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  • 1
    Online Resource
    Online Resource
    Society for Neuroscience ; 2015
    In:  The Journal of Neuroscience Vol. 35, No. 50 ( 2015-12-16), p. 16352-16361
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 35, No. 50 ( 2015-12-16), p. 16352-16361
    Abstract: The integration of visual details into a holistic percept is essential for object recognition. This integration has been reported as a key deficit in patients with autism spectrum disorders (ASDs). The weak central coherence account posits an altered disposition to integrate features into a coherent whole in ASD. Here, we test the hypothesis that such weak perceptual coherence may be reflected in weak neural coherence across different cortical sites. We recorded magnetoencephalography from 20 adult human participants with ASD and 20 matched controls, who performed a slit-viewing paradigm, in which objects gradually passed behind a vertical or horizontal slit so that only fragments of the object were visible at any given moment. Object recognition thus required perceptual integration over time and, in case of the horizontal slit, also across visual hemifields. ASD participants were selectively impaired in the horizontal slit condition, indicating specific difficulties in long-range synchronization between the hemispheres. Specifically, the ASD group failed to show condition-related enhancement of imaginary coherence between the posterior superior temporal sulci in both hemispheres during horizontal slit-viewing in contrast to controls. Moreover, local synchronization reflected in occipitocerebellar beta-band power was selectively reduced for horizontal compared with vertical slit-viewing in ASD. Furthermore, we found disturbed connectivity between right posterior superior temporal sulcus and left cerebellum. Together, our results suggest that perceptual integration deficits co-occur with specific patterns of abnormal global and local synchronization in ASD. SIGNIFICANCE STATEMENT The weak central coherence account proposes a tendency of individuals with autism spectrum disorders (ASDs) to focus on details at the cost of an integrated coherent whole. Here, we provide evidence, at the behavioral and the neural level, that visual integration in object recognition is impaired in ASD, when details had to be integrated across both visual hemifields. We found enhanced interhemispheric gamma-band coherence in typically developed participants when communication between cortical hemispheres was required by the task. Importantly, participants with ASD failed to show this enhanced coherence between bilateral posterior superior temporal sulci. The findings suggest that visual integration is disturbed at the local and global synchronization scale, which might bear implications for object recognition in ASD.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2015
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  • 2
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 109, No. 42 ( 2012-10-16), p. 17034-17039
    Abstract: Small cell lung cancer (SCLC) accounts for about 15% of all lung cancers. The prognosis of SCLC patients is devastating and no biologically targeted therapeutics are active in this tumor type. To develop a framework for development of specific SCLC-targeted drugs we conducted a combined genomic and pharmacological vulnerability screen in SCLC cell lines. We show that SCLC cell lines capture the genomic landscape of primary SCLC tumors and provide genetic predictors for activity of clinically relevant inhibitors by screening 267 compounds across 44 of these cell lines. We show Aurora kinase inhibitors are effective in SCLC cell lines bearing MYC amplification, which occur in 3–7% of SCLC patients. In MYC -amplified SCLC cells Aurora kinase inhibition associates with G2/M-arrest, inactivation of PI3-kinase (PI3K) signaling, and induction of apoptosis. Aurora dependency in SCLC primarily involved Aurora B, required its kinase activity, and was independent of depletion of cytoplasmic levels of MYC. Our study suggests that a fraction of SCLC patients may benefit from therapeutic inhibition of Aurora B. Thus, thorough chemical and genomic exploration of SCLC cell lines may provide starting points for further development of rational targeted therapeutic intervention in this deadly tumor type.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2012
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    detail.hit.zdb_id: 1461794-8
    SSG: 11
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