Axial skeleton anterior-posterior patterning is regulated through feedback regulation between Meis transcription factors and retinoic acid.

Vertebrate axial skeletal patterning is controlled by co-linear expression of Hox genes and axial level-dependent activity of HOX protein combinations. MEIS transcription factors act as co-factors of HOX proteins and profusely bind to Hox complex DNA; however, their roles in mammalian axial patterning remain unknown. Retinoic acid (RA) is known to regulate axial skeletal element identity through the transcriptional activity of its receptors; however, whether this role is related to MEIS/HOX activity remains unknown. Here, we study the role of Meis in axial skeleton formation and its relationship to the RA pathway in mice. Meis elimination in the paraxial mesoderm produces anterior homeotic transformations and rib mis-patterning associated to alterations of the hypaxial myotome. Although Raldh2 and Meis positively regulate each other, Raldh2 elimination largely recapitulates the defects associated with Meis deficiency, and Meis overexpression rescues the axial skeletal defects in Raldh2 mutants. We propose a Meis-RA-positive feedback loop, the output of which is Meis levels, that is essential to establish anterior-posterior identities and patterning of the vertebrate axial skeleton.This research was supported by the Ministerio de Ciencia, Innovación y Universidades (PGC2018-096486-B-I00), the Instituto de Salud Carlos III (RD16/ 0011/0019) and by the Comunidad de Madrid (S2017/BMD3875). The Centro Nacional de Investigaciones Cardiovasculares Carlos III is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro Centro Nacional de Investigaciones Cardiovasculares Carlos III Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). A.C.L.-D. was the recipient of a Formación Personal Investigador fellowship from the Ministerio de Economı́a y Competitividad (BES-2013-064374).S

Association Between Physical Fitness and Bone Strength and Structure in 3- to 5-Year-Old Children

Background: The positive association between physical fitness and bone structure has been widely investigated in children and adolescents, yet no studies have evaluated this influence in young children (ie, preschoolers). Hypothesis: Fit children will present improved bone variables when compared with unfit children, and no sex-based differences will emerge in the sample. Study Design: Cross-sectional study. Level of Evidence: Level 3. Methods: Handgrip strength, standing long jump (SLJ), speed/agility, balance, and cardiorespiratory fitness (CRF) were assessed using the Assessing FITness levels in PREschoolers (PREFIT) test battery in 92 children (50 boys; age range, 3-5 years). A peripheral quantitative computed tomography scan was performed at 38% of the length of the nondominant tibia. Cluster analysis from handgrip strength, SLJ, speed/agility, and CRF was developed to identify fitness groups. Bone variables were compared between sexes and between cluster groups. The association between individual physical fitness components and different bone variables was also tested. Results: Three cluster groups emerged: fit (high values on all included physical fitness variables), strong (high strength values and low speed/agility and CRF), and unfit (low strength, speed/agility, and CRF). The fit group presented higher values than the strong and unfit groups for total and cortical bone mineral content, cortical area, and polar strength strain index (all P < 0.05). The fit group also presented a higher cortical thickness when compared with the unfit group (P < 0.05). Handgrip, SLJ, and speed/agility predicted all bone variables except for total and cortical volumetric bone mineral density. No differences were found for bone variables between sexes. Conclusion: The results suggest that global fitness in preschoolers is a key determinant for bone structure and strength but not volumetric bone mineral density. Clinical Relevance: Physical fitness is a determinant for tibial bone mineral content, structure, and strength in very young children. Performing physical fitness tests could provide useful information related to bone health in preschoolers

Effects of an exercise program on brain health outcomes for children with overweight or obesity

Importance Pediatric overweight and obesity are highly prevalent across the world, with implications for poorer cognitive and brain health. Exercise might potentially attenuate these adverse consequences. Objectives To investigate the effects of an exercise program on brain health indicators, including intelligence, executive function, academic performance, and brain outcomes, among children with overweight or obesity and to explore potential mediators and moderators of the main effects of exercise. Design, Setting, and Participants All preexercise and postexercise data for this 20-week randomized clinical trial of 109 children aged 8 to 11 years with overweight or obesity were collected from November 21, 2014, to June 30, 2016, with neuroimaging data processing and analyses conducted between June 1, 2017, and December 20, 2021. All 109 children were included in the intention-to-treat analyses; 90 children (82.6%) completed the postexercise evaluation and attended 70% or more of the recommended exercise sessions and were included in per-protocol analyses. Interventions All participants received lifestyle recommendations. The control group continued their usual routines, whereas the exercise group attended a minimum of 3 supervised 90-minute sessions per week in an out-of-school setting. Main Outcomes and Measures Intelligence, executive function (cognitive flexibility, inhibition, and working memory), and academic performance were assessed with standardized tests, and hippocampal volume was measured with magnetic resonance imaging. Results The 109 participants included 45 girls (41.3%); participants had a mean (SD) body mass index of 26.8 (3.6) and a mean (SD) age of 10.0 (1.1) years at baseline. In per-protocol analyses, the exercise intervention improved crystallized intelligence, with the exercise group improving from before exercise to after exercise (mean z score, 0.62 [95% CI, 0.44-0.80]) compared with the control group (mean z score, –0.10 [95% CI, –0.28 to 0.09]; difference between groups, 0.72 SDs [95% CI, 0.46-0.97]; P < .001). Total intelligence also improved significantly more in the exercise group (mean z score, 0.69 [95% CI, 0.48-0.89]) than in the control group (mean z score, 0.07 [95% CI, –0.14 to 0.28]; difference between groups, 0.62 SDs [95% CI, 0.31-0.91]; P < .001). Exercise also positively affected a composite score of cognitive flexibility (mean z score: exercise group, 0.25 [95% CI, 0.05-0.44]; control group, –0.17 [95% CI, –0.39 to 0.04]; difference between groups, 0.42 SDs [95% CI, 0.13-0.71]; P = .005). These main effects were consistent in intention-to-treat analyses and after multiple-testing correction. There was a positive, small-magnitude effect of exercise on total academic performance (mean z score: exercise group, 0.31 [95% CI, 0.18-0.44]; control group, 0.10 [95% CI, –0.04 to 0.24]; difference between groups, 0.21 SDs [95% CI, 0.01-0.40]; P = .03), which was partially mediated by cognitive flexibility. Inhibition, working memory, hippocampal volume, and other brain magnetic resonance imaging outcomes studied were not affected by the exercise program. The intervention increased cardiorespiratory fitness performance as indicated by longer treadmill time to exhaustion (mean z score: exercise group, 0.54 [95% CI, 0.27-0.82]; control group, 0.13 [95% CI, –0.16 to 0.41]; difference between groups, 0.42 SDs [95% CI, 0.01-0.82]; P = .04), and these changes in fitness mediated some of the effects (small percentage of mediation [approximately 10%-20%]). The effects of exercise were overall consistent across the moderators tested, except for larger improvements in intelligence among boys compared with girls. Conclusions and Relevance In this randomized clinical trial, exercise positively affected intelligence and cognitive flexibility during development among children with overweight or obesity. However, the structural and functional brain changes responsible for these improvements were not identified

