A mechanism for early branching in lung morphogenesis

The lung is a highly branched fluid-filled structure, that develops by repeated dichotomous branching of a single bud off the foregut, of epithelium invaginating into mesenchyme. Incorporating the known stress response of developing lung tissues, we model the developing embryonic lung in fluid mechanical terms. We suggest that the repeated branching of the early embryonic lung can be understood as the natural physical consequence of the interactions of two or more plastic substances with surface tension between them. The model makes qualitative and quantitative predictions, as well as suggesting an explanation for such observed phenomena as the asymmetric second branching of the embryonic bronchi.     

A possible molecular mechanism for mammalian aging

The following model of aging is proposed: 1) defective proteins with anomalous primary structures are synthesized sometimes; 2) these defective proteins are precipitated in cells and intercellular spaces; 3) the precipitated proteins block them up under the influence of radicals; 4) a decrease of cell functional ability below some level results in the destruction of the organism regulation function. A formula is concluded connecting the life span (Tlife) with DNA-repair velocity (Vrep) and time of protein exchange (Tex): Tlife = (1/3).K.(Vper/Vdum).(Tfix + Tex), where K-admitted share of fixated proteins (fixated/native), Vdam-damage velocity, Tfix-fixation time of defective proteins. This analytical dependence was probed on literature data for man, elephant, cow, rabbit, guinea pig, golden hamster, rat, mouse and shrew. Tfix is shown to equal 5 divided by 10 days. A good agreement between the theoretical dependence Tlife(Tex) and literature data was obtained with the exception of the data for man.     

A possible mechanism for the Na,K-ATPase

A model previously described for the Ca²⁺ pump of sarcoplasmic reticulum has been modified in a thought experiment so that it has the properties of a Na,K-adenosinetriphosphatase (ATPase). When the two Ca²⁺-specific sites are changed into three Na⁺-specific sites, and the channel which opens in the actively transporting conformation made univalent- instead of divalent-cation-selective, the model has the properties of the Na-ATPase which is observed on red cell membranes in the absence of both Na⁺ and K⁺ externally. As in the model for the Ca-ATPase the driving force for transport is generated by a change in solvent structure so that a preformed ionic equilibrium is displaced in favour of less-highly hydrated species; in this case highly hydrated Mg²⁺ ions displace the less highly hydrated Na⁺ ions from binding sites; and Na⁺ diffuses out through a simultaneously opened channel. With the addition of three external K⁺-selective sites per α-polypeptide chain, and the constraint that pump units with their external sites occupied by any univalent cation cannot be phosphorylated by ATP, the model turns out to have the properties of a Na,K-ATPase. It operates in the $\text{Na}{}^{\mathrm{+}}\text{K}{}^{\mathrm{+}}$ exchange, $\text{Na}{}^{\mathrm{+}}\text{Na}{}^{\mathrm{+}}$ exchange, $\text{K}{}^{\mathrm{+}}\text{K}{}^{\mathrm{+}}$ exchange, K⁺-dependent phosphatase, uncoupled Na⁺ efflux and pump reversal modes. It is concluded that if the modified water in the cleft of the phospho-enzymes has properties similar to those of water at 5°C the pump is competent to exchange three intracellular Na⁺ ions for two extracellular K⁺ ions, and one intracellular Na⁺ ion but it is incapable of exchanging three Na⁺ ions for three K⁺ ions.     

A possible mechanism for cadmium-induced hypertension in rats

The mechanism of cadmium-induced hypertension was explored by measuring noradrenaline metabolism. Cadmium $\text{in vitro}$ was shown to inhibit both monoamine oxidase and catechol-$\text{O}$-methyltransferase, the two enzymes which inactivate the neurotransmitters noradrenaline and adrenaline. However, rats which were injected or fed (via the drinking water) with cadmium showed that, among the tissues surveyed, these two enzymes were inhibited significantly only in the aorta. $\text{In vitro}$, cadmium was found to inhibit noradrenaline binding to membranes from the heart, lung, and kidney, while stimulating binding to aortic membranes, which suggests that the effects may be specific. These results suggest that, in the aorta, cadmium may inhibit the two catabolic enzymes of noradrenaline, while at the same time stimulating noradrenaline-binding. Thus the effects of noradrenaline on vascular smooth muscle would be increased as well as prolonged.     

A possible mechanism for cadmium-induced hypertension in rats

The mechanism of cadmium-induced hypertension was explored by measuring noradrenaline metabolism. Cadmium $\text{in vitro}$ was shown to inhibit both monoamine oxidase and catechol-O-methyltransferase, the two enzymes which inactivate the neurotransmitters noradrenaline and adrenaline. However, rats which were injected or fed (via the drinking water) with cadmium showed that, among the tissues surveyed, these two enzymes were inhibited significantly only in the aorta. $\text{In vitro}$, cadmium was found to inhibit noradrenaline binding to membranes from the heart, lung, and kidney, while stimulating binding to aortic membranes, which suggests that the effects may be specific. These results suggest that, in the aorta, cadmium may inhibit the two catabolic enzymes of noradrenaline, while at the same time stimulating noradrenaline-binding. Thus the effects of noradrenaline on vascular smooth muscle would be increased as well as prolonged.     

