Showing papers in "Philosophical Transactions of the Royal Society B in 1970"
TL;DR: Golgi-impregnated retinae of rhesus monkeys have been examined by serial section electron microscopy to establish in a quantitative manner the neural connexions in the outer plexiform layer, and results have shown that there are two types of midget bipolar cell.
Abstract: Golgi-impregnated retinae of rhesus monkeys have been examined by serial section electron microscopy to establish in a quantitative manner the neural connexions in the outer plexiform layer. The results have shown that there are two types of midget bipolar cell, here called the invaginating midget bipolar and the flat midget bipolar. Both types of midget bipolar are exclusive to a single cone. The invaginating midget bipolar has been found to fit a dendritic terminal process into every invagination in the cone pedicle base. The flat midget bipolar has dendritic terminals that make superficial contact on the cone pedicle base. There are twice as many dendritic terminals and points of contact with the cone pedicle on a flat midget bipolar top as compared with an invaginating midget bipolar top. These observations, together with light microscope counts of the numbers of the two types of midget bipolars, suggest that there are two midget bipolars per cone. The diffuse cone bipolar (the flat bipolar) also makes superficial contacts on the cone pedicle base, and serial sections have shown that a flat bipolar contacts about six cones. Rod bipolars connect exclusively to rods and their dendritic terminals always end as one of the central processes that penetrate the invagination. Horizontal cell dendrites end exclusively in cone pedicles and their axon terminals end in rod spherules. The point of contact with both the types of receptor is as the lateral elements of the invaginations. A single small horizontal cell contacts about seven cones and a large horizontal cell contacts about twelve cones. The numbers of contacts per cone pedicle decrease from the centre to the periphery of the horizontal cell's dendritic field, suggesting there is an overlap of four to six horizontal cells onto a single cone pedicle. The horizontal cell axon terminals are too numerous to assess in absolute numbers but there is only one terminal to a given rod spherule from any particular axon.
432 citations
TL;DR: The present series of investigations on proteolytic enzymes is to compare the activity of the enzyme towards peptides of increasing length, diastereoisomeric pairs of peptides in which a particular amino acid residue has been replaced by its antipode, and pairs of substrates inWhich a particular side chain has been replacement by another (say an aromatic group).
Abstract: The active site of an enzyme performs the twofold function of binding a substrate and catalysing a reaction. The efficiency of these actions determines the overall activity of the enzyme towards the particular substrate, i.e. determines the specificity of the enzyme. It is therefore possible to obtain information on the active site by the kinetics of the enzyme’s reactions with different substrates and inhibitors. An important feature of the active site is its size. It should be possible to 'measure’ this by using substrates or inhibitors large enough to show up the interactions of the furthermost parts of the binding site. In the present series of investigations on proteolytic enzymes, our approach is to compare the activity of the enzyme towards ( a ) peptides of increasing length, ( b ) diastereoisomeric pairs of peptides in which a particular amino acid residue has been replaced by its antipode, and ( c ) pairs of substrates in which a particular side chain (say a methyl group) has been replaced by another (say an aromatic group). The influence of these changes on reaction rates as a function of distance from the point of cleavage indicates the extent of the active site (Schechter, Abramowitz & Berger 1965; Abramowitz, Schechter & Berger 1967).
373 citations
TL;DR: It is hypothesized that throughout sexual differentiation in mammals, maleness has to be actively imposed on a system which will become feminine if it escapes this control.
Abstract: 1 Sex differentiates under genetic control during successive periods Classical morphological and experimental data have shown the sexual bipotentiality of the developing structures But, as a matter of fact, several observations indicate that both sexes are not equal or equipotential as to their developmental trends and mechanisms 2 The developmental analysis of the body sex characteristics reveals a hormonal control In animal experiments made by the author and by others it has been observed that many structures or systems develop along the feminine type in the absence of testes during several critical developmental stages These structures include the genital tract, the hypothalamic centres controlling the pituitary function, the nervous structures mediating sex behaviour and possibly other tissues The ovary is unnecessary for the feminine differentiation of these structures; in males, femaleness has to be repressed and maleness imposed by the testes 3 The problem of gonadal sex differentiation is re-evaluated; developmental aspects occurring during normal development or in the gonads of freemartins in cattle are examined During early sexual differentiation of the gonads, testes rapidly differentiate whereas ovaries are first characterized mainly by the fact that they do not become testes These observations can be interpreted by assuming that in males a signal imposes masculinity on the gonadal primordia which otherwise would slowly become ovaries 4 It is hypothesized that throughout sexual differentiation in mammals, maleness has to be actively imposed on a system which will become feminine if it escapes this control
354 citations
TL;DR: Bovine pancreatic juice contains approximately equal amounts of four inactive precursors of endopeptidases (zymogens), but the chymotrypsins, trypsin and elastase have widely different substrate specificities, as seen in their action on the B chain of oxidized insulin.
Abstract: Bovine pancreatic juice contains approximately equal amounts of four inactive precursors of endopeptidases (zymogens): chymotrypsinogen A, chymotrypsinogen B, trypsinogen (Keller, Cohen & Neurath 1958) and a component of procarboxypeptidase which resembles a chymotrypsinogen (Brown, Greenshields, Yamasaki & Neurath 1963). In porcine pancreas another endopeptidase, elastase, is found which is uniquely effective against elastin, the elastic protein of ligaments. Chymotrypsin A and chymotrypsin B are almost identical in enzyme activity (Enenkel & Smillie 1963), but the chymotrypsins, trypsin and elastase have widely different substrate specificities, as seen, for example, in their action on the B chain of oxidized insulin (Naughton & Sanger 1961; figure 1).
224 citations
TL;DR: It is concluded that a hare-like bounding gallop was the most probable type of fast locomotion in Hallopus .
