Modulation of Actin Filament Dynamics by Inward Rectifying of Potassium Channel Kir2.1

Apart from its ion channel properties, the Kir2.1 channel has been found in tumors and cancer cells to facilitate cancer cell motility. It is assumed that Kir2.1 might be associated with cell actin filament dynamics. With the help of structured illumination microscopy (SIM), we show that Kir2.1 overexpression promotes actin filament dynamics, cell invasion, and adhesion. Mutated Kir2.1 channels, with impaired membrane expression, present much weaker actin regulatory effects, which indicates that precise Kir2.1 membrane localization is key to its actin filament remolding effect. It is found that Kir2.1 membrane expression and anchoring are associated with PIP2 affinity, and PIP2 depletion inhibits actin filament dynamics. We also report that membrane-expressed Kir2.1 regulates redistribution and phosphorylation of FLNA (filamin A), which may be the mechanism underlying Kir2.1 and actin filament dynamics. In conclusion, Kir2.1 membrane localization regulates cell actin filaments, and not the ion channel properties. These data indicate that Kir2.1 may have additional cellular functions distinct from the regulation of excitability, which provides new insight into the study of channel proteins

Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to the development of pulmonary arterial hypertension

Aims Pulmonary arterial hypertension [1] is a proliferative disorder associated with enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMCs). Reactive oxygen species (ROS) is implicated in the development of PAH and regulates the vascular tone and functions. However, which cellular signaling mechanisms are triggered by ROS in PAH is still unknown. Hence, here we wished to characterize the signaling mechanisms triggered by ROS. Methods and Results By Western blots, we showed that increased intracellular ROS caused inhibition of the glycolytic pyruvate kinase M2 (PKM2) activity through promoting the phosphorylation of PKM2. Monocrotaline (MCT)-induced rats developed severe PAH and right ventricular hypertrophy, with a significant increase in the P-PKM2 and decrease in pyruvate kinase activity which could be attenuated with the treatments of PKM2 activators, FBP and l-serine. The antioxidant NAC, apocynin and MnTBAP had the similar protective effects in the development of PAH. In vitro assays confirmed that inhibition of PKM2 activity could modulate the flux of glycolytic intermediates in support of cell proliferation through the increased pentose phosphate pathway (PPP). Increased ROS and decreased PKM2 activity also promoted the Cav1.2 expression and intracellular calcium. Conclusion Our data provide new evidence that PKM2 makes a critical regulatory contribution to the PAHs for the first time. Decreased pyruvate kinase M2 activity confers additional advantages to rat PASMCs by allowing them to sustain anti-oxidant responses and thereby support cell survival in PAH. It may become a novel treatment strategy in PAH by using of PKM2 activators

CFTR Deficiency Affects Glucose Homeostasis via Regulating GLUT4 Plasma Membrane Transportation

Cystic Fibrosis (CF) is an autosomal recessive disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CF-related diabetes (CFRD) is one of the most prevalent comorbidities of CF. Altered glucose homeostasis has been reported in CF patients. The mechanism has not been fully elucidated. Besides the consequence of pancreatic endocrine dysfunction, we focus on insulin-responsive tissues and glucose transportation to explain glucose homeostasis alteration in CFRD. Herein, we found that CFTR knockout mice exhibited insulin resistance and glucose tolerance. Furthermore, we demonstrated insulin-induced glucose transporter 4 (GLUT4) translocation to the cell membrane was abnormal in the CFTR knockout mice muscle fibers, suggesting that defective intracellular GLUT4 transportation may be the cause of impaired insulin responses and glucose homeostasis. We further demonstrated that PI(4,5)P2 could rescue CFTR related defective intracellular GLUT4 transportation, and CFTR could regulate PI(4,5)P2 cellular level through PIP5KA, suggesting PI(4,5)P2 is a down-stream signal of CFTR. Our results revealed a new signal mechanism of CFTR in GLUT4 translocation regulation, which helps explain glucose homeostasis alteration in CF patients

A Novel Schema-Oriented Approach for Chinese New Word Identification

With the popularity of network application-s, new words become more common and bring the poor performance of natural lan-guage processing related applications in-cluding web search. Identifying new words automatically from texts is still a very chal-lenging problem, especially for Chinese. In this paper, we propose a novel schema-oriented approach for Chinese new word i-dentification (named “ChNWI”). This ap-proach has three main steps: (1) we suggest three composition schemas that cover nearly all two-character up to four-character Chi-nese word surfaces; (2) we employ support vector machine (SVM) to classify Chinese new words of three schemas using their u-nique linguistic characteristics; and (3) we design various rules to filter identified Chi-nese new words of three schemas. Our ex-tensive evaluations with two corpora (Chi-nese news titles and CIPS-SIGHAN 2012 CSMB) show ChNWI’s efficiency on Chi-nese new word identification.

Efficient Retrieval Of Complex Objects: Query Processing In A Hybrid Db And Ir System

Information retrieval systems are currently being developed to represent and manipulate complex multimedia objects. Such objects contain two types of components, i.e. structured components (e.g. of the type integer, real, fixed-length string, etc.), and unstructured components (e.g. text, images, sounds). Relational database systems (RDBS) are often used to store structured data and retrieve it via exact matching, while unstructured data is organized into inverted files, and accessed by Information storage and Retrieval Systems (IRS), utilizing indeterminate matching. The difficulty is how to fill the gap between the RDBs and inverted files, as well as the gap between the RDBMSs and IRSs based on inverted files. We describe an approach to integrating the two types of systems and the two different types of data. 1 Introduction A decade ago, a clear distinction between database (DB) systems and information retrieval (IR) systems could be based on the kinds of data stored in the systems ..