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  #16  
Old 06-11-18, 06:00 AM
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Re: All disease is preventable (simplified with references added)

From another perspective

1]
Inherited trait is in effect sensitivity (sensory sensitivity) to the environment and hence stress sensitivity evolutionarily selected to enhance survival; it wouldn't pay to be laid back in a world of predators.

2]
-> leads to ->
Increased stress in a standard model of Western living (the need to acquire money to survive in a world where it is becoming increasingly hard to acquire employment) leading to such types being more stressed than others without neural sensitivity.

3]
-> leads to ->
Being stuck in permanent 'fight/flight' state - an association exists between asthma and obesity here as cortisol relates to increasing abdominal fat deposition.

4]
-> leads to ->
Chronic SNS activation and cortisol production leads to SNS and glucocorticoid resistance (requiring exogenous adrenergic agonism / glucocorticoid both of which work spectacularly well in me).

5]
-> leads to ->
Classically stress (hypothalamic CRF) has been associated with alterations in food intake behaviour (the first talk I gave second time around in the group) and of course when people are stressed they opt for comfort foods which invariably associate with Insulin / IGF-1 production ie Sugar/Starch and Animal protein (meat, dairy and gluten are all high in glutamate). Sugar and Glutamate are classical stimulants.

6]
-> leads to ->
A change in food preference from low GI vegetables (no stimulant) to meat/starch eg the burger.

7]
-> leads to ->
A destruction in the gut biome and 'leaky gut syndrome' where gut bacteria are able to enter the bloodstream and cause (because of the LPS on bacterial coats) ie endotoxemia which is worse still if foods consumed have a high bacterial load even if bacteria are destroyed by heating since the endotoxin/LPS remains.

8]
-> leads to ->
Dysregulation in the 'happy' neurotransmitters in the brain as many of them (eg 95% serotonin produced) in the gut - predisposing individuals further - to anxiety/depression.

9]
-> leads to ->
A vicious cycle in which point 5] amplifies worsening core physiological processes.

10]
-> leads to ->
Insulin/IGF-1 switch off autophagy/apoptosis resulting in failure of the body to eliminate the cells of the immune system which mount a specific response to inocuous allergen. In general - failure of autophagy/apoptosis (repair and recycling) from germ cell (giving rise to developmental disorder through de novo mutation) through to somatic mutation (giving rise to cancer) appears to be gathering pace as a common mechanism underlying the diseases of Western (now global) living.

--------------------------------------------------
So - the basis to allergy and asthma ?
---------------------------------------------------
Allergy and Asthma travel together, however allergy arises more through defective autophagy and Asthma results through a defective neuroendocrine system (a blunted stress axis and autonomic nervous system).

All of this ^^^ though - ultimately coming down to the evolutionary selection of 'sensitivity' to external sensory signals - which become a toxic hypersensitivity when this sensitive system is stressed (in the Western world - this takes the form of difficulty in acquiring money but also through immersion in over-stimulating environments ... ... ... taking us back to the Hygiene hypothesis and why kids in the countryside do so well compared to kids growing up in the urban sprawl).

So - the centre of this model is (a)Evolutionary selection for sensory sensitivity and (b)(failed) Autophagy - and it's well known that increased protein/carb result in inhibition of autophagy through increasing TOR (Target of Rapmycin) and rapamycin (which drives autophagy) is a macrolide antibiotic (like erythromycin) which I think that Kenny has researched. Caffeine operates similarly to rapamycin in driving autophagy - but I believe it will only work if we use it (and exercise) in the fasted state; I've just had a hayfever reaction and I've switched it off through MCT oil (stimulates the fasting state) and coffee here at work. Worked like magic.

Now - when we started work at the WTCHG - there was a heavy belief that there'd be a commonality underlying the Western disorder and I believe that this comes down to inflammation - uncontrolled inflammation.

If we combine the model of emergence of sensory sensitivity, a more stressful living environment, easy access to comfort food (blood glutamate/glucose elevation) and consequences as described above - we set up a false physiological environment which predisposes to inflammation to disease ?

