Co-option of a coordinate system defined by the EGFr and Dpp pathways in the evolution of a morphological novelty

Morphological innovation is an elusive and fascinating concept in evolutionary biology. A novel structure may open up an array of possibilities for adaptation, and thus is fundamental to the evolution of complex multicellular life. We use the respiratory appendages on the dorsal-anterior side of the Drosophila eggshell as a model system for morphological novelty. To study the co-option of genetic pathways in the evolution of this novelty we have compared oogenesis and eggshell patterning in Drosophila melanogaster with Ceratitis capitata, a dipteran whose eggs do not bear dorsal appendages.FCT fellowship: (SFRH/BD/33216/2007), Collaborative Research Centre 680 ‘Molecular Basis of Evolutionary Innovations (DFG grant), Fundação Calouste Gulbenkian, Instituto Gulbenkian de Ciência

Panchromatic Imaging of a Transitional Disk: The Disk of GM Aur in Optical and FUV Scattered Light

We have imaged GM Aur with HST, detected its disk in scattered light at 1400A and 1650A, and compared these with observations at 3300A, 5550A, 1.1 microns, and 1.6 microns. The scattered light increases at shorter wavelengths. The radial surface brightness profile at 3300A shows no evidence of the 24AU radius cavity that has been previously observed in sub-mm observations. Comparison with dust grain opacity models indicates the surface of the entire disk is populated with sub-micron grains. We have compiled an SED from 0.1 microns to 1 mm, and used it to constrain a model of the star+disk system that includes the sub-mm cavity using the Monte Carlo Radiative Transfer code by Barbara Whitney. The best-fit model image indicates that the cavity should be detectable in the F330W bandpass if the cavity has been cleared of both large and small dust grains, but we do not detect it. The lack of an observed cavity can be explained by the presence of sub-microns grains interior to the sub-mm cavity wall. We suggest one explanation for this which could be due to a planet of mass <9 Jupiter masses interior to 24 AU. A unique cylindrical structure is detected in the FUV data from the Advanced Camera for Surveys/Solar Blind Channel. It is aligned along the system semi-minor axis, but does not resemble an accretion-driven jet. The structure is limb-brightened and extends 190 +/- 35 AU above the disk midplane. The inner radius of the limb-brightening is 40 +/- 10 AU, just beyond the sub-millimeter cavity wall.Comment: 40 pages, 11 figures, 4 tables, accepted to Ap

A re-annotation pipeline for Illumina BeadArrays: improving the interpretation of gene expression data.

Illumina BeadArrays are among the most popular and reliable platforms for gene expression profiling. However, little external scrutiny has been given to the design, selection and annotation of BeadArray probes, which is a fundamental issue in data quality and interpretation. Here we present a pipeline for the complete genomic and transcriptomic re-annotation of Illumina probe sequences, also applicable to other platforms, with its output available through a Web interface and incorporated into Bioconductor packages. We have identified several problems with the design of individual probes and we show the benefits of probe re-annotation on the analysis of BeadArray gene expression data sets. We discuss the importance of aspects such as probe coverage of individual transcripts, alternative messenger RNA splicing, single-nucleotide polymorphisms, repeat sequences, RNA degradation biases and probes targeting genomic regions with no known transcription. We conclude that many of the Illumina probes have unreliable original annotation and that our re-annotation allows analyses to focus on the good quality probes, which form the majority, and also to expand the scope of biological information that can be extracted

A double ovulation protocol for Xenopus laevis produces doubled fertilisation yield and moderately transiently elevated corticosterone levels without loss of egg quality

The African claw-toed frog, Xenopus laevis, is a well-established laboratory model for the biology of vertebrate oogenesis, fertilisation, and development at embryonic, larval, and metamorphic stages. For ovulation, X. laevis females are usually injected with chorionic gonadotropin, whereupon they lay typically hundreds to thousands of eggs in a day. After being rested for a minimum of three months, animals are re-used. The literature suggests that adult females can lay much larger numbers of eggs in a short period. Here, we compared the standard “single ovulation” protocol with a “double ovulation” protocol, in which females were ovulated, then re-ovulated after seven days and then rested for three months before re-use. We quantified egg number, fertilisation rate (development to cleavage stage), and corticosterone secretion rate as a measure of stress response for the two protocol groups over seven 3-month cycles. We found no differences in egg number-per-ovulation or egg quality between the groups and no long-term changes in any measures over the 21-month trial period. Corticosterone secretion was elevated by ovulation, similarly for the single ovulation as for the first ovulation in the double-ovulation protocol, but more highly for the second ovulation (to a level comparable to that seen following shipment) in the latter. However, both groups exhibited the same baseline secretion rates by the time of the subsequent cycle. Double ovulation is thus transiently more stressful/demanding than single ovulation but within the levels routinely experienced by laboratory X. laevis. Noting that “stress hormone” corticosterone/cortisol secretion is linked to physiological processes, such as ovulation, that are not necessarily harmful to the individual, we suggest that the benefits of a doubling in egg yield-per-cycle per animal without loss of egg quality or signs of acute or long-term harm may outweigh the relatively modest and transient corticosterone elevation we observed. The double ovulation protocol therefore represents a potential new standard practice for promoting the “3Rs” (animal use reduction, refinement and replacement) mission for Xenopus research

