On the pathogenesis of osteogenesis imperfecta: some insights of the Utah paradigm of skeletal physiology

The pathogenesis of osteogenesis imperfecta (OI) baffled physiologists and physicians for over a century. Most past efforts to explain it depended heavily on cell and molecular biology and on changes in the material properties of affected bones (an old idea that OI patients could not make enough bone erred). To such views the still-evolving Utah paradigm of skeletal physiology can add a model for bone and bones that depends on errors in three genetically-determined features. The errors include, 1,2) elevated 'set points' of the strain-dependent thresholds that help to control how lamellar bone modeling and remodeling adapt bone strength, architecture and 'mass' to the voluntary loads on load-bearing bones; 3) and a reduced modeling-rate limit for the appositional rate of the lamellar bone formation drifts that can increase bone strength, outside bone diameters, cortical and trabecular thickness, and bone 'mass'. If only abnormalities #1,#2 occurred, that should limit the eventual strength, architecture and 'mass' of load-bearing bones, while if only #3 occurred that should prolong or delay how long it took to achieve the above limits, but without changing them. Equally, in driving from New York to Boston, stopping at New Haven would prevent reaching Boston no matter how rapidly one drove (a limited trip). But by not stopping one could reach Boston by driving very slowly (a prolonged but not a limited trip). This model concerns general features of bone and bones in OI that would need study and explanation at the tissue, cellular and molecular-biologic levels. Other places and people must discuss any devils in the details, as well as collagenous tissue, auditory, dental and other problems in OI, and the effects of treatment on the above features.     

Critique of ‘Australopithecus afarensis’ as a single species based on dental metrics and morphology

Leonard andHegmon (1987) compare a series of dental metrics of ‘Australopithecus afarensis Johanson, White, andCoppens, 1978’ with criteria for modern apes, to test the hypothesis that ‘A. afarensis’ represents a single species. They also compare the morphology of the lower third premolar. The dental breadth of ‘A. afarensis’ shows a wide range of variation, particularly in the lower third premolar morphology which displays greater variation than in modern apes—yet the study concludes that the single species hypothesis cannot be rejected. The study is flawed by applying criteria for pongids inappropriate for a hominid. When ‘A. afarensis’ is compared with criteria for hominids, the range of variation in dental size, breadth, and third premolar morphology is greater than that in any hominid species. The single species hypothesis is, therefore, once again rejected. Moreover, the name ‘A. afarensis’ is preoccupied byPraeanthropus africanus (Weinert) and must be dropped.     

Palatine fenestrae,the orangutan and hominoid evolution

Although most mammals develop relatively large double anterior palatine fenestrae that patently communicate with the nasal cavity, four extant primates—Homo sapiens, Pongo, Pan andGorilla—do not. While these four have closed-down these foramenal structures,Homo sapiens andPongo are unique in forming a single foramen palatally. Among fossil taxa,Homo, Australopithecus, Sivapithecus (=Ramapithecus) andRudapithecus also develop a single foramen palatally. Dryopithecines, the presumed fossil apes, preserve the two patent fenestrae. In light of dental features that are considered diagnostically “hominid,” which are also found in the orangutan, it is suggested that this “ape,” rather thanPan, is phylogenetically closer toHomo.     

Extracellular matrix control of mammary gland morphogenesis and tumorigenesis: insights from imaging

The extracellular matrix (ECM), once thought to solely provide physical support to a tissue, is a key component of a cell’s microenvironment responsible for directing cell fate and maintaining tissue specificity. It stands to reason, then, that changes in the ECM itself or in how signals from the ECM are presented to or interpreted by cells can disrupt tissue organization; the latter is a necessary step for malignant progression. In this review, we elaborate on this concept using the mammary gland as an example. We describe how the ECM directs mammary gland formation and function, and discuss how a cell’s inability to interpret these signals—whether as a result of genetic insults or physicochemical alterations in the ECM—disorganizes the gland and promotes malignancy. By restoring context and forcing cells to properly interpret these native signals, aberrant behavior can be quelled and organization re-established. Traditional imaging approaches have been a key complement to the standard biochemical, molecular, and cell biology approaches used in these studies. Utilizing imaging modalities with enhanced spatial resolution in live tissues may uncover additional means by which the ECM regulates tissue structure, on different length scales, through its pericellular organization (short-scale) and by biasing morphogenic and morphostatic gradients (long-scale). Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The current state of korean paleoanthropology

