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1. chinaXiv:201605.01809 [pdf]

BMP2-SMAD Signaling Represses the Proliferation of Embryonic Neural Stem Cells through YAP

Yao, Minghui; Wang, Yadong; Zhang, Peng; Chen, Hong; Yuan, Zengqiang; Yao, Minghui; Xu, Zhiheng; Jiao, Jianwei; Wang, Yadong
Subjects: Biology >> Biophysics >> Neurosciences

Previous studies have shown that the Hippo pathway effector yes-associated protein (YAP) plays an important role in maintaining stem cell proliferation. However, the precise molecular mechanism of YAP in regulating murine embryonic neural stem cells (NSCs) remains largely unknown. Here, we show that bone morphogenetic protein-2 (BMP2) treatment inhibited the proliferation of mouse embryonic NSCs, that YAP was critical for mouse NSC proliferation, and that BMP2 treatment-induced inhibition of mouse NSC proliferation was abrogated by YAP knockdown, indicating that the YAP protein mediates the inhibitory effect of BMP2 signaling. Additionally, we found that BMP2 treatment reduced YAP nuclear translocation, YAP-TEAD interaction, and YAP-mediated transactivation. BMP2 treatment inhibited YAP/TEAD-mediated Cyclin D1 (ccnd1) expression, and knockdown of ccnd1 abrogated the BMP2-mediated inhibition of mouse NSC proliferation. Mechanistically, we found that Smad1/4, effectors of BMP2 signaling, competed with YAP for the interaction with TAED1 and inhibited YAP's cotranscriptional activity. Our data reveal mechanistic cross talk between BMP2 signaling and the Hippo-YAP pathway in murine NSC proliferation, which may be exploited as a therapeutic target in neurodegenerative diseases and aging.

submitted time 2016-06-06 Hits3878Downloads1665 Comment 0

2. chinaXiv:201605.01489 [pdf]

MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes

Zhang, Peng; Wang, Jiajia; Huang, Da-Wei; He, Shunmin; Kang, Jun-Yan; Gou, Lan-Tao; Dai, Peng; Liu, Mo-Fang; Kang, Jun-Yan; Gou, Lan-Tao; Dai, Peng; Liu, Mo-Fang; Skogerboe, Geir; Chen, Runsheng; Xue, Yuanchao; Fu, Xiang-Dong; Xue, Yuanchao; Fu, Xiang-Dong
Subjects: Biology >> Biophysics >> Cell Biology

The piRNA machinery is known for its role in mediating epigenetic silencing of transposons. Recent studies suggest that this function also involves piRNA-guided cleavage of transposon-derived transcripts. As many piRNAs also appear to have the capacity to target diverse mRNAs, this raises the intriguing possibility that piRNAs may act extensively as siRNAs to degrade specific mRNAs. To directly test this hypothesis, we compared mouse PIWI (MIWI)-associated piRNAs with experimentally identified cleaved mRNA fragments from mouse testes, and observed cleavage sites that predominantly occur at position 10 from the 5' end of putative targeting piRNAs. We also noted strong biases for U and A residues at nucleotide positions 1 and 10, respectively, in both piRNAs and mRNA fragments, features that resemble the pattern of piRNA amplification by the 'ping-pong' cycle. Through mapping of MIWI-RNA interactions by CLIP-seq and gene expression profiling, we found that many potential piRNA-targeted mRNAs directly interact with MIWI and show elevated expression levels in the testes of Miwi catalytic mutant mice. Reporter-based assays further revealed the importance of base pairing between piRNAs and mRNA targets and the requirement for both the slicer activity and piRNA-loading ability of MIWI in piRNA-mediated target repression. Importantly, we demonstrated that proper turnover of certain key piRNA targets is essential for sperm formation. Together, these findings reveal the siRNA-like function of the piRNA machinery in mouse testes and its central requirement for male germ cell development and maturation.

submitted time 2016-05-12 Hits2497Downloads1587 Comment 0

3. chinaXiv:201605.01479 [pdf]

Identification of lipid droplet structure-like/resident proteins in Caenorhabditis elegans

Na, Huimin; Zhang, Peng; Chen, Yong; Zhu, Xiaotong; Liu, Yi; Liu, Yangli; Xie, Kang; Yang, Fuquan; Zhang, Hong; Liu, Pingsheng; Na, Huimin; Zhang, Peng; Zhu, Xiaotong; Liu, Yangli; Xie, Kang; Xu, Ningyi; Mak, Ho Yi; Xu, Ningyi; Mak, Ho Yi; Yu, Yong
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