Other points that I like include the state that I'm in currently (ketosis) resulting in b-hydroxybutyrate (HDACi and anti-oxidant) eg Science. 2013 Jan 11;339(6116):211-4 and also being pro-mitochondrial biogenesis when engaged in the fasted state and endurance exercise eg Essays In Biochemistry,2010,47,69-84 (Regulation of mitochondrial biogenesis).

So - the above line of connects connectomics to genomics to epigenomics to biomics to loss of control of the immune system and disease - and I think it's right but there's nothing that I can do about it. Nobody will be interested.

I'm 99% sure it's right ! :-)
Loss of control of the immune system and autonomic nervous system through evolutionary selection of sensitivity in a distressing environment ?
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  #17  
Old 06-11-18, 06:17 AM
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Re: All disease is preventable (simplified with references added)

The new paradigm of medicine which wraps the entire process of growth, differentiation and steady-state operation (neural rearrangement) is:


carb (growth) -> <- protein (differentiation)
carb (growth) -/ \
carb (growth) - |
carb (grow SCFA (ketosis) maintenance


carb -> insulin
protein -> IGF-1
fat (SCFA) through soluble fibre fermentation in our gut -> cortisol (maintain blood glucose levels - no fluctuation permitted)

So - how do we shift into ketosis ? Lifestyle ie fasting/physical activity (well documented) and diet type (vegetables + MUFA + MCT oil)

The body's max requirement for nutrition comes in from mother's milk - and thereafter we're meant to be on a sliding trajectory down decreasing hyperglycaemic carbs and protein - however we don't access this trajectory and shift into eating next to nothing because the foods which drive growth/proliferation are the comfort foods which we're reactively driven towards when we're distressed. We can't access autophagy and so can't repair and recycle our cells - so rubbish accumulates on the inside.

Autophagy connects to apoptosis and explains away elimination of self-reactive antigen and inocuous allergen reactive cell removal ie we can't (in a distressful environment) access autophagy -> apoptosis and so we 'choose' our own premature demise (or rather it's forced onto us) in an environment of quite severe psychosocial stress.

Environmental change underlying psychosocial stress and not the biomedical model therefore wins out. It's not that any of the mechanisms which molecular genetics reveals are wrong per se - it's that we don't particularly need them - though they are nice to string together in order to provide the mechanistic basis to environmental change giving rise to an elimination (prevention) of all disease.
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  #18  
Old 06-11-18, 06:25 AM
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Re: All disease is preventable (simplified with references added)

Could we have put in pace a mechanism without -omics ?

So - we can connect up lots of epidemiological association ie
diabetes -> obesity
obesity -> cancer
diabetes -> Alzheimer's
stress -> food intake preference change

- and we could have connected all of the above into a line which more or less suggested that:

elimination of distress (distressors defined using epidemiology) -> behavioural change (physical activity type and food type) but the Markram model of novel emergence of a novel neural structure (in Intense World Theory) and the detailed mechanisms of autophagy, mitochondrial biogenesis and immune system regulation have been useful.

Don't know - we have the info now - and so let's use it.

The ultimate distressor to man is the need for money (as this is required for survival) - decouple happy survival from need for money - and then (and thereby) permit people the freedom to choose their own path in life (in this voluntary global system) and everything should rationalise. No human beings will suffer from disease (until the very end) - see pattern of death on Mount Athos for likely pattern of death in man in a fair world .. ... more generally though all problems of man will be eliminated - as they all result from reward reinforcing greed through supporting power-based hierarchies (where money is the General of power) ie where money has become the chief proxy for power of man over man - or the generation of animal-like hierarchies instead of a flat structure of man (globally) - where we collaborate instead of compete to make ourselves better.
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  #19  
Old 06-11-18, 08:20 AM
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Re: All disease is preventable (simplified with references added)

This is ridiculous

paper -- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783344/
Keywords: aging, animal models, FOXO transcription factors, insulin and IGF‐1 signaling pathway, longevity

paper -- link


Protein/Carb
IGF-1/Insulin
-- SWITCH OFF AUTOPHAGY - prevent repair and recycling result in ALL allergic, autoimmune, neurodegenerative, cancer, infectious disease, developmental disorders - the mechanism is trivial

It's simply down to the regulation of food intake.
Distressed -> stimulant foods
Eustressed -> fasting/SCFAs

The Atkins is destroyed as a particularly nasty approach to ketosis
- we need fasting-centric vegan ketosis.

