The Cytoskeletal Regulator Zyxin is Required for Viability in Drosophila melanogasterRenfranz, Patricia J.; Blankman, Elizabeth; Beckerle, Mary C.
doi: 10.1002/ar.21193pmid: 20648572
The zyxin family of proteins function as cytoskeletal regulators in adhesion, actin assembly, and cell motility. Though fibroblasts derived from zyxin‐null mice show striking defects in motility and response to mechanical stimuli, the mice are viable and fertile. In Drosophila melanogaster, the family is represented by a single homologue, Zyx102. To study the role of zyxin during development, we generated a zyx102 RNA‐interference transgenic line that allows for the conditional knockdown of Zyx102. When UAST‐zyx102‐dsRNAi expression is driven broadly by Actin5C‐GAL4, loss of Zyx102 results in lethality during the pharate adult stage, a narrow developmental window during which the fly must molt, resorb molting fluid, fill adult trachea with air, and execute a behavioral program to eclose. Zyx102 knockdown animals attempt to emerge, but their adult trachea do not fill with air. If dissected from the pupal case, knockdown individuals appear morphologically normal, but remain inviable. Anat Rec 293:1455–1469, 2010. © 2010 Wiley‐Liss, Inc.
IL‐13 upregulates GPIIb expression in megakaryocytic cell lines via STAT6Shi, Xiaoyu; Cai, Wei; Zhou, Ying; Zhang, Xuejun; Xiong, Lixia; Li, Rong; Yu, Xuemei; Li, Wenlin
doi: 10.1002/ar.21144pmid: 20652946
Interleukin 13 (IL‐13) is a key cytokine involved in the regulation of inflammatory, immune responses, and cell differentiation. The present study was to investigate the effect of IL‐13 on the expression of glycoprotein IIb (GPIIb), a megakaryocytic gene, in Dami cells (human megakaryoblastic leukemia cell line) and HEL cells (human erythroleukemic cell line, which has both erythroid and megakaryocytic markers). Furthermore, it addresses the mechanisms governing the regulation of GPIIb expression by IL‐13. The molecular responses of Dami cells and HEL cells to IL‐13 treatment were analyzed by RT‐PCR, Western blot, chromatin immunoprecipitation (ChIP) and flow cytometry analysis. We show that IL‐13Rα1 and IL‐4Rα are expressed in Dami cells and HEL cells. The expression of GPIIb was significantly upregulated at the mRNA and protein levels by treatment with IL‐13. Moreover, IL‐13 induced phosphorylation of signal transducer and activator of transcription 6(STAT6). By using a STAT6‐specific antibody and PCR primers designed to yield a product, which encompasses the STAT6 binding site of the GPIIb promoter, we have shown the binding of the IL‐13‐mediated activation of STAT6 to the promoter of GPIIb gene. These results broaden the involvement of IL‐13 into megakaryocyte differentiation by STAT6 pathway. Anat Rec 293:1470–1476, 2010. © 2010 Wiley‐Liss, Inc.
The Global Impact of Sutures Assessed in a Finite Element Model of a Macaque CraniumWang, Qian; Smith, Amanda L.; Strait, David S.; Wright, Barth W.; Richmond, Brian G.; Grosse, Ian R.; Byron, Craig D.; Zapata, Uriel
doi: 10.1002/ar.21203pmid: 20652940
The biomechanical significance of cranial sutures in primates is an open question because their global impact is unclear, and their material properties are difficult to measure. In this study, eight suture‐bone functional units representing eight facial sutures were created in a finite element model of a monkey cranium. All the sutures were assumed to have identical isotropic linear elastic material behavior that varied in different modeling experiments, representing either fused or unfused sutures. The values of elastic moduli employed in these trials ranged over several orders of magnitude. Each model was evaluated under incisor, premolar, and molar biting conditions. Results demonstrate that skulls with unfused sutures permitted more deformations and experienced higher total strain energy. However, strain patterns remained relatively unaffected away from the suture sites, and bite reaction force was likewise barely affected. These findings suggest that suture elasticity does not substantially alter load paths through the macaque skull or its underlying rigid body kinematics. An implication is that, for the purposes of finite element analysis, omitting or fusing sutures is a reasonable modeling approximation for skulls with small suture volume fraction if the research objective is to observe general patterns of craniofacial biomechanics under static loading conditions. The manner in which suture morphology and ossification affect the mechanical integrity of skulls and their ontogeny and evolution awaits further investigation, and their viscoelastic properties call for dynamic simulations. Anat Rec 293:1477–1491, 2010. © 2010 Wiley‐Liss, Inc.
