David J Glass MD
@davidjglassMD
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Book: Experimental Design for Biologists. Journal: Skeletal Muscle. Focus areas: Aging; Muscle. Works for a biotech company; views are mine.
New York
Joined December 2013
We found that most published RNAseq studies may be underpowered: Optimized murine sample sizes for RNAsequencing studies revealed from large scale comparative analysis https://t.co/0xKPaRGe18
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At King's, she did the experimental work resulting in both the pictures and HER subsequent calculations that were used to determine DNA's structure. You can debate whether she independently got there, but you can't debate that her data got people there.
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People here lazily fit the Rosalind Franklin defense into a critique of "woke-ness." Franklin was a world-class X-ray diffraction expert before King's. After, she trained Krug; their work on the TMV virus catalyzed his work which later won another Nobel prize. He gave her credit
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Highlighting this anti-semitism so people can see what I'm seeing. It's eye-opening to realize this is still the way some people view the world - through prejudice.
@davidjglassMD @doodlestein This thread only lacked the ethnocentric Jew bounding in to give credit for a scientific discovery to a co-ethnic of his...
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The biggest problem for me with the Watson & Crick paper is that they did zero experiments, literally lied that they saw Franklin's experimental data, and thus set themselves up as these supposed geniuses who intuited the structure of DNA from thin air. I'd retract their paper.
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I thought this biography of Rosalind Franklin was quite interesting: https://t.co/9UNfzqRZFu
harpercollins.com
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Her parameters strongly constrained the possible models for DNA (requiring paired, antiparallel chains). Crick later acknowledged seeing this report. I don't think even scientists today understand how much W&C lifted from her without attribution. It wasn't just a photo.
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In her biography, the author cites the 1952 MRC report from King’s College DNA group. That internal report summarized Franklin’s key calculations—including the 34 Å repeat and C2 space group symmetry, showing she fully realized that DNA was a double helix.
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By now, it seems most historians agree that Watson & Crick used Franklin's data without her knowledge. The details of the structure were made possible using her calculations. Just consider their claim of ignorance of her work in the body of the paper versus what they wrote later
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It's worth reading the Watson & Crick paper. Note this part: "We were not aware of the details of the results presented [in the Franklin paper] when we devised our structure" That statement was contradicted in the Acknowledgement, and in detail later https://t.co/SP4IgVqJno
nature.com
Nature - The determination in 1953 of the structure of deoxyribonucleic acid (DNA), with its two entwined helices and paired organic bases, was a tour de force in X-ray crystallography. But more...
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Catch up on FSHD: DUX4 at 25: how it emerged from “junk DNA” to become the cause of facioscapulohumeral muscular dystrophy https://t.co/HmQg7jnpNb
link.springer.com
Skeletal Muscle - Double Homeobox 4 (DUX4) is a potent transcription factor encoded by a retrogene mapped in D4Z4 repeated elements on chromosome 4q35. DUX4 has emerged as pivotal in the...
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Don't write something in a review that you wouldn't appreciate reading from a reviewer. I don't care if you've been traumatized by prior hostile reviewers. Be better.
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The Reverend Bayes' original example was figuring out how close a billiard ball was to a line on the pool table. You can posit multiple potential possibilities, assigning priors to each; the data updates your priors, getting you to reality. There's no binary "yes/no" involved.
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Scientists who argue that aging isn't programmed need to explain how you get a 6-fold difference in lifespan between rats and squirrels (both rodents; both the same size, etc) without programming. Or consider budgies vs african grey parrots - 5 to 6 fold difference in lifespan.
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Another feature of a query-based experimental framework is that it eliminates the "positive vs negative" data binary. If your data answers the question you've posed, it's simply data - neither positive nor negative. This significantly decreases the incentive to cherry-pick.
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If you frame an experiment with a hypothesis or expectation, and then set out to test that claim, you're always at risk of both confirmation bias and, even worse, establishing a system only capable of finding what you're looking for. Framing with a question forces a wide net.
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As to "why do we age?" I don't find "why" questions very helpful. The fact is we do age, in a reproducible manner. If aging weren't programmed, we wouldn't see reproducible gene expression changes at specific times throughtout life. We'd break down randomly - like a car.
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I guess the most straightforward evidence that aging is programmed is that related species have different, but reproducible lifespans. Rats live around 2.5 years. Squirrels can live 15 years. Both are rodents, similarly sized, but there's a reproducible 6x difference in lifespan
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Here is one thing I think I understand about aging, which is pretty amazing: aging is programmed. We've performed aging gene signatures - assessing changes in gene expression with age via RNAseq - and you see the same changes happening at the same time in the same tissues.
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