Search

Self-renewal and pluripotency are two fundamental characteristics of embryonic stem cells (ESCs) and are controlled by diverse regulatory factors, including pluripotent factors, epigenetic regulators and microRNAs (miRNAs). Although histone methyltransferases are key epigenetic regulators, whether and how a histone methyltransferase forms a network with miRNAs and the core pluripotent factor system to regulate ESC stemness is little known. Here, we show that the protein arginine methyltransferase 7 (PRMT7) is a pluripotent factor essential for the stemness of mouse ESCs. PRMT7 repressed the miR-24-2 gene encoding miR-24-3p and miR-24-2-5p by upregulating the levels of symmetrically dimethylated H4R3. Notably, miR-24-3p targeted the 3′ untranslated regions (UTRs) of the major pluripotent factors Oct4, Nanog, Klf4 and c-Myc, whereas miR-24-2-5p silenced Klf4 and c-Myc expression. miR-24-3p and miR-24-2-5p also targeted the 3′UTR of their repressor gene Prmt7. miR-24-3p and miR-24-2-5p induced mouse ESC differentiation, and their anti-sense inhibitors substantially reversed spontaneous differentiation of PRMT7-depleted mouse ESCs. Oct4, Nanog, Klf4 and c-Myc positively regulated Prmt7 expression. These findings define miR-24-3p and miR-24-2-5p as new anti-pluripotent miRNAs and also reveal a novel epigenetic stemness-regulatory mechanism in which a double-negative feedback loop consisting of PRMT7 and miR-24-3p/miR24-2-5p interplays with Oct4, Nanog, Klf4 and c-Myc to control ESC stemness.

Histone acetylation, including acetylated H3K14 (H3K14ac), is generally linked to gene activation. Monomethylated histone H3 lysine 4 (H3K4me1), together with other gene-activating marks, denotes active genes. In contrast to usual gene-activating can function of H3K14ac and H3K4me1, we here show that the dual histone modification mark H3K4me1-H3K14ac is recognized by ZMYND8 (also called RACK7) and can function to counteract gene expression. We identified ZMYND8 as a transcriptional corepressor of the H3K4 demethylase JARID1D. ZMYND8 antagonized the expression of metastasis-linked genes, and its knockdown increased the cellular invasiveness in vitro and in vivo. The plant homeodomain (PHD) and Bromodomain cassette in ZMYND8 mediated the combinatorial recognition of H3K4me1-H3K14ac and H3K4me0-H3K14ac by ZMYND8. These findings uncover an unexpected role for the signature H3K4me1-H3K14ac in attenuating gene expression and reveal a previously unknown metastasis-suppressive epigenetic mechanism in which ZMYND8’s PHD-Bromo cassette couples H3K4me1-H3K14ac with downregulation of metastasis-linked genes.

The stemness maintenance of embryonic stem cells (ESCs) requires pluripotency transcription factors, including Oct4, Nanog, and Sox2. We have previously reported that protein arginine methyltransferase 7 (PRMT7), an epigenetic modifier, is an essential pluripotency factor that maintains the stemness of mouse ESCs, at least in part, by down-regulating the expression of the anti-stemness microRNA (miRNA) miR-24-2. To gain greater insight into the molecular basis underlying PRMT7-mediated maintenance of mouse ESC stemness, we searched for new PRMT7-down-regulated anti-stemness miRNAs. Here, we show that miR-221 gene–encoded miR-221-3p and miR-221-5p are anti-stemness miRNAs whose expression levels in mouse ESCs are directly repressed by PRMT7. Notably, both miR-221-3p and miR-221-5p targeted the 3′ untranslated regions of mRNA transcripts of the major pluripotency factors Oct4, Nanog, and Sox2 to antagonize mouse ESC stemness. Moreover, miR-221-5p silenced also the expression of its own transcriptional repressor PRMT7. Transfection of miR-221-3p and miR-221-5p mimics induced spontaneous differentiation of mouse ESCs. CRISPR-mediated deletion of the miR-221 gene, as well as specific antisense inhibitors of miR-221-3p and miR-221-5p, inhibited the spontaneous differentiation of PRMT7-depleted mouse ESCs. Taken together, these findings reveal that the PRMT7-mediated repression of miR-221-3p and miR-221-5p expression plays a critical role in maintaining mouse ESC stemness. Our results also establish miR-221-3p and miR-221-5p as anti-stemness miRNAs that target Oct4, Nanog, and Sox2 mRNAs in mouse ESCs.

