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https://www.readbyqxmd.com/read/28334870/annealing-helicase-harp-closes-rpa-stabilized-dna-bubbles-non-processively
#1
Daniel R Burnham, Bas Nijholt, Iwijn De Vlaminck, Jinhua Quan, Timur Yusufzai, Cees Dekker
We investigate the mechanistic nature of the Snf2 family protein HARP, mutations of which are responsible for Schimke immuno-osseous dysplasia. Using a single-molecule magnetic tweezers assay, we construct RPA-stabilized DNA bubbles within torsionally constrained DNA to investigate the annealing action of HARP on a physiologically relevant substrate. We find that HARP closes RPA-stabilized bubbles in a slow reaction, taking on the order of tens of minutes for ∼600 bp of DNA to be re-annealed. The data indicate that DNA re-anneals through the removal of RPA, which is observed as clear steps in the bubble-closing traces...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334043/cc-223-blocks-mtorc1-c2-activation-and-inhibits-human-hepatocellular-carcinoma-cells-in-vitro-and-in-vivo
#2
Zichen Xie, Jiqin Wang, Mei Liu, Deshan Chen, Chao Qiu, Keyu Sun
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related human mortalities. Over-activation of mammalian target of rapamycin (mTOR) is important for HCC tumorigenesis and progression. The current study assessed the potential anti-HCC activity by a novel mTOR kinase inhibitor, CC-223. We demonstrate that CC-223, at nM concentrations, induced profound cytotoxic and anti-proliferative activities against established HCC cell lines (HepG2, KYN-2 and Huh-7) and primary human HCC cells. Meanwhile, CC-223 activated caspase-3/-9 and apoptosis in the above HCC cells...
2017: PloS One
https://www.readbyqxmd.com/read/28332630/pml-nuclear-bodies-contribute-to-the-basal-expression-of-the-mtor-inhibitor-ddit4
#3
Jayme Salsman, Alex Stathakis, Ellen Parker, Dudley Chung, Livia E Anthes, Kara L Koskowich, Sara Lahsaee, Daniel Gaston, Kimberly R Kukurba, Kevin S Smith, Ian C Chute, Daniel Léger, Laura D Frost, Stephen B Montgomery, Stephen M Lewis, Christopher Eskiw, Graham Dellaire
The promyelocytic leukemia (PML) protein is an essential component of PML nuclear bodies (PML NBs) frequently lost in cancer. PML NBs coordinate chromosomal regions via modification of nuclear proteins that in turn may regulate genes in the vicinity of these bodies. However, few PML NB-associated genes have been identified. PML and PML NBs can also regulate mTOR and cell fate decisions in response to cellular stresses. We now demonstrate that PML depletion in U2OS cells or TERT-immortalized normal human diploid fibroblasts results in decreased expression of the mTOR inhibitor DDIT4 (REDD1)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330294/immuno-hybrid-algorithm-a-novel-hybrid-approach-for-grn-reconstruction
#4
A S Jereesh, V K Govindan
Bio-inspired algorithms are widely used to optimize the model parameters of GRN. In this paper, focus is given to develop improvised versions of bio-inspired algorithm for the specific problem of reconstruction of gene regulatory network. The approach is applied to the data set that was developed by the DNA microarray technology through biological experiments in the lab. This paper introduced a novel hybrid method, which combines the clonal selection algorithm and BFGS Quasi-Newton algorithm. The proposed approach implemented for real world E...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28327750/dynamic-studies-of-the-interaction-of-a-ph-responsive-amphiphilic-polymer-with-a-dopc-lipid-membrane
#5
Sivaramakrishnan Ramadurai, Marco Werner, Nigel K H Slater, Aaron Martin, Vladimir A Baulin, Tia E Keyes
Deeper understanding of the molecular interactions between polymeric materials and the lipid membrane is important across a range of applications from permeation for drug delivery to encapsulation for immuno-evasion. Using highly fluidic microcavity supported lipid bilayers, we studied the interactions between amphiphilic polymer PP50 and a DOPC lipid bilayer. As the PP50 polymer is pH responsive the studies were carried out at pH 6.5, 7.05 and 7.5, corresponding to fully, partly protonated (pH = pKa = 7.05) and fully ionized states of the polymer, respectively...
