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251.
Ori Eytan Fanny Morice-Picard Ofer Sarig Khaled Ezzedine Ofer Isakov Qiaoli Li Akemi Ishida-Yamamoto Noam Shomron Tomer Goldsmith Dana Fuchs-Telem Noam Adir Jouni Uitto Seth?J. Orlow Alain Taieb Eli Sprecher 《American journal of human genetics》2013,93(4):752-757
The coexistence of abnormal keratinization and aberrant pigmentation in a number of cornification disorders has long suggested a mechanistic link between these two processes. Here, we deciphered the genetic basis of Cole disease, a rare autosomal-dominant genodermatosis featuring punctate keratoderma, patchy hypopigmentation, and uncommonly, cutaneous calcifications. Using a combination of exome and direct sequencing, we showed complete cosegregation of the disease phenotype with three heterozygous ENPP1 mutations in three unrelated families. All mutations were found to affect cysteine residues in the somatomedin-B-like 2 (SMB2) domain in the encoded protein, which has been implicated in insulin signaling. ENPP1 encodes ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which is responsible for the generation of inorganic pyrophosphate, a natural inhibitor of mineralization. Previously, biallelic mutations in ENPP1 were shown to underlie a number of recessive conditions characterized by ectopic calcification, thus providing evidence of profound phenotypic heterogeneity in ENPP1-associated genetic diseases. 相似文献
252.
Angela Feechan Claire Anderson Laurent Torregrosa Angelica Jermakow Pere Mestre Sabine Wiedemann‐Merdinoglu Didier Merdinoglu Amanda R. Walker Lance Cadle‐Davidson Bruce Reisch Sebastien Aubourg Nadia Bentahar Bipna Shrestha Alain Bouquet Anne‐Françoise Adam‐Blondon Mark R. Thomas Ian B. Dry 《The Plant journal : for cell and molecular biology》2013,76(4):661-674
The most economically important diseases of grapevine cultivation worldwide are caused by the fungal pathogen powdery mildew (Erysiphe necator syn. Uncinula necator) and the oomycete pathogen downy mildew (Plasmopara viticola). Currently, grapegrowers rely heavily on the use of agrochemicals to minimize the potentially devastating impact of these pathogens on grape yield and quality. The wild North American grapevine species Muscadinia rotundifolia was recognized as early as 1889 to be resistant to both powdery and downy mildew. We have now mapped resistance to these two mildew pathogens in M. rotundifolia to a single locus on chromosome 12 that contains a family of seven TIR‐NB‐LRR genes. We further demonstrate that two highly homologous (86% amino acid identity) members of this gene family confer strong resistance to these unrelated pathogens following genetic transformation into susceptible Vitis vinifera winegrape cultivars. These two genes, designated r esistance to P lasmopara v iticola (MrRPV1) are the first resistance genes to be cloned from a grapevine species. Both MrRUN1 and MrRPV1 were found to confer resistance to multiple powdery and downy mildew isolates from France, North America and Australia; however, a single powdery mildew isolate collected from the south‐eastern region of North America, to which M. rotundifolia is native, was capable of breaking MrRUN1‐mediated resistance. Comparisons of gene organization and coding sequences between M. rotundifolia and the cultivated grapevine V. vinifera at the MrRUN1/MrRPV1 locus revealed a high level of synteny, suggesting that the TIR‐NB‐LRR genes at this locus share a common ancestor. 相似文献
253.
Hamid Manzoor Jani Kelloniemi Annick Chiltz David Wendehenne Alain Pugin Benoit Poinssot Angela Garcia‐Brugger 《The Plant journal : for cell and molecular biology》2013,76(3):466-480
Like their animal counterparts, plant glutamate receptor‐like (GLR) homologs are intimately associated with Ca2+ influx through plasma membrane and participate in various physiological processes. In pathogen‐associated molecular patterns (PAMP)‐/elicitor‐mediated resistance, Ca2+ fluxes are necessary for activating downstream signaling events related to plant defense. In this study, oligogalacturonides (OGs), which are endogenous elicitors derived from cell wall degradation, were used to investigate the role of Arabidopsis GLRs in defense signaling. Pharmacological investigations indicated that GLRs are partly involved in free cytosolic [Ca2+] ([Ca2+]cyt) variations, nitric oxide (NO) production, reactive oxygen species (ROS) production and expression of defense‐related genes by OGs. In addition, wild‐type Col‐0 plants treated with the glutamate‐receptor antagonist 6,7‐dinitriquinoxaline‐2,3‐dione (DNQX) had a compromised resistance to Botrytis cinerea and Hyaloperonospora arabidopsidis. Moreover, we provide genetic evidence that AtGLR3.3 is a key component of resistance against H. arabidopsidis. In addition, some OGs‐triggered immune events such as defense gene expression, NO and ROS production are also to different extents dependent on AtGLR3.3. Taken together, these data provide evidence for the involvement of GLRs in elicitor/pathogen‐mediated plant defense signaling pathways in Arabidopsis thaliana. 相似文献
254.
Rachel M. Bristol Rachel Tucker Deborah A. Dawson Gavin Horsburgh Robert P. Prys‐Jones Alain C. Frantz Andy Krupa Nirmal J. Shah Terry Burke Jim J. Groombridge 《Molecular ecology》2013,22(18):4644-4662
Re‐introduction is an important tool for recovering endangered species; however, the magnitude of genetic consequences for re‐introduced populations remains largely unknown, in particular the relative impacts of historical population bottlenecks compared to those induced by conservation management. We characterize 14 microsatellite loci developed for the Seychelles paradise flycatcher and use them to quantify temporal and spatial measures of genetic variation across a 134‐year time frame encompassing a historical bottleneck that reduced the species to ~28 individuals in the 1960s, through the initial stages of recovery and across a second contemporary conservation‐introduction‐induced bottleneck. We then evaluate the relative impacts of the two bottlenecks, and finally apply our findings to inform broader re‐introduction strategy. We find a temporal trend of significant decrease in standard measures of genetic diversity across the historical bottleneck, but only a nonsignificant downward trend in number of alleles across the contemporary bottleneck. However, accounting for the different timescales of the two bottlenecks (~40 historical generations versus <1 contemporary generation), the loss of genetic diversity per generation is greater across the contemporary bottleneck. Historically, the flycatcher population was genetically structured; however, extinction on four of five islands has resulted in a homogeneous contemporary population. We conclude that severe historical bottlenecks can leave a large footprint in terms of sheer quantity of genetic diversity lost. However, severely depleted genetic diversity does not render a species immune to further genetic erosion upon re‐introduction. In some cases, the loss of genetic diversity per generation can, initially at least, be greater across re‐introduction‐induced bottlenecks. 相似文献
255.
Fran?ois Lefebvre Géraldine Fazio Béatrice Mounaix Alain J. Crivelli 《Proceedings. Biological sciences / The Royal Society》2013,280(1754)
Quantifying the fitness cost that parasites impose on wild hosts is a challenging task, because the epidemiological history of field-sampled hosts is often unknown. In this study, we used an internal marker of the parasite pressure on individual hosts to evaluate the costs of parasitism with respect to host body condition, size increase and reproductive potential of field-collected animals for which we also determined individual age. In our investigated system, the European eel Anguilla anguilla and the parasitic invader Anguillicoloides crassus, high virulence and severe impacts are expected because the host lacks an adaptive immune response. We demonstrated a nonlinear relationship between the severity of damage to the affected organ (i.e. the swimbladder, our internal marker) and parasite abundance and biomass, thus showing that the use of classical epidemiological parameters was not relevant here. Surprisingly, we found that the most severely affected eels (with damaged swimbladder) had greater body length and mass (+11% and +41%, respectively), than unaffected eels of same age. We discuss mechanisms that could explain this finding and other counterintuitive results in this host–parasite system, and highlight the likely importance of host panmixia in generating great inter-individual variability in growth potential and infection risk. Under that scenario, the most active foragers would not only have the greatest size increase, but also the highest probability of becoming repeatedly infected—via trophic parasite transmission—during their continental life. 相似文献
256.
Pyridoxal 5′-phosphate is the active form of vitamin B6 and its deficiency is directly related with several human disorders, which make human pyridoxal kinase (hPLK) an important pharmacologic target. In spite of this, a carefully kinetic characterization of hPLK including the main species that regulates the enzymatic activity is at date missing. Here we analyse the catalytic and regulatory mechanisms of hPLK as a function of a precise determination of the species involved in metal–nucleotide equilibriums and describe new regulatory mechanisms for this enzyme. hPLK activity is supported by several metals, being Zn2+ the most effective, although the magnitude of the effect observed is highly dependent on the relative concentrations of metal and nucleotide used. The true substrate for the reaction catalyzed by hPLK is the metal nucleotide complex, while ATP4? and HATP3? did not affect the activity. The enzyme presents substrate inhibition by both pyridoxal (PL) and ZnATP2?, although the latter behaves as a weakly inhibitor. Our study also established, for the first time, a dual role for free Zn2+; as an activator at low concentrations (19 μM optimal concentration) and as a potent inhibitor with a IC50 of 37 μM. These results highlighted the importance of an accurate estimation of the actual concentration of the species involved in metal–nucleotide equilibriums in order to obtain reliable values for the kinetic parameters, and for determine the true regulators of the PLK activity. They also help to explain the dissimilar kinetic parameters reported in the literature for this enzyme. 相似文献
257.
