View Full Version : Alpha-synuclein


SB_UK
09-04-15, 02:29 AM
Thanks to acdc01
http://www.addforums.com/forums/showpost.php?p=1744029&postcount=67

In 1 sentence the link arises from

ADHD is characterized by:

https://en.wikipedia.org/wiki/Alpha-synuclein
Knock-out mice with the targeted inactivation of the expression of alpha-synuclein show impaired spatial learning and working memory.[25] (https://en.wikipedia.org/wiki/Alpha-synuclein#cite_note-pmid22469626-25)
Full connection in next post

SB_UK
09-04-15, 09:53 AM
Sorry - long way round.

wikiP/dopamine
Outside the nervous system, dopamine functions in several parts of the body as a local chemical messenger. In the blood vessels, it inhibits norepinephrine (https://en.wikipedia.org/wiki/Norepinephrine) release and acts as a vasodilator at normal concentrations; in the kidneys, it increases sodium excretion and urine output; in the pancreas, it reduces insulin production; in the digestive system, it reduces gastrointestinal motility (https://en.wikipedia.org/wiki/Gastrointestinal_motility) and protects intestinal mucosa.^^^

I've experienced/read about ALL of the above when in ketosis ie associated with adopting ketone usage as a fuel - this is important

Aside

Liu G, Zhang C, Yin J, Li X, Cheng F, Li Y, Yang H, Uéda K, Chan P, Yu S (May 2009). "alpha-Synuclein is differentially expressed in mitochondria from different rat brain regions and dose-dependently down-regulates complex I activity". Neuroscience Letters 454 (3):

and

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281591/

[quote]Supporting an instrumental role for complex I dysfunction in PD-related dopaminergic neurodegeneration, the feeding of the mitochondrial ETC directly at complex II by means of the ketone body D-β-hydroxybutyrate was shown to bypass complex I blockade, enhance oxidative phosphorylation, and attenuate dopaminergic neurodegeneration in MPTP-intoxicated mice ... ...
Mitochondria within a strong neuromelanin environment crying out to be set free.

Loss of dopamine producing cells in Substantia nigra in Parkinson's disease.
Loss of neuromelanin characterized cells in Substantia nigra in Parkinson's disease.

Noting (for later)
http://www.pnas.org/content/109/23/8943.full.pdf
... ... the exotic electrical properties of melanin-*-

Melanin and friends don't simply suck up free radicals (ie not just protection).
Don't simply detoxify us by absorbing metals eg iron (http://www.ncbi.nlm.nih.gov/pubmed/8113797) (ie not just protection).

That's dull - 'doped' melanin is going to be ... ... ...


(Thiamine) TPP Oxidative decarboxylation (http://www.chemistryexplained.com/knowledge/Oxidative_decarboxylation.html) Prosthetic group B 2
(Riboflavin (http://www.chemistryexplained.com/knowledge/Riboflavin.html)) FAD Oxidation/Reduction Prosthetic group B 3
(Pantothenate (http://www.chemistryexplained.com/knowledge/Pantothenic_acid.html)) CoA - Coenzyme A Acyl group transfer Cosubstrate B 6
(Pyridoxine) PLP Transfer of groups to and from amino acids Prosthetic group B 12
(Cobalamin) 5-deoxyadenosyl cobalamin Intramolecular rearrangements Prosthetic group
Niacin NAD + Oxidation/Reduction Cosubstrate
Folic acid Tetrahydrofolate One carbon group transfer Prosthetic group
Biotin Biotin Carboxylation Prosthetic group

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0000457
Irradiated melanin manifested a 4-fold increase in its capacity to reduce NADH

-*-


Overall, these results demonstrate that the presence of melanin contributes to the enhancement of cellular growth upon exposure to ionizing radiation in conditions of limited nutrients.

Ketosis mimics fasting.

SB_UK
09-04-15, 02:58 PM
What's going on ?

Peripheral Dopamine
and
Ketoadaptaion - using ketones as fuel

- are having the exact same effects.
In a synergistic central and peripheral way, dopamine participates in glucose homeostasis and body weight. Additionally, dopamine inhibits angiogenesis and has been shown to influence growth and apoptosis of tumoral cells. Hence, dysregulation of dopamine signaling alters cancer cell proliferation. The newly described roles of dopamine in glucose metabolism, body weight, and tumor growth should be considered in the context of chronic treatment with antipsychotic drugs influencing dopamine signaling. Additionally, dopamine-related drugs might be envisaged as new targets in the metabolic syndrome, cardiovascular diseases, diabetes, obesity, and cancer. It might be hypothesized that environmental and lifestyle changes could influence the development of diseases through readjustment of dopamine balance. Future delineation of the role of dopamine in metabolic homeostasis and cell growth might open new avenues in the prevention and treatment of obesity and cancer.
http://press.endocrine.org/doi/full/10.1210/en.2010-0745

SB_UK
09-05-15, 01:36 AM
adhd is characterized by:
https://en.wikipedia.org/wiki/alpha-synuclein
knock-out mice with the targeted inactivation of the expression of alpha-synuclein show impaired spatial learning and working memory.


so - we have repetition training intrinsic quality.
This is true for walking and building the mind.

The mind is a model of understanding which strives towards the scientific model of simplest explanatory model - making it a natural equivalent to learning to walk.

Learning to walk - movement in external space
learning to use the mind - movement in internal space.
knock-out mice with the targeted inactivation of the expression of alpha-synuclein show impaired spatial learning and working memory.12345

SB_UK
09-05-15, 01:45 AM
What drives the nerve is towards the evolutionary equivalent of parsimony/Occam's razor/simplest workable explanatory model.

The nerve (sensory - cerebellar - motor loop) is driven towards efficient orientation towards completion of a task - the principle of parsimony is intrinsically built in.

We're endowed with the natural tendency (much as a chemical reaction is governed by energetics) towards parsimony in all controlling features regulated by the nerve.

So - as such
Enlightenment - structural re-arrangement of the mind towards understanding individual context, morality and holistic logical consistency is inevitable.

We won't feel 'real' unless our nerves rationalise into the parsimonious structure which matches our internal perspective over external (logos) reality.

(the generative principle of the Universe)

http://vignette3.wikia.nocookie.net/matrix/images/0/0f/X6a5jqez2r4mm4z.jpg/revision/latest?cb=20110127022313

In the Shawshank Redemption - appreciating freedom (The Land of the Free) was only possible following false imprisonment.