-*-

All that is needed is a definition of what is distressful and what is eustressful to solve all human problems.

This is simple to work out - ensure that all people are equal through access to what they need for happy survival - and thereafter for people to choose their own path in life.
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  #20  
Old 06-11-18, 08:30 AM
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Re: All disease is preventable (simplified with references added)

No responses - NOBODY wants to stop people getting sick.
The entire medical establishment is using sick people to make money.

Hi {name removed},

Is it possible for ask for a few words of advice ?

This is going to seem like peculiar timing, but I've just had an email exchange with {name removed} (in which I appear to have made him believe that I'm completely bonkers :-)).

As described in our email exchange, I've become a bit of a born-again epidemiologist and am now an overwhelming believer in nutrition, diet, lifestyle and stress (the final one of which is missing from your job listing) underpinning ALL disease. I've become a huge believer in the biopsychosocial model and lost faith in the biopharmacogenetic model.

I am (consequently) at a bit of a loose end as I've trained in bioinformatics, statistical genetics, experimental biology ... ... but have ended not really being particularly interested in any of that any longer, and wanting to look at how to help people in making nutritional, diet and lifestyle change. The problem that I'm having is that I've grown a little jaded with -omics changes (polymorphisms, epigenetic variation etc) which have statistical but not clinical significance.

I want to do precisely the job that you are offering but haven't ever been a proper epidemiologist before and so was wondering whether there are ever more junior roles which come up with exactly that type of job specification.

The only other point that I'd bring up (and as referenced above) - is that I'm adding one factor into the job advert which I think is key. I am absolutely convinced that we need to examine the role of (biopsychosocial) (di)stress in preventing broad-sense lifestyle change. I don't believe that a healthy lifestyle will ever be chosen whilst people are under a level of (di)stress. Or put in other terms distress prevents eustress. I've talked to all of the scientists around me in passing - and the ones with an unhealthy profile do 'appear' to have issues with stress, evident by their character.

This (ie stress sensitivity and exposure) is my overwhelming interest in solving not only the current diabesity epidemic - but also all of the many common diseases (cancer, Alzheimer's) with strong association to diabesity.

I've personally solved *all* of my own problems (allergies) by changes in nutrition (predominantly fasting and I'm a low GI raw vegan now), exercise (daily runs at 5am and 8 hour walks with my dog) and lifestyle (early to sleep, stimulant (sugar, starch, caffeine) elimination etc) ... ... but (di)stress as opposed to eustress remains; my current place of work (a biotechnology company on the Babraham Research site) has just been acquired (with predictable consequences) by one of the major players in the diabetes market (Abbott Pharmaceuticals).

So - I am in a position where I can simply apply for more of what I've done previously (ie more functional genomics and I've found ten or so suitable positions in our area) or write this email to you and ask you for some advice. I guess the one point that I do want to emphasize is that I am completely preoccupied by every aspect of 'stress' (distress vs eustress) and the need to understand it if we're to drive any change in human behaviour towards electing to a healthy lifestyle. I'm not too sure how to go about a switch into the field of epidemiology in such a way that I might make some meaningful contribution to this field.

Anyway - apologies for emailing you out of the blue. No worries if you think that it's too late or difficult to make the switch, or if you think that the subject of stress (how to study and how to alleviate it) is too difficult. I've thought about it heavily for some time and would love to perform the epidemiology of glucocorticoid resistance in appropriate cohorts to show that it exists. Personally I'd love to study the Mount Athos monks as my control group. I'd also like to show why human beings are under such stress - however ... ... I suspect I know why it exists (referencing Michael Marmot's Whitehall Study and the work of the social epidemiologist (Richard Wilkinson and Kate Pickett)).

