Nidogen 1 regulates proliferation and migration/invasion in murine claudin-low mammary tumor cells

Nidogen 1 (NID1) is a glycoprotein found in basement membranes involved in cross-linking collagen IV and laminin. The role of NID in breast cancer has only been evaluated in a small number of studies and the findings of these studies have been inconsistent. Our previous work revealed that highly tumorigenic murine mammary tumor cells express high levels of Nid1 while weakly tumorigenic mammary tumor cells express low levels of Nid1. To investigate Nid1, two stable knockdown lines were created, and Nid1 knockdown was confirmed at both the mRNA and protein level. Nid1 knockdown significantly reduced cell proliferation and migration/invasion and these reductions in proliferation and migration/invasion could be rescued by conditioned media containing NID1 protein. The reduced migration/invasion observed in the Nid1 knockdown cells was not associated with significant alterations in the epithelial gene Cdh1 or the mesenchymal genes Snai1, Snai2, Twist1, Twist2, Zeb1 and Zeb2. Therefore, suppression of Nid1 expression reduces proliferation and migration/invasion in claudin-low murine mammary tumor cells.     

A Stable Q Compensated Reverse Time Migration Method Based on Excitation Amplitude Imaging Condition

The stability and efficiency, especially the stability, are generally concerned issues in Q compensated reverse time migration (Q-RTM). The instability occurs because of the exponentially boosted high frequency ambient noise during the forward or backward seismic wavefield propagation. The regularization and low-pass filtering methods are two effective strategies to control the instability of the wave propagation in Q-RTM. However, the regularization parameters are determined experimentally, and the wavefield cannot be recovered accurately. The low-pass filtering method cannot balance the selection of cutoff frequency for varying Q values, and may damage the effective signals, especially when the signal-to-noise ratio (SNR) of the seismic data is low, the Q-RTM will be a highly unstable process. In order to achieve the purpose of stability, the selection of cutoff frequency will be small enough, which can cause great damage to the effective high frequency signals. In this paper, we present a stable Q-RTM algorithm based on the excitation amplitude imaging condition, which can compensate both the amplitude attenuation and phase dispersion. Unlike the existing Q-RTM algorithms enlarging the amplitude, the exponentially attenuated seismic wavefield will be used during both the forward and backward wavefield propagation of Q-RTM. Therefore, the new Q-RTM algorithm is relative stable, even for the low SNR seismic data. In order to show the accuracy and stability of our stable Q-RTM algorithm clearly, an example based on Graben model will be illustrated. Then, a realistic BP gas chimney model further demonstrates that the proposed method enjoys good stability and anti-noise performance compared with the traditional Q-RTM with amplitude amplification. Compare the Q-RTM images of these two models to the reference images obtained by the acoustic RTM with acoustic seismic data, the new Q-RTM results match the reference images quite well. The proposed method is also tested using a field seismic data, the result shows the effectiveness of our proposed method.     

Regeneration of kidney tubular epithelial cells

Conclusion The mechanisms that regulate regeneration of kidney epithelial cells after acute tubular necrosis are poorly understood. Repair of the nephron can take place in the adverse systemic metabolic setting caused by failure of renal function. This clinical observation suggests that factors released at the site of the tubular insult can mediate repair. Studies carried out in this and other laboratories show that kidney epithelial cells can release and respond to polypeptide growth factors which may thereby contribute to renal regeneration by autocrine and paracrine mechanisms. Specific growth factors secreted by cells and deposited in the tubular basement membrane prior to injury may subsequently participate in nephron repair. In addition, adenine nucleotides released from injured or dying cells at the injury site or provided exogenously could stimulate surviving renal epithelial cells at the edges of the wound to migrate along the basement membrane to rapidly reepithelialize the nephron and subsequently initiate mitogenesis to replace cells lost by necrosis.The nephrotoxic effect of many agents used in cancer chemotherapy and the older age of patients undergoing complicated surgical procedures has increased the incidence of ARF, whereas the mortality rate has not changed since the early 1950s [22]. Thus there is considerable need for innovative therapeutic strategies. An important goal of future research efforts is to identify new growth factors that facilitate migration, differentiation, and proliferation of renal epithelial cells at sites of tubular necrosis. Isolation and use of these agents in combination with dialysis and nutritional support could speed renal regeneration and thereby improve the outcome in patients with this condition.Abbreviations ARF acute renal failure - ECM extracellular matrix - EGF epidermal growth factor - FGF fibroblast growth factor - IGF insulin-like growth factor - MGSA melanocyte growth-stimulating activity - PDGF platelet-derived growth factor - IGF transforming growth factor     

Migratory, invasive and metastatic capacity of NCAM transfected rat glioma cells

A cDNA encoding a transmembrane 140 kDa isoform of the neural cell adhesion molecule, NCAM, was transfected into the rat glioma cell line BT4Cn. Transfectants with a homogeneously high expression of NCAM-B showed a decreased capacity for penetration of an artificial basement membrane when compared to cells transfected with expression-vector alone or untransfected cells. However, when injected subcutaneously into nude mice, both NCAM expressing cells and control cells produced invasive tumors. Nude mice injected with NCAM positive cells developed tumors with slower growth rates as compared to those induced by NCAM negative cells. This implies that NCAM may not only be involved in adhesive and motile behaviour of glioma cells, but also in their growth regulation.     