Which indices of cardiorespiratory fitness are more strongly associated with brain health in children with overweight/obesity?

This is the final version. Available on open access from Wiley via the DOI in this record.data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.PURPOSE: To compare the strength of associations between different indices of cardiorespiratory fitness (CRF) and brain health outcomes in children with overweight/obesity. METHODS: Participants were 100 children aged 8-11 years. CRF was assessed using treadmill exercise test (peak oxygen uptake [V̇O2peak ], treadmill time, and V̇O2 at ventilatory threshold) and 20-metre shuttle run test (20mSRT, laps, running speed, estimated V̇O2peak using the equations by Léger et al., Mahar et al., and Matsuzaka et al.). Intelligence, executive functions, and academic performance were assessed using validated methods. Total gray matter and hippocampal volumes were assessed using structural MRI. RESULTS: V̇O2peak /body mass (β = 0.18, 95% CI = 0.01-0.35) and treadmill time (β = 0.18-0.21, 95% CI = 0.01-0.39) were positively associated with gray matter volume. 20mSRT laps were positively associated with executive functions (β = 0.255, 95% CI = 0.089-0.421) and academic performance (β = 0.199-0.255, 95% CI = 0.006-0.421), and the running speed was positively associated with executive functions (β = 0.203, 95% CI = 0.039-0.367). Estimated V̇O2peak/Léger et al. was positively associated with intelligence, executive functions, academic performance, and gray matter volume (β = 0.205-0.282, 95% CI = 0.013-0.500). Estimated V̇O2peak/Mahar et al. and V̇O2peak/Matsuzaka et al. (speed) were positively associated with executive functions (β = 0.204-0.256, 95% CI = 0.031-0.436). CONCLUSION: Although V̇O2peak is considered the gold standard indicator of CRF in children, peak performance (laps or running speed) and estimated V̇O2peak/Léger et al. derived from 20mSRT had stronger and more consistent associations with brain health outcomes than other indices of CRF in children with overweight/obesity.European CommissionEuropean Regional Development Fund (ERDF)Fundación Alicia KoplowitzJuho Vainion SäätiöSpanish ministry of economy and competitivenes

The K2K SciBar Detector

A new near detector, SciBar, for the K2K long-baseline neutrino oscillation expe riment was installed to improve the measurement of neutrino energy spectrum and to study neutrino interactions in the energy region around 1 GeV. SciBar is a 'fully active' tracking detector with fine segmentation consisting of plastic scintillator bars. The detector was constructed in summer 2003 and is taking data since October 2003. The basic design and initial performance is presented.Comment: 7 pages, 4figures, Contributed to Proceedings of the 10th Vienna Conference on Instrumentation, Vienna, February 16-21, 200

Measurement of inclusive charged current interactions on carbon in a few-GeV neutrino beam

The SciBooNE Collaboration reports a measurement of inclusive charged current interactions of muon neutrinos on carbon with an average energy of 0.8 GeV using the Fermilab Booster Neutrino Beam. We compare our measurement with two neutrino interaction simulations: NEUT and NUANCE. The charged current interaction rates (product of flux and cross section) are extracted by fitting the muon kinematics, with a precision of 6-15% for the energy dependent and 3% for the energy integrated analyses. We also extract CC inclusive interaction cross sections from the observed rates, with a precision of 10-30% for the energy dependent and 8% for the energy integrated analyses. This is the first measurement of the CC inclusive cross section on carbon around 1 GeV. These results can be used to convert previous SciBooNE cross section ratio measurements to absolute cross section values.Comment: 21 pages, 16 figures. Accepted by Phys. Rev. D. Minor revisions to match the accepted versio

Search for Charged Current Coherent Pion Production on Carbon in a Few-GeV Neutrino Beam

The SciBooNE Collaboration has performed a search for charged current coherent pion production from muon neutrinos scattering on carbon, \nu_\mu ^{12}C \to \mu^- ^{12}C \pi^+, with two distinct data samples. No evidence for coherent pion production is observed. We set 90% confidence level upper limits on the cross section ratio of charged current coherent pion production to the total charged current cross section at 0.67\times 10^{-2} at mean neutrino energy 1.1 GeV and 1.36\times 10^{-2} at mean neutrino energy 2.2 GeV.Comment: 18 pages, 16 figures, Minor revisions to match version accepted for publication in Physical Review