Jumping without Using Legs: The Jump of the Click-Beetles (Elateridae) Is Morphologically Constrained

To return to their feet, inverted click-beetles (Elateridae) jump without using their legs. When a beetle is resting on its dorsal side, a hinge mechanism is locked to store elastic energy in the body and releases it abruptly to launch the beetle into the air. While the functional morphology of the jumping mechanism is well known, the level of control that the beetle has over this jumping technique and the mechanical constraints governing the jumps are not entirely clear. Here we show that while body rotations in air are highly variable, the jumps are morphologically constrained to a constant “takeoff” angle (79.9°±1.56°, n = 9 beetles) that directs 98% of the jumping force vertically against gravity. A physical-mathematical model of the jumping action, combined with measurements from live beetle, imply that the beetle may control the speed at takeoff but not the jumping angle. In addition, the model shows that very subtle changes in the exact point of contact with the ground can explain the vigorous rotations of the body seen while the beetle is airborne. These findings suggest that the evolution of this unique non-legged jumping mechanism resulted in a jumping technique that is capable of launching the body high into the air but it is too constrained and unstable to allow control of body orientation at landing

Dynamic interaction of PTP mu with multiple cadherins in vivo

There is a growing body of evidence to implicate reversible tyrosine phosphorylation as an important mechanism in the control of the adhesive function of cadherins. We previously demonstrated that the receptor protein tyrosine phosphatase PTP mu associates with the cadherin-catenin complex in various tissues and cells and, therefore, may be a component of such a regulatory mechanism (Brady-Kalnay, S.M., D.L. Rimm, and N.K. Tonks. 1995. J. Cell Biol. 130:977-986). In this study, we present further characterization of this interaction using a variety of systems. We observed that PTP mu interacted with N-cadherin, E-cadherin, and cadherin-4 (also called R-cadherin) in extracts of rat lung. We observed a direct interaction between PTP mu, and E-cadherin after coexpression in Sf9 cells. In WC5 cells, which express a temperature-sensitive mutant form of v-Src, the complex between PTP mu and E-cadherin was dynamic, and conditions that resulted in tyrosine phosphorylation of E-cadherin were associated with dissociation of PTP mu from the complex. Furthermore, we have demonstrated that the COOH-terminal 38 residues of the cytoplasmic segment of E-cadherin was required for association with PTP mu in WC5 cells. Zondag et al. (Zondag, G., W. Moolenaar, and M. Gebbink. 1996. J. Cell Biol. 134: 1513-1517) have asserted that the association we observed between PTP mu and the cadherin-catenin complex in immunoprecipitates of the phosphatase arises from nonspecific cross-reactivity between BK2, our antibody to PTP mu, and cadherins. In this study we have confirmed our initial observation and demonstrated the presence of cadherin in immunoprecipitates of PTP mu. obtained with three antibodies that recognize distinct epitopes in the phosphatase. In addition, we have demonstrated directly that the anti-PTP mu antibody BK2 that we used initially did not cross-react with cadherin. Our data reinforce the observation of an interaction between PTP mu, and E-cadherin in vitro and in vivo, further emphasizing the potential importance of reversible tyrosine phosphorylation in regulating cadherin function

Wind-Powered Wheel Locomotion, Initiated by Leaping Somersaults, in Larvae of the Southeastern Beach Tiger Beetle (Cicindela dorsalis media)

Rapid movement is challenging for elongate, soft-bodied animals with short or no legs. Leaping is known for only a few animals with this “worm-like” morphology. Wheel locomotion, in which the animal's entire body rolls forward along a central axis, has been reported for only a handful of animals worldwide. Here we present the first documented case of wind-powered wheel locomotion, in larvae of the coastal tiger beetle Cicindela dorsalis media. When removed from their shallow burrows, larvae easily can be induced to enter a behavioral sequence that starts with leaping; while airborne, larvae loop their body into a rotating wheel and usually either “hit the ground rolling” or leap again. The direction larvae wheel is closely related to the direction in which winds are blowing; thus, all our larvae wheeled up-slope, as winds at our study site consistently blew from sea to land. Stronger winds increased both the proportion of larvae wheeling, and the distance traveled, exceeding 60 m in some cases. In addition, the proportion of larvae that wheel and the distance traveled by wheeling larvae are significantly greater on smooth sandy beaches than on beach surfaces made rough and irregular by pedestrian, equestrian, and vehicular traffic. Like other coastal species of tiger beetles, C. dorsalis media has suffered major declines in recent years that are clearly correlated with increased human impacts. The present study suggests that the negative effects of beach traffic may be indirect, preventing larvae from escaping from predators using wheel locomotion by disrupting the flat, hard surface necessary for efficient wheeling

A novel Nav1.5-dependent feedback mechanism driving glycolytic acidification in breast cancer metastasis

