Internet of Things in San Francisco


, , , , , ,


As a teaser, I am in receipt of several interesting emails from genetics researchers concerning the Guillain-Barre’ spectrum. Yes, Guillain-Barre’ has been promoted from a mere syndrome to a group of syndromes. So far, no clearly implicated genes, but several “genes of interest”. And a book about whether Franklin Roosevelt was misdiagnosed with polio in 1921. Unfortunately, if he really had Guillain-Barre’  it is not clear what else or what more could have been done for him (or anyone else) back then. Alas, after nearly 100 years it is not obvious that diagnostic methods are widely applied or that there is a treatment for each of the various syndromes.


With apologies to Cole Porter, repeat the repeat


, , , , , , ,

Several previous blog entries discussed trinucleotide repeats. From two scientists about as physically far apart as one can get on our planet comes information about two genes that have what are called hexanucleotide repeats.

  1. The NOP56 gene is in the p13 region of chromosome 20. In much DNA there are untranslated regions (abbreviated at UTRs), introns and exons. When the translation of the DNA is being done UTRs and exons are kept but introns are dropped. There can be multiple introns and exons. In an area called intron1 the sequence GGCCTG is typically repeated 3 to 14 times. It is not clear (yet) what exactly the repeats do, but Spinocerebellar ataxia type 36 (SCA36) has been linked to people with 650 (!) or more repeats. One preliminary finding is that distortions in NOP56 may disrupt the functioning of  a nearby gene called MIR1292 which provides instructions for making a type of RNA that regulates the activity of genes that produce proteins called glutamate receptors. Of interest here is that we may be seeing an example of what some have charmingly called MORON = ‘mutate one ruin one nearby ‘ in the manner of BOGO (=buy one get one) seen in marketing.
  2.  The c9orf72 gene is in the p21.2 region of chromosome 9.  Here the hexanucleotide repeat is GGGGCC. This can occur up to 30 times with no immediate negative effect on gene function. It is strongly believed that more than 30 repeats causes amyotrophic lateral sclerosis (ALS). It is also possible to show symptoms of frontotemporal dementia (FTD). More work is going on.


Tetranucleotide repeats


, , , ,

In a trinucleotide repeat a trio of bases – perhaps the infamous CAG triplet – repeats multiple times. Depending on the chromosome and location the number of repeats usually varies from normal to tolerable (more than normal but no known immediate effect) and then to carrier and symptoms. In some cases increases beyond the threshold level for symptoms can cause earlier onset or more severe symptoms. However, in a sequence of xxx CAG CAG CAG yyy the interpretation of the xxx and yyy triplets will not be altered by the CAG repeats because the vast bulk of DNA translation occurs in threes.

Enter the CNBP gene located on chromosome 3 in the q21.3 region. What repeats here is the CCTG sequence. Evidence suggests that up to 26 repeats is probably tolerable. Note that 4 x 3 = 3 x 4 which means here that if we have xxx CCTG CCTG CCTG yyy the xxx and yyy triplets will be interpreted correctly and the central bases will be CCT GCC TGC CTG. However, xxx CCTG CCTG CCTG CCTG yyy zzz should be read as xxx CCT GCC TGC CTG CCT Gyy yzz and so.

Also known as ZNF9, the CNBP gene provides instructions for making a protein called CCHC-type zinc finger nucleic acid binding protein. This protein has seven regions, called zinc finger domains, which are thought to bind to specific sites on DNA and RNA. The CNBP protein is found in many of the body’s tissues, especially the heart and the skeletal muscles. So far, the exact function of this protein is unknown, but it likely regulates other genes. The CNBP protein is necessary for normal embryonic development. A CNPB mutation that increases the repeats of the CCTG segment to higher than 75 (as of 2017 the most reported is more than 11,000 repeats) causes type 2 myotonic dystrophy.

