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https://www.readbyqxmd.com/read/29774516/periodic-variation-of-aak1-in-an-a%C3%AE-1-42-induced-mouse-model-of-alzheimer-s-disease
#1
Xue Fu, Meiling Ke, Weihua Yu, Xia Wang, Qian Xiao, Min Gu, Yang Lü
Inhibition of endocytosis in an Alzheimer's disease (AD) model has been shown to be able to prevent amyloid β (Aβ)-induced damage and to exert a beneficial effect in treating AD. Adaptor-associated kinase 1 (AAK1), which binds to the adaptor protein complex 2 (AP-2), regulates the process of clathrin-mediated endocytosis. However, how AAK1 expression varies over the course of AD is unknown. In this study, we investigated AAK1 levels in AD model mice over time. Aβ1-42 was used to establish a mouse AD model, and the Morris water maze test was used to characterize the time course of Aβ1-42 -induced cognition changes...
May 17, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29760237/identification-of-a-wells-dawson-polyoxometalate-based-ap-2%C3%AE-inhibitor-with-pro-apoptotic-activity
#2
Jiamiao Hu, Si Kee Tan, Michelle Gek Liang Lim, Shie Hong Chang, Guimei Cui, Shanshan Liu, Kamesh Narasimhan, Siu Yee New, Xuecong Wang, Congling Chen, Harapriya Chakravarty, Prasanna R Kolatkar, Kin Yip Tam, Qian Lu, Xiaodi Su, Ralf Jauch, Edwin Cheung
AP-2 gamma (AP-2γ) is a transcription factor that plays pivotal roles in breast cancer biology. To search for small molecule inhibitors of AP-2γ, we performed a high-throughput fluorescence anisotropy screen and identified a polyoxometalate compound with Wells-Dawson structure K6 [P2 Mo18 O62 ] (Dawson-POM) that blocks the DNA binding activity of AP-2γ. We showed this blocking activity is due to the direct binding of Dawson-POM to AP-2γ. We also provide evidence to show that Dawson-POM decreases AP-2γ dependent transcription similar to silencing the gene...
May 14, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29757604/a-symmetric-molecule-produced-by-mycobacteria-generates-cell-length-asymmetry-during-cell-division-and-thereby-cell-length-heterogeneity
#3
Nagaraja Mukkayyan, Deepti Sharan, Parthasarathi Ajitkumar
Diadenosine polyphosphates, Ap(2-7)A, which contain two adenosines in a 5',5' linkage through phosphodiester bonds involving 2-7 phosphates, regulate diverse cellular functions in all the organisms, from bacteria to humans, under normal and stress conditions. We had earlier reported consistent occurrence of asymmetric constriction during division (ACD) in 20-30% of dividing mycobacterial cells in culture, irrespective of different growth media, implying exogenous action of some factor of mycobacterial origin...
May 14, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29715367/conditional-deletion-of-ap-2%C3%AE-and-ap-2%C3%AE-in-the-developing-murine-retina-leads-to-altered-amacrine-cell-mosaics-and-disrupted-visual-function
#4
Emily Anne Hicks, Mizna Zaveri, Paula A Deschamps, Michael D Noseworthy, Alexander Ball, Trevor Williams, Judith A West-Mays
Purpose: The combined action of the activating protein-2 (AP-2) transcription factors, AP-2α and AP-2β, is important in early retinal development, specifically in the formation of horizontal cells. However, in previous studies, it was not possible to analyze postnatal development and function of additional retinal subtypes. Methods: We used a double conditional deletion of AP-2α and AP-2β from the retina to further examine the combinatory role of these genes in retinal cell patterning and function in postnatal adult mice as measured by Voronoi domain area and nearest-neighbor distance spatial analyses and ERGs, respectively...
May 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29674317/the-atypical-mitogen-activated-protein-kinase-erk3-is-essential-for-establishment-of-epithelial-architecture
#5
Chika Takahashi, Koichi Miyatake, Morioh Kusakabe, Eisuke Nishida
Epithelia contribute to physical barriers that protect internal tissues from the external environment and also support organ structure. Accordingly, establishment and maintenance of epithelial architecture are essential for both embryonic development and adult physiology. Here, using gene knockout and -down techniques along with gene profiling, we show that extracellular signal-regulated kinase 3 (ERK3), a poorly characterized atypical mitogen-activated protein kinase (MAPK), regulates the epithelial architecture in vertebrates...