J E'S US
Passover - emergence

To uncover (realise) each of our individual Buddha natures

SB_UK
09-05-15, 02:00 AM
Melanized fungal spores are common in the sediment layers of the early Cretaceous period when many species of animals and plants died out which coincides with the Earth's crossing the “magnetic zero” resulting in the loss of its : “shield” against cosmic radiation [12] (http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0000457#pone.0000457-Hulot1).

http://www.esa.int/var/esa/storage/images/esa_multimedia/images/2013/10/swarm_constellation/13069393-1-eng-GB/Swarm_constellation_medium.jpg

The European Space Agency's SWARM project.

http://i.ytimg.com/vi/rxo6L255Pp0/maxresdefault.jpg

SB_UK
09-05-15, 02:23 AM
https://en.wikipedia.org/wiki/Alpha-synuclein

required for learning through assisting in neural pruning.

http://www.nature.com/articles/srep07989

The dynamic refinement of synaptic connections is essential not only for the appropriate wiring of neural circuits, but also for behavioral responses to a changing environment as well as for learning and memory2 (http://www.nature.com/articles/srep07989#ref2). In mammalian nervous system, synapse pruning events A better understanding of the molecular mechanisms underlying synaptic pruning by microglia and its regulatory mechanisms by neuronal exosomes ...
Neuronal exosomes have also been implicated in the development of neurodegenerative diseases, as they carry several disease-related proteins such as β-amyloid, α-synuclein and TDP-43, which are involved in the pathogenesis of Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, respectively44 (http://www.nature.com/articles/srep07989#ref44),45 (http://www.nature.com/articles/srep07989#ref45),46 (http://www.nature.com/articles/srep07989#ref46).-*-

Ketosis corrects aberrant a-synuclein expression.

https://lh3.googleusercontent.com/-eQA5V61xcjc/TXVIgitfhNI/AAAAAAAAABw/rM2QMOIct8E/s400/Ketosis+Brain+Cartoon.jpg

SB_UK
09-05-15, 02:35 AM
Summarisin

Genomic self-assembly (physical developmental biology) from meiosis*
->- to ->-
Neural self-assembly (central learning)are associated with their own respective reward systems.

A switch from anabolic to catabolic/maintenance (autophagy) cf (http://www.cimr.cam.ac.uk/research/principal-investigators/principal-investigators-q-z/rubinsztein) ... ... (http://www.cimr.cam.ac.uk/research/principal-investigators/principal-investigators-q-z/rubinsztein)

This represents a transition in fuels within the insulin/IGF-1 to the leptin axis.
The genomic model (synonymous with quantity eg viral expansion) is meant to give way to the neural (quality) model of behaviour.

Maintain glycolysis in the CNS as learning progresses and learning is impeded.

Metabolic transition (seeded by the genomic program) is the fundamental basis upon which the generation of internal, intrinsic quality (cerebellar automatising/learning) develops.
But of course - metabolic transition isn't enough - the individual also needs to 'train'.
In places where training is possible (the classical Western World style which is found worldwide these days) - the metabolic transition is reversed ie tendency towards pro-insulin secreting diets.
In places where metabolic transition is possible (the poor/developing world style which is found worldwide also) - access to training is not afforded.
So - 2 models, sequentially arrayed - describing what it is to be human.

The genomic and neural programs
Metabolic shift from carbs to ketone usage.
The acquisition through training towards the accumulation of personal, intrinsic, innate quality.

-*-

Apparent heritability is not caused by genomic but is caused by epi-genomic variation.

Epi-allele persistence (not re-programmed) invalidates complex disease geneticshttp://www.addforums.com/forums/showthread.php?t=170941&highlight=epi-allele+persistence

SB_UK
09-05-15, 02:53 AM
... ... and so in Conclusion
ADHD [== sensitivity at empathic, systematizing and sensory levels *] represents the pained sensory overload emergence of a metabolically efficient pro-social species in an anti-social environment.

* via cortical microcircuit formation

It's all about (materialism to beauty) survival.

SB_UK
09-05-15, 03:02 AM
Cortical microcircuit formation is the mechanism by which our immersion in reality increases in resolution.
rrreality more rr{...}real

which is paraphrase of Markram's and parent to autistic children 'Intense World'.

SB_UK
09-08-15, 12:20 AM
α-Synuclein redistributes to neuromelanin lipid in the substantia nigra early in Parkinson's diseasehttp://brain.oxfordjournals.org/content/128/11/2654
The distribution and tempo of neuronal loss in Parkinson's disease correlates poorly with the characteristic and more widely spread intracellular changes associated with the disease process (Lewy bodies and Lewy neurites). To determine early intracellular changes in regions where cell loss is most marked (dopaminergic A9 substantia nigra) versus regions with Lewy bodies but where cell loss is limited, we assessed 13 patients with definite Parkinson's disease at various disease stages in comparison with controls. Using immunohistochemistry for α-synuclein, we confirmed the concentration of this protein in the soma of normal A9 neurons and in Lewy body pathology in brainstem catecholamine neurons in Parkinson's disease. Analysis of the degree of cell loss in brainstem catecholamine cell groups revealed that only the A9 substantia nigra had consistent significant cell loss early in the disease course with greater A9 cell loss correlating with increasing disease duration. To assess the earliest intracellular changes differentiating neurons more likely to degenerate, pigmented A9 and A10 neurons with and without obvious pathology were targeted, cell size and pigment density measured, and intracellular changes in α-synuclein location and lipid components analysed at both the light and electron microscope levels. There were no changes observed in healthy A10 neurons in Parkinson's disease compared with controls. Pigmented A9 neurons in later stages of degeneration with obvious Lewy body formation had a significant reduction in intracellular pigment, as previously described. In contrast, A9 neurons of normal morphological appearance and no characteristic pathology in Parkinson's disease exhibited significantly increased pigment density associated with a concentration of α-synuclein to the lipid component of the pigment and a loss of associated cholesterol. These changes in vulnerable but apparently healthy A9 neurons occurred without any change in cell size or in the amount of intracellular pigment compared with controls. The increase in pigment density is consistent with previously reported increases associated with oxidation and iron loading, reactions known to precipitate α-synuclein. The selectivity of the changes observed in A9 nigral neurons suggests that these early intracellular changes predispose these neurons to more rapid cell loss in Parkinson's disease. The increased concentration of neuronal α-synuclein and pigment in normal A9 neurons may already predispose these neurons to precipitate α-synuclein around pigment-associated lipid under oxidative conditions. Overall, these changes may trigger a cascade of events leading to larger intracellular aggregates of α-synuclein and the dispersement of protective pigment to precipitate cell death in Parkinson's disease.In sections without pre-treatment, the cytoplasm was largely devoid of α-synuclein in controls (G) with immunopositive staining and Lewy bodies observed in some of the remaining neurons in Parkinson's disease (H)http://brain.oxfordjournals.org/content/128/11/2654

-*-

What is oxidation ?
Over-working.

wildly fluctuating up <- Balance -> wildly fluctuating down

Triggered Neuromelanin a-synuclein accumulation and ... ... ...


ahhhhh!!
:D

SB_UK
09-08-15, 12:40 AM
Nerves are killed off if persistently/chronically activated.

