To investigate the importance of the 3'-untranslated region (UTR) of the mouse cholesterol 7alpha-hydroxylase (cyp7) mRNA in post-transcriptional regulation of expression of the cyp7 gene, chimaeric genes encoding mRNA containing the structural sequence of chloramphenicol acetyltransferase (CAT) linked to either the 3'-UTR of the mouse cyp7 mRNA or the SV40 early gene mRNA were constructed. The human cytomegalovirus (CMV) promoter was used to drive the expression of all the chimaeric genes. Thus the transgenes had identical sequences in the promoter, the regions encoding the 5'-UTR and translated sequence but differed in the region encoding the 3'-UTR of their respective mRNA species. The transgene containing the entire cyp7 3'-UTR (designated CMV.CAT.CYP7) gave rise to CAT activity in transfected hepatoma cells that was one-quarter of that obtained in cells transfected with the transgene containing the SV40 3'-UTR (designated CMV.CAT.SV40). The 3'-UTR of the cyp7 mRNA contains sequences resembling AU-rich elements (AREs). Deleting eight of nine putative AREs from the CYP7 3'-UTR sequence increased the CAT activity to a level greater than that observed for CMV.CAT. SV40, whereas deletion of the intron region had no effect. These results show that the AREs of the 3'-UTR of the cyp7 mRNA decrease transgene expression. Bile acids are known to repress the expression of the cyp7 gene. To test whether the 3'-UTR of the cyp7 mRNA has a role in this process, the expression of the chimaeric genes was evaluated in hepatoma cells competent for bile acid uptake. Conjugated bile acids, but not unconjugated bile acids, further decreased the expression of the CMV.CAT.CYP7 transgene. The same bile acids had no effect on the expression of the CMV.CAT.SV40 transgene. Deletion of the intron from the cyp7 sequence did not alter the CAT activity compared with the parental plasmid, and also did not alter the sensitivity of the transgene to the conjugated bile acids. Deletion of the AREs from the cyp7 3'-UTR, which increased the expression of the transgene, did not abolish the sensitivity of the transgene to repression by conjugated bile acids. Thus the 3'-UTR of the mouse cyp7 mRNA also contains elements that facilitate the further repression of transgene expression in the presence of conjugated bile acids. The results indicate that the 3'-UTR of the mouse cyp7 mRNA contains information specifying regulation at the post-transcriptional level.

No abstract

Reading requires efficient communication between brain regions that are situated all over the cortex. These brain areas are structurally connected by white-matter pathways that develop over the period of reading acquisition. Here, we conducted a cross-sectional study to assess the relationship between white-matter tracts and reading performance across the lifespan. Methods: Behavioral (reading performance) and neuroimaging (diffusion tensor imaging [DTI]) data were collected from participants aged 3–21 years as a part of the multi-site project called the pediatric imaging neurocognition genetics study. DTI measures (fractional anisotropy [FA], mean diffusivity, radial diffusivity and axial diffusivity) of bilateral dorsal tracts (arcuate fasciculus, superior longitudinal fasciculus, and posterior superior longitudinal fasciculus) and ventral tracts (uncinate fasciculus, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus) were extracted. Reading performance was calculated as the number of items correctly read (words for older children and letters in the case of young children). Correlational and regression analyses were conducted between the DTI measures and reading scores. Results: During the early stages of reading acquisition (ages 3–6), the dorsal tracts were positively related to reading performance (as FA goes up, reading performance goes up). For ages 6–10, the dorsal tracts remain positively associated with reading performance and a relationship between ventral tracts and reading performance emerges. From the age of 10 onwards, the dorsal tracts no longer correlate with reading performance, and a brain-behavior relationship in the right ventral tracts begins to shift, whereby higher FA is associated with lower reading performance. In addition to the involvement of left hemispheric tracts, this study revealed the initial engagement of right hemispheric tracts during the early stages of reading acquisition. Conclusion: We discuss these different associations of white-matter tracts with reading during development in the context of the biological processes model of myelination and pruning.

Reading is a complex process that includes the integration of information about letters (graphemes) and sounds (phonemes). In many circumstances, such as noisy environments, response inhibition is an additional factor that plays a marked role in successful oral reading. Response inhibition can take the form of task relevant inhibition (i.e., foils in a go/no-go task) and task irrelevant inhibition (i.e., distractor information). Here we investigated task relevant inhibition by having participants (N = 30) take part in two tasks: go/no-go naming with nonwords foils (GNG-NW) and go/no-go naming with pseudohomophones foils (GNG-PH). Also, we investigated the addition of task irrelevant inhibition by having participants (N = 28) take part in two tasks: GNG-NW + information masking and GNG-PH + information masking. We provide evidence that during a task relevant inhibition task, sub-word sound level information can be successfully inhibited, as evidenced by comparable response times for regular words and exception words, provided the foils do not contain familiar sound-based information (GNG-NW). In contrast, regular words were read aloud faster than exception words in a GNG-PH task, indicating that sub-word level interference occurs when the foils contain familiar sound-based information. The addition of task irrelevant inhibition (i.e., information masking at the phoneme level), served to increase response time overall, but did not impact the pattern of response times between regular words and exception words. Together these findings provide useful information regarding the role of response inhibition in word recognition and may be useful in computational models of word recognition and future work may benefit from accounting for the effects outlined in this paper.

No abstract