Epigenetic information for gene expression (Was: Question)

On Tue, 10 Feb 2004 00:14:46 +0000 (UTC), [email hidden] (CNCabej)

Quoted message said:

On Sun. 8 Feb 2004 00:05:30 + 0000 (UTC) r norman wrote: On Sat. 7 Feb 2004 0:52:56 + 000 (UTC),
[email hidden] (CNCabej) wrote:
.......................................................................... ............

Quoted message said:

Quoted message said:

As we well know, pineal cells do not receive the stimulus (day-night

cycles); they are invariably in darkness. That stimulus is received by retinal neurons (they,
nevertheless, do not produce melatonin, which code it in the form ofspecific electrical signals
(this is the information on the nature of the stimulus). But this information is no "intelligible"
to genes. This is why it is once more processed in the complex melatonin circuit, which releases a
chemical signal that via signal transduction pathways affects expression of genes responsible for
melatonin synthesis in pineal cells<<
.......................................................................... .............

Quoted message said:

Quoted message said:

It is not the external stimulus per se , but the chemical output

(=information) generated by processing of the stimulusin the neural circuit that via the respective
signal transduction pathways reaches the genes responsible for the synthesis of melatonin, which is
intelligible to (i.e. contains informatio for) activating those genes. This information is processing-
dependent, hence epigenetic; it does not exist but is computationally generated i response to
external/internal stimuli.

Let me try an analogy from linguistics (my hobby). When I spell Messapian (an ancient indoeuropean
language spoken in southern Italy more than 2 thoussand years ago) the word "bila" it conveys no
information to you as a receiver, although it did for the Messapians. Now, I make it inteligible to
you by translating it into the English "daughter". Similarly, the neural circuits "translate" the
external stimulus, which is "senseless" to genes, into a specific epigenetic information for their
activation/inactivation. Do you agree?<<
........................................................................... r n:

Quoted message said:

I still think that "information translation" is not a proper way of looking at

the situation. Light entering the eye causes genes to be expressed in specific cells. There are a
lot of intermediate steps, but there is a demonstrable chain-and-effect events that can be
described linking stimulus to response. It is not necessary to talk in terms of information
generation, merely in terms of "event A causes event B causes event C causes event D causes...
causes eventZ. Light in a rod or cone cell is translatedinto electrical potential, but that
involves a whole series of intermediate steps. Changes in electrical potential inrod and cone cells
in the retina cause release of synaptic transmitter onto melatonin secreting cells in the pineal,
but that involves a whole series of intermediate steps. Synaptic transmitter binding to receptors
on melatonin secreting cells in the pineal activate genes in the cell nucleus, but that involves a
whole series of intermediate steps.

The problem is one of cell physiology, not of information translation.<

If I got it right, you argue that the fact that "a whole series of intermediate steps" are involved
in the signal cascade from the external stimulus to genes, this fact per se, excludes the
possibility of any information being transmitted via the cascade. Without the necessary
explanation, this idea seems hardly defensible to me.

Applying the same criterium to the process of gene expression, which also involves many
"intermediate steps", would lead us to the conclusion that no genetic information is transmitted
from genes to proteins, which is no less difficult to defend.

You correctly describe those pathways as chains of events where "event A causes event B causes
event C causes event D causes....causes event Z." where the effect of each element on the
downstream element (secretion of hypothalamic TRH, e.g. stimulates the pituitary TSH, stimulates
thyroid hormone, etc.) is determined by stereochemical and thermodynamical properties of the
interacting molecules and of the environment.

What takes place in the case of melatonin synthesis is different in an essential respect. The
external stimulus per se is neutral to any known pathway in metazoans, it can't activate any
specific gene. In order that it serve as a cue, the input on the stimulus must first be processed
in the retinal neurons (a computational process), which codes it in the form of a specific pattern
of electrical signals. But the "electrically coded" stimulus is nothing less than information on
the stimulus. It is different from the stimulus itself in the same way that my name identifies me
but is not identical with me.

The information generated by processing the stimulus is not determined by the stimulus itself but
by computational properties in which the stimulus is processed. That information is not stimulus-
dependent but processing-dependent.

