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This page lists all time most cited articles for this title. Please use the publication date filters on the left if you would like to restrict this list to recently published content, for example to articles published in the last three years. The number of times each article was cited is displayed to the right of its title and can be clicked to access a list of all titles this article has been cited by.
- Cited by 940
The anatomy of language: contributions from functional neuroimaging
- CATHY J. PRICE
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- 23 November 2000, pp. 335-359
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This article illustrates how functional neuroimaging can be used to test the validity of neurological and cognitive models of language. Three models of language are described: the 19th Century neurological model which describes both the anatomy and cognitive components of auditory and visual word processing, and 2 20th Century cognitive models that are not constrained by anatomy but emphasise 2 different routes to reading that are not present in the neurological model. A series of functional imaging studies are then presented which show that, as predicted by the 19th Century neurologists, auditory and visual word repetition engage the left posterior superior temporal and posterior inferior frontal cortices. More specifically, the roles Wernicke and Broca assigned to these regions lie respectively in the posterior superior temporal sulcus and the anterior insula. In addition, a region in the left posterior inferior temporal cortex is activated for word retrieval, thereby providing a second route to reading, as predicted by the 20th Century cognitive models. This region and its function may have been missed by the 19th Century neurologists because selective damage is rare. The angular gyrus, previously linked to the visual word form system, is shown to be part of a distributed semantic system that can be accessed by objects and faces as well as speech. Other components of the semantic system include several regions in the inferior and middle temporal lobes. From these functional imaging results, a new anatomically constrained model of word processing is proposed which reconciles the anatomical ambitions of the 19th Century neurologists and the cognitive finesse of the 20th Century cognitive models. The review focuses on single word processing and does not attempt to discuss how words are combined to generate sentences or how several languages are learned and interchanged. Progress in unravelling these and other related issues will depend on the integration of behavioural, computational and neurophysiological approaches, including neuroimaging.
- Cited by 664
Synaptic organisation of the basal ganglia
- J. P. BOLAM, J. J. HANLEY, P. A. C. BOOTH, M. D. BEVAN
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- 01 May 2000, pp. 527-542
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The basal ganglia are a group of subcortical nuclei involved in a variety of processes including motor, cognitive and mnemonic functions. One of their major roles is to integrate sensorimotor, associative and limbic information in the production of context-dependent behaviours. These roles are exemplified by the clinical manifestations of neurological disorders of the basal ganglia. Recent advances in many fields, including pharmacology, anatomy, physiology and pathophysiology have provided converging data that have led to unifying hypotheses concerning the functional organisation of the basal ganglia in health and disease. The major input to the basal ganglia is derived from the cerebral cortex. Virtually the whole of the cortical mantle projects in a topographic manner onto the striatum, this cortical information is ‘processed’ within the striatum and passed via the so-called direct and indirect pathways to the output nuclei of the basal ganglia, the internal segment of the globus pallidus and the substantia nigra pars reticulata. The basal ganglia influence behaviour by the projections of these output nuclei to the thalamus and thence back to the cortex, or to subcortical ‘premotor’ regions. Recent studies have demonstrated that the organisation of these pathways is more complex than previously suggested. Thus the cortical input to the basal ganglia, in addition to innervating the spiny projection neurons, also innervates GABA interneurons, which in turn provide a feed-forward inhibition of the spiny output neurons. Individual neurons of the globus pallidus innervate basal ganglia output nuclei as well as the subthalamic nucleus and substantia nigra pars compacta. About one quarter of them also innervate the striatum and are in a position to control the output of the striatum powerfully as they preferentially contact GABA interneurons. Neurons of the pallidal complex also provide an anatomical substrate, within the basal ganglia, for the synaptic integration of functionally diverse information derived from the cortex. It is concluded that the essential concept of the direct and indirect pathways of information flow through the basal ganglia remains intact but that the role of the indirect pathway is more complex than previously suggested and that neurons of the globus pallidus are in a position to control the activity of virtually the whole of the basal ganglia.
