Volume 11 Issue 9, September 2014

We announce a change in leadership at Nature Methods and wish Daniel Evanko, our departing chief editor and the new head of editorial services at Nature Publishing Group, every success.

Proteins 'breathe' in an ultrafast way that can be captured with XFELs.

Quality is often more important than quantity.

An ion-current map characteristic of four nucleotides traversing a protein nanopore allows resequencing of long DNA reads.

The red light–sensitive optogenetic inhibitor Jaws enables the modulation of neural activity deep inside the brain.

The protein-RNA specificity code of an RNA-binding protein can be used to target diverse transcripts in the cell for regulation.

A method to study the domain architecture of long noncoding RNAs provides insights into their biological functions.

Genome-editing technologies generally stay on target, but researchers should remain vigilant for variants acquired during experimental manipulation.

'Irreproducibility' is symptomatic of a broader challenge in measurement in biomedical research. From the US National Institute of Standards and Technology (NIST) perspective of rigorous metrology, reproducibility is only one aspect of establishing confidence in measurements. Appropriate controls, reference materials, statistics and informatics are required for a robust measurement process. Research is required to establish these tools for biological measurements, which will lead to greater confidence in research results.

We argue that standard thermodynamic considerations and scaling laws show that a single cell cannot substantially raise its temperature by endogenous thermogenesis. This statement seriously questions the interpretations of recent work reporting temperature heterogeneities measured in single living cells.

X-ray free-electron lasers (XFELs) offer opportunities beyond classic X-ray crystallography, particularly for proteins that are difficult to crystallize.

A new distributed computing framework for data analysis enables neuroscientists to meet the computational demands of modern experimental technologies.

Single guide RNAs driven by a T7 promoter target Cas9 to two endogenous loci, leading to fast and efficient genome editing in the malaria parasite P. falciparum.

A series of technical and analytical improvements to light sheet microscopy is described, permitting dynamic imaging of the beating zebrafish heart at cellular resolution.

A 'protein quake' is directly monitored on the picosecond timescale using the method of time-resolved wide-angle X-ray scattering at an X-ray free-electron laser.

High-resolution, three-dimensional protein structures can be solved using MicroED, an electron diffraction method that uses three-dimensional microcrystals. An improved MicroED data collection approach described here increases data quality and resolution and extends its broad applicability.

The compositional heterogeneity of proteoliposome reconstitution can skew the results of ensemble-average measurements of transmembrane protein structure and function. These compositional heterogeneities can be exploited, however, with a single-proteoliposome, high-content screening method.

To find causative mutations in rare disorders, the Phen-Gen software combines disease symptoms and sequencing data with prior knowledge about the gene.

Integration of genome visualization with Bioconductor-based analysis tools allows rapid and interactive analysis of genomes, transcriptomes and epigenomes.

An open-source library of analytical tools for mapping large-scale patterns of brain activity using cluster computing finds structure in two-photon imaging data from mouse and whole-brain light-sheet functional imaging data from behaving larval zebrafish. Vladimirov et al., also in this issue, describes the light-sheet functional imaging system used here.

This paper describes automated methods for the accurate segmentation and tracking of tens of thousands of nuclei in time-lapse imaging data of developing embryos.

The combination of selective 2'-hydroxyl acylation of RNA with high-throughput sequencing of the transcribed cDNA allows identification of chemically modified sites as mutations in the sequence that then yield highly accurate secondary-structure models of the RNA.

Application of the founder principle from population genetics to variant selection after recombineering allows the isolation of rare unselected recombinants.