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https://www.readbyqxmd.com/read/28107095/chibby1-knockdown-promotes-mesenchymal-to-epithelial-transition-like-changes
#1
Victoria Fischer, Michael Wong, Feng-Qian Li, Ken-Ichi Takemaru
Chibby1 (Cby1) was originally isolated as a binding partner for β-catenin, a dual function protein in cell-cell adhesion and in canonical Wnt signaling. The canonical Wnt/β-catenin pathway is dysregulated in various diseases including cancer, most notably of the gastrointestinal origin. To investigate the role of Cby1 in colorectal tumorigenesis, we generated stable Cby1-knockdown (KD) SW480 colon cancer cells. Unexpectedly, we found that Cby1 KD induces mesenchymal-to-epithelial transition (MET)-like changes in SW480 as well as in HEK293 cells...
January 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28106805/synthetic-assembly-of-mannose-moieties-using-polymer-chemistry-and-the-biological-evaluation-of-its-interaction-towards-concanavalin-a
#2
Deepti Diwan, Kohei Shinkai, Toshihiro Tetsuka, Bin Cao, Hidenao Arai, Tetsuo Koyama, Ken Hatano, Koji Matsuoka
Protein-carbohydrate interactions exhibit myriad intracellular recognition events, so understanding and investigating their specific interaction with high selectivity and strength are of crucial importance. In order to examine the effect of multivalent binding on the specificity of protein-carbohydrate interactions, we synthesized mannose glycosides as a novel type of glycosylated monomer and glycopolymers of polyacrylamide derivatives with α-mannose (α-Man) by radical polymerization and monitored their strength of interaction with concanavalin A (Con A) by surface plasmon resonance (SPR) detection...
January 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106687/superficial-parotidectomy-plane-for-debulking-surgery-in-kimura-disease
#3
Rohit Sharma
Kimura disease (KD) is a rare chronic inflammatory disorder of unknown etiology representing as solitary or multiple subcutaneous nodules predominantly in the head and neck region. Common sites of involvement are preauricular region, forehead and scalp. The soft tissue localization is often associated with regional lymphadenopathy and enlargement of the major salivary gland. The authors report a patient with KD involving the right parotid and left temporal region managed successfully at our center using a combination of debulking superficial parotidectomy and medicinal therapy...
January 18, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28106388/mechanistic-studies-of-single-step-styrene-production-using-a-rhodium-i-catalyst
#4
Benjamin A Vaughan, Sarah K Khani, J Brannon Gary, James D Kammert, Michael S Webster-Gardiner, Bradley A McKeown, Robert J Davis, Thomas R Cundari, T Brent Gunnoe
The direct and single-step conversion of benzene, ethylene, and a Cu(II) oxidant to styrene using the Rh(I) catalyst ((Fl)DAB)Rh(TFA)(η(2)-C2H4) [(Fl)DAB = N,N'-bis(pentafluorophenyl)-2,3-dimethyl-1,4-diaza-1,3-butadiene; TFA = trifluoroacetate] has been reported to give quantitative yields (with Cu(II) as the limiting reagent) and selectivity combined with turnover numbers >800. This report details mechanistic studies of this catalytic process using a combined experimental and computational approach. Examining catalysis with the complex ((Fl)DAB)Rh(OAc)(η(2)-C2H4) shows that the reaction rate has a dependence on catalyst concentration between first- and half-order that varies with both temperature and ethylene concentration, a first-order dependence on ethylene concentration with saturation at higher concentrations of ethylene, and a zero-order dependence on the concentration of Cu(II) oxidant...
January 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28106325/a-pde6%C3%AE-kras-inhibitor-chemotype-with-up-to-seven-h-bonds-and-picomolar-affinity-that-prevents-efficient-inhibitor-release-by-arl2
#5
Pablo Martín-Gago, Eyad K Fansa, Christian H Klein, Sandip Murarka, Petra Janning, Marc Schürmann, Malte Metz, Shehab Ismail, Carsten Schultz-Fademrecht, Matthias Baumann, Philippe I H Bastiaens, Alfred Wittinghofer, Herbert Waldmann
Small-molecule inhibition of the interaction between the KRas oncoprotein and the chaperone PDE6δ impairs KRas spatial organization and signaling in cells. However, despite potent binding in vitro (KD <10 nm), interference with Ras signaling and growth inhibition require 5-20 μm compound concentrations. We demonstrate that these findings can be explained by fast release of high-affinity inhibitors from PDE6δ by the release factor Arl2. This limitation is overcome by novel highly selective inhibitors that bind to PDE6δ with up to 7 hydrogen bonds, resulting in picomolar affinity...
