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https://www.readbyqxmd.com/read/29168892/functional-properties-of-dopamine-transporter-oligomers-after-copper-linking
#1
Juan Zhen, Maarten E A Reith
Although it is universally accepted that dopamine transporters (DATs) exist in monomers, dimers and tetramers (i.e. dimers of dimers), it is not known whether the oligomeric organization of DAT is a prerequisite for its ability to take up dopamine (DA), or whether each DAT protomer-the subunit of quaternary structure- functions independently in terms of DA translocation. In the present work copper phenanthroline (CuP) was used to selectively target surface DAT: increasing concentrations of CuP gradually cross-linked natural DAT dimers in LLC-PK1 cells stably expressing hDAT and thereby reduced DA uptake functionality until all surface DATs were inactivated...
November 23, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29167465/coupling-of-polo-kinase-activation-to-nuclear-localization-by-a-bifunctional-nls-is-required-during-mitotic-entry
#2
David Kachaner, Damien Garrido, Haytham Mehsen, Karine Normandin, Hugo Lavoie, Vincent Archambault
The Polo kinase is a master regulator of mitosis and cytokinesis conserved from yeasts to humans. Polo is composed of an N-term kinase domain (KD) and a C-term polo-box domain (PBD), which regulates its subcellular localizations. The PBD and KD can interact and inhibit each other, and this reciprocal inhibition is relieved when Polo is phosphorylated at its activation loop. How Polo activation and localization are coupled during mitotic entry is unknown. Here we report that PBD binding to the KD masks a nuclear localization signal (NLS)...
November 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29165489/perylenediimide-based-glycoclusters-as-high-affinity-ligands-of-bacterial-lectins-synthesis-binding-studies-and-anti-adhesive-properties
#3
Marion Donnier-Maréchal, Nicolas Galanos, Teddy Grandjean, Yoann Pascal, Ding-Kun Ji, Lei Dong, Emilie Gillon, Xiao-Peng He, Anne Imberty, Eric Kipnis, Rodrigue Dessein, Sébastien Vidal
The synthesis of eight perylenediimide-based glycoclusters was readily performed from hexa- and tetra-propargylated cores through azide-alkyne "click" conjugation. Variations in the carbohydrate epitope (Glc, Gal, Man, Fuc) and the linker arm provided molecular diversity. Interactions with LecA and LecB, two proteins involved in the adhesion of Pseudomonas aeruginosa to host tissues, were evaluated by microcalorimetry (ITC). In both cases high affinities were obtained with Kd values in the nanomolar range. Further evaluation of their anti-adhesive properties using cultured epithelial cells demonstrated their potent anti-adhesive activities against Pseudomonas aeruginosa with only 30-40% residual adhesion observed...
November 22, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29163883/effects-of-electron-transfer-on-the-stability-of-hydrogen-bonds
#4
Tyler M Porter, Gavin P Heim, Clifford P Kubiak
The measurement of the dimerization constants of hydrogen-bonded ruthenium complexes (12, 22, 32) linked by a self-complementary pair of 4-pyridylcarboxylic acid ligands in different redox states is reported. Using a combination of FTIR and UV/vis/NIR spectroscopies, the dimerization constants (KD) of the isovalent, neutral states, 12, 22, 32, were found to range from 75 to 130 M(-1) (ΔG(0) = -2.56 to -2.88 kcal mol(-1)), while the dimerization constants (K2-) of the isovalent, doubly-reduced states, (12)(2-), (22)(2-), (32)(2-), were found to range from 2000 to 2500 M(-1) (ΔG(0) = -4...
November 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29162464/biochemical-and-biophysical-characterization-of-curcumin-binding-to-human-mitotic-kinesin-eg5-iinsights-into-the-inhibitory-mechanism-of-curcumin-on-eg5
#5
Darpan Raghav, Jomon Sebastian, Krishnan Rathinasamy
In this study we have characterized the biochemical and biophysical interactions of curcumin with the mitotic kinesin Eg5 which plays a pivotal role in the separation of centrosomes during cell division. Curcumin bound to the purified Eg5 (Eg5-437H) with a Kd value of 7.8mM. The temperature dependent binding analysis and evaluation of thermodynamic parameters indicated the involvement of static quenching mechanism in the binding process. Evidences from competition experiment with monastrol indicated that curcumin bound to Eg5 at a novel druggable site...
