A review of malaria vaccine clinical projects based on the WHO rainbow table

Development and Phase 3 testing of the most advanced malaria vaccine, RTS,S/AS01, indicates that malaria vaccine R&D is moving into a new phase. Field trials of several research malaria vaccines have also confirmed that it is possible to impact the host-parasite relationship through vaccine-induced immune responses to multiple antigenic targets using different platforms. Other approaches have been appropriately tested but turned out to be disappointing after clinical evaluation. As the malaria community considers the potential role of a first-generation malaria vaccine in malaria control efforts, it is an apposite time to carefully document terminated and ongoing malaria vaccine research projects so that lessons learned can be applied to increase the chances of success for second-generation malaria vaccines over the next 10 years. The most comprehensive resource of malaria vaccine projects is a spreadsheet compiled by WHO thanks to the input from funding agencies, sponsors and investigators worldwide. This spreadsheet, available from WHO's website, is known as "the rainbow table". By summarizing the published and some unpublished information available for each project on the rainbow table, the most comprehensive review of malaria vaccine projects to be published in the last several years is provided below.     

Differences in functional traits among distinct populations of the plant invader Bunias orientalis

入侵植物疣果匙荠不同种群间的功能性状差异 特定环境下植物扩大领域入侵到其他区域时,其功能性状会发生改变。原产地环境已形成植物原有功能性状,当植物居住环境发生改变时,其功能性状亦会随之改变。本文旨在探讨居于常见条件与原产地气候条件的原状态、入侵状态、归化状态下不同疣果匙荠(Bunias orientalis)种群间的性状变异。自8个国家收集了12种疣果匙荠种子(每种状态各4种),将其种植于标准条件下的同质园中,并比较不同状态不同种类的物候、生长、繁殖等功能性状变化。 研究结果表明, 物候不因植物状态而异,但某些原产于常年低温地区的原状态植物并未开花。相比原状态植物,入侵状态植物的叶子更多,这表明了其在积累植被生物量上的活力。短角果的数量和质量,以及其他的生长性状在不同的状态间没有差异,但在不同种群间存在差异。一些功能性状的变异可能是由于原生地对当地条件的长期适应和遗传多样性所致,而其他环境因素在新环境下的差异可能导致了较高的性状变异。     

Uncoupling of Elastin Complex Receptor during In Vitro Aging Is Related to Modifications in Its Intrinsic Sialidase Activity and the Subsequent Lactosylceramide Production

Degradation of elastin leads to the production of elastin-derived peptides (EDP), which exhibit several biological effects, such as cell proliferation or protease secretion. Binding of EDP on the elastin receptor complex (ERC) triggers lactosylceramide (LacCer) production and ERK1/2 activation following ERC Neu-1 subunit activation. The ability for ERC to transduce signals is lost during aging, but the mechanism involved is still unknown. In this study, we characterized an in vitro model of aging by subculturing human dermal fibroblasts. This model was used to understand the loss of EDP biological activities during aging. Our results show that ERC uncoupling does not rely on Neu-1 or PPCA mRNA or protein level changes. Furthermore, we observe that the membrane targeting of these subunits is not affected with aging. However, we evidence that Neu-1 activity and LacCer production are altered. Basal Neu-1 catalytic activity is strongly increased in aged cells. Consequently, EDP fail to promote Neu-1 catalytic activity and LacCer production in these cells. In conclusion, we propose, for the first time, an explanation for ERC uncoupling based on the age-related alterations of Neu-1 activity and LacCer production that may explain the loss of EDP-mediated effects occurring during aging.     

Prediction accuracies for growth and wood attributes of interior spruce in space using genotyping-by-sequencing

Background

Genomic selection (GS) in forestry can substantially reduce the length of breeding cycle and increase gain per unit time through early selection and greater selection intensity, particularly for traits of low heritability and late expression. Affordable next-generation sequencing technologies made it possible to genotype large numbers of trees at a reasonable cost.

