FAM129B, an antioxidative protein, reduces chemosensitivity by competing with Nrf2 for Keap1 binding.

BackgroundThe transcription factor Nrf2 is a master regulator of antioxidant response. While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy. Thus, Nrf2 has been considered as a key pharmacological target. Unfortunately, there are no specific Nrf2 inhibitors for therapeutic application. Moreover, high Nrf2 activity in many tumors without Keap1 or Nrf2 mutations suggests that alternative mechanisms of Nrf2 regulation exist.MethodsInteraction of FAM129B with Keap1 is demonstrated by immunofluorescence, colocalization, co-immunoprecipitation and mammalian two-hybrid assay. Antioxidative function of FAM129B is analyzed by measuring ROS levels with DCF/flow cytometry, Nrf2 activation using luciferase reporter assay and determination of downstream gene expression by qPCR and wester blotting. Impact of FAM129B on in vivo chemosensitivity is examined in mice bearing breast and colon cancer xenografts. The clinical relevance of FAM129B is assessed by qPCR in breast cancer samples and data mining of publicly available databases.FindingsWe have demonstrated that FAM129B in cancer promotes Nrf2 activity by reducing its ubiquitination through competition with Nrf2 for Keap1 binding via its DLG and ETGE motifs. In addition, FAM129B reduces chemosensitivity by augmenting Nrf2 antioxidative signaling and confers poor prognosis in breast and lung cancer.InterpretationThese findings demonstrate the important role of FAM129B in Nrf2 activation and antioxidative response, and identify FMA129B as a potential therapeutic target. FUND: The Chang Gung Medical Foundation (Taiwan) and the Ministry of Science and Technology (Taiwan)

The Importance of Mindfulness in the Achievement of Optimal Functioning: Conceptualization for Research Development

The concept of ‘optimal functioning’ has emerged as a major line of research development in educational psychology. Optimal functioning, which reflects the paradigm of positive psychology, is concerned with a person’s achievement of maximization in his/her functioning, whether it is mental, cognitive, emotional, or social. This inquiry places strong emphasis on importance of flourishing, happiness, and the proactivity of human endeavors. An important question then for consideration, from this testament, is how researchers optimize the achievement of optimal functioning. We have recently made progress by focusing on empirical research development and methodological conceptualizations into the study of optimization. Our conceptualizations, collectively, contend that there are psychological, educational, and psychosocial variables that operate as sources of ‘energization’, which then stimulate the buoyancy of motivation, personal resolve, effective functioning, strength, and effort expenditure. Energization, in its totality, from our postulation, may then arouse, intensify, and sustain a person’s internal state of functioning. Our cross-institutional, cross-cultural research collaboration (e.g., Australia, Malaysia, and Taiwan), to date, has considered one notably construct that could serve as a source of internal energization for the achievement of functioning: mindfulness. We strongly believe that the totality of mindfulness, positive in nature, could play a central role in the psychological processes of human agency

Abnormal Mammary Gland Development and Growth Retardation in Female Mice and MCF7 Breast Cancer Cells Lacking Androgen Receptor

Phenotype analysis of female mice lacking androgen receptor (AR) deficient (AR−/−) indicates that the development of mammary glands is retarded with reduced ductal branching in the prepubertal stages, and fewer Cap cells in the terminal end buds, as well as decreased lobuloalveolar development in adult females, and fewer milk-producing alveoli in the lactating glands. The defective development of AR−/− mammary glands involves the defects of insulin-like growth factor I–insulin-like growth factor I receptor and mitogen-activated protein kinase (MAPK) signals as well as estrogen receptor (ER) activity. Similar growth retardation and defects in growth factor–mediated Ras/Raf/MAPK cascade and ER signaling are also found in AR−/− MCF7 breast cancer cells. The restoration assays show that AR NH2-terminal/DNA-binding domain, but not the ligand-binding domain, is essential for normal MAPK function in MCF7 cells, and an AR mutant (R608K), found in male breast cancer, is associated with the excessive activation of MAPK. Together, our data provide the first in vivo evidence showing that AR-mediated MAPK and ER activation may play important roles for mammary gland development and MCF7 breast cancer cell proliferation

Predicting and enhancing students' positive emotions: An empirical study from a Taiwanese sociocultural context

