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Computational systems biology approaches provide insights to understand complex molecular phenomena in living systems. Such understanding demands the need to systematically interrogate and review existing literature to refine and distil key molecular pathways. This paper explores a methodological process to identify key molecular pathways from systematic bioinformatics literature review. This process is used to identify molecular pathways for a ubiquitous molecular process in all plant biological systems: C1 metabolism and formaldehyde detoxification, specific to maize. The C1 metabolism is essential for all organisms to provide one-carbon units for methylation and other types of modifications, as well as for nucleic acid, amino acid, and other biomolecule syntheses. Formaldehyde is a toxic one-carbon molecule which is produced endogenously and found in the environment, and whose detoxification is an important part of C1 metabolism. This systematic review involves a five-part process: 1) framing of the research question; 2) literature collection based on a parallel search strategy; 3) relevant study selection based on search refinement; 4) molecular pathway identification; and 5) integration of key molecular pathway mechanisms to yield a well-defined set molecular systems associated with a particular biochemical function. Findings from this systematic review produced three main molecular systems: a) methionine biosynthesis; b) the methylation cycle; and c) formaldehyde detoxification. Specific insights from the resulting molecular pathways indicate that normal C1 metabolism involves the transfer of a * Corresponding author. P. Deonikar et al.572 carbon group from serine through a folate-mediated pathway to methionine, and eventually the methylation of a biomolecule. In photosynthetic tissues, C1 metabolism often proceeds in reverse towards serine biosynthesis and formate oxidation. C1 metabolism, in maize, appears to be present in the developing embryo and endosperm indicating that these cells are vulnerable to perturbations in formaldehyde detoxification. These insights demonstrate the value of a systematic bioinformatics literature review process from a broad spectrum of domain literature to specific and relevant molecular pathways.

Introduction Research shows associations between chronotype and behavior. While eveningness is associated with lower levels of self-control, morningness is associated with increased conscientiousness. Additionally, throughout the day, the increase in homeostatic sleep pressure due to wakefulness can affect executive functioning, including emotional regulation. Napping is an effective countermeasure to sleepiness and associated emotional dysregulation, but the impact of chronotype on this benefit is unknown. Therefore, this study aimed to examine the impact of chronotype and a midday nap on an aspect of emotional regulation: frustration tolerance. Methods 40 participants between the ages of 18–50 were randomized into a 60-minute, midday nap or no-nap condition. Chronotype was measured using the Horne-Östberg Morningness-Eveningness Questionnaire (MEQ). Frustration tolerance (FT) was measured pre and post nap using an adaption of Feather’s frustration tolerance task where FT was measured as the time spent on an impossible task. To examine the association of chronotype and FT, correlational analysis was used. Chronotype was also determined using a median split of the MEQ due to few true morning and evening types in the sample. This data was then subjected to a repeated measures ANOVA with condition (pre or post-nap) as a within-subjects factor and group (nap or no-nap; high or low MEQ score) as between-subject factors. Results Results revealed a significant correlation between MEQ score and change in time spent on the impossible task, with those with lower MEQ scores (more evening) showing an increase in time spent on the impossible task, r(20) = -.51, p = .016. Similarly, results of the ANOVA revealed a significant condition (pre or post-nap) by group (nap, no nap; high, low MEQ) interaction, F(1,1) = 4.694, p = .039, such that, those in the nap group with lower MEQ (more evening) spent more time on the impossible task following the nap. Conclusion Our results indicate that chronotype may impact a nap’s positive effect on emotional regulation, with greater benefit for those with the eveningness chronotype. Because napping is currently practiced by 1/3 of American adults, from a personalized medicine perspective, it’s imperative that its chronotype-dependent benefits be investigated further to effectively guide evidence-based recommendations. Support (if any):

Introduction Sleep deprivation impairs hippocampal-dependent memory, and hippocampal-dependent memory impairments occur in some dementias, including Alzheimer’s disease. As our population continues to age, understanding the molecular basis for memory impairments is increasingly important. We hypothesized that early life sleep fragmentation would result in lasting increases in hippocampal calcium transient activity. Methods B6 mice were randomized to 12wk of sleep fragmentation or rested control conditions at age 8wk. Mice were microinjected with AAV9-CamKII-GCamp6F into the hippocampus and later implanted with a GRIN Lens into CA1 secured to a baseplate along with chronic EEG/EMG electrodes and recording connector. Calcium recordings were obtained two to three months after injection and recordings were obtained across sleep-wake cycles>4mins of wake and NREM sleep. Individual cells across animal were combined into sleep fragmented (n = 521 cells) or rested (n = 443 cells) groups during wake or sleep. Average FFx was analyzed by group and condition by T-tests, paired for within and unpaired across groups. A spatial object recognition assay was also performed on all mice (n=16 for both groups) and performance across group was analyzed by paired T-tests. Results Rested mice showed normal spatial object recognition (n = 16, p<0.05). In contrast, SF mice showed impaired spatial object recognition (n = 16, N.S.). There were no differences across sleep conditions in calcium transient FFx for waking (p>0.05). However, in sleep, cells in SF mice had significantly higher average FFx values than cells in rested mice (p<0.0001). Conclusion Early-life sleep fragmentation has long-lasting impacts on memory. Since spatial memory is dependent on hippocampal function, the calcium transient FFx data suggests that a driver of this hippocampal memory impairment may be higher firing rates in sleep and/or greater calcium exposure in hippocampal CamKII neurons in sleep, both of which may perturb microglial maintenance of synapses. Understanding the molecular drivers behind this calcium dysfunction will be essential in our understanding of neurodegeneration, dementia, and Alzheimer’s disease. Support (If Any) NIH AG054104; AG064231