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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 Hits2055Downloads710 Comment 0

2. chinaXiv:201605.01808 [pdf]

Significant Expansion of Fluorescent Protein Sensing Ability through the Genetic Incorporation of Superior Photo-Induced Electron-Transfer Quenchers

Liu, Xiaohong; Jiang, Li; Li, Jiasong; Wang, Li; Zhou, Qing; Lv, Xiaoxuan; Gong, Weimin; Wang, Jiangyun; Lu, Yi; Lu, Yi; Yu, Yang
Subjects: Biology >> Biophysics

Photo-induced electron transfer (PET) is ubiquitous for photosynthesis and fluorescent sensor design. However, genetically coded PET sensors are underdeveloped, due to the lack of methods to site-specifically install PET probes on proteins. Here we describe a family of acid and Mn(III) turn-on fluorescent protein (FP) sensors, named iLovU, based on PET and the genetic incorporation of superior PET quenchers in the fluorescent flavoprotein iLov. Using the iLovU PET sensors, we monitored the cytoplasmic acidification process, and achieved Mn(III) fluorescence sensing for the first time. The iLovU sensors should be applicable for studying pH changes in living cells, monitoring biogentic Mn(III) in the environment, and screening for efficient manganese peroxidase, which is highly desirable for lignin degradation and biomass conversion. Our work establishes a platform for many more protein PET sensors, facilitates the de novo design of metalloenzymes harboring redox active residues, and expands our ability to probe protein conformational dynamics.

submitted time 2016-05-18 Hits1330Downloads619 Comment 0

3. chinaXiv:201605.01807 [pdf]

7T Transmit/Receive Arrays Using ICE Decoupling for Human Head MR Imaging

Yan, Xinqiang; Feng, Baotong; Ma, ChuangXin; Wei, Long; Yan, Xinqiang; Zhang, Xiaoliang; Zhang, Xiaoliang; Xue, Rong
Subjects: Biology >> Biophysics

In designing large-sized volume type phased array coils for human head imaging at ultrahigh fields, e.g., 7T, minimizing electromagnetic coupling among array elements is technically challenging. A new decoupling method based on induced current compensation or elimination (ICE) for a microstrip line planar array has recently been proposed. In this study, an eight-channel transmit/receive volume array with ICE-decoupled loop elements was built and investigated to demonstrate its feasibility and robustness for human head imaging at 7T. Isolation between adjacent loop elements was better than - 25 dB with a human head load. The worst-case of the isolation between all of the elements was about - 17.5 dB. All of the MRI experiments were performed on a 7T whole-body human MR scanner. Images of the phantom and human head were acquired and g-factor maps were measured and calculated to evaluate the performance of the coil array. Compared with the conventional capacitively decoupled array, the ICE-decoupled array demonstrated improved parallel imaging ability and had a higher SNR. The experimental results indicate that the transceiver array design with ICE decoupling technique might be a promising solution to designing high performance transmit/receive coil arrays for human head imaging at ultrahigh fields.

submitted time 2016-05-18 Hits1356Downloads611 Comment 0

4. chinaXiv:201605.01806 [pdf]

Polymer-Ag Nanocomposites with Enhanced Antimicrobial Activity against Bacterial Infection

Mei, Lin; Lu, Zhentan; Zhang, Xinge; Li, Chaoxing; Jia, Yanxia; Jia, Yanxia
Subjects: Biology >> Biophysics

Herein, a nontoxic nanocomposite is synthesized by reduction of silver nitrate in the presence of a cationic polymer displaying strong antimicrobial activity against bacterial infection. These nanocomposites with a large concentration of positive charge promote their adsorption to bacterial membranes through electrostatic interaction. Moreover, the synthesized nanocomposites with polyvalent and synergistic antimicrobial effects can effectively kill both Gram-positive and Gram-negative bacteria without the emergence of bacterial resistance. Morphological changes obtained by transmission electron microscope observation show that these nanocomposites can cause leakage and chaos of intracellular contents. Analysis of the antimicrobial mechanism confirms that the lethal action of nanocomposites against the bacteria started with disruption of the bacterial membrane, subsequent cellular internalization of the nanopartides, and inhibition of intracellular enzymatic activity. This novel antimicrobial material with good cytocompatibility promotes healing of infected wounds in diabetic rats, and has a promising future in the treatment of other infectious diseases.