January 20, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28104787/binding-characteristics-of-galectin-3-fusion-proteins
#6
Sophia Böcker, Lothar Elling
Galectin-3 modulates cell adhesion and signaling events by specific binding and cross-linking galactoside containing carbohydrate ligands. Proteolytic cleavage by metalloproteinases yields in vivo N-terminally truncated galectin-3 still bearing the carbohydrate recognition domain. Truncated galectin-3 has been demonstrated to act in vivo as a negative inhibitor of galectin-3 due to higher affinity for carbohydrate ligands. We here present our studies on a series of twelve human galectin-3 protein constructs...
January 19, 2017: Glycobiology
https://www.readbyqxmd.com/read/28104552/a-novel-salt-tolerant-bacterial-consortium-for-biodegradation-of-saline-and-recalcitrant-petrochemical-wastewater
#7
Mehdi Ahmadi, Sahand Jorfi, Raheleh Kujlu, Shokouh Ghafari, Reza Darvishi Cheshmeh Soltani, Nematollah Jaafarzadeh Haghighifard
Treatment of a saline petrochemical wastewater with BOD5/COD ratio of less than 0.1 was investigated using a consortium consisted of three isolated salt-tolerant bacteria namely, Kocuria turfanesis, Halomonas alkaliphila and Pseudomonas balearica. Selected bacteria were isolated from petrochemical wastewater containing mineral salt mediums of 3% salinity. A lab-scale activated sludge bioreactor was used for startup in batch mode operation and after obtaining the MLSS concentration of about 3000 mg/L, the operation was changed to continuous flow mode to determine the biokinetic coefficients under different organic loading rates of 0...
January 16, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28104527/b7-h3-targeted-212-pb-radioimmunotherapy-of-ovarian-cancer-in-preclinical-models
#8
Benjamin B Kasten, Rebecca C Arend, Ashwini A Katre, Harrison Kim, Jinda Fan, Soldano Ferrone, Kurt R Zinn, Donald J Buchsbaum
INTRODUCTION: Novel therapies that effectively kill both differentiated cancer cells and cancer initiating cells (CICs), which are implicated in causing chemotherapy-resistance and disease recurrence, are needed to reduce the morbidity and mortality of ovarian cancer. These studies used monoclonal antibody (mAb) 376.96, which recognizes a B7-H3 epitope expressed on ovarian cancer cells and CICs, as a carrier molecule for targeted α-particle radioimmunotherapy (RIT) in preclinical models of human ovarian cancer...
January 10, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28104341/water-level-fluctuations-influence-sediment-porewater-chemistry-and-methylmercury-production-in-a-flood-control-reservoir
#9
Chris S Eckley, Todd P Luxton, Jennifer Goetz, John McKernan
Reservoirs typically have elevated fish mercury (Hg) levels compared to natural lakes and rivers. A unique feature of reservoirs is water-level management which can result in sediment exposure to the air. The objective of this study is to identify how reservoir water-level fluctuations impact Hg cycling, particularly the formation of the more toxic and bioaccumulative methylmercury (MeHg). Total-Hg (THg), MeHg, stable isotope methylation rates and several ancillary parameters were measured in reservoir sediments (including some in porewater and overlying water) that are seasonally and permanently inundated...
January 16, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28103285/radioiodinated-exendin-4-is-superior-to-the-radiometal-labelled-glucagon-like-peptide-1-receptor-probes-overcoming-their-high-kidney-uptake
#10
Tilman Läppchen, Roswitha Tönnesmann, Jos Eersels, Philipp T Meyer, Helmut R Maecke, Svetlana N Rylova
GLP-1 receptors are ideal targets for preoperative imaging of benign insulinoma and for quantifying the beta cell mass. The existing clinical tracers targeting GLP-1R are all agonists with low specific activity and very high kidney uptake. In order to solve those issues we evaluated GLP-1R agonist Ex-4 and antagonist Ex(9-39) radioiodinated at Tyr40 side by side with [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4 (68Ga-Ex-4) used in the clinic. The Kd, Bmax, internalization and binding kinetics of [Nle14,125I-Tyr40-NH2]Ex-4 and [Nle14,125I-Tyr40-NH2]Ex(9-39) were studied in vitro using Ins-1E cells...
