Integrin α2β1 in nonactivated conformation can induce focal adhesion kinase signaling.

Conformational activation of integrins is generally required for ligand binding and cellular signalling. However, we have previously reported that the nonactivated conformation of α2β1 integrin can also bind to large ligands, such as human echovirus 1. In this study, we show that the interaction between the nonactivated integrin and a ligand resulted in the activation of focal adhesion kinase (FAK) in a protein kinase C dependent manner. A loss-of-function mutation, α2E336A, in the α2-integrin did not prevent the activation of FAK, nor did EDTA-mediated inactivation of the integrin. Full FAK activation was observed, since phosphorylation was not only confirmed in residue Y397, but also in residues Y576/7. Furthermore, initiation of downstream signaling by paxillin phosphorylation in residue Y118 was evident, even though this activation was transient by nature, probably due to the lack of talin involvement in FAK activation and the absence of vinculin in the adhesion complexes formed by the nonactivated integrins. Altogether these results indicate that the nonactivated integrins can induce cellular signaling, but the outcome of the signaling differs from conventional integrin signaling

Stimulus duration has little effect on auditory, visual and audiovisual temporal order judgement

Some classical studies on temporal order judgments (TOJ) suggested a single central process comparing stimulus onsets across modalities. The prevalent current view suggests that there is modality-specific timing estimation followed by a cross-modal stage. If the latter view is correct, TOJ's may vary depending on stimulus modality. Further, if TOJ is based only on onsets, stimulus duration should be irrelevant. To address these issues, we used both unisensory and multisensory stimuli to test whether unisensory duration processing influences cross-modal TOJ's. The stimuli were auditory noise bursts, visual squares, and their cross-modal combinations presented at 10, 40 and 500 ms durations, and various stimulus onset asynchronies. Psychometric functions were measured with an identical task in all conditions: On each trial, two stimuli were presented, one to the left, the other to the right of fixation. The participants judged which one started first. TOJ's were little affected by stimulus duration, implying that they are mainly determined by stimulus onsets. Throughout, the cross-modal just noticeable differences were larger than the unisensory ones. In accordance with the current view, our results suggest that cross-modal TOJ's require a comparison of timing after modality-specific estimations.Peer reviewe

Inference of viral quasispecies with a paired de Bruijn graph

Motivation: RNA viruses exhibit a high mutation rate and thus they exist in infected cells as a population of closely related strains called viral quasispecies. The viral quasispecies assembly problem asks to characterize the quasispecies present in a sample from high-throughput sequencing data. We study the de novo version of the problem, where reference sequences of the quasispecies are not available. Current methods for assembling viral quasispecies are either based on overlap graphs or on de Bruijn graphs. Overlap graph-based methods tend to be accurate but slow, whereas de Bruijn graph-based methods are fast but less accurate. Results: We present viaDBG, which is a fast and accurate de Bruijn graph-based tool for de novo assembly of viral quasispecies. We first iteratively correct sequencing errors in the reads, which allows us to use large k-mers in the de Bruijn graph. To incorporate the paired-end information in the graph, we also adapt the paired de Bruijn graph for viral quasispecies assembly. These features enable the use of long-range information in contig construction without compromising the speed of de Bruijn graph-based approaches. Our experimental results show that viaDBG is both accurate and fast, whereas previous methods are either fast or accurate but not both. In particular, viaDBG has comparable or better accuracy than SAVAGE, while being at least nine times faster. Furthermore, the speed of viaDBG is comparable to PEHaplo but viaDBG is able to retrieve also low abundance quasispecies, which are often missed by PEHaplo.Peer reviewe

Brightness and transparency in the early visual cortex

Peer reviewe

Understanding the evolution of native pinewoods in Scotland will benefit their future management and conservation

Scots pine (Pinus sylvestris L.) is a foundation species in Scottish highland forests and a national icon. Due to heavy exploitation, the current native pinewood coverage represents a small fraction of the postglacial maximum. To reverse this decline, various schemes have been initiated to promote planting of new and expansion of old pinewoods. This includes the designation of seed zones for control of the remaining genetic resources. The zoning was based mainly on biochemical similarity among pinewoods but, by definition, neutral molecular markers do not reflect local phenotypic adaptation. Environmental variation within Scotland is substantial and it is not yet clear to what extent this has shaped patterns of adaptive differentiation among Scottish populations. Systematic, rangewide common-environment trials can provide insights into the evolution of the native pinewoods, indicating how environment has influenced phenotypic variation and how variation is maintained. Careful design of such experiments can also provide data on the history and connectivity among populations, by molecular marker analysis. Together, phenotypic and molecular datasets from such trials can provide a robust basis for refining seed transfer guidelines for Scots pine in Scotland and should form the scientific basis for conservation action on this nationally important habitat

Spring phenology shows genetic variation among and within populations in seedlings of Scots pine (Pinus sylvestris L.) in the Scottish Highlands

Background: Genetic differentiation in phenotypic traits is often observed among forest tree populations, but less is known about patterns of adaptive variation within populations. Such variation is expected to enhance the survival likelihood of extant populations under climate change. Aims: Scots pine (Pinus sylvestris) occurs over a spatially and temporally heterogeneous landscape in Scotland. Our goal was to examine whether populations had differentiated genetically in timing of bud flush in response to spatial heterogeneity and whether variation was also maintained within populations. Methods: Two common-garden studies, involving maternal families of seedlings from 21 native pinewoods, were established and variation in the trait was measured at the beginning of the second growing season. Results: Populations showed genetic differences in the trait correlated with the length of growing season at their site of origin, but the majority of variation was observed within populations. Populations also differed in their levels of variation in the trait; a pattern that may be influenced by spatial variation in the extent of temporal climate variability. Conclusions: Our findings suggest that populations have adapted to their home environments and that they also have substantial ability to adapt in situ to changes in growing season length

Visual working memory for amplitude-modulated shapes

Peer reviewe

Radial Frequency Analysis of Contour Shapes in the Visual Cortex

Cumulative psychophysical evidence suggests that the shape of closed contours is analysed by means of their radial frequency components (RFC). However, neurophysiological evidence for RFC-based representations is still missing. We investigated the representation of radial frequency in the human visual cortex with functional magnetic resonance imaging. We parametrically varied the radial frequency, amplitude and local curvature of contour shapes. The stimuli evoked clear responses across visual areas in the univariate analysis, but the response magnitude did not depend on radial frequency or local curvature. Searchlight-based, multivariate representational similarity analysis revealed RFC specific response patterns in areas V2d, V3d, V3AB, and IPS0. Interestingly, RFC-specific representations were not found in hV4 or LO, traditionally associated with visual shape analysis. The modulation amplitude of the shapes did not affect the responses in any visual area. Local curvature, SF-spectrum and contrast energy related representations were found across visual areas but without similar specificity for visual area that was found for RFC. The results suggest that the radial frequency of a closed contour is one of the cortical shape analysis dimensions, represented in the early and mid-level visual areas.Peer reviewe