Abstract: The unique holotype of Hallopus victor (Marsh), from the Upper Jurassic of Garden Park, Colorado, is redescribed. The bones previously identified as pubes (Marsh 1890) or ischia (von Huene 1914) are regarded here as the left radius and ulna, and the ‘ ulna5 and ‘radius5 of previous workers are considered to be the left radiale and ulnare. Marsh’s identification (1890) of the ischium and his orientation of the scapula and femur (1896) are upheld. The presence of a humerus on the larger slab is confirmed. Hallopus is interpreted as a highly specialized, cursorial crocodilian, with slender, hollow bones, a greatly elongated radiale and ulnare, and a roller-like joint between these and the metacarpals. The manus is pentadactyl with a symmetrical distribution of lengths about the central axis and some proximal wedging-out of the metacarpals. The iliac blade is elongated and resembles that of Orthosuchus , the ischium is reminiscent of that of Protosuchus . The femur has a lesser trochanter, a fourth trochanter and a ‘pseudointernal9 trochanter, but no greater trochanter. The tibia is longer than the femur. The tarsus is basically crocodilian in pattern, but greatly compressed and specialized. The first metatarsal is reduced to an elongated splint, permanently recessed into metatarsal II. Metatarsals II to IV are symmetrical in length with III longest, metatarsal V is reduced, pointed, and lacks phalanges. The interpretation put forward provides a consistent explanation of the peculiarities of the skeleton of Hallopus as a variant on the basic crocodilian plan. The details of the articulation of the carpal and tarsal joints are described as far as preservation permits, and possible movements are considered. The carpometacarpal and tarsal joints are simple hinges, but the proximal carpal joint appears to have been relatively immobile and the elongation of the radiale and ulnare is viewed as a device to compensate for the increase in length of the tibia. The femur has an off-set, ball-like head and evidently moved essentially in a parasagittal plane. The pes is functionally tridactyl, with the metatarsals locked together proximally. It is concluded that both fore- and hind-feet were digitigrade during movement, although in a stationary pose the metatarsus may have been in contact with the ground. Some aspects of the pelvic and hind-limb musculature are briefly discussed. Functional analogies from the locomotory point of view are limited by the lack of cursorial quadrupedal archosaurs for comparison. It is concluded that a hare-like bounding gallop was the most probable type of fast locomotion in Hallopus . Although no skull bones have been identified, evidence from the postcranial skeleton is adduced to show that Hallopus is of pedeticosaurid descent. The relationships of early crocodilomorphs are discussed, and it is deduced that two basic stocks diverged from a common ancestry during the middle part of the Trias. These two groups are included in an expanded Order Crocodylomorpha. The Suborder Crocodylia has the Triassic Stegomosuchidae as its radicle and contains ‘ normal ’ crocodiles (including the Sebecosuchia but not the Baurusuchidae). The suborder Paracrocodylia is proposed for mainly cursorial forms, to include the infraorders Pedeticosauria, Baurusuchia and Hallopoda. Diagnoses for these groupings are presented. An origin for both stocks from a form close to Cerritosaurus is postulated. Erpetosuchus and Dyoplax are not now regarded as crocodilomorphs. The possibility of an early cursorial phase in crocodilian evolution is briefly discussed, and it is tentatively suggested that the gallop occasionally observed in young crocodiles (Cott 1961) may be a relic of a primitive type of locomotion in the group. The significance of this to the emergence of the crocodilian type of shoulder-girdle is considered.
223 citations
TL;DR: Reflecting surfaces of fish are formed of stacks of thin, flat crystals composed of guanine, as the major component, and hypoxanthine as the minor component.
Abstract: Reflecting surfaces of fish are formed of stacks of thin, flat crystals composed of guanine, as the major component, and hypoxanthine, as the minor component. The broad surfaces of these crystals are not, in general, parallel to the surfaces in which they lie in the fish but they are orientated at angles which depend on the function which they serve. The stacks of crystals in different situations also differ in the number and thickness of crystals and in spectral reflectivity. The organization of these crystals is described, in relation to function, for the silvery surfaces of bony fish, the herring and mackerel, for the reflecting tapeta found in the shark and dogfish, for the photophores of the deep-sea hatchet fish and, finally, for the eye of the scallop.
202 citations
TL;DR: Variants of the Golgi-Colonnier (1964) selective silver procedure have been used to show up neurons in insect brains and neural elements are particularly clearly impregnated in the optic lobes.
Abstract: Variants of the Golgi-Colonnier (1964) selective silver procedure have been used to show up neurons in insect brains. Neural elements are particularly clearly impregnated in the optic lobes. Three classes of nerve cells can be distinguished; perpendicular (class I), tangential (class II) and amacrine cells (class III). There are many types of neurons in each class which together have a very wide variety of form. Their components are related to specific strata in the optic lobe regions. Short visual cells from the retina terminate in the lamina in discrete groups of endings (optic cartridges). Pairs of long visual fibres from ommatidia pass through the lamina and end in the medulla. Class I cells link these two regions in parallel with the long visual fibres and groups of these elements define columns in the medulla. These in turn give rise to small-field fibres that project to the lobula complex. Tangential processes intersect the parallel arrays of class I cells at characteristic levels. Some are complex in form and may invade up to three regions. Another type provides a direct link between the ipsi- and contralateral optic lobe. Amacrine cells are intrinsic to single lobe regions and have processes situated at the same levels as those of classes I and II cells. A fifth optic lobe region, the optic tubercle, is connected to the medulla and lobula and also receives a set of processes from the mid-brain. There are at least six separate types of small-field relays which could represent the retina mosaic arrangement in the lobula.
195 citations
TL;DR: The migration of the germ cells into the mammalian gonad and their subsequent differentiation has been the subject of many investigations and controversies but sufficient facts have accumulated that Witschi (1962) to state that ‘the formerly controversial subject of the origin and unbroken continuity of the Germ cell lines can now be considered settled’.
Abstract: The migration of the germ cells into the mammalian gonad and their subsequent differentiation has been the subject of many investigations and controversies. However, sufficient facts have accumulated which led Witschi (1962) to state that ‘the formerly controversial subject of the origin and unbroken continuity of the germ cell lines can now be considered settled’. Histo-chemical techniques for alkaline phosphatase have made it possible to selectively stain and identify primordial germ cells (McKay, Hertig, Adams & Danziger 1953; Chiquoine 1954; Mintz 1959). The path and development of the germ cells has been described in detail in histological investigation (for review see Brambell 1956; Mintz 1960; Franchi, Mandl & Zuckerman 1962) and recently labelling techniques have made the continuity of the germ cell line ‘visible’ (Rudkin & Griech 1962; Peters, Levy & Crone 1962; Kennelly & Foote 1966; Borum 1966; Peters & Crone 1967).
178 citations
TL;DR: An account is given of the benthic marine algae (and sea grasses) collected on the 1965 Royal Society Expedition to the Solomon Islands, comprising some 71 species of Chlorophyta, 27 of Phaeophyta), 121 of Rhodophyta and 14 of Cyanophyta.
