siderea: (Default)
[personal profile] siderea
2025 Dec 24: ScienceDaily [press release?]: "Scientists reverse Alzheimer’s in mice and restore memory":
By examining both human Alzheimer's brain tissue and multiple preclinical mouse models, the team identified a key biological failure at the center of the disease. They found that the brain's inability to maintain normal levels of a critical cellular energy molecule called NAD+ plays a major role in driving Alzheimer's. Importantly, maintaining proper NAD+ balance was shown to not only prevent the disease but also reverse it in experimental models.
WARNING WARNING WARNING: Yes, there are OTC supplements for tinkering with your NAD+, but they are apparently/allegedly CARCINOGENIC (cause CANCER) at typical doses. DO NOT run out and do something stupid. Tinkering with your whole-body cellular metabolism has some gnarly failure modes. From this article:
Why This Approach Differs From Supplements

Dr. Pieper cautioned against confusing this strategy with over the counter NAD+-precursors. He noted that such supplements have been shown in animal studies to raise NAD+ to dangerously high levels that promote cancer. The method used in this research relies instead on P7C3-A20, a pharmacologic agent that helps cells maintain healthy NAD+ balance during extreme stress, without pushing levels beyond their normal range.
Continuing from the article:
NAD+ levels naturally decline throughout the body, including the brain, as people age. When NAD+ drops too low, cells lose the ability to carry out essential processes needed for normal function and survival. The researchers discovered that this decline is far more severe in the brains of people with Alzheimer's. The same pattern was seen in mouse models of the disease.

[...]

Amyloid and tau abnormalities are among the earliest and most significant features of Alzheimer's. In both mouse models, these mutations led to widespread brain damage that closely mirrors the human disease. This included breakdown of the blood-brain barrier, damage to nerve fibers, chronic inflammation, reduced formation of new neurons in the hippocampus, weakened communication between brain cells, and extensive oxidative damage. The mice also developed severe memory and cognitive problems similar to those seen in people with Alzheimer's.

[...]

This approach built on the group's earlier work published in Proceeding of the National Academy of Sciences USA, which showed that restoring NAD+ balance led to both structural and functional recovery after severe, long-lasting traumatic brain injury. In the current study, the researchers used a well-characterized pharmacologic compound called P7C3-A20, developed in the Pieper laboratory, to restore NAD+ balance.

The results were striking. Preserving NAD+ balance protected mice from developing Alzheimer's, but even more surprising was what happened when treatment began after the disease was already advanced. In those cases, restoring NAD+ balance allowed the brain to repair the major pathological damage caused by the genetic mutations.

Both mouse models showed complete recovery of cognitive function. This recovery was also reflected in blood tests, which showed normalized levels of phosphorylated tau 217, a recently approved clinical biomarker used to diagnose Alzheimer's in people. These findings provided strong evidence of disease reversal and highlighted a potential biomarker for future human trials.
Note, potential conflict of interest: the head of the lab, Dr Pieper, above, has a serious commercial interest in this proving out:
The technology is currently being commercialized by Glengary Brain Health, a Cleveland-based company co-founded by Dr. Pieper.
The actual research article:

2025 Dec 22: Cell Reports Medicine [peer-reviewed scientific journal]: Pharmacologic reversal of advanced Alzheimer's disease in mice and identification of potential therapeutic nodes in human brain by Kalyani Chaubey et al. (+35 other authors!):
Abstract:

Alzheimer's disease (AD) is traditionally considered irreversible. Here, however, we provide proof of principle for therapeutic reversibility of advanced AD. In advanced disease amyloid-driven 5xFAD mice, treatment with P7C3-A20, which restores nicotinamide adenine dinucleotide (NAD+) homeostasis, reverses tau phosphorylation, blood-brain barrier deterioration, oxidative stress, DNA damage, and neuroinflammation and enhances hippocampal neurogenesis and synaptic plasticity, resulting in full cognitive recovery and reduction of plasma levels of the clinical AD biomarker p-tau217. P7C3-A20 also reverses advanced disease in tau-driven PS19 mice and protects human brain microvascular endothelial cells from oxidative stress. In humans and mice, pathology severity correlates with disruption of brain NAD+ homeostasis, and the brains of nondemented people with Alzheimer's neuropathology exhibit gene expression patterns suggestive of preserved NAD+ homeostasis. Forty-six proteins aberrantly expressed in advanced 5xFAD mouse brain and normalized by P7C3-A20 show similar alterations in human AD brain, revealing targets with potential for optimizing translation to patient care.
Full text here: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00608-1

