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https://www.readbyqxmd.com/read/28544907/micrornas-that-affect-the-fanconi-anemia-brca-pathway-are-downregulated-in-imatinib-resistant-chronic-myeloid-leukemia-patients-without-detectable-bcr-abl-kinase-domain-mutations
#1
E Yap, Z A Norziha, A Simbun, N R Tumian, S K Cheong, C F Leong, C L Wong
Chronic myeloid leukemia (CML) patients who do not achieve landmark responses following treatment with imatinib mesylate (IM) are considered IM-resistant. Although IM-resistance can be due to BCR-ABL kinase domain (KD) mutations, many IM-resistant patients do not have detectable BCR-ABL KD mutations. MicroRNAs (miRNAs) are short non-coding RNAs that control gene expression. To investigate the role of miRNAs in IM-resistance, we recruited 8 chronic phase CML patients with IM-resistance who tested negative for BCR-ABL KD mutations and 2 healthy normal controls...
May 18, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28544088/antivitamin-b12-inhibition-of-the-human-b12-processing-enzyme-cblc-crystal-structure-of-an-inactive-ternary-complex-with-glutathione-as-the-cosubstrate
#2
Markus Ruetz, Aranganathan Shanmuganathan, Carmen Gherasim, Agnes Karasik, Robert Salchner, Christoph Kieninger, Klaus Wurst, Ruma Banerjee, Markos Koutmos, Bernhard Kräutler
B12 antivitamins are important and robust tools for investigating the biological roles of vitamin B12 . Here, the potential antivitamin B12 2,4-difluorophenylethynylcobalamin (F2PhEtyCbl) was prepared, and its 3D structure was studied in solution and in the crystal. Chemically inert F2PhEtyCbl resisted thermolysis of its Co-C bond at 100 °C, was stable in bright daylight, and also remained intact upon prolonged storage in aqueous solution at room temperature. It binds to the human B12 -processing enzyme CblC with high affinity (KD =130 nm) in the presence of the cosubstrate glutathione (GSH)...
May 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28542183/a-comparison-of-the-predictive-validity-of-the-combination-of-the-neutrophil-to-lymphocyte-ratio-and-platelet-to-lymphocyte-ratio-and-other-risk-scoring-systems-for-intravenous-immunoglobulin-ivig-resistance-in-kawasaki-disease
#3
Seiichiro Takeshita, Takashi Kanai, Yoichi Kawamura, Yusuke Yoshida, Shigeaki Nonoyama
BACKGROUND: We recently reported that the combination of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) is a novel and useful predictor of intravenous immunoglobulin (IVIG)-resistance in Kawasaki disease (KD). In the present study, to evaluate the effectiveness of the new risk score, we compared its predictive validity to that of previously reported risk scores. MATERIALS AND METHODS: The laboratory records of 437 patients with KD before IVIG therapy were retrospectively analyzed, and the IVIG-responsive (n = 344) and IVIG-resistant (n = 93) patients were compared...
2017: PloS One
https://www.readbyqxmd.com/read/28541659/multifunctional-screening-platform-for-the-highly-efficient-discovery-of-aptamers-with-high-affinity-and-specificity
#4
Shao-Li Hong, Ya-Tao Wan, Man Tang, Dai-Wen Pang, Zhi-Ling Zhang
Aptamers have attracted much attention as next generation of affinity reagents. Unfortunately, the selection efficiency remains a critical bottleneck for the widespread application of aptamers. Herein, to accelerate aptamers discovery, a multifunctional microfluidic selection platform was developed, on which the selection efficiency was greatly improved and high affinity and specificity aptamers were generated within two round selections. The multifunctional screening platform, precisely manipulating magnetic beads on micrometer scale, improved selection performance based on microfluidic continuous flow and enhanced the selection process control via in-situ monitoring and real-time evaluation...
May 25, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28539286/-expression-purification-and-activity-analysis-of-ggdef-and-eal-domain-containing-proteins-from-lactobacillus-acidophilus
#5
Jia-Hui He, Jie-Li Sun, Wen-Juan Yan, Fang Wang
OBJECTIVE: To identify the functions of the proteins containing the GGDEF or EAL domain in Lactobacillus acidophilus for investigation of the regulatory mechanism of c-di-GMP in this strain. METHODS: The DNA fragments of NH13_07045-GGDEF, NH13_07050 and NH13_07055 from Lactobacillus acidophilus ATCC4356 were amplified by PCR and cloned into the expression vector pMAL-His-c2. After sequencing, the recombinant plasmids were transformed into competent Escherichia coli cells, which were induced by IPTG to express the recombinant proteins fused with maltose binding protein (MBP)...
