Deletion of Tsc2 in nociceptors reduces target innervation, ion channel expression, and sensitivity to heat

AbstractThe mechanistic target of rapamycin complex 1 (mTORC1) is known to regulate cellular growth pathways, and its genetic activation is sufficient to enhance regenerative axon growth following injury to the central or peripheral nervous systems. However, excess mTORC1 activation may promote innervation defects, and mTORC1 activity mediates injury-induced hypersensitivity, reducing enthusiasm for the pathway as a therapeutic target. While mTORC1 activity is required for full expression of some pain modalities, the effects of pathway activation on nociceptor phenotypes and sensory behaviors are currently unknown. To address this, we genetically activated mTORC1 in mouse peripheral sensory neurons by conditional deletion of its negative regulator Tuberous Sclerosis Complex 2 (Tsc2). Consistent with the well-known role of mTORC1 in regulating cell size, soma size and axon diameter of C-nociceptors were increased in Tsc2-deleted mice. Glabrous skin and spinal cord innervation by C-fiber neurons were also disrupted. Transcriptional profiling of nociceptors enriched by fluorescence-associated cell sorting (FACS) revealed downregulation of multiple classes of ion channels as well as reduced expression of markers for peptidergic nociceptors in Tsc2-deleted mice. In addition to these changes in innervation and gene expression, Tsc2-deleted mice exhibited reduced noxious heat sensitivity and decreased injury-induced cold hypersensitivity, but normal baseline sensitivity to cold and mechanical stimuli. Together, these data show that excess mTORC1 activity in sensory neurons produces changes in gene expression, neuron morphology and sensory behavior.</jats:p

Influence of aerosol and surface reflectance variability on hyperspectral observed radiance

Current aerosol retrievals based on visible and near infrared remote-sensing, are prone to loss of accuracy, where the assumptions of the applied algorithm are violated. This happens mostly over land and it is related to misrepresentation of specific aerosol conditions or surface properties. New satellite missions, based on high spectral resolution instruments, such as PRISMA (Hyperspectral Precursor of the Application Mission), represent a valuable opportunity to improve the accuracy of &amp;tau;&lt;sup&gt;a&lt;/sup&gt;&lt;sub&gt;550&lt;/sub&gt; retrievable from a remote-sensing system developing new atmospheric measurement techniques. This paper aims to address the potential of these new observing systems in more accurate retrieving &amp;tau;&lt;sup&gt;a&lt;/sup&gt;&lt;sub&gt;550&lt;/sub&gt;, specifically over land in heterogeneous and/or homogeneous areas composed by dark and bright targets. The study shows how the variation of the hyperspectral observed radiance can be addressed to recognise a variation of &amp;Delta;&amp;tau;&lt;sup&gt;a&lt;/sup&gt;&lt;sub&gt;550&lt;/sub&gt; = 0.02. The goal has been achieved by using simulated radiances by combining two aerosol models (urban and continental) and two reflecting surfaces: dark (represented by water) and bright (represented by sand) for the PRISMA instrument, considering the environmental contribution of the observed radiance, i.e., the adjacency effect. Results showed that, in the continental regime, the expected instrument sensitivity would allow for retrieval accuracy of the aerosol optical thickness at 550 nm of 0.02 or better, with a dark surface surrounded by dark areas. The study also showed that for the urban regime, the surface plays a more significant role, with a bright surface surrounded by dark areas providing favourable conditions for the aerosol load retrievals, and dark surfaces representing less suitable situations for inversion independently of the surroundings. However, over all, the results obtained provide evidence that high resolution observations of Earth spectrum between 400 and 1000 nm would allow for a significant improvement of the accuracy of the &amp;tau;&lt;sup&gt;a&lt;/sup&gt;&lt;sub&gt;550&lt;/sub&gt; for anthropogenic/natural aerosols over land

Performance analysis of MPEG-4 decoder and encoder

© 2002 Croatian Soc. Electronics in Marine-ELMAR. A performance analysis of MPEG-4 encoder and decoder programs on a standard personal computer is presented. The paper first describes the MPEG-4 computational load and discusses related works, then outlines the performance analysis. Experimental results show that while the decoder program can be easily executed in real time, the encoder requires execution times in the order of seconds per frame which call for substantial optimisation to satisfy real-time constraints

