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Showing papers in "Anatomical Record-advances in Integrative Anatomy and Evolutionary Biology in 2004"


Journal ArticleDOI
TL;DR: This work experimentally confirms and quantify the essential ultrastructural elements in a theoretical model that provides a possible mechanism by which mechanical loading-induced fluid flow in the lacuno-canalicular system can produce cellular-level strains on the osteocyte processes that are at least one order of magnitude larger than bone tissue deformations.
Abstract: Osteocytes are believed to be the mechanical sensor cells in bone. One potential physical mechanism for the mechanosensing process is that osteocytes directly sense the deformation of the substrate to which they are attached. However, there is a fundamental paradox in this theory: tissue-level strains in whole bone are typically <0.2%, yet an extensive range of in vitro experiments show that dynamic substrate strains must be at least an order of magnitude larger in order for intracellular biochemical responses to occur. Recently, a theoretical model was developed (You et al. J. Biomech., 2001; 34:1375-1386) that provides a possible mechanism by which mechanical loading-induced fluid flow in the lacuno-canalicular system, under routine physical activity, can produce cellular-level strains on the osteocyte processes that are at least one order of magnitude larger than bone tissue deformations. This would resolve the fundamental paradox mentioned above. In this work we experimentally confirm and quantify the essential ultrastructural elements in this model: 1) the presence of the transverse elements that bridge the pericellular space surrounding the osteocyte process, which interact with the fluid flow and lead to an outward hoop tension on the process; and 2) the presence of bundled F-actin in the osteocyte processes, which resists the outward hoop tension and limits the cell process membrane deformation. Morphological data to support these assumptions are scant. Special staining techniques employing ruthenium III hexamine trichloride (RHT) were developed to elucidate these structures in the humeri of adult mice.

313 citations


Journal ArticleDOI
TL;DR: It is considered that a subset of EPDCs continue to differentiate in a variety of different cell types (including coronary endothelium, coronary smooth muscle cells (CoSMCs), interstitial fibroblasts, and atrioventricular cushion mesenchymal cells), whereas other EPDC remain in a more or less undifferentiated state.
Abstract: After its initial formation the epicardium forms the outermost cell layer of the heart. As a result of an epithelial-to-mesenchymal transformation (EMT) individual cells delaminate from this primitive epicardial epithelium and migrate into the subepicardial space (Perez-Pomares et al., Dev Dyn 1997; 210:96-105; Histochem J 1998a;30:627-634). Several studies have demonstrated that these epicardially derived cells (EPDCs) subsequently invade myocardial and valvuloseptal tissues (Mikawa and Fischman, Proc Natl Acad Sci USA 1992;89:9504-9508; Mikawa and Gourdie, Dev Biol 1996;174:221-232; Dettman et al., Dev Biol 1998;193:169-181; Gittenberger de Groot et al., Circ Res 1998;82:1043-1052; Manner, Anat Rec 1999;255:212-226; Perez-Pomares et al., Dev. Biol. 2002b;247:307-326). A subset of EPDCs continue to differentiate in a variety of different cell types (including coronary endothelium, coronary smooth muscle cells (CoSMCs), interstitial fibroblasts, and atrioventricular cushion mesenchymal cells), whereas other EPDCs remain in a more or less undifferentiated state. Based on its specific characteristics, we consider the EPDC as the ultimate 'cardiac stem cell'. In this review we briefly summarize what is known about events that relate to EPDC development and differentiation while at the same time identifying some of the directions where EPDC-related research might lead us in the near future.

287 citations


Journal ArticleDOI
TL;DR: Until recently it was generally assumed that the precursor cells in postnatal individuals were limited to lineage-committed progenitor cells specific for various tissues, but studies by Young, his colleagues, and others have demonstrated the presence of two categories of precursor cells that reside within the organs and tissues of postnatal animals.
Abstract: Development of a multicellular organism is accomplished through a series of events that are preprogrammed in the genome. These events encompass cellular proliferation, lineage commitment, lineage progression, lineage expression, cellular inhibition, and regulated apoptosis. The sequential progression of cells through these events results in the formation of the differentiated cells, tissues, and organs that constitute an individual. Although most cells progress through this sequence during development, a few cells leave the developmental continuum to become reserve precursor cells. The reserve precursor cells are involved in the continual maintenance and repair of the tissues and organs throughout the life span of the individual. Until recently it was generally assumed that the precursor cells in postnatal individuals were limited to lineage-committed progenitor cells specific for various tissues. However, studies by Young, his colleagues, and others have demonstrated the presence of two categories of precursor cells that reside within the organs and tissues of postnatal animals. These two categories of precursor cells are lineage-committed (multipotent, tripotent, bipotent, and unipotent) progenitor cells and lineage-uncommitted pluripotent (epiblastic-like, ectodermal, mesodermal, and endodermal) stem cells. These reserve precursor cells provide for the continual maintenance and repair of the organism after birth.

276 citations


Journal ArticleDOI
TL;DR: Early primates retained this basic organization and also had a larger posterior parietal region that mediated sensorimotor functions via connections with motor and premotor areas, and Posterior parietal cortex expanded into more areas that related to frontal cortex.
Abstract: Inferences about how the complex somatosensory systems of anthropoid primates evolved are based on comparative studies of such systems in extant mammals. Experimental studies of members of the major clades of extant mammals suggest that somatosensory cortex of early mammals consisted of only a few areas, including a primary area, S1, bordered by strip-like rostral and caudal somatosensory fields, SR and SC. In addition, the second somatosensory area, S2, and the parietal ventral area, PV, were probably present. S1, S2, and PV were activated independently via parallel projections from the ventroposterior nucleus, VP. Little posterior parietal cortex existed, and it was unlikely that a separate primary motor area, M1, existed until placental mammals evolved. Early primates retained this basic organization and also had a larger posterior parietal region that mediated sensorimotor functions via connections with motor and premotor areas. The frontal cortex included M1, dorsal and ventral premotor areas, supplementary motor area, and cingulate motor fields. Ventroposterior superior and ventroposterior inferior nuclei were distinct from the ventroposterior nucleus in the thalamus. In early anthropoid primates, areas S1, SR, and SC had differentiated into the fields now recognized as areas 3b, 3a, and 1. Areas 3b and 1 contained parallel mirror-image representations of cutaneous receptors and a parallel representation in area 2 was probable. Serial processing became dominant, so that neurons in areas 1, S2, and PV became dependent on area 3b for activation. Posterior parietal cortex expanded into more areas that related to frontal cortex. Less is known about changes that might have occurred with the emergence of apes and humans, but their brains were larger and posed scaling problems most likely solved by increasing the number of cortical areas and reducing the proportion of long connections.

