João T. Costa

Excitotoxicity Downregulates TrkB.FL Signaling and Upregulates the Neuroprotective Truncated TrkB Receptors in Cultured Hippocampal and Striatal Neurons.

Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival through activation of TrkB receptors. The trkB gene encodes a full-length receptor tyrosine kinase (TrkB.FL) and its truncated (T1/T2) isoforms. We investigated the changes in TrkB protein levels and signaling activity under excitotoxic conditions, which are characteristic of brain ischemia, traumatic brain injury, and neurodegenerative disorders. Excitotoxic stimulation of cultured rat hippocampal or striatal neurons downregulated TrkB.FL and upregulated a truncated form of the receptor (TrkB.T). Downregulation of TrkB.FL was mediated by calpains, whereas the increase in TrkB.T protein levels required transcription and translation activities. Downregulation of TrkB.FL receptors in hippocampal neurons correlated with a decrease in BDNF-induced activation of the Ras/ERK and PLCγ pathways. However, calpain inhibition, which prevents TrkB.FL degradation, did not preclude the decrease in signaling activity of these receptors. On the other hand, incubation with anisomycin, to prevent the upregulation of TrkB.T, protected to a large extent the TrkB.FL signaling activity, suggesting that truncated receptors may act as dominant-negatives. The upregulation of TrkB.T under excitotoxic conditions was correlated with an increase in BDNF-induced inhibition of RhoA, a mediator of excitotoxic neuronal death. BDNF fully protected hippocampal neurons transduced with TrkB.T when present during excitotoxic stimulation with glutamate, in contrast with the partial protection observed in cells overexpressing TrkB.FL or expressing GFP. These results indicate that BDNF protects hippocampal neurons by two distinct mechanisms: through the neurotrophic effects of TrkB.FL receptors and by activation of TrkB.T receptors coupled to inhibition of the excitotoxic signaling.

Finite-difference frequency-domain method for the extraction of effective parameters of metamaterials

Here, we report a numerical implementation of the nonlocal homogenization approach recently proposed in [M. G. Silveirinha, Phys. Rev. B 75, 115104 (2007)], using the finite-difference frequency-domain method to discretize the Maxwell equations. We apply the developed formalism to characterize the nonlocal dielectric function of several structured materials formed by dielectric and metallic particles and, in particular, we extract the local permittivity, permeability, and magnetoelectric coupling parameters when these are meaningful. It is shown that the finite-difference frequency-domain implementation of the homogenization method is stable and robust, yielding very accurate results.

Achromatic lens based on a nanowire material with anomalous dispersion.

Achromatic doublets made of materials with normal dispersion have been used for decades to minimize the effects of chromatic aberrations inherent to single-glass optical lenses. Here, we propose a fundamentally different solution to correct the chromatic aberrations based on a nanowire metamaterial with low loss broadband anomalous dispersion in the visible domain. It is theoretically and numerically shown that the proposed metamaterial lens practically eliminates the chromatic aberrations for all the colors of light, and may be an interesting alternative to conventional achromatic doublets.

Gephyrin Cleavage in In Vitro Brain Ischemia Decreases GABAA Receptor Clustering and Contributes to Neuronal Death.

GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the central nervous system, and changes in GABAergic neurotransmission modulate the activity of neuronal networks. Gephyrin is a scaffold protein responsible for the traffic and synaptic anchoring of GABAA receptors (GABAAR); therefore, changes in gephyrin expression and oligomerization may affect the activity of GABAergic synapses. In this work, we investigated the changes in gephyrin protein levels during brain ischemia and in excitotoxic conditions, which may affect synaptic clustering of GABAAR. We found that gephyrin is cleaved by calpains following excitotoxic stimulation of hippocampal neurons with glutamate, as well as after intrahippocampal injection of kainate, giving rise to a stable cleavage product. Gephyrin cleavage was also observed in cultured hippocampal neurons subjected to transient oxygen-glucose deprivation (OGD), an in vitro model of brain ischemia, and after transient middle cerebral artery occlusion (MCAO) in mice, a model of focal brain ischemia. Furthermore, a truncated form of gephyrin decreased the synaptic clustering of the protein, reduced the synaptic pool of GABAAR containing γ2 subunits and upregulated OGD-induced cell death in hippocampal cultures. Our results show that excitotoxicity and brain ischemia downregulate full-length gephyrin with a concomitant generation of truncated products, which affect synaptic clustering of GABAAR and cell death.

Reversed rainbow with a nonlocal metamaterial

One of the intriguing potentials of metamaterials is the possibility to realize a nonlocal electromagnetic reaction, such that the effective medium response at a given point is fundamentally entangled with the macroscopic field distribution at long distances. Here, it is experimentally and numerically verified that a microwave nonlocal metamaterial formed by crossed metallic wires enables a low-loss broadband anomalous material response such that the refractive index decreases with frequency. Notably, it is shown that an electromagnetic beam refracted by our metamaterial prism creates a reversed microwave rainbow.

Numerical modeling of the electromagnetic response of complex shaped spatially dispersive bodies

The solution of scattering problems in scenarios wherein electromagnetic waves interact with arbitrary shaped bodies with a spatially dispersive response cannot be found using analytical methods. Here, we develop a completely general and efficient spatially dispersive finite-difference frequency-domain (FDFD) based method that accurately models the electromagnetic response of complex shaped wire media with arbitrary geometries. Moreover, we prove that it is fundamental to properly model the internal degrees of freedom of the metamaterial at the interfaces.

Suppression of chromatic aberrations based on a metamaterial with anomalous dispersion

In this work we show that the chromatic aberrations inherent to optical glass lenses may be eliminated for all the wavelengths of the visible spectrum by coating a standard glass lens with a nanowire spatially dispersive metamaterial characterized by anomalous frequency dispersion. A finite-difference frequency-domain (FDFD) based method is proposed to solve the Maxwell-Equations in the presence of spatially dispersive bodies.