The other uses of amyloid (not all bad)

Neurologists and drug chemists pretty much view amyloid as a bad thing.  It is the major component of the senile plaque of Alzheimer’s disease, and when deposited in nerve causes amyloidotic polyneuropathy.  A recent paper and editorial casts amyloid in a different light [ Cell vol. 173 pp. 1068 – 1070, 1244 – 2253 ’18 ].  However if amyloid is so bad why do cytomegalovirus, herpes simplex viruses and E. Coli make proteins to prevent a type of amyloid from forming.

Cell death isn’t what it used to be.  Back in the day, they just died when things didn’t go well.  Now we know there are a variety of ways that cells die, and all of them have rather specific mechanisms.  Apoptosis (aka programmed cell death) is a mechanism of cell death used widely during embryonic development.  It allows the cell to die very quietly without causing inflammation.  Necroptosis is entirely different, it is another type of programmed cell death, designed to cause inflammation — bringing the immune system in to attack invading pathogens.

Two proteins (Receptor Interacting Protein Kinase 1 — RIPK1, and RIPK3) bind to each other forming amyloid, that looks for all the world like typical amyloid –it binds Congo Red, shows crossBeta diffraction and has a filamentous appearance.  Fascinating chemistry aside, the amyloid formed is crucial for necroptosis to occur, which is why various bugs try to prevent it.

The paper above describes the structure of the amyloid formed — unusual in itself, because until now amyloid was thought to involve the aggregation of a single protein.

The proteins are large: RIPK1 contains 671 amino acids, and RIPK3 contains 518.  They  both contain RHIMs (Receptor interacting protein Homotypic Interaction Motifs) which are fairly large themselves (amino acids 496 – 583 of RIPK1 and 388 – 518 of RIPK3).  Yet the amyloid the two proteins form use a very small stretches (amino acids 532 – 543 from RIPK1 and 451 – 462 from RIPK3).  How the rest of these large proteins pack around the beta strands of the 11 amino acid stretches isn’t discussed in the paper.  Even within these stretches, it is two consensus tetrapeptides (IQIG from RIPK1, and VQVG from RIPK3) that do most of the binding.

Even if you assume that I (Isoleucine) Q (glutamine) G (glycine) V (valine) occur at a frequency of 5%, in our proteome of 20,000 proteins assuming a length of amino acids IQIG and VQVG should occur 10 times each.  This may explain why 300/20,000 of our proteins contain a 100 amino acid  segment called BRICHOS which acts as a chaperone preventing amyloid formation. For details see —

Just another reason to take up the research idea in the link and find out just what other things amyloid is doing within our cells in the course of their normal functioning.



Relativity becomes less comprehensible

“To get Hawking radiation we have to give up on the idea that spacetime always had 3 space dimensions and one time dimension to get a quantum theory of the big bang.”  I’ve been studying relativity for some years now in the hopes of saying something intelligent to the author (Jim Hartle), if we’re both lucky enough to make it to our 60th college reunion in 2 years.  Hartle majored in physics under John Wheeler who essentially revived relativity from obscurity during the years when quantum mechanics was all the rage. Jim worked with Hawking for years, spoke at his funeral and wrote this in an appreciation of Hawking’s work [ Proc.Natl. Acad. Sci. vol. 115 pp. 5309 – 5310 ’18 ].

I find the above incomprehensible.  Could anyone out there enlighten me?  Just write a comment.  I’m not going to bother Hartle

Addendum 25 May

From a retired math professor friend —

I’ve never studied this stuff, but here is one way to get more actual dimensions without increasing the number of apparent dimensions:
Start with a 1-dimensional line, R^1 and now consider a 2-dimensional cylinder S^1 x R^1.  (S^1 is the circle, of course.)  If the radius of the circle is small, then the cylinder looks like a narrow tube.  Make the radius even smaller–lsay, ess than the radius of an atomic nucleus.  Then the actual 2-dimensional cylinder appears to be a 1-dimensional line.
The next step is to rethink S^1 as a line interval with ends identified (but not actually glued together.  Then S^1 x R^1 looks like a long ribbon with its two edges identified.  If the width of the ribbon–the length of the line interval–is less, say, than the radius of an atom, the actual 2-dimensional “ribbon with edges identified” appears to be just a 1-dimensional line.
Okay, now we can carry all these notions to R^2.  Take S^1 X R^2, and treat S^1 as a line interval with ends identified.  Then S^1 x R^2 looks like a (3-dimensional) stack of planes with the top plane identified, point by point, with the bottom plane.  (This is the analog of the ribbon.)  If the length of the line interval is less, say, than the radius of an atom, then the actual 3-dimensional s! x R^2 appears to be a 2-dimensional plane.
That’s it.  In general, the actual n+1-dimensional S^1 x R^n appears to be just n-space R^n when the radius of S^1 is sufficiently small.
All this can be done with a sphere S^2, S^3, … of any dimension, so that the actual k+n-dimensional manifold S^k x R^n appears to be just the n-space R^n when the radius of S^k is sufficiently small.  Moreover, if M^k is any compact manifold whose physical size is sufficiently small, then the actual k+n-dimensional manifold M^k x R^n appears to be just the n-plane R^n.
That’s one way to get “hidden” dimensions, I think. “