submitted time 2016-05-18 Hits1261Downloads566 Comment 0

5. chinaXiv:201605.01805 [pdf]

Attention-Dependent Early Cortical Suppression Contributes to Crowding

Chen, Juan; He, Yingchen; Zhu, Ziyun; Peng, Yujia; Zhang, Xilin; Fang, Fang; Chen, Juan; He, Yingchen; Zhu, Ziyun; Peng, Yujia; Zhang, Xilin; Fang, Fang; Fang, Fang; Fang, Fang; Zhou, Tiangang
Subjects: Biology >> Biophysics >> Neurosciences

Crowding, the identification difficulty for a target in the presence of nearby flankers, is ubiquitous in spatial vision and is considered a bottleneck of object recognition and visual awareness. Despite its significance, the neural mechanisms of crowding are still unclear. Here, we performed event-related potential and fMRI experiments to measure the cortical interaction between the target and flankers in human subjects. We found that the magnitude of the crowding effect was closely associated with an early suppressive cortical interaction. The cortical suppression was reflected in the earliest event-related potential component (C1), which originated in V1, and in the BOLD signal in V1, but not other higher cortical areas. Intriguingly, spatial attention played a critical role in the manifestation of the suppression. These findings provide direct and converging evidence that attention-dependent V1 suppression contributes to crowding at a very early stage of visual processing.

submitted time 2016-05-18 Hits1633Downloads670 Comment 0

6. chinaXiv:201605.01804 [pdf]

An Iron-Containing Dodecameric Heptosyltransferase Family Modifies Bacterial Autotransporters in Pathogenesis

Lu, Qiuhe; Yao, Qing; Xu, Yue; Li, Lin; Li, Shan; Gao, Wenqing; Niu, Miao; Chen, She; Shao, Feng; Xu, Yue; Liu, Yanhua; Liu, Xiaoyun; Liu, Yanhua; Liu, Xiaoyun; Sharon, Michal; Ben-Nissan, Gili; Zamyatina, Alla; Shao, Feng; Shao, Feng
Subjects: Biology >> Biophysics

Autotransporters deliver virulence factors to the bacterial surface by translocating an effector passenger domain through a membrane-anchored barrel structure. Although passenger domains are diverse, those found in enteric bacteria autotransporters, including AIDA-I in diffusely adhering Escherichia coli (DAEC) and TibA in enterotoxigenic E. coli, are commonly glycosylated. We show that AIDA-I is heptosylated within the bacterial cytoplasm by autotransporter adhesin heptosyltransferase (AAH) and its paralogue AAH2. AIDA-I heptosylation determines DAEC adhesion to host cells. AAH/AAH2 define a bacterial autotransporter heptosyltransferase (BAHT) family that contains ferric ion and adopts a dodecamer assembly. Structural analyses of the heptosylated TibA passenger domain reveal 35 heptose conjugates forming patterned and solenoid-like arrays on the surface of a beta helix. Additionally, CARC, the AIDA-like autotransporter from Citrobacter rodentium, is essential for colonization in mice and requires heptosylation by its cognate BAHT. Our study establishes a bacterial glycosylation system that regulates virulence and is essential for pathogenesis.

submitted time 2016-05-18 Hits1260Downloads557 Comment 0

7. chinaXiv:201605.01803 [pdf]

PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation

Wu, Yanwei; Wu, Yanwei; Cheng, Shiya; Zou, Wei; Wang, Xiaochen; Zhao, Hongyu; Zhang, Hong; Yoshina, Sawako; Mitani, Shohei; Yoshina, Sawako; Mitani, Shohei
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

Autophagosome formation is promoted by the PI3 kinase complex and negatively regulated by myotubularin phosphatases, indicating that regulation of local phosphatidylinositol 3-phosphate (PtdIns3P) levels is important for this early phase of autophagy. Here, we show that the Caenorhabditis elegans myotubularin phosphatase MTM-3 catalyzes PtdIns3P turnover late in autophagy. MTM-3 acts downstream of the ATG-2/EPG-6 complex and upstream of EPG-5 to promote autophagosome maturation into autolysosomes. MTM-3 is recruited to autophagosomes by PtdIns3P, and loss of MTM-3 causes increased autophagic association of ATG-18 in a PtdIns3P-dependent manner. Our data reveal critical roles of PtdIns3P turnover in autophagosome maturation and/or autolysosome formation.

