Showing papers in "Biological Reviews in 1954"

Fatty acid oxidation in soluble systems of animal tissues

Abstract: Summary 1. The half-century of investigations directed towards an understanding of the mechanism of β-oxidation of fatty acids may be divided into three periods: (a) from 1904 to 1939 when the oxidation could be studied at the level of the intact animal or isolated organ or tissue slice; (b) from 1939 to 1952 when it could be studied at the mitochondrial level; and (c) from 1952 onwards when it could be reconstructed in non-mitochondrial and soluble enzyme systems. 2. The Knoop-Dakin theory of β-oxidation could not be directly confirmed owing to the non-accumulation of any intermediates. The theory was based on deductions from the nature of the end-products of the metabolism of phenyl fatty acids. 3. The study of fatty acid oxidation at the mitochondrial level led to the recognition that the fatty acids are not oxidized as such but only in the form of some derivative whose formation is tied up with oxidative phosphorylation and the production of adenosine triphosphate (ATP). 4. The transition from the mitochondrial system to soluble enzymes was facilitated first by the discovery that coenzyme A (CoA) was concerned in acyl transfer reactions and later by the recognition that the active fatty acids are indeed the fatty acyl derivatives of CoA. 5. There are four known enzymatic processes by which fatty acyl CoA's are formed: (a) oxidation of pyruvate to acetyl CoA; (b) conversion of fatty acids to fatty acyl CoA's by ATP; (c) replacement of the succinyl group of succinyl CoA by short-chain fatty acids; and (d) cleavage of β-ketoacyl CoA's by CoA with formation of a fatty acyl CoA and acetyl CoA. 6. Two separate enzymes are known to catalyse the oxidation of fatty acyl CoA's to their corresponding transα, β-unsaturated derivatives. The first is a green dehydrogenase containing copper and flavin as prosthetic groups which is active upon acyl CoA's from C3 to C8. The metal is essential for the interaction of this dehydrogenase with cytochrome c. The second is a yellow flavoprotein which is active upon acyl CoA's from C4 to C18. 7. Unsaturated fatty acyl CoA hydrase catalyses the hydration of transα, β- or β, γ-unsaturated CoA's to their corresponding l(+)-β-hydroxyacyl CoA derivatives. The enzyme acts upon all unsaturated derivatives from C4 to at least C12. At equilibrium (pH 9, 250) the ratio β-hydroxyacyl CoA:total unsaturated acyl CoA is 1. 4:1. 8. The β-hydroxyacyl CoA dehydrogenase catalyses the oxidation of l(+)-β-hydroxyacyl CoA by DPN+. The product of oxidation is the corresponding β-ketoacyl CoA. The enzyme is active over the entire range of fatty acid chain length. The E0of the reaction couple at pH 7.0 and 220 is – 0.224 V. The equilibrium point of the oxidation is strongly pH dependent. 9. The β-ketoacyl CoA cleavage enzyme catalyses the reversible cleavage of β-ketoacyl CoA's by another molecule of CoA to form acetyl CoA and a new acyl CoA with two carbon atoms less than the parent β-ketoacyl CoA. 10. The new fatty acyl CoA generated in the cleavage reaction undergoes a repeat cycle of β-oxidation while the C2 unit (acetyl CoA) undergoes condensation with oxalacetate to form citrate. 11. Each of the component reactions in the β-oxidation cycle has been shown to be reversible. 12. The asymmetric labelling of acetoacetate formed during oxidation of labelled fatty acids by liver homogenates or mitochondrial suspensions is a phenomenon which can readily be explained in terms of the mechanism of the β-ketoacyl CoA cleavage enzyme. 13. The factors which militate against the accumulation of intermediates during fatty acid oxidation are discussed. 14. The accumulation of acetoacetate in any tissue requires a combination of two essential conditions: (a) presence of acyl CoA deacylase; and (b) absence of a β-ketoacid activation enzyme. 15. Assuming that in the diabetic the operation of the citric acid cycle is subnormal by virtue of reduced conversion of glucose to pyruvate, it is possible to explain the accumulation of ketone bodies and its abolition by insulin in terms of the known enzyme reactions of the β-oxidation cycle. 16. The predominance of C16 and C18 fatty acids in lipids may be due to the fact that only the acyl CoA's of these particular acids dissociate to a sufficient degree from combination with the enzymes of the fatty acid oxidizing system as to become available for ester synthesis. It is a great pleasure to acknowledge my indebtedness to Dr Helmut Beinert for his advice and assistance in the preparation of the manuscript and to Drs H. R. Mahler, D. R. Sanadi and S. J. Wakil for their suggestions.

