bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional Regulation of Olfactory Bulb Neurogenesis
Authors: Díaz‐Guerra Eva , Pignatelli Jaime , Nieto‐Estévez Vanesa , Vicario‐Abejón Carlos
Published: June 2014

The neurons in the olfactory bulb originate from molecularly defined and spatially distinct proliferative regions. Glutamatergic projection neurons are generated during the embryonic period in the local ventricular zone of the olfactory bulb, a territory in the dorsal telencephalon in which the transcription factor Pax6 is expressed. Some cells in this zone also express Tbr1, a marker of glutamatergic neurons. By contrast, embryonic olfactory bulb interneurons are derived from Gsx2 expressing cells in the dorsal lateral ganglionic eminence of the ventral telencephalon, and from progenitors outside the dorsal lateral ganglionic eminence, including the olfactory bulb neuroepithelium. Postnatally, interneurons arise from the subventricular zone of the lateral ventricle, although the rostral migratory stream and the olfactory bulb also appear to serve as a source of neurons. Transcription factors are crucial to generate all classes of neurons and glia in the olfactory bulb, both during development and adulthood. In this article, we discuss and propose models on how the spatial and temporal regulation of transcription factor expression controls the self‐renewal, proliferation and cell fate of neural stem cells and progenitors, which finally leads to the generation of distinct functional subtypes of neurons in the developing and adult olfactory bulb. Anat Rec, 296:1364‐1382, 2013. © 2013 Wiley Periodicals, Inc.
A World Without the Olfactory Dimension
Authors: Tafalla Marta
Published: June 2014

This article aims to describe what is it like to perceive reality when suffering from congenital anosmia. Nevertheless, this objective entails a fundamental difficulty. Since I have never had the experience of olfaction, it seems natural to me to live in a world lacking the olfactory dimension; this subjective perception is the only one I know and in consequence it is difficult to describe. For this reason, in recent years I have begun to develop long conversations with other people suffering from congenital anosmia, people who have lost their sense of olfaction in adulthood and also people with a good sense of smell. My goal is to draw a map showing the principal differences that might allow us to develop a systematic comparison. Obviously, this is not an experimental or quantitative scientific procedure, but only a modest attempt to compare personal stories about subjective experiences. It is a philosophical‐literary exercise, and does not aim to be anything other than that. But I hope it will help to formulate meaningful questions, which would then need a properly scientific approach. In the first part of this article I want to try to describe how I became aware that other people could smell; and in a second part, I will try to examine the consequences of anosmia in different areas of everyday life: nourishment, relationships with people, own body perception, natural or urban environments perception, time perception, and finally aesthetic appreciation and the implications of living in a world without stench. Anat Rec, 296:1287‐1296, 2013. © 2013 Wiley Periodicals, Inc.
SND1 Affects Proliferation of Hepatocellular Carcinoma Cell Line SMMC‐7721 by Regulating IGFBP3 Expression
Authors: Yin Jie , Ding Jianmin , Huang Li , Tian Xiao , Shi Xuebin , Zhi Lei , Song Juan , Zhang Yi , Gao Xingjie , Yao Zhi , Jing Xiang , Yang Jie
Published: June 2014

Staphylococcal nuclease domain containing 1 (SND1) is a ubiquitously expressed multifunctional protein involved in transcriptional regulation, RNA splicing and RNA metabolism. Ectopic expression of SND1 has been observed in various tumors including colon cancer, breast cancer, prostate cancer and hepatocellular carcinoma (HCC), indicating a positive role of SND1 in tumor initiation and progression. However, the exact role of SND1 in cancers has not been thoroughly investigated. In the present study, we investigated the role of SND1 in HCC. Immunohistochemistry analysis revealed that the expression level of SND1 was higher in HCC tissues than in adjacent nontumor tissues. Stable knock‐down of SND1, performed on the HCC cell line SMMC‐7721 using shRNA lentiviral expression system, led to reduced cell proliferation, clone formation and tumor formation in nude mice. The insulin‐like growth factor (IGF) signaling pathway was frequently dysregulated in HCC, which could facilitate tumor progression. Screening of gene expression levels of the IGF pathway, using real‐time PCR, revealed that a decrease in SND1 expression could increase the expression of IGF‐binding protein 3 (IGFBP3), which can negatively regulate activation of the IGF pathway by restricting interactions between IGF and IGF receptors. Results from previous studies showed that the downregulation of IGFBP3 expression is a common feature in HCC, and the upregulation of IGFBP3 expression could suppress HCC cells proliferation. We further confirmed that stable knock‐down of IGFBP3 could promote SMMC‐7721 cells proliferation. Therefore, we concluded that SND1 could affect SMMC‐7721 cells proliferation by regulating IGFBP3 expression and IGF signaling pathway. Anat Rec, 296:1568–1575, 2013. © 2013 Wiley Periodicals, Inc.
Dens Invaginatus in Ancient Chinese Teeth of 2,000 Years Ago
Authors: Shi Sasa , Duan Xiaohong , Shao Jinling , Duan Qingbo , Peng Shaobin
Published: June 2014

