Cortactin Is a Substrate of Activated Cdc42-Associated Kinase 1 (ACK1) during Ligand-induced Epidermal Growth Factor Receptor Downregulation

Background Epidermal growth factor receptor (EGFR) internalization following ligand binding controls EGFR downstream pathway signaling activity. Internalized EGFR is poly-ubiquitinated by Cbl to promote lysosome-mediated degradation and signal downregulation. ACK1 is a non-receptor tyrosine kinase that interacts with ubiquitinated EGFR to facilitate EGFR degradation. Dynamic reorganization of the cortical actin cytoskeleton controlled by the actin related protein (Arp)2/3 complex is important in regulating EGFR endocytosis and vesicle trafficking. How ACK1-mediated EGFR internalization cooperates with Arp2/3-based actin dynamics during EGFR downregulation is unclear. Methodology/Principal Findings Here we show that ACK1 directly binds and phosphorylates the Arp2/3 regulatory protein cortactin, potentially providing a direct link to Arp2/3-based actin dynamics during EGFR degradation. Co-immunoprecipitation analysis indicates that the cortactin SH3 domain is responsible for binding to ACK1. In vitro kinase assays demonstrate that ACK1 phosphorylates cortactin on key tyrosine residues that create docking sites for adaptor proteins responsible for enhancing Arp2/3 nucleation. Analysis with phosphorylation-specific antibodies determined that EGFR-induced cortactin tyrosine phosphorylation is diminished coincident with EGFR degradation, whereas ERK1/2 cortactin phosphorylation utilized in promoting activation of the Arp2/3 regulator N-WASp is sustained during EGFR downregulation. Cortactin and ACK1 localize to internalized vesicles containing EGF bound to EGFR visualized by confocal microscopy. RNA interference and rescue studies indicate that ACK1 and the cortactin SH3 domain are essential for ligand-mediated EGFR internalization. Conclusions/Significance Cortactin is a direct binding partner and novel substrate of ACK1. Tyrosine phosphorylation of cortactin by ACK1 creates an additional means to amplify Arp2/3 dynamics through N-WASp activation, potentially contributing to the overall necessary tensile and/or propulsive forces utilized during EGFR endocytic internalization and trafficking involved in receptor degradation

Vocal mimicry in the spotted bowerbird Ptilonorhynchus maculatus

Vocal mimicry is well documented in songbirds, yet the function of this behaviour is poorly understood. I studied vocal mimicry in a wild population of male spotted bowerbirds Ptilonorhynchus maculatus to determine whether there was any support for the proposed functional hypotheses invoked to explain this behaviour. I collected observational data to determine what species male bowerbirds mimicked and how their mimetic repertoires related to the acoustic environment. Spotted bowerbirds preferentially mimicked the vocalisations of aggressive species, which is consistent with mimicry acting to deter predators or competitors (Batesian mimicry). However, these sounds were also relatively simple in terms of their structure, and may be mimicked purely due to their simplicity and similarity to the species-specific hiss. A survey of mimetic repertoires at three geographically isolated populations revealed a similar pattern in model choice: mimetic repertoires were predominantly composed of aggressive and predatory species but these sounds were also structurally simple. To test whether mimicry was used in a Batesian context I determined what contexts mimicry was produced in. Consistent with predictions, I found that males did not increase their mimetic rate in the presence of conspecifics but did increase their mimetic rate in response to human activity around the bower. To determine how mimetic sounds are acquired in this species, I compared the mimetic repertoires of individuals within a population and found that males with bowers closer together mimicked more of the same species than did males with bowers that were further apart. Closer inspection of two of these mimicked sounds revealed that neighbouring males did not produce structurally similar mimicry,which suggests that mimetic sounds are learned directly from the species being mimicked. Males did not increase their rate of species-specific vocalisation when mimetic rate increased, so these vocalisations are unlikely to serve the same function. Males increased their rate of species-specific hissing when in the presence of conspecifics and this vocalisation is likely to function in intraspecific communication. Males also produced ‘advertisement’ calls when alone at the bower that are likely to attract females to the bower or deter rival males. These vocalisations are a long distance signal that varied in structure in three populations of bowerbird. I discuss potential explanations for geographic variation in the structure of bowerbird vocalisations. Vocalisations may be part of the multi-component sexual signal produced by bowerbirds, but I found no relationship between any aspect of male vocalisation and predicted mating success, so these vocalisations are unlikely to indicate male quality to potential mates or rival males. In conclusion, it seems most likely that mimicry in this species is used to deter predators or competitors, but I cannot exclude the hypothesis that mimetic sounds are learned as a result of their relative simplicity and salience in the acoustic environment. Furthermore, I have shown that mimetic sounds in this species are most likely acquired directly from the species being mimicked. These findings are a useful step towards understanding the function and evolution of this fascinating behaviour

Recoiling black holes: prospects for detection and implications of spin alignment