The hominid fossil and Paleolithic archaeology records from the Korean Peninsula are extensive, but relatively little is known about the Korean human evolutionary record outside this region. The Korean paleoanthropological record is reviewed here in light of major research issues, including the hominid fossil record, relative and chronometric dating, lithic analysis, hominid subsistence, and the presence of bone tools, art and symbolism. Some of the major conclusions drawn from this review include: (1) hominid fossils have been found in nine separate sites on the Korean Peninsula; (2) possible Homo erectus fossils are present in North Korea; (3) Ryonggok Cave, in North Korea, has exposed the remains of at least five archaic Homo sapiens individuals; (4) a possible burial of an anatomically modern Homo sapiens child, discovered in Hungsu Cave in South Korea, has been tentatively dated to roughly 40,000 years ago; (5) handaxes and cleavers have been found at a number of sites near Chongokni and they appear to date to at least 100,000 years ago; and (6) taphonomic studies are necessary for addressing issues related to determining the nature of hominid-carnivore interaction over similar resources (e.g. carcasses and shelter); and the presence/absence of Early Paleolithic bone tools, art, and symbolism in Korea.     

A determination of the minimum sizes of representative volume elements for the prediction of cortical bone elastic properties

At its highest level of microstructural organization—the mesoscale or millimeter scale—cortical bone exhibits a heterogeneous distribution of pores (Haversian canals, resorption cavities). Multi-scale mechanical models rely on the definition of a representative volume element (RVE). Analytical homogenization techniques are usually based on an idealized RVE microstructure, while finite element homogenization using high-resolution images is based on a realistic RVE of finite size. The objective of this paper was to quantify the size and content of possible cortical bone mesoscale RVEs. RVE size was defined as the minimum size: (1) for which the apparent (homogenized) stiffness tensor becomes independent of the applied boundary conditions or (2) for which the variance of elastic properties for a set of microstructure realizations is sufficiently small. The field of elastic coefficients and microstructure in RVEs was derived from one acoustic microscopy image of a human femur cortical bone sample with an overall porosity of 8.5%. The homogenized properties of RVEs were computed with a finite element technique. It was found that the size of the RVE representative of the overall tissue is about 1.5 mm. Smaller RVEs (~0.5 mm) can also be considered to estimate local mesoscopic properties that strongly depend on the local pores volume fraction. This result provides a sound basis for the application of homogenization techniques to model the heterogeneity of cortical microstructures. An application of the findings to estimate elastic properties in the case of a porosity gradient is briefly presented.     

First record of a middle pliocene hominid from the Siwalik Hills of South Asia

The Siwalik Hills have yielded what is perhaps the world’s most ancient early hominid. In December 1992 I discovered a hominid mandibular ramus and a hominid femur in association with stone tools in the Tatrot Formation of the upper Siwalik. The discovery was made from the Tatrot Formation exposed at Khetpurali Village in Haryana, North India. The teeth are bunodont, having a lingually inclined wear plane. The P3 is molariform and single rooted. The femur is platymeric and has medullary stenosis. The stone tools are chopper types. Magnetostratigraphic dating of the Tatrot Formation ranges from 2.47 Myr at the top to 5.44 Myr at the base. The hominid — yielding bed is dated at 3.40 Myr — Middle Pliocene. The palaeoecology of the Tatrot Formation suggests open savannah. The discovery will cast new light on the origin and migration of the early hominids, and hopefully will contribute to a solution of the 100-year-old dispute about the African or Asian origin of humans.     

The Inability of Primary School to Introduce Children to the Theory of Biological Evolution

A great number of research papers in the English literature of science education present difficulties pupils have in understanding natural selection. Studies show that children have essentialist and teleological intuitive ideas when dealing with organisms and that these biases hinder their ability to understand the theory of evolution by natural selection. Consequently, it is interesting to ascertain if and how the school education offered today deals with the problem, i.e., helps the children confront these biases. To that purpose, this study answered the two following research questions: (a) How is biological evolution presented—from the past to the present day—in the official documentation of primary school education, namely the science curricula and the textbooks of Greece? and (b) what are the conceptions held by Greek primary school teachers of the concepts of evolutionary theory and relevant issues that they have to teach? Our research found that not only are the intuitive ideas not “confronted” but they are also “affirmed” in Greek primary education. This phenomenon, as some other international studies have shown, must not be only a Greek one. A drastic change in the content and structure of primary school curricula and the training of educators is necessary in order to improve and facilitate the teaching of biological evolution.     

