Biology subjects

Lu, Z.

Publications and source records attributed to Lu, Z..

274 records · Page 16Linked to original sources

bioRxiv2017

SHP2 Is Required for BCR-ABL1-Induced Hematologic Neoplasms

BCR-ABL1-targeting tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome-positive (Ph+) hematologic neoplasms. Nevertheless, acquired TKI resistance remains a major problem in chronic myeloid leukemia (CML), and TKIs are less effective against Ph+ B-cell acute lymphoblastic leukemia (B-ALL). GAB2, a scaffolding adaptor that binds and activates SHP2, is essential for leukemogenesis by BCR-ABL1, and a GAB2 mutant lacking SHP2 binding cannot mediate leukemogenesis. Using a genetic loss-of-function approach and bone marrow transplantation (BMT) models for CML and BCR-ABL1+ B-ALL, we show that SHP2 is required for BCR-ABL1-evoked myeloid and lymphoid neoplasia. Ptpn11 deletion impairs initiation and maintenance of CML-like myeloproliferative neoplasm, and compromises induction of BCR-ABL1+ B-ALL. SHP2, and specifically, its SH2 domains, PTP activity and C-terminal tyrosines, is essential for BCR-ABL1+, but not WT, pre-B cell proliferation. The MEK/ERK pathway is regulated by SHP2 in WT and BCR-ABL1+ pre-B cells, but is only required for the proliferation of BCR-ABL1+ cells. SHP2 is required for SRC family kinase (SFK) activation only in BCR-ABL1+ pre-B cells. RNAseq reveals distinct SHP2-dependent transcriptional programs in BCR-ABL1+ and WT pre-B cells. Our results suggest that SHP2, via SFKs and ERK, represses MXD3/4 to facilitate a MYC-dependent proliferation program in BCR-ABL1-transformed pre-B cells.

cancer biology↗

bioRxiv2017

Dynamic interhemispheric coordination in face processing

Our conscious experience of the world is normally unified. The brain coordinates different processes from the left and right hemispheres into one experience. However, the neural mechanisms underlying interhemispheric coordination remain poorly understood. A mechanistic approach to understanding interhemispheric coordination is \"communication through coherence\" (Fries, 2005; 2015). Using a recently developed time-resolved psychophysics (Fiebelkorn, Saalmann, & Kastner, 2013; Landau & Fries, 2012; Song, Meng, Chen, Zhou, & Luo, 2014), combined with fMRI decoding method, we investigated the interhemispheric coordination through coherence, by focusing on a quintessential case of hemispheric lateralized brain function: face processing in the left and right fusiform face area (FFA). We observed coherent oscillatory fMRI multi-voxel patterns in the left and right FFA when two stimuli presented successively cross visual fields, either initiating coordination from the left hemisphere or right hemisphere. When interhemispheric coordination started from the dominant right hemisphere, a coherent 44{degrees} phase difference between the left and right FFA in 3-4 Hz was observed; whereas when interhemispheric coordination started from the non-dominant left hemisphere, a coherent -17{degrees} phase difference between the left and right FFA in 5.5-6.5 Hz was observed. These results suggest that different phase coherence might mediate the interhemispheric coordination of face perception, depending on whether the initiating hemisphere is dominant or non-dominant. Our findings provide compelling fMRI evidence for interhemispheric coordination through coherence. The time-resolved fMRI decoding approach would be a useful starting point for a more promising approach for future investigation in interhemispheric dynamic coordination with fine-grained spatial and temporal resolution.

neuroscience↗

bioRxiv2017

Fluctuations of fMRI activation patterns reveal theta-band dynamics of visual object priming

The brain dynamically creates predictions about upcoming stimuli to guide perception efficiently. Recent behavioral results suggest theta-band oscillations contribute to this prediction process, however litter is known about the underlying neural mechanism. Here, we combine fMRI and a time-resolved psychophysical paradigm to access fine temporal-scale profiles of the fluctuations of brain activation patterns corresponding to visual object priming. Specifically, multi-voxel activity patterns in the fusiform face area (FFA) and the parahippocampal place area (PPA) show temporal fluctuations at a theta-band (~5 Hz) rhythm. Importantly, the theta-band power in the FFA negatively correlates with reaction time, further indicating the critical role of the observed cortical theta oscillations. Moreover, alpha-band (~10 Hz) shows a dissociated spatial distribution, mainly linked to the occipital cortex. These findings, to our knowledge, are the first fMRI study that indicates temporal fluctuations of multi-voxel activity patterns and that demonstrates theta and alpha rhythms in relevant brain areas.

neuroscience↗

bioRxiv2016

On expert curation and sustainability: UniProtKB/Swiss-Prot as a case study

MOTIVATIONBiological knowledgebases, such as UniProtKB/Swiss-Prot, constitute an essential component of daily scientific research by offering distilled, summarized, and computable knowledge extracted from the literature by expert curators. While knowledgebases play an increasingly important role in the scientific community, the question of their sustainability is raised due to the growth of biomedical literature.\n\nRESULTSBy using UniProtKB/Swiss-Prot as a case study, we address this question by using different literature triage approaches. With the assistance of the PubTator text-mining tool, we tagged more than 10,000 articles to assess the ratio of papers relevant for curation. We first show that curators read and evaluate many more papers than they curate, and that measuring the number of curated publications is insufficient to provide a complete picture. We show that a large fraction of published papers found in PubMed is not relevant for curation in UniProtKB/Swiss-Prot and demonstrate that, despite appearances, expert curation is sustainable.\n\nAVAILABILITYUniProt is freely available at http://www.uniprot.org/.\n\nCONTACTsylvain.poux@sib.swiss

bioinformatics↗