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  • 1
    Online Resource
    Online Resource
    Aberrant topologies and reconfiguration pattern of functional brain network in children with second language reading impairment
    Wiley ; 2016
    In:  Developmental Science Vol. 19, No. 4 ( 2016-07), p. 657-672
    Details
    In: Developmental Science, Wiley, Vol. 19, No. 4 ( 2016-07), p. 657-672
    Abstract: Prior work has extensively studied neural deficits in children with reading impairment ( RI ) in their native language but has rarely examined those of RI children in their second language (L2). A recent study revealed that the function of the local brain regions was disrupted in children with RI in L2, but it is not clear whether the disruption also occurs at a large‐scale brain network level. Using fMRI and graph theoretical analysis, we explored the topology of the whole‐brain functional network during a phonological rhyming task and network reconfigurations across task and short resting phases in Chinese children with English reading impairment versus age‐matched typically developing ( TD ) children. We found that, when completing the phonological task, the RI group exhibited higher local network efficiency and network modularity compared with the TD group. When switching between the phonological task and the short resting phase, the RI group showed difficulty with network reconfiguration, as reflected in fewer changes in the local efficiency and modularity properties and less rearrangement of the modular communities. These findings were reproducible after controlling for the effects of in‐scanner accuracy, participant gender, and L1 reading performance. The results from the whole‐brain network analyses were largely replicated in the task‐activated network. These findings provide preliminary evidence supporting that RI in L2 is associated with not only abnormal functional network organization but also poor flexibility of the neural system in responding to changing cognitive demands.
    Type of Medium: Online Resource
    ISSN: 1363-755X , 1467-7687
    URL: Issue
    URL: Article
    DOI: 10.1111/desc.2016.19.issue-4
    DOI: 10.1111/desc.12440
    Language: English
    Publisher: Wiley
    Publication Date: 2016
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    SSG: 5,2
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  • 2
    Online Resource
    Online Resource
    Leader emergence through interpersonal neural synchronization
    Proceedings of the National Academy of Sciences ; 2015
    In:  Proceedings of the National Academy of Sciences Vol. 112, No. 14 ( 2015-04-07), p. 4274-4279
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 14 ( 2015-04-07), p. 4274-4279
    Abstract: The neural mechanism of leader emergence is not well understood. This study investigated ( i ) whether interpersonal neural synchronization (INS) plays an important role in leader emergence, and ( ii ) whether INS and leader emergence are associated with the frequency or the quality of communications. Eleven three-member groups were asked to perform a leaderless group discussion (LGD) task, and their brain activities were recorded via functional near infrared spectroscopy (fNIRS)-based hyperscanning. Video recordings of the discussions were coded for leadership and communication. Results showed that the INS for the leader–follower (LF) pairs was higher than that for the follower–follower (FF) pairs in the left temporo-parietal junction (TPJ), an area important for social mentalizing. Although communication frequency was higher for the LF pairs than for the FF pairs, the frequency of leader-initiated and follower-initiated communication did not differ significantly. Moreover, INS for the LF pairs was significantly higher during leader-initiated communication than during follower-initiated communications. In addition, INS for the LF pairs during leader-initiated communication was significantly correlated with the leaders’ communication skills and competence, but not their communication frequency. Finally, leadership could be successfully predicted based on INS as well as communication frequency early during the LGD (before half a minute into the task). In sum, this study found that leader emergence was characterized by high-level neural synchronization between the leader and followers and that the quality, rather than the frequency, of communications was associated with synchronization. These results suggest that leaders emerge because they are able to say the right things at the right time.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1422930112