The information contained in the electrical code is still "unintelligible" to genes in the meaning
that it can't activate the signal transduction pathway for expression of melatonin genes. It must
be further processed in the described complex neural circuit, which ultimately transforms it in a
chemical signal that can activate that signal transduction pathway in all the "intermediate steps"
you talk of. This ultimate chemical form that makes possible the expression of melatonin genes, is
different from the stimulus itself; it is information on that stimulus that is generated (not
preexisting) in the neural circuits. No melatonin genes can be expressed without this information.

This processing of stimuli in the CNS is necessary not only for external stimuli, but for most of
the internal stimuli, since because of the blood-brain barrier most of the chemical signals
(protein hormones, growth factors and other secreted proteins) have no access to the CNS. It makes
it possible for them than in response to the same internal stimuli to activate genes that are not
expressed in other types of cells.

We seem to be talking at such cross purposes that we cannot understand each other. I find your
discussion of the requirement for information processing (as in your final paragraph) to be
essentially incomprehesible.

I do not understand why you are making a simple situation very complicated. If you chill me for a
substantial period of time, my thyroid gland secretes thyroxin. That process may also be associated
with the transcription of genes coding for proteins in the thyroxin synthesis pathway. If you shine
light into my eyes, it affects the way that my pineal gland secretes melatonin. That process may
also be associated with the transcription of genes coding for proteins in the melatonin synthesis
pathway. There is no conceptual difference. There is absolutely NOTHING in the nervous system that
codes for "thyroxin" or for "melatonin" or for "transcribe this particular gene" or anything at all
like that. All that happens is that a chemical binds to a receptor in the membrane of the thyroid or
pineal gland cell and makes that cell "do its thing". That "thing" may involve gene transcription,
or maybe not. Whatever, the stimulus simply "doesn't care" what the target cell does with the
signal. The signal, in fact, doesn't carry any information other than "I have a message for you". It
is completely up to the target cell to "know" how to respond.

On Wed, 11 Feb 2004 00:46:11 +0000 (UTC) r norman rsn_@_comcast.net wrote:

N.C. wrote: ..............

Quoted message said:

Quoted message said:

r n:

Quoted message said:

I still think that "information translation" is not a proper way of looking

at

Quoted message said:

the situation. Light entering the eye causes genes to be expressed in specific cells. There are a
lot of intermediate steps, but there is a demonstrable

chain-and-effect

Quoted message said:

events that can be described linking stimulus to response. It is not

necessary

Quoted message said:

to talk in terms of information generation, merely in terms of "event A

causes

Quoted message said:

event B causes event C causes event D causes... causes eventZ. Light in a

rod

Quoted message said:

or cone cell is translated into electrical potential, but that involves a

whole

Quoted message said:

series of intermediate steps. Changes in electrical potential in rod and cone cells in the retina
cause release of synaptic transmitter onto melatonin secreting cells in the pineal, but that
involves a whole series of

intermediate

Quoted message said:

steps. Synaptic transmitter binding to receptors on melatonin secreting

cells

Quoted message said:

in the pineal activate genes in the cell nucleus, but that involves a whole series of
intermediate steps.

The problem is one of cell physiology, not of information translation.<

Quoted message said:

Quoted message said:

If I got it right, you argue that the fact that "a whole series of

intermediate

Quoted message said:

steps" are involved in the signal cascade from the external stimulus to

genes,

Quoted message said:

this fact per se, excludes the possibility of any information being

transmitted

Quoted message said:

via the cascade. Without the necessary explanation, this idea seems hardly defensible to me.

Applying the same criterium to the process of gene expression, which also involves many
"intermediate steps", would lead us to the conclusion that no genetic information is transmitted
from genes to proteins, which is no less difficult to defend.

You correctly describe those pathways as chains of events where "event A

causes

Quoted message said:

event B causes event C causes event D causes....causes event Z." where the effect of each element
on the downstream element (secretion of hypothalamic TRH, e.g. stimulates the pituitary TSH,
stimulates thyroid hormone, etc.)

is

Quoted message said:

determined by stereochemical and thermodynamical properties of the

interacting

Quoted message said:

molecules and of the environment.