Write every day: Day 24

Dec. 24th, 2025 11:32 pm
luzula: a Luzula pilosa, or hairy wood-rush (Default)
[personal profile] luzula
Day 24: Alibi editing, but that's fine, since the 24th is the main Christmas celebration in Sweden. How about you?

Tally:
Read more... )
Day 23: [personal profile] luzula, [personal profile] trobadora, [personal profile] sylvanwitch, [personal profile] sanguinity, [personal profile] goddess47, [personal profile] chanter1944, [personal profile] cornerofmadness, [personal profile] china_shop, [personal profile] badly_knitted, [personal profile] chestnut_pod

Day 24: [personal profile] luzula, [personal profile] china_shop

Bonus farm news: Put my chainsaw lesson to use by cutting down our Christmas tree. : D

Yuletide 2025 Anonymous Period

Dec. 24th, 2025 04:14 pm
yuletidemods: A hippo lounges with laptop in hand, peering at the screen through a pair of pince-nez and smiling. A text bubble with a heart emerges from the screen. The hippo dangles a computer mouse from one toe. By Oro. (Default)
[personal profile] yuletidemods posting in [community profile] yuletide_admin
Hello, Yuletiders–as you may have noticed, the anonymous setting on the Yuletide collection, which should hide all author names until reveals on January 1st, does not seem to be working as expected, and shortly after our planned works reveals, we had an unplanned reveal of author names. We’re very sorry for this unexpected breaking of anonymity!

We’re reaching out to AO3 to help us resolve the problem. In the meantime, we have updated all works manually, and author names should now be hidden again. If you notice we have missed any, please reach out to us privately at yuletideadmin@gmail.com.

Again, our apologies–and we hope you enjoy the collection!

Yuletide Madness is scheduled to reveal at 9 PM UTC on 25 December, but this may be delayed if necessary to ensure author anonymity.

ETA: We know many of you have received email notifications to say, "The collection maintainers of Yuletide 2025 have changed the status of your work [work] to anonymous..." This is a result of us updating them manually to hide author names, in order to achieve the same effect you would expect from reveals in an ordinary Yuletide. Sorry for the confusion! You can safely ignore these notifications; we will reveal author names on January 1st, manually if we have to.


Schedule, Rules, & Collection | Contact Mods | Participant DW | Participant LJ | Pinch Hits on DW | Discord | Tag set | Tag set app

Please either comment logged-in or sign a name. Unsigned anonymous comments will be left screened.

Happy Yuletide!

Dec. 24th, 2025 01:03 pm
rachelmanija: (Autumn: small leaves)
[personal profile] rachelmanija
The Yuletide collection is live!

Enjoy browsing the collection! Leave kudos and/or comments if you enjoy a story! Comment here to recommend stories, and/or recommend them at the [community profile] yuletide comm!

I have three stories in the collection. Can you find them?

I shall now spend the rest of the day cuddling with my cats and reading Yuletide stories.

Yuletide 2025 is live!

Dec. 24th, 2025 02:59 pm
yuletidemods: A hippo lounges with laptop in hand, peering at the screen through a pair of pince-nez and smiling. A text bubble with a heart emerges from the screen. The hippo dangles a computer mouse from one toe. By Oro. (Default)
[personal profile] yuletidemods posting in [community profile] yuletide_admin
Yuletide 2025 Collection Is Live Here!


Enjoy 1539 works in 992 fandoms! (The number will go up as wranglers canonize fandoms - this will take a little time, though.)

The reveals process takes a little while to work in a collection of this size; if a story in the collection is still a mystery work an hour after opening, please let us know.