Woodlice and the land habitat

Abstract: Summary A comparative study of woodlice which show different degrees of fitness for terrestrial life provides information about the evolution of land faunas and underlines the significance of water relations in this respect. Species of woodlice differ as regards rates of transpiration and survival in dry air. They may be considered as physical bodies so far as the effects of temperature and humidity upon evaporation are concerned, and they probably lack an epicuticular wax. No simple relation has been found between those climatic factors which affect evaporation and period of survival; neither is it expected on theoretical grounds. Transpiration from the region of the pleopods is greater, per unit area, than from elsewhere. Pseudotracheae assist respiration in dry air. In moist air oxygen is absorbed through regions of the integument other than the pleopods; but such integumental respiration decreases in importance in more terrestrial species. The only adaptation to land as regards excretion is a general suppression (compared with aquatic isopods) of nitrogen metabolism. Uric acid in small quantities is retained in the tissues. The faeces are moist. The tegumental glands are not an important source of water loss. The pleopods are not moistened by glandular secretions. Desiccated woodlice can restore their original weight by absorption of moisture, by mouth and anus, from free water surfaces, and by mouth from moist surfaces, even though the ambient air is unsaturated. The higher forms possess external capillary channels which assist in irrigation of the pleopods. The osmotic pressure of the blood of Ligia oceanica is higher than that of sea water; that of the other species measured is somewhat lower. Osmotic regulation is possible for Ligia in dilute sea water down to 50%, but adaptation to land on the part of most woodlice seems to be secured by osmotic tolerance rather than regulation. Woodlice can withstand higher ambient temperatures, for short exposures, in air at 50% R.H. than in saturated air, and this is the result of rapid transpiration. In the field transpiration plays a significant part in determining body temperature, and may be of survival value during exposure to direct insolation. All species require saturated air or a moist substrate in their permanent habitats, and it is probable that they differ as regards tolerance of suboptimal conditions during wandering rather than dryness of the normal retreat. With this proviso the families which have been investigated stand substantially in the following order of increasing terrestrialness of habitat: Ligiidae, Trichoniscidae, Oniscidae, Porcel-lionidae, Armadillidiidae. They also stand approximately in the same order as regards various morphological and physiological specializations associated with life on land (Table 1). What success the group has achieved on land may be ascribed to avoidance of the rigours of true terrestrial conditions by means of behavioural mechanisms which retain them in the cryptozoic niche, rather than to morphological or physiological adaptations. Further information is needed along three lines: (i) precise microclimatic measurements linked with observations of behaviour in the field, (ii) laboratory analysis of orientation mechanisms, (iii) neurophysiological investigation of the sensory mechanisms involved. The geological age of the group is uncertain, but there were probably land-living oniscoids before the Tertiary. Their comparative lack of progress subsequently may be the result of retaining a water-permeable integument, which is necessary for cooling during brief exposures to high temperatures and also for respiration.

The female reproductive organs of conifers and taxads

Abstract: SUMMARY 1 The morphology of the female conifer cones has long been a matter of dispute. In 1900 an account of the theories put forward so far was given by Worsdell. After a brief characterization of the situation at that time, the present article deals with the later history of the subject. 2 At the turn of the century there were rivalling concepts of the nature of the so-called ovuliferous scale in the conifers: (a) the Excrescence or Ligular theory of Sachs-Eichler, (b) the general Brachyblast theory of Braun, Caspary, celakovský and others, (c) van Tieghem's modification of the Brachyblast theory, and (d) the Foliolar theory of Delpino-Penzig. 3 In the subsequent three decades the discussion proceeded on the same or similar lines. The Excrescence theory retained a strong position until the end of the nineteen-twenties, but, as before, some morphologists professed the general Brachyblast theory. Herzfeld and Wettstein considered that the axillary conifer strobilus had one or more reduced carpels (megasporophylls) which were used up in the formation of terminal ovules, as well as an ‘ovuliferous scale’ consisting of secondary outgrowths from the strobilar axis. In Goebeľs opinion these outgrowths were instead produced by the megasporophylls. Doubts were expressed of the unity of the true conifer group, but Eames showed that the apparently widely different female cones of the Pinaceae and Araucariaceae are homologous, and that the Araucariaceae, Taxodiaceae and Podocarpaceae exhibit complete transitions by fusion and reduction from types with distinctly compound strobilar units–each with an ‘ovuliferous scale’ in the axil of a bract–to others of the most simple form. In contradistinction to the true conifers, the genus Taxus has no compound strobilus, and its ovule is a direct continuation of the axis of the fertile short shoot (Dupler). 4 In the first half of the period after 1930 opinions differed as much as ever, although the general Brachyblast theory now prevailed over the Excrescence theory and other concepts. Chadefaud believed the ‘ovuliferous scale’ and the bract to represent between them a carpel derived from a prototype analogous to the pinnate megasporophyll of Cycas. Hirmer interpreted the ‘ovuliferous scale’ and the bract as formed by a serial splitting of one single member. Lanfer supported Goebeľs views of the terminal position of the conifer ovules on reduced megasporophylls, and of the nature of the ‘ovuliferous scale’. In Hagerup's opinion the female cones of most true conifers are compound and have a short secondary axis developed axillary to each bract. This axis was supposed to carry two transversal prophylls, fertile (megasporangial) or sterile, and a varying number of sterile leaves; and the megasporophyll, with a megasporangium on its upper side, to constitute the integument of the ovule, and be homologous to a lycopod sporophyll. 5 Florin (1938-45) found that the Palaeozoic cordaites and conifers furnished the principal clue to the interpretation of the true conifer cones of Mesozoic and more recent age. Primarily, the fertile seed-scale complex in the axil of each bract was a radially symmetrical short shoot (strobilus) with several sterile scales and one to a few uniovulate megasporophylls; the ovules were terminal in position. The later types of cones have arisen by the reduction and transformation of this primitive organization, which in the majority of cases has differentiated the strobilus into a proximal fertile part facing the cone axis and a distal sterile part (‘ovuliferous scale’), while its anterior sector facing the bract became totally suppressed. Exceptionally, no ‘ovuliferous scale’ at all was developed, and the strobilus became wholly fertile. The ovular integument is a continuation of the megasporophyll, and appears to arise out of two transversal primordia at its apex. The taxads differ from the true conifers by their simple strobili being placed axillary on reduced vegetative shoots. Their ovules are seated terminally on the strobilar axis itself; megasporophylls are accordingly absent. The living and extinct genera which have previously as a rule been considered coniferous represent therefore two separate subdivisions of the gymnosperms–the true conifers, and the taxads. 6 Earlier concepts of the morphology of the female cones of the conifers, and of the nature of the integument of their ovules, are in part or wholly untenable.