What takes place in the case of melatonin synthesis is different in an essential respect. The
external stimulus per se is neutral to any known

pathway

Quoted message said:

in metazoans, it can't activate any specific gene. In order that it serve as

a

Quoted message said:

cue, the input on the stimulus must first be processed in the retinal

neurons

Quoted message said:

(a computational process), which codes it in the form of a specific pattern

of

Quoted message said:

electrical signals. But the "electrically coded" stimulus is nothing less

than

Quoted message said:

information on the stimulus. It is different from the stimulus itself in the same way that my name
identifies me but is not identical with me.

The information generated by processing the stimulus is not determined by

the

Quoted message said:

stimulus itself but by computational properties in which the stimulus is processed. That
information is not stimulus-dependent but

processing-dependent.

Quoted message said:

The information contained in the electrical code is still "unintelligible"

to

Quoted message said:

genes in the meaning that it can't activate the signal transduction pathway

for

Quoted message said:

expression of melatonin genes. It must be further processed in the described complex neural
circuit, which ultimately transforms it in a chemical signal that can activate that signal
transduction pathway in all the "intermediate steps" you talk of. This ultimate chemical form that
makes possible the expression of melatonin genes, is different from the stimulus itself; it is
information on that stimulus that is generated (not preexisting) in the

neural

Quoted message said:

circuits. No melatonin genes can be expressed without this information.

This processing of stimuli in the CNS is necessary not only for external stimuli, but for most of
the internal stimuli, since because of the

blood-brain

Quoted message said:

barrier most of the chemical signals (protein hormones, growth factors and other secreted
proteins) have no access to the CNS. It makes it possible for them than in response to the same
internal stimuli to activate genes that

are

Quoted message said:

not expressed in other types of cells.

We seem to be talking at such cross purposes that we cannot understand each other. I find your
discussion of the requirement for information processing (as in your final paragraph) to be
essentially incomprehesible.

I do not understand why you are making a simple situation very complicated. If you chill me for a
substantial period of time, my thyroid gland secretes thyroxin. That process may also be associated
with the transcription of genes coding for proteins in the thyroxin synthesis pathway. If you shine
light into my eyes, it affects the way that my pineal gland secretes melatonin. That process may
also be associated with the transcription of genes coding for proteins in the melatonin synthesis
pathway. There is no conceptual difference. There is absolutely NOTHING in the nervous system that
codes for "thyroxin" or for "melatonin" or for "transcribe this particular gene" or anything at all
like that. All that happens is that a chemical binds to a receptor in the membrane of the thyroid
or pineal gland cell and makes that cell "do its thing". That "thing" may involve gene
transcription, or maybe not. Whatever, the stimulus simply "doesn't care" what the target cell does
with the signal. The signal, in fact, doesn't carry any information other than "I have a message
for you". It is completely up to the target cell to "know" how to respond.

Quoted message said:

Let me try once again to show you the "conceptual" difference between the classical way of gene
expression and the expression of genes in neural tissues? In the classical mode of gene expression,
the effect of the stimulus is determined by stereochemical and thermodynamical properties of the
stimulus and the respective pathway. Unlike that, the activation/inactivation of genes in the CNS
does not depend on the stereochemical and thermodynamical properties of the stimulus but on the
computational properties of the neural circuit that processes the stimulus: in response to the same
external stimulus ( with the same stereochemical and thermodynamical properties) the CNS is able to
manipulatively and adaptively activate different genes (examples bound). This does not happen
anywhere else in the body. It is the processing of the stimulus in neural circuits that makes
possible "manipulative" activation in the CNS of genes (such as melatonin and thyroxin you mention)
that can't be activated in other types of cells.

You say that "All that happens is that a chemical binds to a receptor in the membrane of the thyroid
or pineal gland cell and makes the cell "do its thing"". Unfortunately, this is neither "all" nor
the essential that happens. In both examples you see just the proximal link in a long cascade,
ignoring the series of signals and especially the "essential" processing of those stimuli (chill and
darkness) in neural circuits, without which neither thyroxin nor melatonin is produced. You know
better than me that chill applied to thyroid won't make it synthesize thyroxin (only hypothalamic
TRH will, which in turn is synthesized according to signals generated computationally by processing
of the stimulus in neural circuits in other parts of the brain). The same I have explained for
melatonin synthesis.

What makes unique the thyroid in producing thyroxin and pineal in producing melatonin is the
INFORMATION (computationally generated in neural circuits) they receive on the external stimulus
(not the stimulus itself). Deprived of this INFORMATION generated in neural circuits, no other type
of cell in the animal body is capable of synthesizing those chemicals.

