ND-Track: Tractography utilising parametric models of white matter fibre orientation dispersion

This work develops a tractography algorithm to leverage fibre dispersion estimates derived from fitting parametric models of orientation dispersion to diffusion data. Tractography techniques are powerful tools to probe white matter (WM) connectivity non-invasively. Most current techniques follow a small number of discrete directions per voxel to identify WM connections. This approach addresses the limitation of traditional DTI-based tractography for regions with crossing fibres. However, it remains an oversimplification for regions with fanning and bending configurations, where the underlying fibre orientation distributions are continuous rather than discrete [2]. Following only a discrete set of directions in this case misrepresents the underlying anatomy and is likely to result in false negative connectivity estimates. Recent parameterized models of fibre dispersion represent such sub-voxel fibre architecture more realistically and provide more accurate estimates of dispersion than non-parametric techniques such as spherical deconvolution, which are vulnerable to noise [3]. Here, we present a new tractography algorithm, hereby referred to as ND-Track (Neurite Dispersion Tracking), that leverages directional information gathered from parametric models of dispersion. We investigate the advantages of tracking with dispersion measures on a simple phantom and in in-vivo data, tracking through the coronal radiata, a region known to exhibit a significant degree of fibre dispersion. We further demonstrate that this approach does not compromise the tracking of the WM pathways for which the standard technique works well

Beyond Crossing Fibers: Tractography Exploiting Sub-voxel Fibre Dispersion and Neighbourhood Structure

In this paper we propose a novel algorithm which leverages models of white matter fibre dispersion to improve tractography. Tractography methods exploit directional information from diffusion weighted magnetic resonance (DW-MR) imaging to infer connectivity between different brain regions. Most tractography methods use a single direction (e.g. the principal eigenvector of the diffusion tensor) or a small set of discrete directions (e.g. from the peaks of an orientation distribution function) to guide streamline propagation. This strategy ignores the effects of within-bundle orientation dispersion, which arises from fanning or bending at the sub-voxel scale, and can lead to missing connections. Various recent DW-MR imaging techniques estimate the fibre dispersion in each bundle directly and model it as a continuous distribution. Here we introduce an algorithm to exploit this information to improve tractography. The algorithm further uses a particle filter to probe local neighbourhood structure during streamline propagation. Using information gathered from neighbourhood structure enables the algorithm to resolve ambiguities between converging and diverging fanning structures, which cannot be distinguished from isolated orientation distribution functions. We demonstrate the advantages of the new approach in synthetic experiments and in vivo data. Synthetic experiments demonstrate the effectiveness of the particle filter in gathering and exploiting neighbourhood information in recovering various canonical fibre configurations and experiments with in vivo brain data demonstrate the advantages of utilising dispersion in tractography, providing benefits in practical situations. © 2013 Springer-Verlag

Discovery of sea urchin NGFFFamide receptor unites a bilaterian neuropeptide family

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MultiSig: a new high-precision approach to the analysis of complex biomolecular systems

MultiSig is a newly developed mode of analysis of sedimentation equilibrium (SE) experiments in the analytical ultracentrifuge, having the capability of taking advantage of the remarkable precision (~0.1 % of signal) of the principal optical (fringe) system employed, thus supplanting existing methods of analysis through reducing the ‘noise’ level of certain important parameter estimates by up to orders of magnitude. Long-known limitations of the SE method, arising from lack of knowledge of the true fringe number in fringe optics and from the use of unstable numerical algorithms such as numerical differentiation, have been transcended. An approach to data analysis, akin to ‘spatial filtering’, has been developed, and shown by both simulation and practical application to be a powerful aid to the precision with which near-monodisperse systems can be analysed, potentially yielding information on protein-solvent interaction. For oligo- and poly-disperse systems the information returned includes precise average mass distributions over both cell radial and concentration ranges and mass-frequency histograms at fixed radial positions. The application of MultiSig analysis to various complex heterogenous systems and potentially multiply-interacting carbohydrate oligomers is described

No Detectable Fertility Benefit from a Single Additional Mating in Wild Stalk-Eyed Flies

Background: Multiple mating by female insects is widespread, and the explanation(s) for repeated mating by females has been the subject of much discussion. Females may profit from mating multiply through direct material benefits that increase their own reproductive output, or indirect genetic benefits that increase offspring fitness. One particular direct benefit that has attracted significant attention is that of fertility assurance, as females often need to mate multiply to achieve high fertility. This hypothesis has never been tested in a wild insect population.Methodology/Principal Findings: Female Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their lifetime, and have been shown to be sperm limited under both laboratory and field conditions. Here we ask whether receiving an additional mating alleviates sperm limitation in wild females. In our experiment one group of females received a single additional mating, while a control group received an interrupted, and therefore unsuccessful, mating. Females that received an additional mating did not lay more fertilised eggs in total, nor did they lay proportionately more fertilised eggs. Female fertility declined significantly through time, demonstrating that females were sperm limited. However, receipt of an additional mating did not significantly alter the rate of this decline.Conclusions/Significance: Our data suggest that the fertility consequences of a single additional mating were small. We discuss this effect (or lack thereof), and suggest that it is likely to be attributed to small ejaculate size, a high proportion of failed copulations, and the presence of X-linked meiotic drive in this species