213 citations


Journal ArticleDOI
TL;DR: It is suggested that NS treatment exerts a therapeutic protective effect in diabetes by decreasing oxidative stress and preserving pancreatic beta-cell integrity, and may be clinically useful for protecting beta-cells against oxidative stress.
Abstract: The aim of the present study was to evaluate the possible protective effects of Nigella sativa L. (NS) against beta-cell damage from streptozotocin (STZ)-induced diabetes in rats. STZ was injected intraperitoneally at a single dose of 50 mg/kg to induce diabetes. NS (0.2 ml/kg/day, i.p.) was injected for 3 days prior to STZ administration, and these injections were continued throughout the 4-week study. Oxidative stress is believed to play a role in the pathogenesis of diabetes mellitus (DM). To assess changes in the cellular antioxidant defense system, we measured the activities of antioxidant enzymes (such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD), and catalase (CAT)) in pancreatic homogenates. We also measured serum nitric oxide (NO) and erythrocyte and pancreatic tissue malondialdehyde (MDA) levels, a marker of lipid peroxidation, to determine whether there is an imbalance between oxidant and antioxidant status. Pancreatic beta-cells were examined by immunohistochemical methods. STZ induced a significant increase in lipid peroxidation and serum NO concentrations, and decreased antioxidant enzyme activity. NS treatment has been shown to provide a protective effect by decreasing lipid peroxidation and serum NO, and increasing antioxidant enzyme activity. Islet cell degeneration and weak insulin immunohistochemical staining was observed in rats with STZ-induced diabetes. Increased intensity of staining for insulin, and preservation of beta-cell numbers were apparent in the NS-treated diabetic rats. These findings suggest that NS treatment exerts a therapeutic protective effect in diabetes by decreasing oxidative stress and preserving pancreatic beta-cell integrity. Consequently, NS may be clinically useful for protecting beta-cells against oxidative stress.

212 citations


Journal ArticleDOI
TL;DR: The likelihood of pheromonal communication in humans is assessed with a discussion of chemical compounds produced by the axilla that may function as phersomones; the likelihood that the vomeronasal organ (VNO), a putative pheromone receptor organ in many other mammals, is functional in humans; and the possible ways pheramones operate in humans.
Abstract: Among primates in general, pheromones are of variable importance to social communication. Data on humans have generated the greatest controversy regarding the existence of pheromonal communication. In this review, the likelihood of pheromonal communication in humans is assessed with a discussion of chemical compounds produced by the axilla that may function as pheromones; the likelihood that the vomeronasal organ (VNO), a putative pheromone receptor organ in many other mammals, is functional in humans; and the possible ways pheromones operate in humans. In the human axilla, the interactions between the cutaneous microflora and axillary secretions render this region analogous to scent glands found in other primates. Both the chemistry of axillary secretions and their effects on conspecifics in humans appear to be analogous to other mammalian pheromone systems. Whichever chemical compounds serve a pheromonal function in humans, another unknown is the receptor. Although the VNO has been implicated in the reception of pheromones in many vertebrates, it is not the only pathway through which such information has access to the central nervous system; there is ample evidence to support the view that the olfactory epithelium can respond to pheromones. Furthermore, if a chemical activates receptors within the VNO, this does not necessarily mean that the compound is a pheromone. An important caveat for humans is that critical components typically found within the functioning VNO of other, nonprimate, mammals are lacking, suggesting that the human VNO does not function in the way that has been described for other mammals. In a broader perspective, pheromones can be classified as primers, signalers, modulators, and releasers. There is good evidence to support the presence of the former three in humans. Examples include affects on the menstrual cycle (primer effects); olfactory recognition of newborn by its mother (signaler); individuals may exude different odors based on mood (suggestive of modulator effects). However, there is no good evidence for releaser effects in adult humans. It is emphasized that no bioassay-guided study has led to the isolation of true human pheromones, a step that will elucidate specific functions to human chemical signals. © 2004 Wiley-Liss, Inc.

212 citations


Journal ArticleDOI
TL;DR: Great caution is therefore necessary when interpreting functional outcomes of so-called specific hepatic denervation studies, because of the specific anatomical organization of hepatic nerves, selection for the vagal or sympathetic division, or for efferents and afferents, is nearly impossible.
Abstract: Vagal and spinal afferent innervation of the portal hepatic area has not been studied as thoroughly as the innervation of other important organs. It is generally agreed that unlike noradrenergic sympathetic efferent nerve fibers, sensory nerve fibers of either vagal or dorsal root/spinal origin do not directly innervate hepatocytes, but are restricted to the stroma surrounding triades of hepatic vasculature and bile ducts, and to extrahepatic portions of the portal vein and bile ducts. For vagal afferent innervation, retrograde and anterograde tracing studies in the rat have clearly shown that only a minor portion of the common hepatic branch innervates the liver area, while the major portion descends in the gastroduodenal branch toward duodenum, pancreas, and pylorus. Hepatic paraganglia, bile ducts, and portal vein receive the densest vagal afferent innervation. Calretinin may be a relatively specific marker for vagal afferent innervation of the portal-hepatic space. Calcitonin gene-related peptide (CGRP) is a specific marker for dorsal root afferents, and CGRP-immunoreactive fibers are mainly present near the intrahepatic vascular bundles and bile ducts, and in the same extrahepatic compartments that contain vagal afferents. Because of the specific anatomical organization of hepatic nerves, selective hepatic denervation, whether selective for the vagal or sympathetic division, or for efferents and afferents, is nearly impossible. Great caution is therefore necessary when interpreting functional outcomes of so-called specific hepatic denervation studies.

