Table of contents


Special feature

International Year of Chemistry



Special Feature: International Year of Chemistry

The year of the chemist p607


The year 2011 has been designated the International Year of Chemistry. Nature Methods joins in the celebration with a special feature in this issue.


This Month

The author file: Carl Hansen p609

Monya Baker


A million picoliter PCR chambers give quick, precise answers.

Points of view: Simplify to clarify p611

Bang Wong





OpenFreezer: a reagent information management software system pp612 - 613

Marina Olhovsky, Kelly Williton, Anna Yue Dai, Adrian Pasculescu, John Paul Lee, Marilyn Goudreault, Clark D. Wells, Jin Gyoon Park, Anne-Claude Gingras, Rune Linding, Tony Pawson & Karen Colwill



Research Highlights

Thwarting amyloid fibers p615

Irene Kaganman


Two structure-driven studies of the culprits behind diseases associated with amyloid fibers give clues to stopping these agents in their tracks.

Predicting neurogenesis pp616 - 617

Natalie de Souza


Expression of a microRNA cluster predicts whether or not a particular human pluripotent stem cell line will differentiate well into neurons.

Swift, flexible knockouts pp616 - 617

Monya Baker


Researchers produce a mouse embryonic stem cell library along with convenient vectors.

News in brief p617


Next-generation protein binding p619

Daniel Evanko


A next-generation sequencing instrument allows deep quantitative measurement of protein-DNA binding affinity.

An affinity for motifs p620

Allison Doerr


Antibodies targeting short sequence motifs found in multiple proteins can be used in a discovery array–based platform.

Taming crystals' whimsy p622

Petya V Krasteva


Molecularly imprinted polymers act as 'smart' nucleants for protein crystallization.


Technology Feature

Special Feature: International Year of Chemistry

Protein engineering: navigating between chance and reason pp623 - 626

Monya Baker


Researchers use large libraries, focused libraries and rational design to engineer useful proteins.


News and Views

From journal articles to computational models: a new automated tool pp627 - 628

Tom M. Mitchell


Automated methods can now extract brain-image coordinates appearing in hundreds of publications in targeted topic areas and then integrate these data to form computational models that classify new brain-image data.

See also: Article by Yarkoni et al.

Seeing the light: integrating genome engineering with double-strand break repair pp628 - 630

Matthew Porteus


The two-color traffic light reporter reads out what pathway is used to repair a DNA break and will increase insights into genome engineering.

See also: Article by Certo et al.

Simply quantifying ubiquitin complexity pp630 - 631

Eric J Bennett & J Wade Harper


An absolute quantification approach combined with differential affinity capture provides a means by which to accurately measure distinct pools of ubiquitin in cells or tissues.

See also: Article by Kaiser et al.



Historical Commentary

Special Feature: International Year of Chemistry

A century of mass spectrometry: from atoms to proteomes pp633 - 637

John R Yates III


Long before mass spectrometry became an important tool for cell biology, it was yielding scientific insights in physics and chemistry. Here is a brief history of how the technology has expanded from a tool for studying atomic structure and characterizing small molecules to its current incarnation as the most powerful technique for analyzing proteomes.



Special Feature: International Year of Chemistry

Bringing chemistry to life pp638 - 642

Michael Boyce & Carolyn R Bertozzi


Bioorthogonal chemistry allows a wide variety of biomolecules to be specifically labeled and probed in living cells and whole organisms. Here we discuss the history of bioorthogonal reactions and some of the most interesting and important advances in the field.

Special Feature: International Year of Chemistry

Fluorescent probes for sensing and imaging pp642 - 645

Tasuku Ueno & Tetsuo Nagano


A diverse array of small molecule–based fluorescent probes is available for many different types of biological experiments. Here we examine the history of these probes and discuss some of the most interesting applications.


Chemistry Methods

Special Feature: International Year of Chemistry

Chemistry Methods pp646 - 647



Brief Communications

Megapixel digital PCR pp649 - 651

Kevin A Heyries, Carolina Tropini, Michael VanInsberghe, Callum Doolin, Oleh I Petriv, Anupam Singhal, Kaston Leung, Curtis B Hughesman & Carl L Hansen


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.

