Activity-dependent trafficking of lysosomes in dendrites and dendritic spines.

In neurons, lysosomes, which degrade membrane and cytoplasmic components, are thought to primarily reside in somatic and axonal compartments, but there is little understanding of their distribution and function in dendrites. Here, we used conventional and two-photon imaging and electron microscopy to show that lysosomes traffic bidirectionally in dendrites and are present in dendritic spines. We find that lysosome inhibition alters their mobility and also decreases dendritic spine number. Furthermore, perturbing microtubule and actin cytoskeletal dynamics has an inverse relationship on the distribution and motility of lysosomes in dendrites. We also find trafficking of lysosomes is correlated with synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors. Strikingly, lysosomes traffic to dendritic spines in an activity-dependent manner and can be recruited to individual spines in response to local activation. These data indicate the position of lysosomes is regulated by synaptic activity and thus plays an instructive role in the turnover of synaptic membrane proteins

The Bell Laboratories (13)CO Survey: Longitude-Velocity Maps

A survey is presented of the Galactic plane in the J=1-0 transition of (13)CO. About 73,000 spectra were obtained with the 7 m telescope at Bell Laboratories over a ten-year period. The coverage of survey is (l, b) = (-5 to 117, -1 to +1), or 244 square degrees, with a grid spacing of 3' for |b| < 0.5, and a grid spacing of 6' for |b| > 0.5. The data presented here have been resampled onto a 3' grid. For 0.68 km/s channels, the rms noise level of the survey is 0.1 K on the $T_R^*$ scale. The raw data have been transformed into FITS format, and all the reduction processes, such as correcting for emission in the reference positions, baseline removal and interpolation were conducted within IRAF using the FCRAO task package and additional programs. The reduced data are presented here in the form of longitude-velocity color maps at each latitude. These data allow identification and classification of molecular clouds with masses in excess of ~ 1,000 solar masses throughout the first quadrant of the Galaxy. Spiral structure is manifested by the locations of the largest and brightest molecular clouds.Comment: 23 pages, 7 figures, ApJS submitted (out of 41 frames of Figure4, only one is included becaue of size limit

FK506 suppression of heart and liver allograft rejection: II: The induction of graft acceptance in rats

Lewis recipients of orthotopic ACI livers had permanent graft acceptance induced with 3 doses of i.m. FK506 in the early postoperative period. They were studied 100 and 300 days posttransplantation. The re-cipients rejected ACI as well as Brown Norway (BN) (third-party) skin grafts, and had lymphocytes with substantial reactivity by mixed lymphocyte culture testing against ACI and third-party (BN) alloantigens. Lymphocyte subset redistribution had not occurred in the peripheral blood or spleens of these animals, and there was no evidence of Suppressor cell activation by in vitro and in vivo tests. Graft-versus-host reactivity in splenic lymphoid tissues of these recipients was demonstrated with the popliteal lymph node assay. Attempts at adaptive transfer with recipient lymphocytes were unsuccessful. Heart graft acceptance was far more difficult to accomplish than liver graft acceptance, and probably was never permanent. ACI heart graft Prolongation in LEW recipients after a brief induction with FK506 lasted for no more than 3 months in most animals. The temporary heart graft acceptance was specific for hearts of the original ACI donor strain but not for ACI skin. Results of studies of lymphocyte subsets and suppressor cell activity were similar to those in the liver recipients. These studies illustrate how poorly graft acceptance is understood and how badly further work is needed to clarify its mechanism. © 1990 by Williams & Wilkins

Die Computertomographie bei der Bildgebung von Kindern mit kongenitalen Herzvitien