Tom Wolfe R. I. P

Tom Wolfe has passed on.  It’s worth republishing an appreciation of him and how he changed writing in America. It contains links to a 3 part review of what was probably his last book “The Kingdom of Speech”

Tom Wolfe — an appreciation

Tom Wolfe’s writing style and the genre he created have been part of the intellectual wallpaper for so long, that it’s easy to forget how badly he was needed. The following is quite autobiographical, but it does put his emergence in context.

Intellectually isolated adolescents in the early 50s read books, lots of them (minimal TV of any intellectual content, no internet etc. etc.) I had plenty of time in high school, with two 16 mile rides on the school bus each day. So I managed to read a book a day my senior year in high school. I particularly loved Balzac and Dickens for the way they wrote about all levels of society.

So although I was fairly well read on entry into Princeton in the fall of 1956, I was a geographic naif, never really having travelled west of Philly. I was a social naif as well, with only 6/24 boys in my high school class going on to collage. The ones that didn’t went into the military, law enforcement or the trades. None of the 24 girls got further education, initially at least. This was not a high or wealthy social background. I was the first member of my family not to go to Rutgers (the state school of New Jersey).

The Princeton Triangle Club put on a rather sophomoric show each year which toured the east coast and midwest on Christmas break. Earlier famous members included Jimmy Stewart and Josh Logan. Later, after women were admitted, Brooke Shields. I was good enough to make pianist in the pit band for the show and did this for two years.  The incredibly creative guy writing the shows was Clark Gesner, who soon after wrote “You’re a Good Man Charlie Brown” and essentially retired in his late 20s.

The class of 1959 was the first at Princeton to have more High School graduates than preppies. To the alums that put us up in their homes after the show, it was assumed that we were to the manor born (as many of them were).

Seeing upper class society was quite an education. After each show the performers (and band) were invited to debutante parties. I’d never seen anything like it, and none of the American novels I’d read dealt with it. The musicians in the band would listen to the society orchestras playing (Lester Lanin, Peter Duchin, Meyer Davis) and dance with the debs. In Chicago, I even was the male presenting one debutante, rather than a local — probably because she was Jewish and none of the locals would do it. In Grosse Point Michigan the following exchange occurred with a deb who seemed intelligent. Where do you go to school? Oh someplace back East. How do you like the party? Enough for me to decide not to attempt to become part of that world (not that it was ever possible).

Then in grad school at Harvard, I met extremely intelligent guys from the West Coast (Caltech, Berkeley, Brigham Young) who were reading “Road and Track” in all seriousness (camp hadn’t been invented yet). Road and track was for the guys back home who went to work in garages, and dragraced with each other.

No one in the 50s and early 60s was writing about this stuff — here’s a link to the best-sellers of the 50s —
if you don’t believe me. Some were good (To Kill a Mockingbird). A lot were by foreigners (Dr. Zhivago, Francois Sagan, Simone de Beauvoir).

We had this fascinating diverse society, and our literature wasn’t dealing with it — that is until Tom Wolfe came along. He wrote about car customizers, astronauts, high society, low society, enjoying it all. These weren’t thought to be the stuff of serious literature until then. Some of the best sellers back then bore the same relationship to reality (Marjorie Morningstar, Not as a Stranger) as the Doris Day Rock Hudson movies of the time bore to the sexual interactions of male and female.

