Showing papers in "Nature in 1976"
TL;DR: This is an interpretive review of first-order difference equations, which can exhibit a surprising array of dynamical behaviour, from stable points, to a bifurcating hierarchy of stable cycles, to apparently random fluctuations.
Abstract: First-order difference equations arise in many contexts in the biological, economic and social sciences. Such equations, even though simple and deterministic, can exhibit a surprising array of dynamical behaviour, from stable points, to a bifurcating hierarchy of stable cycles, to apparently random fluctuations. There are consequently many fascinating problems, some concerned with delicate mathematical aspects of the fine structure of the trajectories, and some concerned with the practical implications and applications. This is an interpretive review of them.
6,118 citations
TL;DR: The study reported here demonstrates a previously unrecognised influence of vision upon speech perception, on being shown a film of a young woman's talking head in which repeated utterances of the syllable [ba] had been dubbed on to lip movements for [ga].
Abstract: MOST verbal communication occurs in contexts where the listener can see the speaker as well as hear him. However, speech perception is normally regarded as a purely auditory process. The study reported here demonstrates a previously unrecognised influence of vision upon speech perception. It stems from an observation that, on being shown a film of a young woman's talking head, in which repeated utterances of the syllable [ba] had been dubbed on to lip movements for [ga], normal adults reported hearing [da]. With the reverse dubbing process, a majority reported hearing [bagba] or [gaba]. When these subjects listened to the soundtrack from the film, without visual input, or when they watched untreated film, they reported the syllables accurately as repetitions of [ba] or [ga]. Subsequent replications confirm the reliability of these findings; they have important implications for the understanding of speech perception.
5,506 citations
TL;DR: A balance between formation of anti- and pro-aggregatory substances by enzymes could also contribute to the maintenance of the integrity of vascular endothelium and explain the mechanism of formation of intra-arterial thrombi in certain physiopathological conditions.
Abstract: Microsomes prepared from rabbit or pig aortas transformed endoperoxides (PGG2 or PGH2) to an unstable substance (PGX) that inhibited human platelet aggregation. PGX was 30 times more potent in this respect than prostaglandin E1. PGX contracted some gastrointestinal smooth muscle and relaxed certain isolated blood vessels. Prostaglandin endoperoxides cause platelet aggregation possibly through the generation by platelets of thromboxane A2. Generation of PGX by vessel walls could be the biochemical mechanism underlying their unique ability to resist platelet adhesion. A balance between formation of anti- and pro-aggregatory substances by enzymes could also contribute to the maintenance of the integrity of vascular endothelium and explain the mechanism of formation of intra-arterial thrombi in certain physiopathological conditions.
3,412 citations
TL;DR: A large selection of the 3′ non-coding regions of rabbit and human globin mRN As are 85% homologous, demonstrating that this region is significantly conserved in evolution.
Abstract: The sequence A–A–U–A–A–A is present in six different purified messenger RNA molecules (specifically the α- and β-globulin mRNAs of rabbit and human, the immunoglobulin light chain mRN A of mouse (MOPC 21) and the ovalbumin mRN A of chicken) about 20 residues away from the 3′-terminal poly(A) sequence. In addition, a large selection of the 3′ non-coding regions of rabbit and human globin mRN As (both the α- and β- globin mRN As) are 85% homologous, demonstrating that this region is significantly conserved in evolution.
2,447 citations
TL;DR: A more sensitive method of conductance measurement is reported, which, in appropriate conditions, reveals discrete changes in conductance that show many of the features that have been postulated for single ionic channels.
Abstract: THE ionic channel associated with the acetylcholine (ACh) receptor at the neuromuscular junction of skeletal muscle fibres is probably the best described channel in biological membranes. Nevertheless, the properties of individual channels are still unknown, as previous studies were concerned with average population properties. Macroscopic conductance fluctuations occurring in the presence of ACh were analysed to provide estimates for single channel conductance and mean open times1–3. The values obtained, however, depended on assumptions about the shape of the elementary conductance contribution—for example, that the elementary contribution is a square pulse-like event2. Clearly, it would be of great interest to refine techniques of conductance measurement in order to resolve discrete changes in conductance which are expected to occur when single channels open or close. This has not been possible so far because of excessive extraneous background noise. We report on a more sensitive method of conductance measurement, which, in appropriate conditions, reveals discrete changes in conductance that show many of the features that have been postulated for single ionic channels.
