"Causality in Complex Systems: Biology of the Cell Nucleus".

John Frenster, Editor, Euchromatin Network.
E-mail:  frenster@euchromatin.net
Phone: +1-650-367-6483

The single cell is a complex system, especially in its control system, the cell nucleus, and including each of the subset control systems in chromosomes, chromatin, genome, genes, DNA, RNA, ribosomes, and signal proteins, (Wagner A, 1999 [1] ).

Now that we are engaged in understanding the cell nucleus and RNA, we are increasingly confronted with the question, what is the specific relationship between the RNA cause and the resulting effect within the cell nucleus?

Causality is an epistemological term, concerning the relationship between an agent and its effect in a particular event. Usually the agent precedes the effect in time, and the effect requires that the agent had been present, by itself, or by a surrogate agent.

If the agent and the effect are under study in a given event, a simple classification has been developed to describe the relationship of the agent to the effect:

1. The presence of the agent is necessary and sufficient for the effect to be observed. (Prime-Causal).

2. The presence of the agent is necessary but not sufficient for the effect to be observed. (Co-Causal).

3. The presence of the agent is sufficient but not necessary for the effect to be observed. (Ambi-Causal).

4. The presence of the agent is neither necessary nor sufficient for the effect to be observed. (Non-Causal).

When two or more different agents are competing in a given event to a given effect, the competition can be described in terms of the each agent's speed, amount, concentration, duration, turn-over, affinities, efficiency, and thermodynamics of reaction needed for the effect to be observed [2]. (Competitive Causal).

The causal agents may also be affected by the sum context of other non-causal conditions found in the event.

When two or more agents are found to be causal for a given effect in a given event, their relative contributions to the effect can be measured by Factor Analysis, an analytical process of transforming statistical data (as measurements) into linear combinations of usually independent variables [3].

If the causal agents are not independent of each other, they may then, in fact, be redundant members of a larger system or pathway that may diverge away from the studied effect. In addition, many agents have more than one role within the cell economy, yielding fresh molecular evidence for multitasking among active molecules. Redundancy (two agents, one effect) and multitasking (one agent, two effects) admitedly make precise molecular causal definitions more difficult, and they are quite frequent within the cell nucleus.

Finally, concerning RNA effects on DNA transcription, RNA can function as a primary activator of transcription during a direct interaction with template DNA, or RNA can function as a secondary activator of transcription during a direct interaction with other repressor molecules, in which it achieves repression of a repressor [4].

All of our scientific studies on cell effects are dependent upon our observations, which may reflect random as well as  determined events, and so must be studied under replicated circumstances by replicated observers within a reasonable period of time. The individual significance of each observation can only be determined statistically by an analysis of variance [3].

References:

1. Wagner A, "Causality in Complex Systems", Biology and Philosophy, vol. 14, pp. 83-101 (1999).
http://samba.unm.edu/~wagnera/BiologyPhilosophy1999.pdf

Selected Publications of Prof. Andreas Wagner:  http://samba.unm.edu/~wagnera/Publications.html

2. Stoner DS, Rinkevich B, and Weissman IL, "Heritable germ and somatic cell lineage competitions in chimeric colonial protochordates", Proc. Natl. Acad. Sci. USA, vol. 96, no. 16, pp. 9148-9153 (August 3, 1999).
http://www.pnas.org/cgi/content/full/96/16/9148

3. Bibbins-Domingo K, Lin F, Vittinghoff E, Barrett-Connor E, Hulley SB, Grady D, Shlipak MG, "Predictors of Heart Failure Among Women With Coronary Disease", Published online before print September 7, 2004
(Circulation vol. 110, no.11, pp 1424-1428 (September, 2004).
http://circ.ahajournals.org/cgi/content/full/110/11/1424

4. Frenster JH, "Mechanisms of Repression and De-Repression within Interphase Chromatin", In Vitro, vol. 1, pp. 78-101 (1965).

Further Topics in:  Euchromatin,  active DNA, and  RNA  ribo-regulators:

Links to Euchromatin Activator RNA Reviews:
Links to Euchromatin Activator RNA Research:
Links to Ultrastructural Probes of DNase I-Sensitive Sites:
Links to RNA as a Therapeutic Agent:
Links to Hodgkin Lymphoma Immuno-Pathology:
Links to Activated T-Lymphocyte Immunotherapy:
Links to Medical Systems Biology:
Links to Selective Gene Transcription:
Links to RNA-Induced Epigenetics:
Links to RNA-Induced Embryogenesis:
Links to RNA and Biological Causality:
Links to Reprogramming and Neoplasia:

A Brief History of Activator RNA:

"Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA". (PowerPoint Presentation).

For Further Information and Feedback:
E-mail: frenster@euchromatin.net
Phone:   +1 650 367 6483