Repeated loss of frontal sinuses in arctoid carnivorans

Many mammal skulls contain air spaces inside the bones surrounding the nasal chamber including the frontal, maxilla, ethmoid, and sphenoid, all of which are called paranasal sinuses. Within the Carnivora, frontal sinuses are usually present, but vary widely in size and shape. The causes of this variation are unclear, although there are some functional associations, such as a correlation between expanded frontal sinuses and a durophagous diet in some species (e.g., hyenas) or between absent sinuses and semiaquatic lifestyle (e.g., pinnipeds). To better understand disparity in frontal sinus morphology within Carnivora, we quantified frontal sinus size in relationship to skull size and shape in 23 species within Arctoidea, a clade that is ecologically diverse including three independent invasions of aquatic habitats, by bears, otters, and pinnipeds, respectively. Our sampled species range in behavior from terrestrial (rarely or never forage in water), to semiterrestrial (forage in water and on land), to semiaquatic (forage only in water). Results show that sinuses are either lost or reduced in both semiterrestrial and semiaquatic species, and that sinus size is related to skull size and shape. Among terrestrial species, frontal sinus size was positively allometric overall, but several terrestrial species completely lacked sinuses, including two fossorial badgers, the kinkajou (a nocturnal, arboreal frugivore), and several species with small body size, indicating that factors other than aquatic habits, such as space limitations due to constraints on skull size and shape, can limit sinus size and presence. J. Morphol. 276:22–32, 2015. © 2014 Wiley Periodicals, Inc.     

An allometric study of the frontal sinus in Gorilla, Pan and Pongo

There is considerable speculation about the role and significance of the paranasal sinuses in the Hominoidea, and this study aims to present new data about an old problem from cephalograms of dried crania. Measurements of frontal sinus volumes were determined for Gorilla gorilla gorilla; G. gorilla beringei and Pan troglodytes. By adopting an allometric approach it was determined that the frontal sinus volume of Gorilla is relatively smaller than that of Pan, and that the frontal sinus of G. g. gorilla is relatively smaller than that of G. g. beringei. Frontal sinus volume scales in a positive allometric fashion relative to skull length. Since the slope is steeper for Pan, frontal sinus volume is increasing at a faster rate than in Gorilla. Sexual dimorphism in frontal sinus volume is present. Thirty crania of Pongo were investigated for evidence of pneumatization of the frontal bone. In no case was secondary invasion of the frontal bone by the maxillary antrum observed. In Gorilla, the nasal cavity volume scales isometrically with skull length. The scaling relationships discussed do not support any 'functional' role of the frontal sinus associated with nasal function but suggest a 'structural' role associated with craniofacial architecture.     

颅骨过度气化1例影像表现并文献复习

目的:颅骨过度气化(Craniocervical bone pneumatisation)比较少见,近年来对其报道和认识逐渐增多。本文介绍一例偶然发现的颅骨过度气化的影像表现并对相关文献进行复习。方法:分析我院1例颅骨过度气化的影像学图像。并从国外pubmed数据库(www.pubmed.gov)及国内中国知网数据库(www.cnki.net)查找发表的文献进行文献复习。结果:颅骨过度气化表现为颅骨的气腔形成并局部膨出,多为偶然发现或因并发症就诊,可涉及颅盖骨、颅底骨及颈椎等,近年来对其认识逐渐增多。结论:颅骨过度气化尽管少见,对征象的认知有助于相关科室医师正确识别此征象,从而有利于临床一些相关疑难病例的诊断和操作并对防止漏、误诊具有一定的意义。     

Epigenomic profiling reveals DNA-methylation changes associated with major psychosis

