTR) binding densities than males in the majority of forebrain regions analyzed, including the nucleus accumbens, caudate putamen, lateral septum, bed nucleus of the stria terminalis, medial amygdala, and ventromedial hypothalamus. Interestingly, male social interest correlated positively with OTR binding densities in the medial amygdala, while female social interest correlated negatively with OTR binding densities in the central amygdala. Proestrus/estrus females showed similar social interest to non-estrus females despite increased OTR binding densities in several forebrain areas. Maternal experience had no immediate or long-lasting effects on social interest or OT brain parameters except for higher OTR binding in the medial amygdala in primiparous females. Together, these findings demonstrate that there are robust sex differences in OTR binding densities in multiple forebrain regions of rats and that OTR binding densities correlate with social interest in brain region- and sex-specific ways. 相似文献
6.
Remco Stam Julietta Jupe Andrew J. M. Howden Jenny A. Morris Petra C. Boevink Pete E. Hedley Edgar Huitema 《PloS one》2013,8(3)
Phytophthora species secrete a large array of effectors during infection of their host plants. The Crinkler (CRN) gene family encodes a ubiquitous but understudied class of effectors with possible but as of yet unknown roles in infection. To appreciate CRN effector function in Phytophthora, we devised a simple Crn gene identification and annotation pipeline to improve effector prediction rates. We predicted 84 full-length CRN coding genes and assessed CRN effector domain diversity in sequenced Oomycete genomes. These analyses revealed evidence of CRN domain innovation in Phytophthora and expansion in the Peronosporales. We performed gene expression analyses to validate and define two classes of CRN effectors, each possibly contributing to infection at different stages. CRN localisation studies revealed that P. capsici CRN effector domains target the nucleus and accumulate in specific sub-nuclear compartments. Phenotypic analyses showed that few CRN domains induce necrosis when expressed in planta and that one cell death inducing effector, enhances P. capsici virulence on Nicotiana benthamiana. These results suggest that the CRN protein family form an important class of intracellular effectors that target the host nucleus during infection. These results combined with domain expansion in hemi-biotrophic and necrotrophic pathogens, suggests specific contributions to pathogen lifestyles. This work will bolster CRN identification efforts in other sequenced oomycete species and set the stage for future functional studies towards understanding CRN effector functions. 相似文献
7.
Karen?van Eunen Catharina?M.?L.?Volker-Touw Albert?Gerding Aycha?Bleeker Justina?C.?Wolters Willemijn?J.?van Rijt Anne-Claire?M.?F.?Martines Klary?E.?Niezen-Koning Rebecca?M.?Heiner Hjalmar?Permentier Albert?K.?Groen Terry?G.?J.?Derks Barbara?M.?BakkerEmail author 《BMC biology》2016,14(1):107
Background
Defects in genes involved in mitochondrial fatty-acid oxidation (mFAO) reduce the ability of patients to cope with metabolic challenges. mFAO enzymes accept multiple substrates of different chain length, leading to molecular competition among the substrates. Here, we combined computational modeling with quantitative mouse and patient data to investigate whether substrate competition affects pathway robustness in mFAO disorders.Results
First, we used comprehensive biochemical analyses of wild-type mice and mice deficient for medium-chain acyl-CoA dehydrogenase (MCAD) to parameterize a detailed computational model of mFAO. Model simulations predicted that MCAD deficiency would have no effect on the pathway flux at low concentrations of the mFAO substrate palmitoyl-CoA. However, high concentrations of palmitoyl-CoA would induce a decline in flux and an accumulation of intermediate metabolites. We proved computationally that the predicted overload behavior was due to substrate competition in the pathway. Second, to study the clinical relevance of this mechanism, we used patients’ metabolite profiles and generated a humanized version of the computational model. While molecular competition did not affect the plasma metabolite profiles during MCAD deficiency, it was a key factor in explaining the characteristic acylcarnitine profiles of multiple acyl-CoA dehydrogenase deficient patients. The patient-specific computational models allowed us to predict the severity of the disease phenotype, providing a proof of principle for the systems medicine approach.Conclusion
We conclude that substrate competition is at the basis of the physiology seen in patients with mFAO disorders, a finding that may explain why these patients run a risk of a life-threatening metabolic catastrophe.8.
Bart Spronck Remco T. A. Megens Koen D. Reesink Tammo Delhaas 《Biomechanics and modeling in mechanobiology》2016,15(2):419-432
When studying in vivo arterial mechanical behaviour using constitutive models, smooth muscle cells (SMCs) should be considered, while they play an important role in regulating arterial vessel tone. Current constitutive models assume a strictly circumferential SMC orientation, without any dispersion. We hypothesised that SMC orientation would show considerable dispersion in three dimensions and that helical dispersion would be greater than transversal dispersion. To test these hypotheses, we developed a method to quantify the 3D orientation of arterial SMCs. Fluorescently labelled SMC nuclei of left and right carotid arteries of ten mice were imaged using two-photon laser scanning microscopy. Arteries were imaged at a range of luminal pressures. 3D image processing was used to identify individual nuclei and their orientations. SMCs showed to be arranged in two distinct layers. Orientations were quantified by fitting a Bingham distribution to the observed orientations. As hypothesised, orientation dispersion was much larger helically than transversally. With increasing luminal pressure, transversal dispersion decreased significantly, whereas helical dispersion remained unaltered. Additionally, SMC orientations showed a statistically significant (\(p < 0.05\)) mean right-handed helix angle in both left and right arteries and in both layers, which is a relevant finding from a developmental biology perspective. In conclusion, vascular SMC orientation (1) can be quantified in 3D; (2) shows considerable dispersion, predominantly in the helical direction; and (3) has a distinct right-handed helical component in both left and right carotid arteries. The obtained quantitative distribution data are instrumental for constitutive modelling of the artery wall and illustrate the merit of our method. 相似文献
9.
Solution NMR spectroscopy is an extremely powerful technology for the study of biomolecular dynamics and site-specific molecular interactions. An important limitation in the past has been molecule size, with molecular weights of targets seldom exceeding 50 kDa. New labeling technology and NMR experiments are changing this paradigm so that applications for investigating supramolecular complexes are starting to become feasible. Here we describe a strategy developed in our laboratory that involves the use of labeled methyl groups of isoleucine, leucine and valine residues in proteins as probes, along with experiments that significantly enhance the lifetimes of the resulting signals. We describe the application of these methods to a number of systems with molecular weights in the hundreds of kilodaltons. 相似文献
10.
A conserved transcript pattern in response to a specialist and a generalist herbivore 总被引:24,自引:0,他引:24 下载免费PDF全文
Reymond P Bodenhausen N Van Poecke RM Krishnamurthy V Dicke M Farmer EE 《The Plant cell》2004,16(11):3132-3147