Pathways to Kindergarten Readiness: The Roles of Second Step Early Learning Curriculum and Social Emotional, Executive Functioning, Preschool Academic and Task Behavior Skills

Efforts to improve the achievement gap between low-income children and their more affluent peers has led to the development of classroom interventions and curricula to increase executive functioning (EF) and social-emotional skills (SE), thought to be foundational for learning. The Second Step Early Learning (SSEL) curriculum is a commercially available curriculum designed to improve school readiness by building EF and SE skills. However, although widely used, it has not been widely studied. Modeling SSEL’s underlying theory of change, structural equation modeling (SEM) was used to longitudinally examine the effects of the curriculum on low-income preschool children’s kindergarten school readiness through the hypothesized mediating role of EF and SE skills in improving pre-academic skills and task behavior in preschool. In a cluster randomized trial, 972 children attending 63 preschool classrooms within 13 low-income Head Start or community preschools were individually tested at the beginning (T1) and end of preschool (T2, n = 836) and followed into kindergarten. Children’s average age at T1 was 53 months, with 51% male, 42% Anglo-American, 26% African–American, and 40% Hispanic-American. Children’s EF, social skills, pre-literacy/language, and pre-math skills were assessed by trained child assessors blind to study conditions at T1 and T2. Assessors also rated children’s task behavior in the testing situation at T1 and T2. School records of children’s kindergarten screening scores were obtained on 345 children at T3. It was expected that SSEL would have both direct and indirect effects on kindergarten readiness through improvements in children’s SE and EF skills preschool academic skills and on-task behavior. We found no direct effects of SSEL on either pre-academic or on-task behavior outcomes in preschool, nor on later kindergarten readiness. However, SSEL significantly increased EF, and as expected by SSEL’s theory of change, growth in EF predicted gains in both pre-academics (particularly pre-math), and on-task behavior in preschool. End-of-year pre-academic skills and on task behavior in turn predicted better kindergarten readiness. Further, SE (although not impacted by SSEL) had direct and indirect effects on kindergarten readiness. Thus, overall, our findings largely support SSEL’s theory of change, particularly in relation to EF

SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development

Synaptogenic adhesion molecules play critical roles in synapse formation. SALM5/Lrfn5, a SALM/Lrfn family adhesion molecule implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons, but its presynaptic ligand remains unknown. We found that SALM5 interacts with the Ig domains of LAR family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPδ, and PTPσ). These interactions are strongly inhibited by the splice insert B in the Ig domain region of LAR-RPTPs, and mediate SALM5-dependent presynaptic differentiation in contacting axons. In addition, SALM5 regulates AMPA receptor-mediated synaptic transmission through mechanisms involving the interaction of postsynaptic SALM5 with presynaptic LAR-RPTPs. These results suggest that postsynaptic SALM5 promotes synapse development by trans-synaptically interacting with presynaptic LAR-RPTPs and is important for the regulation of excitatory synaptic strength

Pathways to Kindergarten Readiness: The Roles of Second Step Early Learning Curriculum and Social Emotional, Executive Functioning, Preschool Academic and Task Behavior Skills

Efforts to improve the achievement gap between low-income children and their more affluent peers has led to the development of classroom interventions and curricula to increase executive functioning (EF) and social-emotional skills (SE), thought to be foundational for learning. The Second Step Early Learning (SSEL) curriculum is a commercially available curriculum designed to improve school readiness by building EF and SE skills. However, although widely used, it has not been widely studied. Modeling SSEL\u27s underlying theory of change, structural equation modeling (SEM) was used to longitudinally examine the effects of the curriculum on low-income preschool children\u27s kindergarten school readiness through the hypothesized mediating role of EF and SE skills in improving pre-academic skills and task behavior in preschool. In a cluster randomized trial, 972 children attending 63 preschool classrooms within 13 low-income Head Start or community preschools were individually tested at the beginning (T1) and end of preschool (T2, n = 836) and followed into kindergarten. Children\u27s average age at T1 was 53 months, with 51% male, 42% Anglo-American, 26% African-American, and 40% Hispanic-American. Children\u27s EF, social skills, pre-literacy/language, and pre-math skills were assessed by trained child assessors blind to study conditions at T1 and T2. Assessors also rated children\u27s task behavior in the testing situation at T1 and T2. School records of children\u27s kindergarten screening scores were obtained on 345 children at T3. It was expected that SSEL would have both direct and indirect effects on kindergarten readiness through improvements in children\u27s SE and EF skills preschool academic skills and on-task behavior. We found no direct effects of SSEL on either pre-academic or on-task behavior outcomes in preschool, nor on later kindergarten readiness. However, SSEL significantly increased EF, and as expected by SSEL\u27s theory of change, growth in EF predicted gains in both pre-academics (particularly pre-math), and on-task behavior in preschool. End-of-year pre-academic skills and on task behavior in turn predicted better kindergarten readiness. Further, SE (although not impacted by SSEL) had direct and indirect effects on kindergarten readiness. Thus, overall, our findings largely support SSEL\u27s theory of change, particularly in relation to EF