Arousal increases the representational capacity of cortical tissue

Arousal patently transforms the faculties of complex organisms. Although typical changes in cortical activity such as seen in EEG and LFP measurements are associated with change in state of arousal, it remains unclear what in the constitution of such state dependent activity enables this profound enhancement of ability. We put forward the hypothesis that arousal modulates cortical activity by rendering it more fit to represent information. We argue that representational capacity is of a dual nature—it requires not only that cortical tissue generate complex activity (i.e. spatiotemporal neuronal events), but also a complex cortical activity space (which is comprised of such spatiotemporal events). We explain that the topological notion of complexity—homology—is the pertinent measure of the complexity of neuronal activity spaces, as homological structure indicates not only the degree to which underlying activity is inherently clustered but also registers the effective dimensionality of the configurations formed by such clusters. Changes of this sort in the structure of cortical activity spaces can serve as the basis of the enhanced capacity to make perceptual/behavioral distinctions brought about by arousal. To show the feasibility of these ideas, we analyzed voltage sensitive dye imaging (VSDI) data acquired from primate visual cortex in disparate states of arousal. Our results lend some support to the theory: first as arousal increased so did the complexity of activity (that is the complexity of VSDI movies). Moreover, the complexity of structure of activity space (that is VSDI movie space) as measured by persistent homology—a multi scale topological measure of complexity—increased with arousal as well.     

Fast cortical selection: a principle of neuronal self-organization for perception?

 It is commonly accepted that larger visual objects are represented in the cerebral cortex by specific spatial patterns of neuronal activity. Self-organization is a key concept in the different explanations of such neuronal representations. We here propose as a hypothesis that fast cortical selection (FCS) is an intrinsic functional element of cortical self-organization during perception. Selection is a central concept in theoretical biology which has proved its explanatory power in different fields of our natural and cultural world. The central element in the cortical selection process is the pyramidal cell with its two types of excitatory input. In primary cortical areas one of these inputs comes from any of the sensory organs, determining the topological and typological receptive field properties of the cell and also driving it directly. The other type of input connects reciprocally neighbouring pyramidal cells by axon collaterals and only facilitates the driving input. These two functionally different inputs constitute the elementary selection system working by iterative mutual facilitation as a biological algorithm. A short simulation, based entirely on such biological facts, illustrates the dynamic of this selection process: the activity of cells responding better to the external stimulus ‘grow and survive’ the stimulation, whereas less responsive cells decrease their activity due to competition. Received: 13 June 1995 / Accepted in revised form: 27 May 1997     

Signs of Anger: Representation of Agonistic Behaviour in Invertebrate Cognition

In this essay I shall examine the representation of aggression and its issues in the model animal, the Fruit Fly, Drosophila melanogaster. The Fruit Fly is the model animal for genetics and more recently neuroscience. On the basis of its behaviour conclusions are being drawn that will help in the development of new treatments for clinical entities like aggression and anxiety disorders—the author questions those findings and asks whether more should be done to focus on the actual biology and behaviour—the Umwelt, instead of trying to bridge the gulf between invertebrate and human behaviours.     

Cortical bone maintenance and geometry of the tibia in prehistoric children from Nubia's Batn el Hajar

The relationship between advancing age in adults and patterns of cortical bone maintenance has been extensively documented for archaeological populations (Dewey, et al., 1969; Van Gerven et al., 1969; Perzigian, 1973). Most recently, this research has been expanded to include a more thorough consideration of the geometric properties of bone in relationship to adult age changes (Martin and Atkinsin, 1977; Ruff and Hayes, 1983). To date, however, few studies have documented subadult patterns of cortical bone maintenance in archaeological populations and none have incorporated the relationship between patterns of cortical bone loss and gain and the changing geometric properties of growing bone. Using a sample of 172 tibias from children excavated from the Medieval Christian site of Kulubnarti, located in Nubia's Batn el Hajar, the present research examines the relationship between percent cortical area, bone mineral content, and cross-sectional moments of inertia. Among these children, bone mineral content increases steadily from birth in spite of a reduction in percent cortical area during early and late childhood. It appears, therefore, that tissue quality of the bone is not adversely affected by the reduction. Furthermore, the reduction in percent cortical area in later childhood corresponds to a dramatic increase in bending strength measured by cross-sectional moments of inertia. Thus, whether this cortical reduction is due entirely or in part to either normal modeling or nutritional stress, the tissue and organ quality of the bone is not adversely affected.     