Anyway - would greatly welcome any advice before I dive into making applications for a return to the world of University -omics. It's not that I think that -omics is without merit - it's that I think that epidemiology is the path to introducing policy change in which actual human health will be impacted.

Thanks {name removed}.

--- PS ---
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341031/ - so this idea (to assess glucocorticoid resistance and other measures of chronic stress exposure (at the neuroendocrine levels of adrenal function and the autonomic nervous system))
https://www.ncbi.nlm.nih.gov/pubmed/28327563
https://www.ncbi.nlm.nih.gov/pubmed/16483856 - (using this population - it's genetically heterogeneous and as indicated by these publications, welcome epidemiologist)
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  #21  
Old 06-11-18, 08:48 AM
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Re: All disease is preventable (simplified with references added)

Simply.

Change the level of bad stress we're under and increase the good stress we're under and we will be optimally healthy.

Good stress occurs naturally in the absence of bad stressor.

Bad stressor - the maintenance of human hierarchies.

This has been demonstrated clearly by one of the world's most famous epidemiologists in the Whitehall Study.

What about all other stressors - there are (of course) others - but putting in place a society in which all people are equal through all people contributing equally towards acquisition of what all people need (physiologically/epidemiologically determined) for happy survival - corrects all downstream problems.

How do we get people to do this ?
Realise that the human mind is designed to confer morality which culminates in wisdom by teaching the mechanism of evolution as stated in the Theory of Everything - which is a statement that any given layer of evolution forms through three dual and 1 non-dual (weak) interaction.

This pattern is held - and so in the ToE physics we shift from:
strong / weak / electromagnetic -> 3 x dual interactions
gravity -> 1 x non-polar weak interaction

--- to (currently) ---
man -> mother, wife, daughter -> 3 x dual interactions
man -> all other people -> 1 x non-polar weak interaction

-*-

Understand mechanism of evolution (Stephen Hawking + Albert Einstein) -> Acquire wisdom (a sense of perspective) -> Change from primitive (to take from others) to higher reward system (to give to others) -> Individual/Society changes and in a now nice non-distressful environment -> we elect to eustress --->--- regulation of appetite changes -> a healthy lifestyle is CHOSEN.

We can't force a healthy lifestyle - we need to change society so that people choose a healty lifestyle.

In the rat park experiment - rats choose a healthy lifestyle in the absence of distress.
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Last edited by namazu; 06-11-18 at 01:49 PM.. Reason: Religious ("mind of God") and political discussion are prohibited outside of Debates section.
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  #22  
Old 06-11-18, 10:08 AM
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Re: All disease is preventable (simplified with references added)

Quote:
Their [The mitochondrial] shape is dynamic, continuously remodelled by cycles of fusion and fission events. These do not occur randomly, but are coordinated to respond to specific cellular needs, such as ‘on-demand’ transport of mitochondria at specific subcellular sites and equal division of the mitochondrial progeny between the two daughter cells during mitosis (Shaw and Nunnari, 2002).
https://www.nature.com/articles/1209605

Mitochondrial biogenesis is good (consistent with health)
Eustress -> Mitochondrial fission (requirement for energy/heat)
Distress -> Mtochodrial fusion (eg fasting for extended periods)

Eustress -> leads to -> Distress of we're to careful ie

3-4 days fasts (eustress) -> 40 day fasts (distress)
- body tries to decrease energy usage at 4 days (personal observation) ie decrease 'on demand' of mitochondria - fusion not fission

What kinda' fuel would you expect the mitochondrion to want ?
Of course fat not glucose (osmotically active) - where removal of water will concentrate ions will alter membrane potentials across the mitochondrion - will alter its ability to work
eg
https://www.ncbi.nlm.nih.gov/pubmed/12409316 ie 'high blood glucose disrupts mitochondria' ... ... 'protecting the brain from oxidative stress caused by ROS produced as a consequence of hyperglycemia-induced enhanced respiration.' https://www.ncbi.nlm.nih.gov/pubmed/24076121

b-hydroxybutyrate can bypass glycolysis ie

fat deposited -> b-oxidation -> acetate -> b-hydroxybutyrate

mitochondrial b-oxidation -> takes fat breaks to acetyl CoA -> binds to yield ketone bodies -> powers (directly through Complex II) the mitochondrial electron chain.

