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https://www.readbyqxmd.com/read/28433539/rationally-designed-pi3k%C3%AE-mutants-to-mimic-atr-and-their-use-to-understand-binding-specificity-of-atr-inhibitors
#1
Yipin Lu, Mark Knapp, Kenneth Crawford, Robert Warne, Robert Elling, Kelly Yan, Michael Doyle, Gwynn Pardee, Li Zhang, Sylvia Ma, Mulugeta Mamo, Elizabeth Ornelas, Yue Pan, Dirksen Bussiere, Johanna Jansen, Isabel Zaror, Albert Lai, Paul Barsanti, Janet Sim
ATR, a protein kinase in the PIKK family, plays a critical role in the cell DNA-damage response and is an attractive anticancer drug target. Several potent and selective inhibitors of ATR have been reported showing significant antitumor efficacy, with most advanced ones entering clinical trials. However, due to the absence of an experimental ATR structure, the determinants contributing to ATR inhibitors' potency and specificity are not well understood. Here we present the mutations in the ATP-binding site of PI3Kα to progressively transform the pocket to mimic that of ATR...
April 19, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28433160/thiolated-chitosan-micelles-highly-mucoadhesive-drug-carriers
#2
Arshad Mahmood, Melanie Lanthaler, Flavia Laffleur, Christian W Huck, Andreas Bernkop-Schnürch
Current study was aimed to generate thiolated chitosan micelles based on amphiphilic chitosan-stearic acid conjugate (CSA) and to evaluate adhesive properties on mucosal membranes. Chitosan-stearic acid-thioglycolic acid (CSA-TGA) conjugate was synthesized via stearic acid linkage to chitosan and later, thioglycolic acid was covalently attached to CSA. CSA-TGA and CSA were characterized by degree of amine substitution, thiol group determination, ATR-FTIR and cytotoxicity analysis. Micelle size was 13.40±9...
July 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28431942/chitosan-based-nanocomplexes-for-simultaneous-loading-burst-reduction-and-controlled-release-of-doxorubicin-and-5-fluorouracil
#3
Antonio Di Martino, Pavel Kucharczyk, Zdenka Capakova, Petr Humpolicek, Vladimir Sedlarik
In this work, nanocomplexes based on chitosan grafted by carboxy-modified polylactic acid (SPLA) were prepared with the aim of loading simultaneously two anticancer drugs - doxorubicin and 5-fluorouracil, as well as to control their release, reduce the initial burst and boost cytotoxicity. The SPLA was prepared by a polycondensation reaction, using pentetic acid as the core molecule, and linked to the chitosan backbone through a coupling reaction. Nanocomplexes loaded with both drugs were formulated by the polyelectrolyte complexation method...
April 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28431234/tpp1-blocks-an-atr-mediated-resection-mechanism-at-telomeres
#4
Tatsuya Kibe, Michal Zimmermann, Titia de Lange
No abstract text is available yet for this article.
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28429024/a-highly-efficient-cu-catalyst-system-for-the-radical-reactions-of-%C3%AE-bromocarbonyls
#5
Yushi Noda, Takashi Nishikata
In this communication, we established highly efficient Cu-catalyzed ARGET-ATRS (atom-transfer radical substitution) of alpha-bromocarbonyls with styrenes to produce tert-alkylated styrenes. The maximum TON was up to 12 000. Hünig's base was very important to regenerate active Cu(I). Moreover, a Cu-catalyzed C-C cleavage reaction via SH2' and intermolecular C-H cyclization of α-bromoimide was found.
