Demonstration and Control of “Spoof-Plasmon” Scattering from 3D Spherical Metaparticles

This is the final version. Available on open access from the American Chemical Society via the DOI in this recordData Availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.Geometries that replicate the behavior of metal nanostructures at much lower frequencies via texturing surfaces so they will support a surface wave have been a central pillar of metamaterials research. However, previous work has focused largely on geometries that can be reduced to symmetries in one or two dimensions, such as strips, flat planes, and cylinders. Shapes with isotropic responses in three dimensions are important for applications, such as radar scattering and the replication of certain nanoscale behaviors. This work presents a detailed exploration of the scattering behavior of 3D spherical “spoof plasmonic” metaparticles, based on the platonic solids. Their behavior is compared to an effective medium model through simulation and experiment, and the vast range of behaviors that can be produced from a metal sphere of a given radius via tuning its internal structure is explored in detail.Royal Academy of Engineering (RAE)Engineering and Physical Sciences Research Council (EPSRC

The effect of perceptual expectation on repetition suppression to faces is not modulated by variation in autistic traits

There is substantial variation in the magnitude of the repetition suppression (RS) effects across individuals; however the causes of this variation remain unclear. In a recent study, we found that RS in occipitotemporal cortex was negatively related to individual variation in autistic traits in a neurotypical population. Recent proposals have considered autistic behaviours within a Bayesian framework, suggesting that individuals with autism may have 'attenuated priors' (i.e., their perception is less influenced by prior information). Predictive coding represents a neural instantiation of Bayesian inference, and characterises RS as reduction in prediction error between 'top-down' (prior beliefs) and 'bottom-up' (stimulus related) inputs. In accordance with this, evidence shows that RS is greater when repetition of a stimulus is expected relative to when it is unexpected. Here, using an established paradigm which manipulates the probability of stimulus repetition, we investigated the effect of perceptual expectation on RS in a group of neurotypical individuals varying on a measure of autistic traits. We predicted that the magnitude of the perceptual expectation effect would be negatively related to individual differences in autistic traits. We found a significant effect of perceptual expectation on RS in face-selective regions (i.e., greater RS when repetitions were expected relative to unexpected). However, there was no evidence of a relationship between autistic traits and the magnitude of this effect in any face-selective region of interest (ROI). These findings provide a challenge for the proposal that autism spectrum conditions (ASC) may be associated with the attenuated influence of prior information.This work was supported by the UK Medical Research Council under project codes MC-A060-5PQ50 (Andrew J. Calder) and MC_US_A060_0046 (Richard N. Henson)

TGF-beta 1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

Background: Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-β1-mediated EMT. Methods: A549 cells were examined for evidence of EMT after treatment with TGF-β1. EMT was assessed by: morphology under phase-contrast microscopy; Western analysis of cell lysates for expression of mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA), and expression of epithelial phenotypic markers including E-cadherin (E-cad). Markers of fibrogenesis, including collagens and connective tissue growth factor (CTGF) were also evaluated by measuring mRNA level using RT-PCR, and protein by immunofluorescence or Western blotting. Signaling pathways for EMT were characterized by Western analysis of cell lysates using monoclonal antibodies to detect phosphorylated Erk1/2 and Smad2 after TGF-β1 treatment in the presence or absence of MEK inhibitors. The role of Smad2 in TGF-β1-mediated EMT was investigated using siRNA. Results: The data showed that TGF-β1, but not TNF-α or IL-1β, induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner. The process of EMT was accompanied by morphological alteration and expression of the fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF. MMP-2 expression was also evidenced. TGF-β1-induced EMT occurred through phosphorylation of Smad2 and was inhibited by Smad2 gene silencing; MEK inhibitors failed to attenuate either EMT-associated Smad2 phosphorylation or the observed phenotypic changes. Conclusion: Our study shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT via Smad2 activation. Our data support the concept of EMT in lung epithelial cells, and suggest the need for further studies to investigate the phenomenon

Role of the mesoamygdaloid dopamine projection in emotional learning

Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent

Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1

SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts. © 2013 Fregoso et al

Network effects, cooperation and entrepreneurial innovation in China

The rapid rise of an innovative private manufacturing economy in China challenges standard economic explanations of growth, which typically assume the existence of well-defined formal institutions such as property rights and company laws safeguarding investor and creditor interests. We highlight the social structure of cooperation that enables innovative activity in private manufacturing firms when formal property rights protection remains weak. We show how network effects linked to inter-firm cooperation in industrial clusters allowed private entrepreneurs to quickly develop reliable business norms to reduce the inherent risk of malfeasance and contract breach in formal and informal collaborative efforts. Survey data from a sample of 700 manufacturing firms located in China’s Yangzi Delta region confirms that both formal and informal types of inter-firm collaboration are effective, though in different areas of innovative activity