So hats off to Tom Wolfe. He’s still writing — I recommend his latest – “The Kingdom of Speech” about which I wrote 3 posts. Although the book starts in Victorian England, it winds up in the USA with Chomsky and company and the social high jinks of the left, which Wolfe has been skewering for decades. Here’s a link to one of the posts —

Cultural appropriation, neuroscience division

If Deng Xiaoping can have Socialism with Chinese Characteristics, I can have a Chinese saying with neuroscientific characteristics — “The axon and the dendrite are long and the nucleus is far away” mimicking “The mountains are high and the Emperor is far away”. The professionally offended will react to the latest offense du jour — cultural appropriation  — of course.  But I’m entitled and I spoke to my Chinese daughter in law, and people over there found it flattering and admiring of Chinese culture that the girl in Utah wore a Chinese cheongsam dress to her prom.

Back to the quote.  “The axon and the dendrite are long and the nucleus is far away”.  Well, neuronal ends are far away from the cell body — the best example are axons from the sacral spinal cord which in an NBA player can be a yard long.  But forget that, lets talk about the ends of dendrites which are much closer to the cell body than that.

Presumably neurons have different types of dendrites so they can respond to different types of inputs. Why should dendrites respond identically if their inputs are different? They don’t.    A dendrite responding to acetyl choline will express neurotransmitter receptors distinct from another dendrite on the same neuron distinct from a dendrite responding to dopamine.  The protein cohorts of axons and dendrites are different.  How does this come about?  Because the untranslated part of mRNA on the 3′ end (3’UTR) contains a sequence called a zipcode which binds to specific proteins which then move the mRNA to a specific location in the neuron (axon or dendrite).  Presumably all dendrites initially had the same complement of mRNA.

So depending on what’s happening at a particular dendrite on a neuron, more or less of a given protein is made.   This is way too abstract.  Suppose you want to strengthen a synapse.  You’d make more of a neurotransmitter receptor or an ion channel for whatever transmitter that dendrite is getting.

It is well established that axons and dendrites store mRNAs and make proteins from them far from the nucleus (aka the emperor).  If you think about it, just how a receptor for dopamine gets to a dendrite receiving dopamine and not to a dendrite (on the same neuron) getting glutamic acid as a transmitter, is far from clear.  There are zipcodes distinguishing axons from dendrites, but I’m unaware that there are zipcodes for dopamine dendrites distinct from other types of dendrites.

If that weren’t enough consider [ Neuron vol. 98 pp. 495 – 511 ’18 ].  Even for an mRNA coding for the same protein (presumably transcribed from just one gene), there can be more than one type of 3’UTR (and this in the same cell).  Note also that 3’UTRs are longer in neurons than in other tissues.

So the authors looked at the mRNAs in dendrites — they did this by choosing a tissue (the hippocampus) where rows of cell bodies are well separated from their dendrites.  They found that for a given dendritic mRNA there was more than one 3’UTR, and that the mRNAs with longer 3’UTRs had longer halflives.  Even more exquisitly neuronal activity altered the proportion of the different 3’UTR isoforms. The phenomenon is quite general — over 50% of all genes and over 70% of genes enriched in neurons showed multiple 3′ UTRs.

So there is a whole control system built into the dendritic system, and it varies with what is happening locally.

The emperor emits directives (mRNAs) but what happens locally is anyone’s guess

A Touching Mother’s Day Story

Yes, a touching mother’s day story for you all. It was 51 years ago (yes over half a century ago ! ! ), and I was an intern at a big city hospital on rotation in their emergency room in a rough neighborhood. The ER entrance was half a block from an intersection with a bar on each corner. On a Saturday night, we knew better than to try to get some sleep before 2AM or until we’d put in 2 chest tubes (to drain blood from the lungs, which had been shot or stabbed). The bartenders were an intelligent lot — they had to be quick thinking to defuse situations, and we came to know them by name. So it was 3AM 51 years ago and Tyrone was trudging past on his way home, and I was just outside the ER getting some cool night air, things having quieted down.

“Happy Mother’s day, Tyrone” sayeth I

“Thanks Doc, but every day is Mother’s day with me”

“Why, Tyrone?”

“Because every day I get called a mother— “


Very sad — Nature vol. 557 p. 144 ’18 (10 May) “PNAS resignation On 1 May, Inder Verma, a cancer researcher at the Salk Institute for Biological Sciences in La Jolla, California, resigned as editor-in-chief of the journal Proceedings of the National Academy of Sciences. The move comes after the publication of an investigation by Science, in which several female researchers who were either at the institute or had ties to it between 1976 and 2016 allege that Verma harassed them. Verma, who served on powerful committees at the institute, vehemently denied the allegations in a statement to Nature. The Salk Institute suspended him on 21 April while it investigates the claims.”