March 22, 2017: Soft Matter
https://www.readbyqxmd.com/read/28324600/light-sheet-fluorescence-microscopy-chemical-clearing-and-labeling-protocols-for-ultramicroscopy
#6
Nina Jährling, Klaus Becker, Saiedeh Saghafi, Hans-Ulrich Dodt
Light-sheet microscopy is an effective technique in neuroscience, developmental biology, and cancer research for visualizing and analyzing cellular networks and whole organs in three dimensions. Because this technique requires specimens to be translucent they commonly have to be cleared before microscopy inspection. Here, we provide 3DISCO based protocols for preparing cleared samples of immuno-stained neural networks, lectin-labeled vascular networks, and Methoxy-X04 labeled beta-amyloid plaques in mice. 3DISCO utilizes the lipophilic solvents tetrahydrofuran (THF) and dibenzylether (DBE) for dehydration and successive clearing...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28323110/yeast-mediated-mrna-delivery-polarizes-immuno-suppressive-macrophages-towards-an-immuno-stimulatory-phenotype
#7
Michelle Seif, Jessica Hoppstädter, Frank Breinig, Alexandra K Kiemer
Macrophages have increasingly gained interest as a therapeutic target since they represent an integral component of the tumor microenvironment. In fact, M2 macrophage accumulation in solid tumors is associated with poor prognosis and therapy failure. Therefore, reprogramming M2 macrophages towards an M1 phenotype with anti-tumor activity by gene therapy represents a promising therapeutic approach. Herein, we describe recombinant Saccharomyces cerevisiae as a novel gene delivery vehicle for primary human macrophages...
March 17, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28322946/characterizations-and-hepatoprotective-effect-of-polysaccharides-from-mori-fructus-in-rats-with-alcoholic-induced-liver-injury
#8
Xin Zhou, Qingfang Deng, Huaguo Chen, Enming Hu, Chao Zhao, Xiaojian Gong
Crude polysaccharides of Mori Fructus (MFPs) are found to have anti-inflammatory antioxidant, and immuno-enhancing activities. However, the structure of the polysaccharides was ambiguous and its holistic hepatic protection evaluation was defective. This study was conducted to illustrate the characterization of MFPs, and evaluate its hepatoprotective activities. The results found that MFPs contained 67.93±1.18% carbohydrates, 31.03±0.54% uronic acid, and little protein and sulfate. The average molecular weight was ranging from 112...
March 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28322743/an-experimental-approach-to-the-immuno-modulatory-basis-of-host-parasite-local-adaptation-in-tapeworm-infected-sticklebacks
#9
Madeleine Hamley, Frederik Franke, Joachim Kurtz, Jörn Peter Scharsack
The evolutionary arms race of hosts and parasites often results in adaptations, which may differ between populations. Investigation of such local adaptation becomes increasingly important to understand dynamics of host-parasite interactions and co-evolution. To this end we performed an infection experiment involving pairs of three-spined sticklebacks and their tapeworm parasite Schistocephalus solidus from three geographically separated origins (Germany, Spain and Iceland) in a fully-crossed design for sympatric and allopatric host/parasite combinations...
March 18, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28322428/xenotransplantation-where-do-we-stand-in-2016
#10
Gisella L Puga Yung, Robert Rieben, Leo Bühler, Henk-Jan Schuurman, Jörg Seebach
Worldwide, there is a constant rise in the number of patients with end-stage organ failure in critical need for transplants, but the number of organs/cells available from deceased or living human donors is limited. Xenotransplantation using pig organs/tissues repre-sents a potential solution for this shortage; however, it has been hampered by a number of mainly immuno-logical hurdles. Remarkable progress was presented at the latest biennial (13th) international congress of the International Xenotransplantation Association, November 2015 in Melbourne, Australia, and the American Transplant Congress, May 2016 in Boston, USA...
