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Yilun Deng, Yuejuan Qin, Subramanya Srikantan, Anqi Luo, Zi-Ming Cheng, Shahida K Flores, Kris S Vogel, Exing Wang, Patricia L M Dahia
The TMEM127 tumor suppressor gene encodes a transmembrane protein of unknown function mutated in pheochromocytomas and, rarely, in renal cancers. Tumors with inactivating TMEM127 mutations have increased mTORC1 signaling by undefined mechanisms. Here we report that TMEM127 interacts with the lysosome-anchored complex comprised of Rag GTPases, the LAMTOR pentamer (or 'ragulator') and vATPase, which controls amino acid-mediated mTORC1 activation. We found that in nutrient-rich conditions TMEM127 expression reduces mTORC1 recruitment to Rags...
March 14, 2018: Human Molecular Genetics
Jing Wen, Ruitu Lv, Honghui Ma, Hongjie Shen, Chenxi He, Jiahua Wang, Fangfang Jiao, Hang Liu, Pengyuan Yang, Li Tan, Fei Lan, Yujiang Geno Shi, Chuan He, Yang Shi, Jianbo Diao
N6 -methyladenosine (m6 A) is an abundant modification in eukaryotic mRNA, regulating mRNA dynamics by influencing mRNA stability, splicing, export, and translation. However, the precise m6 A regulating machinery still remains incompletely understood. Here we demonstrate that ZC3H13, a zinc-finger protein, plays an important role in modulating RNA m6 A methylation in the nucleus. We show that knockdown of Zc3h13 in mouse embryonic stem cell significantly decreases global m6 A level on mRNA. Upon Zc3h13 knockdown, a great majority of WTAP, Virilizer, and Hakai translocate to the cytoplasm, suggesting that Zc3h13 is required for nuclear localization of the Zc3h13-WTAP-Virilizer-Hakai complex, which is important for RNA m6 A methylation...
March 15, 2018: Molecular Cell
Rong-Guei Tsai, Pei-Hsuan Tsai
The location information obtained using a sensor is a critical requirement in wireless sensor networks. Numerous localization schemes have been proposed, among which mobile-anchor-node-assisted localization (MANAL) can reduce costs and overcome environmental constraints. A mobile anchor node (MAN) provides its own location information to assist the localization of sensor nodes. Numerous path planning schemes have been proposed for MANAL, but most scenarios assume the absence of obstacles in the environment...
March 16, 2018: Sensors
Valerie Jeanneret, Juan P Ospina, Ariel Diaz, Luis G Manrique, Paola Merino, Laura Gutierrez, Enrique Torre, Fang Wu, Lihong Cheng, Manuel Yepes
Cerebral ischemia causes the presynaptic release of tissue-type plasminogen activator (tPA). The postsynaptic density (PSD) is a postsynaptic structure that provides a matrix where signaling transduction of excitatory synapses takes place. The postsynaptic density protein-95 (PSD-95) is the most abundant scaffolding protein in the postsynaptic density (PSD), where it modulates the postsynaptic response to the presynaptic release of glutamate by regulating the anchoring of glutamate receptors to the PSD. We found that tPA induces the local translation of PSD-95 mRNA and the subsequent recruitment of PSD-95 protein to the PSD, via plasminogen-independent activation of TrkB receptors...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Ze Yang, Xiangyan Shen, Ning Wang, Jianjiang He, Xiaodong Li, Xin Wang, Zhufeng Hou, Kun Wang, Juan Gao, Tonggang Jiu, Changshui Huang
The qualitative and quantitative nitrogen-doping strategy for carbon materials is reported here. Novel porous nanocarbon networks pyrimidine-graphdiyne (PM-GDY) and pyridine-graphdiyne (PY-GDY) films with large areas were successfully prepared. These films are self-supported, uniform, continuous, flexible, transparent, and quantitively doped with merely pyridine-like nitrogen (N) atoms through the facile chemical synthesis route. Theoretical predictions imply these N doped carbonaceous materials are much favorable for storing lithium (Li)-ions since the pyridinic N can enhance the interrelated binding energy...
March 16, 2018: ACS Applied Materials & Interfaces
Koji Yamamoto, Makiko Kawaguchi, Takeshi Shimomura, Aya Izumi, Kazuomi Konari, Arata Honda, Chen-Yong Lin, Michael D Johnson, Yoshihiro Yamashita, Tsuyoshi Fukushima, Hiroaki Kataoka
Hepatocyte growth factor activator inhibitor (HAI)-1/ SPINT1 and HAI-2/ SPINT2 are membrane-anchored protease inhibitors having homologous Kunitz-type inhibitor domains. They regulate membrane-anchored serine proteases, such as matriptase and prostasin. Whereas HAI-1 suppresses the neoplastic progression of keratinocytes to invasive squamous cell carcinoma (SCC) through matriptase inhibition, the role of HAI-2 in keratinocytes is poorly understood. In vitro homozygous knockout of the SPINT2 gene suppressed the proliferation of two oral SCC (OSCC) lines (SAS and HSC3) but not the growth of a non-tumorigenic keratinocyte line (HaCaT)...