Epigenetic misregulation is consistent with various non-Mendelian features of schizophrenia and bipolar disorder. To date, however, few studies have investigated the role of DNA methylation in major psychosis, and none have taken a genome-wide epigenomic approach. In this study we used CpG-island microarrays to identify DNA-methylation changes in the frontal cortex and germline associated with schizophrenia and bipolar disorder. In the frontal cortex we find evidence for psychosis-associated DNA-methylation differences in numerous loci, including several involved in glutamatergic and GABAergic neurotransmission, brain development, and other processes functionally linked to disease etiology. DNA-methylation changes in a significant proportion of these loci correspond to reported changes of steady-state mRNA level associated with psychosis. Gene-ontology analysis highlighted epigenetic disruption to loci involved in mitochondrial function, brain development, and stress response. Methylome network analysis uncovered decreased epigenetic modularity in both the brain and the germline of affected individuals, suggesting that systemic epigenetic dysfunction may be associated with major psychosis. We also report evidence for a strong correlation between DNA methylation in the MEK1 gene promoter region and lifetime antipsychotic use in schizophrenia patients. Finally, we observe that frontal-cortex DNA methylation in the BDNF gene is correlated with genotype at a nearby nonsynonymous SNP that has been previously associated with major psychosis. Our data are consistent with the epigenetic theory of major psychosis and suggest that DNA-methylation changes are important to the etiology of schizophrenia and bipolar disorder.     

Digital volume tomography in the diagnosis of the surgical anatomy of the frontal recess area

Frontal recess anatomy can be very complex, with accessory cells, such as frontal bulla, agger nasi, suprabulla, and frontal ethmoidal (Kuhn) cells, which may lead to obstruction of the frontal sinus. Digital volume tomography of paranasal sinuses used in this investigation revealed the rate of types of development of various anatomic structures and their correlation with frontal sinusitis in patients with (a study) and without the latter (a control group).     

In vivo impact of Dlx3 conditional inactivation in neural crest‐derived craniofacial bones

Mutations in DLX3 in humans lead to defects in craniofacial and appendicular bones, yet the in vivo activities related to Dlx3 function during normal skeletal development have not been fully elucidated. Here we used a conditional knockout approach to analyze the effects of neural crest deletion of Dlx3 on craniofacial bones development. At birth, mutant mice exhibit a normal overall positioning of the skull bones, but a change in the shape of the calvaria was observed. Molecular analysis of the genes affected in the frontal bones and mandibles from these mice identified several bone markers known to affect bone development, with a strong prediction for increased bone formation and mineralization in vivo. Interestingly, while a subset of these genes were similarly affected in frontal bones and mandibles (Sost, Mepe, Bglap, Alp, Ibsp, Agt), several genes, including Lect1 and Calca, were specifically affected in frontal bones. Consistent with these molecular alterations, cells isolated from the frontal bone of mutant mice exhibited increased differentiation and mineralization capacities ex vivo, supporting cell autonomous defects in neural crest cells. However, adult mutant animals exhibited decreased bone mineral density in both mandibles and calvaria, as well as a significant increase in bone porosity. Together, these observations suggest that mature osteoblasts in the adult respond to signals that regulate adult bone mass and remodeling. This study provides new downstream targets for Dlx3 in craniofacial bone, and gives additional evidence of the complex regulation of bone formation and homeostasis in the adult skeleton. J. Cell. Physiol. 228: 654–664, 2013. © 2012 Wiley Periodicals, Inc.     

Nasal cavities and paranasal sinuses in newborns and children]

The paranasal or accessory nasal sinuses begin their development as evaginations of the mucosa during the 3rd and 4th fetal months, but undergo their major expansion after birth according to the development of the facial cranium and the teeth. While in the newborn the sphenoidal and frontal sinuses are still only predispositioned, the ethmoidal labyrinth and particularly the maxillary sinus are of appreciable size. In the 4-year-old the frontal and sphenoidal sinuses are already developed and in the 12-year-old the paranasal sinuses reach their final form and a size equivalent to the adult.     

