Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Gαs/Gαq-mediated protein kinases A/C.

VLGR1 (very large G protein-coupled receptor 1), also known as MASS1 (monogenic audiogenic seizure susceptible 1), is an orphan G protein-coupled receptor that contains a large extracellular N terminus with 35 calcium-binding domains. A truncating mutation in the Mass1 gene causes autosomal recessive, sound-induced seizures in the Frings mouse. However, the function of MASS1 and the mechanism underlying Frings mouse epilepsy are not known. Here, we found that MASS1 protein is enriched in the myelinated regions of the superior and inferior colliculi, critical areas for the initiation and propagation of audiogenic seizures. Using a panel of myelin antibodies, we discovered that myelin-associated glycoprotein (MAG) expression is dramatically decreased in Frings mice. MASS1 inhibits the ubiquitylation of MAG, thus enhancing the stability of this protein, and the calcium-binding domains of MASS1 are essential for this regulation. Furthermore, MASS1 interacts with Gαs/Gαq and activates PKA and PKC in response to extracellular calcium. Suppression of signaling by MASS1 RNAi or a specific inhibitor abrogates MAG up-regulation. We postulate that MASS1 senses extracellular calcium and activates cytosolic PKA/PKC pathways to regulate myelination by means of MAG protein stability in myelin-forming cells of the auditory pathway. Further work is required to determine whether MAG dysregulation is a cause or consequence of audiogenic epilepsy and whether there are other pathways regulated by MASS1

MicroRNA-23a promotes myelination in the central nervous system.

Demyelinating disorders including leukodystrophies are devastating conditions that are still in need of better understanding, and both oligodendrocyte differentiation and myelin synthesis pathways are potential avenues for developing treatment. Overexpression of lamin B1 leads to leukodystrophy characterized by demyelination of the central nervous system, and microRNA-23 (miR-23) was found to suppress lamin B1 and enhance oligodendrocyte differentiation in vitro. Here, we demonstrated that miR-23a-overexpressing mice have increased myelin thickness, providing in vivo evidence that miR-23a enhances both oligodendrocyte differentiation and myelin synthesis. Using this mouse model, we explored possible miR-23a targets and revealed that the phosphatase and tensin homologue/phosphatidylinositol trisphosphate kinase/Akt/mammalian target of rapamycin pathway is modulated by miR-23a. Additionally, a long noncoding RNA, 2700046G09Rik, was identified as a miR-23a target and modulates phosphatase and tensin homologue itself in a miR-23a-dependent manner. The data presented here imply a unique role for miR-23a in the coordination of proteins and noncoding RNAs in generating and maintaining healthy myelin

Toward optimal multistep forecasts in non-stationary autoregressions

This paper investigates multistep prediction errors for non-stationary autoregressive processes with both model order and true parameters unknown. We give asymptotic expressions for the multistep mean squared prediction errors and accumulated prediction errors of two important methods, plug-in and direct prediction. These expressions not only characterize how the prediction errors are influenced by the model orders, prediction methods, values of parameters and unit roots, but also inspire us to construct some new predictor selection criteria that can ultimately choose the best combination of the model order and prediction method with probability 1. Finally, simulation analysis confirms the satisfactory finite sample performance of the newly proposed criteria.Comment: Published in at http://dx.doi.org/10.3150/08-BEJ165 the Bernoulli (http://isi.cbs.nl/bernoulli/) by the International Statistical Institute/Bernoulli Society (http://isi.cbs.nl/BS/bshome.htm

Summary of a Topical Forum FAQ Based on the Chinese Composition Structure

An automatic multiple-document summarization system for producing frequently asked questions (FAQ) of a topical forum can save forum Webmasters a great deal of time in theory. This work will address summary composition issue of a previous work by proposing a structured presentation based on a four-part pattern of traditional Chinese articles. The result of the experiment shows that the enhanced system with both domain-terminology corpus methods produced a significantly better summary presentation than the original system. Recall rate and precision rate performance indices and user evaluations are also presented and discussed to show their practical implications

ANALYZING MEDICAL TRANSACTION DATA BY USING ASSOCIATION RULE MINING WITH MULTIPLE MINIMUM SUPPORTS

The quick development of IS has a huge impact on the healthcare industry. almost all the existing hospitals, clinics and other healthcare-related institutes have adopted a functionally powerful and highly integrated Hospital Information System (HIS) for management of clinic or medical-related affairs. The medical data stored in the HIS are collected from many different medical subsystems, However, problems of failed data sharing and inconsistent data content often occur among these subsystems, resulting in many hospitals collect a large amount of medical data, but not the ability to process and analyse these data properly, letting the valuable data in the HIS all go to waste. In this study, we made a practical visit to a certain hospital in Taiwan and collected radioimmunoassay (RIA) data from the Laboratory Information System (LIS) and the Departmental Registration System (DRS) of this hospital. Further, we proposed a method of the association rule mining in combination with the concept of multiple minimum supports to analyse and find valuable association rules from the RIA data. The analytical results found the method we proposed can indeed find association rules that would not be able to be found with the traditional association mining methods. It is very helpful in improving doctor-patient relationship and upgrading health care quality