- Cited by 539
Fibrocartilage in tendons and ligaments — an adaptation to compressive load
- M. BENJAMIN, J. R. RALPHS
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- 01 November 1998, pp. 481-494
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Where tendons and ligaments are subject to compression, they are frequently fibrocartilaginous. This occurs at 2 principal sites: where tendons (and sometimes ligaments) wrap around bony or fibrous pulleys, and in the region where they attach to bone, i.e. at their entheses. Wrap-around tendons are most characteristic of the limbs and are commonly wider at their point of bony contact so that the pressure is reduced. The most fibrocartilaginous tendons are heavily loaded and permanently bent around their pulleys. There is often pronounced interweaving of collagen fibres that prevents the tendons from splaying apart under compression. The fibrocartilage can be located within fascicles, or in endo- or epitenon (where it may protect blood vessels from compression or allow fascicles to slide). Fibrocartilage cells are commonly packed with intermediate filaments which could be involved in transducing mechanical load. The ECM often contains aggrecan which allows the tendon to imbibe water and withstand compression. Type II collagen may also be present, particularly in tendons that are heavily loaded. Fibrocartilage is a dynamic tissue that disappears when the tendons are rerouted surgically and can be maintained in vitro when discs of tendon are compressed. Finite element analyses provide a good correlation between its distribution and levels of compressive stress, but at some locations fibrocartilage is a sign of pathology. Enthesis fibrocartilage is most typical of tendons or ligaments that attach to the epiphyses of long bones where it may also be accompanied by sesamoid and periosteal fibrocartilages. It is characteristic of sites where the angle of attachment changes throughout the range of joint movement and it reduces wear and tear by dissipating stress concentration at the bony interface. There is a good correlation between the distribution of fibrocartilage within an enthesis and the levels of compressive stress. The complex interlocking between calcified fibrocartilage and bone contributes to the mechanical strength of the enthesis and cartilage-like molecules (e.g. aggrecan and type II collagen) in the ECM contribute to its ability to withstand compression. Pathological changes are common and are known as enthesopathies.
- Cited by 495
Peripheral nerve regeneration and neurotrophic factors
- GIORGIO TERENGHI
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- 01 January 1999, pp. 1-14
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The role of neurotrophic factors in the maintenance and survival of peripheral neuronal cells has been the subject of numerous studies. Administration of exogenous neurotrophic factors after nerve injury has been shown to mimic the effect of target organ-derived trophic factors on neuronal cells. After axotomy and during peripheral nerve regeneration, the neurotrophins NGF, NT-3 and BDNF show a well defined and selective beneficial effect on the survival and phenotypic expression of primary sensory neurons in dorsal root ganglia and of motoneurons in spinal cord. Other neurotrophic factors such as CNTF, GDNF and LIF also exert a variety of actions on neuronal cells, which appear to overlap and complement those of the neurotrophins. In addition, there is an indirect contribution of GGF to nerve regeneration. GGF is produced by neurons and stimulates proliferation of Schwann cells, underlining the close interaction between neuronal and glial cells during peripheral nerve regeneration. Different possibilities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. The studies reviewed in this article show the therapeutic potential of neurotrophic factors for the treatment of peripheral nerve injury and for neuropathies.
