Read our May editorial on political engagement among scientists here.
Comments on this subject are welcome!
Read our May editorial on political engagement among scientists here.
Comments on this subject are welcome!
Meta-analysis is common in clinical research, less so in basic biology, but it is also proving useful in some basic research contexts. It should help improve research reproducibility. You can find our December 2016 editorial on this topic here.
We wrote our November editorial watching the debates leading up to the 2016 US election. You can read it here. The outcome remains too close for comfort. We urge our readers to vote!
Here is this month’s editorial, in which we discuss the role of private sources of funding for scientific research, and outline some steps researchers might consider in order to find and obtain such resources.
You can find this month’s editorial on the importance of methods reporting in human embryo research here.
In our May editorial, we highlight two new archives: for raw X-ray crystallography (the Structural Biology Data Grid, or SBDG) and for cryo-EM (EMPIAR). These archives join the long-established Biological Magnetic Resonance Data Bank, or BMRB (which hosts biomolecular NMR spectral data) as important resources which will facilitate greater transparency and accelerate progress in structural biology.
Note that neither archive is intended as a “data dump”: datasets in the SBDG must be tied to a journal publication and must be sponsored by the principle investigator of the work, and datasets in EMPIAR must be tied to an Electron Microscopy Data Bank (EMDB) EM density map entry.
Though we do not mandate raw X-ray or cryo-EM data deposition at this time, we applaud these efforts and welcome feedback from the structural biology community about how these archives are bolstering community needs.
We remind our readers about our policies on the use of preprints: in short, we support them. A Nature Methods author can post a preprint prior to submission without fearing a penalty.
The full editorial is here.
Our March editorial is on the value of scientific disagreement and can be found here
The papers we refer to in this editorial are:
Genome-wide footprinting: ready for prime time?
Analysis of computational footprinting methods for DNase sequencing experiments
In the March issue of Nature Methods, the technology feature explores some ways that labs are optimizing probes to image cleared tissue. As we interviewed scientists, we learned about published work and ongoing unpublished experiences. Here is a snapshot of how some probes work with some clearing methods. It’s an imperfect table and is likely to evolve as research continues. We welcome your comments. We know there are different viewpoints and varying experiences and we hope it will be helpful to others to hear about them.
We wish this could be a wiki page, then again that might deprive you of your nighttime rest, as you edit one another’s entries. This way, your comments can be seen by all.
| Probe | Labeling shown in large samplesb | Labeling shown in small samples | Does not work well? |
|---|---|---|---|
| Genetically encoded fluorescent proteins | 3DISCO (signal quenched after a few days), CLARITY, CUBIC, ExM (variant)a, PACT/PARS (signal retained 6 months and longer)a, sDISCOa | BABB (signal quenched after a few hours), ClearT2, ExM (variant)a , ExM/ePACTa , ScaleA2, ScaleS, SeeDB, Sucrose, TDE |
|
| Immunolabels | 3DISCO, CLARITY, iDISCO, iDISCO+a, iSeeDB, PACT/PARS, Sucrose, SWITCH | BABB, ClearT, ClearT2, CUBIC, SeeDB, SeeDB2a (in press) Sucrose, TDE, ExM | |
| Specific nucleic acid detection | EDC-CLARITY | CLARITY, ExM (variant)a, PACT/PARS | |
| Dyes and stains | |||
| Congo Red | 3DISCO | ||
| Lipophilic dyes such as DiI, Sudan Black | PACT/PARS (Sudan Black), SWITCH (DiI) | ClearT, ScaleS, SeeDB | |
| Nuclear stains such as DAPI, DRAQ5, SYTO and PI | CUBIC, ExM (variant)a, PACT/PARS, SWITCH | SeeDB, SeeDB2a | |
| SNAP-tags with SiR probes | PACT/PARS, BABB, Scale | SeeDB |
Clearing method: Solvent-based; simple immersion; hyperhydration; hydrogel-based.
aUnpublished information
bIndicates larger samples such as whole organs
Sources: E. Boyden, MIT; K. Chung, MIT, K. Deisseroth, Stanford University; H-U. Dodt, Vienna University of Technology/Medical University of Vienna; V. Gradinaru, Caltech; P. Heppenstall, EMBL; Takeshi Imai, RIKEN; K. Johnsson, EPFL; J. Lichtman, D. Richardson, Harvard University; A. Miyawaki, RIKEN; M. Tessier-Lavigne, N. Renier, Rockefeller University.
*
Glossary of some tissue clearing agent acronyms
3DISCO : Three-dimensional imaging of solvent-cleared organs
sDISCO: Stabilized three-dimensional imaging of solvent-cleared organs
BABB : Benzyl alcohol and benzyl-benzoate
CLARITY : Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging/Immunostaining/In situ hybridization-compatible Tissue-hYdrogel
CUBIC : Clear unobstructed brain imaging cocktails and computational analysis
EDC-CLARITY : 1-Ethyl-3-3-dimethyl-aminopropyl carbodiimide-CLARITY
ePACT: PACT-based expansion clearing.
iDISCO : Immunolabeling-enabled 3D imaging of solvent-cleared organs
iDISCO+ : Immunolabeling-enabled 3D imaging of solvent-cleared organs plus
PACT : Passive Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging/Immunostaining/In situ hybridization-compatible Tissue-hYdrogel
PARS : Perfusion-assisted agent release in situ
SeeDB : See Deep Brain
Spalteholz’s preparation : Benzylbanzoate/methylsalicate
TDE : 2,2′-thiodiethanol
Some lab resource pages
Chung lab resources – Literature, protocols, videos and discussion pages from the MIT lab of Kwanghun Chung related to SWITCH, electrostochastic transport and CLARITY.
CLARITY Resources – Protocols, literature, data and videos related to CLARITY, developed in the lab of Karl Deisseroth at Stanford University. Links to CLARITY Wiki and CLARITY Forum
Expansion microscopy resources – Literature and protocols related to expansion microscopy developed in the MIT lab of Edward Boyden.
iDISCO resources – Literature, protocols and information about validated antibodies related to iDISCO
SeeDB Resources – Protocols, literature videos related to SeeDB developed in the RIKEN lab of Takeshi Imai.
It was not difficult to settle on single-particle cryo-electron microscopy as Method of the Year 2015, considering the boundary-breaking growth and excitement in this field in the recent past. You can link to the editorial describing our rationale for this choice here.