Induction of IDH2 R140Q Mutation in Stem Cells with Doxycycline Increases Rate of Cell Death

From the Washington University Office of Undergraduate Research Digest (WUURD), Vol. 12, 05-01-2017. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Helen Human, Programs Manager and Assistant Dean in the College of Arts and Sciences Mentor: David Spence

Comparative Analysis of Glycoproteomic Software Using a Tailored Glycan Database

Glycoproteomics is a rapidly developing field, and data analysis has been stimulated by several technological innovations. As a result, there are many software tools from which to choose; and each comes with unique features that can be difficult to compare. This work presents a head-to-head comparison of five modern analytical software: Byonic, Protein Prospector, MSFraggerGlyco, pGlyco3, and GlycoDecipher. To enable a meaningful comparison, parameter variables were minimized. One potential confounding variable is the glycan database that informs glycoproteomic searches. We performed glycomic profiling of the samples and used the output to construct matched glycan databases for each software. Up to 19,000 glycopeptide spectra were identified across three replicates of wild-type SH-SY5Y cells. There was substantial overlap among most software for glycoproteins identified, locations of glycosites, and glycans, although Byonic reported a suspiciously large number of glycoproteins and glycosites of questionable reliability. We show that Protein Prospector identified the most glycopeptide spectrum matches with high agreement to known glycosites in UniProt. Overall, our results indicate that glycoproteomic searches should involve more than one software to generate confidence. It may be useful to consider software with peptide-first approaches and with glycan-first approaches

Supporting Performance in the Face of Age-Related Neural Changes: Testing Mechanistic Roles of Cognitive Reserve

Age impacts multiple neural measures and these changes do not always directly translate into alterations in clinical and cognitive measures. This partial protection from the deleterious effects of age in some individuals is referred to as cognitive reserve (CR) and although linked to variations in intelligence and life experiences, its mechanism is still unclear. Within the framework of a theoretical model we tested two potential mechanistic roles of CR to maintain task performance, neural reserve and neural compensation, in young and older adults using functional and structural MRI. Neural reserve refers to increased efficiency and/or capacity of existing functional neural resources. Neural compensation refers to the increased ability to recruit new, additional functional resources. Using structural and functional measures and task performance, the roles of CR were tested using path analysis. Results supported both mechanistic theories of CR and the use of our general theoretical model

Toward the Next Generation of Air Quality Monitoring Indicators

This paper introduces an initiative to bridge the state of scientific knowledge on air pollution with the needs of policymakers and stakeholders to design the "next generation" of air quality indicators. As a first step this initiative assesses current monitoring and modeling associated with a number of important pollutants with an eye toward identifying knowledge gaps and scientific needs that are a barrier to reducing air pollution impacts on human and ecosystem health across the globe. Four outdoor air pollutants were considered e particulate matter, ozone, mercury, and Persistent Organic Pollutants (POPs) e because of their clear adverse impacts on human and ecosystem health and because of the availability of baseline data for assessment for each. While other papers appearing in this issue will address each pollutant separately, this paper serves as a summary of the initiative and presents recommendations for needed investments to provide improved measurement, monitoring, and modeling data for policyrelevant indicators. The ultimate goal of this effort is to enable enhanced public policy responses to air pollution by linking improved data and measurement methods to decision-making through the development of indicators that can allow policymakers to better understand the impacts of air pollution and, along with source attribution based on modeling and measurements, facilitate improved policies to solve it. The development of indicators represents a crucial next step in this process

What Do Healthy Rural Economies Look Like in the U.S., and How Might Conservation Organizations Help Support Them?

Report of the 2012 Berkley Workshop Held at the Wingspread Conference Center, Racine,WI - July 201

Construct Validity of Cognitive Reserve in a Multiethnic Cohort: The Northern Manhattan Study

Cognitive reserve is a hypothetical construct that has been used to inform models of cognitive aging and is presumed to be indicative of life experiences that may mitigate the effects of brain pathology. The purpose of this study was to evaluate the construct validity of cognitive reserve by examining both its convergent and its discriminant validity across three different samples of participants using structural equation modeling. The cognitive reserve variables were found to correlate highly with one another (thereby providing evidence of convergent validity), but demanding tests of discriminant validity indicated that, in two of the samples, the cognitive reserve construct was highly related to an executive functioning construct

