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https://www.readbyqxmd.com/read/28643783/cdt1-stabilizes-an-open-mcm-ring-for-helicase-loading
#1
Jordi Frigola, Jun He, Kerstin Kinkelin, Valerie E Pye, Ludovic Renault, Max E Douglas, Dirk Remus, Peter Cherepanov, Alessandro Costa, John F X Diffley
ORC, Cdc6 and Cdt1 act together to load hexameric MCM, the motor of the eukaryotic replicative helicase, into double hexamers at replication origins. Here we show that Cdt1 interacts with MCM subunits Mcm2, 4 and 6, which both destabilizes the Mcm2-5 interface and inhibits MCM ATPase activity. Using X-ray crystallography, we show that Cdt1 contains two winged-helix domains in the C-terminal half of the protein and a catalytically inactive dioxygenase-related N-terminal domain, which is important for MCM loading, but not for subsequent replication...
June 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28643260/a-simple-protocol-for-loss-of-function-analysis-in-xenopus-tropicalis-founders-using-the-crispr-cas-system
#2
Yuto Sakane, Ken-Ich T Suzuki, Takashi Yamamoto
Xenopus tropicalis is a versatile model organism for studying basic biology such as developmental biology and cell biology, and for biomedical research on human diseases. Current genome editing techniques enable researchers to easily perform gene targeting in various animals. Among them, gene knockout using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated (Cas) (CRISPR-Cas) system has recently become an indispensable strategy for loss-of-function analysis in vivo. Because of its ease of use, time, and cost efficiencies, CRISPR-Cas has also been applied to X...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28642465/structural-basis-for-biologically-relevant-mechanical-stiffening-of-a-virus-capsid-by-cavity-creating-or-spacefilling-mutations
#3
Pablo Guerra, Alejandro Valbuena, Jordi Querol-Audí, Cristina Silva, Milagros Castellanos, Alicia Rodríguez-Huete, Damià Garriga, Mauricio G Mateu, Nuria Verdaguer
Recent studies reveal that the mechanical properties of virus particles may have been shaped by evolution to facilitate virus survival. Manipulation of the mechanical behavior of virus capsids is leading to a better understanding of viral infection, and to the development of virus-based nanoparticles with improved mechanical properties for nanotechnological applications. In the minute virus of mice (MVM), deleterious mutations around capsid pores involved in infection-related translocation events invariably increased local mechanical stiffness and interfered with pore-associated dynamics...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642154/a-boosting-skin-vaccination-with-dissolving-microneedle-patch-encapsulating-m2e-vaccine-broadens-the-protective-efficacy-of-conventional-influenza-vaccines
#4
Wandi Zhu, Winston Pewin, Chao Wang, Yuan Luo, Gilbert X Gonzalez, Teena Mohan, Mark R Prausnitz, Bao-Zhong Wang
The biodegradable microneedle patch (MNP) is a novel technology for vaccine delivery that could improve the immunogenicity of vaccines. To broaden the protective efficiency of conventional influenza vaccines, a new 4M2e-tFliC fusion protein construct containing M2e sequences from different subtypes was generated. Purified fusion protein was encapsulated into MNPs with a biocompatible polymer for use as a boosting vaccine. The results demonstrated that mice receiving a conventional inactivated vaccine followed by a skin-applied dissolving 4M2e-tFliC MNP boost could better maintain the humoral antibody response than that by the conventional vaccine-prime alone...
June 19, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28640996/a-polyoxometalate-based-radiosensitization-platform-for-treating-hypoxic-tumor-by-attenuating-radio-resistance-and-enhancing-radiation-response
#5
Yuan Yong, Chunfang Zhang, Zhanjun Gu, Jiangfeng Du, Zhao Guo, Xinghua Dong, Jiani Xie, Guangjin Zhang, Xiangfeng Liu, Yuliang Zhao
Radioresistance is one of the undesirable impediments in hypoxia tumor, which sharply diminishes therapeutic effectiveness of radiotherapy and eventually results in the failure of their treatments. An attractive strategy for attenuating radioresistance is developing an ideal radiosensitization system with admirable radiosensitization capacity to attenuate tumor hypoxia and reinforce radiotherapy response in hypoxia tumor. Therefore, we describe the development of Gd-containing polyoxometalates-conjugated chitosan (GdW10@CS nanosphere) as a radiosensitization system for simultanous extrinsic and intrinsic radiosensitization, by generating overabundance cytotoxic reactive oxygen species (ROS) using high energy X-ray stimulation and mediating the hypoxia-inducible factor-1a (HIF-1a) siRNA to down-regulate HIF-1α expression and suppress the broken double-stranded DNA self-healing...
