Neural stem cells and neuro‐oncology: Quo vadis?

Conventionally, gliomas are assumed to arise via transformation of an intraparenchymal glial cell that forms a mass that then expands centrifugally, eventually invading surrounding tissues. We propose an alternative model in which gliomas arise via initiation and promotion of cells within the brain's subependymal layer or subventricular zone, the source of a recently characterized pool of neural cells with the properties of self-renewal and multipotentiality (i.e., stem cells) that persists into adulthood. In this model, the particular histological subtype of glioma would represent the effects of temporal and spatial environmental influences rather than the particular cell of origin and the disease's centrifugal point would be the subependymal layer. The implications of such a model are discussed.     

Raf: the holy grail of Ras biology?

Ras proteins regulate cell growth and differentiation, and their mutation plays a major, direct role in causing human cancer. For years, their precise function has been a mystery. One of the pathways Ras controls has recently been identified. It consists of a cascade of kinases (Raf, MEK and MAP kinases) that transmits signals from the plasma membrane to the nucleus. The role of Ras is remarkably simple: it recruits Raf from the cytoplasm to the plasma membrane. Once in the membrane, Raf is activated and the kinase cascade is initiated. Is this the whole story?     

The pH of the Plasmodium falciparum digestive vacuole: holy grail or dead-end trail?

The maintenance of acidic pH in the digestive vacuole of the malaria parasite is thought to be crucial to the digestion of host cell haemoglobin and the subsequent process of heme detoxification. It may also be important in the mode of action of chloroquine and in the mechanism of resistance to the drug. Obtaining a definitive measurement of digestive vacuole pH has been surprisingly difficult. Some of the techniques for the measurement of pH in acid vesicles are outlined here along with some key aspects that are specific to malaria parasites. The use of acridine orange and dextran-tagged dyes as probes for the measurement of digestive vacuole pH has proved problematic, yet some surprising findings have emerged from work with these compounds.     

Migration of red‐backed shrikes from the Iberian Peninsula: optimal or sub‐optimal detour?

The current Northern Hemisphere migration systems are believed to have arisen since the last glaciation. In many cases, birds do not migrate strait from breeding to non‐breeding areas but fly via a detour. All western European populations of red‐backed shrikes Lanius collurio are assumed to reach their southern African wintering grounds detouring via southeast Europe. Based on theoretical considerations under an optimality framework this detour is apparently optimal. Here, we use individual geolocator data on red‐backed shrikes breeding in Spain to show that these birds do indeed detour via southeast Europe en route to southern Africa where they join other European populations of red‐backed shrikes and return via a similar route in spring. Disregarding potential wind assistance, the routes taken for the tracked birds in autumn were not optimal compared to crossing the barrier directly. For spring migration the situation was quite different with the detour apparently being optimal. However, when considering potential wind assistance estimated total air distances during autumn migration were overall similar and the barrier crossing shorter along the observed routes. We conclude that considering the potential benefit of wind assistance makes the route via southeast Europe likely to be less risky in autumn. However, it cannot be ruled out that other factors, such as following a historical colonisation route could still be important.     

Feeding preferences of the red‐billed oxpecker,Buphagus erythrorhynchus: a parasitic mutualist?

The oxpecker–ungulate association of sub‐Saharan Africa is an example of a complicated interspecific association subject to variation in outcome. Oxpeckers (Buphagus spp.) are unusual birds because they not only glean ticks from an array of African ungulates, but they are one of the few avian species known to wound‐feed from their living hosts. The conditions under which oxpeckers wound‐feed and the mechanisms generating variation in this association are unclear. We took a unique approach to studying the relationship by conducting a series of feeding preference experiments on twelve captive red‐billed oxpeckers (B. erythrorhynchus). We assessed how oxpecker feeding behaviour is influenced by changes in tick abundance and tick type. In cafeteria‐style experiments, oxpeckers fed equally on ticks and liquid bovine blood. In experiments using donkeys as the host animal, oxpeckers spent more time wound‐feeding when a less‐preferred tick type was available and when tick abundance was low compared to when a preferred tick type was available and when tick abundance was high. However, oxpeckers still wound‐fed even when offered a large number of the ticks they prefer. Additional experiments incorporating tick species of different stages and multiple ungulate species are necessary to fully reveal the dynamics of this association.     