Why sad?  Because my late Princeton classmate and good friend Nick Cozzarelli edited PNAS for 10 years.  He died far too soon at 68 of Burkitt’s lymphoma after doing great work on DNA gyrase.  From the Wiki about him ” In 1995, Cozzarelli was invited to become the editor-in-chief of the Proceedings of the National Academy of Sciences. He took the position because felt that the journal had great unrealized potential as a scientific publication.[3] During his tenure, he expanded the editorial board from 26 to more than 140 and created a second track to allow scientists to submit manuscripts directly.”

Nick was credited for strongly increasing the quality and influence of PNAS.  This was recognized by the journal in the form of the Cozzarelli prizes established a year after his death.  There are 6 chosen from the more than 3,200 research articles appearing in the journal each year, representing the six broadly defined classes under which the National Academy of Sciences is organized.

A social note:  Although Princeton University was the home of many bluebloods in the late 50s, this was not true of all.  Nick went through Princeton on scholarship (waiting on tables in commons etc. etc.).  He was the son of an immigrant shoemaker from Jersey City.  Hopefully Princeton is still doing this.

Addendum 10 May — a friend said  ”

Your blog post seems to be one big non sequitur.
I doubt that harassment victims are “sad” that their complaints are finally getting heard and acted on. The fact that Verma’s behavior was allowed to continue all these years reflects poorly on the Salk Institute, but I don’t see how it reflects poorly on PNAS, where he was simply an editor and has now resigned. Essentially, Verma received PNAS submissions while sitting at his desk (at the Salk Institute) and declared “yes” or “no.”  I don’t see how your late friend Nick’s PNAS legacy has been sullied by any of that. “
To which I replied

No it’s sad because of what Verma’s behavior (at Salk and likely as PNAS editor) would have meant to Nick (and how he loved PNAS), given the type of guy Nick was.  My late father (an attorney) and uncle (a judge) took things the same way when a lawyer got disbarred for some malfeasance or other, e.g. as a reflection on the institution of the legal profession.   They took it personally as a reflection on them.  Perhaps illogically, but that’s the way they and Nick were. “

A pile of spent bullets — take II

I can tell you after being in neurology for 50 years that back in the day every microscopic inclusion found in neurologic disease was thought to be causative.  This was certainly true for the senile plaque of Alzheimer’s disease and the Lewy body of Parkinsonism.  Interestingly, the protein inclusions in ALS weren’t noticed for decades.

However there are 3 possible explanations for any microscopic change seen in any disease.  The first is that they are causative (the initial assumption).  The second is that they are a pile of spent bullets, which the neuron uses to defend itself against the real killer.  The third is they are tombstones, the final emanations of a dying cell, a marker for the cause of death rather than the cause itself.

An earlier post concerned work that implied that the visible aggregates of alpha-synuclein in Parkinson’s disease were protective rather than destructive —

Comes now Proc. Natl. Acad. Sci. vol. 115 pp. 4661 – 4665 ’18 on Superoxide Dismutase 1 (SOD1) and ALS. Familial ALS is fortunately less common than the sporadic form (under 10% in my experience).  Mutations in SOD1 are found in the familial form.  The protein contains 153 amino acids, and as 6/16 160 different mutations in SOD1 have been found.  Since each codon can contain only 3 mutations from the wild type, this implies that, at a minimum,  53/153 codons of the protein have been mutated causing the disease.  Sadly, there is no general agreement on what the mutations actually do — impair SOD1 function, produce a new SOD1 function, cause SOD1 to bind to something else modifying that function etc. etc.  A search on Google Scholar for SOD1 and ALS produced 28,000 hits.

SOD1 exists as a soluble trimer of proteins or the fibrillar aggregate.   Knowing the structure of the trimer, the authors produced mutants which stabilized the trimer (Glycine 147 –> Proline) making aggregate formation less likely and two mutations (Asparagine 53 –> Isoleucine, and Aspartic acid 101 –> Isoleucine) which destabilized the trimer making aggregate formation more likely.  Then they threw the various mutant proteins at neuroblastoma cells and looked for toxicity.

The trimer stabilizing mutant  (Glycine 147 –> Proline) was toxic and the destabilizing mutants  (Asparagine 53 –> Isoleucine, and Aspartic acid 101 –> Isoleucine)  actually improved survival of the cells.  The trimer stabilizing mutant was actually more toxic to the cells than two naturally occurring SOD1 mutants which cause ALS in people (Alanine 4 –> Valine, Glycine 93 –> Alanine).  Clearly with these two something steric is going on.

