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Defining the molecular networks that drive breast cancer has led to therapeutic interventions and improved patient survival. However, the aggressive triple-negative breast cancer subtype (TNBC) remains recalcitrant to targeted therapies because its molecular etiology is poorly defined. In this study, we used a forward genetic screen to discover an oncogenic network driving human TNBC. SCYL1, TEX14, and PLK1 (“STP axis”) cooperatively trigger degradation of the REST tumor suppressor protein, a frequent event in human TNBC. The STP axis induces REST degradation by phosphorylating a conserved REST phospho-degron and bridging REST interaction with the ubiquitin-ligase βTRCP. Inhibition of the STP axis leads to increased REST protein levels and impairs TNBC transformation, tumor progression, and metastasis. Expression of the STP axis correlates with low REST protein levels in human TNBCs and poor clinical outcome for TNBC patients. Our findings demonstrate that the STP-REST axis is a molecular driver of human TNBC.

Mobile devices have been increasingly utilized in informal learning because of their high degree of portability; mobile guide systems (or electronic guidebooks) have also been adopted in museum learning, including those that combine learning strategies and the general audio-visual guide systems. To gain a deeper understanding of the features and limitations of these guide systems in a museum-learning context and also to provide new designs that better guide learners in interacting with peers and exhibitions, in-depth exploration of learners' actual visits and analyses of their behavioural patterns is crucial. This study was based on empirical observation and analysis of the learning behaviours (recorded on video) of 65 elementary-school students who were placed into three groups: mobile guide with problem-solving strategy, audio-visual mobile guide and paper-based learning-sheet guide. By coding and analysing the video and conducting sequential analysis and frequency analysis of learning-related discussion content, behavioural interaction patterns were determined by which the features and limitations of the different types of guides were compared. Among the findings, it was discovered that the students in the problem-solving mobile guide group showed a higher level of two-way interactions with their peers and the exhibits, as well as more learning-related discussions. Relevant suggestions for teachers, researchers and guide-systems developers are also given.

Digital teaching portfolios have been proposed as an effective tool for teacher learning and professional development, but there is a lack of empirical evidence supporting their effectiveness. This study proposed the design of a structured digital portfolio equipped with multiple aids (e.g. self-assessment, peer assessment, discussion and journal writing) for the professional development of teachers. This study also empirically evaluated the reflection and professional development as demonstrated in digital teaching portfolios with multiple supporting measures. Forty-four in-service substitute teachers participated in a course of classroom assessment and used a Web-based portfolio system. Based on the framework of teacher reflective thinking developed by Sparks-Langer et al., we found that most teachers demonstrated moderate levels of reflection in their journals but only one-third of them showed the highest level of reflection. We also found that the professional knowledge of teachers about classroom assessment--as shown by their implementation of it--improved significantly during the construction of portfolios. The above findings also represent good evidence that digital portfolios with multiple aids are beneficial to teacher reflection and professional development.

MYC (also known as c-MYC) overexpression or hyperactivation is one of the most common drivers of human cancer. Despite intensive study, the MYC oncogene remains recalcitrant to therapeutic inhibition. MYC is a transcription factor, and many of its protumorigenic functions have been attributed to its ability to regulate gene expression programs (1-3). Notably, oncogenic MYC activation has also been shown to increase total RNA and protein production in many tissue and disease contexts (4-7). While such increases in RNA and protein production may endow cancer cells with pro-tumour hallmarks, this increase in synthesis may also generate new or heightened burden on MYC-driven cancer cells to process these macromolecules properly (8). Here we discover that the spliceosome is a new target of oncogenic stress in MYC-driven cancers. We identify BUD31 as a MYC-synthetic lethal gene in human mammary epithelial cells, and demonstrate that BUD31 is a component of the core spliceosome required for its assembly and catalytic activity. Core spliceosomal factors (such as SF3B1 and U2AF1) associated with BUD31 are also required to tolerate oncogenic MYC. Notably, MYC hyperactivation induces an increase in total precursor messenger RNA synthesis, suggesting an increased burden on the core spliceosome to process pre-mRNA. In contrast to normal cells, partial inhibition of the spliceosome in MYC-hyperactivated cells leads to global intron retention, widespread defects in pre-mRNA maturation, and deregulation of many essential cell processes. Notably, genetic or pharmacological inhibition of the spliceosome in vivo impairs survival, tumorigenicity and metastatic proclivity of MYC-dependent breast cancers. Collectively, these data suggest that oncogenic MYC confers a collateral stress on splicing, and that components of the spliceosome may be therapeutic entry points for aggressive MYC-driven cancers., To discover genes and cellular processes required to tolerate oncogenic MYC expression, we previously performed a genome-wide MYC-synthetic lethal screen in human mammary epithelial cells (HMECs) engineered with an inducible [...]

Proposes a Web-based collaborative inquiry learning system and describes a study of undergraduates at the National Taiwan Normal University based on a model system that investigated students' learning processes. Discusses the use of concept maps to anchor and represent knowledge during the inquiry process. (Author/LRW)

A computer-based concept mapping system was developed that provides two learning environments: "construct-by-self," where the system provides students with evaluation results and hints for feedback, and "construct-on-scaffold," where students also receive an incomplete concept map. The "construct-on-scaffold" had better effect for learning biology. Both are helpful for students completing their concept maps. (Author/AEF)

Our previous studies showed that administration of a subtoxic dose of acetaminophen (APAP) to female rats increased generation of carbon monoxide from dichloromethane, a metabolic reaction catalyzed mainly by cytochrome P450 (CYP) 2E1. In this study we examined the changes in metabolism and toxicity of APAP upon repeated administration. An intraperitoneal dose of APAP (500 mg/kg) alone did not increase aspartate aminotransferase, alanine aminotransferase, or sorbitol dehydrogenase activity in serum, but was significantly hepatotoxic when the rats had been pretreated with an identical dose of APAP 18 h earlier. The concentrations and disappearance of APAP and its metabolites in plasma were monitored for 8 h after the treatment. APAP pretreatment reduced the elevation of APAP-sulfate, but increased APAP-cysteine concentrations in plasma. APAP or APAP-glucuronide concentrations were not altered. Administration of a single dose of APAP 18 h before sacrifice increased microsomal CYP activities measured with p-nitrophenol, p-nitroanisole, and aminopyrine as probes. Expression of CYP2E1, CYP3A, and CYP1A proteins in the liver was also elevated significantly. The results suggest that administration of APAP at a subtoxic dose may result in an induction of hepatic CYP enzymes, thereby altering metabolism and toxicological consequences of various chemical substances that are substrates for the same enzyme system. Keywords:: acetaminophen, metabolic activation, cytochrome P450 (CYP), reactive metabolite, hepatotoxicity