- Cited by 311
Changes in muscle mass and phenotype and the expression of autocrine and systemic growth factors by muscle in response to stretch and overload
- GEOFFREY GOLDSPINK
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- 01 April 1999, pp. 323-334
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The study of the underlying mechanisms by which cells respond to mechanical stimuli, i.e. the link between the mechanical stimulus and gene expression, represents a new and important area in the morphological sciences. Several cell types (‘mechanocytes’), e.g. osteoblasts and fibroblasts as well as smooth, cardiac and skeletal muscle cells are activated by mechanical strain and there is now mounting evidence that this involves the cytoskeleton. Muscle offers one of the best opportunities for studying this type of mechanotransduction as the mechanical activity generated by and imposed upon muscle tissue can be accurately controlled and measured in both in vitro and in vivo systems. Muscle is highly responsive to changes in functional demands. Overload leads to hypertrophy, whilst decreased load force generation and immobilisation with the muscle in the shortened position leads to atrophy. For instance it has been shown that stretch is an important mechanical signal for the production of more actin and myosin filaments and the addition of new sarcomeres in series and in parallel. This is preceded by upregulation of transcription of the appropriate genes some of which such as the myosin isoforms markedly change the muscle phenotype. Indeed, the switch in the expression induced by mechanical activity of myosin heavy chain genes which encode different molecular motors is a means via which the tissue adapts to a given type of physical activity. As far as increase in mass is concerned, our group have cloned the cDNA of a splice variant of IGF that is produced by active muscle that appears to be the factor that controls local tissue repair, maintenance and remodelling. From its sequence it can be seen that it is derived from the IGF gene by alternative splicing but it has different exons to the liver isoforms. It has a 52 base insert in the E domain which alters the reading frame of the 3′ end. Therefore, this splice variant of IGF-1 is likely to bind to a different binding protein which exists in the interstitial tissue spaces of muscle, neuronal tissue and bone. This would be expected to localise its action as it would be unstable in the unbound form which is important as its production would not disturb the glucose homeostasis unduly. This new growth factor has been called mechano growth factor (MGF) to distinguish it from the liver IGFs which have a systemic mode of action. Although the liver is usually thought of as the source of circulating IGF, it has recently been shown that during exercise skeletal muscle not only produces much of the circulating IGF but active musculature also utilises most of the IGF produced. We have cloned both an autocrine and endocrine IGF-1, both of which are upregulated in cardiac as well as skeletal muscle when subjected to overload. It has been shown that, in contrast to normal muscle, MGF is not detectable in dystrophic mdx muscles even when subjected to stretch and stretch combined with electrical stimulation. This is true for muscular dystrophies that are due to the lack of dystrophin (X-linked) and due to a laminin deficiency (autosomal), thus indicating that the dystrophin cytoskeletal complex may be involved in the mechanotransduction mechanism. When this complex is defective the necessary systemic as well as autocrine IGF-1 growth factors required for local repair are not produced and the ensuing cell death results in progressive loss of muscle mass. The discovery of the locally produced IGF-1 appears to provide the link between the mechanical stimulus and the activation of gene expression.
- Cited by 308
Review. Articular cartilage chondrons: form, function and failure
- C. ANTHONY POOLE
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- 01 July 1997, pp. 1-13
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The chondrocyte and its pericellular microenvironment together represent the chondron, historically considered the primary structural, functional and metabolic unit of articular and other hyaline cartilages. This review summarises research over the last 10 years to establish the molecular anatomy, functional properties and metabolic contribution of the chondron in articular cartilage homeostasis, and its failure during the initiation and progression of degenerative osteoarthritis.
- Cited by 303
Anatomy of the pig heart: comparisons with normal human cardiac structure
- SIMON J. CRICK, MARY N. SHEPPARD, SIEW YEN HO, LIOR GEBSTEIN, ROBERT H. ANDERSON
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- 01 July 1998, pp. 105-119
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Transgenic technology has potentially solved many of the immunological difficulties of using pig organs to support life in the human recipient. Nevertheless, other problems still remain. Knowledge of cardiac anatomy of the pig (Sus scrofa) is limited despite the general acceptance in the literature that it is similar to that of man. A qualitative analysis of porcine and human cardiac anatomy was achieved by gross examination and dissection of hearts with macrophotography. The porcine organ had a classic ‘Valentine heart’ shape, reflecting its location within the thorax and to the orientation of the pig's body (unguligrade stance). The human heart, in contrast, was trapezoidal in silhouette, reflecting man's orthograde posture. The morphologically right atrium of the pig was characterised by the tubular shape of its appendage (a feature observed on the left in the human heart). The porcine superior and inferior caval veins opened into the atrium at right angles to one another, whereas in man the orifices were directly in line. A prominent left azygous vein (comparable to the much reduced left superior caval or oblique vein in man) entered on the left side of the pig heart and drained via the coronary sinus. The porcine left atrium received only 2 pulmonary veins, whereas 4 orifices were generally observed in man. The sweep between the inlet and outlet components of the porcine right ventricle was less marked than in man, and a prominent muscular moderator band was situated in a much higher position within the porcine right ventricle compared with that of man. The apical components of both porcine ventricles possessed very coarse trabeculations, much broader than those observed in the human ventricles. In general, aortic-mitral fibrous continuity was reduced in the outlet component of the porcine left ventricle, with approximately two-thirds of the aortic valve being supported by left ventricular musculature. Several potentially significant differences exist between porcine and human hearts. It is important that these differences are considered as the arguments continue concerning the use of transgenic pig hearts for xenotransplantation.
