Vocabulary, Metalinguistic Awareness and Language Dominance Among Bilingual Preschool Children

Awareness of language structure has been studied in bilinguals, but there is limited research on how language dominance is related to metalinguistic awareness, and whether metalinguistic awareness predicts vocabulary size. The present study aims to explore the role of language dominance in the relation between vocabulary size in both languages of bilingual children and metalinguistic awareness in the societal language. It evaluates the impact of two metalinguistic awareness abilities, morphological and lexical awareness, on receptive and expressive vocabulary size. This is of special interest since most studies focus on the impact of exposure on vocabulary size but very few explore the impact of the interaction between metalinguistic awareness and dominance. 5–6-year-old preschool children with typical language development participated in the study: 15 Russian-Hebrew bilingual children dominant in the societal language (SL) Hebrew, 21 Russian-Hebrew bilingual children dominant in the Heritage language (HL) Russian and 32 monolingual children. Dominance was determined by relative proficiency, based on standardized tests in the two languages. Tasks of morphological and lexical awareness were administered in SL-Hebrew, along with measures of receptive and expressive vocabulary size in both languages. Vocabulary size in SL-Hebrew was significantly higher for SL-dominant bilinguals (who performed like monolinguals) than for HL-dominant bilinguals, while HL-Russian vocabulary size was higher for HL-dominant bilinguals than for SL-dominant bilinguals. A hierarchical regression analyzing the relationship between vocabulary size and metalinguistic awareness showed that dominance, lexical metalinguistic awareness and the interaction between the two were predictors of both receptive and expressive vocabulary size. Morphological metalinguistic awareness was not a predictor of vocabulary size. The relationship between lexical awareness and SL-vocabulary size was limited to the HL-dominant group. HL-dominant bilinguals relied on lexical metalinguistic awareness, measured by fast mapping abilities, that is, the abilities to acquire new words, in expanding their vocabulary size, whereas SL-dominant bilinguals and monolinguals did not. This difference reflects the milestones of lexical acquisition the different groups have reached. These findings show that metalinguistic awareness should also be taken into consideration when evaluating the variables that influence vocabulary size among bilinguals though different ways in different dominance groups

The Mu-Opioid Receptor Variant N190K is Unresponsive to Peptide Agonists Yet Can be Rescued by Small Molecule Drugs MOL #64188 2 Running Title: Small molecules rescue function of an inactive MOR variant

MOL #64188 3 Abstract The mu-opioid receptor (MOR) plays an important role in modulating analgesia, feeding behavior and a range of autonomic functions. In the current study, we investigated the degree to which thirteen naturally-occurring missense mutations affect the pharmacological properties of the human MOR. Following expression of each receptor in HEK293 cells, signaling (Gα i/omediated) induced by peptide agonists was assessed utilizing luciferase reporter gene assays. Multiple mutants (S66F, S147C, R260H, R265C, R265H and S268P) show a significant reduction in agonist potency. At the N190K variant, agonist-mediated signaling was essentially absent. ELISA, microscopic analysis and radioligand binding assays revealed that this mutant shows markedly reduced cell surface expression, whereas all other receptor variants were expressed at normal levels. Surface expression of the N190K variant could be increased by incubation with the alkaloid agonist buprenorphine, or with either of the structurally related MOR antagonists, naltrexone or naloxone. Surprisingly, both putative antagonists, despite being inactive at the wild type MOR, triggered a concentration-dependent increase in N190K receptor mediated signaling. In contrast, peptidic ligands failed to promote expression or rescue function of the N190K mutant. Subsequent analysis of the N190K variant in an ethnically diverse cohort identified this isoform in a subgroup of African Americans. Taken together, our studies reveal that the N190K mutation leads to severe functional alterations and, in parallel, changes the response to established MOR ligands. The extent to which this mutation results in physiological abnormalities or affects drug sensitivity in selected populations (e.g. those with chronic pain or addiction) remains to be investigated

Two Naturally Occurring Mutations in the Type 1 Melanin-Concentrating Hormone Receptor Abolish Agonist-Induced Signaling

