Monday, March 16, 2020

Can you live forever?

Well, maybe I should say, can you leave longer in a healthy condition? This is what David Sinclair is explaining here and here.

From his  book, Lifespan, by David Sinclair (this summary was done by Andrej Rusakov on the comments of the above video):

- Low levels of leucine, isoleucine, and violin BCAAs correlate with increased lifespan
- Exercise turns on the genes that make us young again
- Hunger and calorie restriction plays a big role in vitality and longevity
- Get exposed to cold
- Shift to vegetarian/vegan diet
- Sauna 7x a week may be great
- NMN molecule boosts NAD - he takes it in supplements + Metformin
- Nicotinamide Riboside (NR) is converged to NMN, it’s cheaper, but it doesn’t raise NAD levels as well as MNM does
- Rapamycin is very powerful, but still very toxic for you
- Stoke development of brown fat (it activates when you get cold)

What David Sinclair does:
- 1g (1000 milligrams) of NMN+ 1g of resveratrol shaken into his homemade yogurt every morning
- 1g of Metformin
- Daily doze of vitamin D, vitamin K2
- 83mg of aspirin
- Keeps sugar, bread and pasta intake as low as possible, no deserts
- skips one meal a day (largely skips lunch)
- Tests blood for dozens of biomarkers every few months and moderates them with food and exercise if not optimal levels
- Takes a lot of steps and runs up stairs daily
- Exercises, sauna, cold plunge pool
- Mostly plant-based diet
- Avoids microwave plastic, excessive UV exposure, X-rays and CT scans
- No smoking
- Stays in the cool side during the day and when he sleeps at night
- Keeps his BMI: 23-25
- Supplements: only from a large manufacturers with good reputation, seek highly pure molecules: >98%; looks for GMP on the label (Good Manufacturing Practices)

Sunday, September 22, 2019

Developmental Biology

This is probably one of my favorite things. Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis," which is the process that gives rise to tissues, organs and anatomy.

In plain words, how one initial cell can transform into so many different ones at the right place to create the final body...


  1. Chapter 21 of Molecular Biology of the Cell is a good intro (I am actually currently reading that).
  2. On simulation tools for that, found this recent review paper and these links:
    1. EmbryoMaker: article and software.
    2. MecaGen: paper and software.
    3. BioDynaMo
  3. Accelerators:
    1. A master thesis for #3. I like the name "speed of life" :)
As usual, sorry for the top level. I'll update as I learn more...

Saturday, August 31, 2019

Shoulder

Best is to see some videos, and this is probably the best series I found, probably best seen in this order...:

  1. Rotator calf muscles Although he is not talking about the other structures in detail, you can see basically how the shoulder holds to your body. He touches on other muscles that are described on the next video. See also the exercise video below who explains this really simply.
  2. Large shoulder muscles. Want more details, names, etc. Check this.
  3. You can quickly go through this one where he talks about the scapula/bones. No need to know so much detail to get the sense of how the shoulder works.
  4. Glenohumeral joint: bones/tendons and movements/actions names.
If you are looking how to solve your shoulder pain (mine, which may have nothing to do with yours) got solved doing this. The video is good even to explain the structure of the shoulder really clearly. This guy is actually talks a lot but he is good also (actually is the first one I saw). The last exercise works like a charm. He has a second video and a 3rd one that I got to try.

Saturday, July 27, 2019

DNA sequencing

You can find a good overview in Wikipedia.

A bit more in detail, the most used approach today (2020) by far is Illumina's. Also called SBS (sequence by synthesis), it belongs to the 2nd generation technologies (there are others, like Thermofisher's...), ironically called also NGS (next generation sequencing) because it was once the next generation :). It has its drawbacks (high investment upfront...) but it works.

From an electronics perspective, the detection method here is a high speed camera.

Moving fwd, "A world of opportunities with nanopore sequencing" gives a good overview on the latest (a bit centered on Oxford Nanopore Technologies' solution). These are called "long read", as, unlike Illumina's, it can read a long strand of DNA while Illumina's is limited to ~100bp that then you have to "glue" together with the others to get the whole thing. Nanopores have other advantages (portability, immediate results, less reagents, potentially lower cost...) and some issues, like less accurate (although they seem to be addressing this), but it is not clear they'll be able to displace Illumina. It is a bit like PoC vs centralize lab model.

From an electronics perspective, we measure very small variations on current levels (pA) although some different pore technologies may result on larger currents. If you want to get a bit more insight on the electronics for the nanopore technologies (and still get a good overview of the previous generations), check "Nanopore-CMOS Interfaces for DNA Sequencing" out.

A hardcore Nature paper "Integrated nanopore sensing platform with sub-microsecond temporal resolution" on nanopore electronics noise.

