Description: The dopaminergic system plays an essential role in various functions of the brain, including locomotion, memory, and reward, and the deregulation of dopaminergic signaling as a result of altered functionality of dopamine D2 receptor (DRD2) is implicated in multiple neurologic and psychiatric disorders. Tetraspanin-7 (TSPAN7) is expressed to variable degrees in different tissues, with the highest level in the brain, and multiple mutations in TSPAN7 have been implicated in intellectual disability. Here, we tested the hypothesis that TSPAN7 may be a binding partner of DRD2 that is involved in the regulation of its functional activity. Our results showed that TSPAN7 was associated with DRD2 and reduced its surface expression by enhancing DRD2 internalization. Immunocytochemical analysis revealed that TSPAN7 that resides in the plasma membrane and early and late endosomes promoted internalization of DRD2 and its localization to endosomal compartments of the endocytic pathway. Furthermore, we observed that TSPAN7 deficiency increased surface localization of DRD2 concurrent with the decrease of its endocytosis, regardless of dopamine treatment. Finally, TSPAN7 negatively affects DRD2-mediated signaling. These results disclosed a previously uncharacterized role of TSPAN7 in the regulation of the expression and functional activity of DRD2 by postendocytic trafficking.—Lee, S.-A., Suh, Y., Lee, S., Jeong, J., Kim, S. J., Kim, S. J., Park, S. K. Functional expression of dopamine D2 receptor is regulated by tetraspanin 7–mediated postendocytic trafficking.

Description: We present mid-infrared (MIR) luminosity functions (LFs) of local ( z  〈 0.3) star-forming (SF) galaxies in the AKARI 's North Ecliptic Pole (NEP)-Wide survey field. In order to derive more accurate LF, we used spectroscopic sample only. Based on the NEP-Wide point source catalogue containing a large number of infrared (IR) sources distributed over the wide (5.4 deg 2 ) field, we incorporated the spectroscopic redshift ( z ) data for ~1790 selected targets obtained by optical follow-up surveys with MMT/Hectospec and WIYN/Hydra. The AKARI 's continuous 2–24 μm wavelength coverage as well as photometric data from optical u * band to near-infrared H band with the spectroscopic redshifts for our sample galaxies enable us to derive accurate spectral energy distributions (SEDs) in the MIR. We carried out SED fit analysis and employed 1/ V max method to derive the MIR (e.g. 8, 12, and 15 μm rest-frame) LFs. We fit our 8 μm LFs to the double power-law with the power index of α = 1.53 and β = 2.85 at the break luminosity 4.95  x  10 9 L . We made extensive comparisons with various MIR LFs from several literatures. Our results for local galaxies from the NEP region are generally consistent with other works for different fields over wide luminosity ranges. The comparisons with the results from the NEP-Deep data as well as other LFs imply the luminosity evolution from higher redshifts towards the present epoch.

Description: We present herein galaxy number counts of the nine bands in the 2–24 μm range on the basis of the AKARI North Ecliptic Pole (NEP) surveys. The number counts are derived from NEP-deep and NEP-wide surveys, which cover areas of 0.5 and 5.8 deg 2 , respectively. To produce reliable number counts, the sources were extracted from recently updated images. Completeness and difference between observed and intrinsic magnitudes were corrected by Monte Carlo simulation. Stellar counts were subtracted by using the stellar fraction estimated from optical data. The resultant source counts are given down to the 80 per cent completeness limit; 0.18, 0.16, 0.10, 0.05, 0.06, 0.10, 0.15, 0.16 and 0.44 mJy in the 2.4, 3.2, 4.1, 7, 9, 11, 15, 18 and 24 μm bands, respectively. On the bright side of all bands, the count distribution is flat, consistent with the Euclidean universe, while on the faint side, the counts deviate, suggesting that the galaxy population of the distant universe is evolving. These results are generally consistent with previous galaxy counts in similar wavebands. We also compare our counts with evolutionary models and find them in good agreement. By integrating the models down to the 80 per cent completeness limits, we calculate that the AKARI NEP survey revolves 20–50 per cent of the cosmic infrared background, depending on the wavebands.