April 21, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28427665/combined-ultrasonic-and-gamma-irradiation-to-prepare-tio2-pet-g-paac-fabric-composite-for-self-cleaning-application
#6
Mohamed Mohamady Ghobashy
The grafting of polyacrylic acid (PAAc) onto the fabric of Poly(ethyleneterephthalate) (PET) was loaded with TiO2 by a mixture sonication of TiO2 dispersed in AAc dissolved in acetone solvent. Ultrasonic irradiation was utilized as a tool for a good dispersion of TiO2 onto the PET fabric. The grafted PET fabrics with acrylic acid AAc monomer were successfully obtained using gamma-ray induced graft polymerization, the degree of grafting PET-g-PAAc fiber was 105%. The chemical compositions and crystal structure of grafted TiO2@PET-g-PAAc fabrics were characterized by ATR-FTIR and XRD...
July 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28426283/identification-of-the-proteome-complement-of-humantlk1-reveals-it-binds-and-phosphorylates-nek1-regulating-its-activity
#7
Vibha Singh, Zachary M Connelly, Xinggui Shen, Arrigo De Benedetti
The Tousled Like kinases (TLKs) are involved in numerous cellular functions, including the DNA Damage Response (DDR), but only a handful of substrates have been identified thus far. Through a novel proteomic screen, we have now identified 165 human proteins interacting with TLK1, and we have focused this work on NEK1 because of its known role in the DDR, upstream of ATR and Chk1. TLK1 and NEK1 were found to interact by coIP, and their binding is strengthened following exposure of cells to H2O2. Following incubation with doxorubicin, TLK1 and NEK1 relocalize with nuclear repair foci along with γH2AX...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28423951/preparation-characterization-and-dynamical-mechanical-properties-of-dextran-coated-iron-oxide-nanoparticles-dionps
#8
Hatice Kaplan Can, Serap Kavlak, Shahed ParviziKhosroshahi, Ali Güner
Dextran-coated iron oxide nanoparticles (DIONPs) with appropriate surface chemistry exhibit many interesting properties that can be exploited in a variety of biomedical applications such as magnetic resonance imaging (MRI) contrast enhancement, tissue repair, hyperthermia, drug delivery and in cell separation. This paper reports the experimental detail for preparation, characterization and investigation of thermal and dynamical mechanical characteristics of the dextran-coated Fe3O4 magnetic nanoparticles. In our work, DIONPs were prepared in a 1:2 ratio of Fe(II) and Fe(III) salt in the HCl solution with NaOH at given temperature...
April 20, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28423586/the-role-of-ros-and-subsequent-dna-damage-response-in-puma-induced-apoptosis-of-ovarian-cancer-cells
#9
Jun Yang, Xinyu Zhao, Mei Tang, Lei Li, Yi Lei, Ping Cheng, Wenhao Guo, Yu Zheng, Wei Wang, Na Luo, Yong Peng, Aiping Tong, Yuquan Wei, Chunlai Nie, Zhu Yuan
PUMA is a member of the "BH3-only" branch of the BCL-2 family. Our previous study suggests a therapeutic potential of PUMA in treating ovarian cancer, however, the action mechanism of PUMA remains elusive. In this work, we found that in PUMA adenovirus-infected A2780s ovarian cancer cells, exogenous PUMA was partially accumulated in the cytosol and mainly located to the mitochondria. We further showed that PUMA induces mitochondrial dysfunction-mediated apoptosis and ROS generation through functional BAX in a ROS generating enzyme- and caspase-independent manner irrespective of their p53 status, and results in activation of Nrf2/HO-1 pathway...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423495/afatinib-radiosensitizes-head-and-neck-squamous-cell-carcinoma-cells-by-targeting-cancer-stem-cells
#10
Muzafar A Macha, Satyanarayana Rachagani, Asif Khurshid Qazi, Rahat Jahan, Suprit Gupta, Anery Patel, Parthasarathy Seshacharyulu, Chi Lin, Sicong Li, Shuo Wang, Vivek Verma, Shosei Kishida, Michiko Kishida, Norifumi Nakamura, Toshiro Kibe, William M Lydiatt, Russell B Smith, Apar K Ganti, Dwight T Jones, Surinder K Batra, Maneesh Jain
The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416396/chitosan-composite-three-dimensional-macrospheric-scaffolds-for-bone-tissue-engineering
#11
Veena Vyas, Tejinder Kaur, Arunachalam Thirugnanam
The present work deals with the fabrication of chitosan composite scaffolds with controllable and predictable internal architecture for bone tissue engineering. Chitosan (CS) based composites were developed by varying montmorillonite (MMT) and hydroxyapatite (HA) combinations to fabricate macrospheric three dimensional (3D) scaffolds by direct agglomeration of the sintered macrospheres. The fabricated CS, CS/MMT, CS/HA and CS/MMT/HA 3D scaffolds were characterized for their physicochemical, biological and mechanical properties...