Perivascular spaces of the mammalian central nervous system

Abstract: Summary The advances in the knowledge of the histology of the central nervous system which have been made possible by improved staining techniques have complicated and confused the anatomical conception of the perivascular and perineuronal spaces. As a first step towards the resolution of this confusion, a clear picture must be formed of the elements which intervene between the tunica media of the cerebral and spinal blood vessels and the neurons. The blood vessels in the central nervous system possess little or no adventitial coat, and this element is replaced by a reticular perivascular sheath continuous with the pia-arachnoid envelope of the brain and spinal cord. The question as to whether this reticular sheath extends to cover the capillaries remains to some extent unanswered, though the probability is that it does not do so. No clearly defined tissue layer serves to separate the outer wall of the reticular perivascular sheath from the neuron and its processes. In fixed preparations a felted network, formed by the perivascular feet of the neuroglia, which resembles a membrane, is seen, but we do not accept the view that this structure is part of the normal anatomy of the central nervous system. There remains an element on which little stress has previously been laid: this is the ground substance of the central nervous system, a tissue which is probably a muco-polysaccharide in constitution, and which by virtue of its physical and chemical properties may well be of considerable importance in relation to the physiology of the central nervous system. The views of the earlier authorities on the anatomy of the perivascular and perineuronal spaces are difficult to reconcile with modern knowledge of the histology of the tissues concerned, and are of interest chiefly because of the influence which they have had on descriptions of these structures which are still accepted to-day. After the first description of the perivascular space by Pestalozzi, important landmarks in the subsequent history of the spaces were: the adoption of the term ‘Virchow-Robin space’ for the perivascular space; the description by His of a second space external to this; the discovery by Obersteiner that the perineuronal spaces were continuous with the space of His, and the confusion by later workers of the space of His with that of Virchow-Robin, so that the perineuronal spaces were described as communicating through a perivascular canalicular system with the subarachnoid space. The most influential figure in moulding the modern conception of the perivascular and perineuronal spaces has been Weed. It appears that he accepted the notion, prevailing at the time at which his researches were carried out, of a complete canalicular system of spaces opening into the subarachnoid space; and it was unfortunate that the limitations of his Prussian blue technique were such as to lead him to support this misconception. Schaltenbrand & Bailey and Patek did much to resolve the confusion produced by the existence of the two systems of spaces, the true perivascular space of Virchow-Robin and the artifact space of His or Held. Schaltenbrand & Bailey regarded the combined outer wall of the reticular perivascular sheath and glial membrane (their ‘Piaglialmembran’) as separating the two systems of spaces. Patek, who used an improved version of Wee?s technique, described one true perivascular space, the Virchow-Robin space, with which the perineuronal spaces did not communicate, and three artifact spaces, with one of which, that between the glial membrane and the brain substance, the perineuronal spaces were in communication. The consideration of the views of previous workers, taken in conjunction with our own observations, leads us to believe that there are two systems of perivascular spaces: (1) the true perivascular spaces bounded by the layers of the reticular perivascular sheath; and (2) a great system of artifact spaces produced by shrinkage in the preparation of histological material and extending from the perineuronal spaces through the artifact perivascular spaces to the epispinal spaces of His. Such a conception of the histology of the perivascular and perineuronal spaces must, if accepted, alter some modern views on certain problems in connexion with the anatomy and physiology of the central nervous system. We suggest that the perivascular spaces serve neither for the production nor the absorption of the cerebro-spinal fluid, but, being channels in which there is no established flow in one direction, act as cushions between the expansile vessels and the nerve cells. We also believe that our investigations show that the anatomical arrangements are such that the perivascular channels can play no significant part in the metabolism of the neuron. Whilst the perivascular and perineuronal spaces have in all probability little relevance to the problems of the blood-brain barrier and the anatomy of the synapse, it is evident that the importance of the ground substance in relation to these problems has not been adequately appreciated.