185 citations


Journal ArticleDOI
TL;DR: To reveal the involvement of the autonomic nervous system in liver function, this study focuses on autonomic nerves and neuroendocrine connections between the hypothalamus and the liver.
Abstract: After receiving information from afferent nerves, the hypothalamus sends signals to peripheral organs, including the liver, to keep homeostasis. There are two ways for the hypothalamus to signal to the peripheral organs: by stimulating the autonomic nerves and by releasing hormones from the pituitary gland. In order to reveal the involvement of the autonomic nervous system in liver function, we focus in this study on autonomic nerves and neuroendocrine connections between the hypothalamus and the liver. The hypothalamus consists of three major areas: lateral, medial, and periventricular. Each area has some nuclei. There are two important nuclei and one area in the hypothalamus that send out the neural autonomic information to the peripheral organs: the ventromedial hypothalamic nucleus (VMH) in the medial area, the lateral hypothalamic area (LHA), and the periventricular hypothalamic nucleus (PVN) in the periventricular area. VMH sends sympathetic signals to the liver via the celiac ganglia, the LHA sends parasympathetic signals to the liver via the vagal nerve, and the PVN integrates information from other areas of the hypothalamus and sends both autonomic signals to the liver. As for the afferent nerves, there are two pathways: a vagal afferent and a dorsal afferent nerve pathway. Vagal afferent nerves are thought to play a role as sensors in the peripheral organs and to send signals to the brain, including the hypothalamus, via nodosa ganglia of the vagal nerve. On the other hand, dorsal afferent nerves are primary sensory nerves that send signals to the brain via lower thoracic dorsal root ganglia. In the liver, many nerves contain classical neurotransmitters (noradrenaline and acetylcholine) and neuropeptides (substance P, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal polypeptide, somatostatin, glucagon, glucagon-like peptide, neurotensin, serotonin, and galanin). Their distribution in the liver is species-dependent. Some of these nerves are thought to be involved in the regulation of hepatic function as well as of hemodynamics. In addition to direct neural connections, the hypothalamus can affect metabolic functions by neuroendocrine connections: the hypothalamus-pancreas axis, the hypothalamus-adrenal axis, and the hypothalamus-pituitary axis. In the hypothalamus-pancreas axis, autonomic nerves release glucagon and insulin, which directly enter the liver and affect liver metabolism. In the hypothalamus-adrenal axis, autonomic nerves release catecholamines such as adrenaline and noradrenaline from the adrenal medulla, which also affects liver metabolism. In the hypothalamus-pituitary axis, release of glucocorticoids and thyroid hormones is stimulated by pituitary hormones. Both groups of hormones modulate hepatic metabolism. Taken together, the hypothalamus controls liver functions by neural and neuroendocrine connections.

168 citations


Journal ArticleDOI
TL;DR: A basic model for future studies on chondrogenesis of hBM-MSCs using the agarose cultures is established, with the cell-agarose constructs of higher initial cell-seeding density exhibiting more cartilage-specific gene expressions.
Abstract: Mesenchymal stem cells derived from human bone marrow (hBM-MSCs) can differentiate into chondrogenic cells for the potential treatment of injured articular cartilage. To evaluate agarose gels as a supportive material for chondrogenesis of hBM-MSCs, this study examined chondrogenesis of hBM-MSCs in the agarose cultures. Pellet cultures were employed to confirm the chondrogenic potential of the hBM-MSCs that were used in agarose cultures. The hBM-MSCs were seeded in 2% agarose constructs at the initial cell-seeding densities of 3, 6, and 9 x 10(6) cells/ml while each of pellets was formed using 2.5 x 10(5) cells. Chondrogenesis of hBM-MSCs was induced by culturing cell-agarose constructs and pellets for 21 days in the presence of a defined medium containing transforming growth factor beta3 (TGF-beta3). The analysis of reverse transcription-polymerase chain reaction showed that hBM-MSCs of agarose and pellet cultures expressed the chondrogenic markers of collagen type II and aggrecan in the presence of TGF-beta3. The deposition of cartilage-specific macromolecules was detected in both agarose and pellet cultures by histological and immunohistochemical assessments. Chondrogenesis of hBM-MSCs in agarose gels directly correlated with the initial cell-seeding density, with the cell-agarose constructs of higher initial cell-seeding density exhibiting more cartilage-specific gene expressions. This study establishes a basic model for future studies on chondrogenesis of hBM-MSCs using the agarose cultures.

166 citations


Journal ArticleDOI
TL;DR: Multiple lines of evidence support the view that sound localization is the selective pressure on smaller primates and on other mammals with short interaural distances for hearing high frequencies.
Abstract: This review discusses hearing performance in primates and selective pressures that may influence it. The hearing sensitivity and sound-localization abilities of primates, as indicated by behavioral tests, are reviewed and compared to hearing and sound localization among mammals in general. Primates fit the mammalian pattern with small species hearing higher frequencies than larger species in order to use spectral/intensity cues for sound localization. In this broader comparative context, the restricted highfrequency hearing of humans is not unusual. All of the primates tested so far are able to hear frequencies below 125 Hz, placing them among the majority of mammals. Sound-localization acuity has been determined for only three primates, and here also they have relatively good localization acuity (with a minimum audible angle roughly similar to other mammals such as cats, pigs, and opossums). This is in keeping with the pattern among mammals in general, in which species with narrow fields of best vision, such as a fovea, are better localizers than those with broad fields of best vision. Multiple lines of evidence support the view that sound localization is the selective pressure on smaller primates and on other mammals with short interaural distances for hearing high frequencies. © 2004 Wiley-Liss, Inc.

