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This study was designed to examine whether infants acquiring languages that place a differential emphasis on nouns and verbs, focus their attention on motions or objects in the presence of a novel word. An infant-controlled habituation paradigm was used to teach 18- to 20-month-old English-, French-, and Japanese-speaking infants' novel words for events. Infants were habituated to two word-event pairings and then presented with new combinations that involved a familiar word with a new object or motion, or both. Children could map the novel word to both the object and the motion, despite the differential salience of object and motion words in their native language. A control experiment with no label confirmed that both object and motion changes were detectable. (Contains 3 figures, 1 table, and 3 footnotes.)

This study explored the psychometric properties and utility of the exposure hierarchy as a measure of treatment outcome for social anxiety disorder (SAD). An exposure hierarchy was created for each of 103 individuals with a diagnosis of SAD who completed a course of cognitive behavioral group therapy. Exposure hierarchy ratings were collected on a weekly basis, and a series of self-report measures were collected before and after treatment. Results indicated that the exposure hierarchy demonstrated high test-retest reliability, as well as significant convergent validity, as participants' exposure hierarchy ratings correlated positively with scores on conceptually related measures. Hierarchy ratings were significantly associated with changes in SAD symptoms over time. However, exposure hierarchy ratings were correlated to general measures of psychopathology, suggesting limited discriminant validity. The study highlights the clinical and scientific utility of the exposure hierarchy. (Contains 4 tables.)

Studied the case of bilingual acquisition across two modalities to examine diverging hypotheses about the types of knowledge underlying early bilingualism. Three children acquiring Langues des Signes Quebecoise and French, and three children acquiring French and English were videotaped over a year while novel and familiar speakers of each child's two languages were empirically manipulated. Results are discussed. (Author/VWL)

The energy-sensing kinase AMP-activated protein kinase (AMPK) is associated with the sodium-potassium-chloride cotransporter NKCC2 in the kidney and phosphorylates it on a regulatory site in vitro. To identify a potential role for AMPK in salt sensing at the macula densa, we have used the murine macula densa cell line MMDD1. In this cell line, AMPK was rapidly activated by isosmolar low-salt conditions. In contrast to the known salt-sensing pathway in the macula densa, AMPK activation occurred in the presence of either low sodium or low chloride and was unaffected by inhibition of NKCC2 with bumetanide. Assays using recombinant AMPK demonstrated activation of an upstream kinase by isosmolar low salt. The specific calcium/calmodulin-dependent kinase kinase inhibitor STO-609 failed to suppress AMPK activation, suggesting that it was not part of the signal pathway. AMPK activation was associated with increased phosphorylation of the specific substrate acetyl-CoA carboxylase (ACC) at [Ser.sup.79], as well as increased NKCC2 phosphorylation at [Ser.sup.126]. AMPK activation due to low salt concentrations was inhibited by an adenovirus construct encoding a kinase dead mutant of AMPK, leading to reduced ACC [Ser.sup.79] and NKCC2 [Ser.sup.126] phosphorylation. This work demonstrates that AMPK activation in macula densa-like cells occurs via isosmolar changes in sodium or chloride concentration, leading to phosphorylation of ACC and NKCC2. Phosphorylation of these substrates in vivo is predicted to increase intracellular chloride and so reduce the effect of salt restriction on tubuloglomerular feedback and renin secretion. AMPK; NKCC2; phosphorylation; sodium reabsorption

Array-based molecular strategies are employed to identify the gene responsible for the onset of action myoclonus-renal failure syndrome (AMRF). The myoclonus epilepsy and focal glomerulosclerosis is usually caused due to the deficiency of SCARB2/LIMP-2 protein in humans.

Kanellis, John, Scott Fraser, Marina Katerelos, and David A. Power. Vascular endothelial growth factor is a survival factor for renal tubular epithelial cells. Am J Physiol Renal Physiol 278: F905-F915, 2000.--Vascular endothelial growth factor (VEGF) acts primarily as an endothelial cell mitogen via the 'endothelial cell-specific' receptors VEGFR-1 (flt-1) and VEGFR-2 (flk-1/KDR). Only a few nonendothelial cells have been shown to possess functional VEGF receptors. We therefore examined the rat renal tubular epithelial cell line NRK52-E. NRK52-E expressed VEGFR-1 and VEGFR-2 mRNA and protein by RT-PCR, Northern blotting, Western blotting, immunofluorescence, and ligand binding. Serumstarved NRK52-E incubated with VEGF showed a significant increase in [[sup.3]H]thymidine incorporation compared with control (2.3-fold at 1-10 ng/ml, P [is less than] 0.05; 3.3-fold at 50-100 ng/ml, P [is less than] 0.01). VEGF also protected NRK52-E from hydrogen peroxide-induced apoptosis and necrosis compared with control (annexin-V-FITC-positive cells, 39 vs. 54%; viable cells, 50.5 vs. 39.7%). Immunohistochemical staining using a variety of antibodies showed expression of both VEGF receptors in normal rat renal tubules in vivo. Because VEGF induced a proliferative and an antiapoptotic response in renal tubular epithelial cells, these data suggest that VEGF may act as a survival factor for renal tubular epithelium in vivo. vascular endothelial growth factor receptors; flt-1; flk-1; vascular endothelial growth factor receptor 1; vascular endothelial growth factor receptor 2; apoptosis