March 21, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28322362/immunopathogenic-oral-diseases-%C3%A2-an-overview-focusing-on-pemphigus-vulgaris-and-mucous-membrane-pemphigoid
#11
Liviu Feller, Raoul Ballyram, Razia Ag Khammissa, Mario Altini, Johan Lemmer
Pemphigus vulgaris, mucosal pemphigoid (mucous membrane pemphigoid), lichen planus, discoid lupus erythematosus and erythema multiforme are a group of immune-mediated mucocutaneous disorders characterised clinically by the formation of blisters, erosions or ulcers. The oral mucosa is often affected, and sometimes the disease is limited to the mouth. The target antigens, autoreactive immune responses, microscopic features, treatment and prognosis vary from one disease to the other. Treatment aims to eliminate exogenous risk factors, suppress the pathogenic immuno-inflammatory reactions, promote healing and prevent infection...
March 20, 2017: Oral Health & Preventive Dentistry
https://www.readbyqxmd.com/read/28321641/transformed-follicular-lymphoma-tfl-consolidation-therapy-may-improve-survival
#12
E Elhassadi, R Flavin, P Browne, E Conneally, P Hayden, F Quinn, E Higgins, E Vandenberghe
PURPOSE: Retrospective study to evaluate the outcome of patients with transformed follicular lymphoma (tFL) treated with rituximab-containing chemotherapy and consolidation. PATIENTS AND METHODS: Patients diagnosed with tFL from 2003 to 2013 treated with consolidation therapy with last follow-up in December 2015 were identified from the institutional lymphoma database and included in this study. Data collected included age, gender, stage, interval to tFL diagnosis, R-IPI score, histological diagnosis and therapy...
March 21, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28321504/quantitative-characterization-of-single-cells-by-use-of-immunocytochemistry-combined-with-multiplex-la-icp-ms
#13
Larissa Mueller, Antje J Herrmann, Sandra Techritz, Ulrich Panne, Norbert Jakubowski
Actual research demonstrates that LA-ICP-MS is capable of being used as an imaging tool with cellular resolution. The aim of this investigation was the method development for LA-ICP-MS to extend the versatility to quantitative and multiplexing imaging of single eukaryotic cells. For visualization of individual cells selected, lanthanide-labeled antibodies were optimized for immuno-imaging of single cells with LA-ICP-MS. The molar content of the artificial introduced labels per cell was quantified using self-made nitrocellulose-coated slides for matrix-matched calibration and calculated amounts were in the range of 3...
March 20, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28319722/bisphenol-s-exposure-modulate-macrophage-phenotype-as-defined-by-cytokines-profiling-global-metabolomics-and-lipidomics-analysis
#14
Chao Zhao, Zhi Tang, Jiacheng Yan, Jing Fang, Hailin Wang, Zongwei Cai
As an important structural analogue of bisphenol A (BPA), bisphenol S (BPS) has been used as alternatives to BPA in industrialized production. However, the immunotoxicity of BPS remains poorly understood. As a critical model in inflammatory responses, macrophages are used to explore the immunotoxic potential and mechanisms of BPS at environmentally relevant concentrations in our study. Here, we are combining molecular toxicology and mass spectrometry (MS)-based global metabolomics and lipidomics study together to estimate the variation of cytokines profiling and metabolism characteristic following BPS exposure...