Finding works
You can find your own gifts on your AO3 gifts page: https://archiveofourown.org/users/YOUR-NAME-HERE/gifts, or by searching the box at the top of the collection works page for the full name you signed up with, or by checking your email if you get email notifications from AO3. Note: your email notifications may bundle together, and it might look like you only got one gift, when in fact you got more.

You can browse the collection by tags or by fandoms. Some fandoms are new and may not show up immediately (wranglers are working on this) or where you expect them; please check labels such as Original Work, 19th Century Historical RPF, Object and Concept Anthropomorphism, and Unspecified Fandom. More info about Unspecified Fandom here.


Anonymity
Yuletide is an anonymous exchange until creator reveals January 1. Please don't give away what you've written. When logged in, you can, if you want, reply to comments on your own works, and you will show up as Anonymous Creator until the authors of the collection are revealed.


Commenting!
Please comment on your gift(s) to let your writer(s) know you appreciate them. We also recommend commenting far and wide to spread the comment joy around! You may enjoy the challenge of a comment bingo card [update for this year's link!].

AO3 changed default comment settings last year. If you want to make sure people can comment on your gifts when they aren't logged in, you may need to change a setting on your work. More information here, under 'Your comment settings'.


Recs
Making work recommendations is a tradition. Please see more information at the participant community ([community profile] yuletide) about where you can post your recs.


Madness
For those still writing, the 2025 Yuletide Madness collection will stay open for new stories to be posted for 24 hours. It will close for posting, and open for reading, at 9pm UTC 25 December. If you're looking for prompts, there's a roundup of links here.


Problems
If there is something wrong with your gift or you have another concern, please contact the mods at yuletideadmin@gmail.com.



Schedule, Rules, & Collection | Contact Mods | Participant DW | Participant LJ | Pinch Hits on DW | Discord | Tag set | Tag set app

Please either comment logged-in or sign a name. Unsigned anonymous comments will be left screened.

Books I've Read: January-April 2025

Dec. 24th, 2025 11:52 am
hrj: (Default)
[personal profile] hrj
It's going to be a bit trickier to create this post while visiting at my Dad's place since my process involves three different windows (spreadsheet of reading notes, Dreamwidth entry, and database for finished reviews) which I can normally pull up on different screens.

A Sorceress Comes to Call by T. Kingfisher -- (audio) The plot is...well, let’s call it “allusive of” rather than “based on” the fairy tale of the goose girl and her talking horse. There’s a horribly abusive mother (whose comeuppance is similar to the climax of my fairy tale The Language of Roses), a sympathetic ingenue, and a lovely second-chance romance involving an older woman (a Kingfisher specialty). Big content notice for violence and coercion. It's a very painful story, so I'm not sure that "enjoyable" is the right description, but I'm glad I read it.

Murder in an English Village by Jessica Ellicott -- (audio) I was exploring some sale books to see if I could find any interesting historic mysteries and thought this book looked interesting. It’s set between the World Wars and involves two old school chums—-one an English spinster and one an American adventuress—-who stumble into several mysteries. It’s a pleasant enough mystery, though I was unwarrantedly hoping for a touch more sapphic subtext, along the lines of Miss Buncle’s Book.

A Room of One's Own by Virginia Woolf -- (audio) Picked up from an audiobook sale, in part because I'd done an interview where the interviewee made the assumption that of course every feminist has read Woolf and I realized I hadn't. A Room of One's Own is broadly about the difficulties of being a woman writer. Pair this classic with Joanna Russ’s How To Suppress Women’s Writing and then sink into a deep depression about how little has changed since those books were written.

All the Painted Stars by Emma Denny -- (audio) A pleasant enough medieval f/f romance with competent prose, but the historic grounding is exceedingly thin and occasionally annoying. Horses aren't cars. Parchment isn't post-its. Village brewers don't work at industrial scale. It wasn’t a matter of large inaccuracies, but of a constant flow of small details that kept distracting me from the endearing main characters. This book is a follow-on from her previous one which focused on a gay male couple. The two stories are connected by family ties.

