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In the triple-negative subtype of breast cancer, for which treatment options are limited, overexpression of the MYC oncoprotein is associated with increased sensitivity to growth inhibition by fatty acid oxidation inhibitors, thus pointing to a new therapeutic strategy. Expression of the oncogenic transcription factor MYC is disproportionately elevated in triple-negative breast cancer (TNBC), as compared to estrogen receptor–, progesterone receptor– or human epidermal growth factor 2 receptor–positive (RP) breast cancer 1 , 2 . We and others have shown that MYC alters metabolism during tumorigenesis 3 , 4 . However, the role of MYC in TNBC metabolism remains mostly unexplored. We hypothesized that MYC-dependent metabolic dysregulation is essential for the growth of MYC-overexpressing TNBC cells and may identify new therapeutic targets for this clinically challenging subset of breast cancer. Using a targeted metabolomics approach, we identified fatty acid oxidation (FAO) intermediates as being dramatically upregulated in a MYC-driven model of TNBC. We also identified a lipid metabolism gene signature in patients with TNBC that were identified from The Cancer Genome Atlas database and from multiple other clinical data sets, implicating FAO as a dysregulated pathway that is critical for TNBC cell metabolism. We found that pharmacologic inhibition of FAO catastrophically decreased energy metabolism in MYC-overexpressing TNBC cells and blocked tumor growth in a MYC-driven transgenic TNBC model and in a MYC-overexpressing TNBC patient–derived xenograft. These findings demonstrate that MYC-overexpressing TNBC shows an increased bioenergetic reliance on FAO and identify the inhibition of FAO as a potential therapeutic strategy for this subset of breast cancer.

In triple-negative breast cancer, the PIM1 kinase is highly expressed, acts to promote tumor cell survival and growth, and increases MYC transcriptional activity. Triple-negative breast cancer (TNBC), in which cells lack expression of the estrogen receptor (ER), the progesterone receptor (PR) and the ERBB2 (also known as HER2) receptor, is the breast cancer subtype with the poorest outcome 1 . No targeted therapy is available against this subtype of cancer owing to a lack of validated molecular targets. We previously reported that signaling involving MYC—an essential, pleiotropic transcription factor that regulates the expression of hundreds of genes—is disproportionally higher in triple-negative (TN) tumors than in receptor-positive (RP) tumors 2 . Direct inhibition of the oncogenic transcriptional activity of MYC has been challenging to achieve 3 . Here, by conducting a shRNA screen targeting the kinome, we identified PIM1, a non-essential serine–threonine kinase, in a synthetic lethal interaction with MYC. PIM1 expression was higher in TN tumors than in RP tumors and was associated with poor prognosis in patients with hormone- and HER2-negative tumors. Small-molecule PIM kinase inhibitors halted the growth of human TN tumors with elevated MYC expression in patient-derived tumor xenograft (PDX) and MYC-driven transgenic mouse models of breast cancer by inhibiting the oncogenic transcriptional activity of MYC and restoring the function of the endogenous cell cycle inhibitor, p27. Our findings warrant clinical evaluation of PIM kinase inhibitors in patients with TN tumors that have elevated MYC expression.

Online educational videos have the potential to enhance undergraduate biology learning, for example by showcasing contemporary scientific research and providing content coverage. Here, we describe the integration of nine videos into a large‐enrollment (n = 356) introductory evolution and ecology course via weekly homework assignments. We predicted that videos that feature research stories from contemporary scientists could reinforce topics introduced in lecture and provide students with novel insights into the nature of scientific research. Using qualitative analysis of open‐ended written feedback from the students on each video assigned throughout the term (n = 133–229 responses per video) and on end‐of‐quarter evaluations (n = 243), we identified common categories of student perspectives. All videos received more positive than negative comments and all videos received comments indicating that students found them intellectually and emotionally stimulating, accessible, and relevant to course content. Additionally, all videos also received comments indicating some students found them intellectually unstimulating, though these comments were generally far less numerous than positive comments. Students responded positively to videos that incorporated at least one of the following: documentary‐style filming, very clear links to course content (especially hands‐on activities completed by the students), relevance to recent world events, clarity on difficult topics, and/or charismatic narrators or species. We discuss opportunities and challenges for the use of online educational videos in teaching ecology and evolution, and we provide guidelines instructors can use to integrate them into their courses. In this case study, we sought to evaluate student perceptions of freely available educational videos and how such videos may contribute to student learning goals. We report the use of nine online videos for teaching concepts and competencies in evolution and ecology in a large‐enrollment introductory biology course. We share the results of our case study and provide guidance for the use of online videos in teaching evolution and ecology in higher education.