February 20, 2018: Oncotarget
Marija Adzic, Nadezda Nedeljkovic
CD73 is a bifunctional glycosylphosphatidylinositol (GPI)-anchored membrane protein which functions as ecto-5'-nucleotidase and a membrane receptor for extracellular matrix protein (ECM). A large body of evidence demonstrates a critical involvement of altered purine metabolism and particularly, increased expression of CD73 in a number of human disorders, including cancer and immunodeficiency. Massive up-regulation of CD73 was also found in reactive astrocytes in several experimental models of human neuropathologies...
2018: Frontiers in Pharmacology
So Young Kim, Sun-June Park, Kap Sung Oh
PURPOSE: With the aim of implementing good projection of the three-dimensional frame (auriculo-cephalic angle) and maintaining projection, a significant issue during the stage of auricular elevation for avoiding the potential for dislodging the cartilage blocks remains. Herein we present an innovative and technically simple method of transcutaneous fixation of the costal cartilage block during the stage of auricular elevation. MATERIALS AND METHODS: After elevation of ear frame from the basement, two suspension stitches on the surface of the elevated ear were used to fix the embedding cartilage block into the auriculo-cephalic sulcus at the upper (bifurcation point of the anti-helix where the inferior and superior crus meet to form the triangular fossa) and lower (projection point of the concha wall, parallel to the level of the tragus) ones...
February 2, 2018: Journal of Cranio-maxillo-facial Surgery
Stanimir Georgiev, Daniel Tanase, Peter Ewert, Christian Meierhofer, Alfred Hager, Jelena Pabst von Ohain, Andreas Eicken
BACKGROUND: To investigate the feasibility and mid-term results of percutaneous pulmonary valve implantation (PPVI) in patients with conduit free or "native" right ventricular outflow tracts (RVOT). METHODS AND RESULTS: We identified all 18 patients with conduit free or "native" right ventricular outflow tract, who were treated with percutaneous pulmonary valve implantation (PPVI) in our institution. They were divided into two groups - these in whom the central pulmonary artery was used as an anchoring point for the preparation of the landing zone (n=10) for PPVI and these, in whom a pulmonary artery branch was used for this purpose (n=8)...
May 1, 2018: International Journal of Cardiology
Aslam Alkadhimi, Ebrahim A Al-Awadhi
INTRODUCTION: In recent years, extensive research has introduced novel ways of reinforcing orthodontic anchorage using a variety of devices temporarily anchored in bone (miniscrews). Currently, there are numerous manufacturers with different miniscrew designs on the market. AIMS: The aim of this paper is to discuss the key design features of different miniscrew systems on the market. Furthermore, to present clinical selection criteria of miniscrews in different settings taking into account the determinant factors...
March 15, 2018: Journal of Orthodontics
Yoshinori Hirano, Yu Amano, Shigenobu Yonemura, Toshio Hakoshima
Mechanotransduction by α-catenin facilitates the force-dependent development of adherens junctions (AJs) by recruiting vinculin to reinforce actin anchoring of AJs. The α-catenin mechanotransducing action is facilitated by its force-sensing device region that autoinhibits the vinculin-binding site 1 (VBS1). Here, we report the high-resolution structure of the force-sensing device region of α-catenin, which shows the autoinhibited form comprised of helix bundles E, F and G. The cryptic VBS1 is embedded into helix bundle E stabilized by direct interactions with the autoinhibitory region forming helix bundles F and G...
March 15, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Ignacio Jiménez-Morales, Sara Cavaliere, Deborah Jones, Jacques Rozière
Niobium and antimony doped tin oxide loose-tubes decorated with Pt nanoparticles present outstanding mass activity and stability, exceeding those of a reference carbon-based electrocatalyst. Physico-chemical characterisation and in particular X-ray photoelectron spectroscopy demonstrate that this observation can be ascribed to the strong metal-support interaction promoting electroactivity and Pt anchoring on doped metal oxide supports.
March 15, 2018: Physical Chemistry Chemical Physics: PCCP
Li-Na Wang, Mei-Hua Gao, Bing Wang, Bei-Bei Cong, Shu-Chao Zhang
Cluster of differentiation 59 (CD59) is a glycosylphosphatidylinositol-anchored protein. Cross-linking of CD59 with specific monoclonal antibodies can cause a series of intracellular signal transduction events. However, the underlying molecular mechanisms are poorly understood. Linker for activation of T-cells (LAT) is a crucial adaptor protein in T-cell signaling, and its phosphorylation and palmitoylation are essential for its localization and function. In a previous study by the present authors, it was demonstrated that CD59 may be responsible for LAT palmitoylation, thereby regulating T-cell signal transduction...
April 2018: Oncology Letters
Yi-Shu Huang, Nien-Yi Chiang, Gin-Wen Chang, Hsi-Hsien Lin
The evolutionarily conserved adhesion G protein-coupled receptors (aGPCRs) play critical roles in biological processes as diverse as brain development, cell polarity and innate immune functions. A defining feature of aGPCRs is the GPCR autoproteolysis inducing (GAIN) domain capable of self-catalytic cleavage, resulting in the generation of an extracellular N-terminal fragment (NTF) and a seven-transmembrane C-terminal fragment (CTF) involved in the cellular adhesion and signaling functions, respectively. Interestingly, two different NTF subtypes have previously been identified, namely an NTF that couples non-covalently with the CTF and a membrane-associated NTF that tethers on cell surface independently...
