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Sphingosine 1-Phosphate Regulates Obesity and Glucose Homeostasis.

One of the major global health and welfare issues is the treatment of obesity and associated metabolic disorders, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease. Obesity, caused by the excessive accumulation of triglycerides in adipose tissues, induces adipocyte dysfunction, followed by inflammation, in adipose tissues and lipotoxicity in nonadipose tissues. Several studies have shown that obesity and glucose homeostasis are influenced by sphingolipid mediators, including ceramide and sphingosine 1-phosphate (S1P). Cellular accumulation of ceramide impairs pancreatic β-cell survival, confers insulin resistance in the liver and the skeletal muscle, and deteriorates adipose tissue inflammation via unknown molecular mechanisms. The roles of S1P are more complicated, because there are five cell-surface S1P receptors (S1PRs: S1P1-5) which have altered functions, different cellular expression patterns, and inapparent intracellular targets. Recent findings, including those by our group, support the notable concept that the pharmacological activation of S1P1 or S1P3 improves obesity and associated metabolic disorders, whereas that of S1P2 has the opposite effect. In addition, the regulation of S1P production by sphingosine kinase (SphK) is an essential factor affecting glucose homeostasis. This review summarizes the current knowledge on SphK/S1P/S1PR signaling in and against obesity, insulin resistance, and associated disorders.

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Opposing Roles of Sphingosine 1-Phosphate Receptors 1 and 2 in Fat Deposition and Glucose Tolerance in Obese Male Mice.

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that regulates fundamental cellular processes such as proliferation, migration, apoptosis, and differentiation through 5 cognate G protein-coupled receptors (S1P1-S1P5). We previously demonstrated that blockade of S1P2 signaling in S1P2-deficient mice attenuates high-fat diet-induced adipocyte hypertrophy and glucose intolerance and an S1P2-specific antagonist JTE-013 inhibits, whereas an S1P1/S1P3 dual antagonist (VPC23019) activates, adipogenic differentiation of preadipocytes. Based on those observations, this study examined whether an S1P1-specific agonist, SEW-2871, VPC23019, or their combination acts on obesity and glucose intolerance in leptin-deficient ob/ob mice. The oral administration of SEW-2871 or JTE-013 induced significant reductions in body/epididymal fat weight gains and epididymal/inguinal fat adipocyte sizes and improved glucose intolerance and adipocyte inflammation in ob/ob mice but not in their control C57BL/6J mice. Both SEW-2871 and JTE-013 decreased messenger RNA levels of tumor necrosis factor-α and CD11c, whereas they increased those of CD206 and adiponectin in the epididymal fats isolated from ob/ob mice with no changes in the levels of peroxisome proliferator activated receptor γ and its regulated genes. By contrast, VPC23019 did not cause any such alterations but counteracted with all those SEW-2871 actions in these mice. In conclusion, the S1P1 agonist SEW-2871 acted like the S1P2 antagonist JTE-013 to reduce body/epididymal fats and improve glucose tolerance in obese mice. Therefore, this study raises the possibility that endogenous S1P could promote obesity/type 2 diabetes through the S1P2, whereas exogenous S1P could act against them through the S1P1.

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Existence of circadian rhythm and its response behavior under different storage conditions of soybean sprouts

The circadian system plays an essential role in plant cells, and numerous physiological events are generally modulated by circadian clock genes. To further improve postharvest handling of fresh produce, it is vital to understanding the behavior of clock gene expression and its underlying interactions with changes in quality. In this study, the effect of temperature and controlled atmosphere storage on the expression of clock genes (GmLCL1, GmPRR7, GmGI, GmTOC1, and GmLUX), postharvest quality characteristics and their related genes in soybean sprouts were investigated. By fitting the obtained gene expression level using the qPCR method with the cosine curve equation, it was successfully found that the circadian rhythm existed under constant dark storage conditions of soybean sprouts. A significant rhythm in clock gene expression was observed in control soybean sprouts. In contrast, low temperature storage diminished the cyclic expression of GmLCL1, GmPRR7, and GmTOC1, which also affected GmGI and GmLUX expression. Additionally, high CO2 concentrations during storage disturbed the circadian clock by affecting the phase and amplitude of each gene; for low O2 concentrations, it was only affected by amplitude. Interestingly, low temperature, low O2, and high CO2 maintained postharvest quality, including reduced respiration, weight loss and browning incidence. The expression behaviors of postharvest quality attribute-related genes (GmFUM1, GmCS, Gm2-OGDH, GmPPO1, GmPAL) were also influenced by the storage treatments. Overall, the findings first suggest a possible link between clock disruption and postharvest quality maintenance of soybean sprouts.