April 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29610526/zinc-finger-protein-471-suppresses-gastric-cancer-through-transcriptionally-repressing-downstream-oncogenic-pls3-and-tfap2a
#6
Lei Cao, Shiyan Wang, Yanquan Zhang, Ka-Chun Wong, Geicho Nakatsu, Xiaohong Wang, Sunny Wong, Jiafu Ji, Jun Yu
Zinc-finger protein 471 (ZNF471) was preferentially methylated in gastric cancer using promoter methylation array. The role of ZNF471 in human cancer is unclear. Here we elucidated the functional significance, molecular mechanisms and clinical impact of ZNF471 in gastric cancer. ZNF471 mRNA was silenced in 15 out of 16 gastric cancer cell lines due to promoter hypermethylation. Significantly higher ZNF471 promoter methylation was also observed in primary gastric cancers compared to their adjacent normal tissues (P < 0...
April 3, 2018: Oncogene
https://www.readbyqxmd.com/read/29561802/selection-and-characterization-of-single-stranded-dna-aptamers-binding-human-b-cell-surface-protein-cd20-by-cell-selex
#7
Mansoureh Haghighi, Hossein Khanahmad, Abbasali Palizban
The B-lymphocyte antigen (CD20) is a suitable target for single-stranded (ss) nucleic acid oligomer (aptamers). The aim of study was selection and characterization of a ssDNA aptamer against CD20 using Cell-Systematic Evolution of Ligands by Exponential Enrichment (Cell-SELEX). The cDNA clone of CD20 (pcDNA-CD20) was transfected to human embryonic kidney (HEK293T) cells. Ten rounds of Cell-SELEX was performed on recombinant HEK-CD20 cells. The final eluted ssDNA pool was amplified and ligated in T/A vector for cloning...
March 21, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29560666/persistent-systemic-inflammatory-response-syndrome-predicts-the-need-for-tertiary-care-in-acute-pancreatitis
#8
Biku Joseph John, Swaminathan Sambandam, Prerna Garg, Gursharan Singh, Maninder Kaur, Rathi Baskaran, Gautham Srinivasan, Venkatakrishnan Leelakrishnan, Krishnaveni 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. MATERIAL AND METHODS: Retrospective analyses of patients admitted with AP over a one year period...
July 2017: Acta Gastro-enterologica Belgica
https://www.readbyqxmd.com/read/29543447/small-molecule-interactome-mapping-by-photoaffinity-labeling-reveals-binding-site-hotspots-for-the-nsaids
#9
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
https://www.readbyqxmd.com/read/29535204/interactions-between-the-hepatitis-c-virus-nonstructural-2-protein-and-host-adaptor-proteins-1-and-4-orchestrate-virus-release
#10
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
https://www.readbyqxmd.com/read/29514909/hiv-1-nef-antagonizes-serinc5-restriction-by-downregulation-of-serinc5-via-the-endosome-lysosome-system
#11
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 major histocompatibility complex class I (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 to CD4 and MHC-I. We confirm that Nef excludes Ser5 from human immunodeficiency virus type 1 (HIV-1) virions by downregulating its cell surface expression via similar functional motifs required for CD4 downregulation...
June 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29513171/persistent-systemic-inflammatory-response-syndrome-predicts-the-need-for-tertiary-care-in-acute-pancreatitis
#12
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
https://www.readbyqxmd.com/read/29476203/first-experience-with-zero-fluoroscopic-ablation-for-supraventricular-tachycardias-using-a-novel-impedance-and-magnetic-field-based-mapping-system
#13
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
https://www.readbyqxmd.com/read/29467543/ap-2%C3%AE%C2%B5-expression-in-developing-retina-contributing-to-the-molecular-diversity-of-amacrine-cells
#14
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
https://www.readbyqxmd.com/read/29439714/tfap2c-promotes-stemness-and-chemotherapeutic-resistance-in-colorectal-cancer-via-inactivating-hippo-signaling-pathway
#15
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
https://www.readbyqxmd.com/read/29407793/promoter-analysis-and-transcriptional-regulation-of-human-carbonic-anhydrase-viii-gene-in-a-merrf-disease-cell-model
#16
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...
March 1, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29383097/efficacy-of-decitabine-loaded-gelatinases-stimuli-nanoparticles-in-overcoming-cancer-drug-resistance-is-mediated-via-its-enhanced-demethylating-activity-to-transcription-factor-ap-2-epsilon
#17
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
https://www.readbyqxmd.com/read/29316491/presynaptic-endocytic-factors-in-autophagy-and-neurodegeneration
#18
REVIEW
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...
February 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29302823/biodegradation-of-sulfonamides-by-shewanella-oneidensis-mr-1-and-shewanella-sp-strain-mr-4
#19
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...
April 2018: Biodegradation
https://www.readbyqxmd.com/read/29288152/cytotoxic-granule-endocytosis-depends-on-the-flower-protein
#20
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...
February 5, 2018: Journal of Cell Biology
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