Abstract: An account is given of the benthic marine algae (and sea grasses) collected on the 1965 Royal Society Expedition to the Solomon Islands. The known algal flora is fairly typical of such a tropical area, comprising some 71 species of Chlorophyta, 27 of Phaeophyta, 121 of Rhodophyta and 14 of Cyanophyta. Pseudobryopsis solomonensis , P. gracilis, Caulerpa spathulata and Cryptonemia ? subdichotoma are newly described. Seven species of sea grasses are also recorded.
172 citations
TL;DR: In this article, the first complete vegetational record of the Hoxnian interglacial from the Lowestoft Late-glacial to the Gipping Earlyglacial periods is presented.
Abstract: At Marks Tey, Essex, Pleistocene lacustrine sediments rest on chalky boulder clay and occupy a deep, narrow trough cut into the subglacial surface. The central deposits of the former lake basin consist of laminated clay muds, partly brecciated, overlain by laminated grey clay, which is at present exploited for brickmaking. Together these strata have a maximum proved thickness of at least 35 m. The marginal sediments of the basin are thinner and more organic, and indicate some fluctuation of water level during deposition. Palaeobotanical evidence suggests that the basin was formed during the Lowestoft glaciation, possibly by subglacial erosion, and was gradually infilled during the course of the entire Hoxnian interglacial and the carliest part of the ensuing Gipping glacial period. Pollen analysis of the lacustrine deposits yielded the first complete vegetational record throughout the Hoxnian interglacial from the Lowestoft Late-glacial to the Gipping Early-glacial periods. The vegetational and climatic development of the interglacial can be reconstructed from the palaeobotanical evidence. The grey clay of Gipping age contained a macroflora of 'full-glacial' aspect. Of particular note are (1) the closing zones of the interglacial (Ho III and Ho IV), which have not been fully recorded before; (2) the occurrence during this period of such exotic plant types as Vitis, Pterocarya and Erica cf. terminalis; and (3) a high non-tree pollen phase during subzone IIo IIc similar to that recorded by West (1956) from the same subzone at Hoxne. A preliminary investigation has been made of diatomaceous lamination structures in the interglacial clay mud. This lamination, which appears to be annual, suggests that the timespan of the interglacial period was of the order of 30 000 to 50 000 years. The interglacial deposits rest on chalky boulder clay, corresponding to the Springfield Till of Clayton (1957, 1960). There is no sign of till overlying the lacustrine deposits. Nearby, other Hoxnian deposits at Copford and Rivenhall End, Kelvedon, rest in a similar stratigraphic position. This fact implies that all the till deposits of south-east Essex belong to the Lowestoft glaciation, and that the Gipping ice advance did not extend as far south as commonly assumed.
170 citations
TL;DR: One interpretation of the results is that all three sets of extrinsic afferents terminate in the middle portion of the apical dendritic tree of pyramidal neurons, and that thalamo-cortical fibres have additional terminals on stellate neurons.
Abstract: In a series of experiments, the extrinsic afferent pathways to the somatic sensory areas have been selectively interrupted and the distribution and mode of termination of degenerating synaptic endings studied at intervals of 2 to 6 days. Degenerating commissural fibres terminate on spines attached to dendrites of medium and small size in all cortical layers, but the endings are concentrated in the deeper parts of layers I and III and in layer IV. Cortical association fibres passing from SII to SI end on spines of small and medium-sized dendrites mainly in the intermediate layers (III, IV and V) of the cortex, but a small number are invariably seen in the molecular layer. Some of the latter are probably derived from thin myelinated axons which spread radially from a lesion and run just beneath the pia mater. Degenerating thalamo-cortical axons terminate on spines and to a lesser extent on shafts of dendrites of small diameter, mainly in layer IV but with overlap into adjacent parts of layers III and V and with an additional small but consistent number ending in the molecular layer. Thus, the molecular layer and layer IV receive the terminations of all extrinsic afferents, while the relations of these to the other laminae and their mode of termination is, in each case, slightly different. One interpretation of the results is that all three sets of extrinsic afferents terminate in the middle portion of the apical dendritic tree of pyramidal neurons, and that thalamo-cortical fibres have additional terminals on stellate neurons. The functional implications of this arrangement are discussed.
TL;DR: The motor innervation of cat spindles was examined in hindlimb muscles using a variety of techniques employed in light and electron microscopy, finding the participation of the α fibres in mammalian fusimotor innervation widespread in the muscles studied and more prevalent in fast muscles (FHL, peroneus digiti quinti) than slow (soleus).
Abstract: The motor innervation of cat spindles was examined in hindlimb muscles using a variety of techniques employed in light and electron microscopy. Observations were made on teased, silver preparations of 267 spindles sampled from the peroneal, flexor hallucis longus, and soleus muscles, hereafter referred to as the PER/FHL/SOL series. The γ innervation. Trail endings are almost invariably present, and innervate both bag and chain muscle fibres. Trail fibres accounted for 64.6 to 74.8% of the total fusimotor supply to samples of spindle poles in the PER/FHL/SOL series, the mean number of fibres per pole varying from 2.7 to 5.0 in the different muscles, and the mean number of ramifications (areas of synaptic contact) per fibre being 3.7. By contrast, the p₂innervation of a spindle pole generally consists of a single fibre supplying only one plate. In the above samples p(2) fibres accounted for 4.1 to 28.0% of the total fusimotor supply, and the mean number of fibres per pole varied from 0.3 to 1.2 in the different muscles. Ninety per cent of p(2) plates innervate bag fibres. The α innervation. The structure of p₁plates as seen in both light and electron microscopy compares very closely with that of extrafusal plates. After nerve section p₁plates degenerate at the same time as extrafusal plates, being the first of the three types of fusimotor ending to disappear. The frequency of the p₁innervation is similar to that of the p₂innervation. In the same samples of PER/FHL/SOL spindle poles as above p₁ fibres accounted for 6.0 to 28.8% of the total fusimotor supply, the mean number of fibres per pole varying from 0.25 to 2.1 in the different muscles. The majority of p₁ fibres enter a pole to terminate in one plate only. Seventy-five per cent of the plates innervate bag fibres. The three types of fusimotor ending are thus not selectively distributed to the two types of intrafusal muscle fibre. All three types of fusimotor fibre may branch within the spindle so as to innervate both bag and chain fibres. Bag fibres receive both types of plate ending as well as trail endings. Most chain fibres receive trail endings only; the rest receive either a p₁or a p₂plate innervation in addition, 25% of the p₁and 10% of the p₂innervation being distributed to chain fibres. The significance of this nonselective innervation is interpreted as indicating that the type of contraction elicited by stimulating a fusimotor fibre depends upon the type of ending initiating it rather than upon the type of muscle fibre executing it. Reasons are given for concluding that the dynamic response is controlled via the p₁and p₂plates, and that the static response is controlled by the trail endings. The participation of the α fibres in mammalian fusimotor innervation, previously regarded as a vestigial feature, proved to be widespread in the muscles studied and more prevalent in fast muscles (FHL, peroneus digiti quinti) than slow (soleus). A low frequency of p₁innervation is offset by a high frequency of p₂(as in peroneus longus), and vice versa (as in FHL). It is unlikely that collaterals from slow α fibres innervating type B muscle fibres are wholly responsible for the high frequency of the p₁innervation in FHL, and it is suggested that collaterals may also be derived from fast α fibres innervating type C muscle fibres. The possibility of there being some motor fibres of α conduction velocity and with an exclusively fusimotor distribution is also taken into account.