Hepatic Stellate Cells in Inflammation‐Fibrosis‐Carcinoma AxisWang, Bin‐Bin; Cheng, Jun‐Yao; Gao, Hong‐Hao; Zhang, Yang; Chen, Zhi‐Nan; Bian, Huijie
doi: 10.1002/ar.21173pmid: 20652939
Almost 80% of hepatocellular carcinoma (HCC) cases are associated with chronic hepatitis and cirrhosis resulting from inflammation and fibrosis. A three‐step process of “inflammation‐fibrosis‐carcinoma” is believed to be involved in hepatocarcinogenesis. The activation of hepatic stellate cells (HSCs) may serve as an important mediator in the process of inflammation‐fibrosis‐carcinoma axis, even in tumor metastasis. A remarkable knowledge of activated HSCs in the pathology of HCC development is mostly focused on the liver fibrosis. The molecular links that connects inflammation and cancer in the activation of HSC are not completely known. This highlights urgent need to increase our understanding of the cellular and molecular mechanisms, by which activation of HSCs is involved in the hepatic inflammation, carcinogenesis, and metastasis. Anat Rec 293:1492–1496, 2010. © 2010 Wiley‐Liss, Inc.
Lymphangiogenesis Is Upregulated in Kidneys of Patients With Multiple MyelomaZimmer, Julia K.; Dahdal, Suzan; Mühlfeld, Christian; Bergmann, Ivo P.; Gugger, Mathias; Huynh‐Do, Uyen
doi: 10.1002/ar.21189pmid: 20648479
Neolymphangiogenesis has recently been demonstrated in transplanted kidneys as well as in chronic interstitial nephritis and IgA nephropathy. However, its significance in kidney disease remains to be defined and a systematic study of renal lymphangiogenesis is warranted. We investigated patients with multiple myeloma (MM) presenting in the great majority with acute renal insufficiency. Controls were allograft kidney donors and patients with renal insufficiency due to acute renal failure (ARF). Lymph vessel length density (LVD) was quantified immunohistochemically by means of antipodoplanin staining followed by computer‐assisted stereology. The mean LVD in kidneys of patients with MM (23.19 mm−2) was higher when compared with allograft donors (7.42 mm−2, P = 0.0003) and patients with ARF (6.78 mm−2, P = 0.0002). The higher LVD was significantly associated with interstitial inflammation, and the newly formed lymph vessels were accompanied by diffuse and nodular interstitial infiltrates composed mainly of CD20+ B cells and CD27+ plasma cells. The infiltrates in patients with MM also displayed a higher expression of the B‐cell chemoattractant CXCL13. These results demonstrate for the first time that lymphangiogenesis is a prominent feature in MM kidneys and that it is associated with a significant accumulation of macrophages, CD20+ and CD27+ B lymphocytes. Further studies should clarify whether these changes represent a beneficial or detrimental factor in the progression of the myeloma‐related kidney damage. Anat Rec 293:1497–1505, 2010. © 2010 Wiley‐Liss, Inc.
Gene Mutations in Epidermal Growth Factor Receptor Signaling Network and Their Association With Survival in Chinese Patients With Metastatic Colorectal CancersLiao, Wangjun; Liao, Yulin; Zhou, Jeff X.; Xie, Jianming; Chen, Jinzhang; Huang, Weizhen; Luo, Rongcheng
doi: 10.1002/ar.21202pmid: 20652941
Mutations of the KRAS, BRAF, and PIK3CA genes have been reported in colorectal cancer (CRC), associated with resistance to epidermal growth factor receptor (EGFR)‐targeted monoclonal antibody therapy. These reports have mainly emanated from Western countries, however, and little is known about the mutation frequencies of these genes and their prognostic value in Asian patients with CRC. In this study, we analyzed the mutation frequencies of these three genes together with EGFR, and their association with overall survival in 61 Chinese patients with metastatic CRC (mCRC). Gene mutations were examined using pyrosequencing. Kaplan‐Meier survival analysis and multivariate Cox proportional hazard analysis were used to assess the prognostic significance of mutations of these four genes for patients' survival. We found that the mutations of KRAS, BRAF, PIK3CA, and EGFR were present in 12 (19.7%), 3 (4.9%), 3 (4.9%), and 0 patients, respectively. Kaplan‐Meier survival analysis showed that none of these gene mutations correlated significantly with patients' overall survival. Multivariate Cox proportional hazard analysis showed only treatment regimens and age to be independent prognostic factors. Our findings indicate that EGFR signaling network genes are frequently mutated in Chinese mCRC patients, and these gene mutations do not seem to be associated with patients' overall survival. Anat Rec 293:1506–1511, 2010. © 2010 Wiley‐Liss, Inc.