Supermassive black hole (BH) mergers produce powerful gravitational wave (GW) emission. Asymmetry in this emission imparts a recoil kick to the merged BH, which can eject the BH from its host galaxy altogether. Recoiling BHs could be observed as offset active galactic nuclei (AGN). Several candidates have been identified, but systematic searches have been hampered by large uncertainties regarding their observability. By extracting merging BHs and host galaxy properties from the Illustris cosmological simulations, we have developed a comprehensive model for recoiling AGN. Here, for the first time, we model the effects of BH spin alignment and recoil dynamics based on the gas-richness of host galaxies. We predict that if BH spins are not highly aligned, seeing-limited observations could resolve offset AGN, making them promising targets for all-sky surveys. For randomly-oriented spins, less than about 10 spatially-offset AGN may be detectable in HST-COSMOS, and > 10^3 could be found with Pan-STARRS, LSST, Euclid, and WFIRST. Nearly a thousand velocity-offset AGN are predicted within the SDSS footprint; the rarity of large broad-line offsets among SDSS quasars is likely due in part to selection effects but suggests that spin alignment plays a role in suppressing recoils. Nonetheless, in our most physically motivated model where alignment occurs only in gas-rich mergers, hundreds of offset AGN should be found in all-sky surveys. Our findings strongly motivate a dedicated search for recoiling AGN.Comment: 30 pages, 19 figures. Accepted to MNRAS after minor revision

California scrub-jays reduce visual cues available to potential pilferers by matching food colour to caching substrate

Some animals hide food to consume later, however these caches are susceptible to theft by conspecifics and heterospecifics. Many caching animals use protection strategies to minimise visual and acoustic cues available to potential pilferers, such as caching behind objects, in shaded areas and in quiet substrate. A widespread method of concealment in the animal kingdom is background matching, a camouflage strategy commonly used by prey animals where they match the colour or patterning of the visual background. Caching animals may also use this tactic to minimise the conspicuousness of caches, for example by hiding coloured food in a similar coloured substrate. We tested whether California scrub-jays (Aphelocoma californica) camouflage their food in this way by offering them coloured food to cache in substrates that either matched or did not match the colour of the food. We also determined whether this caching behavior was sensitive to social context by letting birds cache when a bird could be both seen and heard (visual and acoustic cue present), or heard but not seen (acoustic cues only). When caching events could be both heard and seen by a potential pilferer, birds cached randomly in both coloured substrates. However, they preferentially hid food in the substrate that matched the food colour when only acoustic, and not visual cues were present. These results reveal a novel cache protection strategy employed by a caching animal that is also sensitive to social context.L.A.K. received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement PIIF-GA-2012-327423

A Dynamical Analysis of the Dust Tail of Comet C/1995 O1 (Hale-Bopp) at High Heliocentric Distances

Comet C/1995 O1 (Hale-Bopp) has provided an unprecedented opportunity to observe a bright comet over a wide range of heliocentric distances. We present here Spitzer Space Telescope observations of Hale-Bopp from 2005 and 2008 that show a distinct coma and tail, the presence of which is uncommon given its large heliocentric distance (21.6 AU and 27.2 AU, respectively). The morphology of the dust is compared to dynamical models to understand the activity of the comet. Our analysis shows that the shape of Hale-Bopp's dust tail in these images cannot be explained using the usual Finson-Probstein (solar gravity + solar radiation pressure) dynamical model. Several alternative explanations are explored. The analysis suggests that the most likely cause of the discrepancy is that the dust is being charged by the solar wind, then being affected by the interplanetary magnetic field via the Lorentz force. Though this effect has been explored previously, if correct, this seems to be the first time that the Lorentz force has been required to model a cometary dust tail. The analysis also suggests that Hale-Bopp was actively emitting particles when these images were taken, and the tail characteristics changed between observations.Comment: 23 pages, 10 figures. Accepted to Icarus on 17 March 201

Motivating Moral Behavior: Helping, Sharing, and Comforting in Young Children With Autism Spectrum Disorder

This exploratory study examined the role of social-cognitive development in the production of moral behavior. Specifically, we explored the propensity of children with Autism Spectrum Disorders (ASD) to engage in helping, sharing, and comforting acts, addressing two specific questions: (1) Compared to their typically developing (TD) peers, how do young children with ASD perform on three prosocial tasks that require the recognition of different kinds of need (instrumental, material, and emotional), and (2) are children with ASD adept at distinguishing situations in which an adult needs assistance from perceptually similar situations in which the need is absent? Children with ASD demonstrated low levels of helping and sharing but provided comfort at levels consistent with their TD peers. Children with ASD also tended to differentiate situations where a need was present from situations in which it was absent. Together, these results provided an initial demonstration that young children with ASD have the ability to take another’s perspective and represent their internal need states. However, when the cost of engaging in prosocial behavior is high (e.g., helping and sharing), children with ASD may be less inclined to engage in the behavior, suggesting that both the capacity to recognize another’s need and the motivation to act on behalf of another appear to play important roles in the production of prosocial behavior. Further, differential responding on the helping, sharing, and comforting tasks lend support to current proposals that the domain of moral behavior is comprised of a variety of distinct subtypes of prosocial behavior

The evolution of patterning during movement in a large-scale citizen science game.

The motion dazzle hypothesis posits that high contrast geometric patterns can cause difficulties in tracking a moving target and has been argued to explain the patterning of animals such as zebras. Research to date has only tested a small number of patterns, offering equivocal support for the hypothesis. Here, we take a genetic programming approach to allow patterns to evolve based on their fitness (time taken to capture) and thus find the optimal strategy for providing protection when moving. Our 'Dazzle Bug' citizen science game tested over 1.5 million targets in a touch screen game at a popular visitor attraction. Surprisingly, we found that targets lost pattern elements during evolution and became closely background matching. Modelling results suggested that targets with lower motion energy were harder to catch. Our results indicate that low contrast, featureless targets offer the greatest protection against capture when in motion, challenging the motion dazzle hypothesis