Dens invaginatus (DI) is a developmental anomaly of teeth. Here we observed the characteristics of DI in 517 permanent teeth from 67 ancient Chinese people using micro‐computed tomography (micro‐CT) scanning techniques. The individuals were excavated from Shaanxi province of China and identified to be about 2,000 years old. Four DI categories are proposed to distinguish the different types of DI. The invaginated lingual fossa is classified into three classes. The overall prevalence of DI in 67 individuals was 31.34% (21 of 67). DI was found in 25 of 517 teeth (4.83%). All affected teeth were maxillary lateral incisors. The invaginated lingual fossa (Type I DI) occurred most frequently (84%), followed by radicular grooves (Type II; 16%), while Type III and Type IV were not found in the present study. Some of fossae correspond with radicular grooves (8 of 21; 3 located at mesial, 5 were distal). The bilateral incidence of DI was 19.05%. Comparing our results to those of a retrospective survey of DI from 1873 to present, we found a higher rate of DI in the excavated teeth of Chinese individuals 2,000 years ago. The use of the micro‐CT technique and ethnic origin might have contributed to the higher incidence of DI. Anat Rec, 296:1628–1633, 2013. © 2013 Wiley Periodicals, Inc.
The Distribution of Muscles Fibers and Their Types in the Female Rat Urethra: Cytoarchitecture and Three‐Dimensional Reconstruction
Authors: Lim Seh Hong , Wang Tsyr‐Jiuan , Tseng Guo‐Fang , Lee Yee Fun , Huang Yong‐San , Chen Jeng‐Rung , Cheng Chen‐Li
Published: June 2014

An attempt to explore urethral cytoarchitecture including the distribution of smooth muscles and fast and slow striated muscles of adult female Sprague Dawley rat—a popular model in studying lower urinary tract function. Histological and immunohistochemical stainings were carried out to investigate the distribution of urethral muscle fibers and motor end plates. The urethral sphincter was furthermore three‐dimensionally reconstructed from serial histological sections. The mucosa at the distal urethra was significantly thicker than that of other segments. A prominent inner longitudinal and outer circular layer of smooth muscles covered the proximal end of urethra. Thick circular smooth muscles of the bladder neck region (urethral portion) decreased significantly distalward and longitudinal smooth muscles became 2‐ to 3‐fold thicker in the rest of the urethra. An additional layer of striated muscles appeared externally after neck region (urethra) and in association with motor end plates ran throughout the remaining urethra as the striated sphincter layer. Most striated muscles were fast fibers while relatively fewer slow fibers often concentrated at the periphery. A pair of extraneous striated muscles, resembling the human urethrovaginal sphincter muscles, connected both sides of mainly the distal vagina to the dorsal striated muscles in the wall of the middle urethra. The tension provided by this pair of muscles, and in conjunction with the striated sphincter of the urethral wall, was likely to function to suspend the middle urethra and facilitates its closure. Comprehensive morphological data of urethral sphincter offers solid basis for researchers conducting studies on dysfunction of bladder outlet. Anat Rec, 296:1640–1649, 2013. © 2013 Wiley Periodicals, Inc.
The Olfactory Amygdala in Amniotes: An Evo‐Devo Approach
Authors: Abellán Antonio , Desfilis Ester , Medina Loreta
Published: June 2014

In tetrapods, the medial amygdala is a forebrain center that integrates olfactory and/or vomeronasal signals with the endocrine and autonomic systems, playing a key role in different social behaviors. The vomeronasal system has undergone important changes during evolution, which may be behind some interspecies differences in chemosensory‐mediated social behavior. These evolutionary changes are associated with variations in vomeronasal‐recipient brain structures, including the medial amygdala. Herein, we employed an evolutionary developmental biology approach for trying to understand the function and evolution of the medial amygdala. For that purpose, we reviewed published data on fate mapping in mouse, and the expression of orthologous developmental regulatory genes (Nkx2.1, Lhx6, Shh, Tbr1, Lhx9, Lhx5, Otp, and Pax6) in embryos of mouse, chicken, emydid turtles, and a pipid frog. We also analyzed novel data on Lhx9 and Otp in a lacertid lizard. Based on distinct embryonic origin and genetic profile, at least five neuronal subpopulations exist in the medial amygdala of rodents, expressing either Nkx2.1/Lhx6, Shh, Lhx9, Otp/Lhx5, or Pax6. Each neuronal subpopulation appears involved in different functional pathways. For example, Lhx6 cells are specifically activated by sex pheromones and project to preoptic and hypothalamic centers involved in reproduction. Based on data in nonmammals, at least three of these neuronal subtypes might have been present in the medial amygdala of the amniote common ancestor. During mammalian evolution, the downregulation of Nkx2.1 in the alar hypothalamus may have been a driving force for an increment of the Otp/Lhx5 subpopulation. Anat Rec, 296:1317‐1332, 2013. © 2013 Wiley Periodicals, Inc.
Elements of Olfactory Reception in Adult Drosophila melanogaster
Authors: Martin Fernando , Boto Tamara , Gomez‐Diaz Carolina , Alcorta Esther
Published: June 2014

The olfactory system of Drosophila has become an attractive and simple model to investigate olfaction because it follows the same organizational principles of vertebrates, and the results can be directly applied to other insects with economic and sanitary relevance. Here, we review the structural elements of the Drosophila olfactory reception organs at the level of the cells and molecules involved. This article is intended to reflect the structural basis underlying the functional variability of the detection of an olfactory universe composed of thousands of odors. At the genetic level, we further detail the genes and transcription factors (TF) that determine the structural variability. The fly's olfactory receptor organs are the third antennal segments and the maxillary palps, which are covered with sensory hairs called sensilla. These sensilla house the odorant receptor neurons (ORNs) that express one or few odorant receptors in a stereotyped pattern regulated by combinations of TF. Also, perireceptor events, such as odor molecules transport to their receptors, are carried out by odorant binding proteins. In addition, the rapid odorant inactivation to preclude saturation of the system occurs by biotransformation and detoxification enzymes. These additional events take place in the lymph that surrounds the ORNs. We include some data on ionotropic and metabotropic olfactory transduction, although this issue is still under debate in Drosophila. Anat Rec, 296:1477‐1488, 2013. © 2013 Wiley Periodicals, Inc.
Interneurons and Beta‐Amyloid in the Olfactory Bulb, Anterior Olfactory Nucleus and Olfactory Tubercle in APPxPS1 Transgenic Mice Model of Alzheimer's Disease
Authors: Saiz‐Sanchez Daniel , De La Rosa‐Prieto Carlos , Ubeda‐Bañon Isabel , Martinez‐Marcos Alino
Published: June 2014

