William J Nicolas

@wjnicol.bsky.social

Senior scientist @ Exelixis | Cryo-EM facility lead -- PhD @ CNRS | LBM-Bayer lab Postdoc @ Jensen/Meyerowitz lab Caltech Cryo-EM facility manager @ Gonen lab HHMI -- Website: www.wjnicolas.com Twitter handle: @WiwiSFC

MissAlignment is here to align all our Bananas🍌 and Birds🦅 into beautiful Pineapples🍍 ...Did that make sense? Either way, read Dimitry's thread🧵 for a vivid visual demonstration. This new software cooks! Look how crispy it made the #ChlamyDataset nucleosome👇. #TeamTomo is hitting escape velocity 🚀 🧪

Dimitry Tegunov@dtegunov.bsky.social · 4mo ago

We're super excited to share MissAlignment: a new ML-based approach to reference-free tilt series alignment, spearheaded by @martenchaillet.bsky.social. We think it's going to make your cryo-ET life a lot better. Preprint: www.biorxiv.org/content/10.6... Code: github.com/warpem/miss-... 🧶 Thread:

More evidence also that the federal administration is NOT pursuing actual criminal activity- they have forced out the very prosecutors who were working on the social services fraud cases that had been the proclaimed casus belli for sending federal forces to MN.

Don Moynihan@donmoyn.bsky.social · 7mo ago

You should read this. It is the type of detail that experts in authoritarian regimes see as telling. In this case, state agents are offered impunity from higher ups, and the legal system is rendered inoperative as a mode of accountability. www.nytimes.com/2026/02/07/u...

So many lucid points below. Incl on how to think abt free speech issues brought up by backlash on campuses when illiberal right-wingers are invited to speak. Also, and this has agitated me since Jan 2025: those who railed against cancel culture seem at ease with state-enforced speech restrictions.

How "Free Speech Culture" Is Killing Free Speech: Part One

Blurring The Lines Between Official Censorship And Individual Criticism Built The Intellectual Foundation For Trump's Assault On Free Expression

popehat.com

Initial attempt at replicating in relion (parameters in next post). This is for Aca2-RNA, using a 100k subset of the 2D-classified particles (no prior 3D cleanup). A 1-class ab initio in relion, then local refinement in relion (1.8deg searches+blush) gives a nominally 3.3Å map; 3.5 Å w/out blush.

Sjors Scheres@sjorsscheres.bsky.social · 12mo ago

These results are truly impressive! But I do worry that #cryoEM is moving into a phase where progress is made by optimizing parameter settings for black box programs. The devil is often in the details, and I am not sure how this could be implemented in #relion, as stated, without more info.

A molecular-resolution look into the near-native architecture of the spinach chloroplast🌱. This one was a long time in the oven, but we're happy to finally share our "version of record". What long-standing debates did we settle? Check back for a short thread🧵 on Monday. #TeamTomo #PlantScience 🧪🧶🧬🔬🌾

eLife@elife.bsky.social · 12mo ago

🌱 Using ‘compelling’ methods, including #CryoET, researchers mapped spinach thylakoid membranes at single-molecule precision, revealing how photosynthetic complexes are organised and settling long-standing debates on chloroplast architecture. buff.ly/j3TSIkn

This paper combines two sort-of-crazy (in the best sense) approaches in cryoEM sample preparation: (1) Native, soft-landing electrospray ion beam deposition, followed by (2) deposition of amorphous ice, and reheating and freezing by laser flash melting. Has potential for time-resolved studies.

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bioRxiv Biophysics@biorxiv-biophys.bsky.social · last yr.

Cryo-EM Sample Preparation with Soft-Landing and Laser Flash Melting https://www.biorxiv.org/content/10.1101/2025.06.05.657968v1

This is a view from the surface of Comet 67P. The busy particles in the foreground are cosmic rays or bits of dust and ice. The dots moving in the background are stars.