Browsing by Author "Hu, Bo"

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    Detection and genomic analysis of BRAF fusions in Juvenile Pilocytic Astrocytoma through the combination and integration of multi-omic data
    (2022-12-12) Zwaig, Melissa; Baguette, Audrey; Hu, Bo; Johnston, Michael; Lakkis, Hussein; Nakada, Emily M.; Faury, Damien; Juretic, Nikoleta; Ellezam, Benjamin; Weil, Alexandre G.; Karamchandani, Jason; Majewski, Jacek; Blanchette, Mathieu; Taylor, Michael D.; Gallo, Marco; Kleinman, Claudia L.; Jabado, Nada; Ragoussis, Jiannis
    Abstract Background Juvenile Pilocytic Astrocytomas (JPAs) are one of the most common pediatric brain tumors, and they are driven by aberrant activation of the mitogen-activated protein kinase (MAPK) signaling pathway. RAF-fusions are the most common genetic alterations identified in JPAs, with the prototypical KIAA1549-BRAF fusion leading to loss of BRAF’s auto-inhibitory domain and subsequent constitutive kinase activation. JPAs are highly vascular and show pervasive immune infiltration, which can lead to low tumor cell purity in clinical samples. This can result in gene fusions that are difficult to detect with conventional omics approaches including RNA-Seq. Methods To this effect, we applied RNA-Seq as well as linked-read whole-genome sequencing and in situ Hi-C as new approaches to detect and characterize low-frequency gene fusions at the genomic, transcriptomic and spatial level. Results Integration of these datasets allowed the identification and detailed characterization of two novel BRAF fusion partners, PTPRZ1 and TOP2B, in addition to the canonical fusion with partner KIAA1549. Additionally, our Hi-C datasets enabled investigations of 3D genome architecture in JPAs which showed a high level of correlation in 3D compartment annotations between JPAs compared to other pediatric tumors, and high similarity to normal adult astrocytes. We detected interactions between BRAF and its fusion partners exclusively in tumor samples containing BRAF fusions. Conclusions We demonstrate the power of integrating multi-omic datasets to identify low frequency fusions and characterize the JPA genome at high resolution. We suggest that linked-reads and Hi-C could be used in clinic for the detection and characterization of JPAs.
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    Gastrodin Suppresses the Amyloid β-Induced Increase of Spontaneous Discharge in the Entorhinal Cortex of Rats
    (2014-10-30) Chen, Peng-zhi; Jiang, Hui-hui; Wen, Bo; Ren, Shuan-cheng; Chen, Yang; Ji, Wei-gang; Hu, Bo; Zhang, Jun; Xu, Fenglian; Zhu, Zhi-ru
    Accumulated soluble amyloid beta- (Aβ-) induced aberrant neuronal network activity may directly contribute to cognitive deficits, which are the most outstanding characteristics of Alzheimer’s disease (AD). The entorhinal cortex (EC) is one of the earliest affected brain regions in AD. Impairments of EC neurons are responsible for the cognitive deficits in AD. However, little effort has been made to investigate the effects of soluble Aβ on the discharge properties of EC neurons in vivo. The present study was designed to examine the effects of soluble Aβ1−42 on the discharge properties of EC neurons, using in vivo extracellular single unit recordings. The protective effects of gastrodin (GAS) were also investigated against Aβ1−42-induced alterations in EC neuronal activities. The results showed that the spontaneous discharge of EC neurons was increased by local application of soluble Aβ1−42 and that GAS can effectively reverse Aβ1−42-induced facilitation of spontaneous discharge in a concentration-dependent manner. Moreover, whole-cell patch clamp results indicated that the protective function of GAS on abnormal hyperexcitability may be partially mediated by its inhibitory action on Aβ1−42-elicited inward currents in EC neurons. Our study suggested that GAS may provide neuroprotective effects on Aβ1−42-induced hyperactivity in EC neurons of rats.