In search of sports biomechanics’ holy grail: Can athlete-specific optimum sports techniques be identified?

The development of methods that can identify athlete-specific optimum sports techniques—arguably the holy grail of sports biomechanics—is one of the greatest challenges for researchers in the field. This ‘perspectives article’ critically examines, from a dynamical systems theoretical standpoint, the claim that athlete-specific optimum sports techniques can be identified through biomechanical optimisation modelling. To identify athlete-specific optimum sports techniques, dynamical systems theory suggests that a representative set of organismic constraints, along with their non-linear characteristics, needs to be identified and incorporated into the mathematical model of the athlete. However, whether the athlete will be able to adopt, and reliably reproduce, his/her predicted optimum technique will largely be dependent on his/her intrinsic dynamics. If the attractor valley corresponding to the existing technique is deep, or if the attractor valleys corresponding to the existing technique and the predicted optimum technique are in different topographical regions of the dynamic landscape, technical modifications may be challenging or impossible to reliably implement even after extended practice. The attractor layout defining the intrinsic dynamics of the athlete, therefore, needs to be determined to establish the likelihood of the predicted optimum technique being reliably attainable by the athlete. Given the limited set of organismic constraints typically used in mathematical models of athletes, combined with the methodological challenges associated with mapping the attractor layout of an athlete, it seems unlikely that athlete-specific optimum sports techniques will be identifiable through biomechanical optimisation modelling for the majority of sports skills in the near future.     

Geographical variation in the yellow‐legged gull: introgression or convergence from the herring gull?

Yellow-legged gulls Larus michahellis from the Atlantic Iberian coast exhibit some phenotypic similarities with the herring gull L. argentatus from Western Europe. To assess this phenomenon and its possible origin, we compared Mediterranean yellow-legged gulls, Atlantic Iberian yellow-legged gulls and herring gulls for several phenotypic traits (morphology, plumage), and used genetic data to determine the evolutionary history of the Atlantic Iberian yellow-legged gulls. Data from mitochondrial cytochrome b gene and microsatellite loci clearly indicate that Atlantic Iberian gulls are closely related to Mediterranean yellow-legged gulls, and do not show stronger signs of introgression with herring gulls relative to other populations of yellow-legged gulls. Atlantic Iberian yellow-legged gulls are more similar to herring gulls in body size and shape than to other yellow-legged gulls populations, but not in mantle colour and wing-tip pattern. Body size and other phenotypic and life history similarities with the herring gull ( L. argentatus argenteus ) such as voice, winter plumage and breeding phenology, previously described in several studies, might thus be interpreted as convergent characters. Within the yellow-legged gull, the high F _st-values obtained from four nuclear microsatellite loci indicate substantial population structure and reduced levels of gene flow between gull populations in Mediterranean France and Atlantic Iberia. Differences among these populations in breeding phenology and migration patterns, likely resulting from different local selection pressures, might contribute to this low level of gene flow.     

Flavonoids: True or promiscuous inhibitors of enzyme? The case of deoxyxylulose phosphate reductoisomerase

Flavonoids, due to their physical and chemical properties (among them hydrophobicity and metal chelation abilities), are potential inhibitors of the 1-deoxyxylulose 5-phosphate reductoisomerase and most of the tested flavonoids effectively inhibited its activity with encouraging IC₅₀ values in the micromolar range. The addition of 0.01% Triton X100 in the assays led however, to a dramatic decrease of the inhibition revealing that a non-specific inhibition probably takes place. Our study highlights the possibility of erroneous conclusions regarding the inhibition of enzymes by flavonoids that are able to produce aggregates in micromolar range. Therefore, the addition of a detergent in the assays prevents possible false positive hits in high throughput screenings.     