The core mechanism of neural pruning vs neural re-arrangement.

Alpha-synuclein is specifically upregulated (https://en.wikipedia.org/wiki/Regulation_of_gene_expression) in a discrete population of presynaptic terminals of the brain during a period of acquisition-related synaptic rearrangement.[18] (https://en.wikipedia.org/wiki/Alpha-synuclein#cite_note-pmid7646890-18) It has been shown that alpha-synuclein significantly interacts with tubulin (https://en.wikipedia.org/wiki/Tubulin), ... ...

birth of a nerve cell <- re-arrangement -> death of a nerve cell

'It's like walking a high wire.'

Summarising

We need enough (synaptic re-arrangement).
But either too much or too little will trigger neural pruning loss.

This occurs in Parkinson's disease - excess usage (oxidation) of the primitive reward system.

Balance not (dual) Excesses of up and down.

SB_UK
09-08-15, 12:52 AM
Now what I need.

Is

--->-- ELECTRON FLOW --->-- governed by cellular compartment (partic. mitochondrial) potential difference

Neuromelanin -> tubulin circuits (see Penrose and Hameroff connection to cytoskeleton and (http://www.ncbi.nlm.nih.gov/pubmed/16479502) Each of the alpha, beta and gamma- tubulin groups exhibit major differences in their net electric charge, dipole moments and dipole vector orientations.) -> Mitochondrial inner membrane to generate proton motive force -> NAD/FAD reduction (see PLOS paper on NADH reduction+acetate accumulation in radiotrophic fungae, reduction is gain of electrons) to NADH, FADH2 [<- 2 co-factors involved in the electron transport chain REDOX program]) -> to drive ATP synthesis [cf food]/uncoupling [thermogenesis,'shelter'] -> the 2 human absolute requirements of food and shelter.

The problem with ketosis is that it's too important to require us to manage a fiddly diet.

SB_UK
09-08-15, 12:55 AM
Summarising


--------->-------- ELECTRON FLOW --------->--------

Lunar/Solar EM -> cytoplasmic compartment SN Neuromelanin -> pan-Cytoskeletal tubulin electrical circuitry -> Mitochondrial compartment inner membrane NADH, FADH2 generation

->- drives ATP synthesis / thermogenesis

All~we~need
http://listenonrepeat.com/watch/?v=mTHjFeXmnHs

SB_UK
09-08-15, 01:04 AM
The path to wisdom is the path towards balance.

Physiology is synonymous with maintaining (homeostasis) balance.

To transcend the primitive reward (of need for 'stimulation') system and to be freed (from ourselves).

Taking the route of 'stimulation' increases our desire, increases rate of working of SN NM containing cells, increases oxidation rate, triggers a-synuclein redistribution from outer membrane (ROS handling) to cytoplasm (? ROS handling ?)) triggers cell death (characterizes the synucleopathies (https://en.wikipedia.org/wiki/Synucleinopathies)).

SB_UK
09-08-15, 01:34 AM
Cell group A9
Group A9 is the most densely packed group of dopaminergic cells, and ... is for the most part identical with the pars compacta (https://en.wikipedia.org/wiki/Pars_compacta) of the substantia nigra ...

Densely packed - connotes importance.

The function of the dopamine neurons in the substantia nigra pars compacta (SNc) is complex.
"Dopamine neurons are activated by novel, unexpected stimuli, by primary rewards in the absence of predictive stimuli and during learning".[8] (https://en.wikipedia.org/wiki/Pars_compacta#cite_note-8) Dopamine neurons are thought to be involved in learning to predict which behaviours will lead to a reward (for example food (https://en.wikipedia.org/wiki/Food) or sex (https://en.wikipedia.org/wiki/Sex)). In particular, it is suggested that dopamine neurons fire when a reward is greater than that previously expected; a key component of many reinforcement learning models.

http://digitalbloggers.com/christinegilmartin/files/2014/08/light-bulb-moment1st.jpg


ahhhhh!!
:D

SB_UK
09-08-15, 01:38 AM
Pandering to the Primitive reward system (MONEY,POWER,food,sex,cocaine) -> addictive response -> since -> the onus (need for dopamine release - non-autonomous regulated) to continue grows ever stronger

vs [you cannot have both the constellation of mammon AND true happiness - 'one has to choose' - the fundamental choice for man]

Succumbing to the Higher reward system -> Arraying knowledge (not disconnected knowledge, not amoral knowledge, not knowledge as pointless complexity, not knowledge is power) into understanding -> non-addictive -> since -> upon attaining wisdom, the onus (dopamine release - becomes autonomously regulated) to continue is lost

SB_UK
09-08-15, 02:01 AM
dopamine release - becomes autonomously [<- better should read non-conditionally] regulated

The sun of God.

http://www.addforums.com/forums/showthread.php?p=1753705#post1753705

? Conditional upon sun/heat exposure (partly conditional on living in a sunny place) vs immersed in lunar gamma radiation (non-conditional on geographic localization) ?

-*-

Inuit (living in cold places) -> ketosis -> uncoupling/thermogenesis -> mitohormesis with cold exposure -> ?? should be simple planetary existence ?? not conditional on living in a warm environment,.

-*-

The sun doesn't give light to the moon, assuming the moon's gonna' owe it one.

SB_UK
09-08-15, 02:17 AM
Summarising
Understand one's entire context (simple science) to one's satisfaction (you'll know !) and all else (the addictive addicting allure of self-harming stimulation) will naturally dissipate/rationalise.

SB_UK
09-08-15, 11:37 PM
Summarising
Understand one's entire context (simple science) to one's satisfaction (you'll know !) and all else (the addictive addicting allure of self-harming stimulation) will naturally dissipate/rationalise.

http://www.youtube.com/watch?v=YttE5IUhVHI&list=RDYttE5IUhVHI

SB_UK
09-09-15, 12:24 AM
nerves are killed off if persistently/chronically activated.


12345



otherwise - sensory overload in systematizing/empathizing and sensory levels.

Sensory overload - too much information.
Too much firing.
Increased firing rate - trigger to delete the neurone.

SB_UK
09-10-15, 02:16 AM
Now what I need.

Is

--->-- ELECTRON FLOW --->-- governed by cellular compartment (partic. mitochondrial) potential difference

Neuromelanin -> tubulin circuits (see Penrose and Hameroff connection to cytoskeleton and (http://www.ncbi.nlm.nih.gov/pubmed/16479502) Each of the alpha, beta and gamma- tubulin groups exhibit major differences in their net electric charge, dipole moments and dipole vector orientations.) -> Mitochondrial inner membrane to generate proton motive force -> NAD/FAD reduction (see PLOS paper on NADH reduction+acetate accumulation in radiotrophic fungae, reduction is gain of electrons) to NADH, FADH2 [<- 2 co-factors involved in the electron transport chain REDOX program]) -> to drive ATP synthesis [cf food]/uncoupling [thermogenesis,'shelter'] -> the 2 human absolute requirements of food and shelter.