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
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    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Janus effect of antifreeze proteins on ice nucleation
    Proceedings of the National Academy of Sciences ; 2016
    In:  Proceedings of the National Academy of Sciences Vol. 113, No. 51 ( 2016-12-20), p. 14739-14744
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 51 ( 2016-12-20), p. 14739-14744
    Abstract: The mechanism of ice nucleation at the molecular level remains largely unknown. Nature endows antifreeze proteins (AFPs) with the unique capability of controlling ice formation. However, the effect of AFPs on ice nucleation has been under debate. Here we report the observation of both depression and promotion effects of AFPs on ice nucleation via selectively binding the ice-binding face (IBF) and the non–ice-binding face (NIBF) of AFPs to solid substrates. Freezing temperature and delay time assays show that ice nucleation is depressed with the NIBF exposed to liquid water, whereas ice nucleation is facilitated with the IBF exposed to liquid water. The generality of this Janus effect is verified by investigating three representative AFPs. Molecular dynamics simulation analysis shows that the Janus effect can be established by the distinct structures of the hydration layer around IBF and NIBF. Our work greatly enhances the understanding of the mechanism of AFPs at the molecular level and brings insights to the fundamentals of heterogeneous ice nucleation.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1614379114
    RVK:
    TA 1000
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2016
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  • 4
    Online Resource
    Online Resource
    A nanoparticle formulation that selectively transfects metastatic tumors in mice
    Proceedings of the National Academy of Sciences ; 2013
    In:  Proceedings of the National Academy of Sciences Vol. 110, No. 36 ( 2013-09-03), p. 14717-14722
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 36 ( 2013-09-03), p. 14717-14722
    Abstract: Nanoparticle gene therapy holds great promise for the treatment of malignant disease in light of the large number of potent, tumor-specific therapeutic payloads potentially available for delivery. To be effective, gene therapy vehicles must be able to deliver their therapeutic payloads to metastatic lesions after systemic administration. Here we describe nanoparticles comprised of a core of high molecular weight linear polyethylenimine (LPEI) complexed with DNA and surrounded by a shell of polyethyleneglycol-modified (PEGylated) low molecular weight LPEI. Compared with a state-of-the-art commercially available in vivo gene delivery formulation, i.v. delivery of the core/PEGylated shell (CPS) nanoparticles provided more than a 16,000-fold increase in the ratio of tumor to nontumor transfection. The vast majority of examined liver and lung metastases derived from a colorectal cancer cell line showed transgene expression after i.v. CPS injection in an animal model of metastasis. Histological examination of tissues from transfected mice revealed that the CPS nanoparticles selectively transfected neoplastic cells rather than stromal cells within primary and metastatic tumors. However, only a small fraction of neoplastic cells ( 〈 1%) expressed the transgene, and the extent of delivery varied with the tumor cell line, tumor site, and host mouse strain used. Our results demonstrate that these CPS nanoparticles offer substantial advantages over previously described formulations for in vivo nanoparticle gene therapeutics. At the same time, they illustrate that major increases in the effectiveness of such approaches are needed for utility in patients with metastatic cancer.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1313330110
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
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  • 5
    Online Resource
    Online Resource
    Losartan, an AT1 Antagonist, Prevents Aortic Aneurysm in a Mouse Model of Marfan Syndrome
    American Association for the Advancement of Science (AAAS) ; 2006
    In:  Science Vol. 312, No. 5770 ( 2006-04-07), p. 117-121
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 312, No. 5770 ( 2006-04-07), p. 117-121