June 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/28640858/early-growth-stages-salinity-stress-tolerance-in-cm72-x-gairdner-doubled-haploid-barley-population
#6
Tefera Tolera Angessa, Xiao-Qi Zhang, Gaofeng Zhou, Sue Broughton, Wenying Zhang, Chengdao Li
A doubled haploid (DH) population of barley (Hordeum vulgare L.) generated from salinity tolerant genotype CM72 and salinity sensitive variety Gairdner was studied for salinity stress tolerance at germination, seedling emergence and first leaf full expansion growth stages. Germination study was conducted with deionized water, 150 mM and 300 mM NaCl treatments. Seedling stage salinity tolerance was conducted with three treatments: control, 150 mM NaCl added at seedling emergence and first leaf full expansion growth stages...
2017: PloS One
https://www.readbyqxmd.com/read/28640608/numerical-diculties-computing-electrostatic-potentials-near-interfaces-with-the-poisson-boltzmann-equation
#7
Marcia Oliveira Fenley, Alexander H Boschitsch, Robert C Harris
Many researchers compute surface maps of the electrostatic potential with the Poisson-Boltzmann (PB) equation to relate the structural information obtained from X-ray and NMR experiments to biomolecular functions. Here we demonstrate that the usual method of obtaining these surface maps of electrostatic potential, by interpolating from neighboring grid points on the solution grid generated by a PB solver, generates large errors because of the large discontinuity in the dielectric constant (and thus in the normal derivative of the electrostatic potential) at the surface...
June 22, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28640302/influence-of-substituents-on-dna-and-protein-binding-of-cyclometalated-ir-iii-complexes-and-anticancer-activity
#8
Sujay Mukhopadhyay, Roop Shikha Singh, Rajendra Prasad Paitandi, Gunjan Sharma, Biplob Koch, Daya Shankar Pandey
Synthesis of terpyridyl based ligands 3-([2,2':6',2''-terpyridin]-4'-yl)-7-methoxy-2-(methylthio)-quinolone, (L1); 3-([2,2':6',2''-terpyridin]-4'-yl)-6-methoxyquinolin-2(1H)-one, (L2); 3-([2,2'-:6',2''-terpyridin]-4'-yl)-6-methylquinolin-2(1H)-one (L3) and cyclometalated iridium(iii) complexes [[Ir(ppy)2L1](+)PF6(-) (1), [Ir(ppy)2L2](+)PF6(-) (2), [Ir(ppy)2L3](+)PF6(-) (3) (2-phenylpyridine = Hppy)] involving these ligands has been described. The ligands L1-L3 and complexes 1-3 have been thoroughly characterized by elemental analyses, spectral studies (IR, (1)H, (13)C NMR, UV/vis and fluorescence) ESI-MS, and the structure of 3 has been unambiguously authenticated by single crystal X-ray analyses...
June 22, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28640008/brain-derived-neurotrophic-factor-propeptide-inhibits-proliferation-and-induces-apoptosis-in-c6-glioma-cells
#9
Bangkun Yang, Jun Qin, Ying Nie, Yong Li, Qianxue Chen
There are several forms of brain-derived neurotrophic factor (BDNF), the precursor of BDNF, mature BDNF, and BDNF propeptide. They exert different effects through different transmembrane receptor signaling systems. Precursor of BDNF is enzymatically cleaved, either by intracellular or by extracellular proteases, to generate mature BDNF and its propeptide (BDNF propeptide). The aim of this study was to evaluate the potential molecular mechanisms that underlie the inhibition of glioma cell growth by the BDNF propeptide...