Aphid migration in relation to weather

Abstract: SUMMARY 1. Fluctuations of the numbers of aphids in the air have been regarded in the past as due mainly to weather-controlled changes in flight behaviour. Migration has been envisaged largely as a calm-weather phenomenon, whose intensity is limited mainly by the effects of wind-speed on take-off behaviour. I have called this the ‘flight-activity hypothesis’; it developed from both laboratory and field work and has been in vogue for about 20 years. 2. This hypothesis does not fully explain changes in numbers of aphids in flight. It is apparently inconsistent with the idea of large-scale windborne migrations. Many other discrepancies are discussed. 3. When studying the changes in numbers of aphids migrating, it is helpful to distinguish between aphids migrating from plants on which they bred and those flying from other places subsequently. Aphids from these two classes together make up the general aphid population in the air. The failure to make this distinction in the past and to appreciate that the factors controlling the numbers flying in the two classes are very different, has led to much confusion. 4. A new hypothesis of numbers of Aphis fabae migrating is developed. But it is at present restricted to those flying from breeding sites; in this respect it is considered to be applicable to many species of aphids. The sequence of events is briefly thus: moulting of the winged nymphs into alatae is usually most intense early in the morning; usually one or more additional moulting peaks occur later in the day. The alatae reach flight maturity usually within 24 hr. after moulting. They then usually fly away in ‘flushes’, on the first migratory flight. The numbers in each ‘flush’ depend on the sizes of previous moulting peaks and on the lengths of both the obligatory period for maturation and on the facultative period which follow; thus the effects of vagaries in flight behaviour tend to be obscured. Therefore, the process is only weakly correlated with current weather factors. The numbers of aphids on subsequent flights will also depend on previous population (moulting) changes as well as on behaviour. Aphids lose their ability to fly owing to autolysis of the flight muscles a few days after they have left the original host, and the rapidity with which this occurs will exert a considerable effect on the numbers of aphids on flights subsequent to the first migration and on their ability to spread virus diseases; the quality of their flight may also be affected. Little is known of the biology of aphids after the first migratory flight, nor of the relative effects of the factors affecting their numbers in the air. 5. It is suggested that a considerable proportion of all the aphids in the air are on their first migratory flight; and that the number on subsequent flights may be more limited than seems to have been envisaged. 6. The flight-activity hypothesis is reviewed critically and in detail. Its defects are mainly three-fold. (a) High local concentrations of aphids occurring in occasional calm periods have been thought to account for most of the aphids migrating. This is not so. Most migration is made up of the lower densities on the more numerous windier occasions. (b) Changes in numbers of aphids in the air from day to day were thought to be due mainly to variation in flight behaviour. They are, in fact, mainly collective-population changes and subject to different laws than those applying only at the individual level. (c) Errors in measurement and treatment of data. The data of the previous authors are analysed in detail, to illustrate these errors and to disprove some previous contentions. 7. Various aspects of aphid dispersal are discussed in the light of old and new hypotheses; these are population change and migration; active and passive flight; migratory and non-migratory flight; the supposed effects of humidity; so-called ‘optimum conditions’ for flight. The significance of these aspects to the spread of virus diseases is continually borne in mind. It is a pleasure to acknowledge the help from discussions which I have had with my colleagues Dr J. S. Kennedy, Dr L. Broadbent, Mr L. R. Taylor; also Dr E. Haine and Mr Bruce Johnson who, in addition, have helped respectively with translations and permission to quote unpublished work.

Primary vascular differentiation in plants

Abstract: SUMMARY During the last ten years the differentiation of the primary vascular tissues has been intensively studied in plants developing normally and in those that were treated experimentally. The untreated plants were mainly seed plants. Several critical studies of dicotyledons and gymnosperms have shown that the procambium in vegetative shoots is delimited among the derivatives of the apical meristem in continuity with the vascular tissue in the mature part of the axis; that is, it differentiates acropetally. This procambium appears in the form of strands positionally related to leaves, that is, as leaf traces. The differentiation of procambial cells into phloem cells occurs acropetally and generally continuously. The first xylem, on the other hand, matures in or near a leaf and then differentiates basipetally in the axis and acropetally in the leaf. In the roots of seed plants procambium, phloem and xylem differentiate acropetally and continuously. The procambium shows initial unity in the root-hypocotyl-cotyledon system of the embryo and seedling, but the course of differentiation of the xylem and the phloem does not necessarily duplicate the initial course of the procambium. The procambial connexion between the epicotyl and the hypocotyl may also show initial continuity. The establishment of vascular connexion between an axillary or adventitious bud and the parent organ varies in relation to the time of development of buds. Those that develop close to the apical meristem of the parent shoot may show initial vascular continuity with the latter. Others are usually separated by vacuolated parenchyma from the vascular tissue of the parent organ and may initiate their procambium independently. The information on vascular differentiation in vascular cryptogams is meagre. There is evidence, however, that in microphyllous representatives the main part of the vascular system of the shoot differentiates independently of the leaves. The experimental studies that were used to interpret primary vascular organization consisted of removal of young leaf primordia, of partial isolation of apical meristems by vertical incisions, and of division of apices into sectors by radial longitudinal cuts. These studies were carried out on ferns and dicotyledons. The defoliated parts of axes had vascular systems in the form of relatively compact cylinders or even solid cores. The partially isolated apical meristems gave rise to shoots with normal leaf arrangements. The initial vascular connexion of these shoots with the axis below occurred, in the dicotyledons, by a basipetally differentiating procambium. In the ferns such connexion was usually absent. The dissected shoot apices regenerated one or more new shoots. The manner of connexion of these regenerated shoots with the axis was apparently more complex and more varied than in the partially isolated shoots. The deductions drawn from the experimental studies regarding primary vascular organization were, first, that the apical meristem of the shoot induces the development of the primary vascular system; secondly, that this induction occurs independently of the leaves but that leaf development may later affect the form of the differentiating vascular system; and, thirdly, that the vascular system of the stem of megaphyllous plants consists not only of leaf traces but of cauline tissue as well. These deductions are for the most part hypothetical because they are not based on critical histogenetic evidence.

Micro-Organisms of the Pleuropneumonia Group.

