The neuropeptide complement of the marine annelid Platynereis dumerilii.

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: The marine annelid Platynereis dumerilii is emerging as a powerful lophotrochozoan experimental model for evolutionary developmental biology (evo-devo) and neurobiology. Recent studies revealed the presence of conserved neuropeptidergic signaling in Platynereis, including vasotocin/neurophysin, myoinhibitory peptide and opioid peptidergic systems. Despite these advances, comprehensive peptidome resources have yet to be reported. RESULTS: The present work describes the neuropeptidome of Platynereis. We established a large transcriptome resource, consisting of stage-specific next-generation sequencing datasets and 77,419 expressed sequence tags. Using this information and a combination of bioinformatic searches and mass spectrometry analyses, we increased the known proneuropeptide (pNP) complement of Platynereis to 98. Based on sequence homology to metazoan pNPs, Platynereis pNPs were grouped into ancient eumetazoan, bilaterian, protostome, lophotrochozoan, and annelid families, and pNPs only found in Platynereis. Compared to the planarian Schmidtea mediterranea, the only other lophotrochozoan with a large-scale pNP resource, Platynereis has a remarkably full complement of conserved pNPs, with 53 pNPs belonging to ancient eumetazoan or bilaterian families. Our comprehensive search strategy, combined with analyses of sequence conservation, also allowed us to define several novel lophotrochozoan and annelid pNP families. The stage-specific transcriptome datasets also allowed us to map changes in pNP expression throughout the Platynereis life cycle. CONCLUSION: The large repertoire of conserved pNPs in Platynereis highlights the usefulness of annelids in comparative neuroendocrinology. This work establishes a reference dataset for comparative peptidomics in lophotrochozoans and provides the basis for future studies of Platynereis peptidergic signaling.This work was supported by Max Planck Society Sequencing Grant M.IF.A.ENTW8050 to GJ. The research leading to these results was supported by the European Research Council under European Union Seventh Framework Program FP7/2007–2013 and European Research Council Grant Agreement 260821

Low tropical diversity during the adaptive radiation of early land plants.

The latitudinal biodiversity gradient, with tropical regions acting as 'evolutionary cradles', is a cornerstone of current biogeographical and ecological theory1. In the modern world floral biodiversity and biomass are overwhelmingly concentrated in the tropics, and it is often assumed that the tropics were evolutionary cradles throughout land plant evolutionary history. For example, the origination and diversification of angiosperms is believed to have taken place in the Cretaceous tropics2 and modern gymnosperms in the Permian tropics3. Here, we show that during the first major diversification of land plants, in the Late Silurian-Early Devonian, land plant biodiversity was much lower at the equator compared to medium-high southern latitudes. Throughout this crucial interval of plant evolution, tropical vegetation remained depauperate and of very low taxonomic biodiversity, although with similar morphological disparity to the more diverse higher latitude floras. Possible explanations for this low tropical floral biodiversity include palaeocontinental configuration or adverse palaeotropical environmental conditions. We discount the possibility that it was simply a fortuitous feature of the biogeographical spread of the earliest vascular land plants.National Geographi

Concurrent adaptation to opposing visual displacements during an alternating movement.

It has been suggested that, during tasks in which subjects are exposed to a visual rotation of cursor feedback, alternating bimanual adaptation to opposing rotations is as rapid as unimanual adaptation to a single rotation (Bock et al. in Exp Brain Res 162:513–519, 2005). However, that experiment did not test strict alternation of the limbs but short alternate blocks of trials. We have therefore tested adaptation under alternate left/right hand movement with opposing rotations. It was clear that the left and right hand, within the alternating conditions, learnt to adapt to the opposing displacements at a similar rate suggesting that two adaptive states were formed concurrently. We suggest that the separate limbs are used as contextual cues to switch between the relevant adaptive states. However, we found that during online correction the alternating conditions had a significantly slower rate of adaptation in comparison to the unimanual conditions. Control conditions indicate that the results are not directly due the alternation between limbs or to the constant switching of vision between the two eyes. The negative interference may originate from the requirement to dissociate the visual information of these two alternating displacements to allow online control of the two arms

Conditional embryonic lethality to improve the sterile insect technique in Ceratitis capitata (Diptera: Tephritidae)

<p>Abstract</p> <p>Background</p> <p>The sterile insect technique (SIT) is an environment-friendly method used in area-wide pest management of the Mediterranean fruit fly <it>Ceratitis capitata </it>(Wiedemann; Diptera: Tephritidae). Ionizing radiation used to generate reproductive sterility in the mass-reared populations before release leads to reduction of competitiveness.</p> <p>Results</p> <p>Here, we present a first alternative reproductive sterility system for medfly based on transgenic embryonic lethality. This system is dependent on newly isolated medfly promoter/enhancer elements of cellularization-specifically-expressed genes. These elements act differently in expression strength and their ability to drive lethal effector gene activation. Moreover, position effects strongly influence the efficiency of the system. Out of 60 combinations of driver and effector construct integrations, several lines resulted in larval and pupal lethality with one line showing complete embryonic lethality. This line was highly competitive to wildtype medfly in laboratory and field cage tests.</p> <p>Conclusion</p> <p>The high competitiveness of the transgenic lines and the achieved 100% embryonic lethality causing reproductive sterility without the need of irradiation can improve the efficacy of operational medfly SIT programs.</p

Bimanual grasp planning reflects changing rather than fixed constraint dominance

We studied whether motor-control constraints for grasping objects that are moved to new positions reflect a rigid constraint hierarchy or a flexible constraint hierarchy. In two experiments, we asked participants to move two plungers from the same start locations to different target locations (both high, both low, or one high and one low). We found that participants grasped the plungers symmetrically and at heights that ensured comfortable or easy-to-control end postures when the plungers had the same target heights, but these grasp tendencies were reduced when the plungers had different target heights. In addition, when the plungers had different mass distributions, participants behaved in ways that suggested still-different emphases of the relevant grasp constraints. When the plungers had different mass distributions, participants sacrificed bimanual symmetry for end-state comfort. The results suggest that bimanual grasp planning relies on a flexible rather than static hierarchy. Different constraints take on different degrees of importance depending on the nature of the task and on the level of task experience. The results have implications for the understanding of perceptual-motor skill learning. It may be that one mechanism underlying such learning is changing the priorities of task constraints

Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease

Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2.We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas.36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1-2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline).Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children with TSC.Clinicaltrials.gov NCT00126672