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Jinxu Gao, Adelphe Mfuh, Yuka Amako, Christina M Woo
Many therapeutics elicit cell-type specific polypharmacology that is executed by a network of molecular recognition events between a small molecule and the whole proteome. However, measurement of the structures that underpin the molecular associations between the proteome and even common therapeutics, such as the nonsteroidal anti-inflammatory drugs (NSAIDs), is limited by the inability to map the small molecule interactome. To address this gap, we developed a platform termed small molecule interactome mapping by photoaffinity labeling (SIM-PAL) and applied it to the in cellulo direct characterization of specific NSAID binding sites...
March 15, 2018: Journal of the American Chemical Society
Fei Xiao, Stanley Wang, Rina Barouch-Bentov, Gregory Neveu, Szuyuan Pu, Melanie Beer, Stanford Schor, Sathish Kumar, Vlad Nicolaescu, Brett D Lindenbach, Glenn Randall, Shirit Einav
Hepatitis C virus (HCV) spreads via secreted cell-free particles or direct cell-to-cell transmission. Yet, virus-host determinants governing differential intracellular trafficking of cell-free- and cell-to-cell-transmitted virus remain unknown. The host adaptor proteins (APs) AP-1A, AP-1B, and AP-4 traffic in post-Golgi compartments, and the latter two are implicated in basolateral sorting. We reported that AP-1A mediates HCV trafficking during release, whereas the endocytic adaptor AP-2 mediates entry and assembly...
March 13, 2018: MBio
Jing Shi, Ran Xiong, Tao Zhou, Peiyi Su, Xihe Zhang, Xusheng Qiu, Hongmei Li, Sunan Li, Changqing Yu, Bin Wang, Chan Ding, Thomas E Smithgall, Yong-Hui Zheng
The primate lentiviral accessory protein Nef downregulates CD4 and MHC-I from the cell surface via independent endosomal trafficking pathways to promote viral pathogenesis. In addition, Nef antagonizes a novel restriction factor, SERINC5 (Ser5), to increase viral infectivity. To explore the molecular mechanism of Ser5 antagonism by Nef, we determined how Nef affects Ser5 expression and intracellular trafficking in comparison with CD4 and MHC-I. We confirm that Nef excludes Ser5 from HIV-1 virions by downregulating its cell surface expression via similar functional motifs required for CD4-downregulation...
March 7, 2018: Journal of Virology
B J John, S Sambandam, P Garg, G Singh, B Edizer, M Kaur, R Baskaran, G Srinivasan, V Leelakrishnan, K Janarthan
INTRODUCTION: Patients with Acute Pancreatitis (AP) presenting with Systemic Inflammatory Response syndrome (SIRS) are more likely to have severe acute pancreatitis and are at increased risk of complications. Additionally, persistence of SIRS at 48 hrs after admission is associated with persistent organ failure and a worse outcome. We investigated the usefulness of SIRS as a criterion for referring patients to a tertiary pancreatic care centre. MATERIALS METHODS: Retrospective analyses of patients admitted with AP over a one year period...
July 2017: Acta Gastro-enterologica Belgica
Katie A Walsh, Joseph Galvin, John Keaney, Edward Keelan, Gabor Szeplaki
AIMS: Zero- and near-zero-fluoroscopic ablation techniques reduce the harmful effects of ionizing radiation during invasive electrophysiology procedures. We aimed to test the feasibility and safety of a zero-fluoroscopic strategy using a novel integrated magnetic and impedance-based electroanatomical mapping system for radiofrequency ablation (RFA) of supraventricular tachycardias (SVTs). METHODS: We retrospectively studied 92 consecutive patients undergoing electrophysiology studies with/without RFA for supraventricular tachycardia (SVT) performed by a single operator at a single center...
February 23, 2018: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
Saket Jain, Darryl D Glubrecht, Devon R Germain, Markus Moser, Roseline Godbout
AP-2 transcription factors play important roles in the regulation of gene expression during development. Four of the five members of the AP-2 family (AP-2α, AP-2β, AP-2γ and AP-2δ) have previously been shown to be expressed in developing retina. Mouse knockouts have revealed roles for AP-2α, AP-2β and AP-2δ in retinal cell specification and function. Here, we show that the fifth member of the AP-2 family, AP-2ε, is also expressed in amacrine cells in developing mammalian and chicken retina. Our data indicate that there are considerably fewer AP-2ε-positive cells in the developing mouse retina compared to AP-2α, AP-2β and AP-2γ-positive cells, suggesting a specialized role for AP-2ε in a subset of amacrine cells...
February 21, 2018: Scientific Reports
Xu Wang, Di Sun, Jiandong Tai, Si Chen, Miao Yu, Dong Ren, Lei Wang
BACKGROUND: Aberrant expression of transcription Factor AP-2 Gamma (TFAP2C) has been reported to be implicated in malignant process of many cancers. The purpose of this study is to investigate the clinical significance and biological roles of TFAP2C in colorectal cancer (CRC). METHODS: TFAP2C expression was evaluated by real-time PCR, Western blot and immunohistochemistry (IHC) respectively in clinical CRC tissues. Statistical analysis was performed to explore the correlation between TFAP2C expression and clinicopathological features, and overall and progression-free survival in CRC patients...