The melanin-concentrating hormone (MCH) receptor type 1 (MCHR1) is a seven-transmembrane domain protein that modulates orexigenic activity of MCH, the corresponding endogenous peptide agonist. MCH antagonists are being explored as a potential treatment for obesity. In the current study, we examined the pharmacological impact of 11 naturally occurring mutations in the human MCHR1. Wild-type and mutant receptors were transiently expressed in human embryonic kidney 293 cells. MCHR1-mediated, Gαi-dependent signaling was monitored by using luciferase reporter gene assays. Two mutants, R210H and P377S, failed to respond to MCH. Five other variants showed significant alterations in MCH efficacy, ranging from 44 to 142% of the wild-type value. At each of the MCH-responsive mutants, agonist potency and inhibition by (S)-methyl 3-((3-(4-(3-acetamidophenyl)piperidin-1-yl)propyl)carbamoyl)-4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (SNAP-7941), an established MCHR1 small-molecule antagonist, were similar to wild type. To explore the basis for inactivity of the R210H and P377S mutants, we examined expression levels of these receptors. Assessment by enzyme-linked immunosorbent assay revealed that cell surface expression of both nonfunctional receptors was comparable with wild type. Overnight treatment with SNAP-7941, followed by washout of antagonist, enhanced MCH induced signaling by the wild-type receptor and restored MCH responsiveness of the P377S but not the R210H variant. It is of note that the two loss-of-function mutants were identified in markedly underweight individuals, raising the possibility that a lean phenotype may be linked to deficient MCHR1 signaling. Formal association studies with larger cohorts are needed to explore the extent to which signaling-deficient MCHR1 variants influence the maintenance of body weight

The μ-Opioid Receptor Variant N190K Is Unresponsive to Peptide Agonists yet Can be Rescued by Small-Molecule DrugsS⃞

The μ-opioid receptor (MOR) plays an important role in modulating analgesia, feeding behavior, and a range of autonomic functions. In the current study, we investigated the degree to which 13 naturally occurring missense mutations affect the pharmacological properties of the human MOR. After expression of each receptor in human embryonic kidney 293 cells, signaling (Gαi/o-mediated) induced by peptide agonists was assessed using luciferase reporter gene assays. Multiple mutants (S66F, S147C, R260H, R265C, R265H, and S268P) show a significant reduction in agonist potency. At the N190K variant, agonist-mediated signaling was essentially absent. Enzyme-linked immunosorbent assay, microscopic analysis, and radioligand binding assays revealed that this mutant shows markedly reduced cell-surface expression, whereas all other receptor variants were expressed at normal levels. Surface expression of the N190K variant could be increased by incubation with the alkaloid agonist buprenorphine or with either naltrexone or naloxone, structurally related MOR antagonists. We were surprised to find that both putative antagonists, despite being inactive at the wild-type MOR, triggered a concentration-dependent increase in N190K receptor-mediated signaling. In contrast, peptidic ligands failed to promote expression or rescue function of the N190K mutant. Subsequent analysis of the N190K variant in an ethnically diverse cohort identified this isoform in a subgroup of African Americans. Taken together, our studies reveal that the N190K mutation leads to severe functional alterations and, in parallel, changes the response to established MOR ligands. The extent to which this mutation results in physiological abnormalities or affects drug sensitivity in selected populations (e.g., those with chronic pain or addiction) remains to be investigated

The STE20/Germinal Center Kinase POD6 Interacts with the NDR Kinase COT1 and Is Involved in Polar Tip Extension in Neurospora crassa

Members of the Ste20 and NDR protein kinase families are important for normal cell differentiation and morphogenesis in various organisms. We characterized POD6 (NCU02537.2), a novel member of the GCK family of Ste20 kinases that is essential for hyphal tip extension and coordinated branch formation in the filamentous fungus Neurospora crassa. pod-6 and the NDR kinase mutant cot-1 exhibit indistinguishable growth defects, characterized by cessation of cell elongation, hyperbranching, and altered cell-wall composition. We suggest that POD6 and COT1 act in the same genetic pathway, based on the fact that both pod-6 and cot-1 can be suppressed by 1) environmental stresses, 2) altering protein kinase A activity, and 3) common extragenic suppressors (ropy, as well as gul-1, which is characterized here as the ortholog of the budding and fission yeasts SSD1 and Sts5, respectively). Unlinked noncomplementation of cot-1/pod-6 alleles indicates a potential physical interaction between the two kinases, which is further supported by coimmunoprecipitation analyses, partial colocalization of both proteins in wild-type cells, and their common mislocalization in dynein/kinesin mutants. We conclude that POD6 acts together with COT1 and is essential for polar cell extension in a kinesin/dynein-dependent manner in N. crassa