SHP2 regulates GluA2 tyrosine phosphorylation required for AMPA receptor endocytosis and mGluR-LTD.

Posttranslational modifications regulate the properties and abundance of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that mediate fast excitatory synaptic transmission and synaptic plasticity in the central nervous system. During long-term depression (LTD), protein tyrosine phosphatases (PTPs) dephosphorylate tyrosine residues in the C-terminal tail of AMPA receptor GluA2 subunit, which is essential for GluA2 endocytosis and group I metabotropic glutamate receptor (mGluR)-dependent LTD. However, as a selective downstream effector of mGluRs, the mGluR-dependent PTP responsible for GluA2 tyrosine dephosphorylation remains elusive at Schaffer collateral (SC)-CA1 synapses. In the present study, we find that mGluR5 stimulation activates Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) by increasing phospho-Y542 levels in SHP2. Under steady-state conditions, SHP2 plays a protective role in stabilizing phospho-Y869 of GluA2 by directly interacting with GluA2 phosphorylated at Y869, without affecting GluA2 phospho-Y876 levels. Upon mGluR5 stimulation, SHP2 dephosphorylates GluA2 at Y869 and Y876, resulting in GluA2 endocytosis and mGluR-LTD. Our results establish SHP2 as a downstream effector of mGluR5 and indicate a dual action of SHP2 in regulating GluA2 tyrosine phosphorylation and function. Given the implications of mGluR5 and SHP2 in synaptic pathophysiology, we propose SHP2 as a promising therapeutic target for neurodevelopmental and autism spectrum disorders.

Identification of Biomarkers Related to Metabolically Unhealthy Obesity in Korean Obese Adolescents: A Cross-Sectional Study.

BACKGROUND: The current study aimed to screen for relationships and different potential metabolic biomarkers involved between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in adolescents. METHODS: The study included 148 obese adolescents aged between 14 and 16. The study participants were divided into MUO and MHO groups based on the age-specific adolescent metabolic syndrome (MetS) criteria of the International Diabetes Federation. The current study was conducted to investigate the clinical and metabolic differences between the MHO and MUO groups. Multivariate analyses were conducted to investigate the metabolites as independent predictors for the odds ratio and the presence of the MetS. RESULTS: There were significant differences in the three acylcarnitines, five amino acids, glutamine/glutamate ratio, three biogenic amines, two glycerophospholipids, and the triglyceride-glucose index between the MUO group and those in the MHO group. Moreover, several metabolites were associated with the prevalence of MUO. Additionally, several metabolites were inversely correlated with MHO in the MUO group. CONCLUSIONS: In this study, the biomarkers found in this study have the potential to reflect the clinical outcomes of the MUO group. These biomarkers will lead to a better understanding of MetS in obese adolescents.

Changes in Plasma Choline and the Betaine-to-Choline Ratio in Response to 6-Month Lifestyle Intervention Are Associated with the Changes of Lipid Profiles and Intestinal Microbiota: The ICAAN Study.

Trimethylamine N-oxide (TMAO) and its precursors, including choline, betaine, and L-carnitine, are gut microbiota-related metabolites associated with the risk of obesity. We aimed (1) to comprehensively examine whether the changes in plasma TMAO and its precursors induced by lifestyle intervention are associated with the improvements in plasma metabolic parameters; and (2) to identify the fecal microbiome profiles and nutrient intakes associated with these metabolites and metabolic index. Data from 40 participants (obese children and adolescents) having the plasma metabolites data related to the changes in BMI z-scores after 6-month lifestyle intervention were analyzed. In this study, we observed that choline and the betaine-to-choline ratio (B/C) showed different patterns depending on the changes in BMI z-scores by the response to lifestyle intervention. During the 6 months, an increase in choline and a decrease in B/C were observed in non-responders. We also found that changes in choline and B/C were associated with the improvements in plasma lipid levels. Individuals who showed reduced choline or increased B/C from the baseline to 6 months had a significant decrease in LDL-cholesterol over 6 months compared to those with increased choline or decreased B/C, respectively. In addition, the increase in choline or decrease in B/C was associated with the increase in plasma triglycerides. The distribution of gut microbiota belonging to the Firmicutes, such as Clostridia, Clostridiales, Peptostreptococcaceae, Romboutsia, and Romboutsia timonensis was altered to be lower during the 6 months both as choline decreased and B/C increased. Moreover, the decrease in choline and the increase in B/C were associated with reduced fat intake and increased fiber intake after the 6-month intervention. Finally, lower abundance of Romboutsia showed the association with lower LDL-cholesterol and higher intake of fiber. In summary, we demonstrated that reduced choline and increased B/C by lifestyle intervention were associated with the improvements of LDL-cholesterol and triglycerides, low-fat and high-fiber intakes, and low abundance of Firmicutes. These indicate that changes to circulating choline and B/C could predict individuals' changes in metabolic compositions in response to the lifestyle intervention.

Metabolomic Signatures for the Effects of Weight Loss Interventions on Severe Obesity in Children and Adolescents.

