Filtering by
- Member of: ASU Regents' Professors Open Access Works
- Member of: ASU Scholarship Showcase
Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]); and 2) genes that are frequently mutated in cancer and whose mutations are functionally important for the emergence of the cancer phenotype evolved within the past 1000 million years, and thus would exhibit an age distribution that is skewed to younger genes. In order to investigate these hypotheses we estimated the evolutionary ages of all human genes and then studied the probability of mutation and their biological function in relation to their age and genomic location for both normal germline and cancer contexts.
We observed that under a model of uniform random mutation across the genome, controlled for gene size, genes less than 500 MY were more frequently mutated in both cases. Paradoxically, causal genes, defined in the COSMIC Cancer Gene Census, were depleted in this age group. When we used functional enrichment analysis to explain this unexpected result we discovered that COSMIC genes with recessive disease phenotypes were enriched for DNA repair and cell cycle control. The non-mutated genes in these pathways are orthologous to those underlying stress-induced mutation in bacteria, which results in the clustering of single nucleotide variations. COSMIC genes were less common in regions where the probability of observing mutational clusters is high, although they are approximately 2-fold more likely to harbor mutational clusters compared to other human genes. Our results suggest this ancient mutational response to stress that evolved among prokaryotes was co-opted to maintain diversity in the germline and immune system, while the original phenotype is restored in cancer. Reversion to a stress-induced mutational response is a hallmark of cancer that allows for effectively searching “protected” genome space where genes causally implicated in cancer are located and underlies the high adaptive potential and concomitant therapeutic resistance that is characteristic of cancer.
Testing mediation models is critical for identifying potential variables that need to be targeted to effectively change one or more outcome variables. In addition, it is now common practice for clinicians to use multiple informant (MI) data in studies of statistical mediation. By coupling the use of MI data with statistical mediation analysis, clinical researchers can combine the benefits of both techniques. Integrating the information from MIs into a statistical mediation model creates various methodological and practical challenges. The authors review prior methodological approaches to MI mediation analysis in clinical research and propose a new latent variable approach that overcomes some limitations of prior approaches. An application of the new approach to mother, father, and child reports of impulsivity, frustration tolerance, and externalizing problems (N = 454) is presented. The results showed that frustration tolerance mediated the relationship between impulsivity and externalizing problems. The new approach allows for a more comprehensive and effective use of MI data when testing mediation models.
Rapid identification of facial expressions can profoundly affect social interactions, yet most research to date has focused on static rather than dynamic expressions. In four experiments, we show that when a non-expressive face becomes expressive, happiness is detected more rapidly anger. When the change occurs peripheral to the focus of attention, however, dynamic anger is better detected when it appears in the left visual field (LVF), whereas dynamic happiness is better detected in the right visual field (RVF), consistent with hemispheric differences in the processing of approach- and avoidance-relevant stimuli. The central advantage for happiness is nevertheless the more robust effect, persisting even when information of either high or low spatial frequency is eliminated. Indeed, a survey of past research on the visual search for emotional expressions finds better support for a happiness detection advantage, and the explanation may lie in the coevolution of the signal and the receiver.
Background: Medical and public health scientists are using evolution to devise new strategies to solve major health problems. But based on a 2003 survey, medical curricula may not adequately prepare physicians to evaluate and extend these advances. This study assessed the change in coverage of evolution in North American medical schools since 2003 and identified opportunities for enriching medical education.
Methods: In 2013, curriculum deans for all North American medical schools were invited to rate curricular coverage and perceived importance of 12 core principles, the extent of anticipated controversy from adding evolution, and the usefulness of 13 teaching resources. Differences between schools were assessed by Pearson’s chi-square test, Student’s t-test, and Spearman’s correlation. Open-ended questions sought insight into perceived barriers and benefits.
