Endoplasmic Reticulum Stress in the β-Cell Pathogenesis of Type 2 Diabetes

Type 2 diabetes is a complex metabolic disorder characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency by β-cell failure. Even if the mechanisms underlying the pathogenesis of β-cell failure are still under investigation, recent increasing genetic, experimental, and clinical evidence indicate that hyperactivation of the unfolded protein response (UPR) to counteract metabolic stresses is closely related to β-cell dysfunction and apoptosis. Signaling pathways of the UPR are “a double-edged sword” that can promote adaptation or apoptosis depending on the nature of the ER stress condition. In this paper, we summarized our current understanding of the mechanisms and components related to ER stress in the β-cell pathogenesis of type 2 diabetes

Movement Type Prediction before Its Onset Using Signals from Prefrontal Area: An Electrocorticography Study

Power changes in specific frequency bands are typical brain responses during motor planning or preparation. Many studies have demonstrated that, in addition to the premotor, supplementary motor, and primary sensorimotor areas, the prefrontal area contributes to generating such responses. However, most brain-computer interface (BCI) studies have focused on the primary sensorimotor area and have estimated movements using postonset period brain signals. Our aim was to determine whether the prefrontal area could contribute to the prediction of voluntary movement types before movement onset. In our study, electrocorticography (ECoG) was recorded from six epilepsy patients while performing two self-paced tasks: hand grasping and elbow flexion. The prefrontal area was sufficient to allow classification of different movements through the area's premovement signals (-2.0 s to 0 s) in four subjects. The most pronounced power difference frequency band was the beta band (13-30Hz). The movement prediction rate during single trial estimation averaged 74% across the six subjects. Our results suggest that premovement signals in the prefrontal area are useful in distinguishing different movement tasks and that the beta band is the most informative for prediction of movement type before movement onset.open

High-resolution analysis of condition-specific regulatory modules in Saccharomyces cerevisiae

A novel approach for identifying condition-specific regulatory modules in yeast reveals functionally distinct coregulated submodules

Vaccinia-Related Kinase 2 Mediates Accumulation of Polyglutamine Aggregates via Negative Regulation of the Chaperonin TRiC

Misfolding of proteins containing abnormal expansions of polyglutamine (polyQ) repeats is associated with cytotoxicity in several neurodegenerative disorders, including Huntington's disease. Recently, the eukaryotic chaperonin TRiC hetero-oligomeric complex has been shown to play an important role in protecting cells against the accumulation of misfolded polyQ protein aggregates. It is essential to elucidate how TRiC function is regulated to better understand the pathological mechanism of polyQ aggregation. Here, we propose that vaccinia-related kinase 2 (VRK2) is a critical enzyme that negatively regulates TRiC. In mammalian cells, overexpression of wild-type VRK2 decreased endogenous TRiC protein levels by promoting TRiC ubiquitination, but a VRK2 kinase-dead mutant did not. Interestingly, VRK2-mediated downregulation of TRiC increased aggregate formation of a polyQ-expanded huntingtin fragment. This effect was ameliorated by rescue of TRiC protein levels. Notably, small interference RNA-mediated knockdown of VRK2 enhanced TRiC protein stability and decreased polyQ aggregation. The VRK2-mediated reduction of TRiC protein levels was subsequent to the recruitment of COP1 E3 ligase. Among the members of the COP1 E3 ligase complex, VRK2 interacted with RBX1 and increased E3 ligase activity on TRiC in vitro. Taken together, these results demonstrate that VRK2 is crucial to regulate the ubiquitination-proteosomal degradation of TRiC, which controls folding of polyglutamine proteins involved in Huntington's disease.open118Ysciescopu

