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931.
Leana Doherty Adrianna Vlachos Valerie Choesmel Marie-Françoise O'Donohue Catherine Clinton Colin A. Sieff Peter E. Newburger Edyta Niewiadomska Bertil Glader Jason E. Farrar Jeffrey M. Lipton Pierre-Emmanuel Gleizes Hanna T. Gazda 《American journal of human genetics》2010,86(2):222-6951
Diamond-Blackfan anemia (DBA), an inherited bone marrow failure syndrome characterized by anemia that usually presents before the first birthday or in early childhood, is associated with birth defects and an increased risk of cancer. Although anemia is the most prominent feature of DBA, the disease is also characterized by growth retardation and congenital malformations, in particular craniofacial, upper limb, heart, and urinary system defects that are present in ∼30%–50% of patients. DBA has been associated with mutations in seven ribosomal protein (RP) genes, RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, and RPS7, in about 43% of patients. To continue our large-scale screen of RP genes in a DBA population, we sequenced 35 ribosomal protein genes, RPL15, RPL24, RPL29, RPL32, RPL34, RPL9, RPL37, RPS14, RPS23, RPL10A, RPS10, RPS12, RPS18, RPL30, RPS20, RPL12, RPL7A, RPS6, RPL27A, RPLP2, RPS25, RPS3, RPL41, RPL6, RPLP0, RPS26, RPL21, RPL36AL, RPS29, RPL4, RPLP1, RPL13, RPS15A, RPS2, and RPL38, in our DBA patient cohort of 117 probands. We identified three distinct mutations of RPS10 in five probands and nine distinct mutations of RPS26 in 12 probands. Pre-rRNA analysis in lymphoblastoid cells from patients bearing mutations in RPS10 and RPS26 showed elevated levels of 18S-E pre-rRNA. This accumulation is consistent with the phenotype observed in HeLa cells after knockdown of RPS10 or RPS26 expression with siRNAs, which indicates that mutations in the RPS10 and RPS26 genes in DBA patients affect the function of the proteins in rRNA processing. 相似文献
932.
The alternative oxidase (AOX) is a non-protonmotive ubiquinol oxidase that is found in all plants, some fungi, green algae, bacteria and pathogenic protozoa. The lack of AOX in the mammalian host renders this protein an important potential therapeutic target in the treatment of pathogenic protozoan infections. Bioinformatic searches revealed that, within a putative ubiquinol-binding crevice in AOX, Gln242, Asn247, Tyr253, Ser256, His261 and Arg262 were highly conserved. To confirm that these amino-acid residues are important for ubiquinol-binding and hence activity substitution mutations were generated and characterised. Assessment of AOX activity in isolated Schizosaccharomyces pombe mitochondria revealed that mutation of either Gln242, Ser256, His261 and Arg262 resulted in >90% inhibition of antimycin A-insensitive respiration suggesting that hydroxyl, guanidino, imidazole groups, polar and charged residues in addition to the size of the amino-acid chain are important for ubiquinone-binding. Substitution of Asn247 with glutamine or Tyr253 with phenylalanine had little effect upon the respiratory rate indicating that these residues are not critical for AOX activity. However replacement of Tyr253 by alanine resulted in a 72% loss of activity suggesting that the benzoquinone group and not hydroxyl group is important for quinol binding. These results provide important new insights into the ubiquinol-binding site of the alternative oxidase, the identity of which maybe important for future rational drug design. 相似文献
933.
934.
Background
Gene expression signatures are typically identified by correlating gene expression patterns to a disease phenotype of interest. However, individual gene-based signatures usually suffer from low reproducibility and interpretability. 相似文献935.