The problem with ketosis is that it's too important to require us to manage a fiddly diet.


More to follow.

MAO

http://www.pharmacology2000.com/Autonomics/Adrenergics1/fad1u.jpg


NADH2 + FADH2 - 2 KEY redox co-factors.

SB_UK
09-10-15, 02:33 AM
Coming through ... ...

Scientists have found that gut bacteria produce neurotransmitters (http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003726) such as serotonin, dopamine and GABA, all of which play a key role in mood (many antidepressants increase levels of these same compounds). http://www.theatlantic.com/health/archive/2015/06/gut-bacteria-on-the-brain/395918/

https://en.wikipedia.org/wiki/Phosphoenolpyruvic_acid
phosphoenolpyruvate -> tyrosine/dopamine via shikimate pathway

95% of body's serotonin produced by gut biome

The gut biome cannot be studied in all its richness - and completely (metabolic complexity) invalidates the human genome as the bible of human function.

oxaloacetate
a-ketoglutarate again

-*-

glycolysis -> phosphoenolpyruvate -> tyrosine -> dopamine / NE / neuromelanin

Neuromelanin

Locus Coerukeus -> NE incorporating polymer <- SNS primitive
Substantia nigra -> dopamine incorporating polymer

J Neurochem. (http://www.ncbi.nlm.nih.gov/pubmed/26156066#) 2015 Jul 6. doi: 10.1111/jnc.13237. [Epub ahead of print]
Norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus.

Using the chemical degradation methods for the determination of catechols in neuromelanin (NM), we have shown that dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), 3,4-dihydroxyphenylethanol (DOPE), and 3,4-dihydroxyphenylalanine (DOPA) are mainly responsible for the structure of NM from substantia nigra (SN), while norepinephrine (NE), 3,4-dihydroxymandelic acid (DOMA), and 3,4-dihydroxyphenylethylene glycol (DOPEG) are additionally responsible for the structure of NM from locus coeruleus (LC).

NE in LC ->
The locus coeruleus (\-si-ˈrü-lē-əs\, also spelled locus caeruleus or locus ceruleus[1] (https://en.wikipedia.org/wiki/Locus_coeruleus#cite_note-1)) is a nucleus (https://en.wikipedia.org/wiki/Nucleus_%28neuroanatomy%29) in the pons (https://en.wikipedia.org/wiki/Pons) (part of the brainstem) involved with physiological (https://en.wikipedia.org/wiki/Physiology) responses to stress (https://en.wikipedia.org/wiki/Stress_%28medicine%29) and panic (https://en.wikipedia.org/wiki/Panic).

To transcend.

SB_UK
09-10-15, 06:01 AM
light (UV,gamma)
.+ CENTRAL catecholamine polymer [Substantia Nigra vs Locus coeruleus]
-> acetate/b-OH-butyrate/butyrate -> PERIPHERAL gut biome (butyrate bacteria seeding microbial ecosystem) for catecholamine biosyntheis
-> CENTRAL catecholamine polymerization

NADH2/FADH2 reconstituted for driving mitochondrial functioning - uncoupling/ATP synthesis.

Pesky co-factors.

SB_UK
09-10-15, 06:15 AM
Substantia Nigra 1 vs Locus coeruleus 2

1 Reward system rational morality - good
2 Reward system 'drama' - not good

SB_UK
09-10-15, 06:19 AM
The
Presence
of
N2-fixing Bacteria
in
the
Intestines
of
Man
and
Animals
http://mic.sgmjournals.org/content/journal/micro/10.1099/00221287-60-1-61?crawler=true&mimetype=application/pdf

This entire story is remarkable.

SB_UK
09-10-15, 06:21 AM
Gut biome (gut - 2nd brain) involved in intimate synergy with brain - gut biome supplies all necessary other reagents - brain supplying solar/lunar generated SCFAs to support biome.

That's sweet.

:-)

Though the other sweet is what we're leaving behind.

-*-
Also - one can tell what's scientifically interesting - because it possesses an intrinsic interest to it; it's fun to think about.

Bad science (data accumulation) feels dull.

Also - every mechanism is in place - a beautiful clockwork mechanism where everything need work for human beings to operate.

Fatal floor of medication - you're breaking a system which is required for optimal functionality.

eg MAO required

- not to be artificially inhibited.

SB_UK
09-10-15, 07:02 AM
So - this is a turn-up for the books -
our mental health biogenic amines are simply a gut produced reagent for N scavenging towards neuromelanin polymerization towards SCFA production for biome ecosystem functioning.

Our mental health is conditional on the gut derived amines.
Our physical health is conditional on our brain derived fatty acids -> ketosis / gut biome diversity

So - we're kinda' bystanders on underlying physical, chemical, microbiological events - and 'we' feel bad when we don't allow the system to work like clockwork.

SB_UK
09-10-15, 08:04 AM
Ther great mind/body problem.

Mind
Improved personal quality -> dopamine production polymerization cf dopaminergic chills ie having fun [learning/improving - becoming 'better']

crosses over with

Body
Gut Biome - Brain (Central neuromelanin) synergy ie aerobic respiration [tendency towards aerobic fitness ie being able to go on and on and on ... ...]

SB_UK
09-11-15, 12:18 AM
Try again
[1]
https://en.wikipedia.org/wiki/Alpha-synuclein
Knock-out mice with the targeted inactivation of the expression of alpha-synuclein show impaired spatial learning and working memory.[25] (https://en.wikipedia.org/wiki/Alpha-synuclein#cite_note-pmid22469626-25)

THIS IS ADHD.

[2]
ADHD, and its core symptoms, have been associated with abnormalities in the neural systems that govern release of neurotransmitters such as dopamine and noradrenaline.[1-6]

ACCEPTED

[3]
[DOPAMINE DERIVATIVES ARE RESPONSIBLE FOR] the structure of NM from substantia nigra (SN),
while
[EPINEPHRINE DERIVATIVES ARE ALSO RESPONSIBLE] for the structure of NM from locus coeruleus (LC).


[4]
SN -> dopamine release
LC -> epinephrine release

[2]
ADHD, and its core symptoms, have been associated with abnormalities in the neural systems that govern release of neurotransmitters such as dopamine and noradrenaline.[1-6]

[5]
Dopamine nt release in SN - reward anticipation ie to encounter a reward which provides a dopaminergic response which exceeds expectation.
Epinephrine nt release in LC - ... to salient stimuli, ie AVERSIVE stimuli ... ... ...
or
novel [APPETITIVE] stimuli ... ... ...
http://www.scholarpedia.org/article/Locus_coeruleus

[6]
This key neuromodulatory system is currently thought to be critical for numerous functions including response to stress, attention, emotion, motivation, decision making and learning and memory.

