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https://www.readbyqxmd.com/read/28109958/optical-barcoding-for-single-clone-tracking-to-study-tumor-heterogeneity
#1
Malte Mohme, Cecile L Maire, Kristoffer Riecken, Svenja Zapf, Tim Aranyossy, Manfred Westphal, Katrin Lamszus, Boris Fehse
Intratumoral heterogeneity has been identified as one of the strongest drivers of treatment resistance and tumor recurrence. Therefore, investigating the complex clonal architecture of tumors over time has become a major challenge in cancer research. We developed a new fluorescent "optical barcoding" technique that allows fast tracking, identification, and quantification of live cell clones in vitro and in vivo using flow cytometry (FC). We optically barcoded two cell lines derived from malignant glioma, an exemplary heterogeneous brain tumor...
January 18, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28108813/relationship-between-il-27-and-coronary-arterial-lesions-in-children-with-kawasaki-disease
#2
Feifei Si, Yao Wu, Fang Gao, Siqi Feng, Ruixi Liu, Qijian Yi
Kawasaki disease (KD) arises due to the disorder of the inflammation response and faulty immune regulation. Interleukin-27 (IL-27) is a novel cytokine with both pro-inflammatory and anti-inflammatory effects. This study investigated the relationship between serum levels of IL-27, Interleukin-17A (IL-17A), Interleukin-10 (IL-10), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and coronary artery lesions (CALs) in patients with KD. We obtained blood samples from 81 children with KD before intravenous immunoglobulin (IVIG) therapy...
January 20, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28108572/use-of-ldl-receptor-targeting-peptide-vectors-for-in-vitro-and-in-vivo-cargo-transport-across-the-blood-brain-barrier
#3
Yves Molino, Marion David, Karine Varini, Françoise Jabès, Nicolas Gaudin, Aude Fortoul, Karima Bakloul, Maxime Masse, Anne Bernard, Lucile Drobecq, Pascaline Lécorché, Jamal Temsamani, Guillaume Jacquot, Michel Khrestchatisky
The blood-brain barrier (BBB) prevents the entry of many drugs into the brain and, thus, is a major obstacle in the treatment of CNS diseases. There is some evidence that the LDL receptor (LDLR) is expressed at the BBB and may participate in the transport of endogenous ligands from blood to brain, a process referred to as receptor-mediated transcytosis. We previously described a family of peptide vectors that were developed to target the LDLR. In the present study, in vitro BBB models that were derived from either wild-type and LDLR knockout animals (ldlr(-/-)) were used to validate the specific LDLR-dependent transcytosis of LDL via a nondegradative route...
January 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28108175/characterization-of-the-synergistic-interaction-between-beauveria-bassiana-strain-gha-and-bacillus-thuringiensis-morrisoni-strain-tenebrionis-applied-against-colorado-potato-beetle-larvae
#4
S P Wraight, M E Ramos
Studies were undertaken to further characterize the previously identified synergistic activity of Bacillus thuringiensis- and Beauveria bassiana-based biopesticides against Colorado potato beetle (CPB). A flowable concentrate of B. thuringiensis morrisoni strain tenebrionis (Bt) (Novodor® FC) and a wettable powder of B. bassiana strain GHA (Bb) (Mycotrol® 22WP) were applied against CPB larval populations infesting potato in field plots. Novodor FC and an oil-dispersion formulation of Bb (Mycotrol ES) were applied against second-instar CPB larvae on potted potato plants in greenhouse tests under low relative humidity (RH), variable-temperature conditions...
January 17, 2017: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/28107624/tocilizumab-alendronate-conjugate-for-treatment-of-rheumatoid-arthritis
#5
Hwiwon Lee, Suk Ho Bhang, Jeong Ho Lee, Hyemin Kim, Sei Kwang Hahn
An autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ) - Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio) propionyl hydrazide (PDPH) - poly(ethylene glycol) - N-hydroxysuccinimide (PDPH-PEG-NHS)...
