Some pressing problems in biology of academic and clinical significance are not yielding to present concepts based on the hard core of the cell theory. The practice of conceiving of the cell in isolation from its environment, although so successful in establishing some recent concepts on biosynthesis and its regulation, has left unrealised broader concepts such as the organization of genetic material, cell differentiation during embryonic development and the origin of cancer.
We formulate the organization of living organisms through the characterization of the class of autopoietic systems to which living things belong. This general characterization is seen at work in a computer simulated model of a minimal case satisfying the conditions for autopoietic organization.
It is generally accepted that cells contain numerous negative feedback control systems which are frequently invoked for their ability to maintain homeostasis. There is no reason to believe that the replicating cell is an exception yet paradoxically it is a highly dynamic entity in that the levels of constituents vary with time. The inconsistency between theory and observation is easily resolvable if (a) the events of the cell cycle reflect the oscillatory behaviour of certain of the regulatory processes, and, (b) proliferation control is exerted via transitions between periodic and aperiodic (or damped periodic) states as the result of changes in the values of the parameters determining the behaviour of the system. This concept is briefly discussed in relation to: the wide variety of agents that can affect replication; the existence of distinct non-proliferative states; the continuous control of proliferation rate; variations in the sensitivity toward cell cycle inhibitory agents; senescence; the ‘loss’ of control of cell division in cancer.
The experiments were conducted to explore the possibility that formic acid could serve as a reducing agent for carbonyl compounds on the prebiotic earth, since it has been shown that formic acid is a product of numerous chemical evolution experiments. The photoreduction of solutions 0.33 M in acetaldehyde or acetone at 2537 Å in 0.167 M formic acid, sodium formate, or both formic acid and sodium formate in a nitrogen atmosphere has been conducted. The formation of the corresponding reduction product, ethanol or isopropyl alcohol, and the disappearance of the reactant were followed as a function of irradiation time by using gas chromatography. Product confirmation was done by NMR analysis and mass spectrometry.
Carbon dioxide can be incorporated into amino acids under conditions simulating the radiation environment of Mars. The mechanism apparently involves carboxyl exchange and may occur with other organic compounds as well. The reaction may play a role in maintaining CO2 equilibrium on the Martian surface.
Time intervals of 12 records of bursting discharges in Aplysia neurons were analysed by digital computer to determine the interrelations between the burst period, the interburst interval and the burst duration. The effects of membrane potential changes on the parameters of bursting discharges were examined also. A low correlation was found between burst duration and burst period in the majority of cases, and this was interpreted as an indication of probable independence between the mechanisms governing these parameters. Also, a specific temporal organization of interspike intervals seems to be present in each type of neuron. The results suggest that the mechanism governing the burst period is characterized by a slow membrane potential oscillation resembling that observed in bursting neurons when actions potentials are blocked by tetrodotoxin. The burst duration would be determined by the response of the neuron to suprathreshold depolarization.
Amongst the available graph theories the one making use of “bond graphs” has been considered the most suitable in network thermodynamics for representing a wide range of physico-chemical processes in the form of networks.
The activation of glycine to yield glycyl hydroxamate has been studied in the absence of enzymes. Activation with ATP in aqueous solution requires only a divalent metal cation. ATP is far more active than other nucleoside triphosphates; AMP and pyrophosphate are inactive. The pH optimum is 4 to 5; activation at pH 7 is most enhanced in the presence of proteinoid microspheres.
The basic issue of this paper is the investigation and description of the multicellular and subcellular systems which are essentially involved in the development (organization) of organismic behaviour, and the modelling of the structure of interconnectedness of these system.
Animal tissue extracts show a derivative (alternating-current) polarographic waves at −1.7 V (B-wave) and frequently a second wave at −1.4 V (A-wave) against S.C.E.
The phosphorylation of thymidine has been studied in a model evaporating pond environment. Evaporation of dilute solutions of thymidine and ammonium oxalate in the presence of apatite leads to the synthesis of nucleotides. The presence of organic compounds such as cyanamide or urea substantially increases the yields of products. Solutions of cyanogen, when heated and evaporated in the presence of nucleoside and apatite, produce similarly high yields of nucleotide without added condensing agents. The mechanism of the reaction appears to involve the hydrolysis of cyanogen to produce ammonium oxalate and urea, among other products. An evolutionary continuum leading from the cosmically abundant CN moiety to the establishment of conditions favorable for phosphorylation on the primitive earth is suggested.
Polarographically active nitrogen containing carbohydrate (“Ch-” and “C-substances”), present in rapidly proliferating normal and cancerous animal and plant tissues appears to be identical. The same substances were also found in the extracts of “germ cells”.
