Nature Methods Contents: December 2015 Volume 12 pp 1099 - 1204

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Advertisement ZEISS LSM 8 family with Airyscan - Revolutionize your confocal imaging Learn how to improve signal-to-noise ratio and resolution of your confocal imaging. Discover how Airyscan, the novel detector for the ZEISS LSM 8 family compares to traditional confocal detectors and download our free white paper with more information: www.zeiss.com/airyscan TABLE OF CONTENTS December 2015 Volume 12, Issue 12 In This Issue Editorial This Month Correspondence Research Highlights Technology Feature News and Views Brief Communications Articles Application Notes Advertisement   ORCA-Flash4.0 V2 Discover the Breakthrough The first sCMOS camera with 82% peak Quantum Efficiency. Available for demonstration and shipping NOW from Hamamatsu. What breakthrough will you make with your extra photons? Tel. 908-231-0960 Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement SEE MORE. CLEARLY. Quick, flexible and affordable, Olympus will help you see those critical fine structures in your samples. The FV-OSR allows you to look deeper into your samples – not your budget. Take a closer look. Improved detection Great dye and wavelength flexibility Peltier cooling technology Your Science Matters at OLYMPUS' BOOTH #813. ASCB: December 12-16, 2015. San Diego.   Advertisement Genomic analysis made possible for biologists without programming.   Trusted by 9.034 researchers, used in 48 publications. Over 428.343 samples analyzed 105.539 times! Testimonial: "InSilico DB changed the way we work. They are the only ones that made us believe and showed us interrogating genomics data was possible. We now use it routinely to compare public and private data"  LEARN MORE   Advertisement nature.com webcasts   Join us for our upcoming webcast with live Q&A: INNOVATIONS IN REGENERATIVE MEDICINE & CURATIVE BIOLOGICS Presented by BioPharma Dealmakers   Date: Wednesday, October 14, 2015 Time: 8am PDT, 11am EDT, 4pm BST and 5pm CEST  REGISTER FOR FREE   Sponsored by: co.don, Asterias Biotherapeutics, SIWA Regenerative Medicine Corporation, Organovo   In This Issue Top In This Issue    Editorial Top Reviewing computational methods   p1099 doi:10.1038/nmeth.3686 Assessing papers that report (or use) computational methods is demanding for referees, but peer review of these methods and related software is crucial for biological research. This Month Top The Author File: Jennifer Elisseeff   p1101 Vivien Marx doi:10.1038/nmeth.3657 Exploring the extracellular matrix in high throughput and leaping across scientific divides as if they weren't there. Points of Significance: Multiple linear regression   pp1103 - 1104 Martin Krzywinski and Naomi Altman doi:10.1038/nmeth.3665 When multiple variables are associated with a response, the interpretation of a prediction equation is seldom simple. Correspondence Top Group-DIA: analyzing multiple data-independent acquisition mass spectrometry data files   pp1105 - 1106 Yuanyue Li, Chuan-Qi Zhong, Xiaozheng Xu, Shaowei Cai, Xiurong Wu et al. doi:10.1038/nmeth.3593 MSPLIT-DIA: sensitive peptide identification for data-independent acquisition   pp1106 - 1108 Jian Wang, Monika Tucholska, James D R Knight, Jean-Philippe Lambert, Stephen Tate et al. doi:10.1038/nmeth.3655 ANOVA and the analysis of drug combination experiments   p1108 John C Ashton doi:10.1038/nmeth.3663 Research Highlights Top Death by super-resolution imaging Researchers report that the illumination intensities used in super-resolution imaging can irreversibly damage live cells. fMRI goes individual Functional magnetic resonance data are traditionally analyzed on a population level, but new work shows that meaningful information can be extracted from individual subjects. Structure in the cellular context Researchers develop an approach based on solid-state nuclear magnetic resonance (NMR) to study the structure of an intrinsically disordered protein under near-native conditions. STOMPing at the bits Spatially targeted optical microproteomics identifies novel amyloid plaque components. New kid on the CRISPR block The small, single RNA–guided nuclease Cpf1 is active in human cells. Nanopores and the helicase two-step A nanopore used for sequencing gives a detailed view of how motor proteins behave on DNA. Methods in Brief Super-resolution imaging of neuronal circuits | Efficient in vivo mutagenesis in bacteria | In silico neocortex | Optogenetics gives drug screening an assist Tools in Brief Speeding up connectome analysis | Keeping score of stem cells | User-friendly software for analyzing MD simulations | Tuning Cas9 function with guide RNA length Methods JOBS of the week Postdoctoral studies in cancer biology (scholarship) - 2 positions Karolinska Institutet (KI) Postdoctoral Research Fellow The University of Queensland - Australian Institute for Bioengineering and Nanotechnology (AIBN) Postdoctoral Scientist Medical Research Council Fred Eshelman Fellowship for Excellence in Biomedical Innovation Eshelman Institute for Innovation Postdoctoral Associate The Scripps Research Institute (TSRI) More Science jobs from Methods EVENT Materials, Methods & Technologies 2016, 18th International Conference 26th June - 30th June 2016 Elenite, Bulgaria More science events from Technology Feature Top Autophagy: eat thyself, sustain thyself   pp1121 - 1125 Vivien Marx doi:10.1038/nmeth.3661 A growing research community studies autophagy—a process of cellular recycling and maintenance—but there are some hot-button methodological issues. News and Views Top Hitting the target   pp1127 - 1128 Yves Leestemaker and Huib Ovaa doi:10.1038/nmeth.3660 Thermal profiling in combination with quantitative proteomics makes it possible to identify cellular membrane protein targets of small molecules. See also: Brief Communication by Reinhard et al. Brief Communications Top Thermal proteome profiling monitors ligand interactions with cellular membrane proteins   pp1129 - 1131 Friedrich B M Reinhard, Dirk Eberhard, Thilo Werner, Holger Franken, Dorothee Childs et al. doi:10.1038/nmeth.3652 A method for profiling changes in membrane protein thermal stability upon ligand binding using mass spectrometry identifies cellular membrane protein targets of small molecules. See also: News and Views by Leestemaker & Ovaa Noncontact three-dimensional mapping of intracellular hydromechanical properties by Brillouin microscopy   pp1132 - 1134 Giuliano Scarcelli, William J Polacheck, Hadi T Nia, Kripa Patel, Alan J Grodzinsky et al. doi:10.1038/nmeth.3616 Brillouin microscopy can be used to analyze the mechanical properties of cells in a contact-free fashion. Cells in 2D and 3D environments are accessible to this technology, which provides measurements of longitudinal moduli at optical resolution. A strategy for dissecting the architectures of native macromolecular assemblies   pp1135 - 1138 Yi Shi, Riccardo Pellarin, Peter C Fridy, Javier Fernandez-Martinez, Mary K Thompson et al. doi:10.1038/nmeth.3617 The molecular architecture of protein complexes can be determined using an optimal approach for isolating GFP-tagged complexes at native levels, combined with cross-linking, mass spectrometry analysis, and structure modeling from mass spectrometry-derived distance restraints. Tissue cartography: compressing bio-image data by dimensional reduction   pp1139 - 1142 Idse Heemskerk and Sebastian J Streichan doi:10.1038/nmeth.3648 Handling and quantitative image analysis of layered tissues is greatly simplified by cartography with the Image Surface Analysis Environment (ImSAnE), as demonstrated on a variety of specimens, including a beating heart. Advertisement NEW NanoDrop One Spectrophotometer Identifies Contaminants Accurately quantify and qualify DNA, RNA, and protein samples with only 1-2 µL in seconds and avoid costly delays from troubleshooting downstream applications. New Thermo Scientific™ NanoDrop™ One spectrophotometers offer standalone design, identify contaminants, calculate corrected concentrations, and provide guided troubleshooting. Auto-Measure feature streamlines workflows and organizes data. Watch the new NanoDrop One instrument in action here:  http://www.nanodrop.com/ProductOneOverview.aspx   Articles Top Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements   pp1143 - 1149 Pratiksha I Thakore, Anthony M D'Ippolito, Lingyun Song, Alexias Safi, Nishkala K Shivakumar et al. doi:10.1038/nmeth.3630 A detailed study of the effects of dCas9-KRAB-sgRNA complexes on enhancer activity, gene expression and heterochromatin formation shows high efficacy and specificity. DNA-binding-domain fusions enhance the targeting range and precision of Cas9   pp1150 - 1156 Mehmet Fatih Bolukbasi, Ankit Gupta, Sarah Oikemus, Alan G Derr, Manuel