Impaired olfaction has been described as an early symptom in Alzheimer's disease (AD). Neuroanatomical changes underlying this deficit in the olfactory system are largely unknown. Given that interneuron populations are crucial in olfactory information processing, we have quantitatively analyzed somatostatin‐ (SOM), parvalbumin‐ (PV), and calretinin‐expressing (CR) cells in the olfactory bulb, anterior olfactory nucleus, and olfactory tubercle in PS1 x APP double transgenic mice model of AD. The experiments were performed in wild type and double transgenic homozygous animal groups of 2, 4, 6, and 8 months of age to analyze early stages of the pathology. In addition, beta‐amyloid (Aβ) expression and its correlation with SOM cells have been quantified under confocal microscopy. The results indicate increasing expressions of Aβ with aging as well as an early fall of SOM and CR expression, whereas PV was decreased later in the disease progression. These observations evidence an early, preferential vulnerability of SOM and CR cells in rostral olfactory structures during AD that may be useful to unravel neural basis of olfactory deficits associated to this neurodegenerative disorder. Anat Rec, 296:1413‐1423, 2013. © 2013 Wiley Periodicals, Inc.
P21‐Activated Kinase 4 Regulates the Cyclin‐Dependent Kinase Inhibitor P57Kip2 in Human Breast Cancer
Authors: Li Yanshu , Wang Di , Zhang Hongyan , Wang Chunyu , Dai Wei , Cheng Zhenguo , Wang Guanqiao , Li Feng
Published: June 2014

The p21‐activated kinases have been implicated in the control of cell cycle progression. However, the biological mechanism underlying the role of p21‐activated kinase 4 (PAK4) in cell cycle control remains unknown. Here, by using quantitative RT–PCR and immunoblot analyses, we discovered that over‐expression of PAK4 could suppress cyclin‐dependent kinase inhibitor 1C (p57Kip2) expression in the MCF‐7 human breast cancer cell line, whereas lentiviral vector‐mediated small interfering RNA (siRNA) knockdown of PAK4 markedly promoted p57Kip2 expression in MCF‐7 cells. Furthermore, PAK4‐mediated down‐regulation of p57Kip2 was reversed by MG132, a specific proteasome inhibitor. The ubiquitination assay confirmed that the activity of PAK4 attenuated p57Kip2 protein stability through the ubiquitin‐proteasome pathway in MCF‐7 cells. Moreover, a significant inverse correlation between PAK4 and p57Kip2 protein levels was observed in breast cancer tissues by immunohistochemical analysis. Taken together, our data demonstrate a novel function for PAK4 in regulating the stability of p57Kip2, possibly through the ubiquitin‐proteasome pathway, leading to increased proliferation of breast cancer cells. Thus, PAK4 may be used as a potential diagnostic and therapeutic target for human breast cancer. Anat Rec, 296:1561–1567, 2013. © 2013 Wiley Periodicals, Inc.
The Human Tongue Slows Down to Speak: Muscle Fibers of the Human Tongue
Authors: Sanders Ira , Mu Liancai , Amirali Asif , Su Hungxi , Sobotka Stanislaw
Published: June 2014

Little is known about the specializations of human tongue muscles. In this study, myofibrillar adenosine triphosphatase (mATPase) histochemical staining was used to study the percentage and distribution of slow twitch muscle fibers (slow MFs) within tongue muscles of four neurologically normal human adults and specimens from a 2‐year‐old human, a newborn human, an adult with idiopathic Parkinson's disease (IPD), and a macaque monkey. The average percentage of slow MFs in adult and the 2‐year‐old muscle specimens was 54%, the IPD was 45%, while the neonatal human (32%) and macaque monkey (28%) had markedly fewer slow MFs. In contrast, the tongue muscles of the rat and cat have been reported to have no slow MFs. There was a marked spatial gradient in the distribution of slow MFs with the highest percentages found medially and posteriorly. Normal adult tongue muscles were found to have a variety of uniquely specialized features including MF‐type grouping (usually found in neuromuscular disorders), large amounts of loose connective tissue, and short branching MFs. In summary, normal adult human tongue muscles have by far the highest proportion of slow MFs of any mammalian tongue studied to date. Moreover, adult human tongue muscles have multiple unique anatomic features. As the tongue shape changes that are seen during speech articulation are unique to humans, we hypothesize that the large proportion of slow MFs and the anatomical specializations observed in the adult human tongue have evolved to perform these movements. Anat Rec, 296:1615–1627, 2013. © 2013 Wiley Periodicals, Inc.
Mechanical and morphological aspects of the calcaneal tendon of mdx mice at 21 days of age
Authors: Nakagaki Wilson Romero , Tomiosso Tatiana Carla , Pimentel Edson Rosa , Camilli José Angelo
Published: June 2014