Data requirements and data sources for biodiversity priority area selection

The data needed to prioritize areas for biodiversity protection are records of biodiversity features — species, species assemblages, environmental classes — for each candidate area. Prioritizing areas means comparing candidate areas, so the data used to make such comparisons should be comparable in quality and quantity. Potential sources of suitable data include museums, herbariums and natural resource management agencies. Issues of data precision, accuracy and sampling bias in data sets from such sources are discussed and methods for treating data to minimize bias are reviewed.     

A Comparison of Micro-CT and Dental CT in Assessing Cortical Bone Morphology and Trabecular Bone Microarchitecture

Objective

The objective of this study was to evaluate the relationship between the trabecular bone microarchitecture and cortical bone morphology by using micro-computed tomography (micro-CT) and dental cone-beam computed tomography (dental CT).

Materials and Methods

Sixteen femurs and eight fifth lumbar vertebrae were collected from eight male Sprague Dawley rats. Four trabecular bone microarchitecture parameters related to the fifth lumbar vertebral body (percent bone volume [BV/TV], trabecular thickness [TbTh], trabecular separation [TbSp], and trabecular number [TbN]) were calculated using micro-CT. In addition, the volumetric cancellous bone grayscale value (vCanGrayscale) of the fifth lumbar vertebral body was measured using dental CT. Furthermore, four cortical bone morphology parameters of the femoral diaphysis (total cross-sectional area [TtAr], cortical area [CtAr], cortical bone area fraction [CtAr/TtAr], and cortical thickness [CtTh]) were calculated using both micro-CT and dental CT. Pearson analysis was conducted to calculate the correlation coefficients (r) of the micro-CT and dental CT measurements. Paired-sample t tests were used to compare the differences between the measurements of the four cortical bone morphology parameters obtained using micro-CT and dental CT.

Results

High correlations between the vCanGrayscale measured using dental CT and the trabecular bone microarchitecture parameters (BV/TV [r = 0.84] and TbTh [r = 0.84]) measured using micro-CT were observed. The absolute value of the four cortical bone morphology parameters may be different between the dental CT and micro-CT approaches. However, high correlations (r ranged from 0.71 to 0.90) among these four cortical bone morphology parameters measured using the two approaches were obtained.

Conclusion

We observed high correlations between the vCanGrayscale measured using dental CT and the trabecular bone microarchitecture parameters (BV/TV and TbTh) measured using micro-CT, in addition to high correlations between the cortical bone morphology measured using micro-CT and dental CT. Further experiments are necessary to validate the use of dental CT on human bone.     

Penetration of cutting tool into cortical bone: Experimental and numerical investigation of anisotropic mechanical behaviour

An anisotropic mechanical behaviour of cortical bone and its intrinsic hierarchical microstructure act as protective mechanisms to prevent catastrophic failure due to natural loading conditions; however, they increase the extent of complexity of a penetration process in the case of orthopaedic surgery. Experimental results available in literature provide only limited information about processes in the vicinity of a tool–bone interaction zone. Also, available numerical models the bone-cutting process do not account for material anisotropy or the effect of damage mechanisms. In this study, both experimental and numerical studies were conducted to address these issues and to elucidate the effect of anisotropic mechanical behaviour of cortical bone tissue on penetration of a sharp cutting tool. First, a set of tool-penetration experiments was performed in directions parallel and perpendicular to bone axis. Also, these experiments included bone samples cut from four different cortices to evaluate the effect of spatial variability and material anisotropy on the penetration processes. Distinct deformation and damage mechanisms linked to different microstructure orientations were captured using a micro-lens high-speed camera. Then, a novel hybrid FE model employing a smoothed-particle-hydrodynamic domain embedded into a continuum FE one was developed based on the experimental configuration to characterise the anisotropic deformation and damage behaviour of cortical bone under a penetration process. The results of our study revealed a clear anisotropic material behaviour of the studied cortical bone tissue and the influence of the underlying microstructure. The proposed FE model reflected adequately the experimental results and demonstrated the need for the use of the anisotropic and damage material model to analyse cutting of the cortical-bone tissue.     

