Nuclear localization of orphan receptor protein kinase (Ror1) is mediated through the juxtamembrane domain

<p>Abstract</p> <p>Background</p> <p>Several receptor tyrosine kinases (RTKs) such as EGFR, FGFR, TRK, and VEGFR are capable of localizing in the cell nucleus in addition to their usual plasma membrane localization. Recent reports also demonstrate that nuclear-localized RTKs have important cellular functions such as transcriptional activation. On the basis of preliminary bioinformatic analysis, additional RTKs, including receptor tyrosine kinase-like orphan receptor 1 (Ror1) were predicted to have the potential for nuclear subcellular localization. Ror1 is a receptor protein tyrosine kinase that modulates neurite growth in the central nervous system. Because the nuclear localization capability of the Ror1 cytoplasmic domain has not been reported, we examined the cellular expression distribution of this region.</p> <p>Results</p> <p>The Ror1 cytoplasmic region was amplified and cloned into reporter constructs with fluorescent tags. Following transfection, the nuclear distribution patterns of transiently expressed fusion proteins were observed. Serial deletion constructs were then used to map the juxtamembrane domain of Ror1 (aa_471-513) for this nuclear translocation activity. Further site-directed mutagenesis suggested that a KxxK-16 aa-KxxK sequence at residues 486-509 is responsible for the nuclear translocation interaction. Subsequent immunofluorescence analysis by cotransfection of Ran and Ror1 implied that the nuclear translocation event of Ror1 might be mediated through the Ran pathway.</p> <p>Conclusions</p> <p>We have predicted several RTKs that contain the nuclear localization signals. This is the first report to suggest that the juxtamembrane domain of the Ror1 cytoplasmic region mediates the translocation event. Ran GTPase is also implicated in this event. Our study might be beneficial in future research to understand the Ror1 biological signaling pathway.</p

A hyperconnected manufacturing collaboration system using the semantic web and Hadoop ecosystem system

With the explosive growth of digital data communications in synergistic operating networks and cloud computing service, hyperconnected manufacturing collaboration systems face the challenges of extracting, processing, and analyzing data from multiple distributed web sources. Although semantic web technologies provide the solution to web data interoperability by storing the semantic web standard in relational databases for processing and analyzing of web-accessible heterogeneous digital data, web data storage and retrieval via the predefined schema of relational / SQL databases has become increasingly inefficient with the advent of big data. In response to this problem, the Hadoop Ecosystem System is being adopted to reduce the complexity of moving data to and from the big data cloud platform. This paper proposes a novel approach in a set of the Hadoop tools for information integration and interoperability across hyperconnected manufacturing collaboration systems. In the Hadoop approach, data is “Extracted” from the web sources, “Loaded” into a set of the NoSQL Hadoop Database (HBase) tables, and then “Transformed” and integrated into the desired format model with Hive's schema-on-read. A case study was conducted to illustrate that the Hadoop Extract-Load-Transform (ELT) approach for the syntax and semantics web data integration could be adopted across the global smartphone value chain

CCN2 Enhances Resistance to Cisplatin-Mediating Cell Apoptosis in Human Osteosarcoma

Osteosarcoma (OS) is the most common form of malignant bone tumor and is an aggressive malignant neoplasm exhibiting osteoblastic differentiation. Cisplatin is one of the most efficacious antitumor drugs for osteosarcoma patients. However, treatment failures are common due to the development of chemoresistance. CCN2 (also known as CTGF), is a secreted protein that binds to integrins, modulates the invasive behavior of certain human cancer cells. However, the effect of CCN2 in cisplatin-mediated chemotherapy is still unknown. Here, we found that CCN2 was upregulated in human osteosarcoma cells after treatment with cisplatin. Moreover, overexpression of CCN2 increased the resistance to cisplatin-mediated cell apoptosis. In contrast, reduction of CCN2 by CCN2 shRNA promoted the chemotherapeutic effect of cisplatin. We also found that CCN2 provided resistance to cisplatin-induced apoptosis through upregulation of Bcl-xL and survivin. Knockdown of Bcl-xL or survivin removed the CCN2-mediated resistance to apoptosis induced by cisplatin. On the other hand, CCN2 also promoted FAK, MEK, and ERK survival signaling pathways to enhance tumor survival during cisplatin treatment. In a mouse xenograft model, overexpression of CCN2 promoted resistance to cisplatin. However, knockdown of CCN2 increased the therapeutic effect of cisplatin. Therefore, our data suggest that CCN2 might be a critical oncogene of human osteosarcoma for cisplatin-resistance and supported osteosarcoma cell growth in vivo and in vitro

Temporomandibular Joint Disorders in Patients with Rheumatoid Arthritis

BackgroundTemporomandibular joint disorders (TMD) are not uncommon in patients with rheumatoid arthritis (RA). However, the extent of involvement and its clinical relevance have not been well characterized. This study evaluated the correlation between the severity of RA-related TMD and RA, as well as determined the potential predictors for early identification and management of TMD in RA patients.MethodsWe sequentially recruited 56 adult RA patients from our Arthritis Clinic. TMD and RA were surveyed, clinically by questionnaires and physical examinations, and radiologically by tomography in TMD and conventional radiography in RA. The patients were stratified into no, mild and severe TMD groups according to the physical and tomographic examinations. The correlation of the severity of TMD and RA were evaluated. The relative importance of relevant predictors of severe TMD was analyzed by a logistic regression model.ResultsPhysical and radiologic temporomandibular joint abnormalities were found to be highly prevalent (85.7% and 74.5%) in these patients, and the occurrence increased to as much as 92.9% when the 2 data sets were combined. More than half of the patients had severe TMD presenting with debilitating symptoms or with a significant degree of bony destruction. The severity of TMD was variably correlated with RA severity. The score of hand-joint space narrowing was found to be the most influential predictor of severe TMD by logistic regression analysis.ConclusionThere was a high prevalence of TMD in RA patients. The severity of TMD variably correlated with RA severity. Clinically, a high score of hand-joint space narrowing may serve as an early indicator of RA patients at risk of severe TMD. This may facilitate early management and prevent the functional impairment of the temporomandibular joint

The Study on Antecedents of Consumer Buying Impulsiveness in an Online Context

The global recession caused by the financial tsunami has seriously impacted numerous industries. Although the market scale of global e-commerce market has declined, global online shopping continues to grow. Many previous researches focused on the effect of website design characteristics on online impulsive buying behavior, and few have explored such behavior from consumer individual internal factor perspectives. This paper aims to explore and integrate individual internal factors influencing consumer online buying impulsiveness, and further to recognize the relationships among these factors. The results showed as follows: (1) hedonic consumption needs, impulsive buying tendency, positive affect and normative evaluations positively influence buying impulsiveness, respectively; (2) hedonic consumption needs positively influence positive affect; (3) impulsive buying tendency positively influences normative evaluations; (4) normative evaluations positively influence positive affect

Experimental and Numerical Study of Tsunami Wave Propagation and Run-Up on Sloping Beaches

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv