https://glyco.me
- That is really insightful regarding the ritual improving outcomes through better communication - something I see reflected in many meetings I turn up to now which involve an introduction round between participants, and anecdotally improves participation in the meeting.
It would be amazing if someone had a link to a page with the MSF story, as that is a great reference to have! My google-fu hasn’t helped me in this case.
- This is great - now I can get the authentic conference experience of a disengaged speaker reading out the slides in a monotone, without all the hassle of international travel and scheduling.
In all seriousness, there could be more utility in this if it helped explain the figures. I jumped ahead to one of the figures in the example video, and no real attention was given to it. In my experience, this is really where presentations live and die, in the clear presentation of datapoints, adding sufficient detail that you bring people along.
- I was ruminating about how Atproto would be great for re-thinking the peer review system for scientific journals.
Imagine a world where a preprint is “published” onto the social web, from which you could aggregate reviews/comments. I eventually ended up thinking about exactly what you raise - it would be great to have some degree of access control on this so both comments and published things can be selectively shared (with an option to make everything public later on, maintaining all the links).
- Arc institute probably.
- It is a real shame that peer review reports were only first published relatively recently. These would have provided valuable training information as to what peer review performs. Unfortunately now, I fully expect the public peer review reports will be poorer in quality, and oftentimes superficial.
On this tool, I fully expect that it will not capture high level conceptual peer review, but could very much serve a role in identifying errors of omission from a manuscript as a checklist to improve quality (as long as this remains an author controlled process).
I will be interested to throw in some of my own published papers to see if it catches all the things I know I would have liked to improve in my papers.
- Not my subject area, but at least one other group looked at ABCA1, and judging from this abstract, it has been linked via GWAS already, and furthermore concludes it doesn’t play a role (I haven’t looked at the data though).
I don’t know, but if we were to reframe this as some software to take a hit from a GWAS, look up the small molecule inhibitor/activator for it, and then do some RNA-seq on it, I doubt it would gain any interest.
https://iovs.arvojournals.org/article.aspx?articleid=2788418
- I guess that whatever recognises the enhancers must be conserved ish in mice for us to be able to drop this region into the mouse genome. That might be interesting alone apart from the functions of the frizzleds. Always a curious question about how much new “machinery” we have in humans, vs us being a specific configuration of common machinery (i.e., if we were to swap out introns/regulatory regions from a mouse with human, and assuming we don’t screw up any checkpoints, how far would it get with looking/acting like a human?).
- My innate immune system is here for chewing gum and binding viral glycans, and I’m all out of specific lectins.
Looks like this works by apparently binding complex N-glycans on the viral envelope. I can’t imagine this is particularly specific, but the good news is that in the mucosa, you should see relatively few N-glycans, so I guess it will hit the right stuff?
- This is pretty interesting, also that they get it down to the amount of mannan in the fungal cell walls being somehow related to the β cell amounts. There's probably a nice project in here to figure out what the receptors are on the macrophages that are modulating this process. Obviously candidates would be some of the lectins they carry (mannose receptor?).
- Ancient medicine solves that problem
- I think what you mean is the MUC1-20 (ish, numbering is a bit sloppy but hopefully we can clean it up in near future) genes encode for mucins, that are synthesised on a ribosome, threaded into ER, shuffled off into the Golgi and then enzymatically modified by the enzymes encoded by the genes GALNT2, 7 & 10 (at least).
There are a further 20-30 ish enzymes that can modify the mucins as they are traversing the Golgi, and depending on the cell type, it can get packaged into vesicles (alongside calcium) for secretion.
So, they meet a lot of enzymes along the way, but harbour no catalytic activity themselves (as far as we know!).
- Mucins aren't enzymes (as far as we know!), and the gut mucins are a bit different from those found on the endothelium, largely because they have different functions. The gut (and generally mucous epithelial) mucus is there for (amongst other things) clearing and maintaining a microbiome. Endothelial glycocalyx probably has some other mucin proteins, but also likely lots of mucin-like proteins, and the set of functions of these are much less clear.
- Yes, something along these lines, and maybe the other pathways as the most interesting possibility. I don’t know if there any reports of sTn in older mice, but that would be pretty wild.
- Catflap is a surprisingly apt analogy. In this case it is an endocytosis receptor, that selects cargo for uptake. Differs from virus to virus of course, but I could see changes in the sugars on these proteins altering behaviour. Mucus/mucins are basically proteins very heavily modified with sugars, so you have this common system that is adapted to do different things.
- Fun fact: The AAVR (AAV receptor) is itself a glycoprotein (carrying the precise type of glycosylation they are trying to repair with the “gene therapy”). Haven’t read up what replacement gene dose ended up being, but entirely within realms of possibility that this could influence which cells get corrected.
- We don’t know is the answer. However, if you were coral, then I would suggest increasing the amount of symbiotic algae, which stimulates mucin secretion (probably a nutrient boost).
A brain normally doesn’t receive enough sunlight for this strategy to work for humans.
- This area is very much in my wheelhouse (both the biosynthetic process, and functions of mucins). They’re a pretty interesting biomolecule, present in all animals (slightly different molecules in other branches of life).
It kind of surprises me that such a low fold-change in core1 synthase yields such a huge change in glycocalyx. Everything we know about this enzyme says it is an absolute rocket on substrates, so I can’t really see this process being enzyme-limited. There might be other (mouse specific) things going on here that this is scratching the surface on.
- First question I have is what kind of nutrient base conditions can we expect to start from? Should it be like Earth, or somewhere a bit more resource constrained (and how would it be constrained)?
I’d like to imagine solar reactors mimicking primordial goo to synthesise the essentials for these materials.
- Colour me unsurprised - even not knowing data leakage had occurred, the hypothesis was underwhelming, as I mentioned in a comment on an earlier discussion. I sometimes despair for the state of thinking in science these days given how quickly people fawn over entirely pedestrian thinking and work.
Possibly popularised by Atul Gawande “The Checklist Manifesto”.
Meta-comment: LLMs continue to impress me in the capabilities with unearthing information from imprecise inputs/queries.