May 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28538210/correlation-of-hamp-gene-polymorphisms-and-expression-with-the-susceptibility-and-length-of-hospital-stays-in-taiwanese-children-with-kawasaki-disease
#6
Ying-Hsien Huang, Kuender D Yang, Yu-Wen Hsu, Hsing-Fang Lu, Henry Sung-Ching Wong, Hong-Ren Yu, Hsing-Chun Kuo, Fu-Chen Huang, Mao-Hung Lo, Kai-Sheng Hsieh, Su-Fen Chen, Wei-Chiao Chang, Ho-Chang Kuo
Kawasaki disease (KD) is a form of systemic vasculitis. Regarding its pathogenesis, HAMP gene encoding hepcidin, which is significant for iron metabolism, has a vital function. In this study, we recruited a total of 381 KD patients for genotyping. Data from 997 subjects (500 subjects from cohort 1; 497 subjects from cohort 2) were used for analysis. Using TaqMan allelic discrimination, we determined five tag SNPs (rs916145, rs10421768, rs3817623, rs7251432, and rs2293689). Treatment outcome data related to such clinical phenotypes as coronary artery lesions (CAL), coronary artery aneurysms (CAA), and intravenous immunoglobulin (IVIG) effects were also collected...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28538150/lanthanides-report-calcium-sensor-in-the-vestibule-of-ryanodine-receptor
#7
Sándor Sárközi, István Komáromi, István Jóna, János Almássy
Ca(2+) regulates ryanodine receptor's (RyR) activity through an activating and an inhibiting Ca(2+)-binding site located on the cytoplasmic side of the RyR channel. Their altered sensitivity plays an important role in the pathology of malignant hyperthermia and heart failure. We used lanthanide ions (Ln(3+)) as probes to investigate the Ca(2+) sensors of RyR, because they specifically bind to Ca(2+)-binding proteins and they are impermeable to the channel. Eu(3+)'s and Sm(3+)'s action was tested on single RyR1 channels reconstituted into planar lipid bilayers...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28537848/influence-of-endurance-training-on-skeletal-muscle-mitophagy-regulatory-proteins-in-type-2-diabetic-men
#8
Christian Brinkmann, Axel Przyklenk, Alexander Metten, Thorsten Schiffer, Wilhelm Bloch, Klara Brixius, Sebastian Gehlert
BACKGROUND: Mitophagy is a form of autophagy for the elimination of mitochondria. Mitochondrial content and function are reduced in the skeletal muscle of patients with type 2 diabetes mellitus (T2DM). Physical training has been shown to restore mitochondrial capacity in T2DM patients, but the role of mitophagy has not been examined in this context. This study analyzes the impact of a 3-month endurance training on important skeletal muscle mitophagy regulatory proteins and oxidative phosphorylation (OXPHOS) complexes in T2DM patients...
May 24, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28534229/production-of-a-gonadotropin-releasing-hormone-2-receptor-knockdown-gnrhr2-kd-swine-line
#9
A T Desaulniers, R A Cederberg, G A Mills, C A Lents, B R White
Swine are the only livestock species that produce both the second mammalian isoform of gonadotropin-releasing hormone (GNRH2) and its receptor (GNRHR2). Previously, we reported that GNRH2 and GNRHR2 mediate LH-independent testosterone secretion from porcine testes. To further explore this ligand-receptor complex, a pig model with reduced GNRHR2 expression was developed. Small hairpin RNA sequences targeting porcine GNRHR2 were subcloned into a lentiviral-based vector, lentiviral particles were generated and microinjected into the perivitelline space of zygotes, and embryos were transferred into a recipient...
May 22, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28533980/mitochondrial-complex-i-deficiency-leads-to-the-retardation-of-early-embryonic-development-in-ndufs4-knockout-mice
#10
Mei Wang, Ya-Ping Huang, Han Wu, Ke Song, Cong Wan, A-Ni Chi, Ya-Mei Xiao, Xiao-Yang Zhao
BACKGROUND: The NDUFS4 gene encodes an 18-kD subunit of mitochondria complex I, and mutations in this gene lead to the development of a severe neurodegenerative disease called Leigh syndrome (LS) in humans. To investigate the disease phenotypes and molecular mechanisms of Leigh syndrome, the Ndufs4 knockout (KO) mouse has been widely used as a novel animal model. Because the homozygotes cannot survive beyond child-bearing age, whether Ndufs4 and mitochondrial complex I influence early embryonic development remains unknown...
