:OUT OF THE BOX

: . MD, PhD, MRCGP, MEPMA

/ ,

 Health = small signals + rapid recovery after a

(nutritional) challenge
Pre-Disease = larger and more sustained signals delayed
and incomplete recovery
Disease = strong signals + no recovery?

Systems Elasticity

Biological clock; a term implying an underlying/internal physiological

mechanism that gives a time sense to every living organisms i.e., when to
eat, sleep/awake etc.

Biological rhythm; a cyclical, repeated variation in a biological function.

Circadian rhythm; a cyclical variation in a metabolic ,

physiological or behvioural process with a period of about 24h when
in constant conditions (the term circadian is derived from the Latin
circa = and diem , =
day).

Ultraradian: Rhythms faster than 24 h

Infradian: Rhythms slower than 24 h

Circaseptan rhythm; a cyclical variation in a metabolic, physiological or

behvioural process with a period of about a week when in constant
conditions.

Circannual rhythm; a cyclical variation in a metabolic, physiological or

behvioural process with a period of about an year.

:
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(The LIFE is the fourth level of quantum organization of nature (after the
nuclear, atomic and molecular ones, Prof.S.Sitko, 1992)

Winfree model
N
i i ( X ( j )) Z ( i )
j 1

Modified general model(Kuramoto)

N

i i K ji f ( j i )
j 1

Wrist watch

SCN (biological clock)

Driven
with
a
predetermined period (nearly
24h)

Driven by a genetic program

with
a
pre-determined
period (~24.1h)

Has error

Has error

Able to re-set

Able to re-set

Free will
We act in accordance or
defiance of the clock

Free will
We act in accordance or
defiance of the clock

Can give to others

Can give to others

:

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, ,
Proceedings of the National Academy of Sciences.

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Circadian rhythms occur in most of the living

organisms, and with a 24hour periodicity govern a
number of physiological and metabolic functions.
During the past few years, an important research effort
has uncovered new trails that intersect between
circadian rhythms and metabolic pathways. At a
molecular level, the clock machinery is responsible for
the establishment of a circadian epigenome, and this
can be modulated by metabolic cues. Indeed,
metabolic control by the circadian clock is manifest in
the development of metabolic diseases when circadian
rhythms are impaired. Thus, pharmacological
modulation of circadian rhythms promises new avenues
for the treatment of metabolic and sleep disorders.

50
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POR (Cytochrome P450 oxidoreductase)
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 Sulfates decorate exterior of cell, e.g., as

heparan sulfate proteoglycans (HSPGs) or as
cholesterol sulfate (Ch-S)
Sulfates carry negative charge and keep
suspended cells from sticking together
Sulfates, as kosmotropes, create exclusion zone
gel-like environment to protect cell

Cell

Cholesterol sulfate supplies

oxygen, sulfur, cholesterol,energy
all the tissues
Sulfate is synthesized from sulfide in
skin and blood stream utilizing energy
in sunlight

Protects from UV damage and keeps

microbes out

Endothelial Nitric Oxide Synthase

(eNOS) performs the magic

The skin is a solar powered

battery!

Cells in the skin produce vitamin D3

sulfate upon exposure to the sun

The precursor to vitamin D3 is 7dehydrocholesterol

Many of the alleged benefits of vitamin D3

are actually benefits of cholesterol sulfate

Protection against cancer, diabetes and

cardiovascular disease; improved immune
function

This corresponds to a 30fold increase in the use of

sunscreen

Sulfated mucopolysaccharides
(glycosaminoglycans)
Steroid sulfates
Phenol sulfates
Tyrosine sulfation
Bilirubin sulfate
Arylamine sulfates
Choline sulfate in lichens, fungi and marine
algae
Sulfolipids

*IH Goldberg, The sulfolipids. J. Lipi Res. Apr. 1961, 2(2

S. Seneff, A. Lauritzen, R. Davidson, and L.

Lentz-Marino, , .
Is Endothelial Nitric Oxide Synthase a
Moonlighting Protein Whose Day Job is
Cholesterol Sulfate Synthesis?
Implications for Cholesterol Transport,
Diabetes and Cardiovascular Disease.
Entropy 2012, 14, 2492-2530.

METS

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