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

Klassevirus Infection in Children, South Korea

To investigate prevalence and clinical characteristics of klassevirus in South Korea, we performed molecular screening in fecal and nasopharyngeal samples from hospitalized children with gastroenteritis. A total of 26 (8.8%) of 294 fecal samples were positive for klassevirus. Klassevirus may be a possible cause of gastroenteritis

The Correction of a Secondary Bilateral Cleft Lip Nasal Deformity Using Refined Open Rhinoplasty with Reverse-U Incision, V-Y Plasty, and Selective Combination with Composite Grafting: Long-term Results

BackgroundThis article presents long-term outcomes after correcting secondary bilateral cleft lip nasal deformities using a refined reverse-U incision and V-Y plasty or in combination with a composite graft in order to elongate the short columella.MethodsA total of forty-six patients underwent surgery between September 1996 and December 2008. The age of the patients ranged from 3 to 19 years of age. A bilateral reverse-U incision and V-Y plasty were used in 24 patients. A composite graft from the helical root was combined with a bilateral reverse-U incision in the 22 patients who possessed a severely shortened columella. The follow-up period ranged between 2 and 10 years.ResultsA total of 32 patients out of 46 were evaluated postoperatively. The average columella length was significantly improved from an average of 3.7 mm preoperatively to 8.5 mm postoperatively. The average ratio of the columella height to the alar base width was 0.18 preoperatively and 0.29 postoperatively. The postoperative basal and lateral views revealed a better shape of the nostrils and columella. The elongated columella, combined with a composite graft, presented good maintenance of the corrected position with no growth disturbance. A composite graft showed color mismatching in several patients. Twenty-six patients demonstrated no alar-columella web deformity and satisfactory symmetry of the nostrils. Four patients experienced a drooping and overhanging of the corrected alar-columella web.ConclusionsA bilateral reverse-U incision with V-Y plasty or in combination with a composite graft was effective in correcting secondary bilateral cleft lip nasal deformity

Fabrication of Stable Cartilage Framework for Microtia in Incomplete Synchondrosis

The synchondrosis between the sixth and seventh costal cartilage is usually used for the base frame in autogenous ear reconstruction. If the synchondrosis is loose, a variety of modifications can be devised. This report introduces new methods for these problems. In cases of incomplete synchondrosis, only the surface of the base block margin was smoothly tapered without carving for the removal of the conchal deepening. The secure fixation of the two segments (helix and antihelix) to the base block using fine wire sutures gave stability to the unstable basal frame. After confirming that all the segments were assembled in one stable piece, the remaining conchal deepening of the basal framework was removed, and the outer lower portion of the basal cartilage was trimmed along its whole length. A total of 10 consecutive patients with microtia, ranging from 8 to 13 years old, were treated from 2008 to 2009. The follow-up period was 6 months to 2 years. Despite incomplete synchondrosis, the stable frameworks were constructed using the authors' method and aesthetically acceptable results were achieved. The proposed method can provide an easy way to make a stable cartilage framework regardless of the variable conditions of synchondrosis

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:

Acute Appendicitis in Henoch-Schönlein Purpura : A Case Report

Common complications of Henoch-Schönlein purpura (HSP) that lead to surgical intervention include intussusception, perforation, necrosis, and massive gastrointestinal bleeding. Acute appendicitis is rarely seen as a complication of HSP. A seven-year-old boy was admitted for arthralgia, abdominal pain, hematochezia, melena, and purpuric rash on the lower extremities. On admission day abdominal ultrasonography was normal, but on day 5, he became pyrexial and developed right iliac fossa pain and tenderness with guarding. Ultrasonography showed distended appendix surrounded by hyperechoic inflamed fat. On exploration an acutely inflamed, necrotic appendix was removed and grossly there was an appendiceal perforation in the appendiceal tip. Microscopically some of the small blood vessels in the submucosa showed fibrinoid necrosis with neutrophilic infiltrations. The authors report the case of a child who developed acute perforative appendicitis requiring appendectomy while on treatment for HSP

CO ameliorates cellular senescence and aging by modulating the miR-34a/Sirt1 pathway

Oxidative stress is recognised as a key factor that can lead to cellular senescence and aging. Carbon monoxide (CO) is produced by haemoxygenase-1 (HO-1), which exerts cytoprotective effects in aging-related diseases, whereas the effect of CO on cellular senescence and aging has not been elucidated. In the current study, we clearly demonstrated that CO delays the process of cellular senescence and aging through regulation of miR-34a and Sirt1 expression. CO reduced H2O2-induced premature senescence in human diploid fibroblast WI-38 cells measured with SA-beta-Gal-staining. Furthermore, CO significantly decreased the expression of senescence-associated secretory phenotype (SASP), including TNF-alpha IL-6, and PAI-1 and increased the transcriptional levels of antioxidant genes, such as HO-1 and NQO1. Moreover, CO apparently enhanced the expression of Sirt1 through down-regulation of miR-34a. Next, to determine whether Sirt1 mediates the inhibitory effect of CO on cellular senescence, we pre-treated WI-38 cells with the Sirt1 inhibitor Ex527 and a miR-34a mimic followed by the administration of H2O2 and evaluated the expression of SASP and antioxidant genes as well as ROS production. According to our results, Sirt1 is crucial for the antiaging and antioxidant effects of CO. Finally, CO prolonged the lifespan of Caenorhabditis elegans and delayed high-fat diet-induced liver aging. Taken together, these findings demonstrate that CO reduces cellular senescence and liver aging through the regulation of miR-34a and Sirt1.

GSK-3β inhibition by curcumin mitigates amyloidogenesis via TFEB activation and anti-oxidative activity in human neuroblastoma cells

© 2020 Informa UK Limited, trading as Taylor & Francis Group.The translocation of transcription factor EB (TFEB) to the nucleus plays a pivotal role in the regulation of basic cellular processes, such as lysosome biogenesis and autophagy. Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome, which is important in maintaining cellular homeostasis during environmental stress. Furthermore, oxidative stress is a critical cause for the progression of neurodegenerative diseases. Curcumin has anti-oxidative and anti-inflammatory activities, and is expected to have potential therapeutic effects in various diseases. In this study, we demonstrated that curcumin regulated TFEB export signalling via inhibition of glycogen synthase kinase-3β (GSK-3β); GSK-3β was inactivated by curcumin, leading to reduced phosphorylation of TFEB. We further showed that H2O2-induced oxidative stress was reduced by curcumin via the Nrf2/HO-1 pathway in human neuroblastoma cells. In addition, we showed that curcumin induced the degradation of amyloidogenic proteins, including amyloid-β precursor protein and α-synuclein, through the TFEB-autophagy/lysosomal pathway. In conclusion, curcumin regulates autophagy by controlling TFEB through the inhibition of GSK-3β, and increases antioxidant gene expression in human neuroblastoma cells. These results contribute to the development of novel cellular therapies for neurodegenerative diseases.