[1]
https://en.wikipedia.org/wiki/Alpha-synuclein
Knock-out mice with the targeted inactivation of the expression of alpha-synuclein show impaired spatial learning and working memory.[25] (https://en.wikipedia.org/wiki/Alpha-synuclein#cite_note-pmid22469626-25)

[7]
http://www.ncbi.nlm.nih.gov/pubmed/18257649
The catecholamines play key roles in orchestrating the response to stress. While this is crucial to handle emergency situations, stress becomes maladaptive when prolonged or repeated, increasing allosteric load and susceptibility to a wide range of serious diseases.

... ... three crucial catecholaminergic locations, the adrenal medulla, sympathetic ganglia and locus coeruleus in male animals.

The locus coeruleus, origin of most of the noradrenergic neurons innervating much of the brain, displays activation of additional signalling pathways and transcription factor with repeated compared to single exposure to stress.

[8]
A fundamental mechanism involved in the CNS of learning aversive and learning appetitive behaviour.
However - in the presence of chronic distress - we overload this system - and under the weight of chronic NE release - under the weight of negative re-inforcement (stick) cannot learn positive re-inforcement.

[9]
Spend our lives being chased by a stick (legal system), locked down in a meaningless life where we cannot step out of the waiting line, ... ... and so cannot develop a sense of personal quality, of a mind of rational morality.

Summary
Excess Aversive over Appetitive learning in our dull society makes Jack a dull, disordered, succumbing to diseases of 'Western living' boy.

SB_UK
09-11-15, 12:25 AM
So - the question becomes - need the stick ever be used ?

The brain is custom-wired to learn.

If learning is dull - then we really haven't mastered teaching.

The orthogonal standing wave model of evolution/creation - provides us with a simple model for how evolution works.

Once we're aware of that - the mind should rationalise.

When rationalised - human beings should stop killing each other for affiliation to political party, religion, football team, colour, gender etc etc - some idea of what it is to be human.

Sandwiched in between a choice of whether to adopt genomic (beat other people) vs neural (collaborate with other people) quality - where only one of these choices recruits personal quality - neural quality is strongly disease protective whereas genomic quality, beating other people - although 'rewarding' (primitive mechanism) - results in significant personal harm.

To actively choose to harm oneself, to harm other people, to damage all species, to damage the survival prospects of future generations.

-*-

To nurture personal, social/moral, rational quality
and not in any way - to assess one's worth
from position in power over any other person.

SB_UK
09-11-15, 12:33 AM
But how will people develop if they aren't forced to attend school ?

Well - if you have no co-ercion - then people will eventually get bored - remember we are hard-wired to learn.

And following our SN/LC machinery into seeking out novel learning (the cerebellar - sensorimotor cortical divining rod) - we'll 'do'.

You can't run aversive and appetitive side-by-side -
the individual and society need to choose.

All of the behaviours which we associate (and which kill children) with laziness -
fast-food, excess alcohol/cigarettes/drugs of addiction, lack of physical activity
- will not be supplied in a world freed from co-ercion (a world free of money) -

as nobody is getting paid to produce the 'food', nobody is getting paid to produce the drugs of addiction, nobody is being paid to drive you anywhere -

- gotta' do it all yourself.

Nobody in their right mind would produce harmful foods, harmful drugs or choose to drive other people around of their personal volition.

The individual HAS to do it all (and so consequently won't choose the 'wrong' option) themselves.


Jack of all trades and not a master of one which is neither here nor there.

SB_UK
09-11-15, 12:52 AM
Why a-synuclein over-expression ? in synucleopaties - general neural degeneration.

[1] from wikiP
a-synuclein Characterization of a novel protein regulated during the critical period for [...] learning
http://www.ncbi.nlm.nih.gov/pubmed/7646890

[2] NE / Dopamine involved in Appetitive vs Aversive learning

[3] In a world which has TOO MANY rules (see legal system which is a ridiculous, massive body of rules - which nobody can ever hope to learn) - we spend our times in constant pursuit of aversive learning involving NE - excess NE production downregulates sensitivity via standard negative feedback (basic physiological mechanism) -
requiring DE / NE re-uptake inhibitors (ADHD meds) to combat sensitivity desensitized through profoundly dull insensitivity <- ADHD (disorder element) is

Summarising
CARROT not STICK by profound global societal re-arrangement in which co-ercion (money) is eliminated.
Human beings will then give human beings permission (the choice of the higher neural reward system) to become personally and collectively better.

SB_UK
09-11-15, 01:06 AM
Gut biome (gut - 2nd brain) involved in intimate synergy with brain - gut biome supplies all necessary other reagents - brain supplying solar/lunar generated SCFAs to support biome.


Summarising

gut (amine) <-> brain (alkane)
.............^
.............|
.....mind (fun - cerebellar automatising learning)
->-
mitochondrial functioning (food,shelter) + H2O

SB_UK
09-11-15, 01:48 AM
Relationship between acid-base and REDOX reactions

[1]
(http://www.quora.com/Whats-the-difference-between-acid-base-reactions-precipitate-reactions-and-redox-reactions)A redox reaction involves the transfer of electrons from one thing to another [whereas an] acid / base reaction (Bronsted) involves the transfer of hydrogen ions.

[2]
The aromatic ring decreases the alkalinity (https://en.wikipedia.org/wiki/Base_%28chemistry%29) of the amine, depending on its substituents. The presence of an amine group strongly increases the reactivity of the aromatic ring, due to an electron-donating effect. Amines are organized into

[3]
Mitochondria - natural batteries - electron transport chan / proton-motive force

H+ H+ H+ ..................|
--------separation--------.|- potential difference
......H+...................|

H+ H+ .v...................|
---v----separation--------.|-> electron flow
...H+ H+...................|

[4]
PLOSone paper acetate accumulation in melanized radiotrophic fungae

[5]
NAD/FAD reduction (see PLOS paper on NADH reduction+acetate accumulation in radiotrophic fungae.
Relationshop between NADH and NADPH

[6]
The ratio of NAD+ to NADH inside the cell is high, while the ratio of NADP+ to NADPH is kept low. The role of NADPH is mostly anabolic reactions, where NADPH is needed as a reducing agent, the role of NADH is mostly in catabolic reactions, where NAD+ is needed as a oxidizing agent.

NADPH - anabolic
REDOX role (reducing agent)
NADH - catabolic
REDOX role (see above)

(7)
States
anabolic + catabolic (growth)
vs
aerobic respiration (maintenance) -> REDOX

Summarising
There's a growth -> maintenance transition in the human life-cycle
which sees
(upon completion of growth - acquisition of wisdom - completion of mind)
- the acquisition of a post-blood glucose elevating (stimulation duality) reward strategy
- to embrace a novel reward system which pulls back the reigns on 'growth'.