Gpr126/Adgrg6 has Schwann cell autonomous and nonautonomous functions in peripheral nerve injury and repair

Schwann cells (SCs) are essential for proper peripheral nerve development and repair, although the mechanisms regulating these processes are incompletely understood. We previously showed that the adhesion G protein-coupled receptor Gpr126/Adgrg6 is essential for SC development and myelination. Interestingly, the expression of Gpr126 is maintained in adult SCs, suggestive of a function in the mature nerve. We therefore investigated the role of Gpr126 in nerve repair by studying an inducible SC-specific Gpr126 knock-out mouse model. Here, we show that remyelination is severely delayed after nerve-crush injury. Moreover, we also observe noncell-autonomous defects in macrophage recruitment and axon regeneration in injured nerves following loss of Gpr126 in SCs. This work demonstrates that Gpr126 has critical SC-autonomous and SC-nonautonomous functions in remyelination and peripheral nerve repair. SIGNIFICANCE STATEMENT Lack of robust remyelination represents one of the major barriers to recovery of neurological functions in disease or following injury in many disorders of the nervous system. Here we show that the adhesion class G protein-coupled receptor (GPCR) Gpr126/Adgrg6 is required for remyelination, macrophage recruitment, and axon regeneration following nerve injury. At least 30% of all approved drugs target GPCRs; thus, Gpr126 represents an attractive potential target to stimulate repair in myelin disease or following nerve injury

Colloidal CuFeS2 Nanocrystals: Intermediate Fe d-Band Leads to High Photothermal Conversion Efficiency

We describe the colloidal hot-injection synthesis of phase-pure nanocrystals (NCs) of a highly abundant mineral, chalcopyrite (CuFeS2). Absorption bands centered at around 480 and 950 nm, spanning almost the entire visible and near infrared regions, encompass their optical extinction characteristics. These peaks are ascribable to electronic transitions from the valence band (VB) to the empty intermediate band (IB), located in the fundamental gap and mainly composed of Fe 3d orbitals. Laser-irradiation (at 808 nm) of an aqueous suspension of CuFeS2 NCs exhibited significant heating, with a photothermal conversion efficiency of 49%. Such efficient heating is ascribable to the carrier relaxation within the broad IB band (owing to the indirect VB-IB gap), as corroborated by transient absorption measurements. The intense absorption and high photothermal transduction efficiency (PTE) of these NCs in the so-called biological window (650-900 nm) makes them suitable for photothermal therapy as demonstrated by tumor cell annihilation upon laser irradiation. The otherwise harmless nature of these NCs in dark conditions was confirmed by in vitro toxicity tests on two different cell lines. The presence of the deep Fe levels constituting the IB is the origin of such enhanced PTE, which can be used to design other high performing NC photothermal agents.Comment: 12 pages, Chemistry of Materials, 31-May-201

Genetic drift at expanding frontiers promotes gene segregation

Competition between random genetic drift and natural selection plays a central role in evolution: Whereas non-beneficial mutations often prevail in small populations by chance, mutations that sweep through large populations typically confer a selective advantage. Here, however, we observe chance effects during range expansions that dramatically alter the gene pool even in large microbial populations. Initially well-mixed populations of two fluorescently labeled strains of Escherichia coli develop well-defined, sector-like regions with fractal boundaries in expanding colonies. The formation of these regions is driven by random fluctuations that originate in a thin band of pioneers at the expanding frontier. A comparison of bacterial and yeast colonies (Saccharomyces cerevisiae) suggests that this large-scale genetic sectoring is a generic phenomenon that may provide a detectable footprint of past range expansions.Comment: Please visit http://www.pnas.org/content/104/50/19926.abstract for published articl

Measurement of Dielectric Suppression of Bremsstrahlung

In 1953, Ter-Mikaelian predicted that the bremsstrahlung of low energy photons in a medium is suppressed because of interactions between the produced photon and the electrons in the medium. This suppression occurs because the emission takes place over on a long distance scale, allowing for destructive interference between different instantaneous photon emission amplitudes. We present here measurements of bremsstrahlung cross sections of 200 keV to 20 MeV photons produced by 8 and 25 GeV electrons in carbon and gold targets. Our data shows that dielectric suppression occurs at the predicted level, reducing the cross section up to 75 percent in our data.Comment: 11 pages, format is postscript file, gzip-ed, uuencode-e