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https://www.readbyqxmd.com/read/28810265/viral-retinopathy-in-experimental-models-of-zika-infection
#1
Zhenyang Zhao, Matthew Yang, Sasha R Azar, Lynn Soong, Scott C Weaver, Jiaren Sun, Yan Chen, Shannan L Rossi, Jiyang Cai
Purpose: Emerging evidence has shown that both congenital and adult Zika virus (ZIKV) infection can cause eye diseases. The goals of the current study were to explore mechanisms and pathophysiology of ZIKV-induced eye defects. Methods: Wild-type or A129 interferon type I receptor-deficient mice were infected by either FSS13025 or Mex1-7 strain of ZIKV. Retinal histopathology was measured at different time points after infection. The presence of viral RNA and protein in the retina was determined by in situ hybridization and immunofluorescence staining, respectively...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28804597/size-and-concentration-analyses-of-extracellular-vesicles-by-nanoparticle-tracking-analysis-a-variation-study
#2
Beate Vestad, Alicia Llorente, Axl Neurauter, Santosh Phuyal, Bente Kierulf, Peter Kierulf, Tore Skotland, Kirsten Sandvig, Kari Bente F Haug, Reidun Øvstebø
Current methods for characterisation of extracellular vesicles (EVs) need further standardisation in order to obtain an acceptable level of data comparability. Size and concentration of EVs can be determined by nanoparticle tracking analysis (NTA). However, both the heterogeneity of EVs and the choice of instrument settings may cause an appreciable analytical variation. Intra-assay (within-day, n = 6) and inter-assay (day-to-day, n = 6) variations (coefficient of variation, % CV) of different preparations of EVs and artificial vesicles or beads were determined using two NanoSight NS500 instruments, located at different laboratories...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28800189/supramolecular-host-guest-inclusion-for-distinguishing-cucurbit-7-uril-based-pseudorotaxanes-from-small-molecule-ligands-in-coordination-assembly-with-uranyl-center
#3
Wei-Qun Shi, Lei Mei, Zhen-Ni Xie, Kong-Qiu Hu, Li-Yong Yuan, Zeng-Qiang Gao, Zhi-Fang Chai
Although the capability of supramolecular pseudorotaxane/rotaxane systems as ligands for coordination with actinides has been identified by the on-going emerging of uranyl-organic polyrotaxane compounds, it is, however, still unknown how supramolecular inclusion affects the coordination assembly of the simple 'axle' ligand with uranyl species. Herein, a semi-rigid organic dicarboxylate compound [BzBPCEt]Br2 (L1) is selected as a small-molecule 'axle' ligand and the corresponding cucurbit[7]uril (CB7)-based [2]pseudorotaxane ligand, [BzBPCEt]Br2@CB7 (L1@CB7) has been also synthesized through CB7-based inclusion in this work...
August 11, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28799754/on-the-threading-of-an-inherently-directional-calixarene-wheel-with-oriented-ammonium-axles
#4
Pellegrino La Manna, Carmen Talotta, Carmine Gaeta, Annunziata Soriente, Margherita De Rosa, Placido Neri
The threading of mono-stoppered alkylbenzylammonium axles 7+ and 8+ with the calix[6]-wheel 3 can occurs by both the routes of entering of the macrocycle 3 in the cone conformation: through-the-exo-rim and the through-the-endo-rim passage. Thus, under thermodynamic conditions, with both the axles 7+ and 8+ the two possible oriented calix[2]pseudorotaxane, namely endo-benzyl and endo-alkyl, are formed with a stereoselectivity controlled by endo-alkyl rule. Interestingly, by 1H NMR monitoring of the threading process between 8+ and 3, we revealed two calix[2]pseudorotaxane isomers in which the calix-weel adopts a 1,2,3-alternate and cone conformations, respectively, the kinetic and thermodynamic species...