The authors wish to acknowledge the roles of the Breast Cancer Now Tissue Bank in collecting and making available the samples and data, and the patients who have generously donated their tissues and shared their data to be used in the generation of this publication. The authors also thank Prof. Miles Whittington (Hull-York Medical School, UK), Dr. John Davey and Dr. Katherine Newling (Technology Facility, University of York, UK), and Prof. Lýdia Vargová (Charles University, Czechia) for providing invaluable advice. For the purpose of open access, a Creative Commons Attribution (CC BY) licence is applied to any author accepted manuscript version arising from this submission.Peer reviewe

Promoting the achievement in schools of children and young people in care

As of March 2017, there were 72,670 children and young people in care in England. The number of looked after children has continued to increase steadily over the last eight years. Sixty per cent of these children are in care because of abuse or neglect and three-quarters are placed in foster care arrangements. Children and young people who are in or have experienced care remain one of the lowest performing groups in terms of educational outcomes. The average Attainment 8 score for children in care is 19.3 compared to 44.5 for non-looked after children and 19.3 for children in need. In 2017 there was an increase in the percentage of children in care achieving a pass in English and Mathematics from 17.4% to 17.5% and also in entering EBacc. Care leavers can experience poorer employment and health outcomes after leaving school compared to their peers. They are over-represented amongst the offender population and those who experience homelessness. However, research is emerging to show that children and young people in care can have very positive experiences of school if they are supported effectively to reach their full potential academically and socially. The purpose of this report is to share practice in local authorities (LA) from across England and Wales that is contributing to improved outcomes and school experiences for children and young people in care. The case studies were all undertaken as part of the Promoting the Achievement of Looked after Children (PALAC) programme between 2014 and 2017. This report presents an account of the programme, including the activities undertaken by the participants and the outcomes of the programme to date for pupils in care and staff in the participating virtual schools (VS) and local authorities

Osteological and Soft-Tissue Evidence for Pneumatization in the Cervical Column of the Ostrich (Struthio camelus) and Observations on the Vertebral Columns of Non-Volant, Semi-Volant and Semi-Aquatic Birds

© 2015 Apostolaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License [4.0], which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

MOLECULAR STRUCTURE OF THE EPIDERMAL EXTRACELLULAR SPACES

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65966/1/j.1365-4362.1979.tb01946.x.pd

Voltage-gated Na⁺ channel activity increases colon cancertranscriptional activity and invasion via persistent MAPK signaling

© 2015 Macmillan Publishers Limited. All rights reserved. Functional expression of voltage-gated Na+ channels (VGSCs) has been demonstrated in multiple cancer cell types where channel activity induces invasive activity. The signaling mechanisms by which VGSCs promote oncogenesis remain poorly understood. We explored the signal transduction process critical to VGSC-mediated invasion on the basis of reports linking channel activity to gene expression changes in excitable cells. Coincidentally, many genes transcriptionally regulated by the SCN5A isoform in colon cancer have an over-representation of cis-acting sites for transcription factors phosphorylated by ERK1/2 MAPK. We hypothesized that VGSC activity promotes MAPK activation to induce transcriptional changes in invasion-related genes. Using pharmacological inhibitors/activators and siRNA-mediated gene knockdowns, we correlated channel activity with Rap1-dependent persistent MAPK activation in the SW620 human colon cancer cell line. We further demonstrated that VGSC activity induces downstream changes in invasion-related gene expression via a PKA/ERK/c-JUN/ELK-1/ETS-1 transcriptional pathway. This is the first study illustrating a molecular mechanism linking functional activity of VGSCs to transcriptional activation of invasion-related genes

Alternative Splicing of the Cardiac Sodium Channel Creates Multiple Variants of Mutant T1620K Channels

Alternative splicing creates several Nav1.5 transcripts in the mammalian myocardium and in various other tissues including brain, dorsal root ganglia, breast cancer cells as well as neuronal stem cell lines. In total nine Nav1.5 splice variants have been discovered. Four of them, namely Nav1.5a, Nav1.5c, Nav1.5d, and Nav1.5e, generate functional channels in heterologous expression systems. The significance of alternatively spliced transcripts for cardiac excitation, in particular their role in SCN5A channelopathies, is less well understood. In the present study, we systematically investigated electrophysiological properties of mutant T1620K channels in the background of all known functional Nav1.5 splice variants in HEK293 cells. This mutation has been previously associated with two distinct cardiac excitation disorders: with long QT syndrome type 3 (LQT3) and isolated cardiac conduction disease (CCD). When investigating the effect of the T1620K mutation, we noticed similar channel defects in the background of hNav1.5, hNav1.5a, and hNav1.5c. In contrast, the hNav1.5d background produced differential effects: In the mutant channel, some gain-of-function features did not emerge, whereas loss-of-function became more pronounced. In case of hNav1.5e, the neonatal variant of hNav1.5, both the splice variant itself as well as the corresponding mutant channel showed electrophysiological properties that were distinct from the wild-type and mutant reference channels, hNav1.5 and T1620K, respectively. In conclusion, our data show that alternative splicing is a mechanism capable of generating a variety of functionally distinct wild-type and mutant hNav1.5 channels. Thus, the cellular splicing machinery is a potential player affecting genotype-phenotype correlations in SCN5A channelopathies