January 20, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28107429/deficient-cholesterol-esterification-in-plasma-of-apoc2-knockout-zebrafish-and-familial-chylomicronemia-patients
#6
Chao Liu, Daniel Gaudet, Yury I Miller
Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Apolipoprotein C-II (APOC2) is an obligatory cofactor for lipoprotein lipase (LPL), the major enzyme catalyzing plasma triglyceride hydrolysis. We have created an apoc2 knockout zebrafish model, which mimics the familial chylomicronemia syndrome (FCS) in human patients with a defect in the APOC2 or LPL gene. In this study, we measured plasma levels of free cholesterol (FC) and cholesterol esters (CE) and found that apoc2 mutant zebrafish have a significantly higher FC to CE ratio (FC/CE), when compared to the wild type...
2017: PloS One
https://www.readbyqxmd.com/read/28106884/excess-reactive-oxygen-species-production-mediates-monoclonal-antibody-induced-human-embryonic-stem-cell-death-via-oncosis
#7
Ji Yun Zheng, Heng Liang Tan, Paul Thomas Matsudaira, Andre Choo
Antibody-mediated cell killing has significantly facilitated the elimination of undesired cells in therapeutic applications. Besides the well-known Fc-dependent mechanisms, pathways of antibody-induced apoptosis were also extensively studied. However, with fewer studies reporting the ability of antibodies to evoke an alternative form of programmed cell death, oncosis, the molecular mechanism of antibody-mediated oncosis remains underinvestigated. In this study, a monoclonal antibody (mAb), TAG-A1 (A1), was generated to selectively kill residual undifferentiated human embryonic stem cells (hESC) so as to prevent teratoma formation upon transplantation of hESC-derived products...
January 20, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28106519/subunit-mass-analysis-for-monitoring-antibody-oxidation
#8
Izabela Sokolowska, Jingjie Mo, Jia Dong, Michael J Lewis, Ping Hu
Methionine oxidation is a common posttranslational modification (PTM) of monoclonal antibodies (mAbs). Oxidation can reduce the in-vivo half-life, efficacy and stability of the product. Peptide mapping is commonly used to monitor the levels of oxidation, but this is a relatively time-consuming method. A high-throughput, automated subunit mass analysis method was developed to monitor antibody methionine oxidation. In this method, samples were treated with IdeS, EndoS and dithiothreitol to generate three individual IgG subunits (light chain, Fd' and single chain Fc)...
January 20, 2017: MAbs
https://www.readbyqxmd.com/read/28106394/green-to-red-electrochromic-fe-ii-metallo-supramolecular-polyelectrolytes-self-assembled-from-fluorescent-2-6-bis-2-pyridyl-pyrimidine-bithiophene
#9
Sandesh Pai, Michael Moos, Maximilian H Schreck, Christoph Lambert, Dirk G Kurth
The structure and properties of metallo-supramolecular polyelectrolytes (MEPEs) self-assembled from rigid 2,6-bis(2-pyridyl)pyrimidine and the metal ions Fe(II) and Co(II) are presented. While FeL1-MEPE (L1 = 1,4-bis[2,6-bis(2-pyridyl)pyrimidin-4-yl]benzene) is deep blue, FeL2- and CoL2-MEPE (L2 = 5,5'-bis[2,6-bis(2-pyridyl)pyrimidin-4-yl]-2,2'-bithiophene) are intense green and red in color, respectively. These novel MEPEs display a high extinction coefficient and solvatochromism. Ligand L2 shows a high absolute fluorescence quantum yield (Φf = 82%)...
January 20, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28106257/limitations-of-polyethylene-glycol-induced-precipitation-as-predictive-tool-for-protein-solubility-during-formulation-development
#10
Melanie Hofmann, Matthias Winzer, Christian Weber, Henning Gieseler
OBJECTIVE: Polyethylene glycol (PEG)-induced protein precipitation is often used to extrapolate apparent protein solubility at specific formulation compositions. The procedure was used for several fields of application such as protein crystal growth but also protein formulation development. Nevertheless, most studies focused on applicability in protein crystal growth. In contrast, this study focuses on applicability of PEG-induced precipitation during high-concentration protein formulation development...
