I should add - because I have been known to complain about peer review lately - that the peer review on this particular work was excellent, resulting substantial improvement. Our thanks to 'reviewer #2' in particular... ...

Efficient, Zero Scrambling Fragmentation of Deuterium Labeled Peptides on the ZenoToF 7600 Electron Activated Dissociation Platform Hydrogen–deuterium exchange (HDX) mass spectrometry (MS) has become an increasingly important tool in protein research, with large-scale applications in biopharmaceutical development and manufacturing...

Ok folks, here it is: Joe Anacleto (with some help from his friends) demonstrates zero sensitivity loss, zero scrambling site specific HDX. Next up: Site specific HDX-MS profiles of drug candidates in *real-world* drug development... And after that? High throughput!

pubs.acs.org/doi/abs/10.1...

Probing the Interactions of Cytochrome c with Anionic Phospholipid Nanodiscs Using Millisecond Hydrogen–Deuterium Exchange Mass Spectrometry The interplay between the anionic phospholipid cardiolipin (CL) and cytochrome c (cyt c) holds significance in the early stages of apoptosis. Despite identification of up to four potential sites of in...

Alright it's been a while, I know, but just in case you were *really* curious about what ms Hydrogen Deuterium Exchange can tell you about cytochrome c membrane interactions, I present to you this work by Vimanda Chow: pubs.acs.org/doi/10.1021/...

Excited to be giving this webinar soon. Hope to see you then!

Rare political repost from me, but this one deserves it for so eloquently exhibiting the moral power of being *moderate*.

Was it York? That sounds like something our 'advancement' office would do...

Hyperphosphorylation of Intrinsically Disordered Tau Protein Induces an Amyloidogenic Shift in Its Conformational Ensemble Tau is an intrinsically disordered protein (IDP) whose primary physiological role is to stabilize microtubules in neuronal axons at all stages of development. In Alzheimer's and other tauopathies, tau...

Yep, and here's why :)... journals.plos.org/plosone/arti...

The Wilson group and collaborators bids you all a Merry Xmas and Happy Holidays!

Sharks with frickin lazers on their heads! :)

What would this animation look like if reviewers were *paid* I wonder?

Welcome!

Not the shortest trek for you, but... Next time!!

#LakeLouise2024

yESI is on his way to his new home in Ontario. He will no doubt find some comfort in the arms of a 13 year old boy who still loves stuffies, but I think he will be deeply disappointed by the lack of mountains... As everyone knows, Ontario is NOT the natural habitat for any species of YETI.

Quick #videogames thought: It seems to me that the current situation on Google's "Play Store" is rather like the situation of #Atari in the mid 1980's. Here's hoping it causes the same sort of crash, and maybe then some marketplace competition.

Time to once again close out the scientific program of the Lake Louise conference on mass spectrometry. To do that, Gary Glish is telling us why what we have all been observing can depend really quite a lot on the particular settings of our instruments. #LakeLouise2024

More seriously, there have been many great talks, but one that stood out for me was Elvin Cabrera (Barran group) coming up with ways to do fast, high resolution IMS + FT Charge detection MS on HUGE protein complexes. Super amazing stuff!

There was one Tal where I learned that my drinking water may be contaminated with the remnants of poop. It would be a depressing thought except... ... ...

I think some might appreciate this spectacular view of the majestic and timeless scenery at the Lake Louise mass spectrometry conference. #LakeLouise2024

#LakeLouise2024

#LakeLouise2024

Don't know... But I think it has something to do with Facebook not crashing...

Just got a 'request to review' where the editor sent me a *table* of papers they can't find reviewers for and asked me to please select one or two that I'd be willing to do. For these (hours) of work they offer 100 points that can be used to purchase services from the publisher. #peerreviewcrisis

...And another critical point. For pedagogy not to subsidize research (which I agree, it shouldn't), tricouncil needs to *substantially increase the indirect cost %* that they pay when profs get funded. In the US, overhead % is *much* higher, driving unis to actually compete for research grants.

I think this is already happening (or has already happened) at many institutions. Even at my relatively 'research light' institution, genuinely research oriented profs rarely teach below 3rd year now. This accompanies the rise of 'alt stream' professors whose job explicitly focuses on pedagogy.

Hydrogen–Deuterium Exchange Mass Spectrometry Reveals Mechanistic Insights into RNA Oligonucleotide-Mediated Inhibition of TDP-43 Aggregation Deposits of aggregated TAR DNA-binding protein 43 (TDP-43) in the brain are associated with several neurodegenerative diseases. It is well established that binding of RNA/DNA to TDP-43 can prevent TDP-43 aggregation, but an understanding of the structure(s) and conformational dynamics of TDP-43, and TDP-43-RNA complexes, is lacking, including knowledge of how the solution environment modulates these properties. Here, we address this challenge using hydrogen–deuterium exchange-mass spectrometry. In the presence of RNA olignoucleotides, we observe protection from exchange in the RNA recognition motif (RRM) domains of TDP-43 and the linker region between the RRM domains, consistent with nucleic acid binding modulating interdomain interactions. Intriguingly, at elevated salt concentrations, the extent of protection from exchange is reduced in the RRM domains when bound to an RNA sequence derived from the 3′ UTR of the TDP-43 mRNA (CLIP34NT) compared to when bound to a (UG)6 repeat sequence. Under these conditions, CLIP34NT is no longer able to prevent TDP-43 aggregation. This suggests that a salt-induced structural rearrangement occurs when bound to this RNA, which may play a role in facilitating aggregation. Additionally, upon RNA binding, we identify differences in exchange within the short α-helical region located in the C-terminal domain (CTD) of TDP-43. These allosterically altered regions may influence the ability of TDP-43 to aggregate and fine-tune its RNA binding repertoire. Combined, these data provide additional insights into the intricate interplay between TDP-43 aggregation and RNA binding, an understanding of which is crucial for unraveling the molecular mechanisms underlying TDP-43-associated neurodegeneration.

Hydrogen–Deuterium Exchange Mass Spectrometry Reveals Mechanistic Insights into RNA Oligonucleotide-Mediated Inhibition of TDP-43 Aggregation #JACS pubs.acs.org/doi/10.1021/...

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Opportunity in chemical biology & #proteomics at Pfizer (Groton CT USA) ref: 4924293 | closing: 06-Dec-2024 #ChemBiol #biochem #chemsky 🧪
pfizer.wd1.myworkdayjobs.com/PfizerCareer...

I guess I should clarify that by 'single, objectively terrible review' I mean that the editor at this major journal was *unable to find more than one reviewer - and zero qualified reviewers - for our manuscript*. That is emblematic of the #peerreviewcrisis . Something fundamental needs to change.

In this case: *what other reviewer?*

Wow. We just got hit full in the face with the #peerreviewcrisis currently facing science publishing. Our manuscript was rejected from a major journal (with invitation to resubmit) on the basis of a single, objectively terrible review that used the word 'sketchy'... Twice! Who's got solutions??