Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate.

Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs) demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages

The unfolded protein response is shaped by the NMD

Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), an essential adaptive intracellular pathway that relieves the stress. Although the UPR is an evolutionarily conserved and beneficial pathway, its chronic activation contributes to the pathogenesis of a wide variety of human disorders. The fidelity of UPR activation must thus be tightly regulated to prevent inappropriate signaling. The nonsense-mediated RNA decay (NMD) pathway has long been known to function in RNA quality control, rapidly degrading aberrant mRNAs, and has been suggested to regulate subsets of normal mRNAs. Here, we report that the NMD pathway regulates the UPR. NMD increases the threshold for triggering the UPR in vitro and in vivo, thereby preventing UPR activation in response to normally innocuous levels of ER stress. NMD also promotes the timely termination of the UPR. We demonstrate that NMD directly targets the mRNAs encoding several UPR components, including the highly conserved UPR sensor, IRE1α, whose NMD-dependent degradation partly underpins this process. Our work not only sheds light on UPR regulation, but demonstrates the physiological relevance of NMD's ability to regulate normal mRNAs

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Location of genetic markers on the Xanthomonas campestris pv. campestris 17 chromosome and lytB gene analysis

Abstract The SwaI and PacI physical maps of Xanthomonas campestris pv. campestris 17 (Xc17) had been constructed. This study is based on those maps take the strategy of gene tagging with PFGE, PCR and Southern hybridization to localize genes. Seven genes has been localized. If the whole chromosome is divided into 100 min, the replication terminus region, the recombination site dif design as 50 min. The tdh gene locates on the PA and WB fragment, the map site is on 34.8 min; the rpoA gene is on the PA and WA fragment, its map site is on 49.2 min; the pilY1-like gene locates on PC and WB fragment, on 13.5 min on map; the dnaK gene locates PD and WD fragment, its map site is on 2 min; besides lytB gene locates on PA and WA fragment, map site is 96 min. moreover, there are two copies of rrn operon on PA and WA fragment and PC and WB fragment, 12.4 min and 93.2 min on the map. This study also has accomplished lytB gene sequence. There are 948 bp in lytB gene could be translated into 315 amino acid. In in vitro data, we predicted the molecular weight of LytB is 34 kDa.中文摘要 Xanthomonas campestris pv. campestris 為十字花科黑腐病的病原菌。 本實驗室在過去的研究中已經建立不少關於此菌遺傳學及分生方面的資訊 。 其中在染色體圖譜的建立上， 已先後完成了 SwaI 及 PacI 的染 色體基 因圖譜，並也已逐步將許多基因定位於圖譜上。 本研究即 是延續前人的 工作， 以已完成之圖譜為基礎， 利用 gene tagging策略， 配合 PFGE 、 PCR 及 Southern hybridation的技 術， 將已發現之基因盡可能的取 得並將其定位。 目前已完成了七個基因的定位。 若將整個染色體以 100 分鐘做分割， 複製終點區基因 dif 處為 50 分鐘。 其中， tdh 基因位於 PA 及 WB 片段上， 圖譜位置在 34.8 分鐘處； rpoA 基因位於 PA 及 WA 片段， 圖譜位置在 89 分鐘處； hrp 基因位於PA 及 WA片段， 圖譜上為 47.2 分鐘處； pilY1-like基因位於 PC 及 WB 片段上， 圖譜上 13.5 分鐘處；dnaK 基因 位於 PD 及 WD 片段上， 圖譜 位置在 2 分鐘處及 lytB 基因 位於PA 及 WA片段上， 圖譜位置 在 96 分鐘處。 此外， 在本研究中得知 Xc17 之 rrn operon 共有兩套分別位於 PA與WA 片段 以及 PC與WB 片段上， 圖譜上 為 12.4 分鐘與 93.2 分鐘處。 本實驗並完成 lytB 基因及其上下游部份 DNA 序列共 1,129 bp。 lytB 基因共有 948 bp 可轉譯成 315 氨基酸， 與 E. coli 及P. fluorescens 之 lytB 基因分別有 63.8% 及 71.3% 的同質性。 輔以 in vitro 實驗分析推測 LytB 之分子量為 34 kDa

A Balanced Scorecard of Sustainable Management in the Taiwanese Bicycle Industry: Development of Performance Indicators and Importance Analysis

The main purpose of this study is to investigate the development of the performance indicators of sustainable management in the Taiwanese bicycle industry and to perform an importance analysis. Based on the Balanced Scorecard concept, the framework of sustainable management is added. Ten experts evaluated the performance indicators of a sustainable Balanced Scorecard in the Taiwanese bicycle industry using five major categories: (1) Financial, (2) Customer, (3) Internal Business Processes, (4) Learning and Growth, and (5) Sustainable Development, and a total of 21 performance indicators were used. The analytic network process (ANP) was used to perform an importance analysis of the various performance indicators. Most of the experts suggested that for the introduction of a sustainable management strategy into the bicycle industry in Taiwan, it is necessary to include the definition of sustainable management and to improve five performance indicators: innovation process, customer satisfaction, operations process, after-sales service, and market share. According to the analysis results, this study proposed relevant management definitions and suggestions to be used as important references for decision-makers to understand the introduction of sustainable management strategies to the current bicycle industry in Taiwan

The unfolded protein response is shaped by the NMD pathway.

Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), an essential adaptive intracellular pathway that relieves the stress. Although the UPR is an evolutionarily conserved and beneficial pathway, its chronic activation contributes to the pathogenesis of a wide variety of human disorders. The fidelity of UPR activation must thus be tightly regulated to prevent inappropriate signaling. The nonsense-mediated RNA decay (NMD) pathway has long been known to function in RNA quality control, rapidly degrading aberrant mRNAs, and has been suggested to regulate subsets of normal mRNAs. Here, we report that the NMD pathway regulates the UPR. NMD increases the threshold for triggering the UPR in vitro and in vivo, thereby preventing UPR activation in response to normally innocuous levels of ER stress. NMD also promotes the timely termination of the UPR. We demonstrate that NMD directly targets the mRNAs encoding several UPR components, including the highly conserved UPR sensor, IRE1α, whose NMD-dependent degradation partly underpins this process. Our work not only sheds light on UPR regulation, but demonstrates the physiological relevance of NMD's ability to regulate normal mRNAs