• Glucose metabolism enhances hematopoietic stem cell formation and function in the vertebrate embryo • Glucose metabolism modulates hif1a activity via mitochondrial generation of reactive oxygen species to impact HSC-relevant gene expressionMany pathways regulating blood formation have been elucidated, yet how each coordinates with embryonic biophysiology to modulate the spatiotemporal production of hematopoietic stem cells (HSCs) is currently unresolved. Here, we report that glucose metabolism impacts the onset and magnitude of HSC induction in vivo. In zebrafish, transient elevations in physiological glucose levels elicited dose-dependent effects on HSC development, including enhanced runx1 expression and hematopoietic cluster formation in the aorta-gonad-mesonephros region; embryonic-to-adult transplantation studies confirmed glucose increased functional HSCs. Glucose uptake was required to mediate the enhancement in HSC development; likewise, metabolic inhibitors diminished nascent HSC production and reversed glucose-mediated effects on HSCs. Increased glucose metabolism preferentially impacted hematopoietic and vascular targets, as determined by gene expression analysis, through mitochondrialderived reactive oxygen species (ROS)-mediated stimulation of hypoxia-inducible factor 1a (hif1a). Epistasis assays demonstrated that hif1a regulates HSC formation in vivo and mediates the dose-dependent effects of glucose metabolism on the timing and magnitude of HSC production. We propose that this fundamental metabolic-sensing mechanism enables the embryo to respond to changes in environmental energy input and adjust hematopoietic output to maintain embryonic growth and ensure viability. (Blood. 2013;121(13):2483-2493

Left-handed (N = 109) and right-handed (N = 115) undergraduates (99 males, 125 females) received the SIBT (a "mental rotation" test), the 3DD (3-dimensional drawing test), and a family sinistrality (FS) questionnaire. Left-handers were further separated into consistent left-handed (CLH) and inconsistent left-handed (ILH) subgroups, based on consistency of hand preference. On the spatial tests, males outperformed females, with no overall handedness effects. Also, for males, CLH's (but not ILH's) performed significantly worse than right-handers on the SIBT, but this difference was not found on the 3DD. For females, no handedness subgroup differences were found on either spatial tasks. Familial sinistrality was twice as common in left-handers as in right-handers. Among males, the incidence of FS+ in the CLH subgroup also was over twice that for ILH's. Thus, where left-handers report a greater incidence of FS+, and are inferior to right-handers in mental rotation skill, it is CLH's (particularly males) who contribute mostly to these effects. The results suggest that previous discrepant findings reported in studies of the cognitive correlates of left-handedness may be due in part to the mixing of two distinct left-handed subgroups. An understanding of the differences between them may be crucial for better understanding the genetic and neurobiological mechanisms underlying handedness.

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Objective The transition from childhood to adulthood is characterized by improved motor and cognitive performance in many domains. Developmental studies focus on average performance in single domains but ignore consistency of performance across domains. Within-individual variability (WIV) provides an index of that evenness and is a potential marker of development. Method We gave a computerized battery of 14 neurocognitive tests to 9138 youths ages 8-21 from the Philadelphia Neurodevelopmental Cohort. Results As expected, performance improved with age, both accuracy and speed peaking in adulthood. WIV, however, showed a U-shaped course: highest in childhood, declining yearly into mid-adolescence, and increasing again into adulthood. Young females outperformed and were less variable than males, but by early adulthood male performance matched that of females despite being more variable. Conclusion We conclude that WIV declines from childhood to adolescence as developmental lags are overcome, and then increases into adulthood reflecting the emergence of cognitive specializations related to skill-honing and brain maturation.