Catherine Laura Searle Lisa K. Belden Betsy A. Bancroft Barbara A. Han Lindsay M. Biga Andrew R. Blaustein 《Oecologia》2010,162(1):237-245
Ultraviolet-B radiation (UVB) is a ubiquitous stressor with negative effects on many aquatic organisms. In amphibians, ambient levels of UVB can result in impaired growth, slowed development, malformations, altered behavior and mortality. UVB can also interact with other environmental stressors to amplify these negative effects on individuals. In outdoor mesocosm and laboratory experiments we studied potential synergistic effects of UVB, a pathogenic fungus, Batrachochytrium dendrobatidis (Bd), and varying temperatures on larval Cascades frogs (Rana cascadae). First, we compared survivorship, growth and development in two mesocosm experiments with UVB- and Bd-exposure treatments. We then investigated the effects of UVB on larvae in the laboratory under two temperature regimes, monitoring survival and behavior. We found reduced survival of R. cascadae larvae with exposure to UVB radiation in all experiments. In the mesocosm experiments, growth and development were not affected in either treatment, and no effect of Bd was found. In the laboratory experiment, larvae exposed to UVB demonstrated decreased activity levels. We also found a trend towards reduced survival when UVB and cold temperatures were combined. Our results show that amphibian larvae can suffer both lethal and sublethal effects when exposed to UVB radiation. 相似文献
936.
937.
Céline Contesto Sandrine Milesi Sophie Mantelin Anouk Zancarini Guilhem Desbrosses Fabrice Varoquaux Catherine Bellini Mariusz Kowalczyk Bruno Touraine 《Planta》2010,232(6):1455-1470
Plant root development is highly responsive both to changes in nitrate availability and beneficial microorganisms in the rhizosphere.
We previously showed that Phyllobacterium brassicacearum STM196, a plant growth-promoting rhizobacteria strain isolated from rapeseed roots, alleviates the inhibition exerted by
high nitrate supply on lateral root growth. Since soil-borne bacteria can produce IAA and since this plant hormone may be
implicated in the high nitrate-dependent control of lateral root development, we investigated its role in the root development
response of Arabidopsis thaliana to STM196. Inoculation with STM196 resulted in a 50% increase of lateral root growth in Arabidopsis wild-type seedlings.
This effect was completely abolished in aux1 and axr1 mutants, altered in IAA transport and signaling, respectively, indicating that these pathways are required. The STM196 strain,
however, appeared to be a very low IAA producer when compared with the high-IAA-producing Azospirillum brasilense sp245 strain and its low-IAA-producing ipdc mutant. Consistent with the hypothesis that STM196 does not release significant amounts of IAA to the host roots, inoculation
with this strain failed to increase root IAA content. Inoculation with STM196 led to increased expression levels of several
IAA biosynthesis genes in shoots, increased Trp concentration in shoots, and increased auxin-dependent GUS staining in the
root apices of DR5::GUS transgenic plants. All together, our results suggest that STM196 inoculation triggers changes in IAA distribution and homeostasis
independently from IAA release by the bacteria. 相似文献
938.
939.
940.
Nathalie Boissot Sophie Thomas Nicolas Sauvion Cécile Marchal Claudie Pavis Catherine Dogimont 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,121(1):9-20
Aphis gossypii and Bemisia tabaci are severe hemipteran pests of melon crops and breeding for resistance to both insects is required to reduce pesticide use. Resistance was evaluated for its effect on behaviour and biotic potential of both hemipterans in a population of recombinant inbred lines (RILs) derived from the cross Védrantais × PI 161375. Insect variability was considered using two A. gossypii clones and two B. tabaci populations. Two additive QTLs affected the whiteflies. Four additive QTLs and two couples of epistatic QTLs affected the aphids. Amongst them, a major QTL affects both behaviour and biotic potential of A. gossypii and therefore a same R gene induces both antixenosis and antibiosis. This major QTL colocalizes with the Vat gene belonging to the NBS-LRR gene family. No loci affected both aphids and whiteflies contrary to what was observed for the Mi1.2 gene, a NBS-LRR gene in tomato. Original populations with different allelic compositions at QTLs affecting A. gossypii were built by one inter-crossing of RILs used for the mapping process. The genetic background was shown homogeneous between these populations what allowed validating QTLs and investigating the effect of allelic combinations at QTLs. Effects of QTLs were stronger than expected and some QTLs had a wider spectrum than expected. This strategy of validation appeared rapid and low cost. 相似文献