2017: PloS One
https://www.readbyqxmd.com/read/28103033/design-synthesis-and-biological-evaluation-of-small-high-affinity-siglec-7-ligands-toward-novel-inhibitors-of-cancer-immune-evasion
#11
Horst Prescher, Martin Frank, Stephan Gütgemann, Elena Kuhfeldt, Astrid Schweizer, Lars Nitschke, Carsten Watzl, Reinhard Brossmer
Natural killer cells are able to directly lyse tumor cells, thereby participating in the immune surveillance against cancer. Unfortunately, many cancer cells use immune evasion strategies to avoid their eradication by the immune system. A prominent escape strategy of malignant cells is to camouflage themselves with Siglec-7 ligands, thereby recruiting the inhibitory receptor Siglec-7 expressed on the NK cell surface which subsequently inhibits NK-cell-mediated lysis. Here we describe the synthesis and evaluation of the first, high-affinity low molecular weight Siglec-7 ligands to interfere with cancer cell immune evasion...
January 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28102866/the-dna-target-determines-the-dimerization-partner-selected-by-bhlhz-like-hybrid-proteins-ahrjun-and-arntfos
#12
Ichiro Inamoto, Gang Chen, Jumi A Shin
The molecular basis of protein-partner selection and DNA binding of the basic helix-loop-helix (bHLH) and basic region-leucine zipper (bZIP) superfamilies of dimeric transcription factors is fundamental toward understanding gene regulation. Because these families share structural similarities, we swapped the bHLH and leucine zipper (LZ) modules between families to uncover how individual modules influence protein-partnering and protein:DNA complexation. We previously described ArntFos, a bHLHZ-like hybrid of the bHLH domain from the bHLH/PAS protein Arnt and LZ from the bZIP protein c-Fos, binding to the Arnt E-box site (TCACGTGA) as a homodimer...
January 19, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28102623/ischemic-stroke-in-kawasaki-disease
#13
Wasana Prangwatanagul, Alisa Limsuwan
Pediatric stroke is considered to be rare. Stroke resulting from cerebral vasculitis is also uncommon in young children. With the increasing prevalence of Kawasaki disease (KD) diagnosis, this acquired vasculitis has been reported with various clinical presentations including neurological symptoms. Herein we describe the case of a KD patient presenting with stroke. A 15-month-old boy was referred due to stroke that occurred on the fifth day of febrile illness. He was initially admitted to another hospital due to fever and diarrhea...
January 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28102235/clumping-factor-a-of-staphylococcus-aureus-interacts-with-annexina2-on-mammary-epithelial-cells
#14
Shoaib Ashraf, Jing Cheng, Xin Zhao
Staphylococcus aureus is one of major pathogens that can cause a series of diseases in different hosts. In the bovine, it mainly causes subclinical and contagious mastitis, but its mechanisms of infection are not fully understood. Considering the fact that virulence factors play key roles in interactions between the bacterium and host cells, this study aimed to identify if a binding partner of S. aureus clumping factor A (ClfA) exists on the bovine mammary epithelial cells. The ClfA protein was used as a bait to pull down lysates of cultured bovine mammary epithelial cells (MAC-T cells)...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101799/antitumor-efficacy-of-slpi-promoter-controlled-expression-of-artificial-microrna-targeting-egfr-in-a-squamous-cell-carcinoma-cell-line
#15
Jia Chen, Shoude Zhang, Yi Lin, Beibei Yang, Jiang Cao
The purpose of this study was to develop a recombinant adenovirus with secretory leukoprotease inhibitor (SLPI) promoter-controlled expression for gene therapy of squamous cell carcinoma (SCC). An artificial microRNA targeting epidermal growth factor receptor (EGFR) was designed, and used to construct a replication-defective recombinant adenovirus with SLPI promoter-controlled expression. The silencing efficiency of this vector (Ad-SLPI-EGFRamiR) was detected in Hep-2 cells. Western blotting showed that the expression of 170 kD EGFR was significantly reduced in Hep-2 cells 72 h after infection with Ad-SLPI-EGFRamiR...