    Abstract: Aortic aneurysm and dissection are manifestations of Marfan syndrome (MFS), a disorder caused by mutations in the gene that encodes fibrillin-1. Selected manifestations of MFS reflect excessive signaling by the transforming growth factor–β (TGF-β) family of cytokines. We show that aortic aneurysm in a mouse model of MFS is associated with increased TGF-β signaling and can be prevented by TGF-β antagonists such as TGF-β–neutralizing antibody or the angiotensin II type 1 receptor (AT1) blocker, losartan. AT1 antagonism also partially reversed noncardiovascular manifestations of MFS, including impaired alveolar septation. These data suggest that losartan, a drug already in clinical use for hypertension, merits investigation as a therapeutic strategy for patients with MFS and has the potential to prevent the major life-threatening manifestation of this disorder.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1124287
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2006
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
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  • 6
    Online Resource
    Online Resource
    Enantioselective cyanation of benzylic C–H bonds via copper-catalyzed radical relay
    American Association for the Advancement of Science (AAAS) ; 2016
    In:  Science Vol. 353, No. 6303 ( 2016-09-02), p. 1014-1018
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 353, No. 6303 ( 2016-09-02), p. 1014-1018
    Abstract: Direct methods for stereoselective functionalization of sp 3 -hybridized carbon–hydrogen [C(sp 3 )–H] bonds in complex organic molecules could facilitate much more efficient preparation of therapeutics and agrochemicals. Here, we report a copper-catalyzed radical relay pathway for enantioselective conversion of benzylic C–H bonds into benzylic nitriles. Hydrogen-atom abstraction affords an achiral benzylic radical that undergoes asymmetric C(sp 3 )–CN bond formation upon reaction with a chiral copper catalyst. The reactions proceed efficiently at room temperature with the benzylic substrate as limiting reagent, exhibit broad substrate scope with high enantioselectivity (typically 90 to 99% enantiomeric excess), and afford products that are key precursors to important bioactive molecules. Mechanistic studies provide evidence for diffusible organic radicals and highlight the difference between these reactions and C–H oxidations mediated by enzymes and other catalysts that operate via radical rebound pathways.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aaf7783
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2016
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 7
    Online Resource
    Online Resource
    Modality- and Task-specific Brain Regions Involved in Chinese Lexical Processing
    MIT Press ; 2009
    In:  Journal of Cognitive Neuroscience Vol. 21, No. 8 ( 2009-08-01), p. 1473-1487
    Details
    In: Journal of Cognitive Neuroscience, MIT Press, Vol. 21, No. 8 ( 2009-08-01), p. 1473-1487
    Abstract: fMRI was used to examine lexical processing in native adult Chinese speakers. A 2 task (semantics and phonology) × 2 modality (visual and auditory) within-subject design was adopted. The semantic task involved a meaning association judgment and the phonological task involved a rhyming judgment to two sequentially presented words. The overall effect across tasks and modalities was used to identify seven ROIs, including the left fusiform gyrus (FG), the left superior temporal gyrus (STG), the left ventral inferior frontal gyrus (VIFG), the left middle temporal gyrus (MTG), the left dorsal inferior frontal gyrus (DIFG), the left inferior parietal lobule (IPL), and the left middle frontal gyrus (MFG). ROI analyses revealed two modality-specific areas, FG for visual and STG for auditory, and three task-specific areas, IPL and DIFG for phonology and VIFG for semantics. Greater DIFG activation was associated with conflicting tonal information between words for the auditory rhyming task, suggesting this region's role in strategic phonological processing, and greater VIFG activation was correlated with lower association between words for both the auditory and the visual meaning task, suggesting this region's role in retrieval and selection of semantic representations. The modality- and task-specific effects in Chinese revealed by this study are similar to those found in alphabetical languages. Unlike English, we found that MFG was both modality- and task-specific, suggesting that MFG may be responsible for the visuospatial analysis of Chinese characters and orthography-to-phonology integration at a syllabic level.
