17 research outputs found

    Enhanced Hippocampal Long-Term Potentiation and Fear Memory in Btbd9 Mutant Mice

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    Polymorphisms in BTBD9 have recently been associated with higher risk of restless legs syndrome (RLS), a neurological disorder characterized by uncomfortable sensations in the legs at rest that are relieved by movement. The BTBD9 protein contains a BTB/POZ domain and a BACK domain, but its function is unknown. To elucidate its function and potential role in the pathophysiology of RLS, we generated a line of mutant Btbd9 mice derived from a commercial gene-trap embryonic stem cell clone. Btbd9 is the mouse homolog of the human BTBD9. Proteins that contain a BTB/POZ domain have been reported to be associated with synaptic transmission and plasticity. We found that Btbd9 is naturally expressed in the hippocampus of our mutant mice, a region critical for learning and memory. As electrophysiological characteristics of CA3-CA1 synapses of the hippocampus are well characterized, we performed electrophysiological recordings in this region. The mutant mice showed normal input-output relationship, a significant impairment in pre-synaptic activity, and an enhanced long-term potentiation. We further performed an analysis of fear memory and found the mutant mice had an enhanced cued and contextual fear memory. To elucidate a possible molecular basis for these enhancements, we analyzed proteins that have been associated with synaptic plasticity. We found an elevated level of dynamin 1, an enzyme associated with endocytosis, in the mutant mice. These results suggest the first identified function of Btbd9 as being involved in regulating synaptic plasticity and memory. Recent studies have suggested that enhanced synaptic plasticity, analogous to what we have observed, in other regions of the brain could enhance sensory perception similar to what is seen in RLS patients. Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS

    Negative feedback regulation of the ERK1/2 MAPK pathway

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    The extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signalling pathway regulates many cellular functions, including proliferation, differentiation, and transformation. To reliably convert external stimuli into specific cellular responses and to adapt to environmental circumstances, the pathway must be integrated into the overall signalling activity of the cell. Multiple mechanisms have evolved to perform this role. In this review, we will focus on negative feedback mechanisms and examine how they shape ERK1/2 MAPK signalling. We will first discuss the extensive number of negative feedback loops targeting the different components of the ERK1/2 MAPK cascade, specifically the direct posttranslational modification of pathway components by downstream protein kinases and the induction of de novo gene synthesis of specific pathway inhibitors. We will then evaluate how negative feedback modulates the spatiotemporal signalling dynamics of the ERK1/2 pathway regarding signalling amplitude and duration as well as subcellular localisation. Aberrant ERK1/2 activation results in deregulated proliferation and malignant transformation in model systems and is commonly observed in human tumours. Inhibition of the ERK1/2 pathway thus represents an attractive target for the treatment of malignant tumours with increased ERK1/2 activity. We will, therefore, discuss the effect of ERK1/2 MAPK feedback regulation on cancer treatment and how it contributes to reduced clinical efficacy of therapeutic agents and the development of drug resistance

    Lateral forces on circularly polarizable particles near a surface

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    Optical forces allow manipulation of small particles and control of nanophotonic structures with light beams. While some techniques rely on structured light to move particles using field intensity gradients, acting locally, other optical forces can push particles on a wide area of illumination but only in the direction of light propagation. Here we show that spin orbit coupling, when the spin of the incident circularly polarized light is converted into lateral electromagnetic momentum, leads to a lateral optical force acting on particles placed above a substrate, associated with a recoil mechanical force. This counterintuitive force acts in a direction in which the illumination has neither a field gradient nor propagation. The force direction is switchable with the polarization of uniform, plane wave illumination, and its magnitude is comparable to other optical forces.This work has been supported, in part, by EPSRC (UK). 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    The High-Order Toroidal Moments and Anapole States in All-Dielectric Photonics

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    All-dielectric nanophotonics attracts ever increasing attention nowadays due to the possibility of controlling and configuring light scattering on high-index semiconductor nanoparticles. It opens a room of opportunities for designing novel types of nanoscale elements and devices, and paves the way for advanced technologies of light energy manipulation. One of the exciting and promising prospects is associated with utilizing the so-called toroidal moment, being the result of poloidal currents excitation, and anapole states, corresponding to the interference of dipole and toroidal electric moments. Here, higher-order toroidal moments of both types (up to the electric octupole toroidal moment) are presented and investigated in detail via the direct Cartesian multipole decomposition allowing new near- and far-field configurations to be obtained. Poloidal currents can be associated with vortex-like distributions of the displacement currents inside nanoparticles, revealing the physical meaning of the high-order toroidal moments and the convenience of the Cartesian multipoles as an auxiliary tool for analysis. High-order nonradiating anapole states accompanied by the excitation of intense near-fields are demonstrated. It is believed that the results are of high importance for both the fundamental understanding of light scattering by high-index particles and a variety of nanophotonics applications and light governing on nanoscale

    ‘Photonic Hook’ based optomechanical nanoparticle manipulator

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    Abstract Specialized electromagnetic fields can be used for nanoparticle manipulation along a specific path, allowing enhanced transport and control over the particle’s motion. In this paper, we investigate the optical forces produced by a curved photonic jet, otherwise known as the “photonic hook”, created using an asymmetric cuboid. In our case, this cuboid is formed by appending a triangular prism to one side of a cube. A gold nanoparticle immersed in the cuboid’s transmitted field moves in a curved trajectory. This result could be used for moving nanoparticles around obstacles; hence we also consider the changes in the photonic hook’s forces when relatively large glass and gold obstacles are introduced at the region where the curved photonic jet is created. We show, that despite the obstacles, perturbing the field distribution, a particle can move around glass obstacles of a certain thickness. For larger glass slabs, the particle will be trapped stably near it. Moreover, we noticed that a partial obstruction of the photonic jet’s field using the gold obstacle results in a complete disruption of the particle’s trajectory

    Information storage and retrieval in a single levitating colloidal particle

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    The binary switch is a basic component of digital information. From phase-change alloys to nanomechanical beams, molecules and atoms, new strategies for controlled bistability hold great interest for emerging technologies. We present a generic methodology for precise and parallel spatiotemporal control of nanometre-scale matter in a fluid, and demonstrate the ability to attain digital functionalities such as switching, gating and data storage in a single colloid, with further implications for signal amplification and logic operations. This fluid-phase bit can be arrayed at high densities, manipulated by either electrical or optical fields, supports low-energy, high-speed operation and marks a first step toward ‘colloidal information’. The principle generalizes to any system where spatial perturbation of a particle elicits a differential response amenable to readout
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