April 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28415748/the-spi1-pu-1-transcription-factor-accelerates-replication-fork-progression-by-increasing-pp1-phosphatase-in-leukemia
#12
Pauline Rimmelé, Michela Esposito, Laure Delestré, Jean-Hugues Guervilly, Maya Ridinger-Saison, Emmanuelle Despras, Françoise Moreau-Gachelin, Filippo Rosselli, Christel Guillouf
Oncogenes trigger replicative stress that can lead to genetic instability, which participates in cancer progression. Thus, determining how cells cope with replicative stress can help our understanding of oncogenesis and lead to the identification of new antitumor treatment targets. We previously showed that constitutive overexpression of the oncogenic transcription factor Spi1/PU.1 leads to pre-leukemic cells that have a shortened S phase duration with an increased replication fork speed and increased mutability in the absence of DNA breaks...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415528/improved-biotribological-properties-of-peek-by-photo-induced-graft-polymerization-of-acrylic-acid
#13
Xiaoduo Zhao, Dangsheng Xiong, Kun Wang, Nan Wang
The keys of biomaterials application in artificial joints are good hydrophilicity and wear resistance. One kind of the potential bio-implant materials is polyetheretherketone (PEEK), which has some excellent properties such as non-toxic and good biocompatibility. However, its bioinert surface and inherent chemical inertness hinder its application. In this study, we reported an efficient method for improving the surface wettability and wear resistance for PEEK, a layer of acrylic acid (AA) polymer brushes on PEEK surface was prepared by UV-initiated graft polymerization...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28415465/photochemical-coating-of-kapton%C3%A2-with-hydrophilic-polymers-for-the-improvement-of-neural-implants
#14
Christoph Hadler, Kirsten Wissel, Gudrun Brandes, Wibke Dempwolf, Günter Reuter, Thomas Lenarz, Henning Menzel
The polyimide Kapton® was coated photochemically with hydrophilic polymers to prevent undesirable cell growth on the polyimide surface. The polymer coatings were generated using photochemically reactive polymers synthesized by a simple and modular strategy. Suitable polymers or previously synthesized copolymer precursors were functionalized with photoactive arylazide groups by a polymer analogous amide coupling reaction with 4-azidobenzoic acid. A photoactive chitosan derivative (chitosan-Az) and photochemically reactive copolymers containing DMAA, DEAA or MTA as primary monomers were synthesized using this method...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28415414/bionanocomposite-systems-based-on-montmorillonite-and-biopolymers-for-the-controlled-release-of-olanzapine
#15
Artur S Oliveira, Ana C S Alcântara, Sibele B C Pergher
Olanzapine (OLZ) is a drug that is used in the treatment of schizophrenia and other psychoses, and it belongs to the thienobenzodiazepine class. The OLZ molecule has low solubility decreasing bioavailability, but has high permeability in membrane biological being classified as a Class II drug substance according to the Biopharmaceutics Classification System. It was reported many side effects of administering OLZ orally. So, in order to increase the bioavailability of drug and possibly reducing some of side effects, this paper proposes a new material able to controllably release the drug in the body...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28414388/infrared-spectroscopy-of-secondary-organic-aerosol-precursors-and-investigation-of-the-hygroscopicity-of-soa-formed-from-the-oh-reaction-with-guaiacol-and-syringol
#16
Waed Ahmad, Cecile Coeur, Alexandre Tomas, Thomas Fagniez, Jean-Blaise Brubach, Arnaud Cuisset
Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) synchrotron analyses supplemented by density functional theory (DFT) anharmonic calculations have been undertaken to study the fundamental vibrational signatures of guaiacol and syringol, two methoxyphenol compounds found at the highest concentrations in fresh wood smoke and precursors of secondary organic aerosols (SOA) affecting the radiative balance and chemistry of the atmosphere. Nitroderivatives of these two compounds have also been studied experimentally for nitroguaiacol and theoretically for nitrosyringol...