Zusammenfassung: Kongenitale Herzfehler sind die häufigsten kongenitalen Fehlbildungen. Echokardiographie und Katheterangiographie gelten allgemein als Goldstandard zur Abklärung angeborener Herzerkrankungen. Die Magnetresonanztomographie ist aufgrund ihrer Fähigkeit, Herzvitien morphologisch und funktionell zu charakterisieren, als ein wichtiges ergänzendes Verfahren anzusehen. Durch mehr und mehr dosissparende Untersuchungsprotokolle der neuesten Gerätegenerationen und eine gleichzeitig bessere zeitliche und räumliche Auflösung findet die Computertomographie zunehmend Eingang in die Abklärung kongenitaler Herzfehler. In der präoperativen Planung und der postoperativen Kontrolle erlaubt sie eine übersichtliche Darstellung komplexer Fehlbildung nicht nur des Herzens, sondern auch der pulmonalvenösen und -arteriellen Zirkulation sowie des systemischen Kreislaufs. Dieser Beitrag gibt eine Übersicht über die technischen Aspekte der kardialen CT und die Anpassung des Untersuchungsprotokolls an die zu erwartende Pathologie und das Alter des Kindes. Zudem werden die Möglichkeiten und Limitationen der unterschiedlichen dosissparenden Protokolle erläuter

STRATEGIC MULTIPLE SENSOR DATA FUSION FOR TIME-CRITICAL NATURAL DISASTER RESPONSE

Recently, large-scale natural disasters have been occurred in the various areas of the world. The super-sized multi-hazards over the world have required more and more scientific and systematic measurement technologies in the fields of management and response of natural disaster. The purpose of this study is to suggest a multi-sources data fusion approach like LiDAR, aerial images, and satellite imagery and evaluate its applicability for timely natural disaster response. In order to achieve a high-accurate mapping in time in disaster situation, we proposed strategic approach using multi-sensors data fusion in this paper. The data fusion approach using the satellite imagery, low altitude aerial imagery from the mini-UAV and the small manned helicopter, and LiDAR point data simultaneously is expected to enhance the capability for more accurate damage analysis and the faster hazard mapping

Glycosylation characterization of therapeutic mAbs by top- and middle-down mass spectrometry

A reference monoclonal antibody IgG1 and a fusion IgG protein were analyzed by top- and middle-down mass spectrometry with multiple fragmentation techniques including electron transfer dissociation (ETD) and matrix-assisted laser desorption ionization in-source decay (MALDI-ISD) to investigate heterogeneity of glycosylated protein species. Specifically, glycan structure, sites, relative abundance levels, and termini structural conformation were investigated by use of Fourier transform ion cyclotron resonance (FT-ICR) or high performance liquid chromatography electrospray ionization (HPLC-ESI) linked to an Orbitrap. Incorporating a limited enzymatic digestion by immunoglobulin G-degrading enzyme Streptococcus pyogenes (IdeS) with MALDI-ISD analysis extended sequence coverage of the internal region of the proteins without pre-fractionation. The data in this article is associated with the research article published in Journal of Proteomics (Tran et al., 2015)

VivaxGEN: An open access platform for comparative analysis of short tandem repeat genotyping data in Plasmodium vivax populations.

BACKGROUND: The control and elimination of Plasmodium vivax will require a better understanding of its transmission dynamics, through the application of genotyping and population genetics analyses. This paper describes VivaxGEN (http://vivaxgen.menzies.edu.au), a web-based platform that has been developed to support P. vivax short tandem repeat data sharing and comparative analyses. RESULTS: The VivaxGEN platform provides a repository for raw data generated by capillary electrophoresis (FSA files), with fragment analysis and standardized allele calling tools. The query system of the platform enables users to filter, select and differentiate samples and alleles based on their specified criteria. Key population genetic analyses are supported including measures of population differentiation (FST), expected heterozygosity (HE), linkage disequilibrium (IAS), neighbor-joining analysis and Principal Coordinate Analysis. Datasets can also be formatted and exported for application in commonly used population genetic software including GENEPOP, Arlequin and STRUCTURE. To date, data from 10 countries, including 5 publicly available data sets have been shared with VivaxGEN. CONCLUSIONS: VivaxGEN is well placed to facilitate regional overviews of P. vivax transmission dynamics in different endemic settings and capable to be adapted for similar genetic studies of P. falciparum and other organisms

