Reversing anterior insular cortex neuronal hypoexcitability attenuates compulsive behavior in juvenile rats

Development of self-regulatory competencies during adolescence is partially dependent on normative brain maturation. Here we report that juvenile rats as compared to adults exhibit impulsive and compulsive-like behavioral traits, the latter being associated with lower expression of mRNA levels of the immediate early gene zif268 in the anterior insula (AI). This observation suggests that deficits in AI function in juvenile rats could explain their immature pattern of interoceptive cue integration in rational decision-making and compulsive phenotype. In support of this, here we report hypoexcitability of juvenile layer-V pyramidal neurons in the AI, concomitant with reduced glutamatergic synaptic input to these cells. Chemogenetic activation of the AI attenuated the compulsive trait suggesting that delayed maturation of the AI results in suboptimal integration of sensory and cognitive information in adolescents and this contributes to inflexible behaviors in specific conditions of reward availability.

STAG2 promotes the myelination transcriptional program in oligodendrocytes

SUMMARYCohesin folds chromosomes via DNA loop extrusion. Cohesin-mediated chromosome loops regulate transcription by shaping long-range enhancer-promoter interactions, among other mechanisms. Mutations of cohesin subunits and regulators cause human developmental diseases termed cohesinopathy. Vertebrate cohesin consists of SMC1, SMC3, RAD21, and either STAG1 or STAG2. To probe the physiological functions of cohesin, we created conditional knockout (cKO) mice with Stag2 deleted in the nervous system. Stag2 cKO mice exhibit growth retardation, neurological defects, and premature death, in part due to insufficient myelination of nerve fibers. Stag2 cKO oligodendrocytes exhibit delayed maturation and downregulation of myelination-related genes. Stag2 loss reduces promoter-anchored loops at downregulated genes in oligodendrocytes. Thus, STAG2-cohesin generates promoter-anchored loops at myelination-promoting genes to facilitate their transcription. Our study implicates defective myelination as a contributing factor to cohesinopathy and establishes oligodendrocytes as a relevant cell type to explore the mechanisms by which cohesin regulates transcription.

Quantification of gaze reaction time in infants with Pediatric Perimeter

Purpose We quantified the eye/head (gaze) reaction time in infants to establish a normative database for the Pediatric Perimeter device. Additionally, we tested the hypothesis that gaze reaction time will reduce with age. Methods A cross-sectional study was conducted. Healthy infants between 3 to 10 months of age were recruited. Peripheral visual field stimuli (hemifield and quadrant stimuli) were presented in the Pediatric Perimeter device. Infant’s gaze to these stimuli was observed, documented in real time, and video recorded for offline analysis. Results A total of 121 infants were tested in three age group bins [3–5 months, n = 44; >5–7 months, n = 30 and >7–10 months, n = 47]. Overall, 3–5 months old had longer reaction time when compared to the older infants particularly for stimuli presented in the quadrants (Kruskal-Wallis, p<0.038). A significantly asymmetric difference (p = 0.025) in reaction time was observed between the upper (median = 820ms, IQR = 659-1093ms) and lower quadrants (median = 601ms, IQR = 540-1052ms) only for the 3–5 months old infants. Conclusion This study provides the normative gaze reaction time of healthy infants. With increase in age, there is reduction in reaction time and disappearance of reaction time asymmetry in quadrant stimuli. The longer reaction time for upward gaze could be due to delayed maturation of neural mechanisms and/or decreased visual attention.

Role of Nrf2 Signaling in Development of Hepatocyte-Like Cells

Generation of hepatocytes from human adipose-derived mesenchymal stem cells (hADSCs) could be a promising alternative source of human hepatocytes. However, mechanisms to differentiate hepatocytes from hADSCs are not fully elucidated. In this study, we investigated the role of nuclear factor erythroid-2 related factor 2 (Nrf2) in differentiation of hepatocyte-like cells (HLCs). We used our established three-step differentiation protocol to develop HLCs from hADSCs. Significant nuclear translocation of Nrf2 occurred from day 11 (Step 2) until the end of HLC differentiation. There were no significant differences in Nrf2 translocation rates among the four experimental groups (activin-A, GSK3 inhibitor, Nrf2 siRNA, and control) at day 6 (end of Step 1). Nuclear translocation of Nrf2 in the GSK3 inhibitor-treated group was obviously higher than the other groups at day 11 (Step 2). Moreover, nuclear translocation of Nrf2 in the GSK3 inhibitor-treated group was notably higher than the other groups during Step 3. CYP3A4 activity (Luciferin-IPA assay) of the GSK3 inhibitor-treated group was significantly higher than the other three groups. Nrf2 was activated during differentiation of HLCs, and inhibition of Nrf2 delayed maturation and impaired the function of HLCs. Thus, Nrf2 might be a notable target for developing highly functional human HLCs.