- Cited by 286
The menisci of the knee joint. Anatomical and functional characteristics, and a rationale for clinical treatment
- KAROLA MESSNER, JIZONG GAO
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- 01 August 1998, pp. 161-178
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The menisci and their insertions into bone (entheses) represent a functional unit. Thanks to their firm entheses, the menisci are able to distribute loads and therefore reduce the stresses on the tibia, a function which is regarded essential for cartilage protection and prevention of osteoarthrosis. The tissue of the hypocellular meniscal body consists mainly of water and a dense elaborate type I collagen network with a predominantly circumferential alignment. The content of different collagens, proteoglycans and nonproteoglycan proteins shows significant regional variations probably reflecting functional adaptation. The meniscal horns are attached via meniscal insertional ligaments mainly to tibial bone. At the enthesis, the fibres of the insertional ligaments attach to bone via uncalcified and calcified fibrocartilages. This anatomical configuration of gradual transition from soft to hard tissue, which is identical to other ligament entheses, is certainly essential for normal mechanical function and probably protects this vulnerable transition between 2 biomechanically different tissues from failure. Clinical treatment of meniscal tears needs to be based on these special anatomical and functional characteristics. Partial meniscectomy will preserve some of the load distribution function of the meniscus only when the meniscal body enthesis entity is preserved. Repair of peripheral longitudinal tears will heal and probably preserve the load distribution function of the meniscus, whereas radial tears through the whole meniscal periphery or more central and complex tears may be induced to heal, but probably do not preserve the load distribution function. There is no proof that replacement of the meniscus with an allograft can reestablish some of the important meniscal functions, and thereby prevent or reduce the development of osteoarthrosis which is common after meniscectomy. After implantation, major problems are the remodelling of the graft to inferior structural, biochemical and mechanical properties and its insufficient fixation to bone which fails to duplicate a normal anatomical configuration and therefore a functional meniscal enthesis.
- Cited by 286
Facial growth in Cercocebus torquatus: an application of three-dimensional geometric morphometric techniques to the study of morphological variation
- PAUL O'HIGGINS, NICHOLAS JONES
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- 01 August 1998, pp. 251-272
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This paper presents a study of 3-dimensional growth in the facial skeleton of the mangabey, Cercocebus torquatus. The pattern of facial cortical remodelling in this species is already well mapped from an earlier study. In this paper we consider the extent to which these remodelling maps relate to ontogenetic changes in size and shape of the face. This study is based on 31 facial landmarks taken from 49 adult and subadult faces. Our analysis draws on some of the tools of geometric morphometrics and we take this opportunity to describe our implementation of these tools for 3D data. The geometric analysis permits the known remodelling maps to be interpreted in the context of the general pattern of facial growth in this species. We are also able to examine sexual dimorphism in the face of this species and consider the extent to which males and females share similar ontogenetic allometries. Our findings indicate that the general pattern of size-related shape variation during facial growth is more or less identical for males and females up to eruption of the third permanent maxillary molar (M3). After this, ontogenetic allometries appear to diverge. The finding of a common growth allometry that is well approximated for younger specimens by a simple linear model is consistent with the earlier findings of a consistent pattern of facial remodelling up to M3 eruption. We consider the implications of these findings in terms of the potential for these approaches in the study of comparative growth in related species.
- Cited by 275
Release of vasoactive substances from endothelial cells by shear stress and purinergic mechanosensory transduction
- GEOFFREY BURNSTOCK
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- 01 April 1999, pp. 335-342
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The evidence for release of vasoactive substances from endothelial cells in response to shear stress caused by the viscous drag of passing fluids is reviewed and, in particular, its physiological significance both in short-term regulation of blood vessel tone and in long-term regulation of cell growth, differentiation, proliferation, and cell death in pathophysiological conditions is discussed. A new concept of purinergic mechanosensory transduction, particularly in relation to nociception, is introduced. It is proposed that distension of tubes (including ureter, vagina, salivary and bile ducts, gut) and sacs (including urinary and gall bladders, and lung) leads to release of ATP from the lining epithelium, which then acts on P2X2/3 receptors on subepithelial sensory nerves to convey information to the CNS.