March 17, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28316970/dgk-%C3%AE-a-checkpoint-in-cancer-mediated-immuno-inhibition-and-target-for-immunotherapy
#15
Elfriede Noessner
Immunotherapy is moving to the forefront of cancer treatments owing to impressive durable responses achieved with checkpoint blockade antibodies and adoptive T-cell therapy. Still, improvements are necessary since, overall, only a small percentage of patients benefit from current therapies. Here, I summarize evidence that DGK-α may represent an immunological checkpoint suppressing the activity of cytotoxic immunocytes in the tumor microenvironment. DGK-inhibitors can restore the antitumor function of tumor-suppressed adaptive and innate cytotoxic immunocytes...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28316968/a-stepwise-pilot-study-of-bovine-colostrum-to-supplement-the-first-enteral-feeding-in-preterm-infants-precolos-study-protocol-and-initial-results
#16
Yanqi Li, Sandra M Juhl, Xuqiang Ye, René L Shen, Elisabeth Omolabake Iyore, Yiheng Dai, Per T Sangild, Gorm O Greisen
STUDY PROTOCOL: The optimal feeding for preterm infants during the first weeks is still debated, especially when mother's own milk is lacking or limited. Intact bovine colostrum (BC) contains high amounts of protein, growth factors, and immuno-regulatory components that may benefit protein intake and gut maturation. We designed a pilot study to investigate the feasibility and tolerability of BC as the first nutrition for preterm infants. The study was designed into three phases (A, B, and C) and recruited infants with birth weights of 1,000-1,800 g (China) or gestational ages (GAs) of 27 + 0 to 32 + 6 weeks (Denmark)...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28315558/toxicity-management-development-of-a-novel-and-immune-mediated-adverse-events-algorithm%C3%A2
#17
Haleigh Mistry, Sheryl G Forbes, Nathan Fowler
BACKGROUND: Novel immunotherapy and biologic agents are being developed with the potential to improve outcomes and reduce long-term toxicities among individuals with hematologic malignancies. These emerging drugs affect neoplastic cells and the surrounding microenvironment, causing unique immune-mediated toxicities.
. OBJECTIVES: The aim was to develop an algorithm for clinical staff to manage unique toxicities associated with next-generation immunotherapies indicated in the hematologic population, using a system-focused approach...
April 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28303024/lessons-from-immuno-oncology-a-new-era-for-cancer-nanomedicine
#18
Wen Jiang, Hengfeng Yuan, Charles K Chan, Christina A von Roemeling, Zuoqin Yan, Irving L Weissman, Betty Y S Kim
Despite a decade of intensive preclinical research, the translation of cancer nanomedicine to the clinic has been slow. Here, we discuss how recent lessons learned from the successes with immuno-oncology therapies could be applied to cancer nanomedicine and how this may help to overcome some of the key technical challenges in this field.
March 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28302075/renal-effects-of-metallothionein-induction-by-zinc-in-vitro-and-in-vivo
#19
Moritz Schanz, Lea Schaaf, Juergen Dippon, Dagmar Biegger, Peter Fritz, Mark Dominik Alscher, Martin Kimmel
BACKGROUND: Metallothionein (MTT) is an endogenous antioxidant that can be induced by both zinc (Zn) and ischemia. In kidneys, increased MTT expression exerts a putative protective role in diabetes and hypoxia. Our goal was to further investigate the behavior of MTT under the influence of Zn and hypoxia in vitro and in vivo. METHODS: MTT expression was measured in vitro in cell cultures of proximal tubular cells (LCC-PK1) by immune-histochemistry and real-time PCR after incubation with increasing concentrations of Zn under hypoxic and non-hypoxic conditions...
March 16, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28302019/the-breakthroughs-in-cancer-immune-checkpoint-based-therapy-a-review-of-development-in-immune-checkpoint-study-and-its-application
#20
Yao Huang, Dong Liang, Jingfeng Liu, Jinhua Zeng, Yongyi Zeng
Recently, immunotherapy has attracted more attentions to fight cancer due to its selectivity, long lasting effects, and demonstrated better overall survival and tolerance, when compared to patients treated with conventional chemotherapy or radiotherapy alone. The anti-tumor response of patient with cancer is improved either by increasing the effector cell number, the production of soluble mediators, or by modulating the host's immune checkpoint. Over the last decades, many new approaches in immunotherapy have been developed, such as immune checkpoint inhibitors, chimeric antigen receptor T cells (CART), specific T-cell -receptor T cells (TCRT) and cancer vaccine, some of which has been approved by FDA to treat several cancer types...
March 15, 2017: Combinatorial Chemistry & High Throughput Screening
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