Lattice instabilities of cubic NiTi from first principles

The phonon dispersion relation of NiTi in the simple cubic B2 structure is computed using first-principles density-functional perturbation theory with pseudopotentials and a plane-wave basis set. Lattice instabilities are observed to occur across nearly the entire Brillouin zone, excluding three interpenetrating tubes of stability along the (001) directions and small spheres of stability centered at R. The strongest instability is that of the doubly degenerate M5' mode. The atomic displacements of one of the eigenvectors of this mode generate a good approximation to the observed B19' ground-state structure.Comment: 11 pages, 3 figure

Seminal plasma as a source of prostate cancer peptide biomarker candidates for detection of indolent and advanced disease

Background:Extensive prostate specific antigen screening for prostate cancer generates a high number of unnecessary biopsies and over-treatment due to insufficient differentiation between indolent and aggressive tumours. We hypothesized that seminal plasma is a robust source of novel prostate cancer (PCa) biomarkers with the potential to improve primary diagnosis of and to distinguish advanced from indolent disease. &lt;br&gt;Methodology/Principal Findings: In an open-label case/control study 125 patients (70 PCa, 21 benign prostate hyperplasia, 25 chronic prostatitis, 9 healthy controls) were enrolled in 3 centres. Biomarker panels a) for PCa diagnosis (comparison of PCa patients versus benign controls) and b) for advanced disease (comparison of patients with post surgery Gleason score &#60;7 versus Gleason score &#62;&gt;7) were sought. Independent cohorts were used for proteomic biomarker discovery and testing the performance of the identified biomarker profiles. Seminal plasma was profiled using capillary electrophoresis mass spectrometry. Pre-analytical stability and analytical precision of the proteome analysis were determined. Support vector machine learning was used for classification. Stepwise application of two biomarker signatures with 21 and 5 biomarkers provided 83% sensitivity and 67% specificity for PCa detection in a test set of samples. A panel of 11 biomarkers for advanced disease discriminated between patients with Gleason score 7 and organ-confined (&#60;pT3a) or advanced (&#8805;pT3a) disease with 80% sensitivity and 82% specificity in a preliminary validation setting. Seminal profiles showed excellent pre-analytical stability. Eight biomarkers were identified as fragments of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase​,prostatic acid phosphatase, stabilin-2, GTPase IMAP family member 6, semenogelin-1 and -2. Restricted sample size was the major limitation of the study.&lt;/br&gt; &lt;br&gt;Conclusions/Significance: Seminal plasma represents a robust source of potential peptide makers for primary PCa diagnosis. Our findings warrant further prospective validation to confirm the diagnostic potential of identified seminal biomarker candidates.&lt;/br&gt

Whole-genome sequencing to understand the genetic architecture of common gene expression and biomarker phenotypes.

Initial results from sequencing studies suggest that there are relatively few low-frequency (&lt;5%) variants associated with large effects on common phenotypes. We performed low-pass whole-genome sequencing in 680 individuals from the InCHIANTI study to test two primary hypotheses: (i) that sequencing would detect single low-frequency-large effect variants that explained similar amounts of phenotypic variance as single common variants, and (ii) that some common variant associations could be explained by low-frequency variants. We tested two sets of disease-related common phenotypes for which we had statistical power to detect large numbers of common variant-common phenotype associations-11 132 cis-gene expression traits in 450 individuals and 93 circulating biomarkers in all 680 individuals. From a total of 11 657 229 high-quality variants of which 6 129 221 and 5 528 008 were common and low frequency (&lt;5%), respectively, low frequency-large effect associations comprised 7% of detectable cis-gene expression traits [89 of 1314 cis-eQTLs at P &lt; 1 × 10(-06) (false discovery rate ∼5%)] and one of eight biomarker associations at P &lt; 8 × 10(-10). Very few (30 of 1232; 2%) common variant associations were fully explained by low-frequency variants. Our data show that whole-genome sequencing can identify low-frequency variants undetected by genotyping based approaches when sample sizes are sufficiently large to detect substantial numbers of common variant associations, and that common variant associations are rarely explained by single low-frequency variants of large effect