- Cited by 265
The study of morphological variation in the hominid fossil record: biology, landmarks and geometry
- PAUL O'HIGGINS
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- 01 July 2000, pp. 103-120
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This review considers some recent advances in shape analysis based on landmark data, and focuses on the application of these methods to the study of skeletal evolution in primates. These advances have provoked some controversy. The major aims of this review are to put these debates in context and to provide an overview for the nonmathematician. The purpose of morphometric studies is considered, together with issues relating to the nature, significance and identification of landmarks before turning to a review of available technologies for the analysis of morphological variation. These are considered in terms of underlying models and assumptions in order to clarify when each is appropriate. To illustrate the application of these methods, 3 example studies are presented. The first examines differences amongst ancient and modern adult human crania using 2-dimensional data. The second illustrates the extension of these methods into 3 dimensions in a study of facial growth in monkeys. The third presents an application to the analysis of the form of the hominoid talus. The review ends with an account of available software resources for shape analysis.
- Cited by 214
VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy
- MARK I. HOBSON, COLIN J. GREEN, GIORGIO TERENGHI
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- 06 February 2001, pp. 591-605
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Whilst there is an increased understanding of the cell biology of nerve regeneration, it remains unclear whether there is a direct interrelationship between vascularisation and efficacy of nerve regeneration within a nerve conduit. To establish this is important as in clinical surgery peripheral nerve conduit grafting has been widely investigated as a possible alternative to the use of nerve autografts. The aim of this study was to assess whether vascular endothelial growth factor (VEGF), a highly specific endothelial cell mitogen, can enhance vascularisation and, indirectly, axonal regeneration within a silicone nerve regeneration chamber. Chambers containing VEGF (500–700 ng/ml) in a laminin-based gel (Matrigel) were inserted into 1 cm rat sciatic nerve defects and nerve regeneration examined in relation to angiogenesis between 5 and 180 d. Longitudinal sections were stained with antibodies against endothelial cells (RECA-1), axons (neurofilament) and Schwann cells (S-100) to follow the progression of vascular and neural elements. Computerised image analysis demonstrated that the addition of VEGF significantly increased blood vessel penetration within the chamber from d 5, and by d 10 this correlated with an increase of axonal regeneration and Schwann cell migration. The pattern of increased nerve regeneration due to VEGF administration was maintained up to 180 d, when myelinated axon counts were increased by 78% compared with plain Matrigel control. Furthermore the dose-response of blood vessel regeneration to VEGF was clearly reflected in the increase of axonal regrowth and Schwann cell proliferation, indicating the close relationship between regenerating nerves and blood vessels within the chamber. Target organ reinnervation was enhanced by VEGF at 180 d as measured through the recovery of gastrocnemius muscle weights and footpad axonal terminal density, the latter showing a significant increase over controls (P < 0.05). The results demonstrate an overall relationship between increased vascularisation and enhanced nerve regeneration within an acellular conduit, and highlight the interdependence of the 2 processes.
- Cited by 209
The role of laminins in basement membrane function
- MONIQUE AUMAILLEY, NEIL SMYTH
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- 01 July 1998, pp. 1-21
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Laminins are a family of multifunctional macromolecules, ubiquitous in basement membranes, and represent the most abundant structural noncollagenous glycoproteins of these highly specialised extracellular matrices. Their discovery started with the difficult task of isolating molecules produced by cultivated cells or extracted from tissues. The development of molecular biology techniques has facilitated and accelerated the identification and the characterisation of new laminin variants making it feasible to identify full-length polypeptides which have not been purified. Further, genetically engineered laminin fragments can be generated for studies of their structure-function relationship, permitting the demonstration that laminins are involved in multiple interactions with themselves, with other components of the basal lamina, and with cells. It endows laminins with a central role in the formation, the architecture, and the stability of basement membranes. In addition, laminins may both separate and connect different tissues, i.e. the parenchymal and the interstitial connective tissues. Laminins also provide adjacent cells with a mechanical scaffold and biological information either directly by interacting with cell surface components, or indirectly by trapping growth factors. In doing so they trigger and control cellular functions. Recently, the structural and biological diversity of the laminins has started to be elucidated by gene targeting and by the identification of laminin defects in acquired or inherited human diseases. The consequent phenotypes highlight the pivotal role of laminins in determining heterogeneity in basement membrane functions.