163 citations


Journal ArticleDOI
TL;DR: Studies on the effects of stimuli from multiple sensory modalities on the brain of humans and some other higher primates are reviewed, striking that humans and other catarrhines interface the visual system to other sensory systems in the orbitofrontal cortex.
Abstract: In primates, stimuli to sensory systems influence motivational and emotional behavior via neural relays to the orbitofrontal cortex. This article reviews studies on the effects of stimuli from multiple sensory modalities on the brain of humans and some other higher primates. The primate orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odors is represented. A somatosensory input is revealed by neurons that respond to the viscosity of food in the mouth, to the texture (mouth feel) of fat in the mouth, and to the temperature of liquids placed into the mouth. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas. Information about each of these modalities is represented separately by different neurons, but in addition, other neurons show convergence between different types of sensory input. This convergence occurs by associative learning between the visual or olfactory input and the taste. In that emotions can be defined as states elicited by reinforcers, the neurons that respond to primary reinforcers (such as taste and touch), as well as learn associations to visual and olfactory stimuli that become secondary reinforcers, provide a basis for understanding the functions of the orbitofrontal cortex in emotion. In complementary neuroimaging studies in humans, it is being found that areas of the orbitofrontal cortex are activated by pleasant touch, by painful touch, by taste, by smell, and by more abstract reinforcers such as winning or losing money. Damage to the orbitofrontal cortex in humans can impair the learning and reversal of stimulus-reinforcement associations and thus the correction of behavioral responses when these are no longer appropriate because previous reinforcement contingencies change. It is striking that humans and other catarrhines, being visual specialists like other anthropoids, interface the visual system to other sensory systems (e.g., taste and smell) in the orbitofrontal cortex.

Journal ArticleDOI
TL;DR: It is shown that brain size increased significantly in two critical phases in the evolution of odontocetes, and was accompanied by a decrease in body size in Delphinoidea only by 15 million years ago.
Abstract: Toothed whales (order Cetacea: suborder Odontoceti) are highly encephalized, possessing brains that are significantly larger than expected for their body sizes. In particular, the odontocete superfamily Delphinoidea (dolphins, porpoises, belugas, and narwhals) comprises numerous species with encephalization levels second only to modern humans and greater than all other mammals. Odontocetes have also demonstrated behavioral faculties previously only ascribed to humans and, to some extent, other great apes. How did the large brains of odontocetes evolve? To begin to investigate this question, we quantified and averaged estimates of brain and body size for 36 fossil cetacean species using computed tomography and analyzed these data along with those for modern odontocetes. We provide the first description and statistical tests of the pattern of change in brain size relative to body size in cetaceans over 47 million years. We show that brain size increased significantly in two critical phases in the evolution of odontocetes. The first increase occurred with the origin of odontocetes from the ancestral group Archaeoceti near the Eocene-Oligocene boundary and was accompanied by a decrease in body size. The second occurred in the origin of Delphinoidea only by 15 million years ago.

Journal ArticleDOI
TL;DR: Results indicate that age is an important factor for strain and growth of the cranium in miniature swine.
Abstract: Cranial bones and sutures are mechanically loaded during mastication. Their response to masticatory strain, however, is largely unknown, especially in the context of age change. Using strain gages, this study investigated masticatory strain in the posterior interfrontal and the anterior interparietal sutures and their adjacent bones in 3- and 7-month-old miniature swine (Sus scrofa). Double-fluorochrome labeling of these animals and an additional 5-month group was used to reveal suture and bone growth as well as features of suture morphology and fusion. With increasing age, the posterior interfrontal suture strain decreased in magnitude and changed in pattern from pure compression to both compression and tension, whereas the interparietal suture remained in tension and the magnitude increased unless the suture was fused. Morphologically, the posterior interfrontal suture was highly interdigitated at 3 months and then lost interdigitation ectocranially in older pigs, whereas the anterior interparietal suture remained butt-ended. Mineralization apposition rate (MAR) decreased with age in both sutures and was unrelated to strain. Bone mineralization was most vigorous on the ectocranial surface of the frontal and the parietal bones. Unlike the sutures, with age bone strain remained constant while bone MARs significantly increased and were correlated with bone thickness. Fusion had occurred in the interparietal suture of some pigs. In all cases fusion was ectocranial rather than endocranial. Fusion appeared to be associated with increased suture strain and enhanced bone growth on the ectocranial surface. Collectively, these results indicate that age is an important factor for strain and growth of the cranium. .

Journal ArticleDOI
TL;DR: Comparisons between the two primate suborders demonstrate that haplorhines and strepsirrhines differ significantly in eye morphology, and it is revealed that diurnal anthropoids have smaller relative cornea sizes than most nonprimate mammals.
Abstract: Comparative studies of mammalian eye morphology have shown that relative cornea size is an important correlate of visual ecology. Nocturnal species tend to have large corneas relative to eye size as an adaptation for increasing visual sensitivity. By contrast, diurnal species tend to have smaller corneas relative to eye size because their eye morphology maximizes visual acuity. Although qualitative analyses suggest that activity pattern may have a similar influence on eye morphology in primates, various current hypotheses have proposed that either diurnal anthropoids or diurnal lemurs have visual systems that diverge from those of other diurnal mammals. The goal of this analysis is to quantify the relationship between eye morphology and activity pattern in primates and to determine whether primates exhibit variation in eye morphology comparable to that of other mammals. Data on eye size and cornea size were collected for 147 specimens of 55 primate species. These data reveal that, within primate suborders, diurnal species have significantly smaller relative cornea sizes than nocturnal or cathemeral species. Both haplorhines and strepsirrhines thus exhibit variation in eye morphology that is consistent with functional expectations. However, comparisons between the two primate suborders demonstrate that haplorhines and strepsirrhines differ significantly in eye morphology. Whereas strepsirrhines have relative cornea sizes that are similar to nonprimate mammals of comparable activity pattern, diurnal anthropoids have smaller relative cornea sizes than most nonprimate mammals. This derived eye morphology in anthropoids probably evolved in the anthropoid stem lineage as a result of selection for highly acute diurnal vision.