The serine/threonine kinase Akt plays a central role in cell proliferation, survival and metabolism, and its hyperactivation is linked to cancer progression. Here we report that Akt undergoes K64 methylation by SETDB1, which is crucial for cell membrane recruitment, phosphorylation and activation of Akt following growth factor stimulation. Furthermore, we reveal an adaptor function of histone demethylase JMJD2A, which is important for recognizing Akt K64 methylation and recruits E3 ligase TRAF6 and Skp2-SCF to the Akt complex, independently of its demethylase activity, thereby initiating K63-linked ubiquitination, cell membrane recruitment and activation of Akt. Notably, the cancer-associated Akt mutant E17K displays enhanced K64 methylation, leading to its hyper-phosphorylation and activation. SETDB1-mediated Akt K64 methylation is upregulated and correlated with Akt hyperactivation in non-small-cell lung carcinoma (NSCLC), promotes tumour development and predicts poor outcome. Collectively, these findings reveal complicated layers of Akt activation regulation coordinated by SETDB1-mediated Akt K64 methylation to drive tumorigenesis. Wang et al. show that Akt methylation by SETDB1 is recognized by demethylase JMJD2A, which then recruits E3 ligases to induce K63-linked Akt ubiquitination, leading to Akt activation and tumorigenesis.

The development of a culture system for Chlorella sp. GD to efficiently produce biomass and oil for biodiesel production was investigated. Chlorella sp. GD was cultivated with 0%, 25%, 50%, 75% and 100% piggery wastewater (diluted by medium) at 300 μmol m(-2) s(-1), a 2% CO2 aeration rate of 0.2 vvm and 26±1°C; after a 10-day culture in batch cultures, the maximum specific growth rate and biomass productivity of the microalga obtained in 100% piggery wastewater were 0.839 d(-1) and 0.681 g L(-1) d(-1), respectively. The highest lipid content and lipid productivity were 29.3% and 0.155 g L(-1) d(-1) at 25% wastewater, respectively. In semi-continuous cultures, the biomass and lipid productivities with 25-75% wastewater ratios were greater than 0.852 and 0.128 g L(-1) d(-1), respectively. These results show that Chlorella sp. GD grows efficiently in piggery wastewater, and that a stable growth performance was achieved for long-term microalgal cultivation in a semi-continuous culture.

Using wastewater for microalgal cultures is beneficial for minimizing the use of freshwater, reducing the cost of nutrient addition, removing nitrogen and phosphorus from wastewater and producing microalgal biomass as bioresources for biofuel or high-value by-products. There are three main sources of wastewater, municipal (domestic), agricultural and industrial wastewater, which contain a variety of ingredients. Some components in the wastewater, such as nitrogen and phosphorus, are useful ingredients for microalgal cultures. In this review, the effects on the biomass and lipid production of microalgal Chlorella cultures using different kinds of wastewater were summarized. The use of the nutrients resource in wastewater for microalgal cultures was also reviewed. The effect of ammonium in wastewater on microalgal Chlorella growth was intensively discussed. In the end, limitations of wastewater-based of microalgal culture were commented in this review article.

In this work, a novel harvesting strategy using ferrofluids coupled with flocculation as a magnetic directional harvesting system was developed, providing a fast and easy way to effectively collect microalgae with no further modifications made to the ferrofluids. With a ferrofluid dosage of 25mgL-1, a high harvesting efficiency of 95-100% was achieved within 1min. In addition, we successfully performed a wastewater recycling strategy coupled with a microalgal ferrofluid-harvesting dynamic flow-through system to harvest biomass of Chlorella sp. MTF-7 which could achieve over 80% of the maximum level after three repeated recycling cultivations. This work demonstrated the use of an integrated microalgal ferrofluid-harvesting dynamic flow-through system to develop a simple and effective strategy to enhance microalgal harvesting efficiency, along with wastewater recycling, in a marine microalgal Chlorella sp. MTF-7.

Death receptor-mediated tumor cell death, either alone or in combination with other anticancer drugs, is considered as a new strategy for anticancer therapy. In this study, we have investigated the effects and molecular mechanisms of 5-aminoimidazole-4-carboxamide riboside [AICAR; a pharmacologic activator of AMP-activated protein kinase (AMPK)] in sensitizing tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL)– and TNFα-induced apoptosis of human colon cancer HCT116 cells. The cytotoxic action of AICAR requires AMPK activation and may occur at various stages of apoptotic pathways. AICAR cotreatment with either TRAIL or TNFα enhances activities of caspase-8, caspase-9, and caspase-3; down-regulates the antiapoptotic protein Bcl-2; increases the cleavage of Bid and results in the decrease of mitochondrial membrane potential; potentiates activation of p38 and c-Jun NH2-terminal kinase; and inhibits nuclear factor-κB activity. In addition, this sensitized cell apoptosis was neither observed in p53-null HCT116 cells nor affected by the cotreatment with mevalonate. In summary, we have developed a novel strategy of combining AICAR with TRAIL for the treatment of colon cancer cells. The sensitization effect of AICAR in cell apoptosis was mediated through AMPK pathway, requires p53 activity, and involves mitochondria-dependent apoptotic cascades, p38 and c-Jun NH2-terminal kinase. [Mol Cancer Ther 2007;6(5):1562–71]

