National Science Education Standards

Evaluating Model Fit

Cells transmit information through molecular signals that often show complex dynamical patterns. The dynamic behavior of the tumor suppressor p53 varies depending on the stimulus; in response to double-strand DNA breaks, it shows a series of repeated pulses. Using a computational model, we identified a sequence of precisely timed drug additions that alter p53 pulses to instead produce a sustained p53 response. This leads to the expression of a different set of downstream genes and also alters cell fate: Cells that experience p53 pulses recover from DNA damage, whereas cells exposed to sustained p53 signaling frequently undergo senescence. Our results show that protein dynamics can be an important part of a signal, directly influencing cellular fate decisions.

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p53 dynamics control cell fate.

Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli. Crosstalk and commonly identified mutations that occur within these pathways that contribute to abnormal activation and cancer growth will also be addressed. Finally the recently described roles of these pathways in cancer stem cells, cellular senescence and aging will be evaluated. Controlling the expression of these pathways could ameliorate human health.

/pdf/roles-of-the-raf-mek-erk-and-pi3k-pten-akt-mtor-pathways-in-2me5en3kzv.pdf

Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging

LETTERS to the EDITORPhilosophy of science

Cellular senescence, the limited ability of cultured normal cells to divide, can result from cellular damage triggered through oncogene activation (premature senescence) or the loss of telomeres following successive rounds of DNA replication (replicative senescence). Although both processes require a functional p53 signaling pathway, relevant downstream p53 targets have been difficult to identify. Discovery of senescence activators is important because induction of tumor cell senescence may represent a therapeutic approach for the treatment of cancer. In microarray studies in which p53 was reactivated in MCF7 cells, we discovered that Yippee-like-3 (YPEL3), a member of a recently discovered family of putative zinc finger motif coding genes consisting of YPEL1-5, is a p53-regulated gene. YPEL3 expression induced by DNA damage leads to p53 recruitment to a cis-acting DNA response element located near the human YPEL3 promoter. Physiologic induction of YPEL3 results in a substantial decrease in cell viability associated with an increase in cellular senescence. Through the use of RNAi and H-ras induction of cellular senescence, we show that YPEL3 activates cellular senescence downstream of p53. Consistent with its growth suppressive activity, YPEL3 gene expression is repressed in ovarian tumor samples. One mechanism of YPEL3 downregulation in ovarian tumor cell lines seems to be hypermethylation of a CpG island upstream of the YPEL3 promoter. We believe these findings point to YPEL3 being a novel tumor suppressor, which upon induction triggers a permanent growth arrest in human tumor and normal cells.

https://cancerres.aacrjournals.org/content/canres/70/9/3566.full.pdf

YPEL3, a p53-regulated gene that induces cellular senescence.

This article describes revisions to four of the eight constructs of the Duncan molecular genetics learning progression [Duncan, Rogat, & Yarden, (2009)]. As learning progressions remain hypothetical models until validated by multiple rounds of empirical studies, these revisions are an important step toward validating the progression. Our revisions are based on empirical data obtained from tenth grade students in three classroom contexts (n = 121); although our study was done with students at the upper bounds of the progression, students held naive ideas prior to instruction which allowed us to track their ideas through all the levels of each construct during the course of one academic year. We revised the four constructs that center around the molecular model of genetics using students’ pre/post assessments and interviews. We found that tenth grade students do hold ideas consistent with the hypothesized levels in the progression as well as several intermediate ideas not included. Our revisions include adding student ideas that are important conceptual stepping stones in each construct as well as other modifications such as splitting and combining levels, moving ideas to other constructs, changing the conceptual progression of a construct and splitting a construct. Along with the revisions, we identified challenges in each construct. Even after instruction, students had difficulties understanding that genes code for proteins, that proteins connect genes and traits, and how differential gene expression leads to different repertoires of proteins inside of specialized cells. Our findings indicate that classroom instruction should focus more on proteins: how they are created, what their functions are, and how cells express different proteins.