IE the mitochondria carry with them - all that's required to denature and handle fat and use it appropriately.

Problem - blood glucose / blood urea / blood salt eg takeaway food like the McDonalds burger destroy the mitochondrion - water loss by osmosis will disrupt local ionic concentrations disturbs membrane potentials - alters the operation of the proton pump and its capacity to convert 'fat' into ATP.

Mitochondrial operation destroyed by distress.

Note - there's a line between eustress and distress - which we must not cross - this was described in the first 'all disease may be prevented' thread as the inverted U curve - initially there's benefit - however that benefit ceases with continued exposure.

People need to be able to step away from eustress to avoid distress - this is only possible if we're in a world where people aren't exposed to psychological distress (any form of human hierarchy) in their daily lives.

All human beings are equal and so should form a society in which this is reflected.

Simple - definition of a global collaborative village in which each person helps the other to be as great (personally) as the person 'd like to be.

-*-

Note - this story is consistent with human evolution through persistence hunting ie feast and fast ... ... if we don't fast we don't clean ourselves up.
Personal observation - I love fasting - but it's impossible under distress - fluctuating blood glucose levels lead to hunger (triggered on hypoglycaemia).

-*-

Many people report tightness in back - note b-hydroxybutyrate through GABA induction should (see benzodiazepene) -> muscular relaxation ie permitting us access to endurance running.

-*-

The basis to prevention of ALL human diseases comes through changing the structure of society globally such tht all people are equal and co-operate through personal contribution of time to survival essentials - and thereafter chase whatever they'd like under a model of personal improvement for improvement's sake - and collective improvement - to spend life attempting to see how good you can become at whatever tickles your fancy.
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  #23  
Old 06-11-18, 10:20 AM
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Re: All disease is preventable (simplified with references added)

The triumviracy of human genomes

Mitochondrial genomics -> increase mitochondrial number through demand
Human genomics -> b-hydroxybutyrate is a HDACi ie shuts down growth/proliferation events for maintenance (aerobic respiration and increasing quality through neural rearrangement)
Gut biome genomics -> the diet above is proven to lead to increased bacterial diversity (don't worry about how the bacteria, viruses or fungae of our biome interact) - simply chase diversity.
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  #24  
Old 06-11-18, 01:26 PM
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Re: All disease is preventable (simplified with references added)

From genome to protein

  • People are looking for proteins which go up or down in a condition
  • The object appears to be growth/proliferation -> maintenance to stop protein production ie to shift to straight aerobic respiration (mitochondrial biogenesis + neural growth are very slow processes, as is neural rearrangement)
  • Ca2+ influx accompanies cellular work ie efflux neurotransmitters/insulin (hormone)/degranulation events (mast cells) - so wildly fluctuating Ca2+ upon the cell working hard - similarly in muscle (works harder on Ca2+ influx)
  • Ca2+ influx appears to operate as a measure of cellular work
  • Ca2+ increase (mitochondrial translocation) -> stress -> apoptosis
  • Over-work endangers mitochondrial operation - compromises the process of mitochondrial protection eg viral infection -> overwork -> leading to mitochondrial autophagy -> apoptosis
  • Once again - elimination of distress -> eliminate N and C -> autophagy to apoptosis only in the case of infected (hence overworking) cells and not enforced pointless excessive behaviour - enhanced protein production/secretion
  • Over-work -> ROS -> oxidation (AGEs) and atherosclerotic plaques ... ... ...

