K-OPLS package: Kernel-based orthogonal projections to latent structures for prediction and interpretation in feature space

Background  

Kernel-based classification and regression methods have been successfully applied to modelling a wide variety of biological data. The Kernel-based Orthogonal Projections to Latent Structures (K-OPLS) method offers unique properties facilitating separate modelling of predictive variation and structured noise in the feature space. While providing prediction results similar to other kernel-based methods, K-OPLS features enhanced interpretational capabilities; allowing detection of unanticipated systematic variation in the data such as instrumental drift, batch variability or unexpected biological variation.     

Proliferation of Ewing sarcoma cell lines is suppressed by the receptor tyrosine kinase inhibitors gefitinib and vandetanib

Background  

Tyrosine kinase inhibitors (TKIs) have gained much attention in recent years as targeted agents for the treatment of a wide range of human cancers. We have investigated the effect of the TKIs gefitinib and vandetanib on tumor cell lines derived from Ewing sarcoma, a highly malignant tumor affecting bone and soft tissue in children and young adults. Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase activity (EGFR) and vandetanib selectively targets vascular endothelial growth factor receptor-2 (VEGFR-2) with additional activity against VEGFR-3, EGFR and RET kinase receptors.     

Aglomerular hemipteran antennal lobes--basic neuroanatomy of a small nose

We have compared the basic organization of the primary olfactory centre, the antennal lobe (AL), in 4 hemipteran species representing the 2 major lineages in this order. The Homoptera were represented by the psyllid Trioza apicalis and its aphid relatives the grain aphid Sitobion avenae Fabricius and the rose-grain aphid Metopolophium dirhodum Walker, whereas the Heteroptera were represented by the pentatomid stink bug Euschistus heros Fabricius. The olfactory systems of psyllids and aphids are generally very small, with low numbers of afferents in comparison to other insect groups, and the smallest described so far belongs to T. apicalis, comprising less than 50 olfactory receptor neurons (ORNs). Originally, we tried to estimate numbers of olfactory glomeruli in the AL of T. apicalis, which in insects generally correspond closely to the number of different types of ORNs. Neither immunocytochemical staining nor anterograde staining of ORNs revealed any glomerular structures in the ALs of T. apicalis or the 2 aphids that were included for comparison. In contrast, the ALs of the pentatomid stink bug E. heros displayed numerous distinct and well-delineated glomeruli, showing that aglomerular ALs are not typical of all insects within the order Hemiptera. Glomeruli are hallmark features of olfactory lobes in many different phyla, and the absence of glomerular structures in psyllids and aphids appears to be unique in insects that depend on olfactory orientation.     

The relationship between homozygosity and the frequency of the most frequent allele

Homozygosity is a commonly used summary of allele-frequency distributions at polymorphic loci. Because high-frequency alleles contribute disproportionately to the homozygosity of a locus, it often occurs that most homozygotes are homozygous for the most frequent allele. To assess the relationship between homozygosity and the highest allele frequency at a locus, for a given homozygosity value, we determine the lower and upper bounds on the frequency of the most frequent allele. These bounds suggest tight constraints on the frequency of the most frequent allele as a function of homozygosity, differing by at most 14 and having an average difference of 23 - pi(2)/18 approximately 0.1184. The close connection between homozygosity and the frequency of the most frequent allele-which we illustrate using allele frequencies from human populations-has the consequence that when one of these two quantities is known, considerable information is available about the other quantity. This relationship also explains the similar performance of statistical tests of population-genetic models that rely on homozygosity and those that rely on the frequency of the most frequent allele, and it provides a basis for understanding the utility of extended homozygosity statistics in identifying haplotypes that have been elevated to high frequency as a result of positive selection.     

Conflicting selection pressures on reproductive functions and speciation in plants

Recent developments in the field of genetic divergence and speciation focus more on diversifying processes than on geographic mode of speciation (i.e. allopatric versus sympatric). Some of these new theories concern speciation driven by conflicts between the sexes. Even though it is well known that the two reproductive functions in plants can have different selective optima, sexual selection in plants is by many assumed to be weak or non-existent. Here we outline potential sexual conflicts in plants and discuss how selection pressures generated by such conflicts may influence genetic divergence. There is opportunity for conflicting selection pressures between individuals, such as manipulative pollen traits that enhance male reproductive success at the expense of the female reproductive function. Within individual plants, fitness of the male function (pollen export) and fitness of the female function (pollen import) may be optimised by different traits, leading to conflicting selection pressures in relation to pollen transfer. This may affect selection for floral specialisation versus floral generalisation in animal-pollinated species. We believe that selection pressures generated by sexual conflict need to be appreciated in order to fully understand microevolutionary processes which may lead to genetic divergence and speciation in plants.     