Serial allocations of isolated mandibular molars of unknown taxonomic affinities from the Shungura and Unso Formations,Ethiopia, a combined method approach

The early hominid dental remains from the Omo succession represent a fragmentary but important source of information regarding hominid evolution during the 2 to 3 myr time period. As an initial step toward the evaluation of taxonomic affinities and evolutionary significance, the present study attempts serial allocations of 21 isolated mandibular molars from the Shungura and Usno Formations. A comparative sample consisting of 250 mandibular molars ofA.afarensis, A.africanus, A.robustus, A.boisei and earlyHomo was used to compile the baseline data for allocating the isolated Omo molars to serial positions. The methods employed in the present study include morphometric analyses of 5 cusp areas, 8 linear variables reflecting crown shape, and 4 measurements of fissure pattern. It was found that by combining morphological observations with both “restricted” and “non-restricted” applications of discriminant function analyses (sensu Albrecht, 1992), sufficiently reliable serial allocations could be attained.     

“Silenced” polydendrocytes: a new cell type within the oligodendrocyte progenitor cell population?

Oligodendrocyte progenitor cells (OPCs) were first described more than two decades ago. Novel labeling techniques have shown them to be cells with more than just progenitor functions, with their classification as a fourth glial cell type in addition to astrocytes, oligodendrocytes, and microglial cells. Another term used for this cell type is polydendrocytes, owing to both their morphology and to the evolving knowledge about their diverse functions. Recently, an exclusive hallmark of neurons—the generation of action potentials—became debatable, because a subset of polydendrocytes was reported to generate action potentials in response to adequate stimuli. The new technique of inducible reporter gene expression has brought new insights into the fate and function of polydendrocytes. In recent studies, so-called “silenced” OPCs were detected in cortical tissue, and which underwent proliferation with subsequent cell cycle exit, but without any signs of differentiation. Within this review, we focus on the identification of this new subset of polydendrocytes and their possible functions within cortical networks.     

The assessment of trabecular bone parameters and cortical bone strength: A comparison of micro-CT and dental cone-beam CT

This study compared the capabilities of micro-computed tomography (micro-CT) and dental cone-beam computed tomography (CBCT) in assessing trabecular bone parameters and cortical bone strength. Micro-CT and CBCT scans were applied to 28 femurs from 14 rats to obtain independent measurements of the volumetric cancellous bone mineral density (vCanBMD) in the femoral head, volumetric cortical bone mineral density (vCtBMD) in the femoral diaphysis, cross-sectional moment of inertia (CSMI), and bone strength index (BSI) (=CSMI×vCtBMD). Five structural parameters of the trabecular bone of the femoral head were calculated from micro-CT images. A three-point bending test was then conducted to measure the fracture load of each femur. Bivariate linear Pearson analysis was conducted to calculate the correlation coefficients (r values) of the micro-CT, dental CBCT, and three-point bending measurements. The statistical analyses showed a strong correlation between vCanBMD values obtained using micro-CT and dental CBCT (r=0.830). There were strong or moderate correlation between vCanBMD measured using dental CBCT and five parameters of trabecular structure measured using micro-CT. Additionally, the results were satisfactory regardless of whether micro-CT or dental CBCT was used to measure the femoral diaphysis vCtBMD (r=0.733 and 0.680, respectively), CSMI (r=0.756 and 0.726, respectively), or BSI (r=0.846 and 0.847, respectively) to predict fracture loads. This study has yielded a new method for using dental CBCT to evaluate bone parameters and bone strength; however, further studies are necessary to validate the use of dental CBCT on humans.     

Ultrastructural studies of human basophils and mast cells.

Ultrastructural studies of human mast cells (HMCs) and basophils (HBs) are reviewed. Sources of HMCs include biopsies of tissue sites and in situ study of excised diseased organs; isolated, partially purified samples from excised organs; and growth-factor-stimulated mast cells that develop de novo in cultures of cord blood cells. Sources of HBs for study include partially purified peripheral blood basophils, basophils in tissue biopsies, and specific growth factor-stimulated basophils arising de novo from cord blood cells. The ultrastructural studies reviewed deal with identity, secretion, vesicles, recovery, and synthesis issues related to the biology of these similar cells.     

Biomedical and Environmental Ethics Alliance: Common Causes and Grounds

In the late 1960s Van Rensselaer Potter, a biochemist and cancer researcher, thought that our survival was threatened by the domination of military policy makers and producers of material goods ignorant of biology. He called for a new field of Bioethics—“a science of survival.” Bioethics did develop, but with a narrower focus on medical ethics. Recently there have been attempts to broaden that focus to bring biomedical ethics together with environmental ethics. Though the two have many differences—in habits of thought, scope of concern, and value commitments—in this paper we argue that they often share common cause and we identify common ground through an examination of two case studies, one addressing drug development, the other food production.