We have long known that language is lateralized to the left hemisphere (LH) in most neurologically healthy adults. In contrast, findings on lateralization of function during development are more complex. As in adults, anatomical, electrophysiological, and neuroimaging studies in infants and children indicate LH lateralization for language. However, in very young children, lesions to either hemisphere are equally likely to result in language deficits, suggesting that language is distributed symmetrically early in life. We address this apparent contradiction by examining patterns of functional MRI (fMRI) language activation in children (ages 4 through 13) and adults (ages 18 through 29). In contrast to previous studies, we focus not on lateralization per se but rather on patterns of left-hemisphere (LH) and right-hemisphere (RH) activation across individual participants over age. Our analyses show significant activation not only in the LH language network but also in their RH homologs in all of the youngest children (ages 4 through 6). The proportion of participants showing significant RH activation decreases over age, with over 60% of adults lacking any significant RH activation. A whole-brain correlation analysis revealed an age-related decrease in language activation only in the RH homolog of Broca’s area. This correlation was independent of task difficulty. We conclude that, while language is left-lateralized throughout life, the RH contribution to language processing is also strong early in life and decreases through childhood. Importantly, this early RH language activation may represent a developmental mechanism for recovery following early LH injury.
Pseudomonas aeruginosa and species of the Burkholderia cepacia complex are the primary bacterial pathogens contributing to lung disease in patients with cystic fibrosis. Quorum sensing systems using N-acyl homoserine lactone (AHL) signal molecules are involved in the regulation of a number of virulence factors in these species. Extracts of mucopurulent respiratory secretions from 13 cystic fibrosis patients infected with P. aeruginosa and/or strains of the B. cepacia complex were fractionated using reverse-phase fast pressure liquid chromatography and analyzed for the presence of AHLs using a traI-luxCDABE-based reporter that responds to AHLs with acyl chains ranging between 4 and 12 carbons. Using this assay system, a broad range of AHLs were detected and identified despite being present at low concentrations in limited sample volumes. N-(3-oxo-dodecanoyl)-l-homoserine lactone, N-(3-oxo-decanoyl)-l-homoserine lactone and N-octanoyl-l-homoserine lactone (OHL) were the AHLs most frequently identified. OHL and N-decanoyl-l-homoserine lactone were detected in nanomolar concentrations compared to picomolar amounts of the 3-oxo-derivatives of the AHLs identified.
The Burkholderia cenocepacia cepIR quorum-sensing system regulates expression of extracellular proteases, chitinase, and genes involved in ornibactin biosynthesis, biofilm formation, and motility. In a genome-wide screen we identified cepIR-regulated genes by screening a random promoter library of B. cenocepacia K56-2 constructed in a luminescence reporter detection plasmid for differential expression in response to N-octanoyl-L-homoserine lactone (OHL). Eighty-nine clones were identified; in 58 of these clones expression was positively regulated by cepIR, and in 31 expression was negatively regulated by cepIR. The expression profiles of the 89 promoter clones were compared in the cepI mutant K56-dI2 in medium supplemented with 30 pM OHL and K56-2 to confirm that the presence of OHL restored expression to wild-type levels. To validate the promoter library observations and to determine the effect of a cepR mutation on expression of selected genes, the mRNA levels of nine genes whose promoters were predicted to be regulated by cepR were quantitated by quantitative reverse transcription-PCR in the wild type and cepI and cepR mutants. The expression levels of all nine genes were similar in the cepI and cepR mutants and consistent with the promoter-lux reporter activity. The expression of four selected cepIR-regulated gene promoters was examined in a cciIR mutant, and two of these promoters were also regulated by cciIR. This study extends our understanding of genes whose expression is influenced by cepIR and indicates the global regulatory effect of the cepIR system in B. cenocepacia.
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