- Cited by 198
If bone is the answer, then what is the question?
- R. HUISKES
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- 20 October 2000, pp. 145-156
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In the 19th century, several scientists attempted to relate bone trabecular morphology to its mechanical, load-bearing function. It was suggested that bone architecture was an answer to requirements of optimal stress transfer, pairing maximal strength to minimal weight, according to particular mathematical design rules. Using contemporary methods of analysis, stress transfer in bones was studied and compared with anatomical specimens, from which it was hypothesised that trabecular architecture is associated with stress trajectories. Others focused on the biological processes by which trabecular architectures are formed and on the question of how bone could maintain the relationship between external load and architecture in a variable functional environment. Wilhelm Roux introduced the principle of functional adaptation as a self- organising process based in the tissues. Julius Wolff, anatomist and orthopaedic surgeon, entwined these 3 issues in his book The Law of Bone Remodeling (translation), which set the stage for biomechanical research goals in our day. ‘Wolff's Law’ is a question rather than a law, asking for the requirements of structural optimisation. In this article, based on finite element analysis (FEA) results of stress transfer in bones, it is argued that it was the wrong question, putting us on the wrong foot. The maximal strength/minimal weight principle does not provide a rationale for architectural formation or adaptation; the similarity between trabecular orientation and stress trajectories is circumstantial, not causal. Based on computer simulations of bone remodelling as a regulatory process, governed by mechanical usage and orchestrated by osteocyte mechanosensitivity, it is shown that Roux's paradigm, conversely, is a realistic proposition. Put in a quantitative regulatory context, it can predict both trabecular formation and adaptation. Hence, trabecular architecture is not an answer to Wolff's question, in the sense of this article's title. There are no mathematical optimisation rules for bone architecture; there is just a biological regulatory process, producing a structure adapted to mechanical demands by the nature of its characteristics, adequate for evolutionary endurance. It is predicted that computer simulation of this process can help us to unravel its secrets.
- Cited by 194
Human evolution: taxonomy and paleobiology
- BERNARD WOOD, BRIAN G. RICHMOND
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- 01 July 2000, pp. 19-60
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This review begins by setting out the context and the scope of human evolution. Several classes of evidence, morphological, molecular, and genetic, support a particularly close relationship between modern humans and the species within the genus Pan, the chimpanzee. Thus human evolution is the study of the lineage, or clade, comprising species more closely related to modern humans than to chimpanzees. Its stem species is the so-called ‘common hominin ancestor’, and its only extant member is Homo sapiens. This clade contains all the species more closely-related to modern humans than to any other living primate. Until recently, these species were all subsumed into a family, Hominidae, but this group is now more usually recognised as a tribe, the Hominini. The rest of the review sets out the formal nomenclature, history of discovery, and information about the characteristic morphology, and its behavioural implications, of the species presently included in the human clade. The taxa are considered within their assigned genera, beginning with the most primitive and finishing with Homo. Within genera, species are presented in order of geological age. The entries conclude with a list of the more important items of fossil evidence, and a summary of relevant taxonomic issues.
- Cited by 191
Asymmetry in the epithalamus of vertebrates
- MIGUEL L. CONCHA, STEPHEN W. WILSON
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- 23 August 2001, pp. 63-84
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The epithalamus is a major subdivision of the diencephalon constituted by the habenular nuclei and pineal complex. Structural asymmetries in this region are widespread amongst vertebrates and involve differences in size, neuronal organisation, neurochemistry and connectivity. In species that possess a photoreceptive parapineal organ, this structure projects asymmetrically to the left habenula, and in teleosts it is also situated on the left side of the brain. Asymmetries in size between the left and right sides of the habenula are often associated with asymmetries in neuronal organisation, although these two types of asymmetry follow different evolutionary courses. While the former is more conspicuous in fishes (with the exception of teleosts), asymmetries in neuronal organisation are more robust in amphibia and reptiles. Connectivity of the parapineal organ with the left habenula is not always coupled with asymmetries in habenular size and/or neuronal organisation suggesting that, at least in some species, assignment of parapineal and habenular asymmetries may be independent events.