Childhood obesity has increased worldwide, and many clinical and public interventions have attempted to reduce morbidity. We aimed to determine the metabolomic signatures associated with weight control interventions in children with obesity. Forty children from the "Intervention for Children and Adolescent Obesity via Activity and Nutrition (ICAAN)" cohort were selected according to intervention responses. Based on changes in body mass index z-scores, 20 were responders and the remaining non-responders. Their serum metabolites were quantitatively analyzed using capillary electrophoresis time-of-flight mass spectrometry at baseline and after 6 and 18 months of intervention. After 18 months of intervention, the metabolite cluster changes in the responders and non-responders showed a difference on the heatmap, but significant metabolites were not clear. However, regardless of the responses, 13 and 49 metabolites were significant in the group of children with obesity intervention at 6 months and 18 months post-intervention compared to baseline. In addition, the top five metabolic pathways (D-glutamine and D-glutamate metabolism; arginine biosynthesis; alanine, aspartate, and glutamate metabolism; TCA cycle (tricarboxylic acid cycle); valine, leucine, and isoleucine biosynthesis) including several amino acids in the metabolites of obese children after 18 months were significantly changed. Our study showed significantly different metabolomic profiles based on time post obesity-related intervention. Through this study, we can better understand and predict childhood obesity through metabolite analysis and monitoring.

Film-thickness-driven superconductor to insulator transition in cuprate superconductors.

The superconductor-insulator transition induced by film thickness control is investigated for the optimally doped cuprate superconductor La1.85Sr0.15CuO4. Epitaxial thin films are grown on an almost exactly matched substrate LaAlO3 (001). Despite the wide thickness range of 6 nm to 300 nm, all films are grown coherently without significant relaxation of the misfit strain. Electronic transport measurement exhibits systematic suppression of the superconducting phase by reducing the film thickness, thereby inducing a superconductor-insulator transition at a critical thickness of ~10 nm. The emergence of a resistance peak preceding the superconducting transition is discussed based on the weak localization. X-ray photoelectron spectroscopy results show the possibility that oxygen vacancies are present near the interface.

Association between Physical Fitness and Cardiometabolic Risk of Children and Adolescents in Korea.

BACKGROUND: This study aimed to investigate the association between physical fitness and cardiometabolic health of Korean children and adolescents. METHODS: In total, 168 participants (89 boys and 79 girls) aged 10-16 years were recruited for the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition Study in 2016. The subjects were categorized into two groups using the definition of metabolic syndrome by the International Diabetes Federation: metabolically unhealthy (with at least two of the five criteria) and healthy groups (with less than one criterion). Correlation analysis of the participants' general characteristics was performed. Odds ratios (ORs) of physical fitness for cardiometabolic risk were evaluated via logistic regression. RESULTS: Metabolically unhealthy children showed greater weight, height, and body mass index, higher Children's Depression Inventory score, and longer screen time than did the metabolically healthy children. Metabolically healthy children showed greater upper and lower extremity muscular strength than did the metabolically unhealthy children (P=0.04 and P<0.001, respectively). In the multiple logistic regression analysis, lower extremity muscle strength was inversely related to the clustered cardiometabolic risk of the children and adolescents with or without adjustment for confounders (OR, 4.32; 95% confidence interval [CI], 1.87-9.97; OR, 7.64; 95% CI, 1.55- 37.74, respectively). CONCLUSION: Physical fitness, especially lower extremity muscle strength, is significantly inversely associated with individual and clustered cardiometabolic risks in Korean children and adolescents.

Intake and blood concentrations of folate and their association with health-related behaviors in Korean college students.

The purpose of this study is to assess folate intake, and serum and red blood cell (RBC) folate concentrations, and investigate the association between folate status and health-related behaviors among Korean college students. A total of 169 students, aged between 18 and 27 years, participated in this study. Dietary intake data were collected by trained interviewers using a 24-hour recall method for three non-consecutive days in 2009. Information on health-related behaviors was obtained by a self-administered questionnaire. Serum and RBC folate concentrations were measured by microbiological assay. The average intakes of folate were 456 µgDFE and 347 µgDFE in male and female students, respectively. While the average serum folate concentration was significantly lower in male students (8.9 ng/mL) compared to female students (12.5 ng/mL), RBC concentrations were not significantly different between male (398.6 ng/mL) and female students (405.3 ng/mL). In male students, low serum folate concentrations were associated with total folate intake less than the Estimated Average Requirement, non-use of folic acid supplements, smoking, alcohol drinking at least once a week and low physical activity. In female students, low serum folate concentrations were associated with smoking and alcohol drinking at least two drinks at a time and BMI ≥ 25. Alcohol drinking and low physical activity were also associated with low RBC folate concentrations in both male and female students. In order to improve folate nutritional status of college students, the practice of desirable health-related behaviors, such as non-smoking, moderate alcohol drinking, regular physical activity, and maintenance of healthy BMI should be encouraged along with consumption of folate-rich foods and supplements.

Sphingobacterium composti sp. nov., isolated from cotton-waste composts.

A Gram-negative, strictly aerobic, short rod-shaped, non-motile bacterial strain designated 4M24(T) was isolated from cotton-waste compost. Analysis of the 16S rRNA gene sequence of strain 4M24(T) revealed that it is a member of the genus Sphingobacterium, sharing 88.5-94.5 % sequence similarity with type strains of the genus Sphingobacterium and being most closely related to Sphingobacterium daejeonense TR6-04(T) (94.5 % sequence similarity) and Sphingobacterium mizutaii ATCC 33299(T) (92.2 % similarity). The major fatty acids of strain 4M24(T) grown on trypticase soy agar medium were summed feature 3 (iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c; 37.5 %), iso-C(15 : 0) (29.5 %) and iso-C(17 : 0) 3-OH (19.7 %). The G+C content of the genomic DNA was 42.3 mol%. On the basis of phenotypic and genotypic characteristics, strain 4M24(T) represents a novel species of the genus Sphingobacterium, for which the name Sphingobacterium composti sp. nov. is proposed. The type strain is 4M24(T) (=KACC 11313(T)=DSM 18850(T)).