February 13, 2018: Journal of Experimental & Clinical Cancer Research: CR
Che-Min Lo, Yi-Shing Ma, Yau-Huei Wei, Benjamin Y T Hsieh, Mingli Hsieh
Myoclonic epilepsy with ragged-red fibers (MERRF) is a maternally inherited mitochondrial neuromuscular disease. We previously reported a significant decrease of mRNA and protein levels of nuclear DNA-encoded carbonic anhydrase VIII (CA8) in MERRF cybrids harboring A8344G mutation in mitochondrial DNA (mtDNA). In this study, we established a reporter construct of luciferase gene-carrying hCA8 promoter containing several putative transcription factor-binding sites, including GC-box, AP-2 and TATA-binding element in the 5'flanking region of the hCA8 gene...
January 31, 2018: Archives of Biochemistry and Biophysics
Yi-Dong Hong, Jian Zhang, Ming Zhuang, Wei Li, Puy-Uan Wu, Ru-Tian Li, Nan Hu, Bao-Xiang Bian, Zi-Yan Song, Feng-Lei Wu
Hypermethylation of the transcription factor AP-2 epsilon (TFAP2E) gene affects 5-fluorouridine (5-FU) resistance in gastric cancer (GC) patients. The epigenetic inhibitor 5-Aza-2'-deoxycytidine (DAC), which reverses DNA methylation by targeting DNA methyltransferases (DNMTs), has potential to sensitize GC to 5-FU. Nevertheless, DNA demethylation only DAC transiently occurs since DAC is unstable in aqueous solutions, which limits its potential. Here we developed intelligent nanoparticles (NPs) comprising gelatinase with polyethylene glycol (PEG) and poly-ε-caprolactone) (PCL) to specifically deliver DAC (DAC-TNPs) to tumors...
December 29, 2017: Oncotarget
Domenico Azarnia Tehran, Marijn Kuijpers, Volker Haucke
Neuronal signaling depends on the exocytic fusion and subsequent endocytic retrieval and reformation of neurotransmitter-containing synaptic vesicles at synapses. Recent findings have uncovered surprising roles of presynaptic endocytic proteins in the formation and transport of autophagosomes. These include functions of the membrane remodelling protein endophilin and its downstream effector, the phosphoinositide phosphatase synaptojanin, in autophagosome formation and in Parkinson's disease, the endocytic sorting adaptor CALM in protein degradation via the autophagy/lysosomal pathway in Alzheimer's disease, and the clathrin adaptor complex AP-2 in retrograde transport of signaling autophagosomes to prevent neurodegeneration...
January 6, 2018: Current Opinion in Neurobiology
Fei Mao, Xiaohong Liu, Kang Wu, Chen Zhou, Youbin Si
Because of extensive sulfonamides application in aquaculture and animal husbandry and the consequent increase in sulfonamides discharged into the environment, strategies to remediate sulfonamide-contaminated environments are essential. In this study, the resistance of Shewanella oneidensis MR-1 and Shewanella sp. strain MR-4 to the sulfonamides sulfapyridine (SPY) and sulfamethoxazole (SMX) were determined, and sulfonamides degradation by these strains was assessed. Shewanella oneidensis MR-1 and Shewanella sp...
January 4, 2018: Biodegradation
Hsin-Fang Chang, Stefanie Mannebach, Andreas Beck, Keerthana Ravichandran, Elmar Krause, Katja Frohnweiler, Claudia Fecher-Trost, Claudia Schirra, Varsha Pattu, Veit Flockerzi, Jens Rettig
Cytotoxic T lymphocytes (CTLs) kill target cells by the regulated release of cytotoxic substances from granules at the immunological synapse. To kill multiple target cells, CTLs use endocytosis of membrane components of cytotoxic granules. We studied the potential calcium dependence of endocytosis in mouse CTLs on Flower, which mediates the calcium dependence of synaptic vesicle endocytosis in Drosophila melanogaster Flower is predominantly localized on intracellular vesicles that move to the synapse on target cell contact...
December 29, 2017: Journal of Cell Biology
Maisam Abu-El-Haija, Soma Kumar, Jose Antonio Quiros, Keshawadhana Balakrishnan, Bradley Barth, Samuel Bitton, John F Eisses, Elsie Jazmin Foglio, Victor Fox, Denease Francis, Alvin Jay Freeman, Tanja Gonska, Amit S Grover, Sohail Z Husain, Rakesh Kumar, Sameer Lapsia, Tom Lin, Quin Y Liu, Asim Maqbool, Zachary M Sellers, Flora Szabo, Aliye Uc, Steven L Werlin, Veronique D Morinville
BACKGROUND: Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed. METHODS: The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to management considerations in adult and pediatric AP. The literature was summarized, quality of evidence reviewed, and statements of recommendations developed...