A synthetic growth switch based on controlled expression of RNA polymerase

International audienceThe ability to control growth is essential for fundamental studies of bacterial physiology and biotechnological applications. We have engineered an Escherichia coli strain in which the transcription of a key component of the gene expression machinery, RNA polymerase, is under the control of an inducible promoter. By changing the inducer concentration in the medium, we can adjust the RNA polymerase concentration and thereby switch bacterial growth between zero and the maximal growth rate supported by the medium. We show that our synthetic growth switch functions in a medium-independent and reversible way, and we provide evidence that the switching phenotype arises from the ultrasensitive response of the growth rate to the concentration of RNA polymerase. We present an application of the growth switch in which both the wild-type E. coli strain and our modified strain are endowed with the capacity to produce glycerol when growing on glucose. Cells in which growth has been switched off continue to be metabolically active and harness the energy gain to produce glycerol at a twofold higher yield than in cells with natural control of RNA polymerase expression. Remarkably, without any further optimization, the improved yield is close to the theoretical maximum computed from a flux balance model of E. coli metabolism. The proposed synthetic growth switch is a promising tool for gaining a better understanding of bacterial physiology and for applications in synthetic biology and biotechnology

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Utilising measures of fiber dispersion in white matter tractography

This paper proposes a new tractography algorithm utilising measures of fiber dispersion derived from diffusion weighted magnetic resonance (DW-MR) imaging. Tractography estimates connectivity by integrating a pathway from a seed point following directional information derived from DW-MR images. Current tractography techniques follow a discrete set of directions given in each voxel of a DW-MR image and probabilistic techniques account for noise induced uncertainty on those discrete directions. Histological evidence suggests that fiber orientation dispersion exists in areas of white matter such as the centrum semiovale, representing a continuum of potential fiber orientations which cannot be accurately summarised by a limited set of discrete directions. Recent studies have shown that measures of fiber dispersion in brain white matter can be directly measured from DW-MR imaging data and explicitly represented in the orientation distribution function (ODF) of a voxel, but such measures have yet to be used in guiding tractography algorithms. We present a tracking algorithm which makes use of ODFs which account for underlying fiber dispersion to trace potential fiber pathways, we compare this method with traditional tracking methods on simulated data and in vivo human data, showing that measures of fiber dispersion can aid tractography in finding connectivity commonly missed by current tractography methods

Age-related delay in information accrual for faces: Evidence from a parametric, single-trial EEG approach

Background: In this study, we quantified age-related changes in the time-course of face processing by means of an innovative single-trial ERP approach. Unlike analyses used in previous studies, our approach does not rely on peak measurements and can provide a more sensitive measure of processing delays. Young and old adults (mean ages 22 and 70 years) performed a non-speeded discrimination task between two faces. The phase spectrum of these faces was manipulated parametrically to create pictures that ranged between pure noise (0% phase information) and the undistorted signal (100% phase information), with five intermediate steps. Results: Behavioural 75% correct thresholds were on average lower, and maximum accuracy was higher, in younger than older observers. ERPs from each subject were entered into a single-trial general linear regression model to identify variations in neural activity statistically associated with changes in image structure. The earliest age-related ERP differences occurred in the time window of the N170. Older observers had a significantly stronger N170 in response to noise, but this age difference decreased with increasing phase information. Overall, manipulating image phase information had a greater effect on ERPs from younger observers, which was quantified using a hierarchical modelling approach. Importantly, visual activity was modulated by the same stimulus parameters in younger and older subjects. The fit of the model, indexed by R2, was computed at multiple post-stimulus time points. The time-course of the R2 function showed a significantly slower processing in older observers starting around 120 ms after stimulus onset. This age-related delay increased over time to reach a maximum around 190 ms, at which latency younger observers had around 50 ms time lead over older observers. Conclusion: Using a component-free ERP analysis that provides a precise timing of the visual system sensitivity to image structure, the current study demonstrates that older observers accumulate face information more slowly than younger subjects. Additionally, the N170 appears to be less face-sensitive in older observers

Using twins to better understand sibling relationships

We compared the nature of the sibling relationship in dyads of varying genetic relatedness, employing a behavioural genetic design to estimate the contribution that genes and the environment have on this familial bond. Two samples were used—the Sisters and Brothers Study consisted of 173 families with two target non-twin children (mean ages = 7.42 and 5.22 years respectively); and the Twins, Family and Behaviour study included 234 families with two target twin children (mean age = 4.70 years). Mothers and fathers reported on their children’s relationship with each other, via a postal questionnaire (the Sisters and Brothers Study) or a telephone interview (the Twins, Family and Behaviour study). Contrary to expectations, no mean level differences emerged when monozygotic twin pairs, dizygotic twin pairs, and non-twin pairs were compared on their sibling relationship quality. Behavioural genetic analyses also revealed that the sibling bond was modestly to moderately influenced by the genetic propensities of the children within the dyad, and moderately to substantially influenced by the shared environment common to both siblings. In addition, for sibling negativity, we found evidence of twin-specific environmental influence—dizygotic twins showed more reciprocity than did non-twins. Our findings have repercussions for the broader application of results from future twin-based investigations