So, in this experimental system at least, the aggregate is protective and what you can’t see (microscopically) is what kills cells.

How Badly are Thy Genomes, Oh Humanity — take II

With apologies to Numbers 24:5, “How goodly are thy tents, Oh Jacob” —  a recent paper shows how shockingly error ridden our genomes actually are [ Science vol. 360 pp. 327 – 331  ’18 ].  I’d written about this in 2012 (see the end), but technology has marched on.  Back then only the parts of the genome coding for protein (the exome) were sequenced.  The present work did whole genome sequencing (WGS) to a mean coverage of 40+ (e.g. they sequenced the other 98 percent of the genome).

The authors were studying families in which one or more children had autism spectrum disorder to find genome abnormalities which might have caused the ASD. They were looking for structural variants (SVs) by which they mean ” biallelic deletion, tandem duplications, inversions, four classes of complex SV, and four families of mobile element insertions”

Why?  Because studying proteins alone doesn’t tell you how they are controlled.  That’s in the DNA surrounding them.  Structural variants are more likely to affect control elements than the proteins themselves.

Showing how technology has marched on they determined the whole genomes of 9274 subjects from 2600 families affected by ASD.

The absolutely mindboggling point in the article is the following direct quote “An average of 3746 SVs were detected per individual”.  That’s simply incredible (assuming the above isn’t a misprint).

Here’s the older post

How Badly Are Thy Genomes, Oh Humanity

With apologies to Numbers 24:5, “How goodly are thy tents, Oh Jacob” —  a recent paper shows how shockingly error ridden our genomes actually are [ Science vol. 337 pp. 64 – 69 ’12 ].  The authors sequenced roughly three quarters of the genes coding for proteins in some 2,439 people — e.g. 15,585 protein coding genes.  This left 98% of the genome untouched, primarily because we really don’t know what it does or how it does it, despite the fact that it controls, when, where and how much of each protein is made.  So they basically looked at the bricks from which we are built (the proteins) and not the plans (the 98%).

The news is not very good.  The subjects came from two groups: 1,351 Europeans and 1,088 Africans (the latter, because genetic diversity is far higher among Africans as that’s where humanity arose, and where mutations have had the longest time to accumulate).

The news is not very good. First, some background.

Recall that each nucleotide is one of four possibilities (A, T, G, C), and that each 3 nucleotides therefore has 4^3 = 64 possibilities.  61/64 combinations code for amino acids which, since we have only 20 gives a certain redundancy of the famed genetic code.   The other 3 combinations code for no amino acid (usually) and tell the machinery making proteins to stop.  Although crucial to our existence, these are called nonsense codons.

The genetic code is therefore 3fold degenerate (on average).  However, some amino acids are coded for by just 1 combination of 3 nucleotides while others are coded by as many as 6.  So some single nucleotide variants (SNVs) leave the amino acid coded for the same (these are the synonymous SNVs), while others change the amino acid (nonSynonymous SNVs), and possibly protein function.

Ask some one with sickle cell anemia how much trouble just one nonSynonymous SNV can cause — it’s only 1 amino acid out of 147.  Even worse, ask someone with cystic fibrosis where just one of 1,480 amino acids is missing.

Here’s the bad news.  In the population as a whole, they found 500,000 single nucleotide variants (SNVs).  If you’re still not sure what is meant by this, the 5 articles in should be all the background you need.

More than 400,000 of the variants were previously unknown.  Also more than 400,000 of them were found either in Africans or Europeans but not both.  If you divide 500,000 by 2,439 you get 205 variants per person.  However, SNVs are far more common than that, and each individual contains an average of 14,000.

Well, how many of the 500,000 or so SNVs they found are nonSynonymous? One would think about 1/3 statistically.  However, They found more than half 292,125/500,000 — nearly 60% — were nonSynonymous.

It get’s worse: 6,165 of the nonSynonymous variants are nonSense codons.  This means that the protein coded for by such a gene, terminates prematurely, meaning that it can terminate anywhere.  On average one would expect that half of these nonsense codons result in a protein of less than half the normal length.   This would very likely obliterate whatever function the protein had.

Obviously, they couldn’t test all 500,000 SNVs to see how they affected protein function (and we really only have a decent idea of what half our 20,000 or so proteins are doing).  They had to guess.  They came up with a figure of 2 – 4% of the 14,000 SNVs being functionally significant — That’s 280 – 560 significant mutations per individual.