Task Difficulty Modulates Young-Old Differences in Network Expression

The extent of task-related fMRI activation can vary as a function of task difficulty. Also the efficiency or capacity of the brain networks underlying task performance can change with aging. We asked whether the expression of a network underlying task performance would differ as a function of task demand in old and young individuals. 26 younger and 23 older healthy adults performed a delayed item recognition task that used the response signal method to parametrically manipulate the extrinsic difficulty of the task by imposing five different deadlines for recognition response. Both age groups showed a speed-accuracy trade-off, but the younger group achieved greater discriminability at the longer deadlines. We identified a spatial pattern of fMRI activation during the probe phase whose expression increased as the response deadline shortened and the task became more difficult. This pattern was expressed to a greater degree by the old group at the long deadlines, when the task was easiest. By contrast, this pattern was expressed to a greater degree by the younger group at the short deadlines, when the task was hardest. This suggests reduced efficiency and capacity of this network in older subjects. These findings suggest that neuroimaging studies comparing task-related activation across groups with different cognitive abilities must be interpreted in light of the relative difficulty of the task for each group

Association of Childhood Lead Exposure with Adult Personality Traits and Lifelong Mental Health

Importance. Millions of adults now entering middle-age were exposed to high levels of lead, a developmental neurotoxin, as children. While childhood lead exposure has been linked to disrupted behavioral development, the long-term consequences for adult mental and behavioral health have not been fully characterized. Objective. To test the hypothesis that childhood lead exposure is associated with greater psychopathology across the life-course and with differences in adult personality. Design, Setting, and Participants. Prospective cohort study based on a population-representative 1972-73 birth cohort from New Zealand, the Dunedin Multidisciplinary Health and Development Study, followed to age 38 years. Exposure. Childhood lead exposure ascertained as blood-lead levels measured at age 11 years. Blood-lead levels were unrelated to family socioeconomic status. Main Outcomes and Measures. Primary outcomes were: adult mental disorder symptoms, assessed via clinical interview at ages 18, 21, 26, 32, and 38, and transformed through confirmatory factor analysis into continuous measures of General Psychopathology (the "p-factor") and Internalizing, Externalizing, and Thought Disorder symptoms (all standardized to M=100, SD=15); and adult personality, assessed via informant-report using the Big Five Personality Inventory (assessing Neuroticism, Extraversion, Openness-to-Experience, Agreeableness, and Conscientiousness) at ages 26, 32, and 38 (all scores standardized to M=0, SD=1). Hypotheses were formulated after data-collection; an analysis plan was posted in advance.Results. Of 1037 original participants, 579 (56%) were lead-tested at age 11 years (54% male). Mean blood-lead level was 11.08µg/dL (SD=4.96). After adjusting for study covariates, each 5µg/dL increase in childhood blood lead-level was associated with a 1.34-point increase in General Psychopathology (95%CI: 0.11, 2.57, P=.033), driven by Internalizing (b=1.41, 95%CI: 0.19, 2.62, P=.024) and Thought Disorder (b=1.30, 95%CI: 0.06, 2.54, P=.040) symptoms. Each 5µg/dL increase in childhood blood lead-level was also associated with a .10-SD increase in Neuroticism (95%CI:.02, .18, P=.016), a .09-SD decrease in Agreeableness (95%CI:.-.18, -.01, P=.033), and a .14-SD decrease in Conscientiousness (95%CI:.-.25, -.03, P=.010). Associations with informant-rated Extraversion and Openness-to-Experience were non-significant. Conclusion and Relevance. In this multi-decade, longitudinal study of lead-exposed children, higher childhood blood-lead level predicted greater psychopathology across the life-course and more problematic adult personality styles. Childhood lead exposure may have long-term consequences for adult mental health and personality <br/

The paradox of high greenness and poor health in rural Central Appalachia.

While many studies have found positive correlations between greenness and human health, rural Central Appalachia is an exception. The region has high greenness levels but poor health. The purpose of this commentary is to provide a possible explanation for this paradox: three sets of factors overwhelming or attenuating the health benefits of greenness. These include environmental (e.g., steep typography and limited access to green space used for outdoor recreation), social (e.g., chronic poverty, declining coal industry, and limited access to healthcare), and psychological and behavioral factors (e.g., perceptions about health behaviors, healthcare, and greenness). The influence of these factors on the expected health benefits of greenness should be considered as working hypotheses for future research. Policymakers and public health officials need to ensure that greenness-based interventions account for contextual factors and other determinants of health to ensure these interventions have the expected health benefits