A relationship between compromised muscles and other tissues has been demonstrated in mdx mouse, an animal model studied for understanding of Duchenne muscular dystrophy. The hypothesis is that changes in the calcaneal tendon of mdx mice occur previous to the onset of rigorous and most marked episodes of muscle degeneration, which start suddenly after 21 days of life. Thus, this study aimed to identify possible alterations in the calcaneal tendon of mdx mouse at 21 days of age. Control and mdx tendons were submitted to mechanical tensile testing, quantification of hydroxyproline, and staining with toluidine blue and picrosirius red. Hydroxyproline content was similar between mdx and control groups. The control tendon presented higher mechanical strength (load, stress, and elastic modulus) and its morphological analysis showed a larger number of round fibroblasts, nuclei with well‐decondensed chromatin, and slightly metachromatic well‐stained cytoplasmic material, different from that observed in mdx tendons. The results suggest that the absence of dystrophin in mdx mouse can provoke directly or indirectly alterations in the mechanical properties and morphology of the calcaneal tendon. Anat Rec, 296:1546–1551, 2013. © 2013 Wiley Periodicals, Inc.
Linear and Angular Measurements of the Foot of Modern Humans: A Test of Morton'S Foot Types
Authors: Lautzenheiser Steven G. , Kramer Patricia Ann
Published: June 2014

In his classic research, Morton established two functionally different configurations of the bipedal and non‐bipedal primate foot: one optimized for stability, with a stiff longitudinal arch and adducted first metatarsal, and the other for compliance. Modern human feet were seen as conforming to the bipedal norm and variation from it as pathology, even though clinical evidence has been clear that variation from the norm of a stiff longitudinal arch or adducted first metatarsal exists. This study aims to document the variation in linear and angular measurements of the foot, using weight‐bearing radiographs of 50 randomly selected people (25 men) from an urban US Level 1 trauma center. The radiographs were obtained to “rule‐out” a foot fracture after trauma or as comparison films for a contralateral foot injury. Measurements were made using Osirix and correlations among the angular and length measurements were determined using Stata with P < 0.05 and Bonferroni correction for multiple comparisons. We found that foot length was not correlated with angular measurements, except for the angle between the first and fifth metatarsal. People with lower medial longitudinal arches also had more abducted first metatarsals and more vertical posterior facets, in accordance with Morton's foot types. Whether or not this variation in modern humans is linked to functionally important consequences remains to be determined in future research. With the new evidence of a more variable foot structure in fossil hominins, understanding the relationship between foot morphology and function becomes more urgent. Anat Rec, 296:1526–1533, 2013. © 2013 Wiley Periodicals, Inc.
Supplementation With Quercetin Attenuates 4‐Nitrophenol‐Induced Testicular Toxicity in Adult Male Mice
Authors: Mi Yuling , Tu Longlong , Wang Huimin , Zeng Weidong , Zhang Caiqiao
Published: June 2014

The beneficial effects of quercetin on reproductive damage elicited by 4‐nitrophenol (PNP) were studied in adult male mice. A six‐week treatment of weekly intraperitoneal injections of PNP (50 mg/kg) resulted in severe damage to the seminiferous tubules, a remarkable increase in both hydroxyl radical and malondiadehyde production, and notably decreased glutathione peroxidase and superoxide dismutase activities. Moreover, PNP treatment induced germ cell apoptosis, inhibited Bcl‐xl expression, and then activated Bax expression and the caspase‐3 enzyme. Exposure to PNP also increased XBP‐1 and HO‐1 mRNAs levels. However, simultaneous supplementation with quercetin (75 mg/kg) attenuated the toxicity induced by PNP through renewal of the antioxidant enzyme's status, alleviating apoptosis by regulating the expressions of Bax and Bcl‐xl, XBP‐1 and HO‐1mRNAs, and the regulation of caspase‐3 activity. Taken together, these findings indicated that the antioxidant quercetin displays a potential preventive effect on PNP‐induced oxidative damage in mouse testes and may represent an efficient supplement to attenuate reproductive toxicity from environmental toxicants in order to ensure reproductive health and sperm production. Anat Rec, 296:1650–1657, 2013. © 2013 Wiley Periodicals, Inc.
Integration of Autophagy and Anoikis Resistance in Solid Tumors
Authors: Yang Jie , Zheng Zhichao , Yan Xiaojie , Li Xia , Liu Zhe , Ma Zhenyi
Published: June 2014

Macroautophagy or autophagy is a lysosome‐dependent process in which enzymatic degradation and recycling of cytosolic components occurred due to stressful conditions. This cellular arrangement imparts anoikis resistance in solid tumors. Anoikis, a special form of apoptosis occurring when cells detach from the extracellular matrix, is a critical mechanism in maintaining tissue homeostasis and development. Anoikis resistance facilitates tumorigenesis and metastasis. However, the complexity of the role of autophagy in tumor is underscored by evidence that autophagy can function as both a pro‐survival or pro‐death depending on the context and the stimuli, which are likely exploitable for tumor therapy. This review focuses on recent progress in understanding anoikis resistance and autophagy signaling, paying particular attention to its relevance in solid tumor metastasis. Anat Rec, 296:1501–1508, 2013. © 2013 Wiley Periodicals, Inc.
Osteological Histology of the Pan‐Alcidae (Aves, Charadriiformes): Correlates of Wing‐Propelled Diving and Flightlessness
Authors: Smith N. Adam , Clarke Julia A.
Published: June 2014