CREST maps somatic structural variation in cancer genomes with base-pair resolution pp652 - 654

Jianmin Wang, Charles G Mullighan, John Easton, Stefan Roberts, Sue L Heatley, Jing Ma, Michael C Rusch, Ken Chen, Christopher C Harris, Li Ding, Linda Holmfeldt, Debbie Payne-Turner, Xian Fan, Lei Wei, David Zhao, John C Obenauer, Clayton Naeve, Elaine R Mardis, Richard K Wilson, James R Downing & Jinghui Zhang


This algorithm uses the soft-clipped, unaligned parts of a sequence read to map structural variation in cancer genomes with high predictive accuracy.

Large-scale phosphosite quantification in tissues by a spike-in SILAC method pp655 - 658

Mara Monetti, Nagarjuna Nagaraj, Kirti Sharma & Matthias Mann


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.

A public genome-scale lentiviral expression library of human ORFs pp659 - 661

Xiaoping Yang, Jesse S Boehm, Xinping Yang, Kourosh Salehi-Ashtiani, Tong Hao, Yun Shen, Rakela Lubonja, Sapana R Thomas, Ozan Alkan, Tashfeen Bhimdi, Thomas M Green, Cory M Johannessen, Serena J Silver, Cindy Nguyen, Ryan R Murray, Haley Hieronymus, Dawit Balcha, Changyu Fan, Chenwei Lin, Lila Ghamsari, Marc Vidal, William C Hahn, David E Hill & David E Root


Two sequence-verified, clonal, publicly available collections of human open reading frames are reported. One collection is in a lentiviral vector for expression in mammalian cells; the other is in the Gateway vector system.

Functional ultrasound imaging of the brain pp662 - 664

Emilie Macé, Gabriel Montaldo, Ivan Cohen, Michel Baulac, Mathias Fink & Mickael Tanter


A new method called functional ultrasound (fUS) is reported that allows imaging of transient changes in blood volume in the whole rat brain with a spatiotemporal resolution not attained by other functional brain imaging modalities.



Large-scale automated synthesis of human functional neuroimaging data pp665 - 670

Tal Yarkoni, Russell A Poldrack, Thomas E Nichols, David C Van Essen & Tor D Wager


A framework and web interface for the large-scale and automated synthesis of human neuroimaging data extracted from the literature is presented. It is used to generate a large database of mappings between neural and cognitive states and to address long-standing inferential problems in the neuroimaging literature.

See also: News and Views by Mitchell

Tracking genome engineering outcome at individual DNA breakpoints pp671 - 676

Michael T Certo, Byoung Y Ryu, James E Annis, Mikhail Garibov, Jordan Jarjour, David J Rawlings & Andrew M Scharenberg


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.

See also: News and Views by Porteus

A large-scale method to measure absolute protein phosphorylation stoichiometries pp677 - 683

Ronghu Wu, Wilhelm Haas, Noah Dephoure, Edward L Huttlin, Bo Zhai, Mathew E Sowa & Steven P Gygi


The functional role of protein phosphorylation is determined not just by whether a particular site is phosphorylated or not but also by the site's stoichiometry. A method to determine the absolute stoichiometries of protein phosphorylation on a proteomic scale is described.

Two-photon polarization microscopy reveals protein structure and function pp684 - 690

Josef Lazar, Alexey Bondar, Stepan Timr & Stuart J Firestein


Membrane protein interactions and conformational changes can be sensitively monitored with two-photon polarization microscopy, a method that takes advantage of the anisotropic absorption properties of fluorescent proteins. The authors applied the method to image G-protein activation and changes in intracellular calcium concentration.

Protein standard absolute quantification (PSAQ) method for the measurement of cellular ubiquitin pools pp691 - 696

Stephen E Kaiser, Brigit E Riley, Thomas A Shaler, R Sean Trevino, Christopher H Becker, Howard Schulman & Ron R Kopito


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.

See also: News and Views by Bennett & Harper