Quercetin reduces obesity-induced hepatosteatosis by enhancing mitochondrial oxidative metabolism via heme oxygenase-1

Background: Obesity-induced hepatic lipid accumulation causes lipotoxicity, mitochondrial dysfunction, oxidative stress, and insulin resistance, and is implicated in non-alcoholic hepatic pathologies such as steatohepatitis and fibrosis. Heme oxygenase-1 (HO-1), an important antioxidant enzyme catalyzing the rate-limiting step in heme degradation, protects against oxidative stress, inflammation, and metabolic dysregulation. Here, we demonstrate that the phytochemical, quercetin, a natural polyphenol flavonoid, protects against hepatic steatosis in obese mice fed a high-fat diet, and that it does so by inducing HO-1 and stimulating increased hepatic mitochondrial oxidative metabolism. Methods: Male C57BL/6 mice were fed a regular diet (RD), a high-fat diet (HFD), and an HFD supplemented with quercetin for 9 weeks. Levels of mitochondrial biogenesis and oxidative metabolic transcripts/proteins were measured by real-time PCR and/or Western blotting. HO-1 transcripts/proteins were measured real-time PCR and/or Western blotting. Results: Quercetin upregulated genes involved in mitochondrial biogenesis and oxidative metabolism in lipid-laden hepatocytes and the livers of HFD-fed obese mice, and this was accompanied by increased levels of the transcription factor, nuclear erythroid 2-related factor 2 (Nrf-2), and HO-1 protein. The HO-1 inducer hemin and the HO-1 byproduct carbon monoxide (CO) also enhanced hepatic oxidative metabolism in HFD-fed obese mice. Moreover, the metabolic changes and the lipid-lowering effects of quercetin were completely blocked by the HO-1 inhibitor ZnPP and by deficiency of Nrf-2. Conclusion: These findings suggest that quercetin stimulates hepatic mitochondrial oxidative metabolism by inducing HO-1 via the Nrf-2 pathway. Quercetin may be useful in protecting against obesity-induced hepatosteatosis

NGL-2 Deletion Leads to Autistic-like Behaviors Responsive to NMDAR Modulation

NGL-2 is a postsynaptic adhesion molecule known to regulate synaptic transmission, but whether NGL-2 regulates synaptic plasticity and specific behaviors remains unknown. Um et al. find that mice lacking NGL-2 display suppressed NMDA receptor-dependent synaptic plasticity and autistic-like social deficits and repetitive behaviors that are responsive to NMDA receptor activation.Netrin-G ligand 2 (NGL-2)/LRRC4, implicated in autism spectrum disorders and schizophrenia, is a leucine-rich repeat-containing postsynaptic adhesion molecule that interacts intracellularly with the excitatory postsynaptic scaffolding protein PSD-95 and trans-synaptically with the presynaptic adhesion molecule netrin-G2. Functionally, NGL-2 regulates excitatory synapse development and synaptic transmission. However, whether it regulates synaptic plasticity and disease-related specific behaviors is not known. Here, we report that mice lacking NGL-2 (Lrrc4−/− mice) show suppressed N-Methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity in the hippocampus. NGL-2 associates with NMDARs through both PSD-95-dependent and -independent mechanisms. Moreover, Lrrc4−/− mice display mild social interaction deficits and repetitive behaviors that are rapidly improved by pharmacological NMDAR activation. These results suggest that NGL-2 promotes synaptic stabilization of NMDARs, regulates NMDAR-dependent synaptic plasticity, and prevents autistic-like behaviors from developing in mice, supporting the hypothesis that NMDAR dysfunction contributes to autism spectrum disorders. © 2018 The Author(s

SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development

Synaptogenic adhesion molecules play critical roles in synapse formation. SALM5/Lrfn5, a SALM/Lrfn family adhesion molecule implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons, but its presynaptic ligand remains unknown. We found that SALM5 interacts with the Ig domains of LAR family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPδ, and PTPσ). These interactions are strongly inhibited by the splice insert B in the Ig domain region of LAR-RPTPs, and mediate SALM5-dependent presynaptic differentiation in contacting axons. In addition, SALM5 regulates AMPA receptor-mediated synaptic transmission through mechanisms involving the interaction of postsynaptic SALM5 with presynaptic LAR-RPTPs. These results suggest that postsynaptic SALM5 promotes synapse development by trans-synaptically interacting with presynaptic LAR-RPTPs and is important for the regulation of excitatory synaptic strength.113131sciescopu

Topological Control of 2D Perovskite Emission in the Strong Coupling Regime

Momentum space topology can be exploited to manipulate radiation in real space. Here we demonstrate topological control of 2D perovskite emission in the strong coupling regime via polaritonic bound states in the continuum (BICs). Topological polarization singularities (polarization vortices and circularly polarized eigenstates) are observed at room temperature by measuring the Stokes parameters of photoluminescence in momentum space. Particularly, in symmetry-broken structures, a very large degree of circular polarization (DCP) of ???0.835 is achieved in the perovskite emission, which is the largest in perovskite materials to our knowledge. In the strong coupling regime, lower polariton modes shift to the low-loss spectral region, resulting in strong emission enhancement and large DCP. Our reciprocity analysis reveals that DCP is limited by material absorption at the emission wavelength. Polaritonic BICs based on 2D perovskite materials combine unique topological features with exceptional material properties and may become a promising platform for active nanophotonic devices

Circularly Polarized Emission from Organic???Inorganic Hybrid Perovskites via Chiral Fano Resonances

Organic-inorganic hybrid perovskites hold great potential for various optoelectronic devices with exceptional properties. Although the direct generation of circularly polarized emission from perovskites would enable various compact devices, achieving a large degree of circular polarization (DCP) at room temperature still remains challenging. Herein, we demonstrate that DCP can be strongly enhanced at the narrow mode position of chiral Fano resonances. In our design, a perovskite film is spin-coated on a symmetry-broken structure with a relatively large feature size. A large DCP of more than 0.5 is achieved at room temperature without the direct patterning of the perovskite layer. Reciprocity calculation reveals that chiral field enhancement enables the emission of opposite helicity to couple into counter-propagating slab modes and leads to a large DCP. Our design is very general and scalable. Our work may lead to circularly polarized light sources based on various perovskite materials

NGL-2 Deletion Leads to Autistic-like Behaviors Responsive to NMDAR Modulation

Summary: Netrin-G ligand 2 (NGL-2)/LRRC4, implicated in autism spectrum disorders and schizophrenia, is a leucine-rich repeat-containing postsynaptic adhesion molecule that interacts intracellularly with the excitatory postsynaptic scaffolding protein PSD-95 and trans-synaptically with the presynaptic adhesion molecule netrin-G2. Functionally, NGL-2 regulates excitatory synapse development and synaptic transmission. However, whether it regulates synaptic plasticity and disease-related specific behaviors is not known. Here, we report that mice lacking NGL-2 (Lrrc4−/− mice) show suppressed N-Methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity in the hippocampus. NGL-2 associates with NMDARs through both PSD-95-dependent and -independent mechanisms. Moreover, Lrrc4−/− mice display mild social interaction deficits and repetitive behaviors that are rapidly improved by pharmacological NMDAR activation. These results suggest that NGL-2 promotes synaptic stabilization of NMDARs, regulates NMDAR-dependent synaptic plasticity, and prevents autistic-like behaviors from developing in mice, supporting the hypothesis that NMDAR dysfunction contributes to autism spectrum disorders. : NGL-2 is a postsynaptic adhesion molecule known to regulate synaptic transmission, but whether NGL-2 regulates synaptic plasticity and specific behaviors remains unknown. Um et al. find that mice lacking NGL-2 display suppressed NMDA receptor-dependent synaptic plasticity and autistic-like social deficits and repetitive behaviors that are responsive to NMDA receptor activation. Keywords: autism, NMDA receptors, repetitive behavior, synaptic adhesion, social interactio