November 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29161696/the-protein-expression-level-of-a-heterogeneous-gene-inserted-in-lipi-1-of-the-listeria-ivanovii-genome-relies-on-its-insertion-orientation
#6
Sijing Liu, Mingjuan Jiang, Lin Su, Tian Tang, Xiang Zhang, Yongyu Li, Qikang Pu, Chenyan Ren, Chuan Wang
Due to its capability to multiply in either phagocytic or nonphagocytic cells, and to subsequently elicit a robust cellular immune response, Listeria ivanovii (LI) is thought to be feasible for developing bacteria-based live attenuated vaccines. We previously generated several recombinant LI strains expressing Mycobacterium tuberculosis antigens. Since the expression level of heterogeneous protein was sometimes very low, we attempted to elucidate the principle of heterogeneous protein expression in such recombinant LI strains...
November 22, 2017: Journal of Molecular Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29159581/inhibition-of-salivary-secretion-by-tolterodine-transdermal-patch
#7
Ji-Yeong Byeon, Young-Hoon Kim, Se-Hyung Kim, Choong-Min Lee, Chang-Ik Choi, Jung-Woo Bae, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee
Tolterodine, a nonselective muscarinic antagonist available only as immediate release (IR) or extended release (ER) oral formulations, is used for the treatment of overactive bladder (OAB). This study aimed to compare the efficacy and extent of dry mouth adverse effects of tolterodine transdermal patch to the oral formulation. The two formulations have been examined through the muscarinic receptor binding tests conducted in bladder and salivary gland tissues and the salivary secretion tests conducted in rats...
November 20, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29156833/targeting-aggressive-prostate-cancer-associated-cd44v6-using-phage-display-selected-peptides
#8
Ying Peng, Austin R Prater, Susan L Deutscher
There is a crucial need to identify new biomarkers associated with aggressive prostate cancer (PCa) including those associated with cancer stem cells (CSCs). CD44v6, generated by alternative splicing of CD44, has been proposed as a CSC biomarker due to its correlation with aggressive PCa disease. We hypothesized that phage display selected peptides that target CD44v6 may serve as theranostic agents for aggressive PCa. Here, a 15 amino acid peptide ("PFT") was identified by affinity selection against a peptide derived from the v6 region of CD44v6...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156763/elas1-induces-apoptotic-death-in-adenocarcinoma-du145-and-squamous-cell-carcinoma-sas-cancer-cells-but-not-in-normal-kd-cells
#9
Toshihiro Uchihashi, Kaori Ota, Yusuke Yabuno, Shouichi Ohno, Kohshiro Fukushima, Yoko Naito, Mikihiko Kogo, Norikazu Yabuta, Hiroshi Nojima
We previously reported that an ELAS1 peptide containing 29 amino acids induces apoptotic death in U2OS human osteosarcoma cells following DNA double-strand break insults. Here, we show that ELAS1 also caused apoptosis in prostate adenocarcinoma DU145 cells and tongue squamous-cell carcinoma SAS cells. ELAS1 appears to be safe because it induced apoptosis only in cancer cells, not in normal KD cells. Because the effect of ELAS1 is dependent on increased stability of p53 and enhanced phosphorylation of p53-S46, we exogenously expressed wild-type p53 protein to fully promote ELAS1-mediated induction of apoptosis in SAS cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156712/radiolabelled-polymeric-iga-from-biodistribution-to-a-new-molecular-imaging-tool-in-colorectal-cancer-lung-metastases
#10
Helene Carpenet, Armelle Cuvillier, Aurélie Perraud, Ophélie Martin, Gaël Champier, Marie-Odile Jauberteau, Jacques Monteil, Isabelle Quelven
By radiolabelling monomeric (m) and polymeric (p) IgA with technetium 99m ((99m)Tc), this study assessed IgA biodistribution and tumour-targeting potency. IgA directed against carcinoembryonic antigen (CEA), a colorectal cancer marker, was selected to involve IgA mucosal tropism. Ig was radiolabelled with (99m)Tc-tricarbonyl after derivatisation by 2-iminothiolane. (99m)Tc-IgA was evaluated by in vitro analysis. The biodistributions of radiolabelled anti-CEA mIgA, pIgA and IgG were compared in normal mice. Anti-CEA pIgA tumour uptake was studied in mice bearing the WiDr caecal orthotopic graft...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156644/akt1-stimulates-homologous-recombination-repair-of-dna-double-strand-breaks-in-a-rad51-dependent-manner
#11