Entire or partial deletions of the male-specific Y chromosome are associated with tumorigenesis, but whether any male-specific genes located on this chromosome play a tumor-suppressive role is unknown. Here, we report that the histone H3 lysine 4 (H3K4) demethylase JARID1D (also called KDM5D and SMCY), a male-specific protein, represses gene expression programs associated with cell invasiveness and suppresses the invasion of prostate cancer cells in vitro and in vivo. We found that JARID1D specifically repressed the invasion-associated genes MMP1, MMP2, MMP3, MMP7, and Slug by demethylating trimethyl H3K4, a gene-activating mark, at their promoters. Our additional results demonstrated that JARID1D levels were highly downregulated in metastatic prostate tumors compared with normal prostate tissues and primary prostate tumors. Furthermore, the JARID1D gene was frequently deleted in metastatic prostate tumors, and low JARID1D levels were associated with poor prognosis in prostate cancer patients. Taken together, these findings provide the first evidence that an epigenetic modifier expressed on the Y chromosome functions as an anti-invasion factor to suppress the progression of prostate cancer. Our results also highlight a preclinical rationale for using JARID1D as a prognostic marker in advanced prostate cancer. Cancer Res; 76(4); 831–43. ©2016 AACR.

This study investigated the possible existence of causal links between anxiety and language learning difficulties by using the Foreign Language Classroom Anxiety Scale (FLCAS) (Horwitz, Horwitz, & Cope, 1986) to examine anxiety and the Foreign Language Screening Instrument for Colleges (FLSI-C) (Ganschow & Sparks, 1991) to explore learning difficulty variables. Factor analysis, correlation analysis, and stepwise multiple regression analysis of data provided by 1,187 college students learning English as a foreign language (EFL) in Taiwan indicate that English learning difficulties account for 36.80% of variance in anxiety. The results show that some anxious students have a history of English learning problems, obtain low grades, suffer difficulties with classroom learning, and exhibit poor developmental skills. The findings are used to discuss both theoretical and practical implications for foreign language anxiety.

The biomass and lipid productivity of Chlorella sp. MTF-15 cultivated using aeration with flue gases from a coke oven, hot stove or power plant in a steel plant of the China Steel Corporation in Taiwan were investigated. Using the flue gas from the coke oven, hot stove or power plant for cultivation, the microalgal strain obtained a maximum specific growth rate and lipid production of (0.827 d(-1), 0.688 g L(-1)), (0.762 d(-1), 0.961 g L(-1)), and (0.728 d(-1), 0.792 g L(-1)), respectively. This study demonstrated that Chlorella sp. MTF-15 could efficiently utilize the CO₂, NOX and SO₂ present in the different flue gases. The results also showed that the growth potential, lipid production and fatty acid composition of the microalgal strain were dependent on the composition of the flue gas and on the operating strategy deployed.

Ganschow and Sparks (1991), reckoning on the correctness of their Linguistic Coding Deficit/Difference Hypothesis (LCDH) to attribute the main source of foreign language learning difficulties to language- based problems, rather than to affective variables, attempted to extend its validity by devising a Foreign Language Screening Instrument for Colleges (FLSI-C) in the USA. The author of this study here proposes to test whether the hypothesis holds for language learning difficulties among Chinese-speaking college students learning English as a foreign language (FL) in Taiwan, and presents evidence for the following two propositions: (1) that a modified Chinese language version of the FLSI-C is a valid and reliable instrument, and (2) that the high-risk and no-risk students identified by the modified instrument differ on the Chinese Language Aptitude Test (CLAT) and, according to self-reports, on the Foreign Language Classroom Anxiety Scale (FLCAS) developed by Horwitz et al. These propositions are accordingly vindicated and lead the author to affirm the validity of the LCDH for interpreting difficulties encountered by Chinese college learners of English.

The ESP profession faces twin problems, namely the lack of teacher training programs in many areas of the world and the dissatisfaction with conventional theory-into-practice training models. In this paper, the author presents an ESP self-training model as a possible solution in part to these problems. A case study applying action research techniques was conducted to illustrate how a general English teacher, even in the absence of supervision, can develop ESP expertise through reflecting on and improving the performance of authentic teaching tasks in the ESP classroom. The study results confirmed that by systematic action research procedures entailing continuous participation in situational decision making and professional involvement in the disciplinary culture in which the learners in question communicate, an ESP practitioner can conceptualize appropriate notions for teaching approaches.

The study is focused on the asymmetric secondary freeform lens (ASFL) design for creating a low glared light-emitting diode (LED) street light. The lens is mounted on a chip on board (COB) LED as the new LED street light module to perform a non-axial symmetric light intensity distribution. The experimental results show that the street light can work without inclining lamps and reach Chinese National Standards (CNS) and Illuminating Engineering Society of North America (IESNA) standards at the same time.