NMDA receptor-dependent long-term potentiation (LTP) and depression (LTD) are forms of synaptic plasticity underlying learning and memory that are expressed through increases and decreases, ...respectively, in dendritic spine size and AMPA receptor (AMPAR) phosphorylation and postsynaptic localization. The A-kinase anchoring protein 79/150 (AKAP79/150) signaling scaffold regulates AMPAR phosphorylation, channel activity, and endosomal trafficking associated with LTP and LTD. AKAP79/150 is targeted to dendritic spine plasma membranes by an N-terminal polybasic domain that binds phosphoinositide lipids, F-actin, and cadherin cell adhesion molecules. However, we do not understand how regulation of AKAP targeting controls AMPAR endosomal trafficking. Here, we report that palmitoylation of the AKAP N-terminal polybasic domain targets it to postsynaptic lipid rafts and dendritic recycling endosomes. AKAP palmitoylation was regulated by seizure activity in vivo and LTP/LTD plasticity-inducing stimuli in cultured rat hippocampal neurons. With chemical LTP induction, we observed AKAP79 dendritic spine recruitment that required palmityolation and Rab11-regulated endosome recycling coincident with spine enlargement and AMPAR surface delivery. Importantly, a palmitoylation-deficient AKAP79 mutant impaired regulation of spine size, endosome recycling, AMPAR trafficking, and synaptic potentiation. These findings emphasize the emerging importance of palmitoylation in controlling synaptic function and reveal novel roles for the AKAP79/150 signaling complex in dendritic endosomes.
We present a survey on coronal prominence cavities conducted using 19 months of data from the
Atmospheric Imaging Assembly
(AIA) instrument aboard the
Solar Dynamics Observatory
(SDO) satellite. ...Coronal cavities are elliptical regions of rarefied density lying above and around prominences. They can be long-lived (weeks to months) but are often observed to eventually erupt as part of a coronal mass ejection (CME). We determine morphological properties of the cavities both by qualitatively assessing their shape, and quantitatively fitting them with ellipses. We demonstrate consistency between these two approaches, and find that fitted ellipses are taller than they are wide for almost all cavities studied, in agreement with an earlier analysis of white-light cavities. We examine correlations between cavity shape, aspect ratio, and propensity for eruption. We find that cavities with a teardrop-shaped morphology are more likely to erupt, and we discuss the implications of this morphology for magnetic topologies associated with CME models. We provide the full details of the survey for broad scientific use as supplemental material.
We present a three-dimensional density model of coronal prominence cavities, and a morphological fit that has been tightly constrained by a uniquely well-observed cavity. Observations were obtained ...as part of an International Heliophysical Year campaign by instruments from a variety of space- and ground-based observatories, spanning wavelengths from radio to soft X-ray to integrated white light. From these data it is clear that the prominence cavity is the limb manifestation of a longitudinally extended polar-crown filament channel, and that the cavity is a region of low density relative to the surrounding corona. As a first step toward quantifying density and temperature from campaign spectroscopic data, we establish the three-dimensional morphology of the cavity. This is critical for taking line-of-sight projection effects into account, since cavities are not localized in the plane of the sky and the corona is optically thin. We have augmented a global coronal streamer model to include a tunnel-like cavity with elliptical cross-section and a Gaussian variation of height along the tunnel length. We have developed a semi-automated routine that fits ellipses to cross-sections of the cavity as it rotates past the solar limb, and have applied it to Extreme Ultraviolet Imager observations from the two Solar Terrestrial Relations Observatory spacecraft. This defines the morphological parameters of our model, from which we reproduce forward-modeled cavity observables. We find that cavity morphology and orientation, in combination with the viewpoints of the observing spacecraft, explain the observed variation in cavity visibility for the east versus west limbs.