Accurate brain-age models for routine clinical MRI examinations

Convolutional neural networks (CNN) can accurately predict chronological age in healthy individuals from structural MRI brain scans. Potentially, these models could be applied during routine clinical examinations to detect deviations from healthy ageing, including early-stage neurodegeneration. This could have important implications for patient care, drug development, and optimising MRI data collection. However, existing brain-age models are typically optimised for scans which are not part of routine examinations (e.g., volumetric T1-weighted scans), generalise poorly (e.g., to data from different scanner vendors and hospitals etc.), or rely on computationally expensive pre-processing steps which limit real-time clinical utility. Here, we sought to develop a brain-age framework suitable for use during routine clinical head MRI examinations. Using a deep learning-based neuroradiology report classifier, we generated a dataset of 23,302 'radiologically normal for age' head MRI examinations from two large UK hospitals for model training and testing (age range = 18-95 years), and demonstrate fast (&lt; 5 seconds), accurate (mean absolute error [MAE] &lt; 4 years) age prediction from clinical-grade, minimally processed axial T2-weighted and axial diffusion-weighted scans, with generalisability between hospitals and scanner vendors (Δ MAE &lt; 1 year). The clinical relevance of these brain-age predictions was tested using 228 patients whose MRIs were reported independently by neuroradiologists as showing atrophy 'excessive for age'. These patients had systematically higher brain-predicted age than chronological age (mean predicted age difference = +5.89 years, 'radiologically normal for age' mean predicted age difference = +0.05 years, p &lt; 0.0001). Our brain-age framework demonstrates feasibility for use as a screening tool during routine hospital examinations to automatically detect older-appearing brains in real-time, with relevance for clinical decision-making and optimising patient pathways.</p

Automated triaging of head MRI examinations using convolutional neural networks

The growing demand for head magnetic resonance imaging (MRI) examinations, along with a global shortage of radiologists, has led to an increase in the time taken to report head MRI scans around the world. For many neurological conditions, this delay can result in increased morbidity and mortality. An automated triaging tool could reduce reporting times for abnormal examinations by identifying abnormalities at the time of imaging and prioritizing the reporting of these scans. In this work, we present a convolutional neural network for detecting clinically-relevant abnormalities in $\text{T}_2$-weighted head MRI scans. Using a validated neuroradiology report classifier, we generated a labelled dataset of 43,754 scans from two large UK hospitals for model training, and demonstrate accurate classification (area under the receiver operating curve (AUC) = 0.943) on a test set of 800 scans labelled by a team of neuroradiologists. Importantly, when trained on scans from only a single hospital the model generalized to scans from the other hospital ($\Delta$AUC $\leq$ 0.02). A simulation study demonstrated that our model would reduce the mean reporting time for abnormal examinations from 28 days to 14 days and from 9 days to 5 days at the two hospitals, demonstrating feasibility for use in a clinical triage environment.Comment: Accepted as an oral presentation at Medical Imaging with Deep Learning (MIDL) 202

Labelling imaging datasets on the basis of neuroradiology reports: a validation study

Natural language processing (NLP) shows promise as a means to automate the labelling of hospital-scale neuroradiology magnetic resonance imaging (MRI) datasets for computer vision applications. To date, however, there has been no thorough investigation into the validity of this approach, including determining the accuracy of report labels compared to image labels as well as examining the performance of non-specialist labellers. In this work, we draw on the experience of a team of neuroradiologists who labelled over 5000 MRI neuroradiology reports as part of a project to build a dedicated deep learning-based neuroradiology report classifier. We show that, in our experience, assigning binary labels (i.e. normal vs abnormal) to images from reports alone is highly accurate. In contrast to the binary labels, however, the accuracy of more granular labelling is dependent on the category, and we highlight reasons for this discrepancy. We also show that downstream model performance is reduced when labelling of training reports is performed by a non-specialist. To allow other researchers to accelerate their research, we make our refined abnormality definitions and labelling rules available, as well as our easy-to-use radiology report labelling app which helps streamline this process