The evolutionary origins of epithalamic structures are uncertain but asymmetry in this region is likely to have existed at the origin of the vertebrate, perhaps even the chordate, lineage. In at least some extant vertebrate species, epithalamic asymmetries are established early in development, suggesting a genetic regulation of asymmetry. In some cases, epigenetic factors such as hormones also influence the development of sexually dimorphic habenular asymmetries. Although the genetic and developmental mechanisms by which neuroanatomical asymmetries are established remain obscure, some clues regarding the mechanisms underlying laterality decisions have recently come from studies in zebrafish. The Nodal signalling pathway regulates laterality by biasing an otherwise stochastic laterality decision to the left side of the epithalamus. This genetic mechanism ensures a consistency of epithalamic laterality within the population. Between species, the laterality of asymmetry is variable and a clear evolutionary picture is missing. We propose that epithalamic structural asymmetries per se and not the laterality of these asymmetries are important for the behaviour of individuals within a species. A consistency of the laterality within a population may play a role in social behaviours between individuals of the species.
- Cited by 171
The distribution of trigeminovascular afferents in the nonhuman primate brain Macaca nemestrina: a c-fos immunocytochemical study
- PETER J. GOADSBY, KAREN L. HOSKIN
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- Published online by Cambridge University Press:
- 01 April 1997, pp. 367-375
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An understanding of migraine must be based on data concerning the anatomy and physiology of the pain-sensitive intracranial structures. Stimulation of the superior sagittal sinus produces changes in brain blood flow and changes in neuropeptide levels similar to those seen in humans during migraine. To better understand the anatomy of the central ramifications of pain-sensitive intracranial structures we have examined the distribution of c-fos immunoreactivity in the monkey when the sinus is stimulated. Six adult Macaca nemestrina monkeys were anaesthetised. The superior sagittal sinus was isolated after a midline craniotomy and a paraffin well created. At 24 h after completion of the surgery the sinus was stimulated electrically for 1 h and the brain subsequently removed and processed for c-fos. In control animals in which the sinus was isolated but not stimulated there was a small amount of c-fos expression in the caudal brainstem and upper cervical spinal cord. Stimulation of the superior sagittal sinus evoked expression of c-fos in the caudal superfical laminae of the trigeminal nucleus and in superficial laminae of the dorsal horn of the C1 level of the upper cervical spinal cord. A lesser amount of c-fos was seen at C2 while no significant labelling above control was observed at C3. These data, while largely confirming the results from the cat concerning the central distribution trigeminovascular afferents, underscore a possibly unique specialisation of trigeminovascular afferents at the C1 level. Given the close evolutionary relationship of the monkey to man it is likely that the cells described in this study represent for primates the nucleus that mediates the pain of migraine.
- Cited by 166
Muscle fibre size and type distribution in thoracic and lumbar regions of erector spinae in healthy subjects without low back pain: normal values and sex differences
- A. F. MANNION, G. A. DUMAS, R. G. COOPER, F. J. ESPINOSA, M. W. FARIS, J. M. STEVENSON
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- 01 June 1997, pp. 505-513
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This study sought to investigate the normal muscle fibre size and type distribution of the human erector spinae, both in thoracic and lumbar regions, in a group of 31 young healthy male (n=17) and female (n=14) volunteers. Two percutaneous muscle biopsy samples were obtained under local anaesthesia, from the belly of the left erector spinae, at the levels of the 10th thoracic and 3rd lumbar vertebrae. Samples were prepared for routine histochemistry for the identification of fibre types. Fibre size (cross-sectional area (CSA) and narrow diameter (ND)) was quantified using computerised image analysis. The mean CSA/ND for each fibre type was greater in the thoracic than the lumbar region, but there was no difference between the 2 regions either for percentage type I (i.e. percentage distribution by number), percentage type I area (i.e. relative area of the muscle occupied by type I fibres) or the ratio describing the size of the type I fibre relative to that of the type II. Men had larger fibres than women, for each fibre type and at both sampling sites. In the men, each fibre type was of a similar mean size, whereas in the women the type I fibres were considerably larger than both the type II A and type II B fibres, with no difference between the latter two. In both regions of the erector spinae there was no difference between men and women for the proportion (%) of a given fibre type, but the percentage type I fibre area was significantly higher in the women.
