Internal ribosome entry site structural motifs conserved among mammalian fibroblast growth factor 1 alternatively spliced mRNAs

Fibroblast growth factor 1 (FGF-1) is a powerful angiogenic factor whose gene structure contains four promoters, giving rise to a process of alternative splicing resulting in four mRNAs with alternative 5' untranslated regions (5' UTRs). Here we have identified, by using double luciferase bicistronic vectors, the presence of internal ribosome entry sites (IRESs) in the human FGF-1 5' UTRs, particularly in leaders A and C, with distinct activities in mammalian cells. DNA electrotransfer in mouse muscle revealed that the IRES present in the FGF-1 leader A has a high activity in vivo. We have developed a new regulatable TET OFF bicistronic system, which allowed us to rule out the possibility of any cryptic promoter in the FGF-1 leaders. FGF-1 IRESs A and C, which were mapped in fragments of 118 and 103 nucleotides, respectively, are flexible in regard to the position of the initiation codon, making them interesting from a biotechnological point of view. Furthermore, we show that FGF-1 IRESs A of murine and human origins show similar IRES activity profiles. Enzymatic and chemical probing of the FGF-1 IRES A RNA revealed a structural domain conserved among mammals at both the nucleotide sequence and RNA structure levels. The functional role of this structural motif has been demonstrated by point mutagenesis, including compensatory mutations. These data favor an important role of IRESs in the control of FGF-1 expression and provide a new IRES structural motif that could help IRES prediction in 5' UTR databases.     

Shape of the lateral mandibular outline in Lemuridae: a quantitative analysis of variability using elliptical Fourier analysis

While several morphometric analyses in lemurids have focused on the craniofacial complex, the characterization of their mandibular morphology has received less attention. The mandibular outline, in lateral perspective, was quantified using elliptical Fourier analysis, in an osteological sample encompassing 189 lemurid mandibles (66 Eulemur, 51 Hapalemur, 22 Lemur and 50 Varecia), and compared using multivariate statistical techniques. The taxonomic value of this outline in Lemuridae was demonstrated by the existence of significant separations between the four genera studied. In particular, the mandibular morphology of Hapalemur was markedly different from that in the group Eulemur-Lemur-Varecia. Excluding Hapalemur from analysis, the distinctions between Eulemur, Lemur and Varecia were enhanced suggesting the existence of more subtle intergeneric differences in mandibular morphology. Variation in mandibular form was greatest in Hapalemur and smallest in Eulemur and Varecia (as demonstrated by the mean values of interindividual distances); variation was higher in Lemur than in Eulemur and Varecia, but not higher than in Hapalemur. This morphological diversity may be related to functional adaptation in response to particular dietary habits. The patterns of intergeneric and intrageneric shape variations of the mandible in Lemuridae presented here provide a valuable resource for the analysis of variation among living and fossil lemurids.     

基于邻接矩阵分解的肿瘤亚型特征提取方法

基于肿瘤基因表达谱的肿瘤分类是生物信息学的一个重要研究内容。传统的肿瘤信息特征提取方法大多基于信息基因选择方法,但是在筛选基因时,不可避免的会造成分类信息的流失。提出了一种基于邻接矩阵分解的肿瘤亚型特征提取方法,首先对肿瘤基因表达谱数据构造高斯权邻接矩阵,接着对邻接矩阵进行奇异值分解,最后将分解得到的正交矩阵特征行向量作为分类特征输入支持向量机进行分类识别。采用留一法对白血病两个亚型的基因表达谱数据集进行实验,实验结果证明了该方法的可行性和有效性。     

Characterization of the AfaD-like family of invasins encoded by pathogenic Escherichia coli associated with intestinal and extra-intestinal infections

The afimbrial adhesive sheath, encoded by the afa-3 gene cluster, is composed of two proteins with different roles in bacterium-HeLa cell interactions. AfaE is required for adhesion and AfaD for internalization. In this study, we found that the AfaD invasin was structurally and functionally conserved among human afa-expressing strains, independently of AfaE subtype and clinical origin of the Escherichia coli isolate. The AggB protein from enteroaggregative E. coli was also found to be an AfaD-related invasin. These data suggest that AfaD is the prototype of a family of invasins encoded by adhesion-associated operons in pathogenic E. coli.     

A comparison of the strength of biodiversity effects across multiple functions

In order to predict which ecosystem functions are most at risk from biodiversity loss, meta-analyses have generalised results from biodiversity experiments over different sites and ecosystem types. In contrast, comparing the strength of biodiversity effects across a large number of ecosystem processes measured in a single experiment permits more direct comparisons. Here, we present an analysis of 418 separate measures of 38 ecosystem processes. Overall, 45 % of processes were significantly affected by plant species richness, suggesting that, while diversity affects a large number of processes not all respond to biodiversity. We therefore compared the strength of plant diversity effects between different categories of ecosystem processes, grouping processes according to the year of measurement, their biogeochemical cycle, trophic level and compartment (above- or belowground) and according to whether they were measures of biodiversity or other ecosystem processes, biotic or abiotic and static or dynamic. Overall, and for several individual processes, we found that biodiversity effects became stronger over time. Measures of the carbon cycle were also affected more strongly by plant species richness than were the measures associated with the nitrogen cycle. Further, we found greater plant species richness effects on measures of biodiversity than on other processes. The differential effects of plant diversity on the various types of ecosystem processes indicate that future research and political effort should shift from a general debate about whether biodiversity loss impairs ecosystem functions to focussing on the specific functions of interest and ways to preserve them individually or in combination.     

New targets of Arabidopsis thioredoxins revealed by proteomic analysis

Proteomics was used to search for putative thioredoxin (TRX) targets in leaves of the model plant, Arabidopsis thaliana. About forty different proteins have been found to be reduced by TRX, after TRX itself has been specifically reduced by its NADPH-dependent reductase. Twenty-one of the identified proteins were already known or recently proposed to be TRX-dependent and nineteen of the proteins were new potential targets. The identified proteins are involved in a wide variety of processes, including the Calvin cycle, metabolism, photosynthesis, folding, defense against oxidative stress and amino acid synthesis. Two proteins from the glycine cleavage complex were also identified as putative TRX targets, and a new role can be postulated in leaves for TRX in defense against herbivores and/or pathogens.     

An alternate sucrose binding mode in the E203Q Arabidopsis invertase mutant: an X-ray crystallography and docking study

In the present study, we report on the X-ray crystallographic structure of a GH32 invertase mutant, (i.e., the Arabidopsis thaliana cell-wall invertase 1-E203Q, AtcwINV1-mutant) in complex with sucrose. This structure was solved to reveal the features of sugar binding in the catalytic pocket. However, as demonstrated by the X-ray structure the sugar binding and the catalytic pocket arrangement is significantly altered as compared with what was expected based on previous X-ray structures on GH-J clan enzymes. We performed a series of docking and molecular dynamics simulations on various derivatives of AtcwINV1 to reveal the reasons behind this modified sugar binding. Our results demonstrate that the E203Q mutation introduced into the catalytic pocket triggers conformational changes that alter the wild type substrate binding. In addition, this study also reveals the putative productive sucrose binding modus in the wild type enzyme.