Although studies of osteological morphology, gross myology, myological histology, neuroanatomy, and wing‐scaling have all documented anatomical modifications associated with wing‐propelled diving, the osteohistological study of this highly derived method of locomotion has been limited to penguins. Herein we present the first osteohistological study of the derived forelimbs and hind limbs of wing‐propelled diving Pan‐Alcidae (Aves, Charadriiformes). In addition to detailing differences between wing‐propelled diving charadriiforms and nondiving charadriiforms, microstructural modifications to the humeri, ulnae and femora of extinct flightless pan‐alcids are contrasted with those of volant alcids. Histological thin‐sections of four species of pan‐alcids (Alca torda, †Alca grandis, †Pinguinus impennis, †Mancalla cedrosensis) and one outgroup charadriiform (Stercorarius longicaudus) were compared. The forelimb bones of wing‐propelled diving charadriiforms were found to have significantly thicker (∼22%) cortical bone walls. Additionally, as in penguins, the forelimbs of flightless pan‐alcids are found to be osteosclerotic. However, unlike the pattern documented in penguins that display thickened cortices in both forelimbs and hind limbs, the forelimb and hind limb elements of pan‐alcids display contrasting microstructural morphologies with thickened forelimb cortices and relatively thinner femoral cortices. Additionally, the identification of medullary bone in the sampled †Pinguinus impennis specimen suggests that further osteohistological investigation could provide an answer to longstanding questions regarding sexual dimorphism of Great Auks. Finally, these results suggest that it is possible to discern volant from flightless wing‐propelled divers from fragmentary fossil remains. Anat Rec, 297:188–199, 2014. © 2013 Wiley Periodicals, Inc.
A re‐examination and re‐evaluation of salamander orbital glands
Authors: Rehorek Susan J. , Grand‐Pierre Alix E. , Cummings Joshua R. , Jewell Bridgette , Constantine Julieanne , Hillenius W. Jaap
Published: June 2014

The amphibian integument contains numerous multicellular glands. Although two of these, the nasolabial and orbital glands and the associated nasolacrimal duct (NLD), have historically received considerable attention, interpretation of the original observations can be problematic in the context of current literature. Salamanders, in particular, are frequently regarded as at least indicative of aspects of the morphology of the common ancestor to all extant tetrapods; hence, an understanding of these glands in salamanders might prove to be informative about their evolution. For this study, the orbitonasal region of salamanders from three families was histologically examined. Three themes emerged: (1) examination of the effect of phylogeny on the nasolabial gland and NLD revealed a combination of features that may be unique to plethodontid salamanders, and may be correlated to their nose‐tapping behavior by which substances are moved into the vomeronasal organ; (2) ecology appears to impact the relative development of the orbital glands, but not necessarily the nasolabial gland, with smaller glands being present in the aquatic species; (3) the nomenclature of the salamander orbital gland remains problematic, especially in light of comparative studies, as several alternate possibilities are viable. From this nomenclatural conundrum, however, it could be concluded that there may be a global pattern in the location of tetrapod orbital gland development. Molecular questions in terms of ontogeny and genetic homology affect the nature of the debate on orbital gland nomenclature. These observations suggest that rather than reflecting an ancestral condition, salamanders may instead represent a case of specialized, convergent evolution. Anat Rec, 296:1789–1796, 2013. © 2013 Wiley Periodicals, Inc.
Growth of the Human Ilium: The Anomalous Sacroiliac Junction
Authors: Yusof Nurul A. , Soames Roger W. , Cunningham Craig A. , Black Sue M.
Published: June 2014

Despite the major anatomical importance of the human ilium in medicine and forensic investigations, little is understood about its pattern of growth. This study was conducted to investigate the changes in the surface area of the human ilium from birth through to adolescence in 80 human ilia. A photographic image of the pelvic surface of each bone was taken and examined using an image quantification package. The surface areas of four regions of interest were quantified: the auricular, post‐auricular (PA), iliac fossa, and whole pelvic surface of the ilium. The results highlight a rapid increase in surface area for all regions in the first few years after birth which continues, albeit at a slower rate, until ∼4 years of age when the rate of growth is further reduced. Although the ilium and its various components continue to grow between 5 years and puberty, the rate of growth is markedly reduced until puberty when growth of the pelvis again increases. Interestingly, analysis of the differential growth of the auricular region compared with the PA region throughout development suggests that the PA region exhibits more advanced growth. This may indicate that its role in structural development for the purposes of preparation and maintenance of bipedal stance and locomotion may have been previously poorly understood. Anat Rec, 296:1688–1694, 2013. © 2013 Wiley Periodicals, Inc.
Tissue Factor Pathway Inhibitor‐2 Silencing Promotes Hepatocellular Carcinoma Cell Invasion In Vitro
Authors: Zhu Bin , Zhang Ping , Zeng Ping , Huang Zhen , Dong Ting‐Fang , Gui Yong‐Kun , Zhang Guang‐Wen
Published: June 2014

Hepatocellular carcinoma (HCC) is a leading cause of cancer‐related death in the world and metastasis is an essential aspect of HCC progression. Tissue factor pathway inhibitor‐2 (TFPI‐2) has been implicated as a potential suppressor gene to regulate tumor invasion and metastasis. In this study, we silenced TFPI‐2 in the HCC cell line MHCC97‐L and evaluated the role of TFPI‐2 in cell invasion and its impact on gene expression. We showed in this study that stable TFPI‐2 downregulation in MHCC97‐L cells resulted in increased cell adhesion and invasion. We also showed that mRNA and protein expression levels of MMP‐1/3, CD44, and ICAM‐1 were increased, while those of MMP‐2/9 were not changed by TFPI‐2 silencing. Furthermore, silencing of TFPI‐2 caused increased Akt phosphorylation level and NF‐κB transcription in MHCC97‐L cells. In conclusion, this study confirms that TFPI‐2 downregulation can contribute to tumor invasion of HCC cells through alteration in the expression of metastasis‐related genes. Anat Rec, 296:1708–1716, 2013. © 2013 Wiley Periodicals, Inc.
The Sensory Innervation of the Human Pharynx: Searching for Mechanoreceptors
Authors: de Carlos F. , Cobo J. , Macías E. , Feito J. , Cobo T. , Calavia M.G. , García‐Suárez O. , Vega J.A.
Published: June 2014

