sjorsscheres.bsky.social
Joint Head of Structural Studies at @mrclmb.bsky.social. Develops & uses #cryoEM to study amyloids in neurodegeneration. #tau, #alphasynuclein, #opensoftware, #RELION. All opinions my own.
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So well deserved! 🤗
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Yes, the actual study shows how nasty the culture wars from the right are. But why the @theguardian.com chose to highlight "forceful bike campaigners" is beyond me. Disappointing.
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This work was initiated by Sofia Lövestam. I only became involved with the #cryoEM image processing at a later stage. That's why she is the corresponding author on this one! 🤗
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We hope that this structure will prove useful in efforts to engineer the vault for drug delivery purposes. 🥰
I think it is also cool that these data have been available on #EMPIAR at @ebi.embl.org since 2021, so anyone could have done this work. #OpenScience!
www.ebi.ac.uk/empiar/EMPIA...
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Although the density at the centre of the cap remains too poor for atomic modeling, it suggests the presence of a 13-stranded beta-barrel that sits within a larger 26-stranded barrel. Given the hydrophobic nature of the corresponding residues, this would form a greasy gate to the vault.
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At its caps, there is no space for 39 MVPs. Using symmetry expansion and partial signal subtraction in #RELION, we show that the symmetry at the caps is broken and 2 out of every 3 MVP monomers gets successively excluded from the cap.
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The vault is made of 2 symmetrical halves, each of which contains 39 copies of the major vault protein (MVP). With a molecular weight of 13 MDa, the vaults spin down together with #amyloid filaments in our brain preps, in this case from progressive supranuclear palsy #PSP.
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Fully agree! That's why this chart is not interesting at all. It indirectly reflects the volume of fields, rather than their disruptiveness.
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By measuring an average score over all papers, the plot may just reflect a growing number of papers with little impact. Would it be more interesting to look at the tails of the distribution?
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I suspect a govt-driven campaign to instruct drivers how to be safe around cyclists, and to generally promote walking and cycling, instead of doing these culture wars, would be more effective. Am disappointed in Labour, as they promised serious govt. The nasty right may benefit in the end. 😬
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I would prefer it if the govt would facilitate making traffic better and safer for everyone. The promotion of cycling should be a part of that. Not everyone can cycle, but each bike on the road is one less car stuck in traffic. Roads can take many more bikes than cars.
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Who wants to tell them that alpha-synuclein filaments are associated with Parkinson's disease, not Alzheimer's... 🤪
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You may need to switch off compilation of the cuda libraries in relion! 😉
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Yes, in a way these are two aspects of the same idea. A good step in this direction is that some grant awarding agencies now ask for a limited number of important papers to be considered. This forces one to focus on writing fewer, better papers.
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This book instigated my recent post that you should stand behind *all* the data in any paper you co-publish. That requires a bandwidth that is impossible for 100s papers per year through large collaborating networks. Would a return to fewer authors per paper lead to better accountability & science?
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The aggressive pitching of this book risks further undermining the image of science for the general public, providing dangerous opportunities for exploitation by nasty politicians. But, ultimately doing fraudulent science will be worse, and this book raises awareness for that problem.
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I still think the book is pitched too aggressively by implying that the entire amyloid field is wrong because of the fraud of a few individuals. Based on the evidence available, the hypothesis that amyloids cause disease remains, IMO, the most attractive one.
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Not really, my main question is whether the introduction of an additional intermediate species, between monomer and filament, is necessary given the data available.
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Sigma sells anti-tau T22 as an oligomeric antibody, but what does that mean? Hilal Lashuel tested 16 anti-alpha-synuclein antibodies. All of the oligomer-specific ones also detected filaments. Are oligomers just small filaments?
www.sciencedirect.com/science/arti...
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Yes, I will be there. Looking forward to seeing those data!
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Are these similar preps to the one we collaborated on, and which I reference in the thread above?
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If you are aware of any convincing evidence for the presence of oligomers of #Abeta, #alphasynuclein or #tau in (diseased) human brain, please do reach out. I would be interested in discussing that. If you can isolate such oligomers from brain, we might even want to have a look by #cryoEM.
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I haven't yet found convincing evidence that such oligomers are present in human brains. Previously, @andrewmstern.bsky.social showed that so-called soluble oligomeric fractions of AD brains contained #Abeta filaments. When spun down, toxicity disappeared!
www.sciencedirect.com/science/arti...
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Most of the work was done by @alysa-kasen.bsky.social in Mike Henderson's lab, with Sofia Lövestam from our group preparing recombinant tau seeds and confirming their structures by #cryoEM.
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So many problems with irreproducibility would disappear if people felt responsible for everything they sign as a co-author. I have declined authorship on papers from several collaborators, because I didn't agree with everything that was written. Science is about pursuing truth, not papers.