Swift X-Ray Observations of Classical Novae. II. The Super Soft Source sample

The Swift GRB satellite is an excellent facility for studying novae. Its rapid response time and sensitive X-ray detector provides an unparalleled opportunity to investigate the previously poorly sampled evolution of novae in the X-ray regime. This paper presents Swift observations of 52 Galactic/Magellanic Cloud novae. We included the XRT (0.3-10 keV) X-ray instrument count rates and the UVOT (1700-8000 Angstroms) filter photometry. Also included in the analysis are the publicly available pointed observations of 10 additional novae the X-ray archives. This is the largest X-ray sample of Galactic/Magellanic Cloud novae yet assembled and consists of 26 novae with super soft X-ray emission, 19 from Swift observations. The data set shows that the faster novae have an early hard X-ray phase that is usually missing in slower novae. The Super Soft X-ray phase occurs earlier and does not last as long in fast novae compared to slower novae. All the Swift novae with sufficient observations show that novae are highly variable with rapid variability and different periodicities. In the majority of cases, nuclear burning ceases less than 3 years after the outburst begins. Previous relationships, such as the nuclear burning duration vs. t_2 or the expansion velocity of the eject and nuclear burning duration vs. the orbital period, are shown to be poorly correlated with the full sample indicating that additional factors beyond the white dwarf mass and binary separation play important roles in the evolution of a nova outburst. Finally, we confirm two optical phenomena that are correlated with strong, soft X-ray emission which can be used to further increase the efficiency of X-ray campaigns.Comment: Accepted to ApJ Supplements. Full data for Table 2 and Figure 17 available in the electronic edition. New version of the previously posted paper since the earlier version was all set in landscape mod

A double ovulation protocol for Xenopus laevis produces doubled fertilisation yield and moderately transiently elevated corticosterone levels without loss of egg quality

The African claw-toed frog, Xenopus laevis, is a well-established laboratory model for the biology of vertebrate oogenesis, fertilisation, and development at embryonic, larval, and metamorphic stages. For ovulation, X. laevis females are usually injected with chorionic gonadotropin, whereupon they lay typically hundreds to thousands of eggs in a day. After being rested for a minimum of three months, animals are re-used. The literature suggests that adult females can lay much larger numbers of eggs in a short period. Here, we compared the standard “single ovulation” protocol with a “double ovulation” protocol, in which females were ovulated, then re-ovulated after seven days and then rested for three months before re-use. We quantified egg number, fertilisation rate (development to cleavage stage), and corticosterone secretion rate as a measure of stress response for the two protocol groups over seven 3-month cycles. We found no differences in egg number-per-ovulation or egg quality between the groups and no long-term changes in any measures over the 21-month trial period. Corticosterone secretion was elevated by ovulation, similarly for the single ovulation as for the first ovulation in the double-ovulation protocol, but more highly for the second ovulation (to a level comparable to that seen following shipment) in the latter. However, both groups exhibited the same baseline secretion rates by the time of the subsequent cycle. Double ovulation is thus transiently more stressful/demanding than single ovulation but within the levels routinely experienced by laboratory X. laevis. Noting that “stress hormone” corticosterone/cortisol secretion is linked to physiological processes, such as ovulation, that are not necessarily harmful to the individual, we suggest that the benefits of a doubling in egg yield-per-cycle per animal without loss of egg quality or signs of acute or long-term harm may outweigh the relatively modest and transient corticosterone elevation we observed. The double ovulation protocol therefore represents a potential new standard practice for promoting the “3Rs” (animal use reduction, refinement and replacement) mission for Xenopus research.N/

The Phylogenetic Origin of oskar Coincided with the Origin of Maternally Provisioned Germ Plasm and Pole Cells at the Base of the Holometabola

The establishment of the germline is a critical, yet surprisingly evolutionarily labile, event in the development of sexually reproducing animals. In the fly Drosophila, germ cells acquire their fate early during development through the inheritance of the germ plasm, a specialized maternal cytoplasm localized at the posterior pole of the oocyte. The gene oskar (osk) is both necessary and sufficient for assembling this substance. Both maternal germ plasm and oskar are evolutionary novelties within the insects, as the germline is specified by zygotic induction in basally branching insects, and osk has until now only been detected in dipterans. In order to understand the origin of these evolutionary novelties, we used comparative genomics, parental RNAi, and gene expression analyses in multiple insect species. We have found that the origin of osk and its role in specifying the germline coincided with the innovation of maternal germ plasm and pole cells at the base of the holometabolous insects and that losses of osk are correlated with changes in germline determination strategies within the Holometabola. Our results indicate that the invention of the novel gene osk was a key innovation that allowed the transition from the ancestral late zygotic mode of germline induction to a maternally controlled establishment of the germline found in many holometabolous insect species. We propose that the ancestral role of osk was to connect an upstream network ancestrally involved in mRNA localization and translational control to a downstream regulatory network ancestrally involved in executing the germ cell program