Enhanced tubular reabsorption of salt is important in the pathogenesis of obesityrelated hypertension, but the mechanisms remain poorly defined. To identify changes in the regulation of salt transporters in the kidney, C57BL/6 mice were fed a 40% fat diet [high-fat diet (HFD)] or a 12% fat diet (control diet) for 14 wk. Compared with control diet-fed mice, HFD-fed mice had significantly greater elevations in weight, blood pressure, and serum insulin and leptin levels. When we examined Na+ transporter expression, Na+-K+-2Cl- cotransporter (NKCC2) was unchanged in whole kidney and reduced in the cortex, Na+-Cl- cotransporter (NCC) and α-epithelial Na+ channel (ENaC) and γ-ENaC were unchanged, and β-ENaC was reduced. Phosphorylation of NCC was unaltered. Activating phosphorylation of NKCC2 at S126 was increased 2.5-fold. Activation of STE-20/SPS1-related prolinealanine- rich protein kinase (SPAK)/oxidative stress responsive 1 kinase (OSR1) was increased in kidneys from HFD-fed mice, and enhanced phosphorylation of NKCC2 at T96/T101 was evident in the cortex. Increased activity of NKCC2 in vivo was confirmed with diuretic experiments. HFD-fed mice had reduced activating phosphorylation of AMP-activated protein kinase (AMPK) in the renal cortex. In vitro, activation of AMPK led to a reduction in phospho-SPAK/ phospho-OSR1 in AMPK+/+ murine embryonic fibroblasts (MEFs), but no effect was seen in AMPK-/- MEFs, indicating an AMPKmediated effect. Activation of the with no lysine kinase/SPAK/OSR1 pathway with low-NaCl solution invoked a greater elevation in phospho- SPAK/phospho-OSR1 in AMPK-/- MEFs than in AMPK+/+ MEFs, consistent with a negative regulatory effect of AMPK on SPAK/OSR1 phosphorylation. In conclusion, this study identifies increased phosphorylation of NKCC2 on S126 as a hitherto-unrecognized mediator of enhanced Na+ reabsorption in obesity and identifies a new role for AMPK in regulating the activity of SPAK/OSR1. [ABSTRACT FROM AUTHOR]

Salt reabsorption is the major energy-requiring process in the kidney, and AMP-activated protein kinase (AMPK) is an important regulator of cellular metabolism. Mice with targeted deletion of the ß1-subunit of AMPK (AMPK-ß1-/- mice) had significantly increased urinary Na+ excretion on a normal salt diet. This was associated with reduced expression of the ß-subunit of the epithelial Na+ channel (ENaC) and increased subapical tubular expression of kidney-specific Na+-K+-2Cl- cotransporter 2 (NKCC2) in the medullary thick ascending limb of Henle. AMPK-ß1-/- mice fed a salt-deficient diet were able to conserve Na+, but renin secretion increased 180% compared with control mice. Cyclooxygenase-2 mRNA also increased in the kidney cortex, indicating greater signaling through the macula densa tubular salt-sensing pathway. To determine whether the increase in renin secretion was due to a change in regulation of fatty acid metabolism by AMPK, mice with a mutation of the inhibitory AMPK phosphosite in acetyl-CoA carboxylase 1 [ACC1-knockin (KI)S79A mice] were examined. ACC1-KIS79A mice on a normal salt diet had no increase in salt loss or renin secretion, and expression of NKCC2, Na+-Cl- cotransporter, and ENaC-ß were similar to those in control mice. When mice were placed on a salt-deficient diet, however, renin secretion and cortical expression of cyclooxygenase-2 mRNA increased significantly in ACC1-KIS79A mice compared with control mice. In summary, our data suggest that renin synthesis and secretion are regulated by AMPK and coupled to metabolism by phosphorylation of ACC1. [ABSTRACT FROM AUTHOR]

The present study investigated whether children's representations of morphosyntactic information are abstract enough to guide early verb learning. Using an infant-controlled habituation paradigm with a switch design, Japanese-speaking children aged 1 ; 8 were habituated to two different events in which an object was engaging in an action. Each event was paired with a novel word embedded in a single intransitive verb sentence frame. The results indicated that only 40% of the children were able to map a novel verb onto the action when the mapping task was complex. However, by simplifying the mapping task, 88% of the children succeeded in verb–action mapping. There were no differences in perceptual salience between the agent and action switches in the task. These results provide strong evidence that Japanese-speaking children aged 1 ; 8 are able to use an intransitive verb sentence frame to guide early verb learning unless the mapping task consumes too much of their cognitive resources. [ABSTRACT FROM PUBLISHER]

Overviews a study of an extraordinary case of bilingual acquisition across two modalities to examine divergent hypothesis concerning types of knowledge underlying early bilinguism. Languages spoken by groups of children under study; Observation of sensitivity of language acquisition in both groups of children under study; Reason given for the capacity to differentiate between languages spoken by children.