The coordinate neural regulation of the upper airways muscles is basic to control airway size and resistance. The superior constrictor pharyngeal muscle (SCPM) forms the main part of the lateral and posterior walls of the pharynx and typically is devoid of muscle spindles, the main type of proprioceptor. Because proprioception arising from SCPM is potentially important in the physiology of the upper airways, we have investigated if there are mechanical sensory nerve endings substitute for the muscle spindles. Samples of human pharynx were analyzed using immunohistochemistry associated to general axonic and Schwann cells markers (NSE, PGP 9.5, RT‐97, and S100P), intrafusal muscle fiber markers, and putative mechanical sense proteins (TRPV4 and ASIC2). Different kinds of sensory corpuscles were observed in the pharynx walls (Pacini‐like corpuscles, Ruffini‐like corpuscles, spiral‐wharves nerve structures, and others) which are supplied by sensory nerves and express putative mechanoproteins. No evidence of muscle spindles was observed. The present results demonstrate the occurrence of numerous and different morphotypes of sensory corpuscles/mechanoreceptors in human pharynx that presumably detect mechanical changes in the upper airways and replace muscle spindles for proprioception. Present findings are of potential interest for the knowledge of pathologies of the upper airways with supposed sensory pathogenesis. Anat Rec, 296:1735–1746, 2013. © 2013 Wiley Periodicals, Inc.
Manipulation of Hematopoietic Stem Cells for Regenerative Medicine
Authors: Nakajima‐Takagi Yaeko , Osawa Mitsujiro , Iwama Atsushi
Published: June 2014

Hematopoietic stem cells (HSCs) are defined by their capacity to self‐renew and to differentiate into all blood cell lineages while retaining robust capacity to regenerate hematopoiesis. Based on these characteristics, they are widely used for transplantation and gene therapy. However, the dose of HSCs available for use in treatments is limited. Therefore, extensive work has been undertaken to expand HSCs in culture and to produce HSCs from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in order to improve the efficiency and outcome of HSC‐based therapies. Various surface markers have been characterized to improve the purification of HSCs and a huge number of cytokines and small‐molecule compounds have been screened for use in the expansion of HSCs. In addition, attempts to generate not only HSCs but also mature blood cells from ESCs and iPSCs are currently ongoing. This review covers recent approaches for the purification, expansion or production of human HSCs and provides insight into problems that need to be resolved. Anat Rec, 297:111–120. 2013. © 2013 Wiley Periodicals, Inc.
PrPc is temporospatially expressed in molar development of rats
Authors: Yoo H.I. , Jang S.M. , Kang J.H. , Kim M.S. , Koh J.T. , Jung J.Y. , Kim W.J. , OH W.M. , Kim S.H.
Published: June 2014

Odontogenesis, tooth development, is derived from two tissue components: ectoderm and neural crest‐derived mesenchyme. Cyto‐differentiation of odontogenic cells during development involves time‐dependent and sequential regulation of genetic programs. This study was conducted to detect molecules implicated in cyto‐differentiation of developing molar germs of rats. Differential display‐PCR revealed that PrPc was differentially expressed between cap/early bell‐staged germs (maxillary 3rd molar germs) and root formation‐staged germs (maxillary 2nd molar germs) at postnatal day 9. Both levels of PrPc mRNA and protein expression were higher in the root formation stage than the cap/early bell stage and increased in a time‐dependent manner. Immunofluorescence revealed for the first time that PrPc was not localized in the enamel organ, but localized in dental follicular cells for the development of the periodontal ligament and cementum as well as odontoblasts, both of which are of neural crest origin. These results suggest that the physiological functions of the PrPc in tooth development may be implicated in the differentiation of neural crest‐derived mesenchyme including the periodontal tissues for root formation rather than epithelial tissue. Anat Rec, 296:1929–1935, 2013. © 2013 Wiley Periodicals, Inc.
Main Effect and Interactions of Brain Regions and Gender in the Calculation of Volumetric Asymmetry Indices in Healthy Human Brains: Ancova Analyses of In Vivo 3T MRI Data
Authors: Roldan‐Valadez Ernesto , Rios Camilo , Suarez‐May Marcela A. , Favila Rafel , Aguilar‐Castañeda Erika
Published: June 2014

Introduction: Macroanatomical right‐left hemispheric differences in the brain are termed asymmetries, although there is no clear information on the global influence of gender and brain‐regions. The aim of this study was to evaluate the main effects and interactions of these variables on the measurement of volumetric asymmetry indices (VAIs). Materials and methods: Forty‐seven healthy young‐adult volunteers (23 males, 24 females) agreed to undergo brain magnetic resonance imaging in a 3T scanner. Image post processing using voxel‐based volumetry allowed the calculation of 54 VAIs from the frontal, temporal, parietal and occipital lobes, limbic system, basal ganglia, and cerebellum for each cerebral hemisphere. Multivariate ANCOVA analysis calculated the main effects and interactions on VAIs of gender and brain regions controlling the effect of age. Results: The only significant finding was the main effect of brain regions (F (6, 9373.605) 44.369, P < .001; partial η2 = .101, and power of 1.0), with no significant interaction between gender and brain regions (F (6, 50.517) .239, P = .964). Conclusion: Volumetric asymmetries are present across all brain regions, with larger values found in the limbic system and parietal lobe. The absence of a significant influence of gender and age in the evaluation of the numerous measurements generated by multivariate analyses in this study should not discourage researchers to report and interpret similar results, as this topic still deserves further assessment. Anat Rec, 296:1913–1922, 2013. © 2013 Wiley Periodicals, Inc.
Mediation of Muscular Control of Rhinarial Motility in Rats by the Nasal Cartilaginous Skeleton
Authors: Haidarliu Sebastian , Kleinfeld David , Ahissar Ehud
Published: June 2014