2,377 citations
TL;DR: It is reported here that all clinically effective antipsychotic drugs (tested so far) block the stereo-specific binding of 3H-haloperidol at concentrations which correlate directly with the clinical potencies.
Abstract: ANTIPSYCHOTIC drugs, or neuroleptics, are thought to act by blocking dopamine receptors in the nervous system1–4. Recent direct evidence, based on stereospecific binding assays, supports this hypothesis of antipsychotic drug action5–9. As only a few antipsychotic drugs had been tested for their effects on the binding of haloperidol5–8, the question remained whether all antipsychotic drugs, regardless of chemical structure, would block the stereospecific binding of haloperidol. We report here that all clinically effective antipsychotic drugs (tested so far) block the stereo-specific binding of 3H-haloperidol at concentrations which correlate directly with the clinical potencies.
1,587 citations
TL;DR: It is demonstrated here that the DNA of normal chicken cells contains nucleotide sequences closely related to at least a portion of the transforming gene(s) of ASV; in addition, similar sequences are widely distributed among DNA of avian species and that they have diverged roughly according to phylogenetic distances among the species.
Abstract: INFECTION of fibroblasts by avian sarcoma virus (ASV) leads to neoplastic transformation of the host cell. Genetic analyses have implicated specific viral genes in the transforming process1–4, and recent results suggest that a single viral gene is responsible4. Normal chicken cells contain DNA homologous to part of the ASV genome5–8; moreover, embryonic fibroblasts from certain strains of chickens can produce low titres of infectious type C viruses either spontaneously9 or in response to various inducing agents10. None of the viruses obtained from normal chicken cells, however, can transform fibroblasts, and results with molecular hybridisation indicate that the nucleotide sequences responsible for transformation by ASV are not part of the genetic complement of the normal cell11. We demonstrate here that the DNA of normal chicken cells contains nucleotide sequences closely related to at least a portion of the transforming gene(s) of ASV; in addition, we have found that similar sequences are widely distributed among DNA of avian species and that they have diverged roughly according to phylogenetic distances among the species. Our data are relevant to current hypotheses of the origin of the genomes of RNA tumour viruses12 and the potential role of these genomes in oncogenesis13.
1,257 citations
TL;DR: The alternative proposed in this article is that connections are genetically specified between classes of cells, but the final wiring pattern depends on the refinement of those collections by selective stabilisation during neuronal activity.
Abstract: The specificity of synapses in the mammalian brain cannot possibly be accounted for by one-to-one biochemical matching. The alternative proposed in this article is that connections are genetically specified between classes of cells, but the final wiring pattern depends on the refinement of those collections by selective stabilisation during neuronal activity.
1,225 citations
TL;DR: A simple diagrammatic representation has been used to show the arrangement of α helices and β sheets in 31 globular proteins, which are classified into four clearly separated classes.
Abstract: A simple diagrammatic representation has been used to show the arrangement of α helices and β sheets in 31 globular proteins, which are classified into four clearly separated classes. The observed arrangements are significantly non-random in that pieces of secondary structure adjacent in sequence along the polypeptide chain are also often in contact in three dimensions.
1,197 citations
TL;DR: It is reported that the injection of kainic acid into the rat striatum causes neuronal degeneration, neurochemical alterations and behavioural responses resembling Huntington's chorea, which could provide an animal model for the study of the disease.
Abstract: THE symptoms of Huntington's chorea, an hereditary movement disorder, result from degeneration of neurones primarily in the basal ganglia1. Several neurochemical abnormalities have been identified in the brains of patients dying with this disorder2–5, but no animal system with similar neuropathological changes has been described. We now report that the injection of kainic acid into the rat striatum causes neuronal degeneration, neurochemical alterations and behavioural responses resembling Huntington's chorea. This procedure could provide an animal model for the study of the disease.
1,178 citations
TL;DR: This work presents a simple method for incorporating various proteins and other macromolecules into non-inflammatory polymers and demonstrates sustained release of biochemically active macromolescules for periods exceeding 100 d.
