Role of Matrix Metalloproteinase 3-mediated alpha-Synuclein Cleavage in Dopaminergic Cell Death

Evidence suggests that the C-terminal truncation of alpha-synuclein is equally important as aggregation of alpha-synuclein in Parkinson disease (PD). Our previous results showed that an endopeptidase, matrix metalloproteinase-3 (MMP3), was induced and activated in dopaminergic (DA) cells upon stress conditions. Here, we report that MMP3 cleaved alpha-synuclein in vitro and in vivo and that alpha-synuclein and MMP3 were co-localized in Lewy bodies (LB) in the postmortem brains of PD patients. Incubation of alpha-synuclein with the catalytic domain of MMP3 (cMMP3) resulted in generation of several peptides, and the peptide profiles of WT alpha-synuclein (WTsyn) and A53T mutant (A53Tsyn) were different. Combined analysis using mass spectrometry and N-terminal determination revealed that MMP3 generated C-terminally truncated peptides of amino acids 1-78, 1-91, and 1-93 and that A53Tsyn produced significantly higher quantities of these peptides. Similar sizes of peptides were detected in N27 DA cells under oxidative stress and RNA interference to knock down MMP3-attenuated peptide generation. Co-overexpression of cMMP3 with either WTsyn or A53Tsyn led to a reduction in Triton X-100-insoluble aggregates and an increase in protofibril-like small aggregates. In addition, overexpression of the 1-93-amino acid peptide in the substantia nigra led to DA neuronal loss without LB-like aggregate formation. The results strongly indicate that MMP3 digestion of alpha-synuclein in DA neurons plays a pivotal role in the progression of PD through modulation of alpha-synuclein in aggregation, LB formation, and neurotoxicity

Development of Web GIS-Based VFSMOD System with Three Modules for Effective Vegetative Filter Strip Design

In recent years, Non-Point Source Pollution has been rising as a significant environmental issue. The sediment-laden water problem is causing serious impacts on river ecosystems not only in South Korea but also in most countries. The vegetative filter strip (VFS) has been thought to be one of the most effective methods to reduce the transport of sediment to down-gradient area. However, the effective width of the VFS first needs to be determined before VFS installation in the field. To provide an easy-to-use interface with a scientific VFS modeling engine, the Web GIS-based VFSMOD system was developed in this study. The Web GIS-based VFSMOD uses the UH and VFSM executable programs from the VFSMOD-w model as core engines to simulate rainfall-runoff and sediment trapping. To provide soil information for a point of interest, the Google Map interface to the MapServer soil database system was developed using the Google Map API, Javascript, Perl/CGI, and Oracle DB programming. Three modules of the Web GIS-based VFSMOD system were developed for various VFS designs under single storm, multiple storm, and long-term period scenarios. These modules in the Web GIS-based VFSMOD system were applied to the study watershed in South Korea and these were proven as efficient tools for the VFS design for various purposes

Prognostic Determinants in Patients with Traumatic Pancreatic Injuries

The aim of this study was to identify factors that predict morbidity and mortality in patients with traumatic pancreatic injuries. A retrospective review was performed on 75 consecutive patients with traumatic pancreatic injuries admitted to the Emergency Medical Center at Masan Samsung Hospital and subsequently underwent laparotomy during the period January 2000 to December 2005. Overall mortality and morbidity rates were 13.3% and 49.3%, respectively. A multivariate regression analysis revealed that greater than 12 blood transfusions and an initial base deficit of less than -11 mM/L were the most important predictors of mortality (p<0.05). On the other hand, the most important predictors of morbidity were surgical complexity and an initial base deficit of less than -5.8 mM/L (p<0.01). These data suggests that early efforts to prevent shock and rapidly control of bleeding are most likely to improve the outcome in patients with traumatic pancreatic injuries. The severity of pancreatic injury per se influenced only morbidity

Development of Web GIS-Based VFSMOD System with Three Modules for Effective Vegetative Filter Strip Design

In recent years, Non-Point Source Pollution has been rising as a significant environmental issue. The sediment-laden water problem is causing serious impacts on river ecosystems not only in South Korea but also in most countries. The vegetative filter strip (VFS) has been thought to be one of the most effective methods to reduce the transport of sediment to down-gradient area. However, the effective width of the VFS first needs to be determined before VFS installation in the field. To provide an easy-to-use interface with a scientific VFS modeling engine, the Web GIS-based VFSMOD system was developed in this study. The Web GIS-based VFSMOD uses the UH and VFSM executable programs from the VFSMOD-w model as core engines to simulate rainfall-runoff and sediment trapping. To provide soil information for a point of interest, the Google Map interface to the MapServer soil database system was developed using the Google Map API, Javascript, Perl/CGI, and Oracle DB programming. Three modules of the Web GIS-based VFSMOD system were developed for various VFS designs under single storm, multiple storm, and long-term period scenarios. These modules in the Web GIS-based VFSMOD system were applied to the study watershed in South Korea and these were proven as efficient tools for the VFS design for various purposes

Saussurea lappa clarkeDerived costunolide prevents TNF alpha induced breast cancer cell migration and invasion by inhibiting NF-

Saussurea lappa Clarke (SLC) has been used as a traditional medicine in Korea, China, and Japan for the treatment of abdominal pain and tenesmus. Costunolide, a sesquiterpene lactone isolated from SLC, has diverse medicinal effects. However, the anticancer effects of costunolide are still unclear in breast cancer. In this study, we demonstrate that costunolide suppresses tumor growth and metastases of MDA-MB-231 highly metastatic human breast cancer cells via inhibiting TNF -induced NF-B activation. Costunolide inhibited MDA-MB-231 tumor growth and metastases without affecting body weights in the in vivo mouse orthotopic tumor growth assays. In addition, costunolide inhibited in vitro TNF -induced invasion and migration of MDA-MB-231 cells. Costunolide further suppressed TNF -induced NF-B signaling activation, resulting in a reduced expression of MMP-9, a wellknown NF-B-dependent gene to mediate breast cancer cell growth and metastases. Therefore, we conclude that SLC and its derivative costunolide suppress breast cancer growth and metastases by inhibiting TNF -induced NF-B activation, suggesting that costunolide as well as SLC may be promising anticancer drugs, especially for metastatic breast cancer

Radiological analysis of transport and storage container for very lowlevel liquid radioactive waste

As NPPs continue to operate, liquid waste continues to be generated, and containers are needed to store and transport them at low cost and high capacity. To transport and store liquid phase very low-level radioactive waste (VLLW), a container is designed by considering related regulations. The design was constructed based on the existing container design, which easily transports and stores liquid waste. The radiation shielding calculation was performed according to the composition change of barium sulfate (BaSO4) using the Monte Carlo N-Particle (MCNP) code. High-density polyethylene (HDPE) without mixing the additional BaSO4, represented the maximum dose of 1.03 mSv/hr (&lt;2 mSv/hr) and 0.048 mSv/ hr (&lt;0.1 mSv/hr) at the surface of the inner container and at 2 m away from the surface, respectively, for a 10 Bq/g of Co-60 source. It was confirmed that the dose from the inner container with the VLLW content satisfied the domestic dose standard both on the surface of the container and 2 m from the surface. Although it satisfies the dose standard without adding BaSO4, a shielding material, the inner container was designed with BaSO4 added to increase radiation safety. (C) 2021 Korean Nuclear Society, Published by Elsevier Korea LLC