The rhinarium is the rostral‐most area of the snout that surrounds the nostrils, and is hairless in most mammals. In rodents, it participates in coordinated behaviors, active tactile sensing, and active olfactory sensing. In rats, the rhinarium is firmly connected to the nasal cartilages, and its motility is determined by movements of the rostral end of the nasal cartilaginous skeleton (NCS). Here, we demonstrate the nature of different cartilaginous regions that form the rhinarium and the nasofacial muscles that deform these regions during movements of the NCS. These muscles, together with the dorsal nasal cartilage that is described here, function as a rhinarial motor plant. Anat Rec, 296:1821–1832, 2013. © 2013 Wiley Periodicals, Inc.
MicroRNA‐127 is Downregulated by Tudor‐SN Protein and Contributes to Metastasis and Proliferation in Breast Cancer Cell Line MDA‐MB‐231
Authors: Zhao Xiujuan , Duan Zhongchao , Liu Xin , Wang Baoya , Wang Xinting , He Jinyan , Yao Zhi , Yang Jie
Published: June 2014

Tudor‐SN is a multifunctional protein that is highly expressed in multiple cancers including breast cancer. Tudor‐SN, as a component in RNA‐induced splicing complex, was recently reported to regulate gene expression in a microRNA (miRNA)‐dependent manner, such as let‐7, miR‐34a and miR‐221. However, how Tudor‐SN is associated with cancer development still remains largely elusive. In the present study, we explored the role of Tudor‐SN in breast cancer. Stable knockdown of endogenous Tudor‐SN, performed on the breast cancer cell line MDA‐MB‐231 by small hairpin RNA expression vectors, suppressed the in vitro migration and invasion ability of the metastatic breast cancer cell line. Interestingly, we found Tudor‐SN as a miRNA regulator according to microarray analysis, and further identified that Tudor‐SN negatively regulated the expression of miR‐127, and consequently increased the expression of the proto‐oncogene BCL6 which was a convincing target of miR‐127. Moreover, overexpression of miR‐127 reduced the in vitro migration and proliferation ability of breast cancer cell MDA‐MB‐231. Collectively, our results suggested a novel mechanism that Tudor‐SN promoted metastasis and proliferation of breast cancer cells via downregulating the miR‐127 expression. Anat Rec, 296:1842–1849, 2013. © 2013 Wiley Periodicals, Inc.
The Effect and Mechanism of CXCR4 Silencing on Metastasis Suppression of Human Glioma U87 Cell Line
Authors: Zhu Yu , Yang Ping , Zhang Xuebin , Zhang Ling , Cui Guiping , Wang Qin , Lv Lixia , Zhang Yi , Xin Xin , Yan Tao , Zhao Meng , Zhang Nan
Published: June 2014

Tumor metastasis is the major cause of treatment failure and poor prognosis of glioma. Inhibiting metastasis has become an important therapeutic strategy for glioma treatment. CXCR4 has been proved to play an important role in the occurrence and development of tumors. In order to illustrate the effect of CXCR4 on glioma metastasis, we investigated the role of CXCR4 in U87 cells metastasis based on the CXCR4 silencing tumor cells. In this study, we found that CXCR4 silencing could suppress U87 cells invasion and adhesion potential, production of TGF‐β1, IL‐6, and IL‐8, and blocked the G0/G1 phase of the cell cycle. We also found that CXCR4 silencing could up‐regulate the mRNA and protein expression of p53, p21, and E‐cadherin, and down‐regulate the mRNA and protein expression of CD44 and MMP‐2/‐9. Meanwhile, CXCR4 silencing could decrease the phosphorylation of p‐AKT and transcription activity of NF‐κB promoter, and increased the phosphorylation of PTEN. The results provided a new research basis for the further study of CXCR4 gene, the screening of human glioma, as well as the target treatment for glioma and its prognosis. Anat Rec, 296:1857–1864, 2013. © 2013 Wiley Periodicals, Inc.
Heart Fields: Spatial Polarity and Temporal Dynamics
Authors: Abu‐Issa Radwan
Published: June 2014

In chick and mouse, heart fields undergo dynamic morphological spatiotemporal changes during heart tube formation. Here, the dynamic change in spatial polarity of such fields is discussed and a new perspective on the heart fields is proposed. The heart progenitor cells delaminate through the primitive streak and migrate in a semicircular trajectory craniolaterally forming the bilateral heart fields as part of the splanchnic mesoderm. They switch their polarity from anteroposterior to mediolateral. The anterior intestinal portal posterior descent inverts the newly formed heart field mediolateral polarity into lateromedial by 125° bending. The heart fields revert back to their original anteroposterior polarity and fuse at the midline forming a semi heart tube by completing their half circle movement. Several names and roles were assigned to different portions of the heart fields: posterior versus anterior, first versus second, and primary versus secondary heart field. The posterior and anterior heart fields define basically physical fields that form the inflow–outflow axis of the heart tube. The first and second heart fields are, in contrast, temporal fields of differentiating cardiomyocytes expressing myosin light chain 2a and undifferentiated and proliferating precardiac mesoderm expressing Isl1 gene, respectively. The two markers present a complementary pattern and are expressed transiently in all myocardial lineages. Thus, Isl1 is not restricted to a portion of the heart field or one of the two heart lineages as has been often assumed. Anat Rec, 297:175–182, 2014. © 2013 Wiley Periodicals, Inc.
Reversing Effect of Sorcin in the Drug Resistance of Human Nasopharyngeal Carcinoma
Authors: Liu Xuebing , Chen Lei , Feng Bin , Liu Gang
Published: June 2014