Results: Despite repeated follow-up, 60 schools (39%) responded to the survey. There was no evidence of sample bias. The three evolutionary principles rated most important were antibiotic resistance, environmental mismatch, and somatic selection in cancer. While importance and coverage of principles were correlated (r = 0.76, P < 0.01), coverage (at least moderate) lagged behind importance (at least moderate) by an average of 21% (SD = 6%). Compared to 2003, a range of evolutionary principles were covered by 4 to 74% more schools. Nearly half (48%) of responders anticipated igniting controversy at their medical school if they added evolution to their curriculum. The teaching resources ranked most useful were model test questions and answers, case studies, and model curricula for existing courses/rotations. Limited resources (faculty expertise) were cited as the major barrier to adding more evolution, but benefits included a deeper understanding and improved patient care.
Conclusion: North American medical schools have increased the evolution content in their curricula over the past decade. However, coverage is not commensurate with importance. At a few medical schools, anticipated controversy impedes teaching more evolution. Efforts to improve evolution education in medical schools should be directed toward boosting faculty expertise and crafting resources that can be easily integrated into existing curricula.
Mexican Americans are one of the largest and fastest growing ethnic groups in the United States, yet we have limited knowledge regarding changes (i.e., developmental trajectories) in cultural orientation based upon their exposure to the Mexican American and mainstream cultures. We examined the parallel trajectories of Mexican American and mainstream cultural values in a sample of 749 Mexican American adolescents (49% female) across assessments during the fifth grade (approximately 11 years of age), the seventh grade (approximately 13 years of age) and the tenth grade (approximately 16 years of age). We expected that these values would change over this developmental period and this longitudinal approach is more appropriate than the often used median split classification to identify distinct types of acculturation. We found four distinct acculturation trajectory groups: two trajectory groups that were increasing slightly with age in the endorsement of mainstream cultural values, one of which was relatively stable in Mexican American cultural values while the other was declining in their endorsement of these values; and two trajectory groups that were declining substantially with age in their endorsement of mainstream cultural values, one of which was also declining in Mexican American cultural values and the other which was stable in these values. These four trajectory groups differed in expected ways on a number of theoretically related cultural variables, but were not highly consistent with the median split classifications. The findings highlight the need to utilize longitudinal data to examine the developmental changes of Mexican American individual’s adaptation to the ethnic and mainstream culture in order to understand more fully the processes of acculturation and enculturation.
Cognitive theories in visual attention and perception, categorization, and memory often critically rely on concepts of similarity among objects, and empirically require measures of “sameness” among their stimuli. For instance, a researcher may require similarity estimates among multiple exemplars of a target category in visual search, or targets and lures in recognition memory. Quantifying similarity, however, is challenging when everyday items are the desired stimulus set, particularly when researchers require several different pictures from the same category. In this article, we document a new multidimensional scaling database with similarity ratings for 240 categories, each containing color photographs of 16–17 exemplar objects. We collected similarity ratings using the spatial arrangement method. Reports include: the multidimensional scaling solutions for each category, up to five dimensions, stress and fit measures, coordinate locations for each stimulus, and two new classifications. For each picture, we categorized the item's prototypicality, indexed by its proximity to other items in the space. We also classified pairs of images along a continuum of similarity, by assessing the overall arrangement of each MDS space. These similarity ratings will be useful to any researcher that wishes to control the similarity of experimental stimuli according to an objective quantification of “sameness.”
The Gratton effect, the observation that the size of the Stroop effect is larger following a congruent trial compared to an incongruent trial, is one pivotal observation in support of the conflict-monitoring hypothesis. Previous reports have demonstrated that non-conflict components, such as feature binding, also contribute to this effect. Critically, Schmidt and De Houwer (2011) report a flanker task and a button-press Stroop task suggesting that there is no conflict adaptation in the Gratton effect; it is entirely caused by feature binding. The current investigation attempts to replicate and extend this important finding across two experiments using a canonical four-choice Stroop task with vocal responses. In contrast to Schmidt and De Houwer, we observe reliable conflict adaptation after controlling for feature binding. We argue that the overall strength of conflict is critical for determining whether a conflict adaptation component will remain in the Gratton effect after explaining binding components.