Excess growth/Unregulated death without metabolic (regulated) autophagy underlies the diseases of excess immune activity, neuro-degeneration and cancer - which make up a large percentage of diseases of Western living.

SB_UK
09-11-15, 01:56 AM
Coming of age of the species

Emergent event

Imminent ?


All available information points to human beings being positioned into a place where we are able to transcend 'worldly' (food,heat,water) requirements for survival.

Not transcending the need for air though

- noting that stupid,greedy,power hungry,anti-social,psychopathic,vicious,materialistic, consumeristic,rapacious,rentier capitalist,money loving,money grabbing human beings have methods of charging people for food, heat and water - but have ABSOLUTELY no way of charging people for being outside (sun/air).

Air - all we needAir - All I Need - Extended Version (http://listenonrepeat.com/watch/?v=Hr7JuEI6qZ4&s=0&e=479#Air_-_All_I_Need_-_Extended_Version)

N2 (air) fixation into amine
O2 (air) reactivity harnessed
Sun (sky) - energy transduced into alkane
H2O - by-product of electron transport chain
ATP - the development of food/shelter by electron transport chain

SB_UK
09-11-15, 08:07 AM
summarising

gut (amine) <-> brain (alkane)
.............^
.............|
.....mind (fun - cerebellar automatising learning)
->-
mitochondrial functioning (food,shelter) + h2o




correction


summarising

gut (amine -> biogenic amine -> base) <-> brain (carboxylic acid -> [fatty] acid)
.......................................^
.......................................|
....................mind (fun - cerebellar automatising learning)
->-
mitochondrial functioning (food,shelter) + h2o

johnny_walker
09-11-15, 02:07 PM
TL : DR:....... so does Johnny need to be on a Ketogenic diet ???

Keep Walking

Johnny Walker

SB_UK
09-11-15, 02:42 PM
Yes ... ... ... but it's not quite that easy.

Why would evolution make a state which is relatively difficult to enter - the default state ?

In the absence of proof that we can transcend food (the evidence isn't there yet) - yes.

How ?

You can get into the state using either a meat, fish, vegetarian, vegan or raw vegan approach.

What's important is that the ketogenic supporting diet is real food.

Why ? A fundamental stress involves altering the physiological ionic milieu from salt loading - Na+, H+ (acidifying foods) through to other ions (eg plants grown in NPK fertilizers shifting their own ionic concentrations).

So - as long as it's real food.

IE no processed food, no artificially grown/reared etc - it just needs to be 'real' and ketogenic-maintaining.

Exptal evidence is easy to obtain re:how much and of what we can eat to remain in the state.

Though for all of its health benefits - there is something wrong here.

There's no elegance in needing to eat.

The elegance is in direct powering of the mitochondria without need to supply them with food-derived fuel; they're wonderful things.

SB_UK
09-11-15, 03:16 PM
Brilliant reference
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677413/


in comparison with control samples, as well the numbers of mitochondria and vacuoles in space-exposed fungi were much higher than in controls.:-) have the answer in the morning.

-*-

New idea - could be sensory information charging a central nervous system battery; discharged in sleep ... ... rapidlu changing this idea.
Why would sensitivity select ?
Why would increased information upload select ?

Wouldn't it be nice if the increased information could power mitochondria directly ?
It can definitely power dopamine release ('musical chills').

An elegant balance in this idea - we get to power wherever we can maintain our senses ?

(still thinking)

SB_UK
09-11-15, 03:31 PM
The connection lies hereionizing radiation enhanced the electron-transfer properties of melanin
->-
mitochondrial electon transport chain

-*-

Gamma rays (https://en.wikipedia.org/wiki/Gamma_ray), X-rays (https://en.wikipedia.org/wiki/X-rays), and the higher ultraviolet (https://en.wikipedia.org/wiki/Vacuum_ultraviolet) part of the electromagnetic spectrum are ionizing

I love the sun.

SB_UK
09-11-15, 04:02 PM
it is interesting to note older literature reporting carbon fixation by fungi under nutrients-limited conditions (26 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677413/#R26)–28 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677413/#R28)). Fungi were reported to use CO2.
This CO2 fixation takes place in white light and leads to increase in biomass as opposed to dark fixation as part gluconeogenesis, which does not lead to a net gain of carbon. It is tempting to suggest that under limited nutrients conditions melanized fungi might use this mechanism of CO2 fixation by utilizing transduced by melanin energy of ionizing radiation instead of white light and perhaps this should be tested experimentally in future work.

previously
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677413/
This study explores the effect of continuous exposure to bright light on neuromelanin formation and dopamine neuron survival in the substantia nigra.
The rats exposed to bright light for 20 days or 90 days showed a relatively greater number of neuromelanin-positive neurons.
The rationale to investigate the effect of light on neuromelanin formation in the substantia nigra arises from evidence that dopamine in complex with iron can absorb in the visible light spectrum. Barreto et al.7 (http://www.nature.com/articles/srep01395#ref7) have shown that in the presence of Fe(NO3)3 two broad bands of dopamine absorbance appear, with maxima at 437 and 740 nm. Although light with longer wavelengths penetrates into the brain more effectively8 (http://www.nature.com/articles/srep01395#ref8), shorter wavelength light can also penetrate into deep brain structures. Gamma rays (https://en.wikipedia.org/wiki/Gamma_ray), X-rays (https://en.wikipedia.org/wiki/X-rays), and the higher ultraviolet (https://en.wikipedia.org/wiki/Vacuum_ultraviolet) part [shorter wavelength light] of the electromagnetic spectrum are ionizing

ionizing radiation enhanced the electron-transfer properties of melanin
->-
mitochondrial electon transport chain

SB_UK
09-11-15, 04:06 PM
I need something like he mechanism above to set people free from a dreary materialistic low quality pointless life of worthlessness.

Little Missy
09-11-15, 04:12 PM
I need something like he mechanism above to set people free from a dreary materialistic low quality pointless life of worthlessness.

Is your life dreary, materialistic, low quality, pointless and worthless? Sometimes your posts make me so sad because you must really be suffering. :(

SB_UK
09-11-15, 10:56 PM
Do you remember all of the years that Andy was in prison in the Shawshank Redemption ?

Perhaps some events occurred of note - but overall ... ...

- his entire period in jail was working towards just one and only one outcome.

-*-

Is life in prison less than we need ?


Why is freedom (becoming free) an enduring (the aspiration to be free) mark of human evolution for thousands of years ?

Are rich people free ?

No.

Money imprisons the mind.

Who has most ?

Out in the distance her order was heard
And the soldier was killed, still waiting for her word
And while the queen went on strangling in the solitude she preferred
The battle continued on

Human beings can create wealth for themselves by supporting the suffering of others.