Negative density‐dependent dispersal in tsetse (Glossina spp): red flag or red herring?

A deterministic model of the distribution of tsetse flies (Glossina spp) was used to assess the extent to which the efficacy of control operations would be affected by three different modes of density dependence in per capita adult dispersal: (i) density‐independent dispersal which has been commonly adopted in previous models, (ii) positive density‐dependent dispersal which has occasionally been discussed in the tsetse literature, (iii) negative density‐dependent dispersal (NDDD). The last has recently been suggested, from genetic studies, to change the dispersal rate of tsetse by up to 200‐fold, thereby posing a severe risk for the success of tsetse control operations. Modelling outputs showed that NDDD poses no such risk, provided the mean daily dispersal of tsetse is below about 1 km, which is greater than any rate actually recorded in the field or indicated by the genetic studies. NDDD can be problematic only if tsetse disperse at rates that appear highly unlikely, or even impossible, on energetic grounds. Under some circumstances these high rates would help rather than hinder the control officer. NDDD is not necessary to explain the results of control operations, and not sufficient to explain the results of successful control programmes.     

The hemolymph proteome of the honeybee: Gel‐based or gel‐free?

The honeybee has an invaluable economic impact and is a model for studying immunity, development and social behavior. The recent sequencing and annotation of the honeybee genome facilitates the study of its hemolymph, which reflects the physiological condition and mediates immune responses. We aimed at making a proteomic reference map of honeybee hemolymph and compared gel‐free and gel‐based techniques. One hundered and four 2‐DE spots corresponding to 62 different proteins were identified. Eight identical 2‐DLC experiments resulted in the identification of 32 unique proteins. One repeat was clearly not representative for the potential of the given 2‐DLC setup. Only 27% of the identified hemolymph proteins were found by both techniques. In addition, we found proteins of three different viruses which creates possibilities for biomarker design. Future hemolymph studies will benefit from this work.     

Overcompensation by plants: Herbivore optimization or red herring?

Summary The increased growth rates, higher total biomass, and increased seed production occasionally found in grazed or clipped plants are more accurately interpreted as the results of growth at one end of a spectrum of normal plant regrowth patterns, rather than as overcompensation, herbivore-stimulated growth, plantherbivore mutualisms, or herbivore enhanced fitness. Plants experience injury from a wide variety of sources besides herbivory, including fire, wind, freezing, heat, and trampling; rapid regrowth may have been selected for by any one of the many types of physical disturbance or extreme conditions that damage plant tissues, or by a combination of all of them. Rapid plant regrowth is more likely to have evolved as a strategy to reduce the negative impacts of all types of damage than as a strategy to increase fitness following herbivory above ungrazed levels. There is no evolutionary justification and little evidence to support the idea that plant-herbivore mutualisms are likely to evolve. Neither life history theory nor recent theoretical models provide plausible explanations for the benefits of herbivory.Several assumptions underlie all discussions of the benefits of herbivory: that plant species are able to evolve a strategy of depending on herbivores to increase their productivity and fitness; that herbivores do not preferentially regraze the overcompensating plants; that resources will be sufficient for regrowth; and that being larger is always better than being smaller. None of these assumptions is necessarily correct.     

Male genes: X‐pelled or X‐cluded?

Two recent studies by Parisi et al. and Ranz et al., catalogue sex differences in gene expression across the whole genome of the fruit fly Drosophila melanogaster. Both report striking associations of sex-biased gene expression with the X chromosome. Genes with male-biased expression are depauperate on the X chromosome, whereas genes with female-biased expression show weaker evidence of being in excess. A number of evolutionary hypotheses for the expulsion or exclusion of male-biased genes from the X chromosome have been suggested. None is entirely consistent with the available evidence.     

Trophic control of mesopredators in terrestrial ecosystems: top‐down or bottom‐up?

