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The bisquaternary bisnaphthalimides are a versatile class of compounds being active against the malaria parasite Plasmodium falciparum in the lower nanomolar range of concentration combined with no cytotoxicity. The series of compounds is designed as choline analogues and interfering agents of the phosphatidylcholine biosynthesis. The qualitative analysis of the structure–activity relationships (SAR) revealed the importance of a long methylene middle chain of at least 8 methylene groups between the two bisquaternary naphthalimides or a monoquaternary naphthalimide consisting of a long alkyl chain attached to the positively charged nitrogen atom. Since the SARs are different from reported biscationic antimalarial drugs the mode of action remains to be elucidated.  相似文献   
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Organisms Diversity & Evolution - The South African coast is known to harbor four different species of intertidal oribatid mites and their distribution strongly correlates with marine...  相似文献   
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BackgroundDNA repair mechanisms play a major role in cancer risk and progression. Germline variants in DNA repair genes may result in altered gene function and/or activity, thereby causing inter-individual differences in a patient's tumor recurrence capacity. In genes of the DNA repair pathway the gene variants RAD51 rs1801320 G > C, XRCC2 rs3218536 G > A and XPD rs13181 A > C have been previously related to genetic predisposition and prognosis of various cancer entities. In this study we investigated the association between these polymorphisms and time to recurrence (TTR) and overall survival (OS) in soft-tissue sarcoma (STS) patients after curative surgery.MethodsTwo hundred sixty STS patients were included in this retrospective study. Germline DNA was genotyped by 5′-exonuclease (TaqMan) technology. Kaplan Meier curves and multivariate Cox proportional models were calculated for TTR and OS.ResultsA statistically significant association was observed between tumor grade and adjuvant radiotherapy and TTR and between tumor grade and OS. No association was found between RAD51 rs1801320 G > C, XRCC2 rs3218536 G > A and XPD rs13181 A > C and TTR and OS in univariate and multivariate analysis.ConclusionOur results underline a prognostic effect of tumor grade and adjuvant radiotherapy in STS patients but indicate no association between RAD51 rs1801320 G > C, XRCC2 rs3218536 G > A and XPD rs13181 A > C and clinical outcome in STS patients after curative surgery.  相似文献   
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The Drosophila melanogaster genes zerknüllt (zen) and fushi tarazu (ftz) are members of the Hox gene family whose roles have changed significantly in the insect lineage and thus provide an opportunity to study the mechanisms underlying the functional evolution of Hox proteins. We have studied the expression of orthologs of zen (DpuHox3) and ftz (Dpuftz) in the crustacean Daphnia pulex (Branchiopoda), both of which show a dynamic expression pattern. DpuHox3 is expressed in a complex pattern in early embryogenesis, with the most anterior boundary of expression lying at the anterior limit of the second antennal segment as well as a ring of expression around the embryo. In later embryos, DpuHox3 expression is restricted to the mesoderm of mandibular limb buds. Dpuftz is first expressed in a ring around the embryo following the posterior limit of the mandibular segment. Later, Dpuftz is restricted to the posterior part of the mandibular segment. This is the first report of expression of a Hox3 ortholog in a crustacean, and together with Dpuftz data, the results presented here show that Hox3 and ftz have retained a Hox-like expression pattern in crustaceans. This is in accordance with the proposed model of Hox3 and ftz evolution in arthropods and allows a more precise pinpointing of the loss of ftz “Hox-like behaviour”: in the lineage between the Branchiopoda and the basal insect Thysanura.  相似文献   
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Some scientists have suggested that the Huancabamba Depression in northern Peru—i.e., the partial interruption of the Andean chain by the Rio Chamaya drainage system—represents a major biogeographical barrier to montane taxa. Others have suggested that the Amotape-Huancabamba Zone in the Andes of northern Peru and the extreme south of Ecuador is an area of particular biological diversity and possibly a phytogeographical zone in its own right. The phytogeography of this area is investigated here with data mainly from the Loasaceae, supplemented by data on other plant and animal groups and by some new data fromPassiflora L. (Passifloraceae) andRibes L. (Grossulariaceae). The Huancabamba Depression itself does not seem to have been a major dispersal barrier for these groups. However, a phytogeographical zone—the Amotape-Huancabamba Zone—between the Río Jubones system in Ecuador and the Río Chamaya system in Peru can be recognized from the available data. This zone seems to be home to numerous endemic species and species groups and has a high level of diversity (6–8 times as high as adjacent areas to the north and to the south in the groups studied). The species of this area show narrow endemicity and often strikingly aberrant morphological characters, compared with representatives of the same groups from other areas. The overlap between northern and southern groups in the area, the mosaic nature of its habitats (geology, geography, and climate), and a varied geological history (habitat fragmentation, secondary contact) seem to be the three most important factors contributing to these patterns of diversification. At least some phylogenetically old taxa appear to have survived in the Amotape-Huancabamba Zone. The region thus seems to be home to a high number of both neoendemics and paleoendemics.  相似文献   
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On the occasion of the observation of the Onycho-osteo-dysplasia syndrome (HOOD syndrome--Nail-Patella syndrome) in a 4-generation family we were impressed by the presence of a Madelung deformity in the four examined family members. A critical review of the literature showed that a true Madelung deformity was present in a great number of previously reported patients but that no specific attention was given to this apparently important symptom.  相似文献   
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Confidence maps provide complementary information for interpreting cryo‐EM densities as they indicate statistical significance with respect to background noise. They can be thresholded by specifying the expected false‐discovery rate (FDR), and the displayed volume shows the parts of the map that have the corresponding level of significance. Here, the basic statistical concepts of confidence maps are reviewed and practical guidance is provided for their interpretation and usage inside the CCP‐EM suite. Limitations of the approach are discussed and extensions towards other error criteria such as the family‐wise error rate are presented. The observed map features can be rendered at a common isosurface threshold, which is particularly beneficial for the interpretation of weak and noisy densities. In the current article, a practical guide is provided to the recommended usage of confidence maps.  相似文献   
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