Journal ArticleDOI
TL;DR: This study illustrates that use of the Euler characteristic and fractionator sampling is a robust and efficient, unbiased principle for the estimation of total alveolar number in the lung or in well-defined parts of it.
Abstract: Estimation of alveolar number in the lung has traditionally been done by assuming a geometric shape and counting alveolar profiles in single, independent sections. In this study, we used the unbiased disector principle to estimate the Euler characteristic (and thereby the number) of alveolar openings in rat lungs and rhesus monkey lung lobes and to obtain robust estimates of average alveolar volume. The estimator of total alveolar number was based on systematic, uniformly random sampling using the fractionator sampling design. The number of alveoli in the rat lung ranged from 17.3 x 10(6) to 24.6 x 10(6), with a mean of 20.1 x 10(6). The average number of alveoli in the two left lung lobes in the monkey ranged from 48.8 x 10(6) to 67.1 x 10(6) with a mean of 57.7 x 10(6). The coefficient of error due to stereological sampling was of the order of 0.06 in both rats and monkeys and the biological variation (coefficient of variance between individuals) was 0.15 in rat and 0.13 in monkey (left lobe, only). Between subdivisions (left/right in rat and cranial/caudal in monkey) there was an increase in variation, most markedly in the rat. With age (2-13 years) the alveolar volume increased 3-fold (as did parenchymal volume) in monkeys, but the alveolar number was unchanged. This study illustrates that use of the Euler characteristic and fractionator sampling is a robust and efficient, unbiased principle for the estimation of total alveolar number in the lung or in well-defined parts of it.

Journal ArticleDOI
TL;DR: Based on orbit convergence, Primates as a group have the largest binocular visual fields among mammals and display a linear relationship.
Abstract: The orbital apertures of Primates are among the most convergent (i.e., facing in the same direction) among mammals. It is often assumed that orbit convergence is associated with binocular visual field overlap and stereoscopic depth perception in primates. Likewise, it is also assumed that orbit orientation reflects the shape of the visual field across mammals. To date, however, no study has demonstrated that orbit and visual field orientation are correlated, much less comparable, across mammals. In this study, data on orbit convergence were collected for a representative sample of mammals for which data on the extent of the visual field are available. Both standard and phylogenetically controlled comparisons were made. The results demonstrate that orbit convergence and binocular visual field overlap are significantly correlated and display a linear relationship. Based on orbit convergence, Primates as a group have the largest binocular visual fields among mammals.

Journal ArticleDOI
TL;DR: The data presented here demonstrate that increased suture complexity was observed in a hypermuscular mouse model (GDF8(-/-)) with significantly increased temporalis muscle mass and bite forces, and suggest that cranial suture connective tissue locally adapts to functional demands of the biomechanical suture environment.
Abstract: The purpose of this study is to test predicted form-function relationships between cranial suture complexity and masticatory muscle mass and biomechanics in a mouse model. Specifically, to test the hypothesis that increased masticatory muscle mass increases sagittal suture complexity, we measured the fractal dimension (FD), temporalis mass, and temporalis bite force in myostatin-deficient (GDF8(-/-)) mice and wild-type CD-1 mice (all male, 6 months old). Myostatin is a negative regulator of muscle mass, and myostatin-deficient mice show a marked increase in muscle mass compared to normal mice. We predicted that increased sagittal suture complexity would decrease suture stiffness. The data presented here demonstrate that increased suture complexity (measured as FD) was observed in a hypermuscular mouse model (GDF8(-/-)) with significantly increased temporalis muscle mass and bite forces. Hypermuscular mice were also found to possess suture connective tissue that was less stiff (i.e., underwent more displacement before failure occurred) when loaded in tension. By decreasing stiffness, suture complexity apparently helps to dissipate mechanical loads within the cranium that are related to chewing. These results suggest that cranial suture connective tissue locally adapts to functional demands of the biomechanical suture environment. As such, cranial sutures provide a novel model for studies in connective tissue mechanotransduction.

Journal ArticleDOI
TL;DR: The current understanding of the origins of vascular SMCs from multipotential stem and progenitor cells in developing as well as adult vasculature is reviewed.
Abstract: Vascular smooth muscle cells (SMCs) originate from multiple types of progenitor cells. In the embryo, the most well studied SMC progenitor is the cardiac neural crest stem cell. Smooth muscle differentiation in the neural crest lineage is controlled by a combination of cell intrinsic factors, including Pax3, Tbx1, FoxC1, and serum response factor, interacting with various extrinsic factors in the local environment such as bone morphogenetic proteins (BMPs), Wnts, endothelin (ET)-1, and FGF8. Additional sources of multipotential cells that give rise to vascular SMCs in the embryo include proepicardial cells and possibly endothelial progenitor cells. In the adult, vascular SMCs must continually repair arterial injuries and maintain functional mass in response to changing demands upon the vessel wall. Recent evidence suggests that this is accomplished, in part, by recruiting multipotential vascular progenitors from bone marrow-derived stem cells as well as from less well defined sources within adult tissues themselves. This article will review our current understanding of the origins of vascular SMCs from multipotential stem and progenitor cells in developing as well as adult vasculature.

Journal ArticleDOI
TL;DR: It is found that torsion is a main determinant of the macro- and microstructural design of long bones in birds and that covariation between variables accounts for as much as 58% of the total variation.
Abstract: Here we study the occurrence of torsion-resisting morphological and histological features (thin bone walls, circular shaft cross-section, oblique collagen fibers, and laminar tissue arrangement) in a sample of 168 long bones from wings and legs of 22 bird species. These structural parameters were measured in mid diaphyseal undemineralized cross-sections and analyzed using uni-, bi-, and multivariate (principal components analysis) data analysis techniques. We found that the four variables are significantly and positively correlated, and that covariation between variables accounts for as much as 58% of the total variation. These results suggest that torsion is a main determinant of the macro- and microstructural design of long bones in birds. Humerus, ulna, and femur generally possess torsion-resisting features, while other bones (radius, carpometacarpus, tibiotarsus, tarsometatarsus, and foot phalanx) rather show bending/axial load-resisting structural properties. These results are congruent with in vivo strain data from the literature, which reported high torsional loading in humerus and ulna during flapping flight, but also in the subhorizontal avian femur during terrestrial locomotion. The precise function of the laminar tissue spatial arrangement, the role of pneumatization, and the influence of flight mode are discussed.

