Jeff Carroll, PhD

Hey that's me! This was a huge and unexpected honor. The HDF and Wexler family has been a huge inspiration for me, and so this couldn't be a nicer recognition to receive.

We speculate that this is due to lowering of HTT1a, a specific form of HTT mRNA that arises from a failure of exon-1 to splice to exon-2, leading to alternate cleavage and polyadenylation that was discovered and characterized by Gill Bates's lab at UCL.

So, we can say that targeting intron-1 with an ASO in this case leads to really striking rescue of molecular features of HD in a knock-in mouse...

Changing transcripts could be good or bad, but if we look at HD people's favorite genes, we see a very striking pattern of rescue when we target intron-1 with an ASO that we don't see if we target downstream:

Surprisingly, this is the first mouse HTT ASO experiment to show robust transcriptional rescue. If we look at just the mutant mice by bulk RNASeq, a more distal HTT ASO (left) changes exactly two transcripts - one of which is HTT itself. But targeting intron-1 leads to a huge change of transcripts:

The ASO targeting intron-1 basically eliminates aggregates while the more downstream one does nothing:

Glad to see this out in the world. We observe remarkable rescue in an HD mouse using an ASO targeting intron-1 of Huntingtin, rather than downstream. The intron-1 targeting ASO essentially completely eliminates aggregates, whereas the more distal ASO does nothing: www.biorxiv.org/content/10.1...

Scientists, especially Seattle ones! One of my research scientists is heading to her PhD and we're looking to fill her spot, if not replace her. If you know someone looking to do cool and impactful translational research give them this:

uwhires.admin.washington.edu/ENG/Candidat...

And cost of living in several key cities (eg Vancouver and Toronto) not feasible with academic salaries in those towns. Even if you can get a grant!

The big beautiful bill reveals the hollowness of Trumponomics Republicans mark America’s birthday with a profligate but insubstantial law

This sub-title from the @economist.com , ouch! But accurate.

www.economist.com/briefing/202...

This is pretty niche!

5. Wars are easy to start and hard to stop

Support the troops baby!!

Tump's bullying is just his psychopathic personality. Vance is, actually, kind of worse because he's strictly doing it to impress other guys he perceives as tougher. He's like the punk ass kid who takes a kick at someone after the bully knocks him down.

A hell of a lot of the California National Guard is made up of people from immigrant communities, fwiw.

Wow, congrats!

Good lord, how can anyone serious about science even consider cutting funding for Flybase?

Just published, expansion in situ genome sequencing, where you can sequence DNA while still inside the cell, mapping its organization relative to proteins and other markers, with the help of expansion microscopy! Led by @jbuenrostro.bksy.social. www.science.org/doi/10.1126/...

God please. One on every corner.

Amazing news that she’s finally free

Being in the military is an interesting experience of what it means to be really filthy, which is kinda what I figure they’d look like?

Trump Has Cut Science Funding to Its Lowest Level in Decades (Gift Article) The lag in funding extends far beyond D.E.I. initiatives, affecting almost every area of science: chemistry, computing, engineering, materials and more.

New York Times article on NSF

www.nytimes.com/interactive/...

1/2

It's painful to read this, 5 years later. Study finds no increase in Covid spread in nursing home after visitation bans were lifted. Implication: The bans, which meant months of isolation for nursing home residents and heartbreak of their families, did no good.
pubmed.ncbi.nlm.nih.gov/40383139/

So, if you search google scholar enough it will just flag you as a bot and then there's absolutely no recourse, nor a human that you can prove you're not a bot. Reminding me we shouldn't be outsourcing such a key academic service to a for profit company that normalized not talking to its customers.

A Liz Truss Moment for America? Financial indicators are flashing yellow

30 year Treasury above 5%. Also, I successfully used AI to do a Trump/Truss crossover, putting a Trump wig on a lettuce
paulkrugman.substack.com/p/a-liz-trus...

Although there has been many positive things happening lately for myself and my lab group, this week we've gotten the bad news of a grant termination, as the lead PI is at Harvard (and they've had all their federal funding terminated). It will be tough to stop the work that only last year 1/2

I remember a story in the Army where a commander was dubious about intelligence soldiers working with people who had connections with the Taliban and could we trust people like that and the intel officer replied "the people who don't work with the Taliban have no information about them."

I'm always intrigued by people who miss very obvious points in art they love. Things like: people who are mad that "Star Trek is woke" or Paul Ryan loving Rage Against the Machine.

The profile that Vinay Prasad deserves. He's presence in this administration is sign of Trump's commitment to endangering public health. Excellent work @lauralew105.bsky.social ! 🩺 #medsky

newrepublic.com/article/1949...