Results

Genotyping-by-sequencing was used to genotype 1,126 Interior spruce trees representing 25 open-pollinated families planted over three sites in British Columbia, Canada. Four imputation algorithms were compared (mean value (MI), singular value decomposition (SVD), expectation maximization (EM), and a newly derived, family-based k-nearest neighbor (kNN-Fam)). Trees were phenotyped for several yield and wood attributes. Single- and multi-site GS prediction models were developed using the Ridge Regression Best Linear Unbiased Predictor (RR-BLUP) and the Generalized Ridge Regression (GRR) to test different assumption about trait architecture. Finally, using PCA, multi-trait GS prediction models were developed. The EM and kNN-Fam imputation methods were superior for 30 and 60% missing data, respectively. The RR-BLUP GS prediction model produced better accuracies than the GRR indicating that the genetic architecture for these traits is complex. GS prediction accuracies for multi-site were high and better than those of single-sites while multi-site predictability produced the lowest accuracies reflecting type-b genetic correlations and deemed unreliable. The incorporation of genomic information in quantitative genetics analyses produced more realistic heritability estimates as half-sib pedigree tended to inflate the additive genetic variance and subsequently both heritability and gain estimates. Principle component scores as representatives of multi-trait GS prediction models produced surprising results where negatively correlated traits could be concurrently selected for using PCA2 and PCA3.

Conclusions

The application of GS to open-pollinated family testing, the simplest form of tree improvement evaluation methods, was proven to be effective. Prediction accuracies obtained for all traits greatly support the integration of GS in tree breeding. While the within-site GS prediction accuracies were high, the results clearly indicate that single-site GS models ability to predict other sites are unreliable supporting the utilization of multi-site approach. Principle component scores provided an opportunity for the concurrent selection of traits with different phenotypic optima.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1597-y) contains supplementary material, which is available to authorized users.     

Foraging and pollination behaviour of Xylocopa calens Lepeletier (Hymenoptera: Apidae) on Phaseolus coccineus L. (Fabaceae) flowers at Yaounde (Cameroon)

To evaluate impact of carpenter bee, Xylocopa calens, on pod and seed set of Phaseolus coccineus, its foraging and pollinating activities were studied in Yaounde, for two seasons (May–July 2008 and April–June 2009). Observations were made on 40 inflorescences per treatment. The treatments included unlimited floral access by all visitors, bagged flowers to deny all visits, and limited visits by X. calens only. In addition, all flower visitors were recorded. The carpenter bee's seasonal rhythm of activity, its foraging behavior on flowers, its pollination efficiency, the fructification rate and the number of seeds per pod were recorded. Individuals from 16 species of insects were recorded visiting flowers of P. coccineus in the 2 years. Xylocopa calens was the most frequent, followed by Chalicodoma cincta cincta and Apis mellifera. Apart from bees, wasps were also recorded as likely predators. Xylocopa calens mainly foraged for nectar resources. The mean foraging speed was 9.62 flowers/min. Flowers visited by X. calens had higher fruiting rate compared with others, while those bagged had the lowest. In addition, seed formation was higher in X. calens‐visited flowers compared with all others. The results show that this crop experiences pollination deficit even under normal circumstances, considering that flowers visited by X. calens had higher yields compared with those under unlimited access by all visitors. The fruiting rate, the number of seeds/pod and the percentage of normal seeds of unprotected inflorescences were significantly higher than those of inflorescences protected from insects. X. calens foraging resulted in a significant increment of the fruiting rate by 25.80%, as well as the number of seeds/pod by 14.97% and the percentage of normal seeds by 27.75% in 2008 and 18.39% in 2009. Conservation of X. calens nests close to P. coccineus fields could be recommended to improve pod and seed production in the region.     

The crystal structure of the mycobacterial trehalose monomycolate transport factor A,TtfA, reveals an atypical fold

Trehalose monomycolate (TMM) represents an essential element of the mycobacterial envelope. While synthesized in the cytoplasm, TMM is transported across the inner membrane by MmpL3 but, little is known regarding the MmpL3 partners involved in this process. Recently, the TMM transport factor A (TtfA) was found to form a complex with MmpL3 and to participate in TMM transport, although its biological role remains to be established. Herein, we report the crystal structure of the Mycobacterium smegmatis TtfA core domain. The phylogenetic distribution of TtfA homologues in non-mycolate containing bacteria suggests that TtfA may exert additional functions.     

