Research articles

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  • An integrated, miniature (1.9 g) fluorescence microscope containing light source, optics and sensor allows high-speed, wide field of view imaging of calcium spiking in hundreds of neurons in freely moving mice. The mass-producible portable microscope is also useful for a variety of fluorescence assays for which size, cost and portability can be concerns.

    • Kunal K Ghosh
    • Laurie D Burns
    • Mark J Schnitzer
    Article
  • This paper reports transgenesis by genetic modification of gametes in the domestic cat. The approach is used to generate transgenic cats expressing a virus restriction factor from rhesus macaque.

    • Pimprapar Wongsrikeao
    • Dyana Saenz
    • Eric Poeschla
    Article
  • An algorithm for linear mixed models substantially reduces memory usage and run time for genome-wide association studies. The improved algorithm scales linearly in cohort size, allowing the application of these models to much larger samples.

    • Christoph Lippert
    • Jennifer Listgarten
    • David Heckerman
    Brief Communication
  • Reprogramming to induced pluripotency of cells from the endangered silver-maned drill and the northern white rhinoceros is reported. Induced pluripotent stem cells from endangered species may prove useful for species preservation in the future.

    • Inbar Friedrich Ben-Nun
    • Susanne C Montague
    • Jeanne F Loring
    Brief Communication
  • Expression profiles of several hundred microRNAs in the blood of individuals with disease, including autoimmune disease, cancers, cardiovascular disease and chronic inflammatory disease are reported.

    • Andreas Keller
    • Petra Leidinger
    • Eckart Meese
    Brief Communication
  • Destabilized mutants of firefly luciferase are characterized as sensors for protein homeostasis (proteostasis). Their use as tools for comparisons of proteostasis capacity is demonstrated in cells and in Caenorhabditis elegans.

    • Rajat Gupta
    • Prasad Kasturi
    • Swasti Raychaudhuri
    Article
  • A method for performing quantitative proteomics experiments in Caenorhabditis elegans using stable-isotope labeling of lysine is described. The method can be coupled with RNA interference to examine global effects on the proteome. Also in this issue, Larance et al. describe a very similar method.

    • Julius Fredens
    • Kasper Engholm-Keller
    • Nils J Færgeman
    Brief Communication
  • A method for performing quantitative proteomics experiments in Caenorhabditis elegans using stable-isotope labeling with amino acids in cell culture (SILAC) is described. The authors used the method to identify heat shock–responsive proteins in worms. Also in this issue, Fredens et al. describe a very similar method.

    • Mark Larance
    • Aymeric P Bailly
    • Angus I Lamond
    Brief Communication
  • Presented is an experimental analysis of the stability of transgene expression, the perturbation of endogenous expression and the perturbation of epigenetic organization upon site-directed delivery of transgenes to the CCR5 and AAVS1 loci in human cells. It provides guidelines for optimal cassette design for stable and nonperturbative gene transfer.

    • Angelo Lombardo
    • Daniela Cesana
    • Luigi Naldini
    Article
  • A fluorescent protein that can be photoswitched with visible light from orange to far-red is presented. The photoconverted form has the most red-shifted excitation peak of all GFP-like fluorescent proteins to date and should be useful for many imaging applications.

    • Oksana M Subach
    • George H Patterson
    • Vladislav V Verkhusha
    Article
  • Two-photon excitation in scanned light-sheet microscopy allows deeper imaging than the one-photon implementation and faster three-dimensional imaging of organism development with no evidence of phototoxicity compared to conventional two-photon point scanning microscopy.

    • Thai V Truong
    • Willy Supatto
    • Scott E Fraser
    Brief Communication
  • Quantitative, large-scale in vivo phosphoproteomics analyses are made possible with a form of spike-in stable-isotope labeling with amino acids in cell culture (SILAC), in which SILAC-labeled cell lines act as an internal standard for mass spectrometry–based tissue phosphoproteome analysis.

    • Mara Monetti
    • Nagarjuna Nagaraj
    • Matthias Mann
    Brief Communication
  • A fluorescent reporter, named traffic light, reads out whether repair of a DNA break occurs by nonhomologous end-joining or by homologous recombination. It should enable the identification of factors that affect repair pathway choice and thus improved approaches for genome engineering.

    • Michael T Certo
    • Byoung Y Ryu
    • Andrew M Scharenberg
    Article
  • Ubiquitin, an important post-translational modification that regulates a variety of biological processes is found in free and conjugated (monoubiquitin and polyubiquitin) forms in the cell. A method for precisely measuring these cellular pools using protein standard absolute quantification mass spectrometry is described; the approach should yield insights into ubiquitin signaling.

    • Stephen E Kaiser
    • Brigit E Riley
    • Ron R Kopito
    Article
  • This digital PCR device arrays samples into one million small-volume reactors, achieving a dynamic range of 107, measurement precision better than 1% and the ability to detect single-nucleotide variants present at less than 1:100,000.

    • Kevin A Heyries
    • Carolina Tropini
    • Carl L Hansen
    Brief Communication