It has been suggested by Sel'kov and by the author that the malignant transformation may be due to a transition between alternative steady states at the metabolic level without necessarily involving a genetic defect. It had previously been indicated by the author that the properties of a cell can be expected to reflect its pattern of temporal organisation. These two aspects are now considered in relation to one another by examining the behaviour of a coupled enzymic system (involving substrate inhibition characteristics) which is capable of exhibiting multiple steady states. It is shown that the phasing of the synthesis of the enzymes concerned during the cell cycle (normal or disturbed as a result of the action of agents) can determine whether a transition occurs or not and also if it is stable or not. It is also pointed out that the phasing between the fluctuations in the levels of inhibitors and activators of the enzymes involved and in their isozyme patterns can be equally significant in these respects. Hence a transition can be effected by a variety of agents acting at diverse sites within or without the cell. The transition is discussed as an example of a process that may be involved in the malignant transformation. It is emphasized that once a transition has occurred in a cell, there is no reason to presuppose that the new state cannot be inherited by the progeny of that cell, despite the removal of the causative agent: reversal is possible, however, and is discussed as an explanation for abortive oncogenic transformation. Other aspects briefly discussed in relation to metabolic steady state transitions include - the random nature and distribution of transformation in culture; the heterogeneity of transformed cells; resistance to transformation; the significance of the timing and duration of action of an oncogenic agent; the effect of gene duplication on the ‘fixation’ of the transformation; cell death. Finally it is pointed out that the same considerations are likely to apply to other systems exhibiting multiple steady states as a result of the existence of the phenomenon of hysteresis and hence probably to genetic switch systems also.
We have attempted to confirm a recent report that kaolin adsorbs D- and L-phenylalanine enantiomers to different extents from aqueous solution at both pH 5.8 and pH 2. After establishing the gross adsorption of D,L-phenylalanine by kaolin under comparable conditions, we have endeavored to demonstrate the possible resolution (i.e. asymmetric adorption) of D,L-phenylalanine by kaolin, using as analytical criteria optical rotatory dispersion, gas chromatography and thin-layer chromatography. In contrast to observations previously reported, we could find no evidence whatsoever for the differential adsorption of D-versus L-phenylalanine by kaolin from either pH 6 or pH 2 solutions.
The frequencies of occurrence of all pairs of peptide residues were computed using a large sampling of multifunctional proteins. Deviations in the frequency of occurrence from that expected for a random distribution for each pair of residues is characterized by a structure factor S(X-Y/X). Some pairs of residues are found much more often, or much less often, than would be expected on a random basis. No definite conclusions can be made about the function of any pair of peptide residues. However, some generalizations can be made concerning which residues can be expected to be partners in peptide pairs which are found more often than expected on a random basis.
Information processing, or selective dissipation, is mediated by switching elements in classical systems and by enzyme catalysis in biochemical systems. There are important differences in the character of this dissipation (from the standpoint of energy and control) in self-reproducing systems based on molecular interactions and those based on conventional computers. Conventional computers process information in a single level mode, i.e., the state of each unit of the system is accessed independently. This includes the manipulable memory units which store the computer program. In contrast, molecular self-reproducing systems process information in a hierarchical mode, based on the fact of hierarchy in molecular structure. In particular, the enzyme is described genetically at the primary level of structure (amino acid sequence) but functions at the higher, tertiary level on the basis of the interactions of many manipulable units. As a consequence it is not possible to program a biochemical system in any conventional sense. However, this is compensated by an increased capacity for accumulating appropriate information through evolution by variation and natural selection. This is possible because systems operating in the hierarchical mode are amenable to gradual modification of function. The degree of gradualness is itself an evolved property of biological molecules.
The binding of eosin Y to ribonuclease A was pH-dependent in that it occurred only at pH values lower than 5, and appeared to be correlated with a change in the ionization of the dye which had a pK of 3.5. In buffered solutions below pH 5, the extent of binding was also affected by the order of mixing, perhaps as a result of ionic strength effects. Binding did not appear to alter the sensitizing efficiency of eosin Y for the photoinactivation of ribonuclease A.
Aqueous solutions of glycine, when heated to dryness between 100 and 140 ° with simple phosphates, give rise to polyglycine and some oligopeptides. Ammonium dihydrogen phosphate and diammonium hydrogen phosphate give the best yields of polyglycine. The effect on the yields of variation in temperature, time of heating and amount of diammonium hydrogen phosphate used is also studied.