The lipid droplet (LD) is a cellular organelle that stores neutral lipids in cells and has been linked with metabolic disorders. Caenorhabditis elegans has many characteristics which make it an excellent animal model for studying LDs. However, unlike in mammalian cells, no LD structure-like/resident proteins have been identified in C. elegans, which has limited the utility of this model for the study of lipid storage and metabolism. Herein based on three lines of evidence, we identified that MDT-28 and DHS-3 previously identified in C. elegans LD proteome were two LD structure-like/resident proteins. First, MDT-28 and DHS-3 were found to be the two most abundant LD proteins in the worm. Second, the proteins were specifically localized to LDs and we identified the domains responsible for this targeting in both proteins. Third and most importantly, the depletion of MDT-28 induced LD clustering while DHS-3 deletion reduced triacylglycerol content (TAG). We further characterized the proteins finding that MDT-28 was ubiquitously expressed in the intestine, muscle, hypodermis, and embryos, whereas DHS-3 was expressed mainly in intestinal cells. Together, these two LD structure-like/resident proteins provide a basis for future mechanistic studies into the dynamics and functions of LDs in C. elegans. (C) 2015 Elsevier B.V. All rights reserved.

submitted time 2016-05-12 Hits2120Downloads1057 Comment 0

4. chinaXiv:201605.01473 [pdf]

Layer-specific response properties of the human lateral geniculate nucleus and superior colliculus

Zhang, Peng; Zhou, Hao; He, Sheng; Wen, Wen; He, Sheng
Subjects: Biology >> Biophysics >> Neurosciences

The human LGN and SC consist of distinct layers, but their layer-specific response properties remain poorly understood. In this fMRI study, we characterized visual response properties of the magnocellular (M) and parvocellular (P) layers of the human LGN, as well as at different depths in the SC. Results show that fMRI is capable of resolving layer-specific signals from the LGN and SC. Compared to the P layers of the LGN, the M layers preferred higher temporal frequency, lower spatial frequency stimuli, and their responses saturated at lower contrast. Furthermore, the M layers are colorblind while the P layers showed robust response to both chromatic and achromatic stimuli. Visual responses in the SC were strongest in the superficial voxels, which showed similar spatiotemporal and contrast response properties as the M layers of the LGN, but were sensitive to color and responded strongly to isoluminant color stimulus. Thus, the non-invasive fMRI measures show that the M and P layers of human LGN have similar response properties as that observed in non-human primates and the superficial layers of the human SC prefer transient inputs but are not colorblind. (C) 2015 Elsevier Inc. All rights reserved.

submitted time 2016-05-12 Hits3457Downloads1537 Comment 0

5. chinaXiv:201605.01470 [pdf]

Brahma regulates the Hippo pathway activity through forming complex with Yki-Sd and regulating the transcription of Crumbs

Zhu, Ye; Wang, Yadong; Pei, Chunli; Yuan, Zengqiang; Zhang, Peng; Li, Dong; Liu, Song; Zhang, Lei
Subjects: Biology >> Biophysics >> Cell Biology

The Hippo signaling pathway restricts organ size by inactivating the Yorkie (Yki)/Yes-associated protein (YAP) family proteins. The oncogenic Yki/YAP transcriptional coactivator family promotes tissue growth by activating target gene transcription, but the regulation of Yki/YAP activation remains elusive. In mammalian cells, we identified Brg1, a major subunit of chromatin-remodeling SWI/SNF family proteins, which interacts with YAP. This finding led us to investigate the in vivo functional interaction of Yki and Brahma (Brm), the Drosophila homolog of Brg1. We found that Brm functions at the downstream of Hippo pathway and interacts with Yki and Scalloped (Sd) to promotes Yki-dependent transcription and tissue growth. Furthermore, we demonstrated that Brm is required for the Crumbs (Crb) dysregulation-induced Yki activation. Interestingly, we also found that crb is a downstream target of Yki-Brm complex. Brm physically binds to the promoter of crb and regulates its transcription through Yki. Together, we showed that Brm functions as a critical regulator of Hippo signaling during tissue growth and plays an important role in the feedback loop between Crb and Yki. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.

submitted time 2016-05-12 Hits2449Downloads1348 Comment 0

6. chinaXiv:201605.01415 [pdf]

A Novel Motion-on-Color Paradigm for Isolating Magnocellular Pathway Function in Preperimetric Glaucoma

Wen, Wen; Liu, Tingting; Zhang, Ting; Sun, Xinghuai; Wen, Wen; Sun, Xinghuai; Wen, Wen; Sun, Xinghuai; Zhang, Peng; He, Sheng; Gao, Jian; Sun, Xinghuai; He, Sheng
Subjects: Biology >> Biophysics

