A comparison of univariate and multivariate gene selection techniques for classification of cancer datasets

Background  

Gene selection is an important step when building predictors of disease state based on gene expression data. Gene selection generally improves performance and identifies a relevant subset of genes. Many univariate and multivariate gene selection approaches have been proposed. Frequently the claim is made that genes are co-regulated (due to pathway dependencies) and that multivariate approaches are therefore per definition more desirable than univariate selection approaches. Based on the published performances of all these approaches a fair comparison of the available results can not be made. This mainly stems from two factors. First, the results are often biased, since the validation set is in one way or another involved in training the predictor, resulting in optimistically biased performance estimates. Second, the published results are often based on a small number of relatively simple datasets. Consequently no generally applicable conclusions can be drawn.     

Light meromyosin paracrystal formation

Studies of paracrystal formation by column purified light meromyosin (LMM) prepared in a variety of ways led to the following conclusions: (a) different portions of the myosin rod may be coded for different stagger relationships. This was concluded from observations that paracrystals with different axial repeat periodicities could be obtained either with LMM framents of different lengths prepared with the same enzyme, or with LMM fragments of identical lengths but prepared with different enzymes. (b) Paracrystals with a 14-nm axial repeat periodicity are most likely formed by the aggregation of sheets with a 44-nm axial repeat within the sheets which are staggered by 14 nm. All of the axial repeat patterns expected from one sheet or aggregates of more than one sheet, on this basis, were observed in the same electron micrograph. (c) C-protein binding probably occurs preferentially to LMM molecules related in some specific way. This was concluded from the observation that the same axial repeat pattern was obtained in paracrystals formed from different LMM preparations in the presence of C-protein, regardless of differences in the axial repeat obtained in the absence of C-protein. (d) Nucleic acid is responsible for the 43-nm axial repeat patterns observed in paracrystals formed by the ethanol-resistant fraction of LMM. In the absence of nuclei acid, paracrystals with a 14nm axial repeat are obtained. (e) The 43-nm axial repeat pattern observed with the ethanol-resistant fraction of LMM is different for LMM preparations obtained by trypsin and papain digestions.     

Assessment of genetic and pheromonal diversity of the Cydia strobilella species complex (Lepidoptera: Tortricidae)

Combining pheromone trapping and genetic analyses can be useful when trying to resolve complexes of closely related insect taxa that are difficult to distinguish based on morphological characters. Nearctic and Palearctic populations of the spruce seed moth, Cydia strobilella L., have been considered taxonomically synonymous since 1983, but more recent work revealing distinct sex pheromones for Canadian and Swedish moths suggest that populations in the two regions belong to different species. In order to test this hypothesis, we performed field trapping using different pheromone lures at ten sites in North America, Europe and Asia, and reconstructed phylogenetic relationships among trapped moths using mitochondrial (cytochrome oxidase subunit I) and nuclear (elongation factor 1 alpha) DNA sequence data. Trapping data and tree topologies for both genes revealed distinct pherotypes in North America and Eurasia. A genetically distinct population from China was investigated further with respect to its sex pheromone. Electrophysiological data indicated that Chinese females produce a deviant ratio of the sex pheromone components (dienic acetates) compared to Swedish females. However, trapping experiments in both areas revealed a similar broad response profile in males to a wide range of acetate ratios, and these populations should be considered taxonomically synonymous. A previous suggestion of an agonistic effect on the attraction of C. strobilella males in Sweden when adding the corresponding alcohols to the binary acetate blend was also tested in Sweden as well as in China, with no observed effect on attraction of males. In conclusion, our study demonstrates the great potential of using pheromone trapping as a tool for identification and delimitation of taxa within cryptic species complexes. Based on our data, Nearctic and Palearctic populations of C. strobilella should be considered different species, and C. youngana Kearfott stat. rev. is resurrected here as valid name for North American populations, which was the case before the revision in 1983.     

Antiangiogenic properties of Koetjapic acid, a natural triterpene isolated from Sandoricum koetjaoe Merr

Background

Angiogenesis, the formation of new blood vessels, has become an important target in cancer therapy. Angiogenesis plays an important role in tumor growth and metastasis. Koetjapic acid (KA) is a seco-A-ring oleanene triterpene isolated from S. koetjape. The solvent extract of this plant species was shown previously to have strong antiangiogenic activity; however the active ingredient(s) that conferred the biological activity and the mode of action was not established. Given the high concentration of KA in S. koetjape, an attempt has been made in this study to investigate the antiangiogenic properties of KA.