It has been argued that widespread extinctions of top predators have changed terrestrial ecosystem structures through mesopredator release, where increased abundances of medium-sized predators have detrimental effects on prey communities. This top-down concept has received much attention within conservation biology, but few studies have demonstrated the phenomenon. The concept has been criticized since alternative explanations involving bottom-up impacts from bioclimatic effects on ecosystem productivity and from anthropogenic habitat change are rarely considered. We analyse the response of a mesopredator (the red fox) to declines in top predators (wolf and Eurasian lynx) and agricultural expansion over 90 years in Sweden, taking bioclimatic effects into account. We show a top-down mesopredator release effect, but ecosystem productivity determined its strength. The impacts of agricultural activity were mediated by their effects on top predator populations. Thus, both top-down and bottom-up processes need to be understood for effective preservation of biodiversity in anthropogenically transformed ecosystems.     

Correlation and studies of habitat selection: problem,red herring or opportunity?

With the advent of new technologies, animal locations are being collected at ever finer spatio-temporal scales. We review analytical methods for dealing with correlated data in the context of resource selection, including post hoc variance inflation techniques, ‘two-stage’ approaches based on models fit to each individual, generalized estimating equations and hierarchical mixed-effects models. These methods are applicable to a wide range of correlated data problems, but can be difficult to apply and remain especially challenging for use–availability sampling designs because the correlation structure for combinations of used and available points are not likely to follow common parametric forms. We also review emerging approaches to studying habitat selection that use fine-scale temporal data to arrive at biologically based definitions of available habitat, while naturally accounting for autocorrelation by modelling animal movement between telemetry locations. Sophisticated analyses that explicitly model correlation rather than consider it a nuisance, like mixed effects and state-space models, offer potentially novel insights into the process of resource selection, but additional work is needed to make them more generally applicable to large datasets based on the use–availability designs. Until then, variance inflation techniques and two-stage approaches should offer pragmatic and flexible approaches to modelling correlated data.     

A skeleton‐less sponge of Caribbean mangroves: invasive or undescribed?

Recent surveys of sponges occurring on Caribbean mangrove roots demonstrated the presence of a skeleton‐less sponge of the genus Halisarca, very similar in its morphology to the temperate H. dujardinii. This study evaluated the possibility that the mangrove sponge was actually H. dujardinii that had been introduced into the Caribbean mangroves. Detailed histology revealed differences between the mangrove sponge and H. dujardinii in cuticle thickness, and in characteristics of the choanocytes, spherulous, and granular cells. Also, phylogenetic reconstruction and genetic distance estimates based on cytochrome oxidase I gene sequences clearly differentiated the mangrove Halisarca sp. from H. dujardinii. Therefore, we rejected the hypothesis of the invasion of H. dujardinii, recognizing instead the mangrove Halisarca sp. as a new species and naming it H. restingaensis sp. nov. Estimated levels of genetic variation in the ribosomal internal transcribed spacers indicated that populations of H. restingaensis sp. nov. are highly differentiated between Venezuela and Panama (F_st=0.71). This level of population differentiation is consistent with the short larval competence period that is common in members of the genus Halisarca.     

Analysis of cause of death: Competing risks or progressive illness‐death model?

The analysis of cause of death is increasingly becoming a topic in oncology. It is usually distinguished between disease‐related and disease‐unrelated death. A frequently used approach is to define death as disease‐related when a progression to advanced phases has occurred before, otherwise as disease‐unrelated. The data are often analyzed as competing risks, while a progressive illness‐death model might in fact describe the situation more precisely. In this study, we investigated under which circumstances this misspecification leads to biased estimations of the state occupation probabilities. We simulated data according to the progressive illness‐death model in various settings, analyzed them with a competing risks model and with a progressive illness‐death model and compared them to the true state occupation probabilities. Censoring was either added independently of the status or based on the patients' status. The simulations showed that the censoring mechanism was decisive for the bias while neither the progression hazard nor the Markov property was important. Further, we found a slightly increased standard deviation for the competing risk estimator when censoring was independent of the patients' status. For illustration, both methods were applied to two practical examples of chronic myeloid leukemia (CML): one randomized controlled trial and one registry data set. While in the first case both estimators yielded almost identical results, in the latter case, visible differences were found between both methods.