TL;DR: The optic lobes of Diptera have been examined by variants of the Golgi-Colonnier selective staining techniques and by reduced silver procedures and some lateral relationships have been reconstructed between elements in regions whose columnar arrangement is clearly discernible in Golgi preparations.
Abstract: The optic lobes of Diptera have been examined by variants of the Golgi-Colonnier selective staining techniques and by reduced silver procedures. All, bar one, of the elements described by the earlier authors (Vigier 1908; Zawarzin 1913; Cajal & Sanchez 1915) have been seen, in part or in their entirely, in these preparations. Many other forms, hitherto unrecognized, have been found. Their perpendicular topographical relationships have been reconstructed in the optic lobe regions. Some lateral relationships have also been reconstructed between elements in regions whose columnar arrangement is clearly discernible in Golgi preparations; these include the lamina and the medulla. In the Diptera the projection pattern of the retina mosaic into the lamina neuropil involves complex chiasmata between the two regions (Braitenberg 1967); these have been confirmed from these species. The retina-lamina mosaic is, essentially, homotopically preserved in the columnar medulla, via long visual fibres and monopolar cells. The medullary mosaic is preserved through its strata by transmedullary cells and the longest small-field amacrine cells. The mosaic is projected to the two regions of the lobula complex by class I cells (see part I). The organization of the tangential cell processes suggests that some of them may interact with large or whole field aggragates of the relayed retinal mosaic. Others, especially in the lobula, may interact with small oval or narrow strip-field aggragates. Although there are many differences of neural form and number of neurons between species, both the Lepidoptera and Diptera have the same fundamental plan of neuroarchitecture.
TL;DR: The detailed atomic interpretation of the 0.20 nm electron density map of CPA is completed, supplying residue identifications where the primary sequence is not available, and the resulting atomic coordinates are subjected to a model building procedure (Diamond 1966) which forces them to conform to standard bond distances and angles.
Abstract: Bovine pancreatic carboxypeptidase Aa (CPA),J the subject of these studies, is a zinc containing enzyme of molecular weight 34 600, which catalyses the hydrolysis of polypeptides and esters at the C-terminal peptide or ester bond. Experiments to date have shown that in order to be hydrolysed, the substrate must contain a C-terminal residue in the l configuration, with the carboxyl group free and α to the peptide or ester bond which is to be cleaved. In addition, the reaction is favoured if the C-terminal residue is aromatic. Our crystallographic studies of CPA have yielded electron density maps of the native enzyme at 0.6 nm (Lipscomb, Coppola, Hartsuck, Ludwig, Muirhead, Searl & Steitz 1966), 0.28 nm (Ludwig, Hartsuck, Steitz, Muirhead, Coppola, Reeke & Lipscomb 1967) and 0.20 nm resolution (Reeke, Hartsuck, Ludwig, Quiocho, Steitz & Lipscomb 1967; Lipscomb, Hartsuck, Reeke, Quiocho, Bethge, Ludwig, Steitz, Muirhead & Coppola 1968). Concurrently, a study of the binding of a number of substrates and inhibitors at 0.6 nm resolution was under way (Steitz, Ludwig, Quiocho & Lipscomb 1967). Subsequently, the most promising of these complexes, that of glycyl-L-tyrosine with CPA, was carried to atomic resolution (Reeke et al. 1967; Lipscomb et al. 1968). Even though chemical sequence is not available for several of the binding and catalytic groups of the enzyme, we have been able to deduce the identity of the binding residue Arg-145 and the catalytic residue Glu-270 (Reeke et al. 1967), to describe the mode of binding of Gly-Tyr, to extrapolate these conclusions to the binding of polypeptides, and to propose a mechanism, with certain ambiguities, for the action of the enzyme (Lipscomb et al. 1968). We have now completed the detailed atomic interpretation of the 0.20 nm electron density map, supplying residue identifications where the primary sequence is not available, and have subjected the resulting atomic coordinates to a model building procedure (Diamond 1966) which forces them to conform to standard bond distances and angles. The improved coordinates have been entered in a structure factor calculation, which gave a standard crystallographic R factor of 0.44.
TL;DR: The epithelium lining the digestive tubules of Cardium edule consists of three cell types, namely mature digestive cells, mature secretory cells and immature flagellated cells which vary from cuboidal to columnar, possess distinctive Golgi elements with characteristic intracisternal membranous elements, and are capable of ingesting exogenous material from the lumen of the tubule.
Abstract: The epithelium lining the digestive tubules of Cardium edule consists of three cell types, namely mature digestive cells, mature secretory cells and immature flagellated cells. Both the secretory and flagellated cells exhibit a pronounced basiphilia and occur in well-defined crypts. The secretory cells are pyramidal in shape and characterized by the possession of a well-developed granular endoplasmic reticulum and Golgi apparatus. Golgi vesicles derived from the latter migrate to the apical region of the cell where they release their contents into the lumen of the tubules. It is possible that the secretion contains enzymes and although it is likely that such enzymes would function primarily in the lumen of the tubules they may also be the source of the weak proteolytic activity which has been recorded in the gastric fluid of many bivalves. The immature flagellated cells are columnar in shape and possess a poorly developed endoplasmic reticulum and numerous free ribosomes. Although no evidence for this was obtained it is suggested that they may serve to replace either or both of the mature cell types. The digestive cells vary from cuboidal to columnar, possess distinctive Golgi elements with characteristic intracisternal membranous elements, and are capable of ingesting exogenous material from the lumen of the tubule. The process of ingestion was examined following feeding experiments with (a) a mixture of iron oxide and colloidal graphite (Aquadag), (b) whole blood from pigeon and (c) ferritin. Individual particles of graphite were enclosed in phagosomes by a process of phagocytosis, while the proteins haemoglobin and ferritin were ingested by a process of pinocytosis; the membrane enclosing the pinocytic vesicles possesses a characteristic outer granular coat. The contents of both the phagocytic and pinocytic vesicles were transferred to larger bodies considered to be primarily phagosomes in the sub-apical regions of the cell. These possess an interconnecting system of membrane-bound channels which ramifies through the apical cytoplasm. Phagolysosomes deeper in the cytoplasm of the cell were identified by the presence of exogenous material and a positive reaction to tests for acid phosphatase activity. They showed changes in appearance which could be put into a series suggestive of the progressive intracellular digestion of the ingested material.
