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High‐resolution definition of humoral immune response correlates of effective immunity against HIV 
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下载免费PDF全文 Galit Alter Karen G Dowell Eric P Brown Todd J Suscovich Anastassia Mikhailova Alison E Mahan Bruce D Walker Falk Nimmerjahn Chris Bailey‐Kellogg Margaret E Ackerman 《Molecular systems biology》2018,14(3)
Defining correlates of immunity by comprehensively interrogating the extensive biological diversity in naturally or experimentally protected subjects may provide insights critical for guiding the development of effective vaccines and antibody‐based therapies. We report advances in a humoral immunoprofiling approach and its application to elucidate hallmarks of effective HIV‐1 viral control. Systematic serological analysis for a cohort of HIV‐infected subjects with varying viral control was conducted using both a high‐resolution, high‐throughput biophysical antibody profiling approach, providing unbiased dissection of the humoral response, along with functional antibody assays, characterizing antibody‐directed effector functions such as complement fixation and phagocytosis that are central to protective immunity. Profiles of subjects with varying viral control were computationally analyzed and modeled in order to deconvolute relationships among IgG Fab properties, Fc characteristics, and effector functions and to identify humoral correlates of potent antiviral antibody‐directed effector activity and effective viral suppression. The resulting models reveal multifaceted and coordinated contributions of polyclonal antibodies to diverse antiviral responses, and suggest key biophysical features predictive of viral control. 相似文献
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Yanxiang Zhao Xilan Cheng Wensheng Zhao Ian A. Taylor Jun Yang Junfeng Liu You‐Liang Peng 《The Plant journal : for cell and molecular biology》2018,96(1):133-146
Fungal avirulence effectors, a key weapon utilized by pathogens to promote their infection, are recognized by immune receptors to boost host R gene‐mediated resistance. Many avirulence effectors share sparse sequence homology to proteins with known functions, and their molecular and biochemical functions together with the evolutionary relationship among different members remain largely unknown. Here, the crystal structure of AvrPib, an avirulence effector from Magnaporthe oryzae, was determined and showed a high degree of similarity to the M . oryzae A vrs and Tox B (MAX) effectors. Compared with other MAX effectors, AvrPib has a distinct positive‐charge patch formed by five positive‐charged residues (K29, K30, R50, K52 and K70) on the surface. These five key residues were essential to avirulence function of AvrPib and affected its nuclear localization into host cells. Moreover, residues V39 and V58, which locate in the hydrophobic core of the structure, cause loss of function of AvrPib by single‐point mutation in natural isolates. In comparison with the wild‐type AvrPib, the V39A or V58A mutations resulted in a partial or entire loss of secondary structure elements. Taken together, our results suggest that differences in the surface charge distribution of avirulence proteins could be one of the major bases for the variation in effector–receptor specificity, and that destabilization of the hydrophobic core is one of the major mechanisms employed by AvrPib for the fungus to evade recognition by resistance factors in the host cell. 相似文献
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L. Pérez‐Pardal J. Grizelj A. Traoré V. Cubric‐Curik G. Arsenos T. Dovenski B. Marković I. Fernández M. Cuervo I. Álvarez A. Beja‐Pereira I. Curik F. Goyache 《Animal genetics》2014,45(1):144-147
A total of 132 mtDNA sequences from 10 Balkan donkey populations were analysed to ascertain their regional genetic structure and to contribute to the knowledge of the spreading of the species after domestication. The Balkan donkey sequences were compared with those from 40 Burkina Faso donkeys as an African outgroup to account for possible local Balkan scenarios. The 172 sequences gave 62 different haplotypes (55 in Balkan donkey). Virtually all the analysed populations had haplotypes assigned to either Clade 1 or Clade 2 even though the relative proportion of Clade 1 or 2 haplotypes differed across populations. Geographical maps constructed using factors computed via principal component analysis showed that the Balkan donkey populations are not spatially structured. AMOVA confirmed a lack of genetic structure in Balkan donkey mtDNA. Balkan populations were poorly differentiated (ΦST = 0.071). Differentiation between the Balkan donkey and the African outgroup also was low. The lack of correspondence between geographical areas and maternal genetic structure is consistent with the hypothesis suggesting a very quick spread of the species after domestication. The current research illustrates the difficulties to trace routes of expansion in donkey, as the species has no geographical structure. 相似文献
