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The fourth anniversary of Nature Methods' arrival on the publishing scene and a change in leadership offer an opportunity for reflection and editorial fine-tuning.
Researchers at two Boston–based neuroscience centers are working to develop new imaging tools and technology with the hope of discovering the secrets behind how the brain functions.
Many different red fluorescent proteins display cytotoxicity substantially higher than EGFP when used for whole-cell labeling of bacterial and mammalian cells with standard high-level expression systems. An improved tetrameric red fluorescent protein called DsRed-Express2 allows high-level labeling with minimal cytotoxicity comparable to that of EGFP.
To determine long-range linkage between single-nucleotide polymorphisms (SNPs) and the repeat-containing region of a disease-related gene, Liu et al. develop SNP linkage by circularization (SLiC) and lay the groundwork for using allele-specific RNA interference to target insertion or deletion mutations in disease-associated genes.
The two major mechanisms for peptide fragmentation by mass spectrometry, collision-activated dissociation (CAD) or a newer method, electron transfer dissociation (ETD), display different efficacies for different peptide chemistries. A decision tree algorithm, which can be embedded into instruments with both CAD and ETD capabilities, selects the optimal fragmentation method to improve the chances of successful peptide identification.
Directed evolution experiments usually rely on high-throughput screening of very large libraries of mutants, but most of the mutants do not even yield stable, functional proteins. The concept of neutral drift can be used to generate small but highly polymorphic and stable mutant libraries as a starting point for further evolution.
The combination of single-molecule fluorescence resonance energy transfer measurements of multiple dye pairs with probabilistic data analysis allows quantitative measurement of the position of flexible domains in macro-molecular complexes. The method was used to determine the three-dimensional probability density of the position of RNA exiting the transcription elongation complex.
A miniature epifluorescence microscope that can be carried by a freely-moving adult mouse allows cellular-level imaging of neuronal spiking or measurement of microcirculation during normal behavioral activities.
Fluorescent proteins with new photoswitching properties allow multilabel imaging at a single detection wavelength and dual-color superresolution microscopy.