Toxicological Effects of the Different Substances in Tobacco Smoke on Human Embryonic Development by a Systems Chemo-Biology Approach

The physiological and molecular effects of tobacco smoke in adult humans and the development of cancer have been well described. In contrast, how tobacco smoke affects embryonic development remains poorly understood. Morphological studies of the fetuses of smoking pregnant women have shown various physical deformities induced by constant fetal exposure to tobacco components, especially nicotine. In addition, nicotine exposure decreases fetal body weight and bone/cartilage growth in addition to decreasing cranial diameter and tibia length. Unfortunately, the molecular pathways leading to these morphological anomalies are not completely understood. In this study, we applied interactome data mining tools and small compound interaction networks to elucidate possible molecular pathways associated with the effects of tobacco smoke components during embryonic development in pregnant female smokers. Our analysis showed a relationship between nicotine and 50 additional harmful substances involved in a variety of biological process that can cause abnormal proliferation, impaired cell differentiation, and increased oxidative stress. We also describe how nicotine can negatively affect retinoic acid signaling and cell differentiation through inhibition of retinoic acid receptors. In addition, nicotine causes a stress reaction and/or a pro-inflammatory response that inhibits the agonistic action of retinoic acid. Moreover, we show that the effect of cigarette smoke on the developing fetus could represent systemic and aggressive impacts in the short term, causing malformations during certain stages of development. Our work provides the first approach describing how different tobacco constituents affect a broad range of biological process in human embryonic development.     

Parameter-free molecular super-structures quantification in single-molecule localization microscopy

Understanding biological function requires the identification and characterization of complex patterns of molecules. Single-molecule localization microscopy (SMLM) can quantitatively measure molecular components and interactions at resolutions far beyond the diffraction limit, but this information is only useful if these patterns can be quantified and interpreted. We provide a new approach for the analysis of SMLM data that develops the concept of structures and super-structures formed by interconnected elements, such as smaller protein clusters. Using a formal framework and a parameter-free algorithm, (super-)structures formed from smaller components are found to be abundant in classes of nuclear proteins, such as heterogeneous nuclear ribonucleoprotein particles (hnRNPs), but are absent from ceramides located in the plasma membrane. We suggest that mesoscopic structures formed by interconnected protein clusters are common within the nucleus and have an important role in the organization and function of the genome. Our algorithm, SuperStructure, can be used to analyze and explore complex SMLM data and extract functionally relevant information.     

Acoustic rhinometry in humans: accuracy of nasal passage area estimates, and ability to quantify paranasal sinus volume and ostium size.

A comprehensive study that compared acoustic rhinometry (AR) data to computed tomography (CT) data was performed to evaluate the accuracy of AR measurements in estimating nasal passage area and to assess its ability of quantifying paranasal sinus volume and ostium size in live humans. Twenty nasal passages of 10 healthy adults were examined by using AR and CT. Actual cross-sectional areas of the nasal cavity, sinus ostia sizes, and maxillary and frontal sinus volumes were determined from CT sections perpendicular to the curved acoustic axis of the nasal passage. Nasal cavity volume (from nostril to choana) calculated from the AR-derived area-distance curve was compared with that from the CT-derived area-distance curve. AR measurements were also done on pipe models that featured a side branch (Helmholtz resonator of constant volume but two different neck diameters) simulating a paranasal sinus. In the anterior nasal cavity, there was good agreement between the cross-sectional areas determined by AR and CT. However, posterior to the sinus ostia, AR overestimated cross-sectional area. The difference between AR nasal volume and CT nasal volume was much smaller than the combined volume of the maxillary and frontal sinuses. The results suggest that AR measurements of the healthy adult nasal cavity are reasonably accurate to the level of the paranasal sinus ostia. Beyond this point, AR overestimates cross-sectional area and provides no quantitative data for sinus volume or ostium size. The effects of paranasal sinuses and acoustic resonances in the nasal cavity are not accounted for in the present AR algorithms.     