The erector spinae display muscle fibre characteristics which are clearly very different from those of other skeletal muscles, and which, with their predominance of relatively large type I (slow twitch) fibres, befit their function as postural muscles. Differences between thoracic and lumbar fascicles of the muscle, and between the muscles of men and women, may reflect adaptive responses to differences in function. In assessing the degree of any pathological change in the muscle of patients with low back pain, it seems clear that (1) sex cannot be disregarded and (2) ‘atrophied’ (using the criteria from other muscles) type II fibres are not necessarily abnormal for the erector spinae, particularly in women.
- Cited by 166
Perivascular spaces in the basal ganglia of the human brain: their relationship to lacunes
- H. POLLOCK, M. HUTCHINGS, R. O. WELLER, E-T. ZHANG
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- Published online by Cambridge University Press:
- 01 October 1997, pp. 337-346
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There is evidence for lymphatic drainage of interstitial fluid from the brain along perivascular spaces in a number of mammalian species. Ultrastructural studies suggest that there are similar drainage pathways in the human cerebral cortex. Perivascular spaces in the basal ganglia, however, differ from those in the cortex in that they dilate to form lacunes and rarely accumulate beta-amyloid (amyloid angiopathy) in Alzheimer's disease; in the cortex, lacunes are rare but amyloid angiopathy is common. The aim of the present study is to compare the structure of perivascular spaces in the basal ganglia and at the anterior perforated substance with perivascular spaces in the cerebral cortex. Eight postmortem brains from patients aged 23–80 years (mean 68 y) were examined by light microscopy, by scanning and transmission electron microscopy and by direct visualisation of etched paraffin blocks. The results show that arteries in the basal ganglia are surrounded by 2 distinct coats of leptomeninges separated by a perivascular space which is continuous with the perivascular space around arteries in the subarachnoid space. The inner layer of leptomeninges closely invests the adventitia of the vessel wall and the outer layer is continuous with the pia mater on the surface of the brain at the anterior perforated substance. Veins in the basal ganglia have no outer layer of leptomeninges and thus the perivascular space is continuous with the subpial space. The anatomy of the periarterial spaces in the basal ganglia differs significantly from that in the cerebral cortex where there is only a single periarterial layer of leptomeninges. Differences in structure of perivascular spaces around arteries may reflect relative efficiencies in the drainage of interstitial fluid from different sites in the brain. Futhermore, the structure of the perivascular spaces may contribute to the relatively high frequency of lacunes in the basal ganglia, and the low frequency of amyloid angiopathy at this site in Alzheimer's disease.
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Curving and looping of the internal carotid artery in relation to the pharynx: frequency, embryology and clinical implications
- FRIEDRICH PAULSEN, BERNHARD TILLMANN, CHRISTOS CHRISTOFIDES, WALBURGA RICHTER, JÜRGEN KOEBKE
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- Published online by Cambridge University Press:
- 23 November 2000, pp. 373-381
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Variations of the course of the internal carotid artery in the parapharyngeal space and their frequency were studied in order to determine possible risks for acute haemorrhage during pharyngeal surgery and traumatic events, as well as their possible relevance to cerebrovascular disease. The course of the internal carotid artery showed no curvature in 191 cases, but in 74 cases it had a medial, lateral or ventrocaudal curve, and 17 preparations showed kinking (12) or coiling (5) out of a total of 265 dissected carotid sheaths and 17 corrosion vascular casts. In 6 cases of kinking and 2 of coiling, the internal carotid artery was located in direct contact with the tonsillar fossa. No significant sex differences were found. Variations of the internal carotid artery leading to direct contact with the pharyngeal wall are likely to be of great clinical relevance in view of the large number of routine procedures performed. Whereas coiling is ascribed to embryological causes, curving is related to ageing and kinking is thought to be exacerbated by arteriosclerosis or fibromuscular dysplasia with advancing age and may therefore be of significance in relation to the occurrence of cerebrovascular symptoms.