Life history traits and dispersal shape neutral genetic diversity in metapopulations

Genetic diversity at population scale, depends on species life-history traits, population dynamics and local and global environmental factors. We first investigate the effect of lifehistory traits on the neutral genetic diversity of a single population using a deterministic mathematical model. When the population is stable, we show that semelparous species with precocious maturation and iteroparous species with delayed maturation exhibit higher diversity because their life history traits tend to balance the lifetimes of non reproductive individuals (juveniles) and adults which reproduce. Then, we extend our model to a metapopulation to investigate the additional effect of dispersal on diversity. We show that dispersal may truly modify the local effect of life history on diversity. As a result, the diversity at the global scale of the metapopulation differ from the local diversity which is only described through local life history traits of the populations. In particular, dispersal usually promotes diversity at the global metapopulation scale.

Delayed maturation of thymic epithelium in mice with specific deletion of β-catenin gene in FoxN1 positive cells

Wnt signalling pathways have been reported to be involved in thymus development but their precise role in the development of both thymic epithelium (TE) and thymocytes is controversial. Herein, we examined embryonic, postnatal and adult thymi of mice with a specific deletion of β-catenin gene in FoxN1+ thymic epithelial cells (TECs). Together with a high postnatal mouse mortality, the analysis showed severe thymic hypocellularity, largely due an important reduction in numbers of developing thymocytes, and delayed, partially blocked maturation of mutant TECs. Affected TECs included largely cortical (c) TEC subsets, such as immature MTS20+ TECs, Ly51+ cTECs and a remarkable, rare Ly51+MTS20+MHCIIhi cell subpopulation previously reported to contain thymic epithelial progenitor cells (TEPCs) (Ulyanchenko et al., Cell Rep 14:2819–2832, 2016). In addition, altered postnatal organization of mutant thymic medulla failed to organize a unique, central epithelial area. This delayed maturation of TE cell components correlated with low transcript production of some molecules reported to be masters for TEC maturation, such as EphB2, EphB3 and RANK. Changes in the thymic lymphoid component became particularly evident after birth, when molecules expressed by TECs and involved in early T-cell maturation, such as CCL25, CXCL12 and Dll4, exhibited minimal values. This represented a partial blockade of the progression of DN to DP cells and reduced proportions of this last thymocyte subset. At 1 month, in correlation with a significant increase in transcript production, the DP cell percentage increased in correlation with a significant fall in the number of mature TCRαβhi thymocytes and peripheral T lymphocytes.

Relative age effect? No “flipping” way! Apparatus dependent inverse relative age effects in elite, women’s artistic gymnastics

In contrast to research on team-sports, delayed maturation has been observed in higher-skilled gymnasts, leading to atypical distributions of the relative age effect. Recent studies have reported intra-sport differences in the relative age effect and given the task demands across gymnastics apparatus, we expected to find evidence for the influence of apparatus specialism. We examined the presence of a relative age effects within a sample of elite, international, women’s artistic gymnasts (N = 806, Ncountries = 87), and further sampled our data from vault, bars, beam, and floor major competition finalists. Poisson regression analysis indicated no relative age effect in the full sample (p = .55; R2 adj. = .01) but an effect that manifested when analysing apparatus independently. The Index of Discrimination (ID) analysis provided evidence of an inverse relative age effect identified for beam (p = .01; ID = 1.27; R2 adj. = .12), a finding that was corroborated by a marginal effect in our vault finalists (p = .08; ID = 1.21; R2 adj. = .06). These novel findings can be attributed to the integrated influence of self-fulfilling prophecy upon coach and gymnast expectations, as well as the technical mechanisms underpinning skill development involved in the underdog hypothesis.

Bagging of bunches and protected production in ‘Niagara Rosada’ vineyard

Vineyards of ‘Niagara Rosada’ have shown great productive potential. However, the grape production has been affected by factors related to climate adversities. Thus, this study aimed to evaluate the effect of plastic cover and bagging of bunches of ‘Niagara Rosada’, in Almirante Tamandaré, PR, Brazil. Plastic cover used was of polyethylene with 250 µm of thickness and bagging of the bunches with white non-woven fabric bags. The treatments were: without plastic cover over the vineyard and without bagging of bunches (control); with plastic cover over the vineyard and without bagging of bunches; with plastic cover over the vineyard and with bagging of bunches; and without plastic cover over the vineyard and with bagging of bunches. To determine the quality of the grapes, we evaluated weight of the bunches and berry, width and length of the bunch, number of berries per bunch, total soluble solids (SS), titratable acidity (TA), pH, and SS/TA ratio. In both crop seasons, treatments with the protected plants or bunches were superior in all evaluated traits. The plastic cover and bagging of bunches delayed maturation and improved the physical and chemical characteristics of bunches and berries of ‘Niagara Rosada’.

ID4 Is Required for Normal Ependymal Cell Development

Ependymal cells are radial glia-derived multiciliated cells lining the lateral ventricles of the brain and spinal cord. Correct development and coordinated cilia beating is essential for proper cerebrospinal fluid (CSF) flow and neurogenesis modulation. Dysfunctions of ependymal cells were associated with transcription factor deregulation. Here we provide evidence that the transcriptional regulator ID4 is involved in ependymal cell development and maturation. We observed that Id4-deficient mice display altered ventricular cell cytoarchitecture, decreased ependymal cell number and enlarged ventricles. In addition, absence of ID4 during embryonic development resulted in decreased ependymal cell number and delayed maturation. Our findings open the way for a potential role of ID4 in ependymal cell development and motor cilia function.