PURPOSE. This study investigated a novel motion-on-color paradigm to functionally isolate the magnocellular pathway and evaluate its diagnostic value in preperimetric glaucoma patients. METHODS. Thirty patients with preperimetric primary open-angle glaucoma and 30 controls participated in this study. They were tested in both the foveal and peripheral locations. Contrast sensitivity was assessed for the direction discrimination of a moving luminance-modulated grating presented on top of a red/green isoluminant grating. The moving test grating was designed to target the magnocellular pathway, while the background red/green isoluminant grating was designed to saturate the parvocellular pathway. The luminance-modulated grating was presented at spatial frequency of 0.5 cyc/deg, moving horizontally at four temporal frequencies (3 Hz, 8 Hz, 15 Hz, 25 Hz). Participants were asked to indicate the direction of motion for the luminance grating. As a comparison condition, frequency-doubling stimuli were also presented in the periphery and participants were asked to detect the occurrence of the frequency-doubled pattern. Two-way repeated-measures analysis of variance was performed with temporal frequency modulations as within-subject factor and group as between-subject factor, while contrast sensitivity was the dependent variable. Receiver operating characteristic (ROC) analysis was used to characterize diagnostic performance of the new procedure in comparison with the frequency-doubling tests for preperimetric glaucoma. RESULTS. The contrast sensitivity function in both the fovea and the periphery showed an inverted "V" shape with highest sensitivity in the intermediate temporal frequencies, consistent with physiological properties of the magnocellular pathway. At the fovea, compared to the control group, the sensitivity for the glaucoma patients was slightly but not significantly reduced (P > 0.05), and there was no significant interaction between groups and temporal frequency (P > 0.05). In the periphery, patients' sensitivity was significantly lower (P < 0.001) than that of normal participants, especially in high temporal frequencies, as supported by a statistically significant interaction between groups and temporal frequency (P < 0.001). The areas under ROC curves (AUROC) obtained for the motion-on-color paradigm in the periphery were 0.957 (25 Hz), 0.870 (15 Hz), 0.758 (8 Hz), and 0.561 (3 Hz) and were 0.761 for the traditional frequency-doubling test. CONCLUSIONS. The motion-on-color paradigm revealed a loss of contrast sensitivity in the peripheral visual field in preperimetric glaucoma. When applied with stimuli at high temporal frequency, the new paradigm had higher diagnostic sensitivity and specificity than the traditional frequency-doubling test. The findings also support the viewpoint that selective evaluation of magnocellular pathway function could facilitate the earlier detection of functional defects in glaucoma before visual field defects by standard perimetry.

submitted time 2016-05-12 Hits1537Downloads852 Comment 0

7. chinaXiv:201605.01383 [pdf]

Novelty seeking is related to individual risk preference and brain activation associated with risk prediction during decision making

Wang, Ying; Yang, Lizhuang; Gu, Feng; Li, Xiaoming; Zha, Rujing; Wei, Zhengde; Pei, Yakun; Zhou, Yifeng; Zhang, Xiaochu; Wang, Ying; Yang, Lizhuang; Gu, Feng; Li, Xiaoming; Zha, Rujing; Wei, Zhengde; Pei, Yakun; Zhou, Yifeng; Zhang, Xiaochu; Liu, Ying; Li, Xiaoming
Subjects: Biology >> Biophysics

Novelty seeking (NS) is a personality trait reflecting excitement in response to novel stimuli. High NS is usually a predictor of risky behaviour such as drug abuse. However, the relationships between NS and risk-related cognitive processes, including individual risk preference and the brain activation associated with risk prediction, remain elusive. In this fMRI study, participants completed the Tridimensional Personality Questionnaire to measure NS and performed a probabilistic decision making task. Using a mathematical model, we estimated individual risk preference. Brain regions associated with risk prediction were determined via fMRI. The NS score showed a positive correlation with risk preference and a negative correlation with the activation elicited by risk prediction in the right posterior insula (r-PI), left anterior insula (l-AI), right striatum (r-striatum) and supplementary motor area (SMA). Within these brain regions, only the activation associated with risk prediction in the r-PI showed a correlation with NS after controlling for the effect of risk preference. Resting-state functional connectivity between the r-PI and r-striatum/l-AI was negatively correlated with NS. Our results suggest that high NS may be associated with less aversion to risk and that the r-PI plays an important role in relating risk prediction to NS.

submitted time 2016-05-12 Hits1530Downloads819 Comment 0

8. chinaXiv:201605.01258 [pdf]

Human BDCA2(+)CD123(+)CD56(+) dendritic cells (DCs) related to blastic plasmacytoid dendritic cell neoplasm represent a unique myeloid DC subset