Abstract: SINCE the first demonstration that silicone rubber1 could be used as an implantable carrier for sustained delivery of low molecular weight compounds in animal tissues, various drug delivery systems have been developed. But except for the reports of Davis2,3 and Girnbrone et al.4, there has been little success in the development of slow release agents for large molecular weight compounds. Furthermore, the polymers used in those studies, polyvinylpyrrolidone and polyacrylamide, are often inflammatory in animal tissues and usually permit only brief periods of sustained release. We now present a simple method for incorporating various proteins and other macromolecules into non-inflammatory polymers. Sustained release of biochemically active macromolecules has been demonstrated for periods exceeding 100 d.
TL;DR: The results suggest that the mesocortical DA system is selectively activated by this stress induced by electric foot shocks, and the antipsychotic effects of neuroleptics are in part related to the blockade of postsynaptic DA receptors localised in areas innervated by the mesolimbic and mesocORTical DA systems.
Abstract: IT is now well established that an important system of dopaminergic (DA) neurones innervates various parts of the cerebral cortex in the rat and other species1–3. In contrast to noradrenergic (NA) terminals which are widely distributed in this structure, the DA terminals are mainly confined to deep layers, particularly in the frontal, the cingular and the entorhinal areas4,5. The results of lesion studies demonstrated that the terminal endings in the frontal cortex originate from the A10 group of DA cell bodies localised in the mesencephalon6–8. This group also contains the cell bodies of the classical mesolimbic DA system projecting to the tuberculum olfactorium, the nucleus accumbens, the nucleus of the stria terminalis, and the amydgala9. The DA terminals found in the cingulate and entorhinal areas of cortex may originate mainly from the A9 group of DA neurones6–8. This group gives rise to the well known nigrostriatal DA system which is implicated in extrapyramidal processes. Its degeneration is in part responsible for some of the symptoms seen in Parkinsonian patients. Little is yet known about the functions of the mesocortical and mesolimbic DA pathways. Electrocoagulation or 6-hydroxydopamine (6-OHDA)-induced lesions of the ventral tegmental area, containing the A10 group, produce a syndrome characterised by “locomotor hyperactivity, serious impairment in tests requiring inhibition of a previously learned response, facilitation of approach learning and of active avoidance and hypoemotivity”10,11. Various workers have suggested that the antipsychotic effects of neuroleptics are in part related to the blockade of postsynaptic DA receptors localised in areas innervated by the mesolimbic and mesocortical DA systems12,13. It seems important to establish whether neurones of these two DA systems correspond to an homogeneous population of cells with similar functional characteristics. We have therefore explored this problem in the rat by examining the reactivity of the mesocortical and mesolimbic DA pathways as well as that of nigrostriatal DA system to stress induced by electric foot shocks. Our results suggest that the mesocortical DA system is selectively activated by this stress.
TL;DR: This work has injected 1 µl of either kainic acid or L-glutamic acid dissolved in isotonic saline directly into the extrapyramidal nuclei of rats, and found that injection into the striatum produced local enzymatic changes duplicating those reported in Huntington's chorea.
Abstract: SYSTEMIC administration of large doses of L-glutamate to immature animals causes degeneration of neurones in the retina and the arcuate nucleus. Olney et al.1 reported that intracerebral injections of the more potent excitatory analogues of glutamate, in particular kainic acid, caused rapid degeneration of certain dendritic and somal structures in the injected area. Presumably the degeneration is related to the ability to bind the ‘excitotoxic’ agent, with necrosis resulting from a sustained increase in membrane permeability. 3H-kainic acid binds more strongly to striatal tissue than to any other area of rat brain tested2. This lends some support to Spencer's theory3—based on antagonism of cortical excitation of striatal neurones by diethyl glutamate—that the massive corticostriatal pathway is glutaminergic. If Huntington's chorea were an excitotoxic phenomenon resulting from chronic overstimulation of glutamate receptors, striatal neurones in particular would be affected because of heavy glutaminergic input. This hypothesis is not readily tested by simple measurement of glutamate in choreic tissue because glutamate is a precursor of γ-aminobutyric acid (GABA) and is also involved in other metabolic activities. As one potential test of this hypothesis, we have injected 1 µl of either kainic acid or L-glutamic acid dissolved in isotonic saline directly into the extrapyramidal nuclei of rats. Injection into the striatum produced local enzymatic changes duplicating those reported in Huntington's chorea.