Description: We present infrared (IR) galaxy luminosity functions (LFs) in the AKARI North Ecliptic Pole (NEP) deep field using recently-obtained, wider Canada–France–Hawaii Telescope (CFHT) optical/near-IR images. AKARI has obtained deep images in the mid-infrared (IR), covering 0.6 deg 2 of the NEP deep field. However, our previous work was limited to the central area of 0.25 deg 2 due to the lack of optical coverage of the full AKARI NEP survey. To rectify the situation, we recently obtained CFHT optical and near-IR images over the entire AKARI NEP deep field. These new CFHT images are used to derive accurate photometric redshifts, allowing us to fully exploit the whole AKARI NEP deep field. AKARI 's deep, continuous filter coverage in the mid-IR wavelengths (2.4, 3.2, 4.1, 7, 9, 11, 15, 18, and 24 μm) exists nowhere else, due to filter gaps of other space telescopes. It allows us to estimate rest-frame 8 and 12 μm luminosities without using a large extrapolation based on spectral energy distribution fitting, which was the largest uncertainty in previous studies. Total infrared (TIR) luminosity is also obtained more reliably due to the superior filter coverage. The resulting rest-frame 8 and 12 μm, and TIR LFs at 0.15 〈  z  〈 2.2 are consistent with previous works, but with reduced uncertainties, especially at the high-luminosity end, thanks to the wide-field coverage. In terms of cosmic infrared luminosity density ( IR ), we found that the IR evolves as (1 +  z ) 4.2 ± 0.4 .

Description: Mitochondrial dysfunction and synaptic damage are important features of Alzheimer's disease (AD) associated with amyloid β (Aβ) and tau. We reported previously that the scaffolding protein RanBP9, which is overall increased in brains of patients with AD and in mutant APP transgenic mice, simultaneously promotes Aβ generation and focal adhesion disruption by accelerating the endocytosis of APP and β1-integrin, respectively. Moreover, RanBP9 induces neurodegeneration in vitro and in vivo and mediates Aβ-induced neurotoxicity. Here we show in primary hippocampal neurons that RanBP9 potentiates Aβ-induced reactive oxygen species (ROS) overproduction, apoptosis, and calcium deregulation. Analyses of calcium-handling measures demonstrate that RanBP9 selectively delays the clearance of cytosolic Ca 2+ mediated by the mitochondrial calcium uniporter through a process involving the translocation of cofilin into mitochondria and oxidative mechanisms. Further, RanBP9 retards the anterograde axonal transport of mitochondria in primary neurons and decreases synaptic mitochondrial activity in brain. These data indicate that RanBP9, cofilin, and Aβ mimic and potentiate each other to produce mitochondrial dysfunction, ROS overproduction, and calcium deregulation, which leads to neurodegenerative changes reminiscent of those seen in AD.—Roh. S.-E., Woo, J. A., Lakshmana, M. K., Uhlar, C., Ankala, V., Boggess, T., Liu, T., Hong, Y.-H., Mook-Jung, I., Kim, S. J., Kang, D. E. Mitochondrial dysfunction and calcium deregulation by the RanBP9-cofilin pathway.