A possible mechanism for the action of some myxoviruses

Summary The redox properties of some myxoviruses [Fowl plaque virus strain Rostock (FPV), New Castle Disease virus strain Italy (NDV), B/Hong Kong, A/Port Chalmers, A/Victoria, A/Scotland, and A/Fort Dix (FD)] have been investigated by means of electron spin resonance (ESR) and electron microscopic studies as well as by the determination of the hemagglutination (HA) titer (antigen efficiency). The results have shown that viruses decrease the spin concentration of Cu²⁺ by acting as a reducing species (electron donor) which will result in the inactivation (oxidation) of the virus. Addition of an oxidizing substance, such as H₂O₂, to a virus suspension also leads to an oxidation of the viruses and, thus, to their inability to reduce Cu²⁺. This result is confirmed by the decrease of the HA titer of viruses with increasing Cu²⁺ concentrations. H₂O₂ could not be applied for the HA titer test since it interacts with the erythrocytes of the chicken blood used for this determination. Therefore, another oxidizing substance (oxidized glutathione, GSS) was selected which exhibited a slightly less pronounced effect than Cu²⁺. Since reduced glutathione (GSH) exerts a similar but less pronounced effect than GSS, it might be concluded that viruses have a redox system of their own and act as reducing or oxidizing substance depending on the biological receptor system. Electron microscopic studies confirm this hypothesis. As can be seen by the electron micrographs, increasing concentrations of either Cu²⁺, GSS, H₂O₂, KMnO₄, or GSH will, finally, result in a complete destruction of the virus. Because of structural similarities it might be assumed that other types of viruses behave very similarly.     

A possible mechanism for cholesteryl ester formation during demyelination

Lecithin: cholesterol acyltransferase (LCAT) activity has been examined in the rat by using a brain homogenate preparation as the phospholipid substrate and blood plasma as the enzyme source. LCAT activity was detected on using 60 l of serum onwards. Successive experiments have also shown that LCAT activity is present in the edematous rat brain tissue homogenate when incubated with inactivated rat plasma as substrate. The results are discussed in relation to cholesteryl ester accumulation in brain during demyelinating diseases.     

A possible flip-flop genetic mechanism for reciprocal gene expression

Innexins are a family of transmembrane proteins involved in the formation of gap junctions, specific intercellular channels, in invertebrates. Analyses of the entire innexin family during Drosophila melanogaster embryonic development shows the occurrence of complex and specific patterns of expression of the different genes. Innexins inx-2 and inx-7, in general, do not appear to exhibit extensive co-expression in different D. melanogaster cellular compartments. We propose here a new and robust mechanism, based on our analysis of the genomic organization of inx-2 and inx-7, that structurally justifies the reciprocal expression of genes.     

A possible transport mechanism for aluminum in biological membranes

The transport mechanism of aluminum in lysosomes extracted from rat liver has been investigated in this paper. The experimental evidence supports the hypothesis that aluminum is transported inside lysosomes in the form of an Al(OH)(3) electroneutral compound, the driving force being the internal acidic pH. This mechanism could help to explain the presence of aluminum in cells in many illnesses.     

A possible mechanism for sugar inhibition of duckweed flowering

Sugar (ca. 1%) reduced the floral index in Lemna gibba G3 byca. 50%, and supplemental addition of cyclic AMP (ca. 10^–5M)removed nearly all of this sugar action. Inhibition by sugarof duckweed flowering may be explained in terms of cataboliterepression. (Received October 9, 1971; )     

The mechanism of leaf morphogenesis

Whether cell division is a driving force in plant morphogenesis has long been debated. In this review, the evidence for the existence of cell division-dependent and cell division-independent mechanisms of plant morphogenesis is discussed. The potential mechanisms themselves are then analysed, as is our understanding of the regulation of these mechanisms and how they are integrated into development, with particular emphasis on data arising from the investigation of leaf morphogenesis. The analysis indicates the existence of both cell division-dependent and cell division-independent mechanisms in leaf morphogenesis and highlights the importance of future investigations to unravel the co-ordination of these mechanisms.     

One-vesicle hypothesis for neurotransmitter release: A possible molecular mechanism

Neurotransmitter-containing vesicles are clustered in release sites. Although a given site can contain tens of vesicles, there is evidence that under a wide range of conditions, following an action potential, rarely is more than one vesicle released from each site. Such findings led to the one vesicle hypothesis, for which this paper suggests a molecular mechanism. The release of a vesicle from a site provides a transient high concentration of transmitter in that site. It is proposed here that the local high transmitter concentration interrupts further vesicle releases from the same release site. The suggested mechanism for this ‘release interruption’ is based on a theory of release control by the authors wherein inhibitory transmitter autoreceptors play a central role. (That transmitter binding to these autoreceptors can inhibit release on a fast time scale has recently been shown experimentally.) A detailed kinetic scheme is presented for the proposed mechanism. Stochastic simulations of this scheme demonstrate how the mechanism accounts for the one vesicle hypothesis. In agreement with recent experiments, the simulations also show that changes in conditions that affect the release process can cause frequent release of more than one vesicle per site.