Simulation modelling in landscape genetics: on the need to go further

With the emergence of landscape genetics, the basic assumptions and predictions of classical population genetic theories are being re‐evaluated to account for more complex spatial and temporal dynamics. Within the last decade, there has been an exponential increase in such landscape genetic studies ( Holderegger & Wagner 2006 ; Storfer et al. 2010 ), and both methodology and underlying concepts of the field are under rapid and constant development. A number of major innovations and a high level of originality are required to fully merge existing population genetic theory with landscape ecology and to develop novel statistical approaches for measuring and predicting genetic patterns. The importance of simulation studies for this specific research has been emphasized in a number of recent articles (e.g., Balkenhol et al. 2009a ; Epperson et al. 2010 ). Indeed, many of the major questions in landscape genetics require the development and application of sophisticated simulation tools to explore gene flow, genetic drift, mutation and natural selection in landscapes with a wide range of spatial and temporal complexities. In this issue, Jaquiéry et al. (2011) provide an excellent example of such a simulation study for landscape genetics. Using a metapopulation simulation design and a novel ‘scale of phenomena’ approach, Jaquiéry et al. (2011) demonstrate the utility and limitations of genetic distances for inferring landscape effects on effective dispersal.     

The Crystal Structure of Cancer Osaka Thyroid Kinase Reveals an Unexpected Kinase Domain Fold

Macrophages are important cellular effectors in innate immune responses and play a major role in autoimmune diseases such as rheumatoid arthritis. Cancer Osaka thyroid (COT) kinase, also known as mitogen-activated protein kinase kinase kinase 8 (MAP3K8) and tumor progression locus 2 (Tpl-2), is a serine-threonine (ST) kinase and is a key regulator in the production of pro-inflammatory cytokines in macrophages. Due to its pivotal role in immune biology, COT kinase has been identified as an attractive target for pharmaceutical research that is directed at the discovery of orally available, selective, and potent inhibitors for the treatment of autoimmune disorders and cancer. The production of monomeric, recombinant COT kinase has proven to be very difficult, and issues with solubility and stability of the enzyme have hampered the discovery and optimization of potent and selective inhibitors. We developed a protocol for the production of recombinant human COT kinase that yields pure and highly active enzyme in sufficient yields for biochemical and structural studies. The quality of the enzyme allowed us to establish a robust in vitro phosphorylation assay for the efficient biochemical characterization of COT kinase inhibitors and to determine the x-ray co-crystal structures of the COT kinase domain in complex with two ATP-binding site inhibitors. The structures presented in this study reveal two distinct ligand binding modes and a unique kinase domain architecture that has not been observed previously. The structurally versatile active site significantly impacts the design of potent, low molecular weight COT kinase inhibitors.     

Volatiles of Geranium purpureum Vill. and Geranium phaeum L.: Chemotaxonomy of Balkan Geranium and Erodium Species (Geraniaceae)

The essential oils obtained by hydrodistillation of Geranium purpureum and G. phaeum were characterized by GC‐FID and GC/MS analyses (the former for the first time in general). In total, 154 constituents were identified, accounting for 89.0–95.8% of the detected GC peak areas. The investigated essential oils consisted mainly of fatty acids and fatty‐acid‐derived compounds (45.4–81.3%), with hexadecanoic acid and (E)‐phytol as the major components. The chemotaxonomic significance of the variations in the essential‐oil composition/production of the presently and previously investigated Geranium and highly related Erodium taxa from Serbia and Macedonia was assessed by multivariate statistical analyses. The main conclusions drawn from the high chemical similarity of the two genera, visible from the obtained dendrograms and biplots, confirm the close phylogenetic relationship between the investigated Geranium and Erodium taxa, i.e., that there is no great intergeneric oil‐composition variability. Changes in the composition and production of essential oils of the herein investigated taxa and 60 other randomly chosen species belonging to different plant genera were also statistically analyzed. The results put forward pro arguments for the oil‐yield–oil‐composition correlation hypothesis.     

Does the protected area network preserve bird species of conservation concern in a rapidly changing climate?

Species ranges are expected to move polewards following the changing climate, which poses novel challenges to the protected area network, particularly at northern latitudes. Here we study how well protected areas are likely to sustain populations of birds of conservation concern under a changing climate in northern Europe, in Finland. We fitted bioclimatic envelope models generated for 100 bird species to climate scenario data for the years 2051–2080 and three alternative emission scenarios in a 10-km grid system to predict changes in the species probability of occurrence. We related the projected changes in the climatic suitability to the amount of protected preferred habitat for the study species in the 10-km grid cells, and based on the cover of four main CORINE Land Cover classes in each conservation area in Finland. The probability of occurrence of all species (except marshland birds) decreased according to all scenarios, the decline being greatest in southern and smallest in northern boreal zones. This decline was slightly greater in unprotected than in protected areas for species of forests, mires and mountain habitats. The climatically suitable areas for the species were predicted to shift northwards, but the potential gain of southern species of conservation concern appears not to compensate for the loss of northern species. Thus, a representative protected area network is needed in all boreal zones. Overall, our results show that species-specific habitat preferences and habitat availability should be taken into account when assessing the efficiency of a protected area network in a changing climate.     