ScFv Antibody-induced Translocation of Cell-surface Heparan Sulfate Proteoglycan to Endocytic Vesicles: EVIDENCE FOR HEPARAN SULFATE EPITOPE SPECIFICITY AND ROLE OF BOTH SYNDECAN AND GLYPICAN*

Cellular uptake of several viruses and polybasic macromolecules requires the expression of cell-surface heparan sulfate proteoglycan (HSPG) through as yet ill defined mechanisms. We unexpectedly found that among several cell-surface-binding single chain variable fragment (scFv) anti-HS antibody (αHS) clones, only one, AO4B08, efficiently translocated macromolecular cargo to intracellular vesicles through induction of HSPG endocytosis. Interestingly, AO4B08-induced PG internalization was strictly dependent on HS 2-O-sulfation and appeared independent of intact N-sulfation. AO4B08 and human immunodeficiency virus (HIV)-Tat, i.e. a well known cell-penetrating peptide, were shown to compete for the internalizing PG population. To obtain a more detailed characterization of this pathway, we have developed a procedure for the isolation of endocytic vesicles by conjugating AO4B08 with superparamagnetic nanoparticles. [³⁵S]sulfate-labeled HSPG was found to accumulate in isolated, AO4B08-containing vesicles, providing the first biochemical evidence for intact HSPG co-internalization with its ligand. Further analysis revealed the existence of both syndecan, i.e. a transmembrane HSPG, and glycosyl-phosphatidyl-inositol-anchored glypican in purified vesicles. Importantly, internalized syndecan and glypican were found to co-localize in AO4B08-containing vesicles. Our data establish HSPGs as true internalizing receptors of macromolecular cargo and indicate that the sorting of cell-surface HSPG to endocytic vesicles is determined by a specific HS epitope that can be carried by both syndecan and glypican core protein.     

Insect Colonisation of Fruiting Bodies of the Wood-decaying Fungus Fomitopsis pinicola at Different Distances from an Old-growth Forest

We studied the colonisation rate of insects inhabiting fruiting bodies of the wood-decaying fungus Fomitopsis pinicola both within and at different distances (up to 1610 m) from an old-growth forest reserve. The colonisation rate of most species was not affected by the distance from the reserve, and none of the species were affected by the size of local sources of fruiting bodies in the managed forest. We suggest that many insect species inhabiting fruiting bodies of wood-decaying fungi can colonise fruiting bodies at a high enough rate to persist in managed forests of Fennoscandia. However, the colonisation rates of the fungivorous beetle Cis quadridens and the predatory fly Medetera apicalis were negatively affected by distance from the reserve. Cis quadridens is rare in many managed forests, but often quite common at sites with high substrate densities. The rarity of this species may therefore be due to weak ability to colonize distant patches. The same may also be true for M. apicalis, but less is known about the biology of this species. Medetera apicalis was the most common insect predator in the old-growth forest, but it was rare at the largest distances from it in the managed forest. Therefore, it seems likely that the overall pressure from natural enemies significantly declined with distance from the reserve.     

Climate warming and heat waves affect reproductive strategies and interactions between submerged macrophytes

Extreme climatic events, such as heat waves, are predicted to increase in frequency and intensity during the next hundred years, which may accelerate shifts in hydrological regimes and submerged macrophyte composition in freshwater ecosystems. Since macrophytes are profound components of aquatic systems, predicting their response to extreme climatic events is crucial for implementation of climate change adaptation strategies. We therefore performed an experiment in 24 outdoor enclosures (400 L) separating the impact of a 4 °C increase in mean temperature with the same increase, that is the same total amount of energy input, but resembling a climate scenario with extreme variability, oscillating between 0 °C and 8 °C above present conditions. We show that at the moderate nutrient conditions provided in our study, neither an increase in mean temperature nor heat waves lead to a shift from a plant‐dominated to an algal‐dominated system. Instead, we show that species‐specific responses to climate change among submerged macrophytes may critically influence species composition and thereby ecosystem functioning. Our results also imply that more fluctuating temperatures affect the number of flowers produced per plant leading to less sexual reproduction. Our findings therefore suggest that predicted alterations in climate regimes may influence both plant interactions and reproductive strategies, which have the potential to inflict changes in biodiversity, community structure and ecosystem functioning.