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Chapter 6. L2 writing and its external correlates

The present meta-analysis examined the overall average correlation between second/foreign language (L2) writing performance and each of 11 key predictor variables frequently investigated in the research domain, and compared the relative importance of those variables. A series of moderator analyses were also carried out to examine the effects of age, L2 proficiency, first language (L1) and L2 distance, learning context, and measurement characteristics for six high-evidence correlates (L2 grammar, L2 vocabulary, L2 reading, L2 speaking, L1 writing, and motivational constructs). By doing so, we examined various L2 proficiency models, writing models, and hypotheses, particularly the core-periphery model proposed by Hulstijn (2015). To this end, a total of 103 retrieved studies contributed 377 effect sizes based on 112,475 independent participants. The results showed that L2 reading and speaking achievement had strong average correlations with L2 writing performance, whereas L1 writing performance had a medium correlation with it. L2 linguistic knowledge (grammar, vocabulary, transcription, decoding) had more medium to strong effects on L2 writing performance than language-general cognitive skills and motivational constructs, which had only weak effects. The effects of metacognitive knowledge were trivial and insignificant. L2 proficiency, age, and certain measurement characteristics were found to be significant moderators for certain components.

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Chapter 5. L2 writing and its internal correlates

This study examined the overall average correlation between second/foreign language (L2) writing performance and frequently investigated features of writing (i.e., writing-internal correlates). The correlates of L2 writing performance included objective measures of text features (syntactic complexity, lexical complexity, accuracy, fluency, and cohesion) as well as subjective measures (content, argument, organization, cohesion, coherence, grammar, vocabulary, language use, mechanics, and accuracy). A series of moderator analyses were also carried out for each type of objective measure to examine the effects of participants’ age, L2 proficiency, learning context, first language (L1) and L2 distance, task type, writing scoring method, and some characteristics of objective measures. By doing so, the present study aimed to identify key correlates of L2 writing performance and compare their relative importance. To this end, a total of 103 retrieved studies contributed 1,045 effect sizes based on 15,537 independent participants. The results for objective measures demonstrated that fluency had the strongest mean correlation with L2 writing performance (r = .570), followed by accuracy (r = .477), lexical complexity (r = .295), syntactic complexity (r = .271), and cohesion (r = .198). All subjective measure components had strong mean correlations with L2 writing performance (r = .668 to .927), but content and language use features had the strongest effects and cohesion and coherence features showed the least effects. Participants’ age, learning context, L1–L2 distance, writing scoring method, and some measurement characteristics were found to be significant moderators for certain components. The findings of this study have implications for L2 instruction suggesting that fluency and language accuracy of L2 writing should be promoted across the various developmental stages of L2 learners in various conditions, whereas lexical and syntactic competence should be more focused upon when instructing child/adolescent or low/intermediate L2 writers.

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Investigation of Maternal Diet and FADS1 Polymorphism Associated with Long-Chain Polyunsaturated Fatty Acid Compositions in Human Milk.

Increasing the amount of long-chain polyunsaturated fatty acids (LCPUFA) in human milk is an important strategy for infant growth and development. We investigated the associations of LCPUFA compositions in human milk with maternal diet (especially fish and shellfish intake), with fatty acid Δ5 desaturase gene (FADS1) polymorphisms, and with gene-diet interactions. The present study was performed as part of an adjunct study of the Japan Environment and Children’s Study. The participants were 304 lactating females, who provided human milk 6–7 months after delivery. Fatty acids in human milk were analyzed by gas chromatography, and dietary surveys were conducted using a brief self-administered diet history questionnaire. We also analyzed a single nucleotide polymorphism of FADS1 (rs174547, T/C). There was a significant difference in arachidonic acid (ARA) composition in human milk among the genotype groups, and the values were decreasing in the order of TT > TC > CC. The concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were also different between TT and CC genotype, indicating a tendency for decreasing values in the same order. The composition of ARA showed significant gene–dietary interactions in multiple regression analysis, and the positive correlation between fish and shellfish intake and ARA composition in human milk was significant only in the CC genotype. Moreover, the factor most strongly associated with EPA and DHA composition in human milk was fish and shellfish intake. Therefore, it was suggested that increasing fish and shellfish intake in mothers may increase EPA and DHA composition in human milk, while increasing fish and shellfish intake in CC genotype mothers may lead to increased ARA composition in human milk.

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