Katharina Mueck, Simone Rebholz, Mozhgan Dehghan Harati, H Peter Rodemann, Mahmoud Toulany
Akt1 is known to promote non-homologous end-joining (NHEJ)-mediated DNA double-strand break (DSB) repair by stimulation of DNA-PKcs. In the present study, we investigated the effect of Akt1 on homologous recombination (HR)-dependent repair of radiation-induced DSBs in non-small cell lung cancer (NSCLC) cells A549 and H460. Akt1-knockdown (Akt1-KD) significantly reduced Rad51 protein level, Rad51 foci formation and its colocalization with γH2AX foci after irradiation. Moreover, Akt1-KD decreased clonogenicity after treatment with Mitomycin C and HR repair, as tested by an HR-reporter assay...
November 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29153883/conformational-dynamics-and-free-energy-of-bhrf1-binding-to-bim-bh3
#12
Mauro Lapelosa
The interaction between the Bim BH3 peptide and the viral protein BHRF1 is pivotal to understanding the fundamental molecular details of the mechanism used by the Epstein-Barr virus to trick the mammalian immune system. Here, we study the mechanism of binding/unbinding and compute the free energy for the association of the Bim peptide to the BHRF1 protein. Key elements of the binding mechanism are the conformational rearrangement together with a main free energy barrier of 11.5kcal/mol. The simulations show complete unbinding and rebinding of the Bim peptide to BHRF1...
November 10, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/29152929/the-role-of-echocardiography-in-kawasaki-disease
#13
Brian W McCrindle, Barbara Cifra
Kawasaki disease (KD) is an acute, self-limited vasculitis affecting young children. It can result in coronary artery abnormalities in a significant proportion of patients, especially if the diagnosis is missed or treatment gets delayed. Echocardiography is the imaging modality of choice for detection of coronary artery abnormalities and assessment of myocardial function. It is also useful for characterization and risk stratification of patients with KD. Echocardiography should be performed at the time of diagnosis and then again at 1-2 weeks and 4-6 weeks after treatment, for uncomplicated cases who do not have significant coronary artery involvement...
November 19, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/29152908/the-genetics-of-kawasaki-disease
#14
Yoshihiro Onouchi
Kawasaki disease (KD) is a complex disorder which affects genetically susceptible infants and children. Several susceptibility genes (e.g., ITPKC, CASP3, CD40 and ORAI) and chromosomal regions have been identified through genome-wide association and genome-wide linkage studies to have association with KD. Knowledge of susceptibility genes involved in the pathogenesis of KD may provide new insights into diagnosis and treatment of this condition. However, there is much that we still do not know about the genetic basis of KD...
November 19, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/29152066/identification-and-validation-of-fgfr2-peptide-for-detection-of-early-barrett-s-neoplasia
#15
Juan Zhou, Lei He, Zhijun Pang, Henry D Appelman, Rork Kuick, David G Beer, Meng Li, Thomas D Wang
The incidence of esophageal adenocarcinoma (EAC) is rising rapidly, and early detection within the precursor state of Barrett's esophagus (BE) is challenged by flat premalignant lesions that are difficult detect with conventional endoscopic surveillance. Overexpression of cell surface fibroblast growth factor receptor 2 (FGFR2) is an early event in progression of BE to EAC, and is a promising imaging target. We used phage display to identify the peptide SRRPASFRTARE that binds specifically to the extracellular domain of FGFR2...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29148818/dissociation-constants-of-cytochrome-p450-2c9-cytochrome-p450-reductase-complexes-in-a-lipid-bilayer-membrane-depend-on-nadph-a-single-protein-tracking-study
#16
Carlo Barnaba, Evan Taylor, James A Brozik
Cytochrome P450-Reductase (CPR) is a versatile NADPH-dependent electron donor located in the cytoplasmic side of the endoplasmic reticulum. It is an electron transferase that is able to deliver electrons to a variety of membrane-bound oxidative partners, including the drug-metabolizing enzymes of the cytochrome P450s (P450). CPR is also stoichiometrically limited compared to its oxidative counterparts and hypotheses have arisen about possible models that can overcome the stochiometric imbalance, including quaternary organization of P450 and diffusion-limited models...