Nurse Migration from a Source Country Perspective: Philippine Country Case Study

Objectives. To describe nurse migration patterns in the Philippines and their benefits and costs.
Principal Findings. The Philippines is a job-scarce environment and, even for those with jobs in the health care sector, poor working conditions often motivate nurses to seek employment overseas. The country has also become dependent on labor migration to ease the tight domestic labor market. National opinion has generally focused on the improved quality of life for individual migrants and their families, and on the benefits of remittances to the nation. However, a shortage of highly skilled nurses and the massive retraining of physicians to become nurses elsewhere has created severe problems for the Filipino health system, including the closure of many hospitals. As a result, policy makers are debating the need for new policies to manage migration such that benefits are also returned to the educational institutions and hospitals that are producing the emigrant nurses.
Conclusions and Recommendations. There is new interest in the Philippines in identifying ways to mitigate the costs to the health system of nurse emigration. Many of the policy options being debated involve collaboration with those countries recruiting Filipino nurses. Bilateral agreements are essential for managing migration in such a way that both sending and receiving countries derive benefit from the exchange.     

Differential Effects of Immunosuppressive Drugs on T-Cell Motility

The best-characterized mechanism of the action of immunosuppressive drugs is to prevent T-cell clonal expansion, thus containing the magnitude of the ensuing immune response. As T-cell recruitment to the inflammatory site is another key step in the development of T-cell-mediated inflammation, we analyzed and compared the effects of two commonly used immunosuppressants, cyclosporin A (CsA) and the rapamycin-related compound SDZ-RAD, on the motility of human CD4+ T cells. We show that CsA, but not SDZ-RAD, inhibits T-cell transendothelial migration in vitro. CsA selectively impaired chemokine-induced T-cell chemotaxis while integrin-mediated migration was unaffected. The inhibition of T-cell chemotaxis correlated with reduced AKT/PKB but not ERK activation following exposure to the chemokine CXCL-12/SDF-1. In addition, CsA, but not SDZ-RAD, prevents some T-cell receptor-mediated effects on T-cell motility. Finally, we show that CsA, but not SDZ-RAD inhibits tissue infiltration by T cells in vivo. Our data suggest a prominent antiinflammatory role for CsA in T-cell-mediated tissue damage, by inhibiting T-cell trafficking into tissues in addition to containing clonal expansion.     

G蛋白耦联受体激酶结合蛋白1通过调节细胞外调节激酶1/2的活性促进成骨细胞迁移

目的探索G蛋白耦联受体激酶结合蛋白1(GITI)在成骨细胞迁移中的作用,并分析其机理。方法通过Western blot方法检测GIT1蛋白在鼠的成骨细胞内的表达；用免疫荧光染色方法确定：在血小板衍生生长因子(PDGF)不刺激和刺激的条件下,GIT1和细胞外调节激酶1/2(ERK1/2)在成骨细胞内的位置；用共同免疫沉淀的方法测定GIT1和ERK1/2相互结合,并且用免疫荧光双染的方法确定这两种蛋白相互结合的位置；用包含GIT1-RNA发夹结构的腺病毒感染成骨细胞后,用免疫荧光染色方法确定磷酸化ERK1/2(pERK1/2)在成骨细胞内的位置,用划痕愈合法检测在PDGF刺激下的迁移能力。结果在成骨细胞内,PDGF刺激导致了GIT1和ERK1/2的相互结合,并且这种结合发生在成骨细胞的局部粘附内。包含GIT1-RNA发夹结构的腺病毒明显抑制了pERK1/2招募至成骨细胞局部粘附内以及PDGF所刺激的成骨细胞的迁移。结论在PDGF刺激下,GIT1招募pERK1/2至成骨细胞的局部粘附内,从而促进成骨细胞的迁移。     

Role of the extracellular matrix in neural crest cell migration

Development of the neural crest involves a remarkable feat of coordinated cell migration in which cells detach from the neural tube, take varying routes of migration through the embryonic tissues and then differentiate at the end of their journey to participate in the formation of a number of organ systems. In general, neural crest cells appear to migrate without the guidance of long-range physical or chemical cues, but rather they respond to heterogeneity in the extracellular matrix that forms their migration substrate. Molecules such as fibronectin and laminin act as permissive substrate components, encouraging neural crest cell attachment and spreading, whereas chondroitin sulphate proteoglycans are nonpermissive for migration. A balance between permissive and nonpermissive substrate components seems to be necessary to ensure successful migration, as indicated by a number of studies in mouse mutant systems where nonpermissive molecules are over-expressed, leading to inhibition of neural crest migration. The neural crest expresses cell surface receptors that permit interaction with the extracellular matrix and may also modify the matrix by secretion of proteases. Thus the principles that govern the complex migration of neural crest cells are beginning to emerge.     

MRI of a family with focal abnormalities of gyration

Focal abnormalities of gyration (FAG) are developmental disorders that may occur in isolated patients or, as in the case being reported, as part of a familial disorder. Analysis of individuals in a family spanning three generations was carried out using MRI. Abnormalities, present in all members of generations II and III, included focal cortical dysplasia (three patients), focal cortical infolding (two patients) and schizencephaly (one patient); associated minor anomalies, such as white matter abnormalities, were seen in the remaining three members of generations II and III. MRI recognition of FAG in the family being reported proved useful in defining their phenotypical expression and providing proper counselling for individual family members. Received: 22 August 1996 Accepted: 7 October 1996