June 21, 2017: Neuroreport
https://www.readbyqxmd.com/read/28639650/mechanisms-of-h-and-co-loss-from-the-uracil-nucleobase-following-low-energy-electron-irradiation
#10
Mark A Fennimore, Tolga N V Karsili, Spiridoula Matsika
Ionising radiation in cells generates secondary low energy electrons (LEEs) which can induce biomolecular damage when incident upon a particular biomolecule. Notable biomolecules include those contained within double-stranded DNA and RNA helices, which upon exposure to LEEs, may form reactive intermediate products that show detriment to their specific structures and functions. Such damaging processes are understood to proceed via dissociative electron attachment (DEA). Using anion resonance stabilisation methods, coupled to state-of-the-art electronic structure methods, and reaction path mapping, the work presented herein highlights the detailed mechanisms associated with molecular elimination of CO and H from the uracil nucleobase following LEE irradiation - providing a rationale for earlier experiments...
June 22, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28639560/mechanical-properties-of-decellularized-extracellular-matrix-coated-with-ticapcon-film
#11
I V Sukhorukova, A N Sheveyko, K L Firestein, Ph V Kiryukhantsev-Korneev, D Golberg, D V Shtansky
For the first time the surface of decellularized extracellular matrix (DECM) was modified via deposition of a multicomponent bioactive nanostructured film for improvement of the DECM's mechanical properties. TiCaPCON films were deposited onto the surface of intact and decellularized ulna, radius, and humerus bones by magnetron sputtering of TiC0.5 + 10%Ca3(PO4)2 and Ti targets in a gaseous mixture of Ar + N2. The film structure was studied using x-ray diffraction, scanning and transmission electron microscopy, and Raman spectroscopy...
June 22, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28639360/the-mechanism-of-coupling-between-oxido-reduction-and-proton-translocation-in-respiratory-chain-enzymes
#12
Sergio Papa, Giuseppe Capitanio, Francesco Papa
The respiratory chain of mitochondria and bacteria is made up of a set of membrane-associated enzyme complexes which catalyse sequential, stepwise transfer of reducing equivalents from substrates to oxygen and convert redox energy into a transmembrane protonmotive force (PMF) by proton translocation from a negative (N) to a positive (P) aqueous phase separated by the coupling membrane. There are three basic mechanisms by which a membrane-associated redox enzyme can generate a PMF. These are membrane anisotropic arrangement of the primary redox catalysis with: (i) vectorial electron transfer by redox metal centres from the P to the N side of the membrane; (ii) hydrogen transfer by movement of quinones across the membrane, from a reduction site at the N side to an oxidation site at the P side; (iii) a different type of mechanism based on co-operative allosteric linkage between electron transfer at the metal redox centres and transmembrane electrogenic proton translocation by apoproteins...
June 21, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28638646/crystal-structure-of-4-4-bis-3-piperidin-1-yl-prop-1-yn-1-yl-1-1-biphen-yl
#13
Anqi Walbaum, E Kim Fifer, Sean Parkin, Peter A Crooks
The title compound, C28H32N2, (I), is one of a second generation of compounds designed and synthesized based on a very potent and selective α9α10 nicotinic acetyl-choline receptor antagonist ZZ161C {1,1'-[[1,1'-biphen-yl]-4,4'-diylbis(prop-2-yne-3,1-di-yl)]bis-(3,4-di-methyl-pyridin-1-ium) bromide}, which has shown analgesic effects in a chemotherapy-induced neuropathy animal model. Compound (I) was synthesized by the reaction of 4,4'-bis-(3-bromo-prop-1-yn-1-yl)-1,1'-biphenyl with piperidine at room temperature in aceto-nitrile...
June 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28638318/maturation-behavioral-activation-and-connectivity-of-adult-born-medium-spiny-neurons-in-a-striatal-song-nucleus
#14
Jennifer Kosubek-Langer, Lydia Schulze, Constance Scharff
Neurogenesis continues in the adult songbird brain. Many telencephalic song control regions incorporate new neurons into their existing circuits in adulthood. One song nucleus that receives many new neurons is Area X. Because this striatal region is crucial for song learning and song maintenance the recruitment of new