Empirical refinements of a molecular genetics learning progression: The molecular constructs

We validate the Measure of Acceptance of the Theory of Evolution (MATE) on undergraduate students using the Rasch model and utilize the MATE to explore qualitatively how students express their acceptance of evolution. At least 24 studies have used the MATE, most with the assumption that it is unidimensional. However, we found that the MATE is best used as two separate dimensions. When used in this way, the MATE produces reliable (α > 0.85) measures for (i) acceptance of evolution facts and data and (ii) acceptance of the credibility of evolution and rejection of non-scientific ideas. Using k-means cluster analysis, we found students express their acceptance of evolution in five distinct profiles: (i) uniform high acceptance; (ii) uniform moderate acceptance; (iii) neutral acceptance; (iv) acceptance of facts, but rejection of credibility; and (v) rejection of both facts and credibility. Furthermore, we found that knowledge of macroevolution moderately explains students’ acceptance profiles, corroborating previous claims that teaching macroevolution may be one way to improve students’ acceptance. We use these findings to express the first set of operational definitions of evolution acceptance and propose that educators continue to explore additional ways to operationalize evolution acceptance. © 2017 Wiley Periodicals, Inc. J Res Sci Teach 54:642–671, 2017

Understanding patterns of evolution acceptance—A new implementation of the Measure of Acceptance of the Theory of Evolution (MATE) with Midwestern university students

We describe the development, validation, and use of the Learning Progression-Based Assessment of Modern Genetics (LPA-MG) in a high school biology context. Items were constructed based on a current learning progression framework for genetics (Shea & Duncan, 2013; Todd & Kenyon, 2015). The 34-item instrument, which was tied to 12 constructs within the genetics learning progression, was administered to 65 high school students at three time points (pre, middle, and post) across a 23-week period of instruction. The LPA-MG, its 12 constructs, and 34 items demonstrated high reliability and construct validity with respect to the Rasch model and indicated by satisfactory fit. Furthermore, it demonstrated utility in providing both quantitative and qualitative information about how students moved along each construct. Using a repeated measures ANOVA design, we found that students made gains across the 23 weeks that were both large and significant at the 95% confidence level. Students also moved along each construct in qualitatively meaningful ways during the 23 weeks of instruction.

Development and Validation of the Learning Progression–Based Assessment of Modern Genetics in a High School Context

We developed and validated a new instrument, called Measuring Concept progressions in Acid–Base chemistry (MCAB) and used it to better understand the progression of undergraduate students’ understandings about acid–base chemistry. Items were developed based on an existing learning progression for acid–base chemistry. We used the Rasch rating scale model for validation and to gain understanding of how students at different ability levels conceptualize the topic. We then used latent class analysis (LCA) to place students into concept classes. We found that three concept classes were sufficient to describe students’ various response patterns and that these concept classes described a progression of understanding related to acid–base chemistry. All items fit well with the Rasch model. The final 33-item instrument measured students along a continuous scale with a reliability of 0.74 and categorized students with a precision of 0.89. All students possessed nonscientific understandings of pH and the pH scale. However, even the most novice students displayed basic scientific understandings about how acid–base indicators work and the Arrhenius model of acids and bases. We discuss the utility of Rasch and LCA procedures for analysis of learning progression-based assessments and suggest a simple algorithm that can be used to help chemistry instructors diagnose students’ misconceptions.

Amber Todd

Papers

YPEL3, a p53-regulated gene that induces cellular senescence.

Empirical refinements of a molecular genetics learning progression: The molecular constructs

Understanding patterns of evolution acceptance—A new implementation of the Measure of Acceptance of the Theory of Evolution (MATE) with Midwestern university students

Development and Validation of the Learning Progression–Based Assessment of Modern Genetics in a High School Context

How Do Undergraduate Students Conceptualize Acid–Base Chemistry? Measurement of a Concept Progression