But all human beings will know, even if they do not acknowledge what they're doing.

And they will feel pain.

It isn't human to take advantage.

It's human to be free from dependency relationships.

The rich person that needs poor people to supply their needs is dependent.
The poor person that desires to be rich - is no different.

The poor and the needy
are selfish and greedy
in her (generally the rich) name.

The dependent (suffering dependency ie addictive -ism) never remarks that a beautiful day is enough.

SB_UK
09-11-15, 11:17 PM
And so the answer to the question - is that in the absence of freedom, whether we admit it to ourselves or not, we are not as we desire to be.

The state of freedom will associate with a global village of voluntaryism.

I can feel the mind running out of places to go.

The world of mind isn't complicated, isn't complicated at all.

We need to fire off Earth v2 and to create collective quality.

Instead of the dull, dreary, grey, nation fighting, hierarchical power -istic armed border-guard structures we have of present.

Even {insert whatever we wish to call fundamental substrate} offered us a 'choice' - not enforced a will

- a choice between rational morality (truth) and selfish greed (the illusion of comfort).

The blue and red pill.

An illusion which the mind cannot re-create once seen through.

You cannot return to the Matrix.

The Matrix concerned itself with human beings as energy generators.

That's what we really should be becoming.

Of note - the connection between the ketosis lifestyle (mimics fasting) and ... ...
under limited nutrients conditions

Why would the mind/brain/body become better unless you train them so to do ?

SB_UK
09-11-15, 11:28 PM
http://optimalprediction.com/wp/radiation-eating-fungi-they-kill-trees-and-they-kill-people/
In the original paper, the researchers Dadachova et al showed (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0000457) that ionizing radiation changes the electronic properties of melanin, and enhances the growth of melanized fungi. So any fungus species that contain melanin have their growth spurred in the presence of ionizing radiation. These are not mutant fungi, they are ordinary fungus species found everywhere in the environment. Some of them are common molds that grow in your basement or bathroom.
So these fungi do not actually feed on radiation, they change the properties of melanin, so that it can be converted into energy for growth. Think of radiation as an enzyme that allows melanin to be “digested”. Effectively, it’s the same thing, though.


That's an all-powerful basis to evolutionary selection.

The major jumps in selection - to lower eukaryotes - melanin/mitochondria in fungae
and to nervous system - melanin/mitochondria/nerve must have been driven by the re-creation of an anutonomous (like plant) radiation harvesting and utilizing biochemical framework.

SB_UK
09-11-15, 11:39 PM
melanin,mitochondria,nerve.summarising

gut (amine -> biogenic amine -> base) <-> brain (carboxylic acid -> [fatty] acid)
.......................................^
.......................................|
....................mind (fun - cerebellar automatising learning)
->-
mitochondrial functioning (food,shelter) + H2O



MIND - BRAIN - BODY

Informational quality -> Melanin/Mitochondria > Gut biome

Of note - the human genome is missing.

[1] Informational quality - does not involve the human genome
[2] Melanin re-arrangement - environmental in nature
[3] Mitochondria - has own genome
[4] Gut biome - individual bacterial genomes

So - to say that the human genome (particularly without stipulation of epigenetic modifications and effects) facilitates an understanding of man -
is incorrect.

We're agents of quality.
And quality acquisition comes through practice, experience and following one's nose into fun.

No gene for it; no medication for it; no homeopathic pill for it and no herbal product for it.
Just one societal infrastructure (capitalism) which prevents it, and one (voluntaryism) which facilitates it.
The fundamental choice between a selfish and a social reward system.

SB_UK
09-12-15, 12:35 AM
Thanks to acdc01
http://www.addforums.com/forums/showpost.php?p=1744029&postcount=67

In 1 sentence the link arises from

ADHD is characterized by:
Knock-out mice with the targeted inactivation of the expression of alpha-synuclein show impaired spatial learning and working memory.[25] (https://en.wikipedia.org/wiki/Alpha-synuclein#cite_note-pmid22469626-25)
https://en.wikipedia.org/wiki/Alpha-synuclein

What is a-synuclein ?

Is it bad ?
No - the genome doesn't do 'bad' - only human beings do that.

[1]Lab reagent - SDS PAGE for size denaturing proteins.
DTT is frequently used to reduce the dissulfide bonds of proteins and, more generally, to prevent intramolecular and intermolecular disulfide bonds from forming between cysteine residues of proteins.
[2]
So if DTT removes structure (quaternary
By breaking the S-S bonds, both the tertiary structure and the quaternary structure of some proteins can be disrupted
https://www.umass.edu/molvis/workshop/imgs/protein-structure2.png
to primary protein structure) then the opposite effect will be to drive pathological potentially - potentially false - quaternary structure - then a strong oxidizing (ROS) environment will trigger assembly (potentially pathological) cf taupathies/synucleopathies.



[3]
Abnormal fibrillization triggering neural degeneration.

[4]
What's the cause of ROS formation ?
Mitochondria

[5]
What's the likely basis to calming the mitochondria ?


Exceptional - to be read

This mechanism may, in part, contribute to the neuroprotective activity of ketones by restoring normal bioenergetic function in the face of oxidative stress.http://www.ncbi.nlm.nih.gov/pubmed/17240074


FULL TEXT
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1865572/

SB_UK
09-12-15, 12:48 AM
Summary
The disorders of Western living are the disorders of Western style living.

the genome doesn't do 'bad' - only human beings do that.

From artificial food, to artificial human relations, to artificial work, to artificial chemicals in the water/air, to artificial material wealth, to artificial emotions, to artificial words
- it's all distressing.

And it's all done for money.

To keep people in jobs.

Why waste your life doing something that doesn't result in life becoming ever better for you ?

This life is more than just a readthrough.

Fail to contribute quality - and life upon reaching death will not have (teardrops on the fire) satisfied (http://www.urbandictionary.com/define.php?term=crying+over+spilled+milk).

http://listenonrepeat.com/watch/?v=jpLt4LB2pVU#Massive_Attack_-_Teardrop_with_Liz_Fraser

SB_UK
09-12-15, 01:34 AM
What are tau/a-synuclein/amyloid-b actually doing ?

The misfolding of intrinsically disordered proteins such as α-synuclein, tau and the Aβ peptide ... ...
http://www.ncbi.nlm.nih.gov/pubmed/24551051
[1]

At birth, the human brain consists of approximately 86 (± 8) billion neurons.[3][not in citation given] The infant brain will increase in size by a factor of up to 5 by adulthood. Two factors contribute to this growth: the growth of synaptic connections between neurons, and the myelination of nerve fibers; the total number of neurons, however, remains the same.[4] Pruning is influenced by environmental factors and is widely thought to represent learning.[4] After adolescence, the volume of the synaptic connections decreases again due to synaptic pruning.[4]
So
in utero neurone growth [GROWTH PHASE cf BLANK SLATE] -> postpartum neural/synaptic pruning, re-arrangement [LEARNING PERSONAL QUALITY] and circuitry 'strengthening'.