RNF213, a new nuclear marker for acanthomorph phylogeny

We show that RNF213 is a nuclear gene suitable for investigating large scale acanthomorph teleosteans interrelationships. The gene recovers many clades already found by several independent studies of acanthomorph molecular phylogenetics and considered as reliable. Moreover, we performed phylogenetic analyses of three other independent nuclear markers, first separately and then of all possible combinations (Dettaï, A., Lecointre, G., 2004. In search of nothothenioid (Teleostei) relatives. Antarct. Sci. 16 (1), 71–85. URL http://dx.doi.org/10.1017/S0954102004) of the four genes. This was coupled with an assessment of the reliability of clades using the repetition index of Li and Lecointre (Li, B., Lecointre, G., 2008. Formalizing reliability in the taxonomic congruence approach. Article accepted by Zoologica Scripta. URL http://dx.doi.org/10.1111/j.1463-6409.2008.00361.x). This index was improved here to handle the incomplete taxonomic overlap among datasets. The results lead to the identification of new reliable clades within the ‘acanthomorph bush’. Within a clade containing the Atherinomorpha, the Mugiloidei, the Plesiopidae, the Blennioidei, the Gobiesocoidei, the Cichlidae and the Pomacentridae, the Plesiopidae is the sister-group of the Mugiloidei. The Apogonidae are closely related to the Gobioidei. A clade named ‘H’ grouping a number of families close to stromateids and scombrids (Stromateidae, Scombridae, Trichiuridae, Chiasmodontidae, Nomeidae, Bramidae, Centrolophidae) is related to another clade named ‘E’ (Aulostomidae, Macrorhamphosidae, Dactylopteridae). The Sciaenidae is closely related to the Haemulidae. Within clade ‘X’ (Dettaï, A., Lecointre, G., 2004. In search of nothothenioid (Teleostei) relatives. Antarct. Sci. 16 (1), 71–85. URL http://dx.doi.org/10.1017/S0954102004), the Cottoidei, the Zoarcoidei, the Gasterosteidae, the Triglidae, the Scorpaenidae, the Sebastidae, the Synanceiidae, and the Congiopodidae form a clade. Within clade ‘L’ (Chen, W.-J., Bonillo, C., Lecointre, G., 2003. Repeatability of clades as a criterion of reliability: a case study for molecular phylogeny of Acanthomorpha (Teleostei) with larger number of taxa. Mol. Phylogenet. Evol. 26, 262–288; Dettaï, A., Lecointre, G., 2004. In search of nothothenioid (Teleostei) relatives. Antarct. Sci. 16 (1), 71–85. URL http://dx.doi.org/10.1017/S0954102004) grouping carangoids with flatfishes and other families (Centropomidae, Menidae, Sphyraenidae, Polynemidae, Echeneidae, Toxotidae, Xiphiidae), carangids are the stem-group of echeneids and coryphaenids, and sphyraenids are the sister-group to the Carangoidei. The Howellidae, the Epigonidae and the Lateolabracidae are closely related. We propose names for most of the clades repeatedly found in acanthomorph phylogenetic studies of various teams of the past decade.     

SuperTRI: A new approach based on branch support analyses of multiple independent data sets for assessing reliability of phylogenetic inferences

Supermatrix and supertree are two methods for constructing a phylogenetic tree by using multiple data sets. However, these methods are not a panacea, as conflicting signals between data sets can lead to misinterpret the evolutionary history of taxa. In particular, the supermatrix approach is expected to be misleading if the species-tree signal is not dominant after the combination of the data sets. Moreover, most current supertree methods suffer from two limitations: (i) they ignore or misinterpret secondary (non-dominant) phylogenetic signals of the different data sets; and (ii) the logical basis of node robustness measures is unclear.To overcome these limitations, we propose a new approach, called SuperTRI, which is based on the branch support analyses of the independent data sets, and where the reliability of the nodes is assessed using three measures: the supertree Bootstrap percentage and two other values calculated from the separate analyses: the mean branch support (mean Bootstrap percentage or mean posterior probability) and the reproducibility index.The SuperTRI approach is tested on a data matrix including seven genes for 82 taxa of the family Bovidae (Mammalia, Ruminantia), and the results are compared to those found with the supermatrix approach. The phylogenetic analyses of the supermatrix and independent data sets were done using four methods of tree reconstruction: Bayesian inference, maximum likelihood, and unweighted and weighted maximum parsimony. The results indicate, firstly, that the SuperTRI approach shows less sensitivity to the four phylogenetic methods, secondly, that it is more accurate to interpret the relationships among taxa, and thirdly, that interesting conclusions on introgression and radiation can be drawn from the comparisons between SuperTRI and supermatrix analyses. To cite this article: A. Ropiquet et al., C. R. Biologies 332 (2009).