Synthesis and Spectral Characterization of Asymmetric Azines Containing a Coumarin Moiety: The Discovery of New Antimicrobial and Antioxidant Agents

Nine unsymmetrical azines containing a coumarin moiety were prepared by the reaction of the hydrazone of 4‐hydroxy‐3‐acetylcoumarin with differently substituted aromatic aldehydes. The azines were fully spectrally characterized, including a complete assignment of ¹H‐ and ¹³C‐NMR resonances, and were assessed for their acute toxicities in the Artemia salina model. Their free radical scavenging activities were tested in the DPPH assay, and in vitro antimicrobial activities were determined against seven bacterial and two fungal strains. The azines containing a p‐hydroxyphenyl group were shown to be the most effective antimicrobial agents, and in the case of resistant strains of Staphylococcus aureus and Acinetobacter baumannii, the activity was comparable to that of chloramphenicol. The derivative having a 3,5‐dimethoxy‐4‐hydroxyphenyl group exhibited pronounced antioxidant power reacting rapidly and in 1 : 1 mol ratio with the DPPH radical.     

Reduced Gaze Following and Attention to Heads when Viewing a "Live" Social Scene

Social stimuli are known to both attract and direct our attention, but most research on social attention has been conducted in highly controlled laboratory settings lacking in social context. This study examined the role of social context on viewing behaviour of participants whilst they watched a dynamic social scene, under three different conditions. In two social groups, participants believed they were watching a live webcam of other participants. The socially-engaged group believed they would later complete a group task with the people in the video, whilst the non-engaged group believed they would not meet the people in the scene. In a third condition, participants simply free-viewed the same video with the knowledge that it was pre-recorded, with no suggestion of a later interaction. Results demonstrated that the social context in which the stimulus was viewed significantly influenced viewing behaviour. Specifically, participants in the social conditions allocated less visual attention towards the heads of the actors in the scene and followed their gaze less than those in the free-viewing group. These findings suggest that by underestimating the impact of social context in social attention, researchers risk coming to inaccurate conclusions about how we attend to others in the real world.     

Semiconductor quantum dots for in vitro diagnostics and cellular imaging

The need for companion diagnostics, point-of-care testing (POCT) and high-throughput screening in clinical diagnostics and personalized medicine has pushed the need for more biological information from a single sample at extremely low concentrations and volumes. Optical biosensors based on semiconductor quantum dots (QDs) can answer these requirements because their unique photophysical properties are ideally suited for highly sensitive multiplexed detection. Many different biological systems have been successfully scrutinized with a large variety of QDs over the past decade but their future as widely applied commercial biosensors is still open. In this review, we highlight recent in vitro diagnostic and cellular imaging applications of QDs and discuss milestones and obstacles on their way toward integration into real-life diagnostic and medical applications.     

The Evolution of Virulence in RNA Viruses under a Competition–Colonization Trade-Off

RNA viruses exist in large intra-host populations which display great genotypic and phenotypic diversity. We analyze a model of viral competition between two viruses infecting a constantly replenished cell pool. We assume a trade-off between the ability of the virus to colonize new cells (cell killing rate or virulence) and its local competitiveness (replicative success within coinfected cells). We characterize the conditions that allow for viral spread by means of the basic reproductive number and show that a local coexistence equilibrium exists, which is asymptotically stable. At this equilibrium, the less virulent competitor has a reproductive advantage over the more virulent colonizer reflected by a larger equilibrium population size of the competitor. The equilibria at which one virus outcompetes the other one are unstable, i.e., a second virus is always able to permanently invade. We generalize the two-virus model to multiple viral strains, each displaying a different virulence. To account for the large phenotypic diversity in viral populations, we consider a continuous spectrum of virulences and present a continuum limit of this multiple viral strains model that describes the time evolution of an initial continuous distribution of virulence without mutations. We provide a proof of the existence of solutions of the model equations, analytically assess the properties of stationary solutions, and present numerical approximations of solutions for different initial distributions. Our simulations suggest that initial continuous distributions of virulence evolve toward a distribution that is extremely skewed in favor of competitors. At equilibrium, only the least virulent part of the population survives. The discrepancy of this finding in the continuum limit with the two-virus model is attributed to the skewed equilibrium subpopulation sizes and to the transition to a continuum. Consequently, in viral quasispecies with high virulence diversity, the model predicts collective virulence attenuation. This result may contribute to understanding virulence attenuation, which has been reported in several experimental studies.