TL;DR: It is not known what the critical property (or properties) is that makes initiated cells so important in carcinogens and the failure to understand and manipulate this early step has been a major impediment to its analysis.
Abstract: THE development of cancer following exposure to chemical carcinogens or to various forms of irradiation is almost invariably slow and prolonged. Although the process can be initiated by a brief exposure to a carcinogenic stimulus, there is no evidence that target cells so altered are cancer cells. Rather, there is abundant indirect evidence from many systems that what is induced is an altered cell or cell population from which malignant neoplasia can gradually develop or evolve1,2. Neoplastic development therefore resembles a chain reaction, triggered by exposure to a carcinogen, in which the links are new populations with altered organisational, structural and biochemical properties. These slowly proliferative new lesions are characteristically focal in distribution, implying that only a small proportion of the original target cell population in any organ or tissue participates. It is not known what the critical property (or properties) is that makes initiated cells so important in carcinogens and the failure to understand and manipulate this early step has been a major impediment to its analysis.
TL;DR: O'Keefe, Westgate and Wisner as mentioned in this paper argue that disasters are more a consequence of socio-economic than natural factors, and they argue that natural disasters are not the cause of all disasters.
Abstract: Phil O'Keefe, Ken Westgate and Ben Wisner argue the case that disasters are more a consequence of socio-economic than natural factors.
TL;DR: The Watson–Crick base-pairing hypothesis is used to explain the origin, nature and level of spontaneous substitution mutations, their enhancement by base analogues, and the unique effects of certain mutator alleles.
Abstract: On the basis of chemical considerations and model building, the Watson–Crick concept of complementary base pairing is extended to a wider range of DNA pairs than A–T and G–C (including A–C, G–T, A–A, G–G and G–A) by invoking imino or enol tautomers (or protonated species) and syn isomers. The virtual absence of these additional base pairs from DNA is explained in terms of the low frequency with which these unfavoured forms occur and the two-step mechanism of DNA synthesis, whereby residues are first incorporated by the DNA polymerase and then checked. This base-pairing hypothesis is used to explain the origin, nature and level of spontaneous substitution mutations, their enhancement by base analogues, and the unique effects of certain mutator alleles.
TL;DR: In this paper, a simple analogy is made between the tectonics of Asia and deformation in a rigidly indented rigid-plastic solid, where India is analogous to the indenter and the great strike-slip faults correspond to slip lines.
Abstract: A simple analogy is made between the tectonics of Asia and deformation in a rigidly indented rigid–plastic solid. India is analogous to the indenter and the great strike-slip faults correspond to slip lines. For various indentation geometries, the sense and linearity (or curvature) of strike-slip faults, convergence at the Burma arc and the existence of the Himalayan Burman Syntax, the conjugate strike-slip faults in Mongolia and the extension at the Baikal and Shansi graben can be predicted. Given the horizontal force necessary to support Tibet, an average shear stress of a few to several hundred bars along faults in Asia is predicted, corresponding to the yield stress of rigid–plastic material.
TL;DR: The concentration of GAG gradually increases from the articular surface to the deep zone, and it is suggested that this particular profile is adapted to the physiological function and mechanical properties of cartilage.
Abstract: ARTICULAR cartilage contains a high concentration of acid glycosaminoglycans (GAG), reaching 6% by wet weight and associated with fixed charge densities up to 0.2 mEq g−1. This leads to considerable swelling pressure within cartilage, due to, first, the strongly non-ideal osmotic pressure, characteristic of polymer solutions, which increases sharply with concentration and, second, the ionic contribution, in accordance with the Gibbs-Donnan equilibrium. Ogston and Wells1–3 have estimated the values of these two components and I have calculated them from my experimental data on cartilage4,5. The two components of swelling pressure are approximately of the same order of magnitude and can reach values as high as 1.7kgcm−2 (refs 4 and 5). Since normal cartilage does not swell in solution, even when it is removed from the joint and cut into thin (250 µm) slices (lowest curve, Fig. 1), this implies that its high swelling pressure must be counteracted by considerable elastic forces within the collagen fibre network. It has been known for some time that the concentration of GAG gradually increases from the articular surface to the deep zone (for example, refs 6 and 7). A typical variation of total GAG content with depth, measured as fixed charge density, is shown in Table 1. I now suggest that this particular profile is adapted to the physiological function and mechanical properties of cartilage.