April 10, 2017: Applied Optics
https://www.readbyqxmd.com/read/28412751/poly-adp-ribose-polymerase-inhibitor-an-effective-radiosensitizer-in-lung-and-pancreatic-cancers
#17
Kedar Hastak, Steven Bhutra, Renate Parry, James M Ford
The development of stereotactic body radiation therapy (SBRT) has revolutionized radiation therapy for lung cancers and is an emerging treatment option for pancreatic cancers. However, there are many questions on how to optimize its use in chemoradiotherapy. The most relevant addition to radiotherapy regimens are inhibitors of DNA repair and DNA damage response pathways. One such class of agents are inhibitors of poly (ADP-ribose) polymerase (PARP). In this study we examined the effects of the PARP inhibitor LT626 in combination with ionizing radiation in lung and pancreatic cancers...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409627/simultaneous-atr-ftir-based-determination-of-malaria-parasitemia-glucose-and-urea-in-whole-blood-dried-onto-a-glass-slide
#18
Supti Roy, David Perez-Guaita, Dean W Andrew, Jack S Richards, Don McNaughton, Philip Heraud, Bayden R Wood
New diagnostic tools that can detect malaria parasites in conjunction with other diagnostic parameters are urgently required. In this study, Attenuated Total Reflection Fourier transform infrared (ATR-FTIR) spectroscopy in combination with Partial Least Square Discriminant Analysis (PLS-DA) and Partial Least Square Regression (PLS-R) have been applied as a point-of-care test for identifying malaria parasites, blood glucose and urea levels in whole blood samples from thick blood films on glass slides. The specificity for the PLS-DA was found to be 98 % for parasitemia levels >0...
April 14, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28409150/mitotic-catastrophe-in-bc3h1-cells-following-yessotoxin-exposure
#19
Mónica Suárez Korsnes, Reinert Korsnes
The marine toxin yessotoxin (YTX) can cause various cytotoxic effects depending on cell type and cell line. It is well known to trigger distinct mechanisms for programmed cell death which may overlap or cross-talk. The present contribution provides the first evidence that YTX can cause genotoxicity and induce mitotic catastrophe which can lead to different types of cell death. This work also demonstrates potential information gain from non-intrusive computer-based tracking of many individual cells during long time...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28406007/uranium-in-water-adsorption-over-nh2-functionalized-ordered-silica
#20
Jeremie Huynh, Ruben Palacio, Fariba Safizadeh, Grégory Lefèvre, Michael Descostes, Lilian Eloy, Nadia Guignard, Julie Rousseau, Sebastien Royer, Emmanuel Tertre, Isabelle Batonneau-Gener
This work goes inside the understanding of U(VI) adsorption mechanism over amino-functionalized mesoporous silica SBA-15 and highlights its high efficiency in aqueous media for U(VI) removal and preconcentration. The samples were synthesized and functionalized by both grafting and co-condensation methods, using different alkyl substituted amine groups, and were characterized by XRD, N2 physisorption, FT-IR spectroscopy and Elemental C-H-N-S analyses. The properties for U(VI) adsorption were evaluated under discontinuous conditions, with effect of several parameters (initial pH, contact time, initial U(VI) concentration, functionalization method and organic moiety composition) determined...
April 13, 2017: ACS Applied Materials & Interfaces
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