Bone Strength During Growth: Influence of Growth Rate on Cortical Porosity and Mineralization

Although it is well accepted that bone architecture adapts to withstand the loads placed on it, the manner in which this occurs in the immature growing skeleton is not fully understood. To investigate the possible mechanisms, we have compared morphometric differences between tibiae from chickens with fast and those with slow growth potential and also distinguished between the effects of genetic potential and growth rate on their impact on bone quality. Two different fast-growing (ad lib modern) strains, one additionally feed-restricted and one slow-growing (control) strain of chicken, were compared at 15 and 42 days of age. The ad lib modern strains had similar final body weights and were approximately twice the weight of the control and restricted-fed birds. Tibiae from the control and restricted birds had a higher ash content and lower porosity than the ad lib modern strain at 42 days. The porosity was a result of rapid primary osteon formation at the periosteal surface and incomplete infilling of the resultant canal by osteoblasts. When adjusted to average body weight of contemporaries, bones from the control strain and the restricted-fed modern birds were stiffer and at least as strong as those from the fast growing ad lib-fed birds. In conclusion, rapid bone deposition at the periosteal surface was associated with decreased mineralization, increased cortical porosity, and altered biomechanical properties. Our results also indicate that growth rate, and not genetic potential, of the fast growing birds was responsible for the rapid periosteal bone deposition.     

Longitudinal assessment of psychopathological domains over late-stage schizophrenia in relation to duration of initially untreated psychosis: 3-year prospective study in a long-term inpatient population

There remains uncertainty regarding any progressive nature of psychopathology and cognitive dysfunction in late-stage schizophrenia, and whether duration of initially untreated psychosis (DUP) might be associated with such 'progression'. This study examines longitudinally, over 3 years, the psychopathology and neuropsychology in 82 inpatients with DSM-IV schizophrenia, many of whom were admitted in the pre-neuroleptic era. Increase in executive dysfunction exceeded that in general cognitive impairment. Positive but not negative symptom severity decreased modestly; the primary predictor of negative symptom severity was DUP. On index assessment, psychopathology evidenced a three-factor structure; at follow-up, psychomotor poverty evidenced greater prominence and cohesion, and was on both occasions predicted primarily by DUP, while reality distortion was altered and disorganisation disassembled into alternative elements. It would appear that as years of chronic, refractory illness accrue, psychomotor poverty becomes more sharply delineated and dominant within the overall structure of psychopathology, and its prominence is predicted enduringly by DUP.     

3D morphometrics of craniofacial dysmorphology reveals sex-specific asymmetries in schizophrenia

Over early fetal life cerebral and craniofacial morphogenesis proceed in embryological intimacy. Therefore, craniofacial shape differences between schizophrenia patients and controls are informative of developmental disturbance(s) in cerebral-craniofacial morphogenesis. 3D craniofacial coordinates were calculated from interlandmark distances for 169 patients with DSM-III-R schizophrenia and 78 matched normal controls. These were analysed using geometric morphometrics with visualisation of the resultant statistical models. Patients of both sexes were characterised by an intricate topography of 3D shape change involving lengthened lower mid-facial height, shortened upper mid-facial height, nasion located posteriorly and a wider face posteriorly; there was sex-specific rotation of the midface such that the base of the nose is more anterior in female patients but more posterior in male patients. Importantly, there were sex-specific asymmetries: in males, controls evidenced marked directional asymmetry while patients showed reduced directional asymmetry; conversely, in females controls evidenced little directional asymmetry while patients showed marked directional asymmetry. In schizophrenia, the topography of craniofacial dysmorphology appears to reflect subtle disruption to a critical 3D trajectory of embryonic-fetal craniofacial growth, particularly along the midline, with disturbance to the establishment of normal asymmetries in a sex-related manner.     

Topographical effects of D1-like dopamine receptor agonists on orofacial movements in mice and their differential regulation via oppositional versus synergistic D1-like: D2-like interactions: cautionary observations on SK&F 82958 as an anomalous agent

Using a novel procedure, the regulation of individual topographies of orofacial movement in the mouse by oppositional versus cooperative/synergistic D1-like: D2-like dopamine receptor interactions was studied. The D1-like agonists SK&F 38393 and SK&F 83959 each induced vertical, but not horizontal, jaw movements, together with tongue protrusions and incisor chattering; however, SK&F 82958 induced a different profile which, consistent with other neurochemical and neurophysiological studies, suggests that this agent shows anomalous properties relative to other D1-like agonists. When given alone, the D2-like agonist quinpirole reduced horizontal jaw movements and incisor chattering. On coadministration, both SK&F 38393- and SK&F 83959-induced vertical jaw movements and tongue protrusions were inhibited by quinpirole, while SK&F 82958 again showed an anomalous profile. These findings indicate that, in the mouse, vertical jaw movements and tongue protrusions are regulated by oppositional D1-like: D2-like interactions, and appear to involve a D1-like receptor that is not coupled to adenylyl cyclase, whereas horizontal jaw movements are inhibited by D2-like receptors. Additionally, results obtained using SK&F 82958 as a probe for D1-like mechanisms should be treated with considerable caution until they are confirmed using other D1-like agonists.     

Identification of proteinaceous material in the bone of the dinosaur Iguanodon

This study has directed attention at the search for bone-related proteins in an extract of demineralized rib bone of the 120 mya Iguanodon. The inner compact bone was demineralized and the GuCl extract resolved into 11 fractions using anion exchange chromatography, which all contained silver-reactive proteins with various amino acid profiles. Two specific fractions, iv and xi, revealed characteristics typical of contemporary phosphoproteins and proteoglycans, respectively. Fraction iv, 43-57 kDa, contained a high ratio of aspartate and serine, although no phosphate was discernable. Fraction xi contained a band of 41-47 kDa and was rich in chondroitin sulphate and hyaluronan. In addition an early eluting fraction was immunoreactive with an antibody against osteocalcin. A cancellous bone fraction from the same bone sample was also analyzed using N-terminal sequencing and revealed potential similarities with cystatin. While we do not claim to have identified the presence of intact proteins, this study has value in demonstrating that extruded extracellular matrix is protected by its capacity to induce mineralization, which subsequently is important in conserving detectable protein products in ancient skeletal tissues.     

Melanopsin in the circadian timing system

In mammals, circadian rhythms are generated by a light-entrainable oscillator located in the hypothalamic suprachiasmatic nucleus (SCN). Light signals reach the SCN via a dedicated retinal pathway, the retinohypothalamic tract (RHT). One question that continues to elude scientists is whether the circadian system has its own dedicated photoreceptor or photoreceptors. It is well established that conventional photoreceptors, rods and cones, are not required for circadian photoreception, suggesting that the inner retinal layer might contribute to circadian photoreception. Melanopsin, a novel photo pigment expressed in retinal ganglion cells (RGCs), has been proposed recently as a candidate circadian photoreceptor. Melanopsin-containing RGCs are intrinsically photosensitive, form part of the RHT, and contain neurotransmitters known to play a critical role in the circadian response to light. Furthermore, melanopsin-containing RGCs do not depend on inputs from rods and cones to transmit light signals to the SCN. However, based on a review of the available information about melanopsin and on new data from our laboratory, we propose that melanopsin, in itself, is not necessary for circadian photoreception. In fact, it appears that of the known photoreceptor systems, none, in and of itself, is necessary for circadian photoreception. Instead, it appears that within the photoreceptive systems there is some degree of redundancy, each contributing in some way to photic entrainment.