January 20, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28103859/treatment-with-soluble-activin-type-iib-receptor-improves-bone-mass-and-strength-in-a-mouse-model-of-duchenne-muscular-dystrophy
#11
Tero Puolakkainen, Hongqian Ma, Heikki Kainulainen, Arja Pasternack, Timo Rantalainen, Olli Ritvos, Kristiina Heikinheimo, Juha J Hulmi, Riku Kiviranta
BACKGROUND: Inhibition of activin/myostatin pathway has emerged as a novel approach to increase muscle mass and bone strength. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that leads to progressive muscle degeneration and also high incidence of fractures. The aim of our study was to test whether inhibition of activin receptor IIB ligands with or without exercise could improve bone strength in the mdx mouse model for DMD. METHODS: Thirty-two mdx mice were divided to running and non-running groups and to receive either PBS control or soluble activin type IIB-receptor (ActRIIB-Fc) once weekly for 7 weeks...
January 19, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28103139/endotoxin-neutralization-by-an-o-antigen-specific-monoclonal-antibody-a-potential-novel-therapeutic-approach-against-klebsiella-pneumoniaest258
#12
Valéria Szijártó, Luis M Guachalla, Katharina Hartl, Cecília Varga, Adriana Badarau, Irina Mirkina, Zehra C Visram, Lukas Stulik, Christine A Power, Eszter Nagy, Gábor Nagy
Klebsiella pneumoniae ST258 is a globally distributed multi-drug resistant pathogen responsible for severe invasive infections. In this study, the different virulence potential of K. pneumoniae ST258 isolates in endotoxin susceptible versus resistant animal models was shown. Furthermore, ST258 clinical isolates were found highly sensitive to the bactericidal effect of naive animal and human serum. These observations imply that LPS, released from the rapidly lysed bacteria, may contribute to the high mortality associated with ST258 bacteremia cases...
January 19, 2017: Virulence
https://www.readbyqxmd.com/read/28103014/reactive-oxygen-species-and-glutathione-dual-redox-responsive-supramolecular-assemblies-with-controllable-release-capability
#13
Yang Kang, Xin Ju, Li-Sheng Ding, Sheng Zhang, Bang-Jing Li
A dual redox and bio-relevant triggered supramolecular system is developed through the non-covalent host-guest interactions between the ferrocene (Fc) on camptothecin (CPT) and β-cyclodextrin (β-CD) at the end of methoxy polyethylene glycol (mPEG). The two segments can form a stable non-covalent supramolecular block copolymer mPEG-β-CD/Fc-CPT, which could further self-assemble into stable micelles in aqueous solution. Interestingly, these supramolecular micelles showed uniform sphere structure, high and constant drug loading content, hyper-fast redox-responsive drug release, and exhibited equal cellular proliferation inhibition toward A549 cancer cells, while the cytotoxicity evaluation of mPEG-β-CD indicated good biocompatibility...
January 19, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28102754/enhancement-of-antibody-functions-through-fc-multiplications
#14
Qun Wang, Yan Chen, Mark Pelletier, Romana Cvitkovic, Jessica Bonnell, Chien-Ying Chang, Adem C Koksal, Ellen O'Connor, Xizhe Gao, Xiang-Qing Yu, Herren Wu, C Kendall Stover, William F Dall'Acqua, Xiaodong Xiao
Antibodies carry out a plethora of functions through their crystallizable fragment (Fc) regions, which can be naturally tuned by the adoption of several isotypes and post-translational modifications. Protein engineering enables further Fc function modulations through modifications of the interactions between the Fc and its functional partners, including FcγR, FcRn, complement complex, and additions of auxiliary functional units. Due to the many functions embedded within the confinement of an Fc, a suitable balance must be maintained for a therapeutic antibody to be effective and safe...
January 19, 2017: MAbs
https://www.readbyqxmd.com/read/28101835/relationships-between-perceived-family-gambling-and-peer-gambling-and-adolescent-problem-gambling-and-binge-drinking
#15
Zu Wei Zhai, Sarah W Yip, Marvin A Steinberg, Jeremy Wampler, Rani A Hoff, Suchitra Krishnan-Sarin, Marc N Potenza
The study systematically examined the relative relationships between perceived family and peer gambling and adolescent at-risk/problem gambling and binge-drinking. It also determined the likelihood of at-risk/problem gambling and binge-drinking as a function of the number of different social groups with perceived gambling. A multi-site high-school survey assessed gambling, alcohol use, presence of perceived excessive peer gambling (peer excess-PE), and family gambling prompting concern (family concern-FC) in 2750 high-school students...