    Type of Medium: Online Resource
    ISSN: 0898-929X , 1530-8898
    URL: Article
    DOI: 10.1162/jocn.2009.21141
    Language: English
    Publisher: MIT Press
    Publication Date: 2009
    SSG: 5,2
    SSG: 7,11
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  • 8
    Online Resource
    Online Resource
    Tumor endothelial marker 1 ( Tem1 ) functions in the growth and progression of abdominal tumors
    Proceedings of the National Academy of Sciences ; 2006
    In:  Proceedings of the National Academy of Sciences Vol. 103, No. 9 ( 2006-02-28), p. 3351-3356
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 103, No. 9 ( 2006-02-28), p. 3351-3356
    Abstract: Tumor endothelial marker 1 ( Tem1 ; endosialin ) is the prototypical member of a family of genes expressed in the stroma of tumors. To assess the functional role of Tem1 , we disrupted the Tem1 gene in mice by targeted homologous recombination. Tem1 −/− mice were healthy, their wound healing was normal, and tumors grew normally when implanted in s.c. sites. However, there was a striking reduction in tumor growth, invasiveness, and metastasis after transplantation of tumors to abdominal sites in mice without functional Tem1 genes. These data indicate that the stroma can control tumor aggressiveness and that this control varies with anatomic site. Therefore, they have significant implications for the mechanisms underlying tumor invasiveness and for models that evaluate this process.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0511306103
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2006
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  • 9
    Online Resource
    Online Resource
    Unexpected Lack of Hypersensitivity in LRRK2 Knock-Out Mice to MPTP (1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine)
    Society for Neuroscience ; 2009
    In:  The Journal of Neuroscience Vol. 29, No. 50 ( 2009-12-16), p. 15846-15850
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 29, No. 50 ( 2009-12-16), p. 15846-15850
    Abstract: Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene are the most common known cause of Parkinson's disease (PD). Whether loss of LRRK2 function accounts for neurodegeneration of dopamine neurons in PD is not known, nor is it known whether LRRK2 kinase activity modulates the susceptibility of dopamine (DA) neurons to the selective dopaminergic toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To better understand the role of LRRK2 in DA neuronal survival and its role in the susceptibility of DA neurons to MPTP, we generated LRRK2 knock-out (KO) mice lacking the kinase domain of LRRK2. Here, we show that LRRK2 KO mice are viable and have no major abnormalities and live to adulthood. The dopaminergic system is normal in LRRK2 KO mice as assessed via HPLC for DA and its metabolites and via stereologic assessment of DA neuron number in young and aged mice. Importantly, there is no significant difference in the susceptibility of LRRK2 KO and wild-type mice to MPTP. These results suggest that LRRK2 plays little if any role in the development and survival of DA neurons under physiologic conditions. Thus, PD due to LRRK2 mutations are likely not due to a loss of function. Moreover, LRRK2 is not required for the susceptibility of DA neurons to MPTP.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.4357-09.2009
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2009
    detail.hit.zdb_id: 1475274-8
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  • 10
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    Online Resource
    Myosins XI modulate host cellular responses and penetration resistance to fungal pathogens
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 38 ( 2014-09-23), p. 13996-14001
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 38 ( 2014-09-23), p. 13996-14001
    Abstract: The rapid reorganization and polarization of actin filaments (AFs) toward the pathogen penetration site is one of the earliest cellular responses, yet the regulatory mechanism of AF dynamics is poorly understood. Using live-cell imaging in Arabidopsis , we show that polarization coupled with AF bundling involves precise spatiotemporal control at the site of attempted penetration by the nonadapted barley powdery mildew fungus, Blumeria graminis f. sp. hordei ( Bgh ). We further show that the Bgh -triggered AF mobility and organelle aggregation are predominately driven by the myosin motor proteins. Inactivation of myosins by pharmacological inhibitors prevents bulk aggregation of organelles and blocks recruitment of lignin-like compounds to the penetration site and deposition of callose and defensive protein, PENETRATION 1 (PEN1) into the apoplastic papillae, resulting in attenuation of penetration resistance. Using gene knockout analysis, we demonstrate that highly expressed myosins XI, especially myosin XI-K, are the primary contributors to cell wall-mediated penetration resistance. Moreover, the quadruple myosin knockout mutant xi-1 xi-2 xi-i xi-k displays impaired trafficking pathway responsible for the accumulation of PEN1 at the cell periphery. Strikingly, this mutant shows not only increased penetration rate but also enhanced overall disease susceptibility to both adapted and nonadapted fungal pathogens. Our findings establish myosins XI as key regulators of plant antifungal immunity.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1405292111
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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