Loss of BCAA Catabolism during Carcinogenesis Enhances mTORC1 Activity and Promotes Tumor Development and Progression

Tumors display profound changes in cellular metabolism, yet how these changes aid the development and growth of tumors is not fully understood. Here we use a multi-omic approach to examine liver carcinogenesis and regeneration, and find that progressive loss of branched-chain amino acid (BCAA) catabolism promotes tumor development and growth. In human hepatocellular carcinomas and animal models of liver cancer, suppression of BCAA catabolic enzyme expression led to BCAA accumulation in tumors, though this was not observed in regenerating liver tissues. The degree of enzyme suppression strongly correlated with tumor aggressiveness, and was an independent predictor of clinical outcome. Moreover, modulating BCAA accumulation regulated cancer cell proliferation in vitro, and tumor burden and overall survival in vivo. Dietary BCAA intake in humans also correlated with cancer mortality risk. In summary, loss of BCAA catabolism in tumors confers functional advantages, which could be exploited by therapeutic interventions in certain cancers

Comparison of IRES and F2A-Based Locus-Specific Multicistronic Expression in Stable Mouse Lines

Efficient and stoichiometric expression of genes concatenated by bi- or multi-cistronic vectors has become an invaluable tool not only in basic biology to track and visualize proteins in vivo, but also for vaccine development and in the clinics for gene therapy. To adequately compare, in vivo, the effectiveness of two of the currently popular co-expression strategies - the internal ribosome entry site (IRES) derived from the picornavirus and the 2A peptide from the foot-and-mouth disease virus (FDMV) (F2A), we analyzed two locus-specific knock-in mouse lines co-expressing SRY-box containing gene 9 (Sox9) and enhanced green fluorescent protein (EGFP) linked by the IRES (Sox9IRES-EGFP) or the F2A (Sox9F2A-EGFP) sequence. Both the constructs expressed Sox9 and EGFP proteins in the appropriate Sox9 expression domains, with the IRES construct expressing reduced levels of EGFP compared to that of the F2A. The latter, on the other hand, produced about 42.2% Sox9-EGFP fusion protein, reflecting an inefficient ribosome ‘skipping’ mechanism. To investigate if the discrepancy in the ‘skipping’ process was locus-dependent, we further analyzed the FLAG3-Bapx1F2A-EGFP mouse line and found similar levels of fusion protein being produced. To assess if EGFP was hindering the ‘skipping’ mechanism, we examined another mouse line co-expressing Bagpipe homeobox gene 1 homolog (Bapx1), Cre recombinase and EGFP (Bapx1F2A-Cre-F2A-EGFP). While the ‘skipping’ was highly efficient between Bapx1 and Cre, the ‘skipping’ between Cre and EGFP was highly inefficient. We have thus demonstrated in our comparison study that the efficient and close to equivalent expression of genes linked by F2A is achievable in stable mouse lines, but the EGFP reporter may cause undesirable inhibition of the ‘skipping’ at the F2A sequence. Hence, the use of other reporter genes should be explored when utilizing F2A peptides

Regionalisation of food & beverage industry to Southeast Asia

114 p.This study discusses the reasons for Singapore food and beverage companies expanding overseas, commonly faced obstacles, factors that contribute to success, key sources in financing the expansion and the extent of government aid used by the companies.ACCOUNTANC

Excessive use of social networking sites and financial well-being among working millennials : a parallel-serial mediation model

Purpose This study aimed to investigate the mediating role of financial attitude and perceived behavioral control with financial behavior in the association between excessive use of social networking sites (SNSs) and financial well-being among working millennials. Design/methodology/approach A crossed-sectional survey was used to obtain data through a self-administered questionnaire. A total of 485 working millennials (M age = 32.28, years, SD age = 4.75) in Malaysia participated in the study based on a purposive sampling technique. Covariance-based structural equation modeling (CB-SEM) was used to evaluate the measurement model and the proposed serial mediation model. Findings The findings of this study revealed that excessive use of SNS is negatively associated with financial well-being. Also, the findings suggested that financial attitude and perceived behavioral with financial behavior serially mediated the negative relationship between excessive use of SNS and financial well-being, respectively. Practical implications Several implications were suggested and discussed to prevent the negative impact of excessive SNS use on financial well-being among young working adults. Policymakers and financial service providers (e.g. banks) can draw from the findings by constantly framing and delivering their messages to increase the young working adults' awareness of pitfalls of excessive use of innovative technologies on their financial attitudes and self-control over their behaviors and financial well-being. Originality/value This study entails some new insights on examining the impact of excessive use of SNS on working millennials' financial well-being as well as the underlying mechanisms behind this phenomeno

A developmental transcriptomic analysis of Pax1 and Pax9 in embryonic intervertebral disc development.