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D. Jakubek M. Le Brun G. Leblon M. DuBow M. Binet 《Letters in applied microbiology》2013,56(2):135-141
Legionella bacteria are ubiquitous in aquatic environments. Members of the species Legionella pneumophila are responsible for more than 98% of cases of Legionnaires' disease in France. Our objective was to validate a molecular typing method called infrequent restriction site PCR (IRS PCR), applied to the study of the ecology of Legionella and to compare this method with reference typing methods, pulsed‐field gel electrophoresis (PFGE) and sequence‐based Typing (SBT). PFGE and SBT are considered as gold methods for the epidemiological typing of Leg. pneumophila strains. However, these methods are not suitable to an ecological monitoring of Legionella in natural environments where a large number of strains has to be typed. Validation of IRS PCR method was performed by the identification of 45 Leg. pneumophila isolates from cooling circuits of thermal power plants by IRS PCR, PFGE and SBT. The parameters of each method were measured and compared to evaluate the effectiveness of IRS PCR. The results of this study showed that IRS PCR has a discriminating power similar or better than that of the reference methods and thus that, by its speed and low cost represents an appropriate tool for the study of the ecology of Legionella in cooling circuits. 相似文献
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Mapping DNA damage‐dependent genetic interactions in yeast via party mating and barcode fusion genetics 下载免费PDF全文
下载免费PDF全文 J Javier Díaz‐Mejía Albi Celaj Joseph C Mellor Atina Coté Attila Balint Brandon Ho Pritpal Bansal Fatemeh Shaeri Marinella Gebbia Jochen Weile Marta Verby Anna Karkhanina YiFan Zhang Cassandra Wong Justin Rich D'Arcy Prendergast Gaurav Gupta Sedide Öztürk Daniel Durocher Grant W Brown Frederick P Roth 《Molecular systems biology》2018,14(5)
Condition‐dependent genetic interactions can reveal functional relationships between genes that are not evident under standard culture conditions. State‐of‐the‐art yeast genetic interaction mapping, which relies on robotic manipulation of arrays of double‐mutant strains, does not scale readily to multi‐condition studies. Here, we describe barcode fusion genetics to map genetic interactions (BFG‐GI), by which double‐mutant strains generated via en masse “party” mating can also be monitored en masse for growth to detect genetic interactions. By using site‐specific recombination to fuse two DNA barcodes, each representing a specific gene deletion, BFG‐GI enables multiplexed quantitative tracking of double mutants via next‐generation sequencing. We applied BFG‐GI to a matrix of DNA repair genes under nine different conditions, including methyl methanesulfonate (MMS), 4‐nitroquinoline 1‐oxide (4NQO), bleomycin, zeocin, and three other DNA‐damaging environments. BFG‐GI recapitulated known genetic interactions and yielded new condition‐dependent genetic interactions. We validated and further explored a subnetwork of condition‐dependent genetic interactions involving MAG1, SLX4, and genes encoding the Shu complex, and inferred that loss of the Shu complex leads to an increase in the activation of the checkpoint protein kinase Rad53. 相似文献
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Katarína Jurdíková Jana Kulichová Helena Bestová Frederik Leliaert Pavel Škaloud 《The Journal of eukaryotic microbiology》2014,61(5):509-519
Freshwater green microalgae are diverse and widely distributed across the globe, yet the population structuring of these organisms is poorly understood. We assessed the degree of genetic diversity and differentiation of the desmid species, Micrasterias rotata. First, we compared the sequences of four nuclear regions (actin, gapC1, gapC2, and oee1) in 25 strains and selected the gapC1 and actin regions as the most appropriate markers for population structure assessment in this species. Population genetic structure was subsequently analyzed, based on seven populations from the Czech Republic and Ireland. Hudson's Snn statistics indicated that nearest‐neighbor sequences occurred significantly more frequently within geographical populations than within the wider panmictic population. Moreover, Irish populations consistently showed higher genetic diversity than the Czech samples. These results are in accordance with the unbalanced distribution of alleles in many land plant species; however, the large genetic diversity in M. rotata differs from levels of genetic diversity found in most land plants. 相似文献