Making sound food and agriculture decisions is important for global society and the environment. Experts tend to view crop genetic engineering, a technology that can improve yields and minimize impacts on the environment, more favorably than the public. Because there is a causal relationship between public opinion and public policy, it is important to understand how opinions about genetically engineered (GE) crops are influenced. The public increasingly seeks science information on the Internet. Here, semantic network analysis is performed to characterize the presentation of the term “GMO (genetically modified organism),” a proxy for food developed from GE crops, on the web. Texts from three sources are analyzed: U.S. federal websites, top pages from a Google search, and online news titles. We found that the framing and sentiment (positive, neutral, or negative attitudes) of “GMO” varies across these sources. It is described how differences in the portrayal of GE food by each source might affect public opinion. A current understanding of the types of information individuals may encounter online can provide insight into public opinion toward GE food. In turn, this knowledge can guide teaching and communication efforts by the scientific community to promote informed decision‐making about agricultural biotechnologies. Web results : A computational approach known as semantic network analysis is used to create visual representations of the way in which “GMO (genetically modified organism),” a proxy for genetically engineered (GE) food, is represented in distinct areas of the Internet. This study empirically shows that the presentation of GE food differs dramatically between sources, including Google search, news titles, and federal webpages.

Triple-negative breast cancer (TNBC), which lacks the expression of the estrogen, progesterone, and HER2 receptors, represents the breast cancer subtype with the poorest outcome1. No targeted therapy is available against this subtype due to lack of validated molecular targets. We previously reported that MYC signaling is disproportionally elevated in triple-negative (TN) tumors compared to receptor-positive (RP) tumors2. MYC is an essential, pleiotropic transcription factor that regulates the expression of hundreds of genes3. Direct inhibition of oncogenic MYC transcriptional activity has remained challenging4,5. The present study conducted an shRNA screen against all kinases to uncover novel MYC-dependent synthetic lethal combinations, and identified PIM1, a non-essential kinase. Here we demonstrate that PIM1 expression was elevated in TN tumors and was associated with poor prognosis in patients with hormone and HER2 receptor-negative tumors. Small molecule PIM kinase inhibitors halted the growth of human TN tumors with elevated MYC expression in patient-derived tumor xenograft (PDX) and MYC-driven transgenic breast cancer models by inhibiting oncogenic transcriptional activity of MYC while simultaneously restoring the function of the endogenous cell cycle inhibitor, p27. Our findings warrant clinical evaluation of PIM kinase inhibitors in patients with TN tumors that exhibit elevated MYC expression.

MYC overexpressing cells frequently exhibit increased dependence on uptake of glutamine and its conversion to glutamate. However, whether MYC shapes downstream glutamate utilization decisions in vivo is poorly understood. We employed integrated gene expression and metabolite profiling analyses to identify novel metabolic pathways that are altered in primary MYC-driven liver cancers. We identified six metabolic pathways deregulated in MYC-driven liver tumors, including glutathione metabolism. In primary, MYC-driven tumors, glutamine-derived carbons preferentially enter central carbon metabolism and proliferative metabolic pathways and have diminished incorporation into glutathione and its precursor metabolite. We find that protein expression of the rate-limiting enzyme of glutathione synthesis, GCLC, is suppressed in a MYC-dependent manner. We further show that GCLC is targeted by a MYC-induced microRNA, miR-18a. MiR-18a expression is elevated in human hepatocellular carcinoma (HCC) and correlates with altered glutathione pathway gene expression. Further, poorly differentiated human HCCs have low tumor glutathione levels. MYC-driven liver tumors compensate for loss of glutathione by upregulating several antioxidant regeneration pathways. However, MYC-driven liver tumors exhibit increased sensitivity to exogenous oxidative stress, as demonstrated by tumor-specific fat accumulation and cell death following treatment with the potent oxidant diquat. Thus, despite sufficient antioxidant capacity at baseline, MYC-driven liver tumors are sensitive to exogenous oxidative stress. In total, we show that MYC regulates glutamate utilization by attenuating glutathione production via miR-18a, leading to preferential shunting of glutamate toward proliferative metabolism in tumors and altering redox homeostasis mechanisms.

While work on the relationship between social media use and adolescent mental health has allowed for some progress, research in this area is still relatively new and shows mixed evidence. This is partly the consequence of a rapidly changing field, resulting in conceptualisation and measurement issues that hinder progress. Given the need for robust conceptualisation, the present study included five focus groups with 26 adolescents aged 11-15 in Northwest England, to understand their experiences, motivations, and perceptions of social media use, relating to mental health and wellbeing. Reflexive thematic analysis was used to analyse the transcripts. We developed five themes and 10 sub-themes. Young people discussed being present and connected on social media (theme A); identity formation and self-presentation (theme B); enjoyment and managing moods (theme C); exposure to risky content and relationships (theme D); and self-control (theme E). Across these themes three direct mental health and wellbeing outcomes were identified: social aspects, anxiety and self-esteem, plus two less clearly defined experiences around coping and self-control. Our findings also demonstrate the heterogeneity and multidimensionality of social media experience, and point to some possibly differences across age and gender. Overall, this study has contributed to our understanding of the salient dimensions and language to inform the development of an adolescent social media experience measure related to mental health.