The Imposition of Unnecessary Obstacles by Malka Older -- (audio) The second in a sapphic space-mystery series. These are novellas set in a colony constructed around Jupiter after humanity fled an uninhabitable Earth. Murder mysteries get solved by a detective and academic duo who are also negotiating a revival of their romance. The books are enjoyable and have a fun time grounding the mysteries in the worldbuilding.

The Golem and the Jinni by Helene Wecker -- (audio) I finally got around to reading this highly praised book, which came out a number of years ago. The novel asks the question: can a naïve and brilliant golem who has lost her immigrant master on the voyage to America, and a metal-working Jinni newly freed from magical entrapment find their way together in early 20th century New York and foil the schemes of the sorcerer who wants to re-enslave them both? This was beautiful and heartbreaking and ultimately triumphant and I don’t know what took me so long to come back to it, given that I’ve owned a hard copy since it first came out.

Gentleman Jack by Anne Choma -- (audio) I don’t usually consume books for the lesbian history blog via audiobook -- it makes it hard to take notes! It made sense in this case because it’s more of a narrative history rather than a scholarly analysis. This is a narrative history of Anne Lister’s life between November 1831 and March 1834, the period covered by the tv series Gentleman Jack. The book was written specifically as a companion to the tv series, giving the actual details of Anne’s life during that period, which differ in various details from the tv series. (The tv series both omitted and invented significant details.) Interspersed in the narrative are extensive quotes from Anne’s diaries. The account is very readable and will give you a solid background of Anne’s life and times. It is neither a scholarly historical analysis (for that, you might try Jill Liddington) nor an extensive and contextualized survey of significant portions of the diaries (for which you want Helena Whitbread). But it hits a sweet spot for the general reader. And if you’re a fan of the tv series, it makes an interesting “compare and contrast” to understand how history gets adapted for the requirements of drama.

The Tomb of Dragons by Katherine Addison -- (audio) I think this finishes up the Cemetaries of Amalo series, set in the same universe as The Goblin Emperor. As with previous books in the series, there are a number of plot threads that braid together in the resolution. Our protagonist, a "witness for the dead" who can communicate with dead souls finds himself representing a murdered dragon. One of the other major plot threads about an escaped insurgent ties back in at the climax in a way that feels a little too convenient. And there's a surprising twist to a hinted-at romance arc that's been developing across the series.

The Suffragette Scandal by Courtney Milan -- (audio) I've read several Courtney Milan historic romances in the past, with mixed impressions. This one worked very well for me, centering around Victorian-era feminist movements and one of her favorite tropes: aristocrats who are desperately trying to escape their fate. But the reason I picked it up was for the very-much-background sapphic romance that has been slipped into the cracks of the main story.

I was originally going to do just January and February in this post, but then there were only two books I finished in March, and none in April, so it made sense to expand the official scope. (April was, of course, my last month on the job and I was a bit distracted.) Looking ahead in the spreadsheet, I may do another four-month set in the next post and then do one post each for the final four months of the year, based on numbers.

Wednesday Reading Meme

Dec. 24th, 2025 02:00 pm
sineala: Detail of Harry Wilson Watrous, "Just a Couple of Girls" (Reading)
[personal profile] sineala
What I Just Finished Reading

Nothing. Working on it.

What I'm Reading Now

Comics Wednesday!

1776 #2, Marvel Winter Break Special 2025 #1, Will of Doom #1, X-Vengers #3 )

What I'm Reading Next

I woke up this morning to find that [personal profile] lysimache had gifted me an ebook entitled Here Comes the Pizzer: The Found Poetry of Baseball Broadcasts, by Eric Poulin, so I guess that's what we'll be doing dramatic readings of aloud for Christmas Eve. While eating pizza.

The title is a reference to this extremely classic Red Sox broadcast moment. Here comes the pizza.

(We usually read the Christmas story in Greek, Latin, or Old English for Christmas Eve but we can probably make some time for this.)

2025 Recap

Dec. 24th, 2025 12:44 pm
ailelie: (Default)
[personal profile] ailelie
I got laid off. I wrote a lot. I got a new job.

That's the year.

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magid

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