TL;DR: A systematic study of small free-living amoebae has been made under standardized and reproducible cultural conditions, and their pathogenicity has been tested in mice, and metronidazole and other anti-amoebic drugs are ineffective against N. aerobia and H. culbertsoni in vitro and in meningo-encephalitis in mice.
Abstract: A systematic study of small free-living amoebae has been made under standardized and reproducible cultural conditions, and their pathogenicity has been tested in mice. Naegleria aerobia, Hartmannella culbertsoni and H. rhysodes are pathogenic; H. castellanii, H. astronyxis, H. palestinensis, H. glebae, H. exundans, H. vermiformis, Schizopyrenus russelli, Didascalus thorntoni and Tetramitus rostratus are non-pathogenic. Strains of H. culbertsoni and H. rhysodes are present in Indian soils. A classification of the order Amocbida Kent into families Schizopyrenidae Singh, Hartmannellidae Volkonsky, 1931 emend. Singh, 1952, and Endamoebidae (Calkins), based on nuclear division, is proposed, and the relation of this classification to previously defined families and genera of amoebae and its bearing on phylogeny are discussed. Metronidazole and other anti-amoebic drugs are ineffective against N. aerobia and H. culbertsoni in vitro and in meningo-encephalitis in mice.
TL;DR: Two main types of neuron may be distinguished electron microscopically in the somatic sensory cortex, pyramidal and nonpyramidal, in the nature of their dendritic ramifications and particularly in their synaptic relationships.
Abstract: Two main types of neuron may be distinguished electron microscopically in the somatic sensory cortex. Pyramidal neurons have a characteristically triangular perikaryon with a high content of ribonucleoprotein consisting mainly of free ribosomes; the nucleus usually shows a single small indentation. Nonpyramidal neurons, which may be large or small, have a higher concentration of all intracytoplasmic organelles and particularly of long cisternae of rough-surfaced endoplasmic reticulum forming Nissl bodies. The nucleus is often deeply indented and crenellated. The two cell types differ also in the nature of their dendritic ramifications and particularly in their synaptic relationships. The majority of axon terminals ending on pyramidal neurons contact dendritic spines and relatively few end on the shafts of dendrites or on the perikaryon. Synapses on spines are typically of the type in which the synaptic thickenings are asymmetrical and the synaptic vesicles spherical. Such synapses, even when they occur on the shafts of pyramidal cell dendrites, are usually associated with a ‘spine apparatus’. Most of the few synapses on the dendritic shafts and somata of pyramidal cells are associated with symmetrical membrane contacts and small, flattened or pleomorphic vesicles. Terminals of this type are commonly en passant endings of long, thin unmyelinated axons oriented vertically or transversely within the cortex. The somata and the usually irregular dendrites of non-pyramidal neurons are typically covered in axon terminals most of which contain flattened vesicles and end in symmetrical complexes, but a few may contain spherical vesicles and end asymmetrically. The axon hillocks and initial segments of both types of cell are postsynaptic to axon terminals containing small, flattened vesicles and ending symmetrically.
TL;DR: The ancestry of captorhinomorph reptiles from the gephyrostegid anthracosaurs can be firmly established and the nature of the amphibian-reptilian transition must be studied on the basis of relicts of earlier groups which are contemporary with true reptiles.
Abstract: Reptiles of several distinct lineages have been described from the lower part of the Upper Carboniferous. Neither reptiles nor any plausible ancestors are known from earlier beds. The nature of the amphibian-reptilian transition must be studied on the basis of relicts of earlier groups which are contemporary with true reptiles. Several genera from the Middle Pennsylvanian locality of Nyrany, Czechoslovakia, have been considered closely related to the ancestry of reptiles. The incomplete nature of the original descriptions of Diplovertebron, Gephyrostegus and Solenodonsaurus has led to considerable confusion as to their taxonomic distinction and phylogenetic significance. Subsequently these taxa have been variously synonymized and considered as being alternately embolomeres, primitive anthracosaurs, seymouriamorphs, extremely primitive reptiles and captorhinomorphs. On the basis of redescription of type material from museums in Berlin, Prague and Cambridge as well as more recently discovered specimens, it is possible to establish the identity of these forms and to describe them in considerable detail. The type of Diplovertebron punctatum can be identified as a small embolomere. The material on which it is based can be distinguished from the types of Solenodonsaurus and Gephyrostegus. The type of Gephyrostegus bohemicus is a primitive anthracosaur. On the basis of this and other material, description of almost the entire skeleton is possible. The vertebral column has 24 presacral segments, each consisting of a large U-shaped pleurocentrum and a smaller, crescentic intercentrum. This genus is an almost ideal relict of the anthracosaur group which gave rise to reptiles. It is clearly distinct from the Permian seymouriamorphs, and could not have given rise to any known members of that group. Eusauropleura digitata from a deposit of equivalent age at Linton, Ohio, is a related, but somewhat more primitive from. The body proportions of these genera indicate that they were terrestrial in habit, with no specifically aquatic adaptations. The type of Solenodonsaurus janenschi is a very primitive reptile. This form retains an otic notch and labyrinthine infolding of the enamel, but the postcranial skeleton is very close to the pattern of romeriid captorhinomorphs. Material of a very immature specimen assigned to this genus by Pearson has a typically reptilian palate and skull roof pattern, but anthracosaurian dorsal and ventral scales. Material (designated by them as specimen I) assigned to the genus Gephyrostegus by Brough & Brough actually pertains to a romeriid captorhinomorph. On the basis of this material, the ancestry of captorhinomorph reptiles from the gephyrostegid anthracosaurs can be firmly established. The families Solenodonsauridae and Limnoscelidae are relicts of more primitive, but still reptilian, lineages which retain a number of anthracosaurian characteristics.