TL;DR: The complete, primary chemical structure of a viral genome has now been established and biological properties, such as ribosome binding and codon interactions can now be discussed on a molecular basis.
Abstract: Bacteriophage MS2 RNA is 3,569 nucleotides long. The nucleotide sequence has been established for the third and last gene, which codes for the replicase protein. A secondary structure model has also been proposed. Biological properties, such as ribosome binding and codon interactions can now be discussed on a molecular basis. As the sequences for the other regions of this RNA have been published already, the complete, primary chemical structure of a viral genome has now been established.
TL;DR: In foetal monkey brain neuronal projections carrying input from the two eyes initially overlap; they segregate during the second half of gestation and become fully separated in subcortical visual centres and partially separated in the cortex three weeks before birth and thus before visual experience.
Abstract: In foetal monkey brain neuronal projections carrying input from the two eyes initially overlap; they segregate during the second half of gestation and become fully separated in subcortical visual centres and partially separated in the cortex three weeks before birth and thus before visual experience.
TL;DR: The model suggests a mechanism by which neurotransmitter signals may be converted into electrophysiological responses in postsynaptic cells.
Abstract: The postsynaptic actions of some neurotransmitters may be mediated through cyclic nucleotides and cyclic nucleotide-dependent phosphorylation of specific membrane proteins in postsynaptic cells. In addition to providing a molecular basis for the actions of several neurotransmitters and of certain drugs affecting behaviour, the model suggests a mechanism by which neurotransmitter signals may be converted into electrophysiological responses in postsynaptic cells.
TL;DR: Some interesting differences in retinal sensitivity in going from the near infrared to the blue wavelengths in the visible spectrum are found in rhesus monkeys exposed to eight monochromatic laser lines from 1,064–441.6 nm.
Abstract: A GROWING body of literature attests to the deleterious effects of long term exposure to light1–8. To define more critically the differences between thermal and photochemical effects, we have exposed the retinae of rhesus monkeys to eight monochromatic laser lines from 1,064–441.6 nm. Thermal damage to the retina is to be expected for the 1,064-nm line since the photopigments are not involved and energy absorption takes place predominantly in the melanin granules of the pigment epithelium and the choroid. Although data on pathogenesis are not yet available, we found some interesting differences in retinal sensitivity in going from the near infrared to the blue wavelengths in the visible spectrum.
TL;DR: Evidence for the release of DA from dendrites of dopaminergic neurones in rat substantia nigra is presented.
Abstract: THERE is increasing evidence that neurotransmitter synthesis, storage and release are not confined to axon terminals. Much of this evidence has come from studies of the dopaminergic neurones of the substantia nigra (see Fig. 1). The terminal dendritic processes of dopamine (DA) neurones in substantia nigra are varicose and contain clusters of small vesicles1,2; histochemical studies have shown that the dendrites contain DA and are able to take it up3,4. There is also evidence that the components necessary for the synthesis and storage of DA are transported somatofugally in dendrites of substantia nigra3,5. Finally, the local application of DA agonists to the substantia nigra produces an inhibition of firing of neurones in the pars compacta that is blocked by DA antagonists6,7. On the basis of these observations, it has been proposed that a local dendritic release of DA may modify the excitability of dopaminergic neurones in substantia nigra7. There has, however, been no direct demonstration of transmitter release from these or other dendrites. In this study we present evidence for the release of DA from dendrites of dopaminergic neurones in rat substantia nigra.
TL;DR: The present study found the distribution of the brain components on Sephadex G-25 to differ from those of previously characterised forms of gastrin and CCK, suggesting that the brain factors resembled CCK-like peptides more closely than gastrin- like peptides.