Mapping bone cell distributions to assess ontogenetic origin of primate midfacial form

Midfacial reduction in primates has been explained as a byproduct of other growth patterns, especially the convergent orbits. This is at once an evolutionary and developmental explanation for relatively short snouts in most modern primates. Here, we use histological sections of perinatal nonhuman primates (tamarin, tarsier, loris) to investigate how orbital morphology emerges during ontogeny in selected primates compared to another euarchontan (Tupaia glis). We annotated serial histological sections for location of osteoclasts or osteoblasts, and used these to create three‐dimensional “modeling maps” showing perinatal growth patterns of the facial skeleton. In addition, in one specimen we transferred annotations from histological sections to CT slices, to create a rotatable 3D volume that shows orbital modeling. Our findings suggest that growth in the competing orbital and neurocranial functional matrices differs among species, influencing modeling patterns. Distinctions among species are observed in the frontal bone, at a shared interface between the endocranial fossa and the orbit. The medial orbital wall is extensively resorptive in primates, whereas the medial orbit is generally depositional in Tupaia. As hypothesized, the orbital soft tissues encroach on available interorbital space. However, eye size cannot, by itself, explain the extent of reduction of the olfactory recess. In Loris, the posterior portion of medial orbit differed from the other primates. It showed evidence of outward drift where the olfactory bulb increased in cross‐sectional area. We suggest the olfactory bulbs are significant to orbit position in strepsirrhines, influencing an expanded interorbital breadth at early stages of development. Am J Phys Anthropol 154:424–435, 2014. © 2014 Wiley Periodicals, Inc.     

The Drosophila SHC adaptor protein is required for signaling by a subset of receptor tyrosine kinases

Receptor tyrosine kinases (RTKs) transduce signals via cytoplasmic adaptor proteins to downstream signaling components. We have identified loss-of-function mutations in dshc, the Drosophila homolog of the mammalian adaptor protein SHC. A point mutation in the phosphotyrosine binding (PTB) domain completely abolishes DSHC function and provides in vivo evidence for the function of PTB domains. Unlike other adaptor proteins, DSHC is involved in signaling by only a subset of RTKs: dshc mutants show defects in Torso and DER but not Sevenless signaling, which is confirmed by epistasis experiments. We show by double-mutant analysis that the adaptors DOS, DRK, and DSHC act in parallel to transduce the Torso signal. Our results suggest that DSHC confers specificity to receptor signaling.     

Muzzle size, paranasal swelling size and body mass in Mandrillus leucophaeus

The drill (Mandrillus leucophaeus), a forest-living Old World monkey, is highly sexually dimorphic, with males exhibiting extreme secondary sexual characteristics, including growth of paranasal swellings on the muzzle. In this study, the size of the secondary bone that forms the paranasal swellings on the muzzles of drills was assessed in relation to body mass proxies. The relationship between the overall size of the muzzle and surrogate measures of body mass was also examined. In female drills, muzzle breadth was positively correlated with two proxies of overall body mass, greatest skull length and upper M1 area. However, there was no such correlation in males. Paranasal swellings in males also appeared to have no significant relationship to body mass proxies. This suggests that secondary bone growth on the muzzles of male drills is independent of overall body size. Furthermore, this secondary bone appears to be vermiculate, probably developing rapidly and in an irregular manner, with no correlation in the sizes of paranasal swelling height and breadth. However, various paranasal swelling dimensions were related to the size of the muzzle. It is suggested that the growth of the paranasal swellings and possibly the muzzle could be influenced by androgen production and reflect testes size and sperm motility. The size and appearance of the paranasal swellings may thus be an indicator of reproductive quality both to potential mates and male competitors. Further work is required to investigate the importance of the paranasal swellings as secondary sexual characteristics in Mandrillus and the relationship between body size and secondary sexual characteristics. Attention should also be paid to the mechanisms and trajectories of facial growth in Mandrillus.     