Journal ArticleDOI
TL;DR: The liver is innervated by aminergic, cholinergic, peptidergic, and nitrergic nerves, and the extent and distribution of intralobular innervation are highly variable as well as species-dependent and may be inversely related to the density of gap junctions between contiguous hepatic parenchymal cells.
Abstract: The role of neural elements in regulating blood flow through the hepatic sinusoids, solute exchange, and parenchymal function is incompletely understood. This is due in part to limited investigation in only a few species whose hepatic innervation may differ significantly from humans. For example, most experimental studies have used rats and mice having livers with little or no intralobular innervation. In contrast, most other mammals, including humans, have aminergic and peptidergic nerves extending from perivascular plexus in the portal space into the lobule, where they course in Disse's space in close relationship to stellate cells (fat storing cells of Ito) and hepatic parenchymal cells. While these fibers extend throughout the lobule, they predominate in the periportal region. Cholinergic innervation, however, appears to be restricted to structures in the portal space and immediately adjacent hepatic parenchymal cells. Neuropeptides have been colocalized with neurotransmitters in both adrenergic and cholinergic nerves. Neuropeptide Y (NPY) has been colocalized in aminergic nerves supplying all segments of the hepatic-portal venous and the hepatic arterial and biliary systems. Nerve fibers immunoreactive for substance P and somatostatin follow a similar distribution. Intralobular distribution of all of these nerve fibers is species-dependent and similar to that reported for aminergic fibers. Vasoactive intestinal peptide and calcitonin gene-related peptide (CGRP) are reported to coexist in cholinergic and sensory afferent nerves innervating portal veins and hepatic arteries and their branches, but not the other vascular segments or the bile ducts. Nitrergic nerves immunoreactive for neuronal nitric oxide (nNOS) are located in the portal tract where nNOS colocalizes with both NPY- and CGRP-containing fibers. In summary, the liver is innervated by aminergic, cholinergic, peptidergic, and nitrergic nerves. While innervation of structures in the portal tract is relatively similar between species, the extent and distribution of intralobular innervation are highly variable as well as species-dependent and may be inversely related to the density of gap junctions between contiguous hepatic parenchymal cells.

Journal ArticleDOI
TL;DR: The dimensions of the outer ear (pinna) were measured in cadaveric specimens representing nearly every primate family and used to calculate a shape ratio, which indicated that most nonanthropoids have ears that are tall and narrow, whereas monkeys and apes are characterized by ears with more equal height and width dimensions.
Abstract: The auditory region contains numerous structures that have proven useful for phylogenetic classification at various taxonomic levels However, little work has been done in primates relating differences in morphology to variations in hearing performance This study documents anatomical and physiological distinctions within primates and begins to address the functional and evolutionary consequences of these and other auditory features The dimensions of the outer ear (pinna) were measured in cadaveric specimens representing nearly every primate family and used to calculate a shape ratio (height/width) It was found that nonanthropoids have a significantly higher ratio than anthropoids, although the actual height was not found to differ This indicates that most nonanthropoids have ears that are tall and narrow, whereas monkeys and apes are characterized by ears with more equal height and width dimensions Eardrum area, stapedial footplate area, and ossicular lever arm lengths were measured in dried specimens to calculate an impedance transformer ratio A distinction was found between anthropoids and strepsirrhines, with the latter group having a transformer ratio indicative of a higher percentage of acoustic energy transmission through the middle ear Audiogram data were gathered from the literature to analyze hearing sensitivity and it was found that platyrrhines illustrate more low-frequency sensitivity than like-sized lorisoids The effects of intraspecific variation on the audiogram results were also examined and were found to produce similar results as the analysis using species mean threshold values Lastly, correlations between morphological and audiogram variables were examined Several measures of hearing sensitivity were found to be correlated with pinna shape but correlations with middle ear transmission properties were weaker In addition to using traditional statistical techniques, phylogenetic corrective methods were applied to address the problem of statistical nonindependence of the data and the results of both analyses are compared These findings are discussed with respect to how sensory adaptations and phylogenetic history may be related to the current radiation of primates

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TL;DR: Results show that greater MC density correlates with the extent to which primates are frugivorous; however, locomotor and/or phylogenetic effects cannot be discounted.
Abstract: Meissner corpuscles (MCs) are specialized mechanoreceptors located exclusively in the papillae of glabrous skin. They are confined largely to cutaneous pads of the extremities and respond to transient, phasic, or vibratory stimuli. Though absent in most eutherian taxa, MCs are reported in all primates studied, being most developed in modern humans. The location of MCs between the internal ridges of the epidermis indicates they are well situated to detect friction or deformation at the external surface. Accordingly, MCs are hypothesized to provide primates generally with an enhanced tactile perception. However, the selective pressures favoring greater somatosensory acuity in primates are seldom considered. Interestingly, primate digital dexterity varies greatly. In general, dexterity improves with the extent to which foraging requires food manipulation or textural evaluation. This observation implies that MC density could vary accordingly. Here we report on the density of MCs in five anthropoid taxa selected to represent diverse dietary regimes. Results show that greater MC density correlates with the extent to which primates are frugivorous; however, locomotor and/or phylogenetic effects cannot be discounted.

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TL;DR: Evidence for adult hemangioblasts began to appear, and recent single-cell bone marrow transplants have confirmed their existence, and there is great hope that either alone, in combination with angiogenic factors, or as gene therapy vectors, these cells can harness to treat ischemic and vascular diseases in the relatively near future.
Abstract: After decades of speculation, proof of embryonic hemangioblasts finally emerged a few years ago. Surprisingly, at about the same time, evidence for adult hemangioblasts began to appear, and recent single-cell bone marrow transplants have confirmed their existence. Embryonic and adult hemangioblasts appear to share antigenic determinants, including CD34, ACC133, and VEGFR2, although their phenotype may be plastic. They also respond to similar factors, prominent among them vascular endothelial growth factor (VEGF). In the adult, hemangioblasts reside principally in the bone marrow, although they may subsequently leave that niche to reside in nonhematopoietic tissues. A number of studies indicate that these cells or their progeny may be a significant source of endothelial cells in adult pathologic and nonpathologic vascularization, and may participate in vascular repair. In addition to hemangioblasts, a more differentiated source of endothelial cell progenitors may be present in the blood, namely, monocytes or monocytic-like cells. The relative importance of the two cell types in vivo is not clear, though endothelial cells derived from the two sources may not be identical, and hemangioblasts seem to provide a stimulus for differentiation of the monocytes. Treatment with exogenous bone marrow-derived cells can promote neovascularization, accelerate restoration of blood flow to ischemic tissues, and improve cardiac function after infarct. Hence, there is great hope that either alone, in combination with angiogenic factors, or as gene therapy vectors, we can harness these cells to treat ischemic and vascular diseases in the relatively near future. Anat Rec Part A 276A:13–21, 2004. © 2004 Wiley-Liss, Inc.

