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burning_hamster

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burning_hamster
·12 tháng trước·discuss
I was going to call BS on this one, but after crunching some numbers, if anything this is likely an underestimate.

human nuclear genome size (haploid): 3.1 billion bp

mitochondrial genome size: 16 000 bp

1 human nuclear genome per egg -> 3.1 billion bp nuclear DNA

100 000 mitochondria, each with 1-10 genomes per mitochondrion [1] -> 1.6-16 billion bp mitochondrial DNA

So the ratio of mitochondrial to nuclear DNA in human eggs is on the order of 0.5 to 5.

[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC4988970/
burning_hamster
·12 tháng trước·discuss
I disagree.

> I think it would be better to describe this as an ‘organelle’ transplant as it would be easier for people to understand and discuss.

Unlike previous attempts, the donor mitochondria are not transferred into the mother egg. Instead the donor cell is denucleated, and the nucleus from a mother's egg is transferred into the denucleated donor cell. Consequently, there is a wide variety of donor specific material, which may influence the early stages of development and only "wash out" after a number of cell divisions.

> But calling it a 3 person baby is unhelpful and misleading as IMO mitochondria DNA is of a different category to chromosomal DNA.

How so? Arguably, mitochondrial genes are much more essential than most nuclear genes.

1. Mutations in any mitochondrial gene often have dire consequences, whereas variants in nuclear genes are much more frequent.

2. Mitochondrial DNA is the most expressed in pretty much any cell by a huge margin. Mitochondria express 13 (IIRC) protein coding genes and two dozen other RNAs. Those 30 odd genes often make up 1-5 % of a cell's whole transcriptome. Only genes coding for ribosomal RNA are more strongly expressed.
burning_hamster
·năm ngoái·discuss
Natural sciences: about 3 years at best.

You finish your degree, and start your PhD. The first year, you are busy learning techniques and getting caught up with the relevant literature. You are far too concentrated on learning new things to get any thinking done.

In your second year of your PhD, you are getting better. You can do most things without thinking about them. This frees up your brain to think about other things. However, your grasp of the wider literature is still lacking, so you use that brainspace to optimise your current experiments (as you should).

In your third year of your PhD, you are starting to write things up: either your thesis, or your first (big) paper. You read a lot more, you know a lot more. The deep thinking can commence.

Your first postdoc is probably your most productive time: you know what you are doing; you know the state of the literature and which parts are reliable and which aren't; you have a clear idea of what problems need solving. You are starting to write your first grant applications, but you only need one for yourself and not several to cover the needs of a full lab. You don't have any kids at home. This is a good time to solve some big problems. It lasts about 2-3 years.

At the start of your second postdoc, you panic. The big problem was harder than you thought and you don't have enough high-impact papers to be competitive in job applications for a principal investigator (PI) role. You start churning out low-value fillers and collaborating with everyone and their hamster to get your name on as many papers as possible. The rest of the time is taken up by applying for grants and PI positions. You don't even make it to the interview stage. You start pondering about life outside of academia.

The big problems are forgotten.
burning_hamster
·năm ngoái·discuss
> A Dutch speaker can't read or understand German.

A Dutch speaker can't necessarily read or understand German. However, a Dutch person nearly always does, and often flawlessly so.
burning_hamster
·năm ngoái·discuss
Garten / garden derive from garte / yard, which just meant an enclosed outdoor space.
burning_hamster
·năm ngoái·discuss
Huge fan of Distill here (and your personal blog).

> In retrospect, I deeply regret trying to run Distill with the expectations of a scientific journal, rather than the freedom of a blog, or wish I'd pushed back more on process. Not only did it occupy enormous amounts of time and energy, but it was just very de-energizing.

Scientific peer review pretty much always is incredibly draining, and (assuming the initial draft is worth publishing) it rarely adds more than a few percent to the quality of the article. However, newcomers are drowning in a sea of low quality SEO spam (if they bother to search & read blogs at all and don't go straight to their LLMs, which tend to regurgitate the same rubbish). The insistence on scientific peer review created a brand, which to this day allows me to blindly recommend Distill articles to people that I am training or teaching. So I, for one, am incredibly grateful that you went the extra-mile(s).
burning_hamster
·năm ngoái·discuss
The range notation indicates 95% confidence intervals, not the minima and maxima. If the lower bounds are close enough to zero (and the interval is large enough), then there may some residual probability mass associated with negative values of the variable.
burning_hamster
·năm ngoái·discuss
I am a biochemist and neuroscientist and also thought it was fantastic read. It's rare that someone manages to cater to both audiences this well. Kudos!
burning_hamster
·năm ngoái·discuss
Some animals get most if not all of their sleep through microsleep [1]. So whatever mechanism "refreshes" the brain, it can work on short time scales. The switch in brain firing dynamics from wake to sleep (NREM) is very fast -- on the order of one to a few seconds. People in team Nedergaard argue that it is the rhythmic neuronal activity during sleep that promotes fluid flow (though to be fair, some argue its arterial pressure). So their answer to your question would be yes, that should be enough time to enhance fluid flow (fluid is flowing all the time, the question debated by scientists is, whether is it being enhanced during sleep).

[1] https://www.science.org/doi/10.1126/science.adh0771
burning_hamster
·năm ngoái·discuss
It is worth noting that these topical applications are quite controversial in the medical literature. The evidence supporting a dermal absorption of magnesium (or other electrolytes) is pretty poor [1]. In that sense: yes, it would be exceedingly difficult to overdose using them.

[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC5579607/
burning_hamster
·năm ngoái·discuss
It is worth noting that these topical applications are quite controversial in the medical literature. The evidence supporting a dermal absorption of magnesium (or other electrolytes) is pretty poor [1].

[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC5579607/
burning_hamster
·năm ngoái·discuss
In theory, there is enough magnesium in your bones (~12 g) to cover your RDA (~400 mg) for 30 days [1]. However, only a third of that is available without strongly negatively affecting your health. So if your Mg stores are full (if!), then you have about 10 days worth "stored". However, your day-to-day Mg homeostasis is done by your kidneys, i.e. on a much, much shorter time scale. So your daily intake does matter, but sporadic deficiencies can be compensated for about 10 days.

[1] Alawi et al. (2018) Magnesium and Human Health: Perspectives and Research Directions; https://pmc.ncbi.nlm.nih.gov/articles/PMC5926493/
burning_hamster
·2 năm trước·discuss
> For example, let's say instead of gradient descent you want to do a Newton descent. Then maybe there's a better way to compute the needed weight updates besides backprop?

IIRC, feedback alignment [1] approximates Gauss-Newton minimization. So there is an easier way, that is potentially biologically more plausible, though not necessarily a better way.

[1] https://www.nature.com/articles/ncomms13276#Sec20