November 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29146291/development-of-ms-binding-assays-targeting-the-binding-site-of-mb327-at-the-nicotinic-acetylcholine-receptor
#17
S Sichler, G Höfner, S Rappenglück, T Wein, K V Niessen, T Seeger, F Worek, H Thiermann, F F Paintner, K T Wanner
The bispyridinium compound MB327 has been shown previously to have a positive pharmacological effect against poisoning with organophosphorous compounds (OPCs). The mechanism by which it exerts its therapeutic effect seems to be directly mediated by the nicotinic acetylcholine receptor (nAChR). In the present study, the development of mass spectrometry based binding assays (MS Binding Assays) for characterization of the binding site of MB327 at the nAChR from Torpedo californica is described. MS Binding Assays follow the principle of radioligand binding assays, but do not, in contrast to the latter, require a radiolabeled reporter ligand, as the readout is in this case based on mass spectrometric detection...
November 13, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29146201/arsenic-speciation-in-environmental-multimedia-samples-from-the-youngsan-river-estuary-korea-a-comparison-between-freshwater-and-saltwater
#18
Seongjin Hong, Sung-Deuk Choi, Jong Seong Khim
Differences in the distribution, partitioning, and bioaccumulation characteristics of arsenicals between freshwater and saltwater systems remain poorly understood. To determine the characteristics of distribution and behavior of arsenicals, multimedia environmental samples including water, suspended particles, zooplankton, sediments, and porewater were collected from inner (five sites, freshwater) and outer (five sites, saltwater) regions of the estuary dike of the Youngsan River Estuary in South Korea (Nov...
November 13, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29146131/dysregulation-of-autophagy-in-melanocytes-contributes-to-hypopigmented-macules-in-tuberous-sclerosis-complex
#19
Fei Yang, Lingli Yang, Mari Wataya-Kaneda, Junya Hasegawa, Tamotsu Yoshimori, Atsushi Tanemura, Daisuke Tsuruta, Ichiro Katayama
BACKGROUND: Tuberous sclerosis complex (TSC) gene mutations lead to constitutive activation of the mammalian target of rapamycin (mTOR) pathway, resulting in a broad range of symptoms. Hypopigmented macules are the earliest sign. Although we have already confirmed that topical rapamycin treatment (an mTOR inhibitor) protects patients with TSC against macular hypopigmentation, the pathogenesis of such lesions remains poorly understood. OBJECTIVE: Recently emerging evidence supports a role for autophagy in skin pigmentation...
November 11, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29143203/relapse-of-nephrotic-syndrome-triggered-by-kawasaki-disease
#20
Ryo Maeda, Yukihiko Kawasaki, Shigeo Suzuki, Shinichiro Ohara, Suyama Kazuhide, Mitsuaki Hosoya
Minor infections, allergies, insect bites, and bee stings are commonly reported causes of nephrotic syndrome (NS). Herein, we report, to the best of our knowledge, the first case of NS relapse due to Kawasaki disease (KD). An 8-year-old boy presented with high fever of 4-day duration. He had developed steroid-dependent NS at the age of 4 years and remained in remission after steroid and mizonbin therapy. Renal biopsy, performed at the age of four, showed minimal change (MC) disease. Upon examination, the patient fulfilled 5 of 6 criteria for KD under the Japanese diagnostic guidelines, with positive proteinuria...
November 15, 2017: CEN Case Reports
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