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TL;DR: Parasympathetic hepatic nerves potentiate the insulin-dependent hepatic glucose extraction when a portal glucose sensor detects prandial glucose delivery from the gut and coordinate the hepatic and extrahepatic glucose utilization to prevent hypoglycemia and, at the same time, warrant efficient disposal of excess glucose.
Abstract: More than any other organ, the liver contributes to maintaining metabolic equilibrium of the body, most importantly of glucose homeostasis. It can store or release large quantities of glucose according to changing demands. This homeostasis is controlled by circulating hormones and direct innervation of the liver by autonomous hepatic nerves. Sympathetic hepatic nerves can increase hepatic glucose output; they appear, however, to contribute little to the stimulation of hepatic glucose output under physiological conditions. Parasympathetic hepatic nerves potentiate the insulin-dependent hepatic glucose extraction when a portal glucose sensor detects prandial glucose delivery from the gut. In addition, they might coordinate the hepatic and extrahepatic glucose utilization to prevent hypoglycemia and, at the same time, warrant efficient disposal of excess glucose.

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TL;DR: Using an in vitro explant analysis, it is shown that BMPs are crucial for myocardium formation, and the spatiotemporal expression patterns of these B MPs in relation to myocardial formation at the distal ends and within the heart suggest a role for BMP's in myocardia formation.
Abstract: Bone morphogentic proteins (BMPs) play an important role in cardiac development. Using an in vitro explant analysis, we show that BMPs are crucial for myocardium formation. As a first approach to identify which BMP may be involved in myocardium formation in intraand extracardiac mesenchyme in vivo, a survey of the expression patterns of BMP2, -4, -5, -6, and -7 mRNA is prepared by in situ hybridization in chicken embryonic hearts from HH5 to 44. During recruitment of mesodermal cells to the outflow tract myocardium (HH10 –23), BMP2, -4, -5, and -7 mRNA are expressed in the distal myocardial border and the flanking mesenchyme. After completion, BMP2 and -4 mRNA become restricted to the mesenchyme and BMP5 and -7 mRNA to the myocardium. At the venous pole, BMP2, -5, and -7 mRNA are expressed in the distal myocardial border of the caval vein, while BMP2, -5, -6, and -7 mRNA are expressed in the distal myocardium around the pulmonary vein. BMP4 mRNA is expressed in the adjacent mesenchyme at both sides. During muscularization of the atrioventricular cushions and the tricuspid valve, the cardiomyocytes that protrude into the mesenchyme express BMP2, -4, -5, and -7 mRNA, whereas BMP6 mRNA is expressed in the cushion mesenchyme. The myocardial protrusions formed in the mesenchymal proximal outlet septum express BMP4, -5, and -7 mRNA, while BMP2 and -6 mRNA are expressed in the mesenchyme. The spatiotemporal expression patterns of these BMPs in relation to myocardium formation at the distal ends and within the heart suggest a role for BMPs in myocardium formation. During delamination of the valves, BMP4 and -6 mRNA are expressed at the ventricular side of the forming mitral valve, BMP4 mRNA at the ventricular side of the forming tricuspid valve, and BMP2, -4, and -6 mRNA at the vascular side of the forming semilunar valves. © 2004 Wiley-Liss, Inc.

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TL;DR: The findings suggest that periostin is involved at the sites of the cell-to-matrix interaction, serving as adhesive equipment for bearing mechanical forces, including occlusal force and tooth eruption.
Abstract: Previous reports have shown expression of immunoreactivity for periostin, originally identified as osteoblast-specific factor-2, in the periosteum and periodontal ligament. However, the developmental changes in its expression and the detailed immunolocalization have remained veiled. The present study was undertaken to examine the spatiotemporal expression of this protein in teeth and their associated tissues of mice during development at light and electron microscopic levels. In tooth germs at cap stage, periostin immunoreactivity was recognizable in the interface between inner enamel epithelium and preodontoblasts as well as in the mesenchymal tissues around cervical loop. Dental follicles around tooth germs at bell stage localized periostin immunopositivity in addition to the immunopositive areas observed in cap-staged tooth germs, although the functional significance of periostin has remained unclear in tooth development. Furthermore, periostin immunoreactivity was also found in the alveolar bone surface. In the incisors of both 7- and 21-day-old mice, immunoreaction for periostin was discernible in the lingual periodontal ligament and labial fibrous tissue adjacent to the papillary layer. After postnatal day 7, immunoreaction for periostin came to be restricted to the fibrous bundles in the periodontal ligament in accordance with the organization of the periodontal fibers, indicating its localization matched the morphogenesis of the periodontal ligament. Immunoelectron microscopic observation of the mature periodontal ligament verified the localization of periostin between the cytoplasmic processes of periodontal fibroblasts and cementoblasts and the adjacent collagen fibrils. Our findings suggest that periostin is involved at the sites of the cell-to-matrix interaction, serving as adhesive equipment for bearing mechanical forces, including occlusal force and tooth eruption.

