LINE FUSION GENES: a database of LINE expression in human genes

BACKGROUND: Long Interspersed Nuclear Elements (LINEs) are the most abundant retrotransposons in humans. About 79% of human genes are estimated to contain at least one segment of LINE per transcription unit. Recent studies have shown that LINE elements can affect protein sequences, splicing patterns and expression of human genes. DESCRIPTION: We have developed a database, LINE FUSION GENES, for elucidating LINE expression throughout the human gene database. We searched the 28,171 genes listed in the NCBI database for LINE elements and analyzed their structures and expression patterns. The results show that the mRNA sequences of 1,329 genes were affected by LINE expression. The LINE expression types were classified on the basis of LINEs in the 5' UTR, exon or 3' UTR sequences of the mRNAs. Our database provides further information, such as the tissue distribution and chromosomal location of the genes, and the domain structure that is changed by LINE integration. We have linked all the accession numbers to the NCBI data bank to provide mRNA sequences for subsequent users. CONCLUSION: We believe that our work will interest genome scientists and might help them to gain insight into the implications of LINE expression for human evolution and disease. AVAILABILITY

Predictors of intentional intoxication using decision tree modeling analysis: a retrospective study

Objective The suicide rate in South Korea is very high and is expected to increase in coming years. Intoxication is the most common suicide attempt method as well as one of the common reason for presenting to an emergency medical center. We used decision tree modeling analysis to identify predictors of risk for suicide by intentional intoxication. Methods A single-center, retrospective study was conducted at our hospital using a 4-year registry of the institute from January 1, 2013 to December 31, 2016. Demographic factors, such as sex, age, intentionality, therapeutic adherence, alcohol consumption, smoking status, physical disease, cancer, psychiatric disease, and toxicological factors, such as type of intoxicant and poisoning severity score were collected. Candidate risk factors based on the decision tree were used to select variables for multiple logistic regression analysis. Results In total, 4,023 patients with intoxication were enrolled as study participants, with 2,247 (55.9%) identified as cases of intentional intoxication. Reported annual percentages of intentional intoxication among patients were 628/937 (67.0%), 608/1,082 (56.2%), 536/1,017 (52.7), 475/987 (48.1%) from 2013 to 2016. Significant predictors identified based on decision tree analysis were alcohol consumption, old age, psychiatric disease, smoking, and male sex; those identified based on multiple regression analysis were alcohol consumption, smoking, male sex, psychiatric disease, old age, poor therapeutic adherence, and physical disease. Conclusion We identified important predictors of suicide risk by intentional intoxication. A specific and realistic approach to analysis using the decision tree modeling technique is an effective method to determine those groups at risk of suicide by intentional intoxication

Prevention of hypoglycemia-induced neuronal death by minocycline

Diabetic patients who attempt strict management of blood glucose levels frequently experience hypoglycemia. Severe and prolonged hypoglycemia causes neuronal death and cognitive impairment. There is no effective tool for prevention of these unwanted clinical sequelae. Minocycline, a second-generation tetracycline derivative, has been recognized as an anti-inflammatory and neuroprotective agent in several animal models such as stroke and traumatic brain injury. In the present study, we tested whether minocycline also has protective effects on hypoglycemia-induced neuronal death and cognitive impairment. To test our hypothesis we used an animal model of insulin-induced acute hypoglycemia. Minocycline was injected intraperitoneally at 6 hours after hypoglycemia/glucose reperfusion and injected once per day for the following 1 week. Histological evaluation for neuronal death and microglial activation was performed from 1 day to 1 week after hypoglycemia. Cognitive evaluation was conducted 6 weeks after hypoglycemia. Microglial activation began to be evident in the hippocampal area at 1 day after hypoglycemia and persisted for 1 week. Minocycline injection significantly reduced hypoglycemia-induced microglial activation and myeloperoxidase (MPO) immunoreactivity. Neuronal death was significantly reduced by minocycline treatment when evaluated at 1 week after hypoglycemia. Hypoglycemia-induced cognitive impairment is also significantly prevented by the same minocycline regimen when subjects were evaluated at 6 weeks after hypoglycemia. Therefore, these results suggest that delayed treatment (6 hours post-insult) with minocycline protects against microglial activation, neuronal death and cognitive impairment caused by severe hypoglycemia. The present study suggests that minocycline has therapeutic potential to prevent hypoglycemia-induced brain injury in diabetic patients

Plasma membrane calcium ATPase regulates bone mass by fine-tuning osteoclast differentiation and survival.

The precise regulation of Ca2+ dynamics is crucial for proper differentiation and function of osteoclasts. Here we show the involvement of plasma membrane Ca2+ ATPase (PMCA) isoforms 1 and 4 in osteoclastogenesis. In immature/undifferentiated cells, PMCAs inhibited receptor activator of NF-B ligand–induced Ca2+ oscillations and osteoclast differentiation in vitro. Interestingly, nuclear factor of activated T cell c1 (NFATc1) directly stimulated PMCA transcription, whereas the PMCA-mediated Ca2+ efflux prevented NFATc1 activation, forming a negative regulatory loop. PMCA4 also had an anti-osteoclastogenic effect by reducing NO, which facilitates preosteoclast fusion. In addition to their role in immature cells, increased expression of PMCAs in mature osteoclasts prevented osteoclast apoptosis both in vitro and in vivo. Mice heterozygous for PMCA1 or null for PMCA4 showed an osteopenic phenotype with more osteoclasts on bone surface. Furthermore, PMCA4 expression levels correlated with peak bone mass in premenopausal women. Thus, our results suggest that PMCAs play important roles for the regulation of bone homeostasis in both mice and humans by modulating Ca2+ signaling in osteoclasts.OAIID:oai:osos.snu.ac.kr:snu2012-01/102/0000026258/8SEQ:8PERF_CD:SNU2012-01EVAL_ITEM_CD:102USER_ID:0000026258ADJUST_YN:NEMP_ID:A076310DEPT_CD:861CITE_RATE:10.264FILENAME:J Cell Biol-2012-Kim-ATPase.pdfDEPT_NM:치의학과EMAIL:[email protected]_YN:YCONFIRM:

Precise stacking of decellularized extracellular matrix based 3D cell-laden constructs by a 3D cell printing system equipped with heating modules

Three-dimensional (3D) cell printing systems allow the controlled and precise deposition of multiple cells in 3D constructs. Hydrogel materials have been used extensively as printable bioinks owing to their ability to safely encapsulate living cells. However, hydrogel-based bioinks have drawbacks for cell printing, e.g. inappropriate crosslinking and liquid-like rheological properties, which hinder precise 3D shaping. Therefore, in this study, we investigated the influence of various factors (e.g. bioink concentration, viscosity, and extent of crosslinking) on cell printing and established a new 3D cell printing system equipped with heating modules for the precise stacking of decellularized extracellular matrix (dECM)-based 3D cell-laden constructs. Because the pH-adjusted bioink isolated from native tissue is safely gelled at 37 degrees C, our heating system facilitated the precise stacking of dECM bioinks by enabling simultaneous gelation during printing. We observed greater printability compared with that of a non-heating system. These results were confirmed by mechanical testing and 3D construct stacking analyses. We also confirmed that our heating system did not elicit negative effects, such as cell death, in the printed cells. Conclusively, these results hold promise for the application of 3D bioprinting to tissue engineering and drug development.119Ysciescopu