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Clonal propagation becomes more abundant with increasing altitudes as environmental conditions worsen. To date, little attention has been paid to the way in which clonal propagation affects genetic diversity and the fine‐scale spatial genetic structure (FSGS) of clonal alpine trees. An AFLP study was undertaken to quantify the clonal and genetic diversity and FSGS of the vulnerable treeline species Polylepis reticulata in Ecuador. We successfully genotyped 32 and 75 ramets within 4 m × 100 m (coarse scale) and 4 m × 4 m (fine scale) transects of one population, respectively. Higher genotypic diversity was detected at the coarse scale than at the fine scale, while lower genetic diversity was detected for P. reticulata than other Polylepis spp. at both scales. Significantly stronger FSGS was detected at the ramet level than the genet level for P. reticulata within a spatial distance of 3 m. The studied P. reticulata population showed pronounced FSGS (Sp = 0.012 at the genet level, a statistic reflecting declining pairwise kinship with distance) revealed restricted gene dispersal, which implies restricted seed dispersal for this population, assuming pollen flow is as extensive as that described for other wind‐pollinated tree species. Our results revealed that clonal diversity is a function of both sample size and the spatial scale of the sampling area. The findings highlights that clonal propagation has affected FSGS within a spatial distance of 3 m for this species. 相似文献
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Shu‐Jun Wei Xu‐Lei Fan Ary A. Hoffmann Li‐Jun Cao Xue‐Xin Chen Zai‐Fu Xu 《Ecology and evolution》2017,7(14):5400-5409
Genetic comparisons of parasitoids and their hosts are expected to reflect ecological and evolutionary processes that influence the interactions between species. The parasitoid wasp, Cotesia vestalis, and its host diamondback moth (DBM), Plutella xylostella, provide opportunities to test whether the specialist natural enemy migrates seasonally with its host or occurs as resident population. We genotyped 17 microsatellite loci and two mitochondrial genes for 158 female adults of C. vestalis collected from 12 geographical populations, as well as nine microsatellite loci for 127 DBM larvae from six separate sites. The samplings covered both the likely source (southern) and immigrant (northern) areas of DBM from China. Populations of C. vestalis fell into three groups, pointing to isolation in northwestern and southwestern China and strong genetic differentiation of these populations from others in central and eastern China. In contrast, DBM showed much weaker genetic differentiation and high rates of gene flow. TESS analysis identified the immigrant populations of DBM as showing admixture in northern China. Genetic disconnect between C. vestalis and its host suggests that the parasitoid did not migrate yearly with its host but likely consisted of resident populations in places where its host could not survive in winter. 相似文献
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Mit mutations that disrupt function of the mitochondrial electron transport chain can, inexplicably, prolong Caenorhabditis elegans lifespan. In this study we use a metabolomics approach to identify an ensemble of mitochondrial‐derived α‐ketoacids and α‐hydroxyacids that are produced by long‐lived Mit mutants but not by other long‐lived mutants or by short‐lived mitochondrial mutants. We show that accumulation of these compounds is dependent on concerted inhibition of three α‐ketoacid dehydrogenases that share dihydrolipoamide dehydrogenase (DLD) as a common subunit, a protein previously linked in humans with increased risk of Alzheimer's disease. When the expression of DLD in wild‐type animals was reduced using RNA interference we observed an unprecedented effect on lifespan – as RNAi dosage was increased lifespan was significantly shortened, but, at higher doses, it was significantly lengthened, suggesting that DLD plays a unique role in modulating length of life. Our findings provide novel insight into the origin of the Mit phenotype. 相似文献
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Pierre Gladieux Jeanne Ropars Hélène Badouin Antoine Branca Gabriela Aguileta Damien M. de Vienne Ricardo C. Rodríguez de la Vega Sara Branco Tatiana Giraud 《Molecular ecology》2014,23(4):753-773
Fungi are ideal model organisms for dissecting the genomic bases of adaptive divergence in eukaryotes. They have simple morphologies and small genomes, occupy contrasting, well‐identified ecological niches and tend to have short generation times, and many are amenable to experimental approaches. Fungi also display diverse lifestyles, from saprotrophs to pathogens or mutualists, and they play extremely important roles in both ecosystems and human activities, as wood decayers, mycorrhizal fungi, lichens, endophytes, plant and animal pathogens, and in fermentation or drug production. We review here recent insights into the patterns and mechanisms of adaptive divergence in fungi, including sources of divergence, genomic variation and, ultimately, speciation. We outline the various ecological sources of divergent selection and genomic changes, showing that gene loss and changes in gene expression and in genomic architecture are important adaptation processes, in addition to the more widely recognized processes of amino acid substitution and gene duplication. We also review recent findings regarding the interspecific acquisition of genomic variation and suggesting an important role for introgression, hybridization and horizontal gene transfers (HGTs). We show that transposable elements can mediate several of these genomic changes, thus constituting important factors for adaptation. Finally, we review the consequences of divergent selection in terms of speciation, arguing that genetic incompatibilities may not be as widespread as generally thought and that pleiotropy between adaptation and reproductive isolation is an important route of speciation in fungal pathogens. 相似文献