    So in
  • eg hormones (insulin) goal is to reduce induction (ie reduce blood glucose),
  • in the case of neurotransmitter the goal is asceticism rather than hedonism ie decreased neurotransmitter increased receptor levels and reduced degranulation events by properly deleting specific immune system response to self-antigens/inocuous allergens
  • and dropping endotoxemia through changing diet into diversity in low GI organic veggies (mostly raw) - reduced degranulation events
The goal is sensitivity in all processes upon completion of bodily 'growth'.

The green smoothie is your friend.
But you're going to want to drink it.

-*-

So the final stage of man appears to be simple mitochondrial aerobic respiration with adequate repair and recycling courtesy of autophagy.

Nobody's looking for everything to quiesce - everybody (the biomedical genetic pharmacologic) who has money is looking to destroy some aspect of a system ie remove organ, remove gene, remove protein which is required in its entirety.
Nobody's looking for the fundamental root cause of disease.

The answer is provided by social/medical epidemiology - human beings are not designed to be in a hierarchy.
Animals are designed to be in a hierarchy.

And yet - the heavily well paid biomedical pharmacogeneticists slither around breaking people for 6 figure annual salaries.

What a lot of nonsense.
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Old 06-11-18, 01:42 PM
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Re: All disease is preventable (simplified with references added)

What's the conclusion ?
You need to be the master of your own destiny and must serve no other (human) masters.

Science has spoken

https://www.nature.com/articles/srep18634
Quote:
Hierarchy is Detrimental for Human Cooperation

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Old 06-11-18, 02:03 PM
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Re: All disease is preventable (simplified with references added)

Quote:
Originally Posted by _ View Post
Nobody's looking for everything to quiesce - everybody (the biomedical genetic pharmacologic) who has money is looking to destroy some aspect of a system ie remove organ, remove gene, remove protein all of which are required.
Nobody's looking for the fundamental root cause of disease.
There isn't a human alive that would throw out some broken part of their car without replacement - so why does the whole of pay-per-medicine rely on this idea ?

Quote:
remove organ, remove gene, remove protein
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Old 06-11-18, 02:29 PM
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Re: All disease is preventable (simplified with references added)

PGC-1α, a member of the peroxisome proliferator-activated receptor gamma (PGC) family of transcriptional coactivators, is the master regulator of mitochondrial biogenesis.

wikip/Mitochondrial_biogenesis

PPAR-alpha is a transcription factor and a major regulator of lipid metabolism in the liver - mice lacking functional PPAR-alpha have low plasma levels of ketone bodies.


wikip/PPARa

Fibrate - treatment of diabetes via PPARa.

PPAR-alpha is activated under conditions of energy deprivation and is necessary for the process of ketogenesis.

Fat/low GI veggies + low carb + low protein through fasting -> sufficient energy and access to the promised land escaping the stimulant (blood glucose and protein elevation - sweet/umami) for sour (lemons alkalize blood cf calcium loss from bones cf acidified oceans degrade coral), bitter (spice - very high anti-oxidant counts) and sufficient saltiness to balance out for salt lost in endurance exercise.

-*-

Diabetes/Obesity result from excess protein/carb intake from which all other diseases (loss of immune control) arise.

Stimulants are only required when 'depressed' by life.

Define what motivates people ?
Autonomy, Mastery Purpose. (research based)

Where I prefer - morality/wisdom opens one's eyes to where you'd like personal (autonomy) excellence (mastery) - as we can't identify our 'thing' until we've a mind - where morality/wisdom acquisition isn't there to be 'better' than other people - we're looking at is a proxy for the development of a mind which can think.

Forget morality as 'holier than thou' - it's simply the sign that one may use (when enforcedly moral / lost desire for money+power) - that one's mind is usable.

Quote:
Originally Posted by stabile / Stephen Hawking
All scientists know the need to calibrate their machinery - at least all bar the one tool which matters - their own mind.
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  #28  
Old 06-11-18, 02:52 PM
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Re: All disease is preventable (simplified with references added)

Sweet/Umami <- growth/proliferation
vs
maintenance
Sour - sumac*/lemon+lime/barberries
Bitter - Turmeric/cocoa/coffee
[amla*/clove*]
Bitter foods: The nutrient-rich antioxidants

A transition from quantity of rubbish [McDonalds accelerated death burgers] to quality in all things [a personally satisfying - sustainable life].