Garber et al. doi:10.1038/nmeth.3624 Fusing a DNA-binding domain to Cas9 with an attenuated, more promiscuous PAM-recognition domain increases the targeting range of Cas9 as well as its specificity. Transparent intracortical microprobe array for simultaneous spatiotemporal optical stimulation and multichannel electrical recording   pp1157 - 1162 Joonhee Lee, Ilker Ozden, Yoon-Kyu Song and Arto V Nurmikko doi:10.1038/nmeth.3620 Transparent micro-optoelectrode arrays enable simultaneous electrical recording and optical stimulation in precise alignment. Depending on the applied light levels, single-unit activity or behavioral responses can be optically evoked. Protein-RNA networks revealed through covalent RNA marks   pp1163 - 1170 Christopher P Lapointe, Daniel Wilinski, Harriet A J Saunders and Marvin Wickens doi:10.1038/nmeth.3651 A fusion of RNA-binding proteins (RBPs) to a poly(U) polymerase allows the tagging of endogenous RNAs bound by the RBPs with a U-tail that can be used to identify the bound RNA by sequencing. RNA tagging is suited to discover RNA-protein networks in vivo. Whole-animal functional and developmental imaging with isotropic spatial resolution   pp1171 - 1178 Raghav K Chhetri, Fernando Amat, Yinan Wan, Burkhard Hoökendorf, William C Lemon et al. doi:10.1038/nmeth.3632 IsoView microscopy achieves rapid isotropic-resolution imaging of large, nontransparent samples using simultaneous light-sheet illumination and fluorescence detection in four orthogonal directions. Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry   pp1179 - 1184 Fan Liu, Dirk T S Rijkers, Harm Post and Albert J R Heck doi:10.1038/nmeth.3603 A crosslinking-mass spectrometry strategy, including a new proteome database search engine called XlinkX, enables the identification of inter- and intra-protein cross-links in cell lysates on a proteome-wide scale. xTract: software for characterizing conformational changes of protein complexes by quantitative cross-linking mass spectrometry   pp1185 - 1190 Thomas Walzthoeni, Lukasz A Joachimiak, George Rosenberger, Hannes L Röst, Lars Malmström et al. doi:10.1038/nmeth.3631 A computational pipeline for analysis and statistical evaluation of quantitative cross-linking-mass spectrometry data facilitates the investigation of protein-complex structural heterogeneity. Continuously tunable nucleic acid hybridization probes   pp1191 - 1196 Lucia R Wu, Juexiao Sherry Wang, John Z Fang, Emily R Evans, Alessandro Pinto et al. doi:10.1038/nmeth.3626 Multiplexed hybridization probes are traditionally difficult to design with high sensitivity and specificity. Here Wu et al. present a method for fine, decoupled and on-the-fly tuning of probe behavior based on the stoichiometric formulation of a molecular competitor species. Tissue matrix arrays for high-throughput screening and systems analysis of cell function   pp1197 - 1204 Vince Z Beachley, Matthew T Wolf, Kaitlyn Sadtler, Srikanth S Manda, Heather Jacobs et al. doi:10.1038/nmeth.3619 High-throughput tissue arrays allow for evaluation of in vitro cellular responses and correlation to matrix composition. Advertisement NanoDrop Loyalty Rewards Program — 15% Off NanoDrop One Own a NanoDrop instrument? If so, you are eligible for a 15% Loyalty discount on a new Thermo Scientific™ NanoDrop™ One spectrophotometer. Whether you own a NanoDrop 1000, 2000, 8000, 3300 or Lite instrument, you qualify! Visit our web site for details and submit your request for a Loyalty price quote. Find Loyalty Rewards details here:  http://www.nanodrop.com/Promotions.aspx   Application Notes Top The Airyscan detector from ZEISS: confocal imaging with improved signal-to-noise ratio and super-resolution    Joseph Huff Nikon's large-format multiphoton system for intravital imaging    Lynne Chang DNA assembly and cloning in an overnight run with the BioXp™ 3200 system    Claudia H Alvarez Top Advertisement Nature Protocols is setting the benchmark for publishing high-quality peer-reviewed protocols for biological and biomedical research, containing all the technical info you need to reproduce experiments in your own lab. Visit the Nature Protocols website to access our step-by-step guides to using and adapting research techniques from the world's leading laboratories. www.nature.com/nprot      Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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