January 18, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28100888/%C3%AE-hydroxybutyrate-levels-in-serum-and-cerebrospinal-fluid-under-ketone-body-metabolism-in-rats
#16
Xiaomeng Wang, Qi Liu, Jian Zhou, Xiuhua Wu, Qingan Zhu
A high-fat, low-carbohydrate diet (KD) or calorie restriction in the form of every-other-day fasting (EODF) results in ketone body metabolism with an increasing β-hydroxybutyrate (βOHB) level. Previous studies have supported that a KD and EODF have a neuroprotective effect. However, the βOHB levels in the cerebrospinal fluid (CSF) resulting from a KD and EODF remain unknown. The aim of this study was to detect βOHB levels in rats fed a KD, EODF diet, and every-other-day ketogenic diet (EODKD) and to compare the serum βOHB level with the CSF βOHB level...
January 19, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28098152/human-farnesyl-pyrophosphate-synthase-is-allosterically-inhibited-by-its-own-product
#17
Jaeok Park, Michal Zielinski, Alexandr Magder, Youla S Tsantrizos, Albert M Berghuis
Farnesyl pyrophosphate synthase (FPPS) is an enzyme of the mevalonate pathway and a well-established therapeutic target. Recent research has focused around a newly identified druggable pocket near the enzyme's active site. Pharmacological exploitation of this pocket is deemed promising; however, its natural biological function, if any, is yet unknown. Here we report that the product of FPPS, farnesyl pyrophosphate (FPP), can bind to this pocket and lock the enzyme in an inactive state. The Kd for this binding is 5-6 μM, within a catalytically relevant range...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28097868/development-of-phenothiazine-based-theranostic-compounds-that-act-both-as-inhibitors-of-%C3%AF-amyloid-aggregation-and-imaging-probes-for-amyloid-plaques-in-alzheimer-s-disease
#18
Pascal Dao, Feifei Ye, Yan Liu, Zhiyun Du, Kun Zhang, Chang-Zhi Dong, Bernard Meunier, Huixiong Chen
Early detection of Alzheimer's disease (AD) is imperative in enabling the understanding and clinical treatment of this disorder, as well as in preventing its progression. Imaging agents specifically targeting Aβ plaques in the brain and the retina may lead to the early diagnosis of AD. Among them, near infrared fluorescent imaging has emerged as an attractive tool to noninvasively identify and monitor diseases during the preclinical and early stages. In the present study, we report the design, synthesis and evaluation of a series of new near-infrared fluorescent probes...
January 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28097746/a-high-neutrophil-to-lymphocyte-ratio-is-associated-with-refractory-kawasaki-disease
#19
Hong-Je Cho, So Young Bak, Su Yeong Kim, Rita Yoo, Hae-Sung Baek, Seung Yang, Il-Tae Hwang, Ji-Eun Ban
BACKGROUND: The clinical significance of the neutrophil to lymphocyte ratio (NLR) has not yet been fully elucidated in patients with Kawasaki disease (KD). The purpose of this study is to investigate the relationship between NLR and the response to intravenous immunoglobulin (IVIG) therapy affecting coronary abnormalities in KD METHODS: A total of 196 patients of KD who were treated with IVIG therapy were analyzed. We evaluated the baseline NLR immediately before IVIG therapy and classified the study patients into 2 groups according to the value of the NLR...
January 18, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28097652/mdm4-is-a-rational-target-for-treating-breast-cancers-with-mutant-p53
#20
Panimaya Jeffreena Miranda, Daniel Buckley, Dinesh Raghu, Jia-Min B Pang, Elena A Takano, Reshma Vijayakumaran, Amina F A S Teunisse, Atara Posner, Tahlia Procter, Marco J Herold, Cristina Gamell, Jean-Christophe Marine, Stephen B Fox, Aart Jochemsen, Sue Haupt, Ygal Haupt
Mutation of the key tumour suppressor p53 defines a transition in the progression toward aggressive and metastatic breast cancer (BC) with the poorest outcome. Specifically, p53 mutation frequency exceeds 50% in Triple Negative BC (TNBC). Key regulators of mutant p53 that facilitate its oncogenic functions are potential therapeutic targets. We report here that the MDM4 protein is frequently abundant in the context of mutant p53 in basal-like BC samples. Importantly, we show that MDM4 plays a critical role in the proliferation of these BC cells...
January 18, 2017: Journal of Pathology
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