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E. Dusi S. Krenek M. Schrallhammer R. Sachse G. Rauch O. Kaltz T. U. Berendonk 《Journal of evolutionary biology》2014,27(4):796-800
Parasites with exclusive vertical transmission from host parent to offspring are an evolutionary puzzle. With parasite fitness entirely linked to host reproduction, any fitness cost for infected hosts risks their selective elimination. Environmental conditions likely influence parasite impact and thereby the success of purely vertical transmission strategies. We tested for temperature‐dependent virulence of Caedibacter taeniospiralis, a vertically transmitted bacterial symbiont of the protozoan Paramecium tetraurelia. We compared growth of infected and cured host populations at five temperatures (16–32 °C). Infection reduced host density at all temperatures, with a peak of ?30% at 28 °C. These patterns were largely consistent across five infected Paramecium strains. Similar to Wolbachia symbionts, C. taeniospiralis may compensate fitness costs by conferring to the host a ‘killer trait’, targeting uninfected competitors. Considerable loss of infection at 32 °C suggests that killer efficacy is not universal and that limited heat tolerance restricts the conditions for persistence of C. taeniospiralis. 相似文献
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Ryan G. Anderson Megan S. Casady Rachel A. Fee Martha M. Vaughan Devdutta Deb Kevin Fedkenheuer Alisa Huffaker Eric A. Schmelz Brett M. Tyler John M. McDowell 《The Plant journal : for cell and molecular biology》2012,72(6):882-893
Diverse pathogens secrete effector proteins into plant cells to manipulate host cellular processes. Oomycete pathogens contain large complements of predicted effector genes defined by an RXLR host cell entry motif. The genome of Hyaloperonospora arabidopsidis (Hpa, downy mildew of Arabidopsis) contains at least 134 candidate RXLR effector genes. Only a small subset of these genes is conserved in related oomycetes from the Phytophthora genus. Here, we describe a comparative functional characterization of the Hpa RXLR effector gene HaRxL96 and a homologous gene, PsAvh163, from the Glycine max (soybean) pathogen Phytophthora sojae. HaRxL96 and PsAvh163 are induced during the early stages of infection and carry a functional RXLR motif that is sufficient for protein uptake into plant cells. Both effectors can suppress immune responses in soybean. HaRxL96 suppresses immunity in Nicotiana benthamiana, whereas PsAvh163 induces an HR‐like cell death response in Nicotiana that is dependent on RAR1 and Hsp90.1. Transgenic Arabidopsis plants expressing HaRxL96 or PsAvh163 exhibit elevated susceptibility to virulent and avirulent Hpa, as well as decreased callose deposition in response to non‐pathogenic Pseudomonas syringae. Both effectors interfere with defense marker gene induction, but do not affect salicylic acid biosynthesis. Together, these experiments demonstrate that evolutionarily conserved effectors from different oomycete species can suppress immunity in plant species that are divergent from the source pathogen’s host. 相似文献
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Shih‐Heng Su Patrick J. Krysan 《The Plant journal : for cell and molecular biology》2016,88(5):867-878
Mitogen‐activated protein kinase cascades are conserved in all eukaryotes. In Arabidopsis thaliana there are approximately 80 genes encoding MAP kinase kinase kinases (MAP3K), 10 genes encoding MAP kinase kinases (MAP2K), and 20 genes encoding MAP kinases (MAPK). Reverse genetic analysis has failed to reveal abnormal phenotypes for a majority of these genes. One strategy for uncovering gene function when single‐mutant lines do not produce an informative phenotype is to perform a systematic genetic interaction screen whereby double‐mutants are created from a large library of single‐mutant lines. Here we describe a new collection of 275 double‐mutant lines derived from a library of single‐mutants targeting genes related to MAP kinase signaling. To facilitate this study, we developed a high‐throughput double‐mutant generating pipeline using a system for growing Arabidopsis seedlings in 96‐well plates. A quantitative root growth assay was used to screen for evidence of genetic interactions in this double‐mutant collection. Our screen revealed four genetic interactions, all of which caused synthetic enhancement of the root growth defects observed in a MAP kinase 4 (MPK4) single‐mutant line. Seeds for this double‐mutant collection are publicly available through the Arabidopsis Biological Resource Center. Scientists interested in diverse biological processes can now screen this double‐mutant collection under a wide range of growth conditions in order to search for additional genetic interactions that may provide new insights into MAP kinase signaling. 相似文献