Diurnality and cone photopigment polymorphism in strepsirrhines: examination of linkage in Lemur catta

Trichromatic color vision is routine among catarrhine primates, but occurs only as a variant form of color vision in some individuals in most platyrrhine genera. This arises from a fundamental difference in the organization of X-chromosome cone opsin genes in these two lineages: catarrhines have two opsin genes specifying middle- and long-wavelength-sensitive cone pigments, while platyrrhines have only a single gene. Some female platyrrhine monkeys achieve trichromacy because of a species polymorphism that allows the possibility of different opsin gene alleles on the two X-chromosomes. Recently, a similar opsin gene polymorphism was detected in some diurnal strepsirrhines, while at the same time appearing to be absent in any nocturnal genera. The aim of this study was to assess whether cone pigment polymorphism is inevitably linked to diurnality in strepsirrhines. Cone photopigments were measured in a species usually classified as diurnal, the ring-tailed lemur (Lemur catta), using electroretinogram flicker photometry, a noninvasive electrophysiological procedure. Each of 12 animals studied was found to have the same middle-wavelength cone pigment, with peak sensitivity at about 547 nm. In conjunction with earlier results, this implies that cone pigment polymorphism is unlikely to exist in this species and that, accordingly, such variation is not a consistently predictable feature of vision in diurnal strepsirrhines.     

TGFbeta-mediated FGF signaling is crucial for regulating cranial neural crest cell proliferation during frontal bone development

The murine frontal bone derives entirely from the cranial neural crest (CNC) and consists of the calvarial (lateral) aspect that covers the frontal lobe of brain and the orbital aspect that forms the roof of bony orbit. TGFbeta and FGF signaling have important regulatory roles in postnatal calvarial development. Our previous study has demonstrated that conditional inactivation of Tgfbr2 in the neural crest results in severe defects in calvarial development, although the cellular and molecular mechanisms by which TGFbeta signaling regulates the fate of CNC cells during frontal bone development remain unknown. Here, we show that TGFbeta IIR is required for proliferation of osteoprogenitor cells in the CNC-derived frontal bone anlagen. FGF acts downstream of TGFbeta signaling in regulating CNC cell proliferation, and exogenous FGF2 rescues the cell proliferation defect in the frontal primordium of Tgfbr2 mutant. Furthermore, the CNC-derived frontal primordium requires TGFbeta IIR to undergo terminal differentiation. However, this requirement is restricted to the developing calvarial aspect of the frontal bone, whereas the orbital aspect forms despite the ablation of Tgfbr2 gene, implying a differential requirement for TGFbeta signaling during the development of various regions of the frontal bone. This study demonstrates the biological significance of TGFbeta-mediated FGF signaling cascade in regulating frontal bone development, suggests that TGFbeta functions as a morphogen in regulating the fate of the CNC-derived osteoblast and provides a model for investigating abnormal craniofacial development.     

A novel application of metabolomics in vertebrate development

Many studies have demonstrated the functions of individual genes associated with embryogenesis and have determined the genome sequences of several organisms. Despite the availability of enormous amount of genetic information, dynamic changes that occur during embryogenesis have not yet been completely understood. In order to understand the dynamic processes involved in embryogenesis, we employed the metabolomic approach. The results of our study indicated that there is a close correlation between metabolomes and developmental stages. Our method enables the identification of embryonic stages using metabolomes as “fingerprints.” In this manner, we could successfully predict embryonic development on the basis of metabolomic fingerprints. This is the first report describing a model for predicting vertebrate development by using metabolomics.     

Relationships between the frontal sinus and climatic conditions: a skeletal approach to cold adaptation

Previous studies in physical anthropology, using superficial facial features, show that the relationship between human facial morphology and climate is not clear. An alternate approach to the problem is the investigation of the deeper facio-anatomical structures (i.e., cranial sinuses and/or foramina) in relation to climatic variables. The present investigation statistically analyses the relationship between climatic conditions (wind chill equivalent temperatures and absolute humidities) and the occurrence and size of frontal sinuses in 153 Eskimo crania. Conditional results from tests of significance of differences and correlation suggest a relationship between low wind chill equivalent temperatures and small frontal sinus surface areas. These results are interpreted in light of cranial sinus function and environmental physiology.