TL;DR: It is emphasized that the diversity of biological characteristics, which experimental cultures reveal, in the offspring of different individuals (termed 'polybiosis') may be of great importance for the exploitation of abnormal circumstances and perhaps even for survival.
Abstract: The characteristic pioneer flora of exposed mud in Britain, here considered, is held to comprise about fifty species, most of which are local in their occurrence, often conspicuously intermittent, and very variable in their abundance. The majority are annuals whilst others, potentially perennial, may behave as annuals. Their provenance is prevailingly Southern or Continental. The fruiting periods exhibit a marked late-summer or autumnal bias corresponding with the season of greatest evaporation and frequency of suitable habitat conditions. Most of the 'mud-species' have greatly diminished in their frequency, the average loss being probably about 40% of their former locations. The importance of recording their biological characteristics in Britain, before they become extinct, is emphasized. The propagules are shown to be generally small, or very small, with transport by adhesion to the feet and feathers of water-birds as probably the most frequent means of more distant dispersal, although internal carriage may be effective for some species over long distances. Estimates respecting the average and observed maximum outputs for 36 species are furnished and, as with other 'intermittently available habitats', these are shown to be very large especially in relation to the size of most of the plants. The mode of germination is illustrated by data from experimental sowings, of freshly ripened propagules, of 38 of these species. The germination behaviour, it is shown, may vary conspicuously as between the different species, sometimes even between individuals of the same taxon, but there is a prevailing tendency, especially marked with some species, towards quasi-simultaneous germination of the seeds or fruits maturing at the same time. Germination experiments, involving large numbers of seeds or fruits from different individuals, have shown that while, frequently, there may be no germination in darkness, the propagules from certain individuals of the same species may yield a small or moderate percentage in the dark. The response to light is probably a matter of degree rather than of kind. Whilst the average behaviour, in this and other respects, is of great significance it is emphasized that the diversity of biological characteristics, which experimental cultures reveal, in the offspring of different individuals (termed 'polybiosis') may be of great importance for the exploitation of abnormal circumstances and perhaps even for survival. Most 'mud-species' have very small propagules and either exhibit no germination in darkness or a very low percentage. The small number of species with relatively large propagules yield appreciable germinations in the dark. These 'mud-species' exhibit, in varying degrees, significant specialization for the colonization of bare mud and are intolerant of competition. Cogent evidence is furnished that emphasizes the importance, for experiments on wild species, of utilizing propagules derived from a single individual to permit of valid conclusions as to the effect of contrasting conditions.
TL;DR: The hydrolysis of chymotrypsin specific substrates is shown to be considerably more complex than is indicated by this previously proposed mechanism and there exist a number of ionization and conformational equilibria which account for the bell-shaped pH-rate profiles observed for chymotin catalysed reactions.
Abstract: Physical and chemical studies of chymotrypsin in solution and kinetic measurements of individual steps in reactions catalysed by this hydrolytic enzyme are reported. The solution studies also provide a basis for correlation of individual reaction steps with structural information obtained by Drs Blow and Hartley and discussed at this Discussion. The rate and equilibrium constants pertaining to the three-step mechanism shown below have been determined for the chymotrypsin catalysed hydrolysis of three specific ester substrates-the ethyl esters of N-acetyl-L-tyrosine, N-acetyl-L-tryptophan, and N-acetyl-L-phenylalanine-at selected pH values with use of both flow and relaxation techniques. $E + S \overset{K'\_S}{\rightleftharpoons} ES
earrow\rightarrow^{P\_1}\_{k\_{23}} EP\_2 \rightarrow\_{k\_{23}} E + P\_2$ where E is enzyme, S is substrate, ES is a complex, EP $\_2$ is an intermediate compound, and the products P $\_1$ and P $\_2$ are, respectively, an alcohol or amine and an acid. The hydrolysis of chymotrypsin specific substrates is shown to be considerably more complex than is indicated by this previously proposed mechanism. In addition to the steps shown, there exist a number of ionization and conformational equilibria which account for the bell-shaped pH-rate profiles observed for chymotrypsin catalysed reactions. A catalytically active enzyme conformation, which is in pH dependent equilibrium with a catalytically inactive conformation, is shown to have its origin in the enzyme activation mechanism. In the chymotrypsin catalysed hydrolysis of an amide substrate, furylacryloyltrypto-phanamide, there has been detected an additional intermediate which differs from the intermediate EP $\_2$ observed in ester hydrolysis.
TL;DR: The present contribution will mainly deal with unusual sex chromosome inheritance, that is the groups (ii), (iii) and (iv) above, but the other two groups will also be briefly discussed and examples will be given.
Abstract: The male has proven to be the heterogametic sex in all mammals studied so far. As is well known, the males usually have the sex chromosomes XY and the females XX. In recent years, however, many exceptions from this general pattern have been discovered. With our present knowledge, the different sex chromosome mechanisms in mammals may be divided into five main groups, and the first of them into subgroups, as follows: (i) Species with XX/XY sex chromosomes: (a) X of original size (see below), Y small; (b) X large, Y small; (c) X large, Y large: (i) end-to-end association of X and Y at male meiosis, (ii) chiasma between X and Y at male meiosis. (ii) Species with XX/XY1Y2 sex chromosomes. (iii) Species with X1X1X2X2/X1X2Y sex chromosomes. (iv) Species with complicated or unknown mechanisms for sex determination. (v) Species with mosaicism of the sex chromosomes, but apparently with an XX/XY mechanism for sex determination. The present contribution will mainly deal with unusual sex chromosome inheritance, that is the groups (ii), (iii) and (iv) above, but the other two groups will also be briefly discussed and examples will be given. Recently Raicu, Kirillova & Hamar (1969) described a new sex chromosome mechanism ( X1X1X2X2/X1X2Y1Y2) in the vole Microtus arvalis , but this observation was not confirmed by Schmid (1969), who found an ordinary XX/XY mechanism with both X and Y readily identifiable and of ‘normal’ size, the X comprising 5.6% of ( n A + X) and Y being the smallest chromosome of the complement. Late DNA replication was demonstrated in the allocyclic X and in the Y. Also Wolf (1969) found normal sex chromosomes in this species with no multivalents at male meiosis.