[2]
We need a mechanism of deleting neurones.

An intrinsically disordered protein - by virtue of its structure - would make the ideal 'trigger' post-oxidation and polymerization for nerve cell death.

It's a biosensor for oxidation. A fundamental part of CNS functioning.

Didn't figure on what we'dd do to it though.

--- FINALLY ---

Physiologically - why would a neurone to be deleted suffer oxidative environment over and above nerves to be maintained ?

- over-use, over-energetic requirement - deletion trigger ie the nerve must neither be used too little or too much.

distress (too little) - synapse/neural deletion <- eustress -> distress (too much) - synapse/neural deletion
distress (too little) [neural degeneration] <- eustress -> distress (too much) [neural degeneration]

Evidence
Too little
The selection of the pruned terminal arbors follow the "use it or lose it" principle seen in synaptic plasticity.

Too much
Desensitization through exposure to stimulus-*-

How do we maintain eustress ?

Ketogenic state with stable blood glucose level.

But but but ... ... ...
I want this entire mechanism to be autonomously regulated without the need for humans to make their usual stupid stupid interventions which mess up otherwise perfectly functional evolutionary systems.

SB_UK
09-12-15, 01:44 AM
Originally Posted by wikipedia/alpha-synuclein
Liu G, Zhang C, Yin J, Li X, Cheng F, Li Y, Yang H, Uéda K, Chan P, Yu S (May 2009). "alpha-Synuclein is differentially expressed in mitochondria from different rat brain regions and dose-dependently down-regulates complex I activity". Neuroscience Letters 454 (3):


Parkinson's disease induction

Evidence of Active Nerve Cell Degeneration
in the Substantia Nigra of Humans Years
after 1-Methyl-4-Phenyl-1,2,3,6-
Tetrahydropyridine Exposure
ref (http://pages.towson.edu/bdevan/Brain%20transplant%20follow-up%20articles/Langston%20et%20al,%201999%20-%20evidence%20of%20active%20cell%20degeneration%20 in%20human%20MPTP%20exposure.pdf)

After reaching the intracellular compartment, MPP is accumulated in mitochondria, where it inhibits complex I of the mitochondrial respiratory chain.-*-

Mitochondria cutting loose.

SB_UK
09-12-15, 02:12 AM
IMPRESSIVE.

question ?


Mitochondrially loaded muscle,
Mitochondrially loaded nerve,
Mitochondrially loaded brown fat cells.


What does mitochondrial uncoupling do in the nerve cell ?

http://www.translationalneurodegeneration.com/content/1/1/3
This review gives a brief insight into the role of mitochondrial dysfunction and oxidative stress in the converging pathogenic processes involved in Parkinson's disease (PD). Mitochondria provide cellular energy in the form of ATP via oxidative phosphorylation, but as an integral part of this process, superoxides and other reactive oxygen species are also produced. Excessive free radical production contributes to oxidative stress. Cells have evolved to handle such stress via various endogenous anti-oxidant proteins. One such family of proteins is the mitochondrial uncoupling proteins (UCPs), which are anion carriers located in the mitochondrial inner membrane. There are five known homologues (UCP1 to 5), of which UCP4 and 5 are predominantly expressed in neural cells. In a series of previous publications, we have shown how these neuronal UCPs respond to 1-methyl-4-phenylpyridinium (MPP+; toxic metabolite of MPTP) and dopamine-induced toxicity to alleviate neuronal cell death by preserving ATP levels and mitochondrial membrane potential, and reducing oxidative stress. We also showed how their expression can be influenced by nuclear factor kappa-B (NF-κB) signaling pathway specifically in UCP4. Furthermore, we previously reported an interesting link between PD and metabolic processes through the protective effects of leptin (hormone produced by adipocytes) acting via UCP2 against MPP+-induced toxicity. There is increasing evidence that these endogenous neuronal UCPs can play a vital role to protect neurons against various pathogenic stresses including those associated with PD. Their expression, which can be induced, may well be a potential therapeutic target for various drugs to alleviate the harmful effects of pathogenic processes in PD and hence modify the progression of this disease.And :p of course

The ketogenic diet increases mitochondrial uncoupling protein levels and activity.
http://www.ncbi.nlm.nih.gov/pubmed/15048898

SB_UK
09-12-15, 02:27 AM
http://www.nature.com/nrm/journal/v6/n3/fig_tab/nrm1592_F3.html

As simple as -

electron transport chain -> mitochondrial proton gradient -> ATP + ROS
So ... ... along comes
ROS + UCP -> dissipates mitochondrial proton gradient -> calms the system -> eliminates ROS

http://www.nature.com/nrm/journal/v6/n3/images/nrm1592-f3.jpg

A ketogenic/UCP/mitochondrial neurodegenerative protective mechanism.

SB_UK
09-12-15, 02:34 AM
Summarising thread
There is a (the neural/collaborative/social/memomic/connectomic) reward system which concerns itself with the individual developing improved/intrinsic sensorimotor-cerebellar personal quality
- which when embraced -
safeguards human health through oxidative damage protection.

Connection to a-synuclein
In physiology - A role in neural/synaptic pruning - the key event (ie learning/synaptic+neural pruning and re-arrangement) which characterizes what it is to be human.
In pathology - Oxidative damage leads to pathological fibrillization in the naturally internally disordered proteins of tau, a-synuclein and b-amyloid.

Connection to ADHD
Environmental physical, psycho and social (di)stress in the sensitive (cortical microcircuits in sensory [so sensitive to 'loud' sensory stimuli], emotional/empathic [so sensitive to immoral/antisocial behaviour] and systematizing [so sensitive to irrational behaviour from the perspective of individual/collective wellbeing] cortical micro-circuits) expressed through increased cellular oxidative stress <- disorder component of ADHD.

We are notable in that we learn.
(eventually)

You live you learn, you love you learn
You cry you learn, you lose you learn
You bleed you learn, you scream you learn

SB_UK
09-12-15, 02:59 AM
The classic divide:

psychology - the mind desires 'quality' and if pursued is neuro-protective
Disorders understood at the level of cortical micro-circuit cerebellar loop formation - failure to generate balanced cerebellar - sensorimotor loops - premature cortical networks without cerebellar balance, failure to generate them (ie personal quality) at all.
Basis to delayed cortical maturation in ADDers.
--- informational [physics] paradigm ---

neurology - the brain issues a material foundation to allow the mind to form.
Disorders understood at the level of metabolic biochemical pathway - failure to handle reactive oxygen species
---- material [chemistry] paradigm ---