Some of this stuff dates from late last year when I was too busy with Menewood stuff to comment. But as some of my favourite things in life (well, the favourite things we can talk about in polite company) are cats, wine, and history, and as one of my ongoing personal concerns is autoimmune disease, I thought, Eh, let's combine them. We'll start with the weighty stuff first then lighten up a little.
Why women get autoimmune disease more often than men
Note: Given the nature of the science under discussion here I'll be using 'women' and 'female' as shorthand for those with XX genotype. But do bear in mind that gender expression, phenotype, and genotype do not necessarily align.
About 80% of people with autoimmune diseases (e.g. lupus, rheumatoid arthritis) are women.1 In most mammals females have two X-chromosomes (XX) and males one X and one Y (XY). People are mammals: women are typically born with XX and men XY.2 Each X chromosome contains the full set of genetic instructions we need to build the proteins that run and maintain all our physical processes: no proteins = no life. But too many proteins are deadly. So one of women's two X chromosomes has to be turned off to avoid fatal duplication. A recent paper in Cell suggests that it's this process that's a major driver of autoimmune disease.
Here's the abstract:
Autoimmune diseases disproportionately affect females more than males. The XX sex chromosome complement is strongly associated with susceptibility to autoimmunity. Xist long non-coding RNA (lncRNA) is expressed only in females to randomly inactivate one of the two X chromosomes to achieve gene dosage compensation. Here, we show that the Xist ribonucleoprotein (RNP) complex comprising numerous autoantigenic components is an important driver of sex-biased autoimmunity. Inducible transgenic expression of a non-silencing form of Xist in male mice introduced Xist RNP complexes and sufficed to produce autoantibodies. Male SJL/J mice expressing transgenic Xist developed more severe multi-organ pathology in a pristane-induced lupus model than wild-type males. Xist expression in males reprogrammed T and B cell populations and chromatin states to more resemble wild-type females. Human patients with autoimmune diseases displayed significant autoantibodies to multiple components of XIST RNP. Thus, a sex-specific lncRNA scaffolds ubiquitous RNP components to drive sex-biased immunity.
Dian R. Dou, et al (2024). Xist ribonucleoproteins promote female sex-biased autoimmunity, Cell, VOLUME 187, ISSUE 3, P733-749.E16, FEBRUARY 01. DOI: https://doi.org/10.1016/j.cell.2023.12.037
What all that boils down to is that something called XIST, made of long strands of RNA, wraps itself around one of the X chromosomes; the RNA attracts all sorts of proteins; and those proteins form complexes that smother the genes inside and prevent them sending out instructions to build more proteins.3 Every cell in a woman's body contains this XIST complex. When in the natural course of things when cells die these complexes are exposed to the immune system. The immune system can then produce autoantibodies—that is, the XIST can trigger an inflammatory immune response as those autoantibodies go after otherwise healthy parts of the body mistaking them for alien intruders.
Why is this interesting? Two reasons. One, if you can pinpoint the exact autoantibody involved in a specific condition then you have an accurate diagnostic tool: you can detect a problem before symptoms manifest. Two, if you understand the specific autoimmune trigger then you cn start looking for ways to block it—which could lead to a hyper-targeted therapy. Today, most autoimmune disease is treated by shutting down huge swathes of the immune system—which is not just only partially successful as a treatment but quite dangerous in itself. Or, as with some drugs used for scleroderma, they target limited pathways of the disease, such as the decline of lung function.4 All drugs that suppress chunks of the immune system are dangerous. A hyper-targeted therapy would not only be more effective it would be much, much safer.
The true origins of wine
The story of wine has previously been told by archaeologists fussing with organic residue on pot sherds, or paleobotanists waxing ecstatic over bits of grape seed or pollen. Using this kind of material evidence, it was previously assumed that wine cultivation dates back 7,000 years, or 6,000 yearsor 9,000 years depending on who you were talking to andi which country. But now a large international group of researchers collected and analyzed 2,503 unique vines from domesticated table and wine grapes and 1,022 wild grapevines. By extracting DNA from the vines and determining the patterns of genetic variations among them, they found it dates back 11,000 years:
When the last Ice Age ended and the glaciers retreated, roughly 11,000 years ago, something appears to have changed among the wild grapevines of Asia. They became domesticated. The first farmers on Earth began cultivating the best vines with the biggest, juiciest grapes. Wine, and civilization, soon followed.
Washington Post
Grapes were probably the first domesticated crop. We have agriculture because of grapes. We have civilization because of grapes. Wine is good.
Pushing back the date of humans in North America
A while ago I was talking about pushing back the date of humans in the Americas. We now have another >20k years ago date, this time from North America—New Mexico, to be precise.
New research confirms that fossil human footprints in New Mexico are likely the oldest direct evidence of human presence in the Americas, a finding that upends what many archaeologists thought they knew about when our ancestors arrived in the New World.
The footprints were discovered at the edge of an ancient lakebed in White Sands National Park and date back to between 21,000 and 23,000 years ago, according to research published Thursday in the journal Science.
AP
According to Nature, the finding supports the idea that "people skirted down the Pacific coast of the Americas after crossing the Bering land bridge, rather than waiting until ice-age glaciers retreated from inland routes." The timeline is also supported by indirect evidence (e.g. carvings made from dateable animal bone and horn) but the footprints are unmistakably and directly human. I'm still betting we can push the timeline back significantly. Stay tuned.
How cats purr—maybe
How do cats purr? I mean, they're small beasties and purrs are deep and resonant—it doesn't make a lot of sense. Deep sounds need long vocal cords. Yes, cats are masters of space and time—obviously they can defy the laws of physics—still, wouldn't it be lovely to have a more down to earth explanation? And now we do! A new study in Current Biology suggests purring is made possible by fibrous pads in the cat's vocal folds. And, what's more, they can take their brains offline to do it. Maybe. (Note: no cats were harmed for the purpose of this study. Larynxes were taken from pets who had to be put to sleep due to old age or illness.)
No comments:
Post a Comment