Primary systemic therapy (PST) for operable breast cancer enables the identification of in vivo biological markers that predict response to treatment. A total of 118 patients with T2-4 N0-1 M0 ...primary breast cancer received six cycles of anthracycline-based PST. Clinical and radiological response was assessed before and after treatment using UICC criteria. A grading system to score pathological response was devised. Diagnostic biopsies and postchemotherapy surgical specimens were stained for oestrogen (ER) and progesterone (PgR) receptor, HER-2 and cell proliferation (Ki-67). Clinical, radiological and pathological response rates were 78, 72 and 38%, respectively. There was a strong correlation between ER and PgR staining (P < 0.0001). Higher Ki-67 proliferation indices were associated with PgR- tumours (median 28.3%, PgR+ 22.9%; P = 0.042). There was no relationship between HER-2 and other biological markers. No single pretreatment or postchemotherapy biological parameter predicted response by any modality of assessment. In all, 10 tumours changed hormone receptor classification after chemotherapy (three ER, seven PgR); HER-2 staining changed in nine cases. Median Ki-67 index was 24.9% before and 18.1% after treatment (P = 0.02); the median reduction in Ki-67 index after treatment was 21.2%. Tumours displaying >75% reduction in Ki-67 after chemotherapy were more likely to achieve a pathological response (77.8 vs 26.7%, P = 0.004).
In the United States alone, over 7400 bird-aircraft collisions (birdstrikes) were reported in 2007. Most of these strikes occurred during takeoff or landing of the flight, and it is during these ...flight phases that aircraft experience their highest risk of substantial damage after colliding with birds. Birdstrikes carry enormous potential costs in terms of lives and money. Using feather remains and other tissue samples collected from the engines of US Airways Flight 1549, which crash landed in the Hudson River in New York City on 15 January 2009 after a birdstrike, we apply molecular tools and stable hydrogen isotopes to demonstrate that migratory Canada geese were responsible for the crash. Determining whether the geese involved in this birdstrike event were resident or migratory is essential to the development of management techniques that could reduce the risk of future collisions. Currently, the US civil aviation industry is not required to report birdstrikes, yet information on frequency, timing, and species involved, as well as the geographic origin of the birds, is critical to reducing the number of birdstrikes. Integrating this information with bird migration patterns, bird-detecting radar, and bird dispersal programs at airports can minimize the risk of such collisions in the future.
To understand the molecular and neural mechanisms underlying alcohol addiction, many models ranging from vertebrates to invertebrates have been developed. In Drosophila melanogaster, behavioral ...paradigms from assaying acute responses to alcohol and to behaviors more closely modeling addiction have emerged in recent years. However, both the CAFÉ assay, similar to a two‐bottle choice consumption assay, as well as conditioned odor preference, where ethanol is used as the reinforcer, are labor intensive and have low throughput. To address this limitation, we have established a novel ethanol consumption preference assay, called FRAPPÉ, which allows for fast, high throughput measurement of consumption in individual flies, using a fluorescence plate reader. We show that naïve flies do not prefer to consume ethanol, but various pre‐exposures, such as ethanol vapor or voluntary ethanol consumption, induce ethanol preference. This ethanol‐primed preference is long lasting and is not driven by calories contained in ethanol during the consumption choice. Our novel experience‐dependent model of ethanol preference in Drosophila—a highly genetically tractable organism—therefore recapitulates salient features of human alcohol abuse and will facilitate the molecular understanding of the development of alcohol preference.
The study of addiction in Drosophila benefits from assays with high face validity and throughput. Here, we establish a novel ethanol consumption preference assay, which allows for fast, and accurate preference measurements in individual flies. We show that naïve flies do not prefer to consume ethanol, but various pre‐exposures, such as ethanol vapor or voluntary ethanol consumption, induce ethanol preference. This ethanol‐primed preference is long lasting and is not driven by calories contained in ethanol during the consumption choice.
Globally, high elevation habitats have been independently colonized by taxa separated by millions of years of evolution. Mountains thus represent excellent systems to study how distantly related ...species adapt to the same environmental challenges. Cold temperatures influence the elevational distribution of birds along montane gradients. Yet the eco‐physiological adaptations that may explain this pattern, such as variation in insulative feather structure across high elevation and low elevation species has not been quantified. We used a comparative approach to understand if elevation, evolutionary history and body size drive variation in thermo‐insulative feather traits across 1715 specimens of 249 Himalayan passerines. Controlling for phylogenetic relationships between species, we found that the proportion of the feather's plumulaceous (downy) section increased with elevation. Body size also had a predictable effect on thermo‐insulative variables with small birds having relatively longer feathers and thus a more insulative plumage than large birds. We show that an increase in the proportion of the feather's downy section at colder temperatures is an evolutionarily widespread response across temperate and tropical taxa, and overall, smaller‐bodied birds tend to have longer and more insulative feathers. Our results reveal convergent patterns in feather structure variation as a response to cold temperatures across species separated by millions of years of evolution.
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