Vanessa S. Oliveira Cecília Pimenteira Diana C.B. da Silva-Alves Laylla L.L. Leal Ricardo A.W. Neves-Filho Daniela M.A.F. Navarro Geanne K.N. Santos Kamilla A. Dutra Janaína V. dos Anjos Thereza A. Soares 《Bioorganic & medicinal chemistry》2013,21(22):6996-7003
The mosquito Aedes aegypti is the vector agent responsible for the transmission of yellow fever and dengue fever viruses to over 80 million people in tropical and subtropical regions of the world. Exhaustive efforts have lead to a vaccine candidate with only 30% effectiveness against the dengue virus and failure to protect patients against the serotype 2. Hence, vector control remains the most viable route to dengue fever control programs. We have synthesized a class of 1,2,4-oxadiazole derivatives whose most biologically active compounds exhibit potent activity against Aedes aegypti larvae (ca. of 15 ppm) and low toxicity in mammals. Exposure to these larvicides results in larvae pigmentation in a manner correlated with the LC50 measurements. Structural comparisons of the 1,2,4-oxadiazole nucleus against known inhibitors of insect enzymes allowed the identification of 3-hydroxykynurenine transaminase as a potential target for these synthetic larvicides. Molecular docking calculations indicate that 1,2,4-oxadiazole compounds can bind to 3-hydroxykynurenine transaminase with similar conformation and binding energies as its crystallographic inhibitor 4-(2-aminophenyl)-4-oxobutanoic acid. 相似文献
258.
Martin Potin-Gautier Véronique Dupuis Alain Castetbon Fernand Moya 《Chemical Speciation and Bioavailability》2013,25(3):95-99
ABSTRACTThe mechanism of erosion of a glass ionomer cement (PR Scell) was studied using two experimental procedures: discs of dental cement were immersed in distilled water under unrenewed conditions as defined by ISO standard or under continuously running distilled water to simulate the oral environment. Both experiments suggest that erosion is important and highly correlated to the cryolithe material included in the formulation of this cement. 相似文献
259.
Jena R. Hickey Janet Nackoney Nathan P. Nibbelink Stephen Blake Aime Bonyenge Sally Coxe Jef Dupain Maurice Emetshu Takeshi Furuichi Falk Grossmann Patrick Guislain John Hart Chie Hashimoto Bernard Ikembelo Omari Ilambu Bila-Isia Inogwabini Innocent Liengola Albert Lotana Lokasola Alain Lushimba Fiona Maisels Joel Masselink Valentin Mbenzo Norbert Mbangia Mulavwa Pascal Naky Nicolas Mwanza Ndunda Pele Nkumu Valentin Omasombo Gay Edwards Reinartz Robert Rose Tetsuya Sakamaki Samantha Strindberg Hiroyuki Takemoto Ashley Vosper Hjalmar S. Kühl 《Biodiversity and Conservation》2013,22(13-14):3085-3104
Habitat loss and hunting threaten bonobos (Pan paniscus), Endangered (IUCN) great apes endemic to lowland rainforests of the Democratic Republic of Congo. Conservation planning requires a current, data-driven, rangewide map of probable bonobo distribution and an understanding of key attributes of areas used by bonobos. We present a rangewide suitability model for bonobos based on a maximum entropy algorithm in which data associated with locations of bonobo nests helped predict suitable conditions across the species’ entire range. We systematically evaluated available biotic and abiotic factors, including a bonobo-specific forest fragmentation layer (forest edge density), and produced a final model revealing the importance of simple threat-based factors in a data poor environment. We confronted the issue of survey bias in presence-only models and devised a novel evaluation approach applicable to other taxa by comparing models built with data from geographically distinct sub-regions that had higher survey effort. The model’s classification accuracy was high (AUC = 0.82). Distance from agriculture and forest edge density best predicted bonobo occurrence with bonobo nests more likely to occur farther from agriculture and in areas of lower edge density. These results suggest that bonobos either avoid areas of higher human activity, fragmented forests, or both, and that humans reduce the effective habitat of bonobos. The model results contribute to an increased understanding of threats to bonobo populations, as well as help identify priority areas for future surveys and determine core bonobo protection areas. 相似文献
260.
J. Roberto Sosa‐López Daniel J. Mennill Adolfo G. Navarro‐Sigüenza 《Journal of avian biology》2013,44(1):027-038
Speciation may be influenced by geographic variation in animal signals, particularly when those signals are important in reproductive decisions. Here, we describe patterns of geographic variation in the song of rufous‐naped wrens Campylorhynchus rufinucha. This species complex is a morphologically variable taxon confined to tropical dry forest areas from Mexico to northwestern Costa Rica. Morphological and genetic analyses suggest that there are at least three partially isolated groups within the complex, including a secondary‐contact zone in coastal western Chiapas between the subspecies C. r. humilus and C. r. nigricaudatus. Based on recordings throughout their geographic range, we investigate the effects of historical isolation on song structure and analyze whether genetic differences or climatic conditions explain observed patterns of variation. Our findings, based on a culturally‐transmitted and sexually‐selected trait, support the hypothesis that three evolutionary units exist within this taxon. Our results suggest that song differences between genetic groups were influenced by historical isolation. We report a strong relationship between vocal dissimilarity and genetic distance, suggesting that differences in vocal characteristics are probably affected by the same factors that drive genetic divergence. We argue that the evolution of song in this taxon is influenced by vicariant events, followed by accumulation of changes in song structure due to several possible factors: cultural drift in song structure; genetic drift in features related to song production; or natural selection acting on features that influence songs, such as body and beak size. 相似文献