Predicting and enhancing positive emotions, reflecting the tenets of positive psychology, is of considerable importance for educators. Positive emotions may consist of a person's indication of happiness, joy, and love. In school and university settings, as research has shown, positive emotions play a pivotal role in helping students adjust, make friends, and engage in proactive social relationships with others. It is imperative for us to consider the design and development of educational programs that could assist in the facilitation of positive emotions. The present study involved examination of an inquiry into the prediction of positive emotion of university students, via means of data drawn from Taiwan. The main question for consideration is to determine the extent to which both social (e.g., the social milieu) and personal (e.g., personal resolve) influences could predict positive emotions. Structural equation modelling yielded support for our proposed a priori model: (a) the direct predictive effects of the social milieu, personal resolve, relating to others, and academic liking experience, and (b) the potential mediating roles of relating to others, and academic liking experience. Overall, the concept of emotions plays a central role and is accounted for by different types of personal and social contextual influences

Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake

Recent work on sprite spectrum in Taiwan

campaigns in Taiwan. We first introduce two types of spectroimagers, the slit and slitless types, and discuss their advantages and shortcomings. Next we explore the instrument development and procedures undertaken for this study. In 2006, a slit spectroimager was installed for a sprite campaign and on 15 August of that year, two sprite spectra were recorded using the slit spectroimager along with seven sprites, one halo, one ELVES emission and two jets. By the end of 2015, a slitless spectroimager had been successfully constructed and was ready to conduct additional investigations. On 7 May 2016, a sprite spectrum was recorded using the slitless spectroimager. Following an examination of the calibrations (comprising detection region field of view, wavelength calibration, and response curve), data analysis, and additional calibrations (comprising elevation and azimuthal angles, atmospheric transmittance, and theoretical wavelength calculations) performed in this study, we present the results from our observed sprite spectra using the slit and slitless spectroimagers

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

Abnormal Mitochondrial Function and Impaired Granulosa Cell Differentiation in Androgen Receptor Knockout Mice

In the ovary, the paracrine interactions between the oocyte and surrounded granulosa cells are critical for optimal oocyte quality and embryonic development. Mice lacking the androgen receptor (AR−/−) were noted to have reduced fertility with abnormal ovarian function that might involve the promotion of preantral follicle growth and prevention of follicular atresia. However, the detailed mechanism of how AR in granulosa cells exerts its effects on oocyte quality is poorly understood. Comparing in vitro maturation rate of oocytes, we found oocytes collected from AR−/− mice have a significantly poor maturating rate with 60% reached metaphase II and 30% remained in germinal vesicle breakdown stage, whereas 95% of wild-type AR (AR+/+) oocytes had reached metaphase II. Interestingly, we found these AR−/− female mice also had an increased frequency of morphological alterations in the mitochondria of granulosa cells with reduced ATP generation (0.18 ± 0.02 vs. 0.29 ± 0.02 µM/mg protein; p < 0.05) and aberrant mitochondrial biogenesis. Mechanism dissection found loss of AR led to a significant decrease in the expression of peroxisome proliferator-activated receptor γ (PPARγ) co-activator 1-β (PGC1-β) and its sequential downstream genes, nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), in controlling mitochondrial biogenesis. These results indicate that AR may contribute to maintain oocyte quality and fertility via controlling the signals of PGC1-β-mediated mitochondrial biogenesis in granulosa cells

Effects of Temperature, Alkali Source, and Mg/Al Ratio on Phase Purity and Yield of Hydrothermal Synthesized Smectites

Smectites are a major type of clay minerals. Hydrothermally synthesized smectites have become a major research topic because of the unstable quality or excessive impurity of natural smectites. The high-phase purity and yield of hydrothermally synthesized smectites are vital in advanced industries and materials applications. In this study, a Taguchi orthogonal array was integrated with eight factors to avoid biased experimental results, thus creating relatively robust factor portfolios to investigate the effects of temperature, alkali sources, and the magnesium (Mg)/aluminum (Al) ratio on the phase purity and yield of hydrothermally synthesized smectites. The synthesized environment was mainly established using trioctahedral smectites based on the formula Na2x(Al2(1−x)Mg2x□)Si4O10(OH)2X-ray diffraction and Rietveld refinement were used for the quantitative analysis of the products’ mineral facies and calculating the synthesized smectites’ phase purity and yield. The Taguchi method was employed to calculate each factor’s effect on the product quality. The results indicated that among the numerous factor portfolios, a relatively high temperature, ammonia solution as the alkali source, and a relatively high Mg/Al ratio were conducive to enhanced phase purity and yield of synthesized smectites. The optimized products of the synthesized smectites achieved a phase purity of 92.5% and a yield of 88.3%