Pax1 and Pax9 play redundant, synergistic functions in the patterning and differentiation of the sclerotomal cells that give rise to the vertebral bodies and intervertebral discs (IVD) of the axial skeleton. They are conserved in mice and humans, whereby mutation/deficiency of human PAX1/PAX9 has been associated with kyphoscoliosis. By combining cell-type-specific transcriptome and ChIP-sequencing data, we identified the roles of Pax1/Pax9 in cell proliferation, cartilage development and collagen fibrillogenesis, which are vital in early IVD morphogenesis. Pax1 is up-regulated in the absence of Pax9, while Pax9 is unaffected by the loss of Pax1/Pax9 We identified the targets compensated by a single- or double-copy of Pax9 They positively regulate many of the cartilage genes known to be regulated by Sox5/Sox6/Sox9 and are connected to Sox5/Sox6 by a negative feedback loop. Pax1/Pax9 are intertwined with BMP and TGF-B pathways and we propose they initiate expression of chondrogenic genes during early IVD differentiation and subsequently become restricted to the outer annulus by the negative feedback mechanism. Our findings highlight how early IVD development is regulated spatio-temporally and have implications for understanding kyphoscoliosis. Biol Open 2017 Feb 15; 6(2):187-199

Cyberbullying Detection Based on Emotion

Due to the detrimental consequences caused by cyberbullying, a great deal of research has been undertaken to propose effective techniques to resolve this reoccurring problem. The research presented in this paper is motivated by the fact that negative emotions can be caused by cyberbullying. This paper proposes cyberbullying detection models that are trained based on contextual, emotions and sentiment features. An Emotion Detection Model (EDM) was constructed using Twitter datasets that have been improved in terms of its annotations. Emotions and sentiment were extracted from cyberbullying datasets using EDM and lexicons based. Two cyberbullying datasets from Wikipedia and Twitter respectively were further improved by comprehensive annotation of emotion and sentiment features. The results show that anger, fear and guilt were the major emotions associated with cyberbullying. Subsequently, the extracted emotions were used as features in addition to contextual and sentiment features to train models for cyberbullying detection. The results demonstrate that using emotion features and sentiment has improved the performance of detecting cyberbullying by 0.5 to 0.6 recall. The proposed models also outperformed the state-of-the-art models by a 0.7 f1-score. The main contribution of this work is two-fold, which includes a comprehensive emotion-annotated dataset for cyberbullying detection, and an empirical proof of emotions as effective features for cyberbullying detection

An Integrative Developmental Genomics and Systems Biology Approach to Identify an In Vivo Sox Trio-Mediated Gene Regulatory Network in Murine Embryos.

Embryogenesis is an intricate process involving multiple genes and pathways. Some of the key transcription factors controlling specific cell types are the Sox trio, namely, Sox5, Sox6, and Sox9, which play crucial roles in organogenesis working in a concerted manner. Much however still needs to be learned about their combinatorial roles during this process. A developmental genomics and systems biology approach offers to complement the reductionist methodology of current developmental biology and provide a more comprehensive and integrated view of the interrelationships of complex regulatory networks that occur during organogenesis. By combining cell type-specific transcriptome analysis and in vivo ChIP-Seq of the Sox trio using mouse embryos, we provide evidence for the direct control of Sox5 and Sox6 by the transcriptional trio in the murine model and by Morpholino knockdown in zebrafish and demonstrate the novel role of Tgfb2, Fbxl18, and Tle3 in formation of Sox5, Sox6, and Sox9 dependent tissues. Concurrently, a complete embryonic gene regulatory network has been generated, identifying a wide repertoire of genes involved and controlled by the Sox trio in the intricate process of normal embryogenesis