Sex differences in the use of delayed semantic context when listening to disrupted speech.

Female as opposed to male listeners were better able to use a delayed informative cue at the end of a long sentence to report an earlier word which was disrupted by noise. Informative (semantically related) or uninformative (semantically unrelated) word cues were presented 2, 6, or 10 words after a target word whose initial phoneme had been replaced with noise. A total of 84 young adults (45 males) listened to each sentence and then repeated it after its offset. The semantic benefit effect (SBE) was the difference in the accuracy of report of the disrupted target word during informative vs. uninformative sentences. Women had significantly higher SBEs than men even though there were no significant sex differences in terms of number of non-target words reported, the effect of distance between the disrupted target word and the informative cue, or kinds of errors generated. We suggest that the superior ability of women to use delayed semantic information to decode an earlier ambiguous speech signal may be linked to women's tendency to engage the hemispheres more bilaterally than men during word processing. Since the maintenance of semantic context under ambiguous conditions demands more right than left hemispheric resources, this may give women an advantage.

A demonstration that task difficulty can confound the interpretation of lateral differences in brain activation between typical and dyslexic readers.

Dyslexic readers (DRs) manifest atypical patterns of brain activity, which may be attributed to aberrant neural connectivity and/or an attempt to activate compensatory pathways. This paper evaluates whether differences in brain activation patterns between DRs and typical readers (TRs) are confounded by task difficulty. Eight DRs and eight TRs matched for age, sex, and nonverbal IQ performed pseudoword rhyming tasks at two levels of difficulty during magnetoencephalography. Task difficulty varied with the number of successive target pseudowords presented before the test pseudoword. Regions of interest were: the temporoparietal area (TPA), the ventral occipital temporal area (VOT), and the inferior frontal gyrus (IFG). Activity was analysed for the 660-ms period after test pseudoword onset. During the discrepant performance condition left hemispheric TPA activation increased across time for TRs, but not DRs, and IFG bihemispheric activation was greater in TRs by the end of the trial. During the equivalent performance condition no group differences in TPA or IFG activation were found. We argue that these results indicate that direct comparison of DR versus TR brain activity is confounded when DRs are more challenged than TRs. This highlights the importance of equating reading group performance during neuroimaging of reading-related tasks.

Diffusion tensor quantification of the relations between microstructural and macrostructural indices of white matter and reading.

Few researchers agree about the relationship between fronto-temporo-parietal white matter microstructure and reading skills. Unlike many previous reports, which only measured fractional anisotropy, we have also measured macroscopic volume (regional white matter tract volume) and three microstructural indices (axial, radial, and mean diffusivity) to increase interpretability of our findings. We examined the reading-related skills and white matter structure in 10 adolescents and adults with a history of poor reading and 20 age-matched typical readers. We applied a diffusion tensor imaging atlas-based algorithm to major white matter pathways. The relation of white matter structural indices to reading group, hemisphere, and reading-related skill was analyzed using linear models. White matter microstructural indices were related to performance on a sublexical decoding task, but the relations between particular microstructural indices and sublexical decoding ability and reading group were different for association (i.e., cortical-cortical) and projection (i.e., subcortical-cortical) white matter pathways. Changes in projection pathways were consistent with alterations in white matter organization and axonal size, whereas changes in association pathways were consistent with alternations in pathway complexity. Changes in macrostructure paralleled changes in microstructure. We conclude that the relations between several microstructural indices and factors related to reading ability are different for association and projection pathways.

Notch2 signaling induces apoptosis and inhibits human MDA-MB-231 xenograft growth.

Notch functions as an oncogene or tumor inhibitor in various cancers, and decreases in Notch2 expression are associated with increasing grade of human breast cancer. We constitutively activated Notch signaling with intracellular domain (ICD) expression in the human adenocarcinoma line MDA-MB-231. Notch2 signaling increased apoptosis, whereas Notch4ICD (int3) significantly increased cell proliferation and growth. Cells with activated Notch2 or Notch4 were injected into nu/nu mice for analysis of in vivo tumor xenograft phenotype. Tumor growth was significantly altered depending on the receptor activated. Notch2ICD potently suppressed tumor take and growth, leading to a 60% decrease in tumors and significantly smaller, necrotic tumors. Despite this, Notch2ICD tumors were highly vascularized, although the vessels were smaller and comprised a more immature network compared with Notch4ICD tumors. Notch4ICD tumors were highly aggressive and well vascularized, indicating a role for Notch4 signaling in the promotion of the malignant phenotype in addition to its transforming ability. Although both NotchICD groups expressed angiogenic factors, Notch4ICD had selective vascular endothelial growth factor-D in both tumor and host stroma, suggesting a differential regulation of cytokines that may impact vascular recruitment and autocrine tumor signaling. Our results demonstrate that Notch2 signaling is a potent inhibitory signal in human breast cancer xenografts.