Abstract: Summary The organisms of the pleuropneumonia group, PPO, AGO and PPLO, constitute a uniform class of microbes. They all grow in small colonies, which can easily be overlooked unless inspected microscopically. Their colony form, a dark central portion embedded in the agar medium and lighter peripheral zone, is characteristic. Their morphology is fundamentally simple. Small granular forms, of the size of vaccinia virus, called minimal reproductive units, can initiate the growth of the larger forms. The organisms lack rigid cell walls, but have a flexible outer boundary (‘plasmalemma’). The shape and size of the organisms vary and depend on environmental conditions. Filamentous forms, small globules, disks and, on solid media, large flat forms are observed. Eventually, all these forms produce the minimal reproductive units. The nutritive requirements of the members of the group are rather exacting. Some grow well on ordinary media, but most of them require an additional factor derived from serum and some other growth factors as well. Suitable media are of paramount importance for the isolation and maintenance of these exacting organisms. Identification of organisms of the pleuropneumonia group in material from lesions by means of fixed and stained preparations is very difficult and liable to error. In most cases only the established culture on penicillin-free media can be regarded as positive evidence of the presence of a PPLO in the specimen. For the identification of species the serological method is most reliable, though some organisms can be distinguished by their special growth characteristics. Pleuropneumonia organisms are killed by disinfectants, organic gold compounds, streptomycin and aureomycin, but not by sulphonamides and penicillin. Some varieties of organisms have been found in humid soil, in decaying plant material and in polluted water, and others have been isolated from the organs or body fluids of animals, or from their mucous membranes. Those that are known as causes of animal diseases, though widely varying in their effect on their hosts, show an interesting similarity in their mechanism of infection. Though the diseases produced are often devastating and lethal, infection in the field does not readily follow exposure to the infective agent. However, outbreaks of the disease often occur in animals exposed to stress, and it appears that these events light up inap-parent infection acquired some time previously; that is to say, the infection becomes manifest when the resistance of the animal is lowered. This has been observed in the great epizootics of bovine pleuropneumonia and agalactia of sheep and goats, where the second factor may be fatigue or, in the case of sheep and goats, parturition and lactation. In laboratory animals also a natural latent infection may become active on application of unspecific substances or of a second infective agent, which may or may not be itself pathogenic for the injected animal. A new line of research has been opened by experiments on mixed infections. When the non-mouse pathogens PPLO, PPO or AGO isolated from acute cases of disease are injected into these rodents, together with the mouse-pathogenic ectro-melia virus, an infection is produced which is more severe than the ectromelia infection alone. The organisms grow abundantly in the organs and exudates of the mice, and the mixed infection can be transferred from one mouse to the other by injection of organ emulsions or exudates. However, when an avirulent PPLO, PPO or AGO or a saprophytic organism is used, together with the ectromelia virus, the organisms are ingested by the phagocytes and killed. This laboratory phenomenon suggests that it may be profitable to search for a second factor or second infective agent in natural diseases associated with PPLO, when a causal relationship between the organism and the disease has not been established. It has been suggested that the organisms of the pleuropneumonia group may represent L phases of hypothetical bacteria. Though there is a morphological similarity between these two forms, evidence for such an assumption is so far lacking. It is possible to distinguish between the L phase of bacteria and genuine PPLO. Promotion of knowledge is better served if the two are regarded as distinct until evidence for a genetic relationship is forthcoming. Classification of the pleuropneumonia group of organisms seems premature. They are not bacteria proper, nor are they viruses. From the size of their minimal reproductive units, from their simple morphology and from their fastidiousness in regard to nutritive requirements, they may be regarded as forms intermediate between viruses and bacteria.

Du determinisme physiologique des migrations

Abstract: RESUME Apres avoir montre par quelques exemples ľimportance de ľintervention des facteurs internes dans le determinisme ?une migration, nous exposons pourquoi il nous a paru logique ?etudier en premier lieu, parmi ces facteurs internes, le systeme neuro-endocrinien. Un cas particulier–dont nous justifions le choix–est envisagee: celui de la migration ?avalaison du jeune Saumon et des modifications du fonctionnement hypophyso-thyroidien la precedant et ľaccompagnant. Il apparait, ?apres quelques donnees encore fragmentaires, que certaines de ces modifications doivent etre retrouvees chez ?autres especes de poissons migrateurs au meme stade de la migration. La comparaison ?especes sedentaires et migratrices suggere ľhypothese que, chez celles-ci, le cycle ?activite neuro-endocrinienne presente des fluctuations plus accusees: Les migrations se manifesteraient a des moments ou ces fluctuations entrainent certains hyperfonctionnements ou disfonctionnements neuro-endo-criniens mettant en rupture ?equilibre ľorganisme et le milieu, ou sensibilisant cet organisme aux variations des facteurs meteorologiques. Nous signalons ?ailleurs que, si nous insistons sur les facteurs internes, trop longtemps meconnus, nous ne sous-estimons nullement le role joue par les facteurs externes dans le declanchement ?une migration. Le mecanisme hypophyso-thyroidien mis en evidence dans le determinisme de cette migration ?avalaison semble bien se retrouver dans les migrations de certains Oiseaux. Il apparait done qu'il existe, comme nous le supposions au debut de cet expose, certains facteurs physiologiques du determinisme des migrations communs a des groupes zoologiques fort eloignes. Une breve incursion dans le domaine des Invertebres montre que, la aussi, le role des glandes endocrines dans le determinisme du comportement migratoire peut etre favorablement envisagee. Nous etablissons un rapprochement entre les mecanismes physiologiques entrainant les migrations et ceux determinant ľhibernation. Ces deux comporte-ments sont le fait ?especes chez lesquelles les activites cycliques neuro-endo-criniennes presentent des fluctuations particulierement accentuees. Cette caracteristique physiologique est enfin envisageee du point de vue evolutif. Est-elle primitive, ou au contraire ľaboutissement ?une longue evolution? La question ne peut evidemment etre tranchee, mais elle est ici discutee, et nous apportions quelques arguments en faveur de la seconde hypothese. SUMMARY Having shown in several cases the part played by internal factors in the causation of migration, reasons are given for studying primarily the neuro-endocrine system. A particular instance is selected, namely the downstream migration of young salmon, with the preceding and accompanying modification in the functioning of thyroid and hypophysis. From evidence that is still fragmentary it appears that some of these modifications must also occur in other species of migratory fish at the same stage of migration. A comparison of sedentary with migratory species suggests the hypothesis that in the latter the neuro-endocrine cycle undergoes more considerable fluctuations. Migrations seem to occur at times when these fluctuations involve neuro-endocrine hyperfunction or disfunction which upsets the equilibrium between organism and environment, or renders the organism sensitive to meteorological changes. It must be emphasized, however, that while the importance is stressed of internal factors, which have been too long neglected, the part played by external factors in initiating migration is by no means overlooked. The hypophyso-thyroid mechanism found in the causation of downstream migration seems also to intervene in the migration of birds. It thus appears that there are certain physiological factors in migration which are common to distantly related zoological groups. A study of certain invertebrates shows that here too endocrines are concerned in migration. A parallel is drawn between the physiological mechanisms of migration and those bringing about hibernation. These two types of behaviour are found in animals in which cyclical neuro-endocrine activities exhibit particularly marked fluctuations. This physiological phenomenon is also considered from an evolutionary point of view. Is it primitive, or, on the contrary, is it the result of long evolution? This question cannot be answered, but it is discussed and certain arguments are presented in favour of the second alternative.