Morphological Study on Microvasculature of Left Ventricular Wall in Infant and Adult YaksHe, Y.Y.; Yu, S.J.; Cui, Y.; Du, P.
doi: 10.1002/ar.21201pmid: 20652942
Observations on the microvasculature in the left ventricular wall of infant and adult yaks under light and scanning electron microscope (SEM) were presented. Moreover, the diameter of different microvasculature and the density of the capillaries in three layers of the ventricular myocardium were measured using Image Pro‐Plus 5.0. The results showed that the average luminal diameter of arterioles and precapillary arterioles in adult yak's hearts were, in most cases, larger than those in infant yaks. On the contrary, the diameters of the capillary in infant yak's hearts were larger than those in adult yaks. The density of capillary in the myocardium of adult yak's heart had significantly higher values (P<0.01) than those in infant yaks. Arterioles of yak's hearts were characterized by the bark‐like structure and the impressions of endothelial cell nuclei, and it always gave rise to capillary after three to four grades of embranchment. The outer surface of capillaries cast in infant yak's hearts was smooth, and no constrictions were found. This was different from adult yak that always had some constrictions. The capillary anastomosis of “H” and “Y” usually existed in the myocardium of both adult and infant yaks; however, those in infant yaks were not typical as in adult yaks in their shape. The peculiar arrangement of the venules in infant yak was a “baggy” or “bulgy” arrangement, while in the adult yak, they had a root‐like pattern. Our findings suggest that the patterns of microvasculature in yak's heart could be propitious to adapt better in their environment following their increase of age. Anat Rec 293:1519–1526, 2010. © 2010 Wiley‐Liss, Inc.
Development of the Tarsometatarsal Skeleton by the Lateral Fusion of Three Cylindrical Periosteal Bones in the Chick Embryo (Gallus gallus)Namba, Yuichi; Yamazaki, Yosuke; Yuguchi, Maki; Kameoka, Shigeo; Usami, Shinji; Honda, Kazuya; Isokawa, Keitaro
doi: 10.1002/ar.21179pmid: 20648480
An avian tarsometatarsal (TMT) skeleton spanning from the base of toes to the intertarsal joint is a compound bone developed by elongation and lateral fusion of three cylindrical periosteal bones. Ontogenetic development of the TMT skeleton is likely to recapitulate the changes occurred during evolution but so far has received less attention. In this study, its development has been examined morphologically and histologically in the chick, Gallus gallus. Three metatarsal cartilage rods radiating distally earlier in development became aligned parallel to each other by embryonic day 8 (ED8). Calcification initiated at ED8 in the midshaft of cartilage propagated cylindrically along its surface. Coordinated radial growth by fabricating bony struts and trabeculae resulted in the formation of three independent bone cylinders, which further became closely apposed with each other by ED13 when the periosteum began to fuse in a back‐to‐back orientation. Bone microstructure, especially orientation of intertrabecular channels in which blood vasculature resides, appeared related to the observed rapid longitudinal growth. Differential radial growth was considered to delineate eventual surface configurations of a compound TMT bone, but its morphogenesis preceded the fusion of bone cylinders. Bony trabeculae connecting adjacent cylinders emerged first at ED17 in the dorsal and ventral quarters of intervening tissue at the mid‐diaphyseal level. Posthatch TMT skeleton had a seemingly uniform mid‐diaphysis, although the septa persisted between original marrow cavities. These findings provide morphological and histological bases for further cellular and molecular studies on this developmental process. Anat Rec 293:1527–1535, 2010. © 2010 Wiley‐Liss, Inc.