August 11, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28790340/verteporfin-inhibits-growth-of-human-glioma-in-vitro-without-light-activation
#5
Ahmad Al-Moujahed, Katarzyna Brodowska, Tomasz P Stryjewski, Nikolaos E Efstathiou, Ioannis Vasilikos, Joanna Cichy, Joan W Miller, Evangelos Gragoudas, Demetrios G Vavvas
Verteporfin (VP), a light-activated drug used in photodynamic therapy for the treatment of choroidal neovascular membranes, has also been shown to be an effective inhibitor of malignant cells. Recently, studies have demonstrated that, even without photo-activation, VP may still inhibit certain tumor cell lines, including ovarian cancer, hepatocarcinoma and retinoblastoma, through the inhibition of the YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma cell lines (LN229 and SNB19)...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28783341/synthesis-of-mechanically-planar-chiral-rac-2-rotaxanes-by-partitioning-of-an-achiral-2-rotaxane-stereoinversion-induced-by-shuttling
#6
Yuta Mochizuki, Katsuhiko Ikeyatsu, Yuichiro Mutoh, Shoichi Hosoya, Shinichi Saito
Mechanically planar chiral [2]rotaxanes were synthesized by the introduction of bulky pyrrole moieties into the axle component of an achiral [2]rotaxane. The enantiomers were separated by chiral HPLC. The shuttling of the ring component between the two compartments at high temperature induced the stereoinversion of the mechanically planar chiral [2]rotaxane. The rate of the stereoinversion was studied quantitatively, and the kinetic parameters were determined.
August 7, 2017: Organic Letters
https://www.readbyqxmd.com/read/28782530/chemotherapeutics-resistance-arms-race-an-update-on-mechanisms-involved-in-resistance-limiting-egfr-inhibitors-in-lung-cancer
#7
REVIEW
Pankaj Kumar Singh, Om Silakari
Clinical reports suggest that EGFR-mutated lung cancer usually respond significantly towards small molecule tyrosine kinase inhibitors. Same studies also report the eventual development of acquired resistance within a median time interval of 9 to 14months. One of the major mechanisms involved in this acquired resistance was found to be a secondary point mutation at gate-keeper residue, EGFR T790M. However, there are other recent studies which disclose the role of few other novel key players such as, ZEB1, TOPK etc...
August 4, 2017: Life Sciences
https://www.readbyqxmd.com/read/28777563/enantioselective-anion-recognition-by-chiral-halogen-bonding-2-rotaxanes
#8
Jason Y C Lim, Igor Marques, Vítor Félix, Paul D Beer
The application of chiral interlocked host molecules for discrimination of guest enantiomers has been largely overlooked, which is surprising given their unique three-dimensional binding cavities capable of guest encapsulation. Herein, we combined the stringent linear geometric interaction constraints of halogen bonding (XB), the non-covalent interaction between an electrophilic halogen atom and a Lewis base, with highly preorganized and conformationally restricted chiral cavities of [2]rotaxanes to achieve enantioselective anion recognition...
August 4, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28768810/mouse-macrophages-show-different-requirements-for-phosphatidylserine-receptor-tim4-in-efferocytosis
#9
Yuichi Yanagihashi, Katsumori Segawa, Ryota Maeda, Yo-Ichi Nabeshima, Shigekazu Nagata
Protein S (ProS) and growth arrest-specific 6 (Gas6) bind to phosphatidylserine (PtdSer) and induce efferocytosis upon binding TAM-family receptors (Tyro3, Axl, and Mer). Here, we produced mouse ProS, Gas6, and TAM-receptor extracellular region fused to IgG fragment crystallizable region in HEK293T cells. ProS and Gas6 bound Ca(2+) dependently to PtdSer (Kd 20-40 nM), Mer, and Tyro3 (Kd 15-50 nM). Gas6 bound Axl strongly (Kd < 1.0 nM), but ProS did not bind Axl. Using NIH 3T3-based cell lines expressing a single TAM receptor, we showed that TAM-mediated efferocytosis was determined by the receptor-binding ability of ProS and Gas6...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28749535/inhibition-of-histone-deacetylases-sensitizes-egfr-tki-resistant-non-small-cell-lung-cancer-cells-to-erlotinib-in-vitro-and-in-vivo
#10
Weiwei Yu, Weiqiang Lu, Guoliang Chen, Feixiong Cheng, Hui Su, Yihua Chen, Mingyao Liu, Xiufeng Pang
BACKGROUND AND PURPOSE: Intrinsic and/or acquired resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) commonly occurs in patients with non-small-cell lung cancer (NSCLC). Here, we develop a combined therapy of histone deacetylase inhibition by a novel HDAC inhibitor, YF454A, with erlotinib to overcome EGFR-TKI resistance in NSCLC. EXPERIMENTAL APPROACH: The sensitization of erlotinib by YF454A was examined in a panel of EGFR-TKI-resistant NSCLC cell lines in vitro and two different erlotinib-resistant NSCLC xenograft mouse models in vivo...