Just a last note. DNA sequencing cannot be replaced on some areas, for some tasks. Nevertheless, one does not need to sequence the whole DNA to do things like finding if an illness is coming from a given virus (see qPCR), if someone is the father of the baby, or to find out that one is the carrier of a "cancer gene"... There are more cost effective methods to do that, still based on DNA/RNA.

Books:
  1. "Molecular Cloning: a Laboratory Manual" is not something that you want to read (I haven't, that's just the index, not online) just for basic learning. Instead is mentioned on the first article as the in depth reference for the basic techniques used for DNA manipulation/preparation...
  2. Single-Channel Recording. Sakmann, B.; Neher, E. Springer; 2009
  3. Ion Channels of Excitable Membranes

Thursday, July 18, 2019

Sizes

Always wondered how big were all these things biologists talk about? :)
  1. DNA base pair (bp): ~3.4 Å (340 pm) of length along the strand. Weight: roughly 618 or 643 daltons for DNA and RNA respectively
  2. DNA chain: ~2 nm diameter, helical pitch 3.4-3.6 nm, 50 nm persistence length (stiffness) [1]
    • See Wikipedia for physical description of the helix. 
  3. Human DNA: The haploid human genome (23 chromosomes) is estimated to be about 3.2 billion bases long and to contain 20,000–25,000 distinct protein-coding genes.
    1. One genome copy weights about 3pg
    2. Each somatic cell has 6.16 pg of DNA (sperm and egg cells have 3.08 pg).
    3. The total amount of related DNA base pairs on Earth is estimated at 5.0×1037 and weighs 50 billion tonnes. In comparison, the total mass of the biosphere has been estimated to be as much as 4 TtC (trillion tons of carbon).
  4. Protein: hemoglobin: 6.5 nm
  5. Virus:
  6. Cell:
    1. (Red blood cell) 10um diameter of the "disc". Contains ~280M hemoglobin molecules.
    2. (White blood cell)
    3. Neuron
    4. Epithelial cell
    5. Endothelial cell
  7. Blood vessel:
  8. Schematic representation of the vessels of the cardiovascular system, with the inner diameter, average blood-flow speed, and Reynolds number from Berger et al. [2].
  9. Almost every cell, in almost every tissue of a vertebrate, is located within 50–100 μm of a capillary [4]. Check [5] for some introductory but nice reading on capillaries. Can we get a 3D image of the capillary network in a volume?
  10. Blood drop: 25 ul
  11. Hair:
  12. Mosquito: 3-6 mm. 5 mg. Fly at ~1-2 km/h. Wing frequency: 500 bps
  13. Hypodermic needle: there is a range of gauges:
    • 21-gauge (0.8 mm/0.5 mm outer/inner diameters) needles are most commonly used for drawing blood for testing purposes, and 16- or 17-gauge needles (~1.5 mm outer diameter) are most commonly used for blood donation.
    • The smallest hypodermic needle typically used (30 gauge) is about 320 μm in outer diameter and 160 μm in inner diameter.
    • Thinking to copy something from the mosquito? :) [3] Newer article here.
  14. Organ sizes:
    1. Brain size: about 1 liter: 10x10x10 cm^3. 10^11, i.e., 100B neurons.


A nice diagram with some of these:





References:
[2] Original: Berger SA, Goldsmith W, Lewis ER. 1996. Introduction to Bioengineering. Oxford, UK: Oxford Univ. Press. Extracted from: Microrobots for Minimally Invasive Medicine, Nelson et al.
[3] Fabrication of a micro needle for a trace blood test
[4] Molecular Biology of the Cell, Bruce Alberts et al.

Tuesday, June 25, 2019

End of life rally

When a terminal patient seems to recover briefly just before dying in the coming days. A NYT article with examples. So far unexplained. And the rest of the article won't either, so feel free to stop here.

This actually happened to my dad. He had pneumonitis, reading for 2-3 days about 65% of oxygen saturation with full supply of oxygen through a mask. Then it started improving, reading close to 80% by the time we left the hospital that night. The next day in the morning he was sitting on his bed eating his breakfast and the mask by the side of his face. The nurse later in the day saw the oxygen saturation again around 65% and made a comment "I knew there had to be something wrong, the nurse in the morning told me an unbelievable good number...". This was not a continuous monitor so we couldn't see the readings and she didn't tell us what the other nurse had read, but I believe that they saw more than 90% that morning when he was doing fine. The next day he died :_(

As the article explains, this is not particular to a given disease and actually it happens with other ones (stroke, dementia, brain cancer, heart disease, colon cancer...). The explanations seem to try to solve the mystery individually for each disease but what if the body had a powerful universal mechanism to try to fight death? Even if it was an individual one, what if we could extend it or replicate it? Hence my interest... As usual, will post as I learn...

Cheers!

PS.: I can't believe no one has done any serious research on this.

Reimbursement/costs

For the US, can't tell private costs but one can search for Medicare/Medicaid reimbursements . For instance: Search physician fee schedu...