Yu, Haisheng; Yin, Xiangyun; Zhang, Liguo; Zhang, Peng; Cui, Ya; Jiang, Taijiao; Yu, Haisheng; Zhang, Peng; Yin, Xiangyun; Yin, Zhao; Shi, Quanxing; Wang, Shouli; Liu, Guanyuan; Piccaluga, Pier Paolo
Subjects: Biology >> Biophysics >> Cell Biology

Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive secretion of type I interferon (IFN-I) in response to nucleic acids through Toll like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56(+) DC population that express typical pDC markers including CD123 and BDCA2 but produce much less IFN-I comparing with pDCs. In addition, CD56(+) DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling. Accordingly, CD56(+) DCs functionally resemble mDCs by producing IL-12 upon TLR4 stimulation and priming naive T cells without prior activation. These data suggest that the CD56(+) DCs represent a novel mDC subset mixed with some pDC features. A CD4(+)CD56(+) hematological malignancy was classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN) due to its expression of characteristic molecules of pDCs. However, we demonstrated that BPDCN is closer to CD56(+) DCs than pDCs by global gene-expression profiling. Thus, we propose that the CD4(+)CD56(+) neoplasm may be a tumor counterpart of CD56(+) mDCs but not pDCs.

submitted time 2016-05-11 Hits1657Downloads980 Comment 0

9. chinaXiv:201605.01242 [pdf]

Intracellular CD24 disrupts the ARF-NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation

Wang, Lizhong; Liu, Runhua; Ye, Peiying; Wong, Chunshu; Chen, Guo-Yun; Sakabe, Kaoru; Jube, Sandro; Zheng, Pan; Liu, Yang; Ye, Peiying; Wong, Chunshu; Chen, Guo-Yun; Sakabe, Kaoru; Jube, Sandro; Zheng, Pan; Liu, Yang; Ye, Peiying; Zhou, Penghui; Zheng, Xincheng; Wu, Wei
Subjects: Biology >> Biophysics

CD24 is overexpressed in nearly 70% human cancers, whereas TP53 is the most frequently mutated tumour-suppressor gene that functions in a context-dependent manner. Here we show that both targeted mutation and short hairpin RNA (shRNA) silencing of CD24 retard the growth, progression and metastasis of prostate cancer. CD24 competitively inhibits ARF binding to NPM, resulting in decreased ARF, increase MDM2 and decrease levels of p53 and the p53 target p21/CDKN1A. CD24 silencing prevents functional inactivation of p53 by both somatic mutation and viral oncogenes, including the SV40 large T antigen and human papilloma virus 16 E6-antigen. In support of the functional interaction between CD24 and p53, in silico analyses reveal that TP53 mutates at a higher rate among glioma and prostate cancer samples with higher CD24 mRNA levels. These data provide a general mechanism for functional inactivation of ARF and reveal an important cellular context for genetic and viral inactivation of TP53.

submitted time 2016-05-11 Hits1672Downloads920 Comment 0

10. chinaXiv:201605.00755 [pdf]

Dysfunction of Wntless triggers the retrograde Golgi-to-ER transport of Wingless and induces ER stress

Zhang, Peng; Zhou, Lujun; Pei, Chunli; Yuan, Zengqiang; Lin, Xinhua; Lin, Xinhua;
Subjects: Biology >> Biophysics

Secreted Wnts play diverse roles in a non-cell-autonomous fashion. However, the cell-autonomous effect of unsecreted Wnts remains unknown. Endoplasmic reticulum (ER) stress is observed in specialized secretory cells and participates in pathophysiological processes. The correlation between Wnt secretion and ER stress remains poorly understood. Here, we demonstrated that Drosophila miR-307a initiates ER stress specifically in wingless (wg)-expressing cells through targeting wntless (wls/evi). This phenotype could be mimicked by retromer loss-of-function or porcupine (porc) depletion, and rescued by wg knockdown, arguing that unsecreted Wg triggers ER stress. Consistently, we found that disrupting the secretion of human Wnt5a also induced ER stress in mammalian cells. Furthermore, we showed that a C-terminal KKVY-motif of Wg is required for its retrograde Golgi-to-ER transport, thus inducing ER stress. Next, we investigated if COPI, the regulator of retrograde transport, is responsible for unsecreted Wg to induce ER stress. To our surprise, we found that COPI acts as a novel regulator of Wg secretion. Taken together, this study reveals a previously unknown Golgi-to-ER retrograde route of Wg, and elucidates a correlation between Wnt secretion and ER stress during development.

submitted time 2016-05-05 Hits1584Downloads888 Comment 0

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