Is this manipulative (processing-dependent) activation/inactivation of genes in the CNS requiring
information ON THE STIMULUS "essentially different both in the the mechanism that makes it possible
and the outcome?

On Fri, 13 Feb 2004 16:49:38 +0000 (UTC), [email hidden] (CNCabej)

Quoted message said:

On Wed, 11 Feb 2004 00:46:11 +0000 (UTC) r norman rsn_@_comcast.net wrote:

N.C. wrote: ..............

Quoted message said:

Quoted message said:

r n:

>I still think that "information translation" is not a proper way of looking

at

Quoted message said:

the situation. Light entering the eye causes genes to be expressed in specific cells. There are a
lot of intermediate steps, but there is a demonstrable

chain-and-effect

Quoted message said:

events that can be described linking stimulus to response. It is not

necessary

Quoted message said:

to talk in terms of information generation, merely in terms of "event A

causes

Quoted message said:

event B causes event C causes event D causes... causes eventZ. Light in a

rod

Quoted message said:

or cone cell is translated into electrical potential, but that involves a

whole

Quoted message said:

series of intermediate steps. Changes in electrical potential in rod and cone cells in the retina
cause release of synaptic transmitter onto melatonin secreting cells in the pineal, but that
involves a whole series of

intermediate

Quoted message said:

steps. Synaptic transmitter binding to receptors on melatonin secreting

cells

Quoted message said:

in the pineal activate genes in the cell nucleus, but that involves a whole series of
intermediate steps.

The problem is one of cell physiology, not of information translation.<

Quoted message said:

Quoted message said:

If I got it right, you argue that the fact that "a whole series of

intermediate

Quoted message said:

steps" are involved in the signal cascade from the external stimulus to

genes,

Quoted message said:

this fact per se, excludes the possibility of any information being

transmitted

Quoted message said:

via the cascade. Without the necessary explanation, this idea seems hardly defensible to me.

Applying the same criterium to the process of gene expression, which also involves many
"intermediate steps", would lead us to the conclusion that no genetic information is transmitted
from genes to proteins, which is no less difficult to defend.

You correctly describe those pathways as chains of events where "event A

causes

Quoted message said:

event B causes event C causes event D causes....causes event Z." where the effect of each element
on the downstream element (secretion of hypothalamic TRH, e.g. stimulates the pituitary TSH,
stimulates thyroid hormone, etc.)

is

Quoted message said:

determined by stereochemical and thermodynamical properties of the

interacting

Quoted message said:

molecules and of the environment.

What takes place in the case of melatonin synthesis is different in an essential respect. The
external stimulus per se is neutral to any known

pathway

Quoted message said:

in metazoans, it can't activate any specific gene. In order that it serve as

a

Quoted message said:

cue, the input on the stimulus must first be processed in the retinal

neurons

Quoted message said:

(a computational process), which codes it in the form of a specific pattern

of

Quoted message said:

electrical signals. But the "electrically coded" stimulus is nothing less

than

Quoted message said:

information on the stimulus. It is different from the stimulus itself in the same way that my
name identifies me but is not identical with me.

The information generated by processing the stimulus is not determined by

the

Quoted message said:

stimulus itself but by computational properties in which the stimulus is processed. That
information is not stimulus-dependent but

processing-dependent.

Quoted message said:

The information contained in the electrical code is still "unintelligible"

to

Quoted message said:

genes in the meaning that it can't activate the signal transduction pathway

for

Quoted message said:

expression of melatonin genes. It must be further processed in the described complex neural
circuit, which ultimately transforms it in a chemical signal that can activate that signal
transduction pathway in all the "intermediate steps" you talk of. This ultimate chemical form
that makes possible the expression of melatonin genes, is different from the stimulus itself; it
is information on that stimulus that is generated (not preexisting) in the

neural

Quoted message said:

circuits. No melatonin genes can be expressed without this information.

This processing of stimuli in the CNS is necessary not only for external stimuli, but for most of
the internal stimuli, since because of the

blood-brain

Quoted message said:

barrier most of the chemical signals (protein hormones, growth factors and other secreted
proteins) have no access to the CNS. It makes it possible for them than in response to the same
internal stimuli to activate genes that

are

Quoted message said:

not expressed in other types of cells.