TL;DR: The combination of electrophysiological and fine structural evidence indicates that in this chordotonal organ the adequate stimulus of the scolopidia is an increase in their longitudinal tension but it is not possible to say which fine structural component responds to strain.
Abstract: The micromorphology of the tibio-tarsal joint of Periplaneta is described, based on the mesothoracic limb. There are two muscles acting on the joint, numbered 144 and 145. There is a connective chordotonal organ, which branches off from the trunk of N5 proximally and inserts on the intersegmental membrane distally. In addition, a previously undescribed group of campaniform sensilla is reported from the tibiotarsal joint. The tibio-tarsal chordotonal organ subdivides into a main branch and two side branches. It contains 26 bipolar sensory neurons, whose dendrites are associated distally with 14 scolopales. These scolopidia are arranged in three groups which differ in position, fine structure and number of cells per scolopale. There is one group I scolopidium in each of the side branches and two proximally in the main branch. Group 2 scolopidia are spread out along the main branch and group 3 scolopidia occur distally in the main branch. Group 1 scolopidia consist of two bipolar neurons, 15 to 20 $\mu m$ in diameter, whose dendrites, heavily sheathed, insert in a single scolopale. Group 2 scolopidia consist of two bipolar neurons, 8 to 15 $\mu m$ in diameter, whose dendrites are less well sheathed and insert in a single scolopale. Group 3 scolopidia consist of a single bipolar neuron, about 10 $\mu m$ in diameter, with a short, poorly sheathed dendrite inserting in a single scolopale. The scolopales of groups 1 and 2 are identical, consisting of the usual pattern of a ring of scolopale rods inserting into a distal cap and enclosing the cilia on the dendrite terminations. In this case, the cap is particularly long and pointed and both the cilia and the scolopale rods penetrate a long way into it. The cilia of the two members of a pair of dendrites are identical but the ciliary roots differ between the two members of a pair. Electrophysiological recordings show that the organ responds to downward and backward deflexion of the tarsus. The response comprises at least two classes of sensory fibre distinguishable both by their size and by their behaviour. The larger fibres show a unidirectional phasic and tonic response to extreme deflexion of the tarsus and are identified with the group 1 scolopidia. The smaller fibres show a unidirectional tonic response to the full range of deflexion of the tarsus and are identified with the group 2 scolopidia. On structural evidence, it is suggested that the differences in adaptation between these two groups of scolopidia is not likely to be caused by differences in mechanical attachment. The combination of electrophysiological and fine structural evidence indicates that in this chordotonal organ the adequate stimulus of the scolopidia is an increase in their longitudinal tension but it is not possible to say which fine structural component responds to strain.
TL;DR: The behavioural traits most extensively studied have been of a similar nature and include testosterone-dependent responses of the male sexual repertoire like mounting, intromission, and ejaculation or oestrogen-progesterone dependent responses ofThe female such as oestrous mounting activity and lordosis.
Abstract: The effects of hormones upon the development of behavioural characteristics have been reviewed extensively in the past few years (Young, Goy & Phoenix 1964; Levine & Mullins 1966; Goy 1966; Phoenix, Resko & Goy 1968; Whalen 1968). Much of the information contained in these reviews is limited to two species of rodents (rat and guinea-pig). A limitation which perhaps has greater consequences for theoretical considerations is the restriction of information to a set of behavioural traits requiring hormonal activation in adulthood before they can be displayed by the individual. An analogous situation in classical reproductive physiology would be the study of the effects of neonatal or foetal hormone treatments upon the development of prostatic secretory activity. In such a study, the prostate would remain non-secretory unless activated by the appropriate and essential hormones supplied during adulthood either by the gonad or by injection. The behavioural traits most extensively studied have been of a similar nature and include testosterone-dependent responses of the male sexual repertoire like mounting, intromission, and ejaculation or oestrogen-progesterone dependent responses of the female such as oestrous mounting activity and lordosis.
TL;DR: In this article, a newly calculated electron density map has allowed a more detailed description of the molecular structure to be given, in relation to the probable existence of hydrogen bonds and the conformations of side chains.
Abstract: A newly calculated electron density map has allowed a more detailed description of the molecular structure to be given. The structure can be described in detail in relation to the probable existence of hydrogen bonds and the conformations of side chains. The discovery of a new buried acid group which is part of a hydrogen bonding system involving the active serine has indicated how this serine can become a powerful nucleophile, by means of a 'charge relay system'. Diffraction studies of the binding of various substituents, coupled with accurate model building, have defined the catalytic binding site.
TL;DR: Three types of sexual cycles are found in mammals; first, the life-cycle—puberty, adulthood, senility; secondly, the breeding season; and thirdly, the oestrous or menstrual cycles, which are to be found in male and female mammals.
Abstract: Three types of sexual cycles are found in mammals. First, the life-cycle—puberty, adulthood, senility; secondly, the breeding season; and thirdly, the oestrous or menstrual cycles. The first two types of cycle are to be found in both male and female mammals, while the third type is found in females alone . Since the early embryo is sexually undifferentiated, it is of interest to see what factors are responsible for bringing about the development of the short and rhythmic oestrous and menstrual cycles in the female mammal, but the steady-state, arhythmic pattern of activity in the male mammal. Relatively recent work has shown that: ( a ) the oestrous and menstrual rhythm is essentially dependent on some neural mechanism in the brain, probably situated in the hypothalamic-preoptic region, and ( b ) that the factors responsible for the development of this neural mechanism in the brain of the female, but not in the male, are basically similar to the factors that bring about the development of the Mullerian duct system in the genetic female and the Wolffian duct system in the genetic male.
TL;DR: It may well be however that the plant and bacterial cysteineproteinases have converged onto a similar mechanism of action by two independent evolutionary pathways, as now seems apparent for the animal and bacterial serine proteinases.