Trinucleotide repeats


, , , , ,

On December 12, 2017 the blog entry discussed some relatively promising news regarding the relatively uncommon group of diseases known collectively as Huntington’s Disease (including the recently defined Huntington’s-like Diseases). A reader e-wrote to ask if there are any other trinucleotide repeats with known consequences. Alas, yes. Below I give gene, location (chromosome and then region) – repeating sequence and associated condition. * = Note that there are four base combinations for alanine  – GCU, GCC, GCA and GCG

  1. FXN – 9q21.11 – GAA – Friedreich ataxia
  2. HTT – 4p16.3 – CAG – Huntington disease (mentioned in December)
  3. AFF2 – Xq28 – CCG –  fragile XE syndrome
  4. ATXN80S – 13q21.33 – TAC/TGC – Spinocerebellar ataxia 8
  5. PABPN1 – 14q11.2 – Alanine (*) – oculopharyngeal muscular dystrophy
  6. ATN1 – 12p13.31 – CAG – Dentatorubral-pallidoluysian atrophy
  7. TRNT1 – 3p26.2 – CCA – sideroblastic anemia
  8. DMPK – 19q13.32 – CTG – Type 1 myotonic dystrophy
  9. GIGYF2 – 2q37.1 – CAG – Parkinson disease 11
  10. AARS – 6q22.1 – Alanine (*) – Charcot-Marie-Tooth disease 2N, Epileptic encephalopathy, early infantile, 29
  11. ATXN1 – 6p22.3 – CAG – Spinocerebellar ataxia type 1 (SCA1)
  12. ATXN2 – 12q24.12 – CAG – Spinocerebellar ataxia type 2 (SCA2), amyotrophic lateral sclerosis (note that there are 22 other genes implicated in various types of ALS)
  13. JPH3 – 16q24.2 – CAG/CTG – Huntington disease-like 2 (HDL2)
  14. PRNP – 20p13 – octapeptide repeat – Huntington disease-like 1 (HDL1); also implicated in prion disease, including Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI) as well as Wilson Disease
  15. TBP – 6q27 – CAG/CAA –  Huntington disease-like 4 (HDL4) and spinocerebellar ataxia type 17 (SCA17)
  16. FOXP2 – 7q31.1 – multiple also deletions, translocations and disomies –  FOXP2-related speech and language disorder
  17. FMR1 – Xq27.3 – CGG – Fragile X syndrome (3 variants)
  18. GPX1 – 3p21.31 –  GCG – Glutathione peroxidase deficiency
  19. PPP2R2B – 5q32 – CAG – Spinocerebellar ataxia 12 (SCA12)
  20. AR – Xq12 – CAG – androgen insensitivity syndrome, Spinal and bulbar muscular atrophy, androgenetic alopecia, a form of hair loss also known as pattern baldness
  21. CACNA1A – 19p13.13 – CAG – Spinocerebellar ataxia type 6 (SCA6)
  22. ATXN3 – 14q32.12 – CAG – Spinocerebellar ataxia type 3 (SCA3)
  23. KMT2D – 12q13.12 – CAG – Kabuki syndrome, various cancers

Coming tomorrow – tetranucleotide repeats

Courage of the heart is very rare


, ,

So a great part of the time in martial arts one settles for courtesy – and perhaps a clever compliment once in a while. Even though it appeared that the Contra Costa Ombudsman organization was fairly focused on assisted living places the thought was perhaps they were plugged into a services network. So we sent them an email explaining the situation – it included “Would you happen to know if there is county agency who might deliver food?”

Nicole Howell, the Executive Director at Ombudsman Services of Contra Costa & Solano, replied at 7:10 AM.  She e-wrote

That reply gets full marks from us – it was prompt, it was from an executive, who was working early, it has a working link and it told us something we likely would not have thought to ask (hospice services).

Recognition of Courage


, , , ,

It is one thing to recognize a courageous act by someone else.  It can be said that recognizing that courage itself takes some courage – the recognizer is likely to be saying to a complete stranger something like “That was a brave thing you just did”.