Biological aspects of senescence

Abstract: Summary 1. Senescence is treated as a generic term for the processes in certain organisms which lead to a decreasing power of homoeostasis with increasing age. 2. The presence of these processes in a species can be inferred from life-tables prepared and interpreted with suitable precautions. It cannot be inferred from the desultory examination of anatomical changes in species of unknown life cycle. Secondary criteria of senescence, e.g. decline of reproductive capacity are of value in judging the degree of age change in individuals of well-studied species. 3. Decreasing homoeostasis with increasing age is known to arise from different causes in different phyla. No single general or ‘inherent’ process can be invoked to explain all types of senescence. 4. Senescence occurs only rarely in the wild state, and except in large or social animals regularly occurring senescence is a feature of domestication. 5. Susceptibility to senescence is apparently not universal in Metazoa, and may not be so in vertebrates. Probable exceptions to its occurrence are among forms where somatic cells are continually replaced, where there is no limiting size, or where virtual attainment of a limiting size is accompanied by a persisting capacity for growth. 6. The ‘senescence’ of asexually reproducing protozoan stocks is not a phenomenon directly analogous to metazoan senescence. 7. The specific age of invertebrates and of mammals can be modified by factors modifying the rate of development. The evidence in mammals indicates that senescence results from the attainment of a developmental stage, or from the exhaustion of developmental ‘programme’ not from the cessation of growth per se. 8. The specific age varies widely between inbred stocks. Longevity is most readily produced by heterosis, and is probably a correlate of heterozygosity. 9. The role of postponed lethal genetic effects, and of the reduction of the selection value of the individual with increasing age, in the evolution of senescence is discussed. The materials for this article were collected during the tenure of a personal grant from the Nuffield Foundation for study and research on the biology of senescence. I am also very grateful to many colleagues who have furnished me with facts and criticisms, without bearing any responsibility for the uses to which I have put them, and to Miss Rosemary Birbeck, for her work in preparing the manuscript.

The zoological affinities of the conodonts.: with a section on the chemical composition of conodonts