Clearly, despite the horrible examples of cystic fibrosis and sickle cell anemia above, most of these can’t be doing very much, because these were normal people being studied.

There are all sorts of implications of this work.  One is the subject of a future post — how hard this diversity makes drug discovery.  Another reiterates the Tolstoy theme mentioned earlier about the genetic defects causing schizophrenia and autism — ““Happy families are all alike; every unhappy family is unhappy in its own way”.  Thus beginneth Anna Karenina.

For details please see  and

A third is that this shows that the 1000 fold expansion of the human population has pretty much obviated much natural selection eliminating these variants.  I’ll leave it to the geneticists to figure out what this means for the eventual survival of the species, as these mutants continue to accumulate.

The paper is fascinating, and sure to change our conception of what a ‘normal’ genome actually is.  Nonetheless, all they did was follow Yogi Berra’s dictum — “You can observe a lot by watching.”   It certainly wasn’t creative or ingenious in any sense.  Sometimes grunt work like this wins the day.

In which we find the new tricks an old dog can do

We all know that the carboxy terminal glycine of ubiquitin forms an amide with with the epsilon amino group of lysine.  Like a double play in baseball, 3 enzymes are involved, which move ubiquitin to E1 (the shortstop) to E2 (the second baseman) to E3 (the first baseman).  We have over 600 E3 enzymes, 40 E2s and 9 E1s.

A new paper [ Nature vol. 556 pp. 381 – 385 ’18 ] describes an E3 enzyme (called MYCBP2 aka PHR1) with a different specificity — it forms esters between the carboxy terminal glycine of ubiquitin and the hydroxyl group of serine or threonine.  The authors speculate a bit, noting that there are a lot of hydroxyl groups around in the cell that aren’t on proteins — sugars and lipids come to mind.   Just how widespread this is and whether any of the other 600 E3’s have similar activity isn’t known.

So now we have yet another new (to us) player in the metabolic life of the cell. It is yet another post-translational protein modification.   The enzyme is found in neurons, making understanding the workings of the brain even harder.

The bias of the unbiased

A hilarious paper from Stanford shows the bias of the unbiased [ Proc. Natl. Acad. Sci. vol. 115 pp. E3635 – E3644 ’18 ].  No one wants to be considered biased or to use stereotypes, but this paper indicts all of us.  They use a technique called word embedding to look at a large body of printed material (Wikipedia, Google news articles etc. etc.) over the past 100 years, to look for word associations  -e.g. male trustworthy female submissive and the like. In word embedding models, each word in a given language is associated with a high dimensional vector (not clear to me how the dimensions are chosen) and the metric between the words is measured.  A metric is simply a mathematical device that takes two objects and associates a number with them.  The distance between cities is a good example.


The vector for France is close to vectors for Austria and Italy.  The difference between London and England (obtained by subtracting them) is parallel to the difference between to the difference between Paris and France.  This allows embeddings to capture analogy relationships such as London is to England as Paris is to France.

So word embeddings were used as a way to study gender and ethnic stereotypes in the 20th and 21st centuries in the USA.  Not only that but they plotted how the biases changed over time.

So in your mind the metric between bias == bad, stereotype == worse is clear

So just as women’s occupations have changed so have the descriptors of women.  Back in the day women, if they worked out of the home at all, were teachers or nurses.  A descendent of Jonathan Edwards was a grade school teacher in the town of my small rural high school.

As women moved into the wider workforce from them the descriptors of them changed.  The following is a pair of direct quotes from the article.”

“More importantly, these correlations are very similar over the decades, suggesting that the relationship between embedding bias score and “reality,” as measured by occupation participation, is consistent over time” ….”This consistency makes the interpretation of embedding bias more reliable; i.e., a given bias score corresponds to approximately the same percentage of the workforce in that occupation being women, regardless of the embedding decade.”

English translation:  As women’s percentage of workers in a given occupation changed the ‘bias score’ changed with it.

So what the authors describe and worse, define, as bias and stereotyping is actually an accurate perception of reality.  We’re all guilty.

The authors are following Humpty Dumpty in Alice in Wonderland  — ““When I use a word,” Humpty Dumpty said, in rather a scornful tone, “it means just what I choose it to mean—neither more nor less.” “The question is,” said Alice, “whether you can make words mean so many different things.” “The question is,” said Humpty Dumpty, “which is to be master—that’s all.”

I find the paper hilarious and an example of the bias of the supposedly unbiased.