Journal ArticleDOI
Shuji Yamashita1
TL;DR: The results indicate that species and tissues differences should be taken into careful consideration in assessing the physiological and pharmacological effects of sex steroids (particularly estrogens) on the reproductive tissues of male rodents.
Abstract: Using immunohistochemical methods, we studied the cell-type- and species-specific expressions of estrogen receptor (ER) isoforms (ERα and ERβ) and androgen receptors (ARs) in the male reproductive tract and accessory sex glands of mature mice and rats. ERα and ERβ showed cell-type- and species-specific distributions, respectively. In contrast, AR was localized in the epithelial and stroma cells of all tissues examined in this study, in both species. In mice, the epithelial cells of the ductuli efferentes showed a strong ERα-immunoreaction, and those of the caput epididymis, coagulating glands, and prostate also exhibited a positive reaction. Stroma cells, except in the ductuli efferentes, showed a positive ERα-immunostaining. In rats, ERα was detected in very few cell types: the epithelial cells of the ductuli efferentes showed a strong reaction, and the stroma cells of the ampullary and urethral glands exhibited a weak reaction. ERβ was localized in the epithelial cells of the prostate in mice, while the reaction was faint or negative in both the epithelial and stroma cells of other tissues. In rats, the ERβ-immunoreaction was strongest in the epithelial cells of the ventral prostate. The epithelial cells of the corpus and cauda epididymis, ductus deferens, and urethral glands, and the stroma cells of the urethral glands were also positively ERβ-immunostained. Almost the same AR distribution pattern was observed in both species. In particular, strong AR-immunostaining was present in the epithelial cells of the caput and corpus epididymis, seminal vesicle, and ventral prostate. These results indicate that species and tissues differences should be taken into careful consideration in assessing the physiological and pharmacological effects of sex steroids (particularly estrogens) on the reproductive tissues of male rodents. © 2004 Wiley-Liss, Inc.

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TL;DR: It is shown that inhibition of the SNS reduced fibrosis in carbon tetrachloride-induced liver injury, and a better understanding of the mechanisms of regeneration could have therapeutic possibilities, which could even obviate the need for orthotopic liver transplantation.
Abstract: Liver progenitor cells as well as hepatic stellate cells have neuroendocrine features. Progenitor cells express chromogranin-A and neural cell adhesion molecule, parathyroid hormone-related peptide, S-100 protein, neurotrophins, and neurotrophin receptors, while hepatic stellate cells express synaptophysin, glial fibrillary acidic protein, neural cell adhesion molecule, nestin, neurotrophins, and their receptors. This phenotype suggests that these cell types form a neuroendocrine compartment of the liver, which could be under the control of the central nervous system. We recently showed that the parasympathetic nervous system promotes progenitor cell expansion after liver injury, since selective vagotomy reduces the number of progenitor cells after chemical injury in the rat. Similarly, after transplantation, which surgically denervates the liver, human livers that develop hepatitis have fewer progenitor cells than native, fully innervated livers with similar degrees of liver injury. There is also accumulating experimental evidence linking the autonomic system, in particular the sympathetic nervous system (SNS), with the pathogenesis of cirrhosis and its complications. Recently, it has been shown that hepatic stellate cells themselves respond to neurotransmitters. Moreover, inhibition of the SNS reduced fibrosis in carbon tetrachloride-induced liver injury. In view of the denervated state of transplanted livers, it is very important to unravel the neural control mechanisms of regeneration and fibrogenesis. Moreover, since there is a shortage of donor organs, a better understanding of the mechanisms of regeneration could have therapeutic possibilities, which could even obviate the need for orthotopic liver transplantation.

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TL;DR: The results of this study support the hypothesis that allometry contributes to the organization of variation in complex morphological structures.
Abstract: Allometry is an important factor of morphological integration that contributes to the organization of the phenotype and its variation. Variation in the allometric shape of the mandible is particularly important in hominid evolution because the mandible carries important taxonomic traits. Some of these traits are known to covary with size, particularly the retromolar space, symphyseal curvature, and position of the mental foramen. The mandible is a well studied system in the context of the evolutionary development of complex morphological structures because it is composed of different developmental units that are integrated within a single bone. In the present study, we investigated the allometric variation of two important developmental units that are separated by the inferior nerve (a branch of CN V3). We tested the null hypothesis that there would be no difference in allometric variation between the two components. Procrustes-based geometric morphometrics of 20 two-dimensional (2D) landmarks were analyzed by multivariate regressions of shape on size in samples from 121 humans, 48 chimpanzees, and 50 gorillas (all recent specimens), eight fossil hominids from Atapuerca, Sima de los Huesos (AT-SH), and 17 Neandertals. The findings show that in all of the examined species, there was significantly greater allometric variation in the supra-nerve unit than in the infra-nerve unit. The formation of the retromolar space exhibited an allometric relationship with the supra-nerve unit in all of the species studied. The formation of the chin-like morphology is an “apodynamic” feature of the infra-nerve unit in the AT-SH hominids. The results of this study support the hypothesis that allometry contributes to the organization of variation in complex morphological structures. Anat Rec Part A 278A:551–560, 2004. © 2004 Wiley-Liss, Inc.

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TL;DR: The structure-function relationship of the AV junction during normal conduction, reentry, and junctional rhythm is investigated, and differential expression of Cx isoforms in this region provides an explanation of longitudinal dissociation, dual-pathway electrophysiology, and AV nodal reentrant arrhythmogenesis.
Abstract: In the normal heart, the atrioventricular node (AVN) is part of the sole pathway between the atria and ventricles. Under normal physiological conditions, the AVN controls appropriate frequency-dependent delay of contractions. The AVN also plays an important role in pathology: it protects ventricles during atrial tachyarrhythmia, and during sinoatrial node failure an AV junctional pacemaker can drive the heart. Finally, the AV junction provides an anatomical substrate for reentry. Using fluorescent imaging with voltage-sensitive dyes and immunohistochemistry, we have investigated the structure-function relationship of the AV junction during normal conduction, reentry, and junctional rhythm. We identified molecular and structural heterogeneity that provides a substrate for the dual-pathway AVN conduction. We observed heterogeneity of expression of three isoforms of connexins: Cx43, Cx45, and Cx40. We identified the site of origin of junctional rhythm at the posterior extension of the AV node in 79% (n = 14) of the studied hearts. This structure was similar to the compact AV node as determined by morphologic and molecular investigations. In particular, both the posterior extension and the compact node express the pacemaking channel HCN4 (responsible for the I(F) current) and neurofilament 160. In the rabbit heart, AV junction conduction, reentrant arrhythmia, and spontaneous rhythm are governed by heterogeneity of expression of several isoforms of gap junctions and ion channels. Uniform neurofilament expression suggests that AV nodal posterior extensions are an integral part of the cardiac pacemaking and conduction system. On the other hand, differential expression of Cx isoforms in this region provides an explanation of longitudinal dissociation, dual-pathway electrophysiology, and AV nodal reentrant arrhythmogenesis.