March 14, 2018: Scientific Reports
Uma Mahesh R Avula, Jonathan J Hernandez, Masatoshi Yamazaki, Carmen R Valdivia, Antony Chu, Alvaro Rojas-Pena, Kuljeet Kaur, Roberto Ramos-Mondragón, Justus M Anumonwo, Stanley Nattel, Héctor H Valdivia, Jérôme Kalifa
BACKGROUND: The mechanisms underlying spontaneous atrial fibrillation (AF) associated with atrial ischemia/infarction are incompletely elucidated. Here, we investigate the mechanisms underlying spontaneous AF in an ovine model of left atrial myocardial infarction (LAMI). METHODS AND RESULTS: LAMI was created by ligating the atrial branch of the left anterior descending coronary artery. ECG loop recorders were implanted to monitor AF episodes. In 7 sheep, dantrolene-a ryanodine receptor blocker-was administered in vivo during the 8-day observation period (LAMI-D, 2...
March 2018: Circulation. Arrhythmia and Electrophysiology
Paulo P Amaral, Tommaso Leonardi, Namshik Han, Emmanuelle Viré, Dennis K Gascoigne, Raúl Arias-Carrasco, Magdalena Büscher, Luca Pandolfini, Anda Zhang, Stefano Pluchino, Vinicius Maracaja-Coutinho, Helder I Nakaya, Martin Hemberg, Ramin Shiekhattar, Anton J Enright, Tony Kouzarides
BACKGROUND: The mammalian genome is transcribed into large numbers of long noncoding RNAs (lncRNAs), but the definition of functional lncRNA groups has proven difficult, partly due to their low sequence conservation and lack of identified shared properties. Here we consider promoter conservation and positional conservation as indicators of functional commonality. RESULTS: We identify 665 conserved lncRNA promoters in mouse and human that are preserved in genomic position relative to orthologous coding genes...
March 15, 2018: Genome Biology
Seung Joong Kim, Javier Fernandez-Martinez, Ilona Nudelman, Yi Shi, Wenzhu Zhang, Barak Raveh, Thurston Herricks, Brian D Slaughter, Joanna A Hogan, Paula Upla, Ilan E Chemmama, Riccardo Pellarin, Ignacia Echeverria, Manjunatha Shivaraju, Azraa S Chaudhury, Junjie Wang, Rosemary Williams, Jay R Unruh, Charles H Greenberg, Erica Y Jacobs, Zhiheng Yu, M Jason de la Cruz, Roxana Mironska, David L Stokes, John D Aitchison, Martin F Jarrold, Jennifer L Gerton, Steven J Ludtke, Christopher W Akey, Brian T Chait, Andrej Sali, Michael P Rout
Nuclear pore complexes play central roles as gatekeepers of RNA and protein transport between the cytoplasm and nucleoplasm. However, their large size and dynamic nature have impeded a full structural and functional elucidation. Here we determined the structure of the entire 552-protein nuclear pore complex of the yeast Saccharomyces cerevisiae at sub-nanometre precision by satisfying a wide range of data relating to the molecular arrangement of its constituents. The nuclear pore complex incorporates sturdy diagonal columns and connector cables attached to these columns, imbuing the structure with strength and flexibility...
March 14, 2018: Nature
Truong Thi Tuong Vi, Selvaraj Rajesh Kumar, Bishakh Rout, Chi-Hsien Liu, Chak-Bor Wong, Chia-Wei Chang, Chien-Hao Chen, Dave W Chen, Shingjiang Jessie Lue
In this work, silver nanoparticles (Ag NPs) were decorated on thiol (-SH) grafted graphene oxide (GO) layers to investigate the antibacterial activities in Gram-positive bacteria ( Staphylococcus aureus ) and Gram-negative bacteria ( Pseudomonas aeruginosa ). The quasi-spherical, nano-sized Ag NPs were attached to the GO surface layers, as confirmed by using field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM), respectively. The average size of GO-Ag nanocomposites was significantly reduced (327 nm) from those of pristine GO (962 nm) while the average size of loaded Ag NPs was significantly smaller than the Ag NPs without GO...
March 14, 2018: Nanomaterials
Adisa Kursumovic, Jenny C Kienzler, Gerrit J Bouma, Richard Bostelmann, Michael Heggeness, Claudius Thome, Larry E Miller, Martin Barth
STUDY DESIGN: Post hoc analysis of a randomized controlled trial. OBJECTIVE: To characterize the morphology and clinical relevance of vertebral endplate changes (VEPC) following limited lumbar discectomy with or without implantation of a bone-anchored annular closure device (ACD). SUMMARY OF BACKGROUND DATA: Implantation of an ACD following limited lumbar discectomy has shown promise in reducing the risk of recurrent herniation in patients with large annular defects...
March 13, 2018: Spine
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