submitted time 2016-05-18 Hits8302Downloads701 Comment 0

8. chinaXiv:201605.01802 [pdf]

Environmentally responsive polymeric materials: effect of the topological structure on self-assembly

Wang, Hui; Zhang, Pei; Shi, Xuefeng; Yu, Danfeng; Wang, Jinben; Yan, Haike; Ji, Gang
Subjects: Biology >> Biophysics

A novel amphiphilic homopolymer (PAGC(8)), containing two hydrophilic head groups and double hydrophobic tails in each repeat unit, has been prepared by solution polymerization and named as "a geminized amphiphilic homopolymer" in this paper, which is capable of self-assembling into various nanoobjects depending on the solution concentration and solvent properties. Characterization of the self-assembly behaviors was carried out by steady-state fluorescence, transmission electron microscopy and nuclear magnetic resonance techniques. Particular emphasis was dedicated to the environmental responsiveness of the assemblies. The morphologies were observed to transform from micelle-type to vesicles on adding a certain amount of ethanol. It is noteworthy that the assemblies were able to trap hydrophilic (rhodamine B) and hydrophobic (Sudan Red) molecules. Subsequently different nanoobjects were found after the encapsulation. To probe the effect of the topological structure on the self-assembly behaviors, the properties of an additional homopolymer with single charge pendant architecture on the backbone were investigated for comparison. Significant differences in structure between the two architectures brought out remarkable variations in aggregates, which were non-responsive to the solvent environment, or encapsulation of molecules. Based on the experimental results, we proposed a possible mechanism of the morphological transitions of the assemblies.

submitted time 2016-05-18 Hits1147Downloads486 Comment 0

9. chinaXiv:201605.01801 [pdf]

Expanding the genetic code for site-specific labelling of tobacco mosaic virus coat protein and building biotin-functionalized virus-like particles

Wu, F. C.; Zhou, Q.; Wu, M.; Tian, Y.; Niu, Z. W.; Huang, Y.; Wu, F. C.; Zhou, Q.; Wu, F. C.; Ballard, Z.; Zhang, H.; Wang, J. Y.
Subjects: Biology >> Biophysics

A method for site-specific and high yield modification of tobacco mosaic virus coat protein (TMVCP) utilizing a genetic code expanding technology and copper free cycloaddition reaction has been established, and biotin-functionalized virus-like particles were built by the self-assembly of the protein monomers.

submitted time 2016-05-18 Hits1121Downloads477 Comment 0

10. chinaXiv:201605.01740 [pdf]

Aberrantly upregulated TRAP1 is required for tumorigenesis of breast cancer

Zhang, Bo; Wei, Peng; Hao, Junfeng; Zhao, Lijing; Zhang, Fenglin; Wei, Taotao; Wang, Jing; Huang, Zhen; Wei, Peng; Liu, Ying; Tu, Yaping
Subjects: Biology >> Biophysics >> Oncology

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is abnormally expressed in many cancers. In this study, we showed that TRAP1 is aberrantly upregulated in breast tumors compared to control tissues. TRAP1 knockdown downregulates mitochondrial aerobic respiratory, sensitizes cells to lethal stimuli, and inhibited tumor growth in MDA-MB-231 and MCF-7 breast cancer cells in vivo. TRAP1 overexpression, however, enhances the capacity to cope with stress conditions. These evidences suggested that TRAP1 is required for tumorigenesis. We also found that TRAP1 regulates the mitochondrial morphology. Relatively lower TRAP1 levels are associated with the rod-shaped mitochondrial phenotype in invasive and metastatic MDA-MB-231 breast cancer cells; on the contrary, higher TRAP1 levels are associated with the tubular network-shaped mitochondrial phenotype in non-invasive MCF-7 cells. Interestingly, the expression of TRAP1 in human breast cancer specimens inversely correlates with tumor grade. Overexpression of TRAP1 in MDA-MB-231 cells causes mitochondrial fusion, triggers mitochondria to form tubular networks, and suppresses cell migration and invasion in vitro and in vivo. These data link TRAP1-regulated mitochondrial dynamics and function with tumorigenesis of breast cancer and suggested that TRAP1 may therefore be a potential target for breast cancer drug development.

submitted time 2016-05-15 Hits1411Downloads538 Comment 0

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