Observations of mixed-species bird flocks at Kichwa Tembo Camp, Kenya

Mixed-species foraging flocks were studied at Kichwa Tembo Camp on the edge of the Masai Mara National Reserve in Kenya between July and September 2004. Observations were made on 29 mixed-species flocks, in which 24 species participated. African Paradise-Flycatcher Terpsiphone viridis, Black-backed Puffback Dryoscopus cubla, Grey-backed Camaroptera Camaroptera brachyura, Collared Sunbird Hedydipna collars and Cabanis's Greenbul Phyllastrephus cabanisi were the most common participants in mixed-species flocks, as well as among the most frequently encountered bird species overall. The Black-backed Puffback was identified as the nuclear species in flocks due to their abundance and frequency with which they were followed by other species. Mixed-species flocks represent another niche dimension in this diverse bird community, but few of these species could be described as flock specialists; most of the birds observed in mixed-species flocks in this study were opportunistic attendant species, including the African Pygmy-Kingfisher Ispidina picta, not previously described as joining mixed-species flocks

SUMOs Mediate the Nuclear Transfer of p38 and p-p38 during Infection

The p38 mitogen activated protein kinase (MAPK) signaling pathway has been suggested to play a significant role in the gastric mucosal inflammatory response to chronic Helicobacter pylori (H. pylori) infection. Nuclear translocation is thought to be important for p38 function, but no nuclear translocation signals have been found in the protein and no nuclear carrier proteins have been identified for p38. We have investigated the role of small ubiquitin-related modifier (SUMO) in the nuclear transfer of p38 in response to H. pylori infection. Exposure of human AGS cells to H. pylori induced the activation of p38 and the expression of SUMOs, especially SUMO-2. SUMO knockdown counteracted the effect of H. pylori infection by decreasing the resulting p38 mediated cellular apoptosis through a reduction in the nuclear fraction of phosphorylated p38. We identified a non-covalent interaction between SUMOs and p38 via SUMO interaction motifs (SIMs), and showed that SUMO-dependent nuclear transfer of p38 was decreased upon mutation of its SIMs. This study has identified a new pathway of p38 nuclear translocation, in response to H. pylori infection. We conclude that in the presence of H. pylori SUMO-2 has a major role in regulating nuclear levels of p38, through non-covalent SUMO-p38 interactions, independent of the p38 phosphorylation state

Big conductance calcium-activated potassium channel openers control spasticity without sedation.

BACKGROUND AND PURPOSE: Our initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis (MS), whilst avoiding the sedative side effects associated with cannabis. VSN16R was synthesized as an anandamide (endocannabinoid) analogue in an anti-metabolite approach to identify drugs that target spasticity. EXPERIMENTAL APPROACH: Following the initial chemistry, a variety of biochemical, pharmacological and electrophysiological approaches, using isolated cells, tissue-based assays and in vivo animal models, were used to demonstrate the activity, efficacy, pharmacokinetics and mechanism of action of VSN16R. Toxicological and safety studies were performed in animals and humans. KEY RESULTS: VSN16R had nanomolar activity in tissue-based, functional assays and dose-dependently inhibited spasticity in a mouse experimental encephalomyelitis model of MS. This effect occurred with over 1000-fold therapeutic window, without affecting normal muscle tone. Efficacy was achieved at plasma levels that are feasible and safe in humans. VSN16R did not bind to known CB1 /CB2 /GPPR55 cannabinoid-related receptors in receptor-based assays but acted on a vascular cannabinoid target. This was identified as the major neuronal form of the big conductance, calcium-activated potassium (BKCa ) channel. Drug-induced opening of neuronal BKCa channels induced membrane hyperpolarization, limiting excessive neural-excitability and controlling spasticity. CONCLUSIONS AND IMPLICATIONS: We identified the neuronal form of the BKCa channel as the target for VSN16R and demonstrated that its activation alleviates neuronal excitability and spasticity in an experimental model of MS, revealing a novel mechanism to control spasticity. VSN16R is a potential, safe and selective ligand for controlling neural hyper-excitability in spasticity

Effectiveness of State and Federal Government Agreements with Major Credit Card and Shipping Companies to Block Illegal Internet Cigarette Sales

Most Internet vendors offer tax-free cigarettes making them cheaper than those sold at stores. This undermines the impact that higher prices have upon reducing consumption. Most Internet tobacco sales have violated taxation and youth access laws, which led to landmark voluntary agreements in 2005 with the major credit card companies and major private shippers to ban payment transactions and shipments for all Internet cigarette sales