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ADHD understood - simple matter of defining purpose (morality) of mind
See Stabile 'enforced moral consistency' ~15 years ago, nothing else since has been of any relevance to ADHD.

Last edited by namazu; 06-11-18 at 04:01 PM.. Reason: Replaced link to blog with print-friendly version of page.
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  #29  
Old 06-12-18, 01:17 AM
SB_UK SB_UK is offline
 
 

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Re: All disease is preventable (simplified with references added)

The human body is an engine and if it's looked after properly then it will be just fine.


All that is required to look after the human body is to look at our most recent evolutionary properties.


Higher motivation (consider spirit) - to develop ourselves and society simultaneously
Mind - to develop morality

Body - to keep it clean


And the combination combats all disease.


The junction between higher motivation, higher mind and appropriately cared for body - where the nature of human beings is to look at the highest property and then work down.


Care for spirit (higher) permits access to mind (an objective enquiry) cares for body (through switching reward system from excess eating into rarely eating).
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ADHD understood - simple matter of defining purpose (morality) of mind
See Stabile 'enforced moral consistency' ~15 years ago, nothing else since has been of any relevance to ADHD.
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Old 06-12-18, 06:43 AM
SB_UK SB_UK is offline
 
 

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Re: All disease is preventable (simplified with references added)

One must have a null hypothesis (ie a model) to be a scientist.

There's too much data which one might recruit - otherwise.
Quote:
Second, HMGCS2 transcription is negatively regulated by mTORC1, one of the human target of rapamycin (TOR) complexes that is activated by insulin signaling or abundant glucose (via AMPK) or amino acids (via Rag)
from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414487/

The story is just soooooo ... ... simple.

-*-

Dying for Dinner.

-*-

Quote:
An evolutionarily conserved role for autophagy in antiviral defense
https://repository.upenn.edu/dissertations/AAI3609213/

Evolutionary conservation is a clear statement of importance.

It is important for the eukaryotic cell to beat off virus.
It is important for the prokaryotic cell to beat off bacteriophage.

Cell ramps up operation in a virally infected system (autophagy) primed to detect Ca2+ changes within a cell and signal elimination.

The system requires discrimination between signal (infection) and noise (background) - all systems require differentiation between signal and noise to drive action.
In the system we have (over-working) - noise (background) lifts to increased work (Insulin/IGF-1 processes through distress-mediated Carb/Protein consumption) - and making it difficult for the immune system to spot and eliminate - autophagy -> apoptosis - infected cells.

Viral (intracellular) infection is of particular note.

-*-

Quote:
When studying the effect of MHC-I cross-linking on the TCR- and B cell antigen receptor (BCR)- mediated increase in [Ca2+]i, respectively ... ...
https://www.ncbi.nlm.nih.gov/pubmed/8912890 and https://viralzone.expasy.org/resources/MHC1_total.jpg

General point - [Ca2+]i increase ramps up activity - we need to knock down all cellular activity such that when something actually happens - Ca2+ influx - it's spotted.

Once we've completed growth +proliferation - we're meant to engage in the slooooow processes of mitochondrial biogenesis, nerve cell grwoth and re-arrangement ie we're not meant to have an internal milieu which is metabolically active - such that optimal sensitivity in all internal components may be achieved.

To be considered a tune up for your body - not your car body - which is (ie the car) a remarkable (in a bad way) thing - in that it represents an individual enjoying (people like cars) enslaving (so much money to buy and run) self (commuting to work) !!
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ADHD understood - simple matter of defining purpose (morality) of mind
See Stabile 'enforced moral consistency' ~15 years ago, nothing else since has been of any relevance to ADHD.

Last edited by SB_UK; 06-12-18 at 07:04 AM..
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