Results

Treatment with 10-50 μg/ml KA resulted in dose dependent inhibition of new blood vessels growth in ex vivo rat aortic ring assay. KA was found to be non-cytotoxic against HUVECs with IC₅₀ 40.97 ± 0.37 μg/ml. KA inhibited major angiogenesis process steps, endothelial cell migration and differentiation as well as VEGF expression.

Conclusions

The non-cytotoxic compound, KA, may be a potent antiangiogenic agent; its activity may be attributed to inhibition of endothelial cells migration and differentiation as well VEGF suppression.     

濒危帽贝铁锈笠螺的活动节律和采食行为的初步观察

铁锈笠螺是地中海最濒危的海洋无脊椎动物,对其生物学知之甚少,缺少对其活动节律和采食行为的了解。使用环氧树脂Eporai1127(原位标记了20个不同外壳长度的个体,并在每个外壳上标有不同的数字,作者在白昼或黑夜的高潮和低潮期收集了有关数据。可能由于云斑厚纹蟹(Pachygrapsus marmoratus)的捕食影响,铁锈笠螺白天的活动和运动多于夜间,但铁锈笠螺采食行为似乎仅限于高潮期。此外,汹涌的海面条件诱导了铁锈笠螺的活动和运动。     

IgG4 can induce an M2-like phenotype in human monocyte-derived macrophages through FcγRI

Antibodies evoke cellular responses through the binding of their Fc region to Fc receptors, most of which contain immunoreceptor tyrosine-based activation motif domains and are thus considered “activating.” However, there is a growing appreciation of these receptors for their ability to deliver an inhibitory signal as well. We previously described one such phenomenon whereby interferon (IFN)γ signaling is inhibited by immune complex signaling through FcγRI. To understand the implications of this in the context of therapeutic antibodies, we assessed individual IgG subclasses to determine their ability to deliver this anti-inflammatory signal in monocyte-derived macrophages. Like IgG1, we found that IgG4 is fully capable of inhibiting IFNγ-mediated events. In addition, F(ab’)2 fragments that interfere with FcγRI signaling reversed this effect. For mAbs developed with either an IgG1 or an IgG4 constant region for indications where inflammation is undesirable, further examination of a potential Fc-dependent contribution to their mechanism of action is warranted.     

A cysteine-rich receptor-like kinase NCRK and a pathogen-induced protein kinase RBK1 are Rop GTPase interactors

In plants, Rop/Rac GTPases have emerged as central regulators of diverse signalling pathways in plant growth and pathogen defence. When active, they interact with a wide range of downstream effectors. Using yeast two-hybrid screening we have found three previously uncharacterized receptor-like protein kinases to be Rop GTPase-interacting molecules: a cysteine-rich receptor kinase, named NCRK, and two receptor-like cytosolic kinases from the Arabidopsis RLCK-VIb family, named RBK1 and RBK2. Uniquely for Rho-family small GTPases, plant Rop GTPases were found to interact directly with the protein kinase domains. Rop4 bound NCRK preferentially in the GTP-bound conformation as determined by flow cytometric fluorescence resonance energy transfer measurements in insect cells. The kinase RBK1 did not phosphorylate Rop4 in vitro , suggesting that the protein kinases are targets for Rop signalling. Bimolecular fluorescence complementation assays demonstrated that Rop4 interacted in vivo with NCRK and RBK1 at the plant plasma membrane. In Arabidopsis protoplasts, NCRK was hyperphosphorylated and partially co-localized with the small GTPase RabF2a in endosomes. Gene expression analysis indicated that the single-copy NCRK gene was relatively upregulated in vasculature, especially in developing tracheary elements. The seven Arabidopsis RLCK-VIb genes are ubiquitously expressed in plant development, and highly so in pollen, as in case of RBK2 . We show that the developmental context of RBK1 gene expression is predominantly associated with vasculature and is also locally upregulated in leaves exposed to Phytophthora infestans and Botrytis cinerea pathogens. Our data indicate the existence of cross-talk between Rop GTPases and specific receptor-like kinases through direct molecular interaction.