Abstract: SUMMARY 1 Conodonts are minute, tooth-like fossils, which exhibit considerable variation in form. Two main types of structure are recognizable, laminated and fibrous. Lamellar conodonts occur in sedimentary rocks from Ordovician to Triassic, while fibrous conodonts appear to be confined to the Ordovician. 2 Conodonts have been classified as isolated specimens, upon which a binomial system of classification has been erected. This classification does not, however, represent a true zoological classification, since recent work has shown that a number of ‘form-genera’ appear to have been present in an individual conodont-bearing animal. This has formed the basis for a zoological classification, which now exists alongside the earlier ‘form-classification’. 3 The fibrous conodonts are frequently attached to basal ‘bone-like’ material. They are apparently confined to the Ordovician, and this suggests that they may represent a distinct group from the lamellar conodonts. 4 The main variations in form in the lamellar conodonts are described. 5 The basal cavity of the lamellar conodonts is variable in form. Keels are developed on the aboral surfaces of a number of types, and a few lamellar conodonts are attached to bone-like material. 6 Their microstructure indicates that conodonts were formed by accretion around a basal cavity. The presence of radial canals, extending from the basal cavity to the surface of the units, has been detected. 7 Conodonts are composed of calcium phosphate which has the structure of the apatite series. Analysis shows their composition to be essentially similar to that of the ‘bone-like’ material to which they are sometimes attached, ridged, bone-like, fragmentary plates, found associated with the conodonts and a typical Devonian fish-plate fragment. There appears to be no difference in composition between the fibrous and the lamellar conodonts. 8 Specimens are recorded in which broken parts of conodonts appear to have been regenerated. The significance of this is discussed. 9 Palaeontological studies indicate that the conodont-bearing animals were adapted to a wide variety of shallow-water, marine environments. 10 Natural conodont assemblages appear to indicate that conodonts are paired, generally in an antero-posteriorly elongated arrangement. A single assemblage may contain 14–22 component conodonts, representing 3–5 different ‘form-genera’. 11 Conodonts are extinct, having existed from Ordovician to Triassic times. Their geological history is discussed and compared with the histories of other animal groups. 12 The denticulated jaw Archeognathus may not necessarily represent a group of fibrous conodonts. It is, however, similar to these, and its form tends to support the theory that fibrous conodonts represent a distinct group of animals from those which bore the lamellar conodonts. 13 The structures on a specimen of Coelacanthus lepturus described by Demanet do not appear to represent conodonts. 14 The arrangement, form, number, chemical composition and faunal associations of conodonts do not appear to favour the theories of their crustacean or molluscan origin. 15 The suggestion of the skeletal function of conodonts does not appear to be favoured by their general form, their assemblage occurrences or the form of their basal cavity. 16 The evidence for the suggestion of the annelid affinities of the conodonts is discussed. The significance of the chemical composition of the conodonts is considered. 17 The chemical composition, size and general form of conodonts, and the arrangement of conodont assemblages, appear to contradict the theory that they functioned as copulatory structures in worms. 18 The reasons for regarding the conodonts as being parts of fish are discussed. The two most important are the chemical composition and the basal attachment of conodonts, but neither of these appears to offer conclusive evidence of the origin of conodonts from fishes. It is suggested that, if the vertebrate origin of conodonts is accepted, they may represent some group of vertebrates, other than fishes, now extinct, and apart from the conodonts, entirely unknown. 19 It is suggested that the general lack of wear, form, size and assemblage arrangement of conodonts tend to support a theory of their annelid affinities. The main problem appears to be whether the internal secretion of calcium phosphate must be regarded as an indication of vertebrate, rather than invertebrate, origin. The answer to this problem largely determines whether the conodonts are considered as representing vertebrates or worm-like creatures. It is suggested that the present state of knowledge does not justify a final conclusion as to the affinities of the conodonts, although they appear to represent an extinct group of either worm-like creatures or primitive vertebrates. It is a pleasure to acknowledge the assistance given by Mr Adrian P. Rhodes in preparing Figs. 1 and 3, Mr Roy Philips for his section on the composition of conodonts, Prof. Harold Scott, of the University of Illinois, for a number of helpful discussions on this subject, Prof. James Cullison, of Florida State University, for supplying information on Archeognathus, Prof. J. B. Cragg and Dr John Phillipson for reading the manuscript, Dr George Kohnstam for translating a paper, Mr G. O'Neill and Mrs J. Harker for assistance in the preparation of the illustrations, and the secretarial staff of the Geology Department of the Durham Colleges for their assistance in the preparation of the typescript.

The liquid medium in tissue culture

Abstract: Summary In the past, largely on an empirical basis, it was found that the most effective liquid media for culturing animal tissue cells consisted of mixtures of physiological saline solutions, tissue extracts (preferably from embryonic tissue) and serum or plasma. The marked influx of investigators with primarily biochemical interests into the tissue culture field in the last few decades has led to determined efforts to learn more of the precise relationships between the composition of these media and the metabolism of the tissues. Since both of these are so complex, and the equilibrium between them is such a delicate one, it is perhaps not surprising that many apparently contradictory results are seen in the current literature. The place of physiological salt solutions in tissue cultures appears to be a relatively simple matter, and their functions are reasonably well understood. The present confusion relates to the role of the tissue extract and serum components of the medium. For certain types of cells there is evidence that a tissue-extract nucleo-protein fraction, supplemented by a surprisingly small group of smaller molecule nutrients, is adequate to support growth, at least for short periods. Various possible mixtures of these smaller components may be effective as a supplement in the same system, although it is probable that optimum combinations exist, again depending on the cell type and the culturing conditions. The tissue nucleoprotein fraction cannot be considered as a ‘growth hormone’, in the conventional sense of that term, since other cell types, or even superficially similar cell types taken from other animal donors, are able to maintain themselves satisfactorily when this fraction is completely absent, at least if serum proteins are present in the medium. It is thus evident that quantitative comparisons of data found by various researchers are of very dubious validity unless it is certain that identical culturing techniques were applied, using identical cell systems. On a more positive note, however, it seems probable that the analytical approach to the liquid medium problem is bringing the long-sought goal of a controlled composition ‘synthetic’ medium for cultured animal cells much nearer to attainment for certain systems sharply defined as to cell type and culturing procedures. There are also indications that ‘growth’, biochemically speaking, as defined by the cell division in a culture, may be a separate process from ‘growth’ as defined by increase in culture mass, protein content or similar criteria. In other words, the chemical and physical conditions required to aid in inducing or in completing the mitotic cycle are not necessarily directly related to the nutritional requirements of growing and maturing individual cells in a healthy culture. There is some evidence that extracts made from tissues of older animals are, in many culture systems, as effective as extracts of embryonic tissue. Since, on the whole, such tissues are more accessible, their wider use by tissue culturists should be investigated more extensively. The role of serum in culture media is still not clear. In some cases it is apparently not required at all, in others it has a beneficial effect. Many of the reported contradictions as to the value or lack of value of serum in culture media are probably related to its variability in composition and state of preservation, and to the age and health of the donor animal. Until more experiments are done with better defined materials, resolving these conflicting results does not appear to be possible. A synthetic medium which would either fully support growth and development of all tissues, or one which would allow growth and development in limited but defined systems, is still the most logical goal as a reference medium and as the starting point for the systematic study of all phases of culture behaviour. The progress toward this goal has been definite but limited. With the tools now available for fractionating biological mixtures, synthesizing compounds of biological interest, and elucidating mechanisms of metabolism, the realization of a completely controlled medium, and possibly a completely synthetic medium, appears now to be merely a matter of time and continued effort. The advances in knowledge of tissue growth and behaviour that have already been achieved in the absence of such a medium are very impressive, and a constantly accelerating rate of significant research results is to be expected as the interest in this field increases.