January 2018: Journal of Pediatric Gastroenterology and Nutrition
Aifang Cheng, Teng Zhao, Kai-Hei Tse, Hei-Man Chow, Yong Cui, Liwen Jiang, Shengwang Du, Michael M T Loy, Karl Herrup
ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) are large PI3 kinases whose human mutations result in complex syndromes that include a compromised DNA damage response (DDR) and prominent nervous system phenotypes. Both proteins are nuclear-localized in keeping with their DDR functions, yet both are also found in cytoplasm, including on neuronal synaptic vesicles. In ATM- or ATR-deficient neurons, spontaneous vesicle release is reduced, but a drop in ATM or ATR level also slows FM4-64 dye uptake...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
Jian-Du Yang, Gong-Bu Zhou, Qi Sun, Xiao-Gang Guo, Xu Liu, Bin Luo, Hui-Qiang Wei, Jackson J Liang, Shuanglun Xie, Fei-Fan Ouyang, Jian Ma
Aims: We aimed to examine the electrocardiographic and electrophysiologic characteristics of anterograde-conducting decremental accessory pathways (DAP) and to identify surrogate criteria to distinguish short atrioventricular (SAV) DAP from atriofascicular (AF) AP and long atrioventricular (LAV) DAP. Methods and results: We identified all patients with DAPs and analysed electrocardiographic and electrophysiologic characteristics. Distal insertion sites were examined using existing criteria, including V-H interval, ventricular activation at the right ventricular apex, and around tricuspid annulus during antidromic atrioventricular re-entrant tachycardia (A-AVRT) or complete pre-excitation and evaluated the AV node-like properties according to the response to adenosine and radiofrequency ablation...
December 13, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Jian-Wen Hou, Wei Li, Yu-Dong Fei, Yi-He Chen, Qian Wang, Yue-Peng Wang, Yi-Gang Li
Rate-dependent repolarization (RDR) of action potential (AP) in cardiomyocyte plays a critical role in the genesis of arrhythmias and RDR in atrium has been linked with atrial fibrillation. However, detailed studies focusing on the role of RDR in rabbit atrium are scant. In this study, atrial cells were isolated from rabbit heart and rate-dependent property was explored in single atrial cell to elucidate the underlying mechanism. Our results indicated that rate-dependent prolongation was evident at the action potential duration at 20% (APD20) and 50% (APD50) repolarization but not at 90% repolarization (APD90) under control condition...
December 14, 2017: Journal of Physiology and Biochemistry
Blake Schouest, Andrea M Weiler, Sanath Kumar Janaka, T Alix Myers, Arpita Das, Sarah C Wilder, Jessica Furlott, Melody Baddoo, Erik K Flemington, Eva G Rakasz, David T Evans, Thomas C Friedrich, Nicholas J Maness
Nef-specific CD8+ T lymphocytes (CD8TL) are linked to extraordinary control of primate lentiviral replication, but the mechanisms underlying their efficacy remain largely unknown. The immunodominant, Mamu-B*017:01+ restricted Nef195-203MW9 epitope in SIVmac239 partially overlaps a sorting motif important for interactions with host AP-2 proteins and, hence, downmodulation of several host proteins including Tetherin (CD317/BST-2), CD28, CD4, SERINC3, and SERINC5. We reasoned that CD8TL-driven evolution in this epitope might compromise Nef's ability to modulate these important molecules...
December 13, 2017: Journal of Virology
Jagadeesh S Rao, Stanley I Rapoport, Francesca Bosetti
This corrects the article DOI: 10.1038/ajg.2016.125.
January 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Eric Van Otterloo, Hong Li, Kenneth L Jones, Trevor Williams
The evolution of a hinged moveable jaw with variable morphology is considered a major factor behind the successful expansion of the vertebrates. DLX homeobox transcription factors are crucial for establishing the positional code that patterns the mandible, maxilla and intervening hinge domain, but how the genes encoding these proteins are regulated remains unclear. Herein, we demonstrate that the concerted action of the AP-2α and AP-2β transcription factors within the mouse neural crest is essential for jaw patterning...
January 25, 2018: Development
Masahiro Yoshida, Takayuki Murata, Keiji Ashio, Yohei Narita, Takahiro Watanabe, H M Abdullah Al Masud, Yoshitaka Sato, Fumi Goshima, Hiroshi Kimura
Latent membrane protein 1 (LMP1) is a major oncogene encoded by Epstein-Barr virus (EBV) and is essential for immortalization of B cells by the virus. Previous studies suggested that several transcription factors, such as PU.1, RBP-Jκ, NFκB, EBF1, AP-2 and STAT, are involved in LMP1 induction; however, the means by which the oncogene is negatively regulated remains unclear. Here, we introduced short mutations into the proximal LMP1 promoter that includes recognition sites for the E-box and Ikaros transcription factors in the context of EBV-bacterial artificial chromosome...
2017: Frontiers in Microbiology
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