Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation.

Recent studies indicate that insulin stimulation of glucose transporter (GLUT)4 translocation requires at least two distinct insulin receptor-mediated signals: one leading to the activation of phosphatidylinositol 3 (PI-3) kinase and the other to the activation of the small GTP binding protein TC10. We now demonstrate that TC10 is processed through the secretory membrane trafficking system and localizes to caveolin-enriched lipid raft microdomains. Although insulin activated the wild-type TC10 protein and a TC10/H-Ras chimera that were targeted to lipid raft microdomains, it was unable to activate a TC10/K-Ras chimera that was directed to the nonlipid raft domains. Similarly, only the lipid raft-localized TC10/ H-Ras chimera inhibited GLUT4 translocation, whereas the TC10/K-Ras chimera showed no significant inhibitory activity. Furthermore, disruption of lipid raft microdomains by expression of a dominant-interfering caveolin 3 mutant (Cav3/DGV) inhibited the insulin stimulation of GLUT4 translocation and TC10 lipid raft localization and activation without affecting PI-3 kinase signaling. These data demonstrate that the insulin stimulation of GLUT4 translocation in adipocytes requires the spatial separation and distinct compartmentalization of the PI-3 kinase and TC10 signaling pathways

Reverse taxonomy for elucidating diversity of insect-associated nematodes: a case study with termites

BACKGROUND: The molecular operational taxonomic unit(MOTU)has recently been applied to microbial and microscopic animal biodiversity surveys. However, in many cases, some of the MOTUs cannot be definitively tied to any of the taxonomic groups in current databases. To surmount these limitations, the concept of "reverse taxonomy" has been proposed, i.e. to primarily list the MOTUs with morphological information, and then identify and/or describe them at genus/species level using subsamples or by re-isolating the target organisms. Nevertheless, the application of "reverse taxonomy" has not been sufficiently evaluated. Therefore, the practical applicability of "reverse taxonomy" is tested using termite-associated nematodes as a model system for phoretic/parasitic organisms which have high habitat specificity and a potential handle (their termite host species) for re-isolation attempts. METHODOLOGY: Forty-eight species (from 298 colonies) of termites collected from the American tropics and subtropics were examined for their nematode associates using the reverse taxonomy method and culturing attempts (morphological identification and further sequencing efforts). The survey yielded 51 sequence types (= MOTUs) belonging to 19 tentatively identified genera. Within these, four were identified based on molecular data with preliminary morphological observation, and an additional seven were identified or characterized from successful culturing, leaving eight genera unidentified. CONCLUSIONS: That 1/3 of the genera were not successfully identified suggests deficiencies in the depth of available sequences in the database and biological characters, i.e. usually isolated as phoretic/parasitic stages which are not available for morphological identification, and too many undiscovered lineages of nematodes. Although there still is the issue of culturability of nematodes, culturing attempts could help to make reverse taxonomy methods more effective. However, expansion of the database, i.e., production of more DNA barcodes tied to biological information by finding and characterizing additional new and known lineages, is necessary for analyzing functional diversity.Natsumi Kanzaki, Robin M. Giblin-Davis, Rudolf H. Scheffrahn, Hisatomo Taki, Alejandro Esquivel, Kerrie A. Davies and E. Allen Herr

Objective and quantitative estimation of the optimal timing for epiretinal membrane surgery on the basis of metamorphopsia

Purpose: To establish an objective and quantitative biomarker of metamorphopsia in epiretinal membranes (ERMs) and determine the optimal timing for ERM surgery. Methods: Retrospectively, 172 eyes with ERM were reviewed. Retinal folds due to tangential traction by ERM were visualized by en face optical coherence tomography (OCT). The maximum depth of retinal folds (MDRF) within the parafovea was quantified. Metamorphopsia was quantified by M-CHARTS. The change in the distance between the retinal vessels after ERM surgery and the preoperative total depth of retinal folds between the vessels were quantified using en face OCT and OCT angiography. Results: Significant correlations were observed between preoperative MDRF and M-CHARTS scores before and at 6 months after surgery (r=0.617 and 0.460, respectively; P Conclusion: MDRF is an objective and quantitative biomarker of metamorphopsia in ERM. To maintain patients’ quality of vision, ERM surgery may be performed when the preoperative MDRF ranges between 69 and 118 μm

Generic User Process Interface for Event Generators

Generic Fortran common blocks are presented for use by High Energy Physics event generators for the transfer of event configurations from parton level generators to showering and hadronization event generators.Comment: Physics at TeV Colliders II Workshop, Les Houches, France, May 2001 14 pages, 6 figure

Bcl-2 genes regulate noise-induced hearing loss

Proteins of the Bcl-2 family have been implicated in control of apoptotic pathways modulating neuronal cell death, including noise-induced hearing loss. In this study, we assessed the expressions of anti- and proapoptotic Bcl-2 genes, represented by Bcl-xL and Bak following noise exposures, which yielded temporary threshold shift (TTS) or permanent threshold shift (PTS). Auditory brainstem responses (ABRs) were assessed at 4, 8, and 16 kHz before exposure and on days 1, 3, 7, and 10 following exposure to 100 dB SPL, 4 kHz OBN, 1 hr (TTS) or 120 dB SPL, 4 kHz OBN, 5 hr (PTS). On day 10, subjects were euthanized. ABR thresholds increased following both exposures, fully recovered following the TTS exposure, and showed a 22.6 dB (4 kHz), 42.5 dB (8 kHz), and 44.9 dB (16 kHz) mean shift on day 10 following the PTS exposure. PTS was accompanied by outer hair cell loss progressing epically and basally from the 4-kHz region. Additional animals were euthanized for immunohistochemical assessment. BcL-xL was robustly expressed in outer hair cells following TTS exposure, whereas Bak was expressed following PTS exposure. These results indicate an important role of the Bcl-2 family proteins in regulating sensory cell survival or death following intense noise. Bcl-xL plays an essential role in prevention of sensory cell death following TTS levels of noise, and PTS exposure provokes the expression of Bak and, with that, cell death. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58028/1/21533_ftp.pd

Prospects for the Search for a Standard Model Higgs Boson in ATLAS using Vector Boson Fusion

The potential for the discovery of a Standard Model Higgs boson in the mass range m_H < 2 m_Z in the vector boson fusion mode has been studied for the ATLAS experiment at the LHC. The characteristic signatures of additional jets in the forward regions of the detector and of low jet activity in the central region allow for an efficient background rejection. Analyses for the H -> WW and H -> tau tau decay modes have been performed using a realistic simulation of the expected detector performance. The results obtained demonstrate the large discovery potential in the H -> WW decay channel and the sensitivity to Higgs boson decays into tau-pairs in the low-mass region around 120 GeV.Comment: 20 pages, 13 ps figures, uses EPJ style fil