Abstract: A NUMBER of peptides including substance P1,2 somatostatin3 and vasoactive intestinal peptide4, have been found both in nerve cells of the brain and gut and in gastrointestinal endocrine-like cells. The biological significance of the occurrence of the same peptides in endocrine and nerve cells is not yet clear, although Pearse has suggested that these cell types might share a common embryological (neuroectodermal) origin5. An antibody to the antral hormone gasrin has recently been shown to cross react with material in extracts of the central nervous system (particularly cerebral hemispheres) of a number of vertebrate species including dog and man6. It is known that in antral mucosa, and in blood, gastrin occurs in several different forms of which the most important are peptides of 17 (G17) and 34 (G34) amino acid residues7. The C-terminal hepta-decapeptide of G34 is identical with G17, and G34 may well be a biosynthetic precursor of G17 (ref. 7). The C-terminal pentapeptide of the two gastrins is also identical with that of the intestinal hormone cholecystokinin (CCK)8, and antibodies specific for the C terminus of gastrin frequently cross react with CCK9. The present study was undertaken to clarify the relationships between the gastrin-like activity in brain and the characteristic forms of gastrin and CCK. We found the distribution of the brain components on Sephadex G-25 to differ from those of previously characterised forms of gastrin and CCK. The pattern of reactivity with different antisera suggests, however, that the brain factors resembled CCK-like peptides more closely than gastrin-like peptides.
TL;DR: In a discussion of the dynamics of protein folding two limiting models (random-search nucleation and chain propagation., diffusion–collision) are considered and it is suggested that the latter may have the dominant role in many proteins.
Abstract: In a discussion of the dynamics of protein folding two limiting models (random-search nucleation and chain propagation., diffusion–collision) are considered. It is suggested that the latter may have the dominant role in many proteins.
TL;DR: The changes which follow cross reinnervation of mammalian fast and slow twitch muscles may reflect a capacity of skeletal muscle to respond adaptively to different functional requirements.
Abstract: The changes which follow cross reinnervation of mammalian fast and slow twitch muscles may reflect a capacity of skeletal muscle to respond adaptively to different functional requirements. This interpretation is supported by experiments in which long-term electrical stimulation was used both to reproduce and to oppose the effects of cross reinnervation.
TL;DR: A bicontinuous structure is a bicountinuous partitioning in which each subvolume is filled with a distinct, not necessarily uniform composition or state of matter.
Abstract: For certain ranges of phase-volume ratio, there are two-phase structures in which both phases are continuous and interfacial area is less than in dispersions of globular units having the same volume ratio and average repeat distance. Included are bicontinuous structures defined by multiply connected minimal surfaces of very high genus and everywhere saddleshaped.
TL;DR: In this article, a model of radio sources is proposed in which the magnetized accretion disk of a massive black hole acts as an electric dynamo producing two oppositely-directed beams of ultra-relativistic particles.
Abstract: A model of radio sources is proposed in which the magnetised accretion disk of a massive black hole acts as an electric dynamo producing two oppositely-directed beams of ultra-relativistic particles.
TL;DR: Poissonian fluctuation of small numbers of generator molecules can explain the individuality of bacterial cells grown in homogeneous conditions and may apply to such processes as differentiation and asynchrony of cultures.
Abstract: The individuality of bacterial cells grown in homogeneous conditions was demonstrated by showing characteristic behavioural differences which persist over their lifespans. Poissonian fluctuation of small numbers of generator molecules can explain this individuality and may apply to such processes as differentiation and asynchrony of cultures.
TL;DR: This work has shown that in the assembly of T7 for example1, heads containing the products of genes 8–10 and 14–16 are apparently formed first, and that at least two other gene products which play no direct structural role are required for the maturation of the heads.
Abstract: RECENT studies have revealed that the packaging of DNA into phage heads is an ordered sequence of structural and biochemical events rather than a simple, spontaneous self-assembly of component molecules. In the assembly of T7 for example1, heads containing the products of genes 8–10 and 14–16 are apparently formed first. Gene 9 protein is removed from the heads before or during the incorporation of DNA. At least two other gene products which play no direct structural role are required for the maturation of the heads. A somewhat similar situation exists for phage λ, which has been shown to require ATP for the in vitro packaging of DNA into preformed heads (petite λ)2.