July 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28742160/sub-classification-of-myopic-glaucomatous-eyes-according-to-optic-disc-and-peripapillary-features
#11
Seungbong Han, Kyung Rim Sung, Jimin Park, Joo Young Yoon, Joong Won Shin
PURPOSE: To investigate the sub-classification of myopic glaucomatous eyes by optic disc and peripapillary features. METHODS: Optic disc tilt and torsion were determined from retinal nerve fiber layer photographs. Based on the location of the Bruch's membrane (BM) opening within the β-zone of the peripapillary atrophy (PPA) area, the widths of β-zone PPA (PPA1W), PPA+BM (PPA2W), and PPA-BM (PPA3W) were measured with enhanced depth imaging spectral-domain optical coherence tomography...
2017: PloS One
https://www.readbyqxmd.com/read/28739278/p38mapk-plays-a-critical-role-in-induction-of-a-pro-inflammatory-phenotype-of-retinal-m%C3%A3-ller-cells-following-zika-virus-infection
#12
Shuang Zhu, Huanle Luo, Hua Liu, Yonju Ha, Elizabeth R Mays, Ryan E Lawrence, Evandro Winkelmann, Alan D Barrett, Sylvia B Smith, Min Wang, Tian Wang, Wenbo Zhang
Zika virus (ZIKV) infection has been associated with ocular abnormalities such as chorioretinal atrophy, optic nerve abnormalities, posterior uveitis and idiopathic maculopathy. Yet our knowledge about ZIKV infection in retinal cells and its potential contribution to retinal pathology is still very limited. Here we found that primary Müller cells, the principal glial cells in the retina, expressed a high level of ZIKV entry cofactor AXL gene and were highly permissive to ZIKV infection. In addition, ZIKV-infected Müller cells exhibited a pro-inflammatory phenotype and produced many inflammatory and growth factors...
July 21, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28734578/phosphatidylserine-is-the-signal-for-tam-receptors-and-their-ligands
#13
REVIEW
Greg Lemke
Nature repeatedly repurposes, in that molecules that serve as metabolites, energy depots, or polymer subunits are at the same time used to deliver signals within and between cells. The preeminent example of this repurposing is ATP, which functions as a building block for nucleic acids, an energy source for enzymatic reactions, a phosphate donor to regulate intracellular signaling, and a neurotransmitter to control the activity of neurons. A series of recent studies now consolidates the view that phosphatidylserine (PtdSer), a common phospholipid constituent of membrane bilayers, is similarly repurposed for use as a signal between cells and that the ligands and receptors of the Tyro3/Axl/Mer (TAM) family of receptor tyrosine kinases (RTKs) are prominent transducers of this signal...
July 19, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28732351/tropomyosin-isoform-tpm2-1-regulates-collective-and-amoeboid-cell-migration-and-cell-aggregation-in-breast-epithelial-cells
#14
HyeRim Shin, Dayoung Kim, David M Helfman
Metastasis dissemination is the result of various processes including cell migration and cell aggregation. These processes involve alterations in the expression and organization of cytoskeletal and adhesion proteins in tumor cells. Alterations in actin filaments and their binding partners are known to be key players in metastasis. Downregulation of specific tropomyosin (Tpm) isoforms is a common characteristic of transformed cells. In this study, we examined the role of Tpm2.1 in non-transformed MCF10A breast epithelial cells in cell migration and cell aggregation, because this isoform is downregulated in primary and metastatic breast cancer as well as various breast cancer cell lines...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28727830/the-receptor-tyrosine-kinase-axl-promotes-migration-and-invasion-in-colorectal-cancer
#15
Diana J Uribe, Edward K Mandell, Adam Watson, Jesse D Martinez, Jonathan A Leighton, Sourav Ghosh, Carla V Rothlin
The receptor tyrosine kinases (RTKs) TYRO3, AXL and MERTK (TAM) have well-described oncogenic functions in a number of cancers. Notwithstanding, TAM RTKs are also potent and indispensable inhibitors of inflammation. The combined deletion of Axl and Mertk in mice enhances chronic inflammation and autoimmunity, including increased inflammation in the gut and colitis-associated cancer. On the other hand, deletion of Tyro3 increases the risk of allergic responses. Therefore, the indiscriminate inhibition of these TAM RTKs could result in undesirable immunological diseases...