2017: PeerJ
https://www.readbyqxmd.com/read/28530293/model-peptide-studies-of-ag-binding-sites-from-the-silver-resistance-protein-sile
#11
V Chabert, M Hologne, O Sénèque, A Crochet, O Walker, K M Fromm
Using model peptides, each of the nine MX2H or HXnM (n = 1, 2) motifs of the silver resistance protein SilE has been shown to coordinate to one Ag(+) ion by its histidine and methionine residues with Kd in the μM range. This suggests an Ag(+) buffering role for SilE in the case of high Ag(+) overload.
May 22, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28530289/ca-nir-a-ratiometric-near-infrared-calcium-probe-based-on-a-dihydroxanthene-hemicyanine-fluorophore
#12
Mayeul Collot, Flavien Ponsot, Andrey S Klymchenko
Fluorescent calcium probes are essential tools for studying the fluctuation of calcium ions in cells. Herein, we developed Ca-NIR, the first ratiometric calcium probe emitting in the near infrared region. This probe arose from the fusion of a BAPTA chelator and a dihydroxanthene-hemicyanine fluorophore. It is efficiently excited with common 630-640 nm lasers and displays two distinct emission bands depending on the calcium concentration (Kd = ∼8 μM). The physicochemical and spectroscopic properties of Ca-NIR allowed for ratiometric imaging of calcium distribution in live cells...
May 22, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28529940/coronary-artery-aneurysms-a-review-of-the-epidemiology-pathophysiology-diagnosis-and-treatment
#13
REVIEW
Sara Abou Sherif, Ozge Ozden Tok, Özgür Taşköylü, Omer Goktekin, Ismail Dogu Kilic
Coronary artery aneurysms (CAAs) are uncommon and describe a localized dilatation of a coronary artery segment more than 1.5-fold compared with adjacent normal segments. The incidence of CAAs varies from 0.3 to 5.3%. Ever since the dawn of the interventional era, CAAs have been increasingly diagnosed on coronary angiography. Causative factors include atherosclerosis, Takayasu arteritis, congenital disorders, Kawasaki disease (KD), and percutaneous coronary intervention. The natural history of CAAs remains unclear; however, several recent studies have postulated the underlying molecular mechanisms of CAAs, and genome-wide association studies have revealed several genetic predispositions to CAA...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28529409/an-experimental-check-of-backscattering-interferometry
#14
Michael M Baksh, M G Finn
Backscattering interferometry (BSI) was used to determine the association constants for four well-known biomolecular interactions: protein A + IgG, trypsin + antitrypsin, trypsin + p-aminobenzamidine, and antithrombin + heparin. Each gave well-defined binding curves and Kd values in close agreement with published findings obtained using other techniques. These results stand in direct contrast to the claims in a 2015 publication in this journal (Discussion of "Back Scattering Interferometry revisited-a theoretical and experimental investigation" Jørgensen, T...
May 2017: Sensors and Actuators. B, Chemical
https://www.readbyqxmd.com/read/28527909/binding-assay-for-characterization-of-protein-kinase-inhibitors-possessing-sub-picomolar-to-sub-millimolar-affinity
#15
Hedi Sinijarv, Shanshan Wu, Taavi Ivan, Kaido Viht, Asko Uri
High demand for inhibitors regulating the activity of protein kinases has stimulated the quest for high throughput and reliable compound screening assays. Here we introduce a method applying a non-metal photoluminescent probe ARC-Lum(Fluo) for determination of dissociation constants of competitive inhibitors of protein kinases. Employing a single probe instead of a combination of antibody and fluorescent tracer makes the assay simpler, cheaper, and more accurate than several other inhibitor-screening technologies...
