A unifying model of the cell proliferation emphasizing plasma membrane fluxes.

The regulation of cellular growth and proliferation is perhaps the most investigated and elusive problem in cell biology and seems to be possible to solve from almost any angle of study chosen. Among the non-systemic factors that have been discussed are genetic damage, genomic control, regulation by stimulatory and inhibitory peptide factors such as EGF, chalones, and fibronectin, protein kinase activation with tyrosine phosphorylation, adenylylcyclase and cAMP, cGMP, membrane perturbations and specifically in tumours the failure of the Pasteur effect in control of glycolysis, excessive membrane ATPase activity, and excessive hydrolytic and proteolytic activities at the cell surface. This article focuses on the central role of fluxes within the plasma membrane and re-examines the possibility that changes of flux of metabolites, ions, and reducing equivalents may be the common denominator regulating cellular proliferation.

Metabolic iteration, evolution and cognition in cellular proliferation.

A model for cellular proliferation is described according to which proliferation ensues when metabolism evolves towards commitment to DNA synthesis, and inhibition of proliferation occurs when enzymic interactions are iterated within a few metabolic pathways, another limiting factor being the supply of metabolites. The model successfully describes cellular growth and division as a 'cognitive process' based on interaction within enzymic elements and the genome, and affords an explanation in these terms of some empirical phenomena which have previously been understood only as isolated observations.

A mathematical approach to cognitive processes.

A mathematical formalization of cognitive processes based on concepts previously given in Experientia is presented. Cognitive processes are described as a set of exponentially decaying interaction probabilities determined by previous interactions between different elements and an association parameter, the inverse of the cognitive stability. The interactions occur in a 'cognitive string' surrounded by a 'cognitive plasma' which carries the contextual information.

Facilitation of actin polymerization by interfilamentous factors.

The polymerization of actin in low ionic strength buffer at 0 degrees C in the presence of 0.25 mM Mg2+ was studied by viscometry, turbidity and absorbance at 232 nm. Under these conditions, significant polymerization occurred only in the viscometer and not in isotropic mixtures.

Validity of Hill's equation in an artificial actomyosin streaming system.

The rotation of an actomyosin motor, assembled from blades, one side onto which F-actin of uniform polarity was attached, suspended in a solution of heavy meromyosin (HMM), was modelled as due to sliding of HMM over the margins of the blades, whereby the work resulting from ATPase activity is used for pushing bulk fluid containing HMM from the leading surface of the blade over the force-generating filaments to the back surface, which leads to increased sliding velocity. The amount of HMM contributing to force-generation is divided into one component perpendicular to the filaments, which is diffusion-limited and regulated by a component parallel to the filaments, represented by the movement of the bulk fluid, the supply of new HMM and the observable velocity of rotation of the blade. Using Hill's equation which essentially states that the product of a virtual force and a virtual velocity is constant within the range of observable forces and velocities, the force can be expressed as velocity, giving a simple first order differential equation.

Determination of sialic acid residues in transferrin by oxidative-reductive immunoassay.

A method is described for the determination of sialic acid residues in glycoproteins displaying microheterogeneity in the sugar residue. The new method is based on combining an oxidative-reductive step with binding of the glycoprotein to an immunoadsorbent. After a mild oxidation with sodium metaperiodate the sugar is reduced with labeled sodiumborotritide.

On the stability of cognitive processes.

An empirical and mathematical model for self-organization is proposed, based on elemental properties, on unique interaction and on the combination of hierarchical elements. In the model, higher elements are stabilized by the 'cognitive' (strong) interaction of subelements, disregarding intermediate elements. This is called 'elementary reductionism' and is illustrated by the sequence quarks-elementary particles-atoms-molecules-cells-organisms- societies.

Ethanol in preweanling rats with dams: body temperature unaffected.

At an ambient temperature of 24 degrees C, the neonatal rat was found to exhibit poikilothermic characteristics if separated from the dam. On day one after birth, at one hour after separation from dams, the body temperature in rat pups was found to be identical with ambient temperature. Preweanling pups, under these circumstances, were unable to maintain a constant body temperature prior to day 19 postnatally.

The effects of ethanol exposure during the brain growth spurt in rats.

The purpose of this study was to determine whether micromorphological changes occur at a low level of ethanol exposure previously shown by us to induce alterations in synaptosomal biochemistry. The results suggest that 4 g ethanol per kg body weight daily throughout the brain growth spurt causes no significant structural changes in the cerebellum, lobule IX, at the light and electron microscopic levels. Although ethanol- and isocaloric sucrose-treated groups did not differ from each other in cumulative percent body weight gain throughout the treatment period, both groups differed significantly in this parameter from isocaloric milk-treated and "handled" control groups.

Effect of ethanol on synaptosomal sialic acid metabolism in the developing rat brain.

The total, glycoprotein-bound and glycolipid-bound sialic acid concentration, ad the activities of ecto-sialyltransferase and neuraminidase were determined in synaptosomes from preweanling ethanol-treated and control rats. The period of treatment corresponded to that of maximal synaptogenesis and peak synthesis of sialoglycocompounds (days 27-37 postconception). The average of the peak blood ethanol concentration was 271 mg/100 ml.

The use of con A Sepharose as an affinity adsorbent in a simple assay of serum sialyl and fucosyltransferase and its application in tumour diagnosis.

A considerably simplified assay for recording sialyl- and fucosyltransferase in human serum is presented. Serum samples incubated with labeled nucleotide-sugar and glycosylated endogenous acceptor molecules were adsorbed to Con A Sepharose and quantitated by scintillation counting. The results correlated with those of a much more time consuming acid precipition method, and displayed a higher diagnostic sensitivity due to the improved specificity of the method and the combined recording of the two activities.

The plasma membrane consists of two polar-nonpolar-polar leaflets.

The implications of a double polar-nonpolar-polar leaflet construction of the plasma membrane are investigated. Experimental data from transmission electron microscopic and enzymologic characterization of plasma membranes are advantageously interpreted in these terms compared to interpretation in terms of lipid bilayer. X-ray diffraction and electron spin resonance studies do not differentiate between the present and previous models for the structure of plasma membranes but electron spin resonance data that fail to indicate a statistical distribution of spin labels also fail to support the fluid mosaic model for cell membranes.

The fluid double polar-nonpolar-polar leaflet model for biological membranes.

A model for biological membranes is proposed according to which the plasma membrane consists of two functionally different polar-nonpolar-polar leaflets separated by a polar space. The binding of water-soluble proteins, integral lipoproteins and spanning proteins to a biological membrane as well as possible conformations of interphase peptides partitioned between polar and nonpolar layers are discussed. A model for the diffusion of water soluble proteins across nonpolar layers of a membrane is described.

The migrating thermodynamic quantum hypothesis for cytoplasmic streaming, sodium pumping and other cell biological phenomena, deduced from biofunctional considerations of the ultrastructure of brush border microvilli.

An attempt is made to reconcile experimental data dealing with, inter alia, cytoplasmic streaming in Characean algae, contraction in actomyosin systems. Na+- and -K+-simtulated ATPase activity and the ultrastructure of brush border microvilli. It is postulated that myosin molecules transfer energy from ATP to an actin-containing filament and that a high energy conformation is subsequently propagated along the filament.