Nasopharyngeal carcinoma (NPC) is one of the most common cancers originating in the nasopharynx, and chemoresistance is an essential aspect of NPC chemotherapy failure. Sorcin has been implicated in multidrug resistance (MDR) of many types of human tumor. However, the effect and mechanism of Sorcin in MDR of human NPC is not fully clear. In this report, we silenced Sorcin in human NPC CNE2/DDP cells, and explored the role of Sorcin in MDR reversal. The results showed an increased cytotoxicity of cisplatin and intracellular accumulation of Rhodamine‐123 and glutathione depletion in Sorcin silencing CNE2/DDP cells. We also found a decreased messenger RNA and protein expression of multidrug resistance gene (MDR1), multidrug resistance‐associated protein (MRP1), excision repair cross‐complementing gene 1 (ERCC1), glutathione S‐transferase‐π (GST‐n), RhoE, Bcl‐2, and Survivin in Sorcin silencing CNE2/DDP cells. The increased expression of PTEN and decreased expression of p‐Akt and NF‐κB suggested that the key cellular signaling pathways were triggered by Sorcin silencing. We concluded that Sorcin silencing would contribute to establish a potent target point for MDR reversal. Anat Rec, 297:215–221, 2014. © 2013 Wiley Periodicals, Inc.
The Linea Aspera: A Virtual Case Study Testing Emergence of Form and Function
Authors: Moore Shannon R. , Milz Stefan , Knothe Tate Melissa L.
Published: June 2014

The linea aspera (LA) forms a characteristic ridge along the posterior aspect of the human femur. Absent in youth, the LA emerges during early puberty and becomes more prominent with advancing age. Pauwels, a pioneer of mechanobiology, hypothesized that the LA forms in the precise location where axial intracortical stresses are greatest, effectively “stiffening” the femur in bending. This study reassesses the mechanical role of the LA in virtual models of human femora, accounting for increasing prominence of the LA at juvenile, young adult and aged stages. Using finite element analysis, peak stresses and the relationship between the LA, neutral axis and centroidal axes (CAs) are evaluated for cross‐sections along the mid‐diaphysis of the virtual femora. Additionally, the relationship between LA and CAs is studied in anatomical cross‐sections from Pauwels' manuscript as well as aged cadaveric donors, indicating that his conclusion may have been stymied by lack of modern computational methods. The results of the current study do not support a mechanical role of the LA as its emergence results in less than a 3% decrease in peak stress, while increasing prominence of the LA also serves to rotate CAs away from calculated stress field, implicating a less “bone centric” view of form and function. Anat Rec, 297:273–280, 2014. © 2013 Wiley Periodicals, Inc.
Anatomy and Adaptations of the Chewing Muscles in Daubentonia (Lemuriformes)
Authors: Perry Jonathan M. G. , Macneill Kristen E. , Heckler Amanda L. , Rakotoarisoa Gilbert , Hartstone‐Rose Adam
Published: June 2014

The extractive foraging behavior in aye‐ayes (Daubentonia madagascariensis) is unique among primates and likely has led to selection for a specialized jaw adductor musculature. Although this musculature has previously been examined in a subadult, until now, no one has reported the fascicle length, weight, and physiological cross‐sectional area (PCSA) for these muscles in an adult aye‐aye specimen. For the present study, we dissected an adult wild‐born aye‐aye from the Tsimbazaza Botanical and Zoological Park, Antananarivo, Madagascar. The aye‐aye follows the general strepsirrhine pattern in its overall jaw adductor muscle anatomy, but has very large muscles and PCSA relative to body size. Fascicle length is also relatively great, but not nearly as much as in the juvenile aye‐aye previously dissected. Perhaps chewing muscle fascicles begin relatively long, but shorten through use and growth as connective tissue sheets expand and allow for pinnation and increased PCSA. Alternately, it may be that aye‐ayes develop fascicular adaptation to wide gapes early in ontogeny, only to increase PCSA through later development into adulthood. The functional demands related to their distinctive manner of extractive foraging are likely responsible for the great PCSA in the jaw adductor muscles of the adult aye‐aye. It may be that great jaw adductor PCSA in the adult, as compared to the juvenile, is a means of increasing foraging efficiency in the absence of parental assistance. Anat Rec, 297:308–316, 2014. © 2013 Wiley Periodicals, Inc.
Maternal Deprivation Decelerates Postnatal Morphological Lung Development of F344 Rats
Authors: Hupa Katharina Luise , Schmiedl Andreas , Pabst Reinhard , Von Hörsten Stephan , Stephan Michael
Published: June 2014

Intensive medical care at premature born infants is often associated with separation of neonates from their mothers. Here, early artificial prolonged separation of rat pups from their dams (Maternal Deprivation, MD) was used to study potential impact on morphological lung maturation. Furthermore, we investigated the influence of an endogenous deficiency of the neuropeptide‐cleaving dipeptidyl peptidase IV (DPP4), since the effects of MD are known to be partly mediated via neuropeptidergic effects, hypothesizing that MD will lead to a retardation of postnatal lung development, DPP4‐dependendly. We used wild type and CD26/DPP4 deficient rats. For MD, the dam was placed each day into a separate cage for 2 h, while the pups remained in the nest on their own. Morphological lung maturation and cell proliferation at the postnatal days 7, 10, 14, and 21 were determined morphometrically. Maternally deprived wild types showed a retarded postnatal lung development compared with untreated controls in both substrains. During alveolarization, an increased thickness of alveolar septa and a decreased surface of septa about 50% were found. At the end of the morphological lung maturation, the surface of the alveolar septa was decreased at about 25% and the septal thickness remained increased about 20%. The proliferation rate was also decreased about 50% on day 14. However, the MD induced effects were less pronounced in DPP4‐deficient rats, due to a significant deceleration already induced by DPP4‐deficiency. Thus, MD as a model for postnatal stress experience influences remarkably postnatal development of rats, which is significantly modulated by the DPP4‐system. Anat Rec, 297:317–326, 2014. © 2013 Wiley Periodicals, Inc.