So what can someone who is autistic or is otherwise struggling with an expressive language disability do when they discern that someone is being courageous? Chatting with anyone, let alone a stranger, is just not in the wheelhouse. What we teach is the student is to close their right fist and point the right thumb upward perpendicular to the fingers. Just for reference, normally the inside tip of the thumb is touching the middle joint of the the middle finger. The fist then touches the chest (gently) over the heart. Then the fist moves two or three inches away from the chest and toward the person whose courage is being recognized.

When a class or the school more formally recognizes someone’s courage we ask them to come to an exhibition. The class will be dressed in formal silks and equipped with eagle-style kwan daos. If the honored guest is entering from stage right, for example, the class will be lined up in single file about 30 inches apart and facing the the right. The kwan dao is in the left hand. As the honored guest walks to his or her seat the students in series will turn ninety degrees left (so back to facing the audience) as the guest passes. The right hand grasps the kwan dao shaft below the left hand and the fingers and wrists are flexed to make the tassel and flag move. The ritual was used years and years ago when the Emperor of all China wanted to impress a visitor. Being saluted in this manner is quite a unique experience.



Postscript to The Courage Business


, , , , ,

So I go over to Loaves and Fishes which is being hosted at the Community Baptist Church on 62 Bella Vista Avenue in Bay Point. As I walk in the sense we describe in the martial arts business as ‘the radar’ goes on. That’s an odd reaction in a church. There was an older woman who was standing slightly right of my center-line and serving as the greeter. There was another older woman seated to my left and a solitary man about 20 feet away eating. There was also at least one person in the cooking area. Strange. One of the universal principles throughout martial arts is “the radar is right”.

I introduced myself and clarified that I did not want a meal, but rather was looking for an answer. I explained that I volunteered at the two Food Bank Community Produce distributions and at the Senior Groceries as well. Then, as I was saying we had a client at the Rio Vista Produce distribution who was dying of cancer and needed food, who should walk out from the kitchen but Sylvia (the client) herself.

One of the key principles in Tai Chi Chuan and a host of other disciplines is to be ready for anything BUT, per the great theorist Sun Tzu,  to try to choose the time and place of combat. Clearly, low marks for me.

Sylvia said, “You didn’t have to come.” Then she paused. “No, you did have to come.”

Assemblyperson (14th District) Timothy Grayson’s office in Concord called back Friday afternoon (very prompt!) and gave me a telephone number for Meals on Wheels. I have sent Meals on Wheels an email.

Stay tuned.


The Courage Business


It is often believed that martial arts focus on kicking and punching and maybe even energy manipulation (Ki or Qi) along meridians. That’s true, but it really represents about one percent (1%) of what is really going on. Similarly, soccer, also known as association football in most of the world, is frequently thought to be a game featuring running and kicking. It does – no doubt of that. But really what soccer TEACHES is, as the English say, ‘do not let down the side’. That means showing up every day for practice and always working wholeheartedly. In the words of the illustrious Dennis Ball: “You are either good or you are no good. If you are good you have to practice well so you get better. If you are no good you have to practice more until you get good.” In The Lord of the Rings on page 83 at the very end of the Chapter ‘Three is Company’ Frodo Baggins, on the run from Black Riders, asks Gildor Inglorion, a High Elf, “But where shall I find courage?”  Gildor replies, “Courage is found in unlikely places.”  Really, deep down, martial arts is in the business of inspiring courage. That requires that the teacher be courageous and that accessible examples be highlighted so students can recognize courage when they see it displayed. There are certainly large-scale examples like the US Marines and Navy at Guadalcanal in 1942. That is definitely not to say that the Japanese Army, Navy and Marines lacked courage either. They were just as far from home, as poorly equipped and coping with the same jungle. Similarly, when the Royal Air Force and the Luftwaffe fought over the English Channel and London during the Battle of Britain there was exemplary courage displayed by both sides.

Much closer in time and space and in a much smaller scale there is a woman named Sylvia who is dying of cancer and just drove to the Food Bank’s Community Produce Program at Rio Vista School in Bay Point because she is now too frail to walk.

That is courage.

So I am going to ask the fine folks at Loaves and Fishes if they know who might be able to deliver food to Sylvia.