Malformations embryonnaires d'origine carentielle

Abstract: Summary The early development of an organism is a critical stage which many factors may influence unfavourably. Maternal nutritional deficiencies, especially vitamin deficiencies, can disturb the development and bring about the most diverse malformations, affecting the nervous system, eye, vascular system, kidneys, limbs, etc. The teratological effects of deficiencies in vitamin A, vitamin B2, pantothenic acid and folic acid are firmly established. Deficiencies not only produce malformations in the embryo. They may merely retard development, but they can also cause various lesions, and among others lesions which are analogous to those brought about in the adult by nutritional deficiencies. The gravity of the result of deficiencies varies greatly. It may be negligible or it may end in the death of the embryo or sterility of the mother. The effect is a function of the intensity of the deficiency, as shown by chemical estimations of the vitamin in question. A slight deficiency may produce a malformation. It may therefore occur readily, the more so as it may result from various causes, such as an insufficient exogenous or endogenous supply, a disequilibrium of the ration, imperfect utilization, etc. Deficiencies act on the embryo as on the adult, by a disturbance of metabolism, for it is known that many vitamins are essential constituents of enzymatic systems. The results of the deficiencies depend upon the tissues or cells with which these systems are specially concerned. At an early stage such metabolic disturbances may affect organizers and so cause anomalies in development, that is, deformities. Here, as elsewhere, genetical factors may intervene in restraining or facilitating the effect of a deficiency. It is probable that these phenomena, observed in several types of birds and mammals, are of general occurrence, to be found also in man and in domestic animals. From the practical point of view it follows that maternal nutrition should be closely supervised.

The chemistry of vision

Abstract: SUMMARY An account is given of the isolation of the outer segments of retinal rods, their internal structure as revealed by the electron microscope, and their chemical composition. The relationship between action spectra (e.g. the scotopic luminosity curve) and absorption spectra is discussed. Provided certain conditions are satisfied, the chemist is able to compare the absorption spectra of pigments isolated from the retina with action spectra which have been recorded for the same type of retina by the physiologist. Thus the absorption spectrum of rhodopsin corresponds to the scotopic luminosity curve. If there was general agreement on a theory of colour vision, this would give valuable information concerning the number of photosensitive pigments to be expected. At present the only photosensitive pigments whose existence is unequivocal are rhodopsin (found in mammals, birds, reptiles, Amphibia, most fish and the squid), porphyropsin (found in some fish and Amphibia) and iodopsin (found so far only in the fowl). Recent claims to have extracted other pigments are discussed. The extraction and examination of rhodopsin is described. Until recently the various products obtained from rhodopsin by the action of light were characterized by their absoprtion spectra only. These consisted of retinene, indicator yellow, lumirhodopsin, meta-rhodopsin and iso-rhodopsin. The retina has an enzyme, believed to be identical with alcohol dehydrogenase, which catalyses the interconversion of vitamin A and retinene in the presence of coenzyme 1. It has been found possible to effect the regeneration of rhodopsin in vitro. Wald and his co-workers have shown that a system containing retinene (or vitamin A, coenzyme i and alcohol dehydrogenase) and the specific protein of rhodopsin, ‘opsin’, will synthesize rhodopsin. However, these workers found that synthetic vitamin A or retinene was not effective, but could be made so by exposure to light. Collins and his co-workers have obtained regeneration in vitro using synthetic vitamin A or retinene; their systems appear to be nearly complete. They have also shown that pyridoxal phosphate augments the amount of regeneration, although no explanation can be given of this result. The rhodopsin system is outlined in a diagram and table. In the next section an account is given of the results of chemical work aimed at identifying the pigments known only by their absorption spectra. The amounts of these pigments are too small to be isolated and indirect methods have to be used. Retinene has now been identified as vitamin A aldehyde. Indicator yellow has been shown not to be an artifact (as suggested by some workers), and to be a Schiffs base of retinene (an N-substituted retinene imine). However, the structure of the acid form of indicator yellow is still unknown. Because of their possible connection with visual pigments, a brief account is given of vitamin A amine and methylamine. Certain other reactions of retinene are described (e.g. the reaction with sulphydryl groups) in order to assist the discussion of the nature of rhodopsin itself. The significance of the fact that vitamin A, retinene and retinene methylimine react with antimony trichloride, sulphuric acid and phosphoric acid to give compounds which have absorption spectra resembling the action spectra obtained by physiologists in various retinas, is discussed. The outstanding problems are: (1) the structure of acid indicator yellow, (2) the structure of active-vitamin A and active-retinene, (3) the role of pyridoxal phosphate, and (4) the role of sulphydryl groups. Possible alternative explanations are presented, and the evidence for and against discussed. I am greatly indebted to Prof. R. A. Morton, F.R.S., for his many helpful criticisms and advice.