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Biomedical subjects

J Chela-Flores

Publications and source records attributed to J Chela-Flores.

10 recordsLinked to original sources

A search for extraterrestrial eukaryotes: physical and paleontological aspects.

Physical and biochemical aspects of a proposed search for extraterrestrial eukaryotes (SETE) are considered. Such a program should approach the distinction between a primitive eukaryote and an archaebacteria. The emphasis on gene silencing suggests a possible assay suitable for a robotic investigation of eukaryoticity, so as to be able to decide whether the first steps towards eukaryogenesis have been taken in an extraterrestrial planet, or satellite. The experiment would consist of searching for cellular division and the systematic related delay in replication of heterochromatic chromosome segments. It should be noticed that the direct search for a membrane-bounded set of chromosomes does not necessarily determine eukaryotic identity, as there are prokaryotes that have membrane-bounded nucleoids. A closer look at the protein fraction of chromatin (mainly histones) does not help either, as there are some eukaryotes that may lack histones; there are also some bacteria as well as archaebacteria with histone-like proteins in their nucleoids. Comments on the recent suggestion of possible environments for a SETE program are discussed: the deep crust of Mars, and the Jovian satellite Europa, provided the existence of an ocean under its ice-covered surface is confirmed by the current Galileo mission.

Biological Evolution↗

First steps in eukaryogenesis: physical phenomena in the origin and evolution of chromosome structure.

Our present understanding of the origin and evolution of chromosomes differs considerably from current understanding of the origin and evolution of the cell itself. Chromosome origins have been less prominent in research, as the emphasis has not shifted so far appreciably from the phenomenon of primeval nucleic acid encapsulation to that of the origin of gene organization, expression, and regulation. In this work we discuss some reasons why preliminary steps in this direction are being taken. We have been led to examine properties that have contributed to raise the ancestral prokaryotic programmes to a level where we can appreciate in eukaryotes a clear departure from earlier themes in the evolution of the cell from the last common ancestor. We shift our point of view from evolution of cell morphology to the point of view of the genes. In particular, we focus attention on possible physical bases for the way transmission of information has evolved in eukaryotes, namely, the inactivation of whole chromosomes. The special case of the inactivation of the X chromosome in mammals is discussed, paying particular attention to the physical process of the spread of X inactivation in monotremes (platypus and echidna). When experimental data is unavailable some theoretical analysis is possible based on the idea that in certain cases collective phenomena in genetics, rather than chemical detail, are better correlates of complex chemical processes.

Animals↗

Towards the theoretical bases of the folding of the 100-A nucleosome filament.

This paper attempts to model DNA packaging at the various stages of ever-increasing DNA folding, from the 100-A nucleosome filament to various further stages leading up to the metaphase chromosome. We have assumed that a phase transition has induced chromatin into a condensed mode. The mean-field model allows the simultaneous discussion of chromatin with packing ratio eta and DNA replication at various stages of folding. We derive a formula correlating (during the S phase of the cell cycle) the DNA polymerase velocity rf (measured in nucleotides per minute) in a relation of inverse proportionality with the degree of DNA packaging: rf = lambda eta-1/2. This model suggests that in the heterochromatic regions of chromatin there is reduced activity of DNA polymerases. We discuss the possible relevance of our model to late replicating telomeres in yeast and several higher eukaryotes.

Animals↗

Towards the molecular bases of polymerase dynamics.

One aspect of the strong relationship that is known to exist between the processes of DNA replication and transcription is manifest in the coupling of the rates of movement of the replication fork (rf) and RNA polymerase (rt). We address two issues concerning the largely unexplored area of polymerase dynamics: (i) The validity of an approximate kinematic formula linking rf and rt suggested by experiments in which transcription is inhibited in some prokaryotes with the antibiotic streptolydigin, and (ii) What are the molecular bases of the kinematic formula? An analysis of the available data suggests possible molecular bases for polymerase dynamics. In particular, we are led to a hypothesis: In active chromatin rt may depend on the length (lambda t) of the transcript of the primary messenger RNA (pre-mRNA). This new effect is subject to experimental verification. We discuss possible experiments that may be performed in order to test this prediction.

Animals↗

Influence of chromatin molecular changes on RNA synthesis during embryonic development.

Two aspects of the chromatin repeat length (rl) are discussed: (i) Why is rl longer for slowly dividing cells than in rapidly dividing cells?, and (ii) Why is the temporal evolution of rl a decreasing function of time (t) in mammalian cortical neurons, whereas it is an increasing function of t for granule cells around the time of birth? These questions are discussed in terms of a hypothesis which assumes a correlation between deoxyribonucleic acid (DNA) packaging, transcription, and replication.

Animals↗

On the possible effects of homeostatic shifts in human embryonic development.

Possible etiological factors of congenital malformations as well as of human trisomies are considered in the framework of the repressor hypothesis. In this approach gene expression is envisaged from the point of view of the functional variations of the total activation energy for normal gene expression in homeostatic equilibrium. We restrict our attention to variations of the total activation energy under the effect of temperature gradients. We discuss the evidence that hyperthermia may be an etiological factor for trisomies in humans.

Animals↗

A kinetic thermodynamic phenomenological approach to genetic expression of heat-shock proteins.

The approach of viewing complex biochemical phenomena as autocatalytic relaxation processes has been introduced previously (Liquori & Tripiciano, 1980; Liquori & Florio, 1985). In the present work this formalism is extended from its original framework regarding cell growth, to the problem of genetic expression. The case of the heat-shock response in organisms ranging from man to bacteria is discussed. Finally, we give some biochemical examples in which the new approach underlines evident temporal co-operativity.

Gene Expression Regulation↗

Evolutionary implication of genetic code deviations.

We formulate the following hypothesis: Life's origin may have occurred during the lower Archaean at a time when the environmental temperature was higher than it is at present. Preliminary consequences of this hypothesis are studied from the point of view of molecular evolution. We restrict our attention to implications regarding the genetic code. We conclude that alternative assignment of termination codons may be understood in terms of: (a) the elevated temperatures to which the progenote may initially have been exposed; and (b) the subsequent response of its genome to the opportunity provided by the eventual loss of hyperthermal genetic expression during a thermal transition (TT) period, which was triggered off by the evolution of the dynamic Earth.

Biological Evolution↗

Towards a collective biology of the gene.

Two features of heterochromatin: heteropycnosis (high values of chromatin condensation), and repressed genetic expression, force upon us the use of cooperative variables, rather than molecular ones. In particular a "repressor" hypothesis is formulated, in which a useful parameter is clearly identified. This enables us to discuss the synchronized repression of a large number, n, of genes (as in the case of the Barr body, in which n is larger than 100). The hypothesis is documented with phenomena known to occur in active chromatin. Possible tests are suggested.

Chromosomes↗

Evolution as a collective phenomenon.

The quantum mechanical description of biosystems, which emphasise their dielectric properties and the presence of an uncorrelated condensate of phonons, (in analogy with Bose-Einstein condensation), is extended to a description of biosystems, in which the condensed phonons show anomalous averages, (in analogy with superconductivity). The theory is used to show that a quantum ultraviolet defence mechanism may have been present at the origin of chemical evolution, removing a difficulty in the standard scenario. Suggestions are made as to how to proceed experimentally to show the existence of a correlated phonon condensate.

Biological Evolution↗