We seem to be talking at such cross purposes that we cannot understand each other. I find your
discussion of the requirement for information processing (as in your final paragraph) to be
essentially incomprehesible.

I do not understand why you are making a simple situation very complicated. If you chill me for a
substantial period of time, my thyroid gland secretes thyroxin. That process may also be
associated with the transcription of genes coding for proteins in the thyroxin synthesis pathway.
If you shine light into my eyes, it affects the way that my pineal gland secretes melatonin. That
process may also be associated with the transcription of genes coding for proteins in the
melatonin synthesis pathway. There is no conceptual difference. There is absolutely NOTHING in the
nervous system that codes for "thyroxin" or for "melatonin" or for "transcribe this particular
gene" or anything at all like that. All that happens is that a chemical binds to a receptor in the
membrane of the thyroid or pineal gland cell and makes that cell "do its thing". That "thing" may
involve gene transcription, or maybe not. Whatever, the stimulus simply "doesn't care" what the
target cell does with the signal. The signal, in fact, doesn't carry any information other than "I
have a message for you". It is completely up to the target cell to "know" how to respond.

Quoted message said:

Let me try once again to show you the "conceptual" difference between the classical way of gene
expression and the expression of genes in neural tissues? In the classical mode of gene expression,
the effect of the stimulus is determined by stereochemical and thermodynamical properties of the
stimulus and the respective pathway. Unlike that, the activation/inactivation of genes in the CNS
does not depend on the stereochemical and thermodynamical properties of the stimulus but on the
computational properties of the neural circuit that processes the stimulus: in response to the same
external stimulus ( with the same stereochemical and thermodynamical properties) the CNS is able to
manipulatively and adaptively activate different genes (examples bound). This does not happen
anywhere else in the body. It is the processing of the stimulus in neural circuits that makes
possible "manipulative" activation in the CNS of genes (such as melatonin and thyroxin you mention)
that can't be activated in other types of cells.

You say that "All that happens is that a chemical binds to a receptor in the membrane of the
thyroid or pineal gland cell and makes the cell "do its thing"". Unfortunately, this is neither
"all" nor the essential that happens. In both examples you see just the proximal link in a long
cascade, ignoring the series of signals and especially the "essential" processing of those stimuli
(chill and darkness) in neural circuits, without which neither thyroxin nor melatonin is produced.
You know better than me that chill applied to thyroid won't make it synthesize thyroxin (only
hypothalamic TRH will, which in turn is synthesized according to signals generated computationally
by processing of the stimulus in neural circuits in other parts of the brain). The same I have
explained for melatonin synthesis.

What makes unique the thyroid in producing thyroxin and pineal in producing melatonin is the
INFORMATION (computationally generated in neural circuits) they receive on the external stimulus
(not the stimulus itself). Deprived of this INFORMATION generated in neural circuits, no other type
of cell in the animal body is capable of synthesizing those chemicals.

Is this manipulative (processing-dependent) activation/inactivation of genes in the CNS requiring
information ON THE STIMULUS "essentially different both in the the mechanism that makes it possible
and the outcome?

I still think we are so far apart that we cannot understand each other. I have a great deal of
difficulty with statements like "the effect of the stimulus is determined by stereochemical and
thermodynamical properties of the stimulus" .

Let me try to be clear. Pineal gland cells are highly differentiated by whatever developmental
processes produce those cells. As a result, they express the genes involved in melatonin synthesis
and are capable of secreting melatonin. That is what I referred to as "their thing". Neural
computation has absolutely nothing to do with it. Other cells express different genes and make
different proteins and secretory products. When you stimulate a pineal gland cell, it "does its
thing" which is actually to secrete melatonin. The computational properties of neurons have nothing
whatsoever to do with it.

In fact, the stmulation of the pineal is through the sympathetic nervous system. That is, if you
drop norepinephrine onto the pineal gland or artificially stimulate the superior cervical ganglion,
the gland will release melatonin just as effectively as if you stopped shining light into the eye.
The nervous system "calculates" only that during daylight it should refrain from sending action
potentials to the superior cervical ganglion destined for the pineal and to resume those action
potentials during the night time. Nowhere does the nervous system calculate just how to activate any
specific genes or how to secrete any specific chemical.