Abstract: The cysteine proteinases form a group of enzymes which depend for their enzymic activity on the thiol group of a cysteine residue. Several which occur in plants have been investigated extensively and include papain, ficin and stem bromelain (Smith & Kimmel i960). Although the term papain, introduced last century to describe the proteolytic principle in papaya latex (Wurtz & Bouchut 1879) is still used to describe crude dried latex, the crystalline enzyme is readily obtained (Kimmel & Smith 1954). Ficin is known to consist of several closely related enzymes which have been resolved (Sgarbieri, Gupte, Kramer & Whitaker 1964), but for most structural and mechanistic studies the unresolved mixture of enzymes has been used. Stem bromelain also appears to be a mixture of at least two proteolytic enzymes which have not yet been resolved (Ota, Moore & Stein 1962; Murachi 1964). In spite of the recognized heterogeneity of ficin and stem bromelain, it does seem that both structurally and mechanistically they are similar to papain. Only one bacterial cysteine proteinase has received a detailed study, namely, streptococcal proteinase, and it appears to have little or no relation in its amino acid sequence with the plant enzymes (Liu, Stein, Moore & Elliott 1965). The functional groups involved in the catalytic mechanism are apparently the same as in the plant proteinases (Gerwin, Stein & Moore 1966; Liu 1967; Husain & Lowe 1968 a , c ), but the mechanism of action has not been extensively studied. It may well be however that the plant and bacterial cysteine proteinases have converged onto a similar mechanism of action by two independent evolutionary pathways, as now seems apparent for the animal and bacterial serine proteinases (Alden, Wright & Kraut, this volume, p. 119). Because the tertiary crystal structure of papain (Drenth, Jansonius, Koekoek, Swen & Wolthers 1968; see also the preceding paper, p. 231) is now known, a critical survey of this enzyme is apposite.
TL;DR: Changes in degenerating axons are similar, except that the largest thalamo-cortical fibres show a stage of neurofilamentous hyperplasia.
Abstract: The nature and immediate postoperative course of experimental degeneration of axon terminals have been studied in the somatic sensory cortex. The first somatic sensory area was examined at intervals of 2 to 6 days following lesions in the thalamus, opposite cortex or ipsilateral second somatic sensory area. There is a characteristic sequence of degenerative changes which affects the terminals of each of the afferent fibre systems studied. This commences as a simple, though marked, increase in electron density of the axoplasm with no loss of synaptic vesicles and little alteration in the size or shape of the terminal. Following this, there is a progressive loss of vesicles and disruption of the mitochondria with shrinkage of the terminal and its compression, invasion and fragmentation by astroglial processes. There is evidence that many fragments are phagocytosed by the invading astroglia but a thin sliver always remains attached at the synaptic contact zone. Within the range of survival periods used, no changes affect the synaptic region nor the postsynaptic profile and if the latter is a dendritic spine, it is not detached from the parent dendrite. Changes in degenerating axons are similar, except that the largest thalamo-cortical fibres show a stage of neurofilamentous hyperplasia. In the cortex at a distance from the lesion only smaller astrocytic processes are involved in breaking down the degenerating products; close to a lesion, however, all astrocytic processes and perikarya become involved and many atypical glial cells which are difficult to classify as astrocytes or oligodendrocytes become visible; the vascular pericytes also display large heterogeneous dense bodies and other inclusions.
TL;DR: It is concluded that the barnacles here tested are osmoconformers, able to adjust to small changes of environmental salinity by tissue acclimation, but evading too severe salinity changes by withdrawing into the protection of the shell.
Abstract: The responses of a number of barnacles to a wide range of salinity have been studied by observation of the activity and measurement of the depression of freezing point of the blood. In active barnacles of the species Elminius modestus, Balanus balanoides, B. crenatus, B. improvisus, B. hameri, B. balanus and Chthamalus stellatus the blood concentration conforms with changes in the external salinity. The concentration of the blood tends to remain slightly hyperosmotic to the fluid in the mantle cavity, and to the medium. With sudden changes of external salinity the blood concentration conforms within a few hours if cirral activity is maintained. When placed in such low salinities that activity is inhibited, E. modestus, B. balanoides, B. crenatus, B. improvisus, B. balanus and C. stellatus close the opercular valves with the result that the blood and mantle cavity fluid are maintained for some time at a level initially considerably hyperosmotic to the medium, but the blood is still only slightly hyperosmotic to the fluid remaining in the mantle cavity. There is no permanent control, and in time the blood concentration approximates to the external level. E. modestus, B. balanoides and B. improvisus from low salinity estuarine habitats, and B. crenatus after gradual reduction of salinity in the laboratory over a matter of days, exhibit tolerance to lower salinities than do specimens of the same species obtained from, or acclimated to normal salinities. Salinity acclimation is typical of osmoconformers lacking specific organs for effective regulation. It is concluded that the barnacles here tested are osmoconformers, able to adjust to small changes of environmental salinity by tissue acclimation, but evading too severe salinity changes by withdrawing into the protection of the shell. The deep sea B. hameri , however, does not close up when immersed in dilute sea water, and appears to be relatively stenohaline with limited ability to acclimate to low salinity. The intertidal E. modestus and B. balanoides , and the low-tidal to sublittoral B. crenatus , are tolerant, after experimental or natural acclimation, of salinities down to 14 to 17 ‰. The estuarine B. improvisus can, with gradual acclimation, be induced to be active in a salinity of about 2 ‰ . This species is remarkably tolerant of dilution of the blood, and its distribution into regions of low salinity is evidently due to a wide tissue resistance and not to any ability to regulate.
TL;DR: The present writer has collected more material from the type locality and has used a comparatively new technique on the petrified axes present, incorporating them into an emended diagnosis of the genus and a lectotype has been designated.
Abstract: The first description of this plant was published by Heard (1927). The present writer has collected more material from the type locality and has used a comparatively new technique on the petrified axes present. This involved sawing the axes into thin sections, grinding these smooth with carborundum powder and then polishing them in chromic oxide powder. These permanent preparations have yielded more precise data on the anatomy of the axes. The spores are described for the first time. A reconstruction of the aerial parts of the plant is given. The results have been incorporated into an emended diagnosis of the genus and a lectotype has been designated. The taxonomic position of Gosslingia is discussed in relation to a new classification of the psilophytes proposed by Banks. One of the most interesting features in Gosslingia is the axillary tubercle, a small protuberance occurring below each dichotomy. A survey of other Devonian plants bearing this structure is given and its morphological nature is discussed in the light of evidence produced here and in other recent work.
TL;DR: The most undesirable side effect of a new gestagen intended for the treatment of pregnancy disturbances is the virilization of female foetuses, and the drug developed in 1961 had to be free of virilizing side effects.
Abstract: The most undesirable side effect of a new gestagen intended for the treatment of pregnancy disturbances is the virilization of female foetuses. In 1961, our drug company developed a new highly effective gestagen, cyproterone acetate (figure 1) (Wiechert & Neumann 1965). We were given the task to test this substance in animal experiments for desirable and undesirable effects, particularly for the occurrence of virilization. As this drug was intended for the treatment of pregnancy disturbances, such as threatening or habitual abortion, it had to be free of virilizing side effects.