2017: PloS One
https://www.readbyqxmd.com/read/28726932/cationic-all-halogen-bonding-rotaxanes-for-halide-anion-recognition
#16
Xiaoxiong Li, Jason Y C Lim, Paul D Beer
A family of cationic halogen bonding [2]rotaxanes have been synthesised via an active-metal template synthetic strategy. (1)H NMR spectroscopic anion titration investigations reveal these interlocked host systems recognize halides selectively over oxoanions in aqueous-organic solvent media. Furthermore, systematically modulating the rigidity and size of the rotaxanes' anion binding cavities via metal complexation, as well as by varying the number of halogen bond-donor groups in the axle component, was found to dramatically influence halide anion selectivity...
July 20, 2017: Faraday Discussions
https://www.readbyqxmd.com/read/28724631/the-axl-kinase-domain-in-complex-with-a-macrocyclic-inhibitor-offers-first-structural-insights-into-an-active-tam-receptor-kinase
#17
Ketan S Gajiwala, Neil Grodsky, Ben Bolaños, Junli Feng, RoseAnn Ferre, Sergei Timofeevski, Meirong Xu, Brion W Murray, Ted W Johnson, Al Stewart
The receptor tyrosine kinase (RTK) family consisting of Tyro3, Axl and Mer (TAM) is one of the most recently identified RTK families. TAM receptors are upregulated postnatally and maintained at high levels in adults. They all play an important role in immunity, but Axl has also been implicated in cancer and therefore is a target in the discovery and development of novel therapeutics. However, of the three members of the TAM family, the Axl kinase domain is the only one that has so far eluded structure determination...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28722020/a-critical-role-of-gas6-axl-signal-in-allergic-airway-responses-during-rsv-vaccine-enhanced-disease
#18
Takehiko Shibata, Manabu Ato
Respiratory syncytial virus (RSV) is a common virus that causes lower respiratory infections across a wide range of ages. A licensed RSV vaccine is not available because vaccination with formalin-inactivated RSV (FI-RSV) and the subsequent RSV infection cause not only insufficient induction of neutralizing antibodies but also severe allergic airway responses, termed FI-RSV vaccine enhanced disease (FI-RSV VED). However, the underlying mechanism has not been identified, although a Th2-biased immune response is known to be a hallmark of this disease...
July 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28720772/blockade-of-axl-signaling-ameliorates-hpv16e6-mediated-tumorigenecity-of-cervical-cancer
#19
Eun-Hee Lee, Kon-Young Ji, Eun-Mi Kim, Su-Man Kim, Hyeong-Woo Song, Ha-Rim Choi, Byung Yeoup Chung, Hyo Jin Choi, Hyoung-Woo Bai, Hyung-Sik Kang
Axl receptor tyrosine kinase is involved in the tumorigenesis and metastasis of many cancers. Axl expression was markedly higher in human papilloma virus type 16E6 (HPV16E6)-overexpressing HeLa (HE6F) cells and lower in HPV16E6-suppressing CaSki (CE6R) cells than in the controls. SiRNA-mediated knockdown of E6 expression led to increased phosphatase and tensin homolog (PTEN) phosphorylation at Ser380 and attenuated AKT phosphorylation. Expression of membrane-associated guanylate kinase inverted-2 (MAGI-2), an E6-induced degradation target, was induced in E6-siRNA-transfected cells...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717059/pharmacological-effects-of-a-vitamin-k1-2-3-epoxide-reductase-vkor-inhibitor-3-acetyl-5-methyltetronic-acid-on-cisplatin-induced-fibrosis-in-rats
#20
Masashi Uchida, Tomoya Miyoshi, Yohei Miyamoto
Cisplatin (CDDP) is a chemotherapeutic agent that is widely used in the treatment of lymphomas and solid malignancies. However, its clinical usage is limited by its severe side effects in the kidneys. Glomerular and tubular injuries in the kidneys commonly progress to interstitial fibrosis and, ultimately, the end stage of renal failure. We previously reported that 3-acetyl-5-methyltetronic acid (AMT) had inhibitory effects on rat renal vitamin K1 2,3-epoxide reductase (VKOR) in vitro and also suppressed mesangial cell proliferation and, consequently, the formation of fibrosis via the vitamin K-dependent activation of the growth arrest-specific 6 (Gas6)/Axl pathway in anti-Thy-1 glomerulonephritis (Thy-1 GN) in rats...
July 16, 2017: Journal of Veterinary Medical Science
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