January 18, 2017: Journal of Gambling Studies
https://www.readbyqxmd.com/read/28101502/pregnant-woman-with-atypical-hemolytic-uremic-syndrome-delivered-a-healthy-newborn-under-eculizumab-treatment
#16
Erol Demir, Halil Yazici, Yasemin Ozluk, Isin Kilicaslan, Aydin Turkmen
Pregnancy-associated thrombotic microangiopathy is a very rare condition; however, it significantly increases fetal or maternal morbidity and mortality. Pregnancy may trigger atypical hemolytic uremic syndrome (aHUS) or thrombotic thrombocytopenic purpura. The risk for pregnancy-associated aHUS is highest during the second pregnancy. The outcome is usually poor with 50-60% mortality; renal dysfunction and hypertension are the rule in those who survive the acute episode. After the development of complement regulation mechanisms and aHUS pathogenesis, eculizumab has been widely used as a first-line treatment in aHUS...
September 2016: Case Reports in Nephrology and Dialysis
https://www.readbyqxmd.com/read/28100567/mecp2-regulated-glycogenes-contribute-to-proliferation-and-apoptosis-of-gastric-cancer-cells
#17
Yannan Qin, Lingyu Zhao, Xiaofei Wang, Dongdong Tong, Christopher Hoover, Fei Wu, Yingxun Liu, Lumin Wang, Liying Liu, Lei Ni, Tusheng Song, Chen Huang
Aberrant glycogene and glycan expression is intimately associated with carcinogenesis, invasion, and metastasis of gastric cancer (GC); however the regulatory mechanisms for glycogenes in GC cells remain unclear. Methyl-CpG-binding protein 2 (MeCP2) regulates genes by binding to methylated promoters, and in our previous work we found that it is overexpressed in GC cell lines and tissues, functioning as an oncogene. In this study we detected the expression of 212 glycogenes in MeCP2 silenced GC cells versus control using the Agilent Whole Human Genome Microarray and mining the data through bioinformatic analysis...
January 18, 2017: Glycobiology
https://www.readbyqxmd.com/read/28100468/feasibility-of-sample-size-calculation-for-rna-seq-studies
#18
Alicia Poplawski, Harald Binder
Sample size calculation is a crucial step in study design but is not yet fully established for RNA sequencing (RNA-seq) analyses. To evaluate feasibility and provide guidance, we evaluated RNA-seq sample size tools identified from a systematic search. The focus was on whether real pilot data would be needed for reliable results and on identifying tools that would perform well in scenarios with different levels of biological heterogeneity and fold changes (FCs) between conditions. We used simulations based on real data for tool evaluation...
January 18, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28100360/-end-tidal-pco-2-for-evaluation-of-severity-of-disease-in-idiopathic-pulmonary-arterial-hypertension-and-chronic-thromboembolic-pulmonary-hypertension
#19
X Shi, G L Yang, Y Chen, J Guo, W L Yang, P Yuan, S G Gong, R Jiang, Q H Zhao, L Wang, J He, T X Chen, J M Liu
Objective: To explore the difference in end tidal PCO(2) (P(ET)CO(2)) between idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH), and to analyze the correlation between P(ET)CO(2) and the indexes of disease severity in IPAH and CTEPH patients. Methods: Data were retrieved from 68 IPAH patients and 52 CTEPH patients who all had received right-heart catheterization, pulmonary function test and cardiopulmonary exercise testing at Shanghai Pulmonary Hospital from October 2011 to October 2014...
January 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28099586/serotoninergic-modulation-of-basal-cardiovascular-responses-and-responses-induced-by-isotonic-extracellular-volume-expansion-in-rats
#20
Isadora Ferraz Semionatto, Adrieli Oliveira Raminelli, Angelica Cristina Alves, Caroline Santos Capitelli, Rosangela Soares Chriguer
Background: Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. Objective: To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE. Methods: We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE...
January 16, 2017: Arquivos Brasileiros de Cardiologia
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