May 17, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28527061/ketogenic-diet-in-migraine-rationale-findings-and-perspectives
#16
Piero Barbanti, Luisa Fofi, Cinzia Aurilia, Gabriella Egeo, Massimiliano Caprio
Ketogenic diet (KD) is an established treatment for refractory pediatric epilepsy and a promising therapy for diverse neurological diseases. Clinical data on KD in migraine-obtained from 150 patients investigated in case reports and prospective studies-suggest that KD may be a rapid onset effective prophylaxis for episodic and chronic migraine. KD would contribute to restore brain excitability and metabolism and to counteract neuroinflammation in migraine, although its precise mechanism is still unclear. Randomized controlled studies are needed to confirm the usefulness of KD in migraine and to investigate its optimal duration, repeatability, feasibility in normal weight subjects, efficacy in pediatric population and association to conventional migraine prophylaxis...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28526683/autoreactivity-to-sulfatide-by-human-invariant-nkt-cells
#17
Annelein M Stax, Jessica Tuengel, Enrico Girardi, Naoki Kitano, Lenka L Allan, Victor Liu, Dongjun Zheng, William J Panenka, Joren Guillaume, Chi-Huey Wong, Serge van Calenbergh, Dirk M Zajonc, Peter van den Elzen
Invariant NKT (iNKT) cells are innate-like lymphocytes that recognize lipid Ags presented by CD1d. The prototypical Ag, α-galactosylceramide, strongly activates human and mouse iNKT cells, leading to the assumption that iNKT cell physiology in human and mouse is similar. In this article, we report the surprising finding that human, but not mouse, iNKT cells directly recognize myelin-derived sulfatide presented by CD1d. We propose that sulfatide is recognized only by human iNKT cells because of the unique positioning of the 3-O-sulfated β-galactose headgroup...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28526535/tnf-%C3%AE-is-superior-to-conventional-inflammatory-mediators-in-forecasting-ivig-nonresponse-and-coronary-arteritis-in-chinese-children-with-kawasaki-disease
#18
Peng Hu, Guang Mei Jiang, Yue Wu, Bao Yu Huang, Si Yan Liu, Dong Dong Zhang, Yao Xu, Yang Fang Wu, Xun Xia, Wei Wei, Bo Hu
BACKGROUND: Tumor necrosis factor (TNF) -α is of inflammatory cytokines produced chiefly by activated monocyte/macrophages, and has been implicated in the pathogenesis of Kawasaki disease (KD). We elucidated the relationship of plasma TNF-α with conventional inflammatory mediators, clinical classification, intravenous immunoglobulin (IVIG) response and coronary arteritis in the course of KD. METHODS: Seventy Chinese children with KD were enrolled and divided into 6 subgroups, including complete KD, incomplete KD, IVIG-responsive KD, IVIG-nonresponsive KD, coronary artery (CA) -noninvolvement KD and CA-involvement KD...
May 16, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28525735/structure-based-rational-design-of-self-inhibitory-peptides-to-disrupt-the-intermolecular-interaction-between-the-troponin-subunits-c-and-i-in-neuropathic-pain
#19
Junmin Yu, Shilei Wang, Junjie Yu, Chuansheng Liu, Fenghe Xu, Shijie Wang, Yusheng Yi, Yanwei Yin
The troponin (Tn) is a ternary complex consisting of three subunits TnC, TnI and TnT; molecular disruption of the Tn complex has been recognized as an attractive strategy against neuropathic pain. Here, a self-inhibitory peptide is stripped from the switch region of TnI interaction interface with TnC, which is considered as a lead molecular entity and then used to generate potential peptide disruptors of TnC-TnI interaction based on a rational molecular design protocol. The region is a helical peptide segment capped by N- and C-terminal disorders...
May 3, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28524918/urotensin-ii-peptidomimetic-incorporating-a-non-reducible-1-5-triazole-disulfide-bond-reveals-a-pseudo-irreversible-covalent-binding-mechanism-to-the-urotensin-g-protein-coupled-receptor
#20
Salvatore Pacifico, Aidan Kerckhoffs, Andrew J Fallow, Rachel E Foreman, Remo Guerrini, John McDonald, David G Lambert, Andrew G Jamieson
The urotensin-II receptor (UTR) is a class A GPCR that predominantly binds to the pleiotropic cyclic peptide urotensin-II (U-II). U-II is constrained by a disulfide bridge that induces a β-turn structure and binds pseudo-irreversibly to UTR and is believed to result in a structural rearrangement of the receptor. However, it is not well understood how U-II binds pseudo-irreversibly and the nature of the reorganization of the receptor that results in G-protein activation. Here we describe a series of U-II peptidomimetics incorporating a non-reducible disulfide bond structural surrogate to investigate the feasibility that native U-II binds to the G protein-coupled receptor through disulfide bond shuffling as a mechanism of covalent interaction...
May 19, 2017: Organic & Biomolecular Chemistry
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