Fifteen Years After the Gozan-Dong Glass Fiber Outbreak, Incheon in 1995

Objectives: In 1995, an outbreak survey in Gozan-dong concluded that an association between fiberglass exposure in drinking water and cancer outbreak cannot be established. This study follows the subjects from a study in 1995 using a data linkage method to examine whether an association existed. The authors will address the potential benefits and methodological issues following outbreak surveys using data linkage, particularly when informed consent is absent. Methods: This is a follow-up study of 697 (30 exposed) individuals out of the original 888 (31 exposed) participants (78.5%) from 1995 to 2007 assessing the cancer outcomes and deaths of these individuals. The National Cancer Registry (KNCR) and death certificate data were linked using the ID numbers of the participants. The standardized incidence ratio (SIR) and standardized mortality ratio (SMR) from cancers were calculated by the KNCR. Results: The SIR values for all cancer or gastrointestinal cancer (GI) occurrences were the lowest in the exposed group (SIR, 0.73; 95% CI, 0.10 to 5.21; 0.00 for GI), while the two control groups (control 1: external, control 2: internal) showed slight increases in their SIR values (SIR, 1.18 and 1.27 for all cancers; 1.62 and 1.46 for GI). All lacked statistical significance. All-cause mortality levels for the three groups showed the same pattern (SMR 0.37, 1.29, and 1.11). Conclusions: This study did not refute a finding of non-association with a 13-year follow-up. Considering that many outbreak surveys are associated with a small sample size and a cross-sectional design, follow-up studies that utilize data linkage should become standard procedure.OAIID:oai:osos.snu.ac.kr:snu2011-01/102/0000040632/15SEQ:15PERF_CD:SNU2011-01EVAL_ITEM_CD:102USER_ID:0000040632ADJUST_YN:YEMP_ID:A077602DEPT_CD:902CITE_RATE:0FILENAME:fifteen years after the gozan-dong glass fiber outbreak, incheon in 1995..pdfDEPT_NM:보건학과CONFIRM:

Sirolimus-eluting stent is superior to paclitaxel-eluting stent for coronary intervention in patients with renal insufficiency: Long-term clinical outcomes

Background: Renal insufficiency (RI) is an independent risk factor for the adverse cardiovascular events. Long-term clinical outcome of percutaneous coronary intervention (PCI) in patients with RI is unknown especially in the era of first generation drug-eluting stents (DES). This study aims at comparing clinical outcomes between sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) based on large scaled registry.Methods: Patients who underwent PCI with DES from January 2004 to December 2009 in the Catholic University of Korea-PCI (COACT) registry were prospectively enrolled. A group of 1,033 patients with RI, defined as estimated glomerular filtration rate under 60 mL/min, were analyzed. Major adverse cardiac events (MACE), including all-cause death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR) according to the type of stents were compared.Results: Median follow-up period was 810 days (interquartile range: from 361 to 1,354 days). A group of 612 (59.2%) patients were treated with SES and 421 (40.8%) patients were treated with PES. The PES vs. SES group had significantly higher rate of MACE (35.9% vs. 28.3%, p = 0.01). In multivariate Cox hazard regression analysis, PES vs. SES group had significantly higher rate of MACE (adjusted hazard ratio [AHR] 1.29, 95% confidence interval [CI] 1.02–1.64, p = 0.033), particularly pronounced by all-cause death (AHR 1.34, 95% CI 1.008–1.770; p = 0.044). In further analysis with propensity score matching, overall findings were consistent.Conclusions: In patients with RI, PCI using PES provides poorer clinical outcomes than SES in terms of MACE and all-cause death

Stochastic electrotransport selectively enhances the transport of highly electromobile molecules

Nondestructive chemical processing of porous samples such as fixed biological tissues typically relies on molecular diffusion. Diffusion into a porous structure is a slow process that significantly delays completion of chemical processing. Here, we present a novel electrokinetic method termed stochastic electrotransport for rapid nondestructive processing of porous samples. This method uses a rotational electric field to selectively disperse highly electromobile molecules throughout a porous sample without displacing the low-electromobility molecules that constitute the sample. Using computational models, we show that stochastic electrotransport can rapidly disperse electromobile molecules in a porous medium. We apply this method to completely clear mouse organs within 1–3 days and to stain them with nuclear dyes, proteins, and antibodies within 1 day. Our results demonstrate the potential of stochastic electrotransport to process large and dense tissue samples that were previously infeasible in time when relying on diffusion.Simons Foundation. Postdoctoral FellowshipLife Sciences Research FoundationBurroughs Wellcome Fund (Career Awards at the Scientific Interface)Searle Scholars ProgramMichael J. Fox Foundation for Parkinson's ResearchUnited States. Defense Advanced Research Projects AgencyJPB FoundationNational Institutes of Health (U.S.)National Institutes of Health (U.S.) (Grant 1-U01-NS090473-01