Description: Alveolar epithelial cell (AEC) mitochondrial dysfunction and apoptosis are important in idiopathic pulmonary fibrosis and asbestosis. Sirtuin 3 (SIRT3) detoxifies mitochondrial reactive oxygen species, in part, by deacetylating manganese superoxide dismutase (MnSOD) and mitochondrial 8-oxoguanine DNA glycosylase. We reasoned that SIRT3 deficiency occurs in fibrotic lungs and thereby augments AEC mtDNA damage and apoptosis. Human lungs were assessed by using immunohistochemistry for SIRT3 activity via acetylated MnSOD K68 . Murine AEC SIRT3 and cleaved caspase-9 (CC-9) expression were assayed by immunoblotting with or without SIRT3 enforced expression or silencing. mtDNA damage was measured by using quantitative PCR and apoptosis via ELISA. Pulmonary fibrosis after asbestos or bleomycin exposure was evaluated in 129SJ/wild-type and SIRT3-knockout mice ( Sirt3 –/– ) by using fibrosis scoring and lung collagen levels. Idiopathic pulmonary fibrosis lung alveolar type II cells have increased MnSOD K68 acetylation compared with controls. Asbestos and H 2 O 2 diminished AEC SIRT3 protein expression and increased mitochondrial protein acetylation, including MnSOD K68 . SIRT3 enforced expression reduced oxidant-induced AEC OGG1 K338/341 acetylation, mtDNA damage, and apoptosis, whereas SIRT3 silencing promoted these effects. Asbestos- or bleomycin-induced lung fibrosis, AEC mtDNA damage, and apoptosis in wild-type mice were amplified in Sirt3 –/– animals. These data suggest a novel role for SIRT3 deficiency in mediating AEC mtDNA damage, apoptosis, and lung fibrosis.—Jablonski, R. P., Kim, S.-J., Cheresh, P., Williams, D. B., Morales-Nebreda, L., Cheng, Y., Yeldandi, A., Bhorade, S., Pardo, A., Selman, M., Ridge, K., Gius, D., Budinger, G. R. S., Kamp, D. W. SIRT3 deficiency promotes lung fibrosis by augmenting alveolar epithelial cell mitochondrial DNA damage and apoptosis.

Description: We present numerical studies of the imaging and caustic properties of the singular isothermal sphere (SIS) under a wide range of external shear (from 0.0 to 2.0). Using a direct inverse-mapping formula for this lensing system,we investigate various lensing properties for both low-shear (i.e.  〈 1.0) and high-shear (i.e.  〉 1.0) cases: the image separations, the total or individual magnifications, the flux ratios of two images, the maximum number of images and the lensing cross-sections. We systematically analyse the effective lensing cross-sections of double-lensing and quadruple-lensing systems, based on the radio luminosity function obtained by the Jodrell–VLA Astrometric Survey (JVAS) and the Cosmic Lens All-Sky Survey (CLASS). We find that the limit of a survey selection bias (i.e. between brighter and fainter images) preferentially reduces the effective lensing cross-sections of two-image lensing systems. By considering the effects of survey selection bias, we demonstrate that the long-standing anomaly over the high quads-to-doubles ratios (i.e. 50–70 per cent for JVAS and CLASS) can be explained by the moderate effective shear of 0.16–0.18, which is half that of previous estimates. The derived inverse-mapping formula could make the SIS + shear lensing model useful for galaxy-lensing simulations.

Description: We present the first galaxy counts at 18 μm using the Japanese AKARI satellite's survey at the North Ecliptic Pole (NEP), produced from the images from the NEP-Deep and NEP-Wide surveys covering 0.6 and 5.8 deg 2 , respectively. We describe a procedure using a point source filtering algorithm to remove background structure and a minimum variance method for our source extraction and photometry that delivers the optimum signal to noise for our extracted sources, confirming this by comparison with standard photometry methods. The final source counts are complete and reliable over three orders of magnitude in flux density, resulting in sensitivities (80 per cent completeness) of 0.15 and 0.3 mJy for the NEP-Deep and NEP-Wide surveys, respectively, a factor of 1.3 deeper than previous catalogues constructed from this field. The differential source counts exhibit a characteristic upturn from Euclidean expectations at around a milliJansky and a corresponding evolutionary bump between 0.2–0.4 mJy consistent with previous mid-infrared surveys with ISO and Spitzer at 15 and 24 μm. We compare our results with galaxy evolution models confirming the striking divergence from the non-evolving scenario. The models and observations are in broad agreement implying that the source counts are consistent with a strongly evolving population of luminous infrared galaxies at redshifts higher than unity. Integrating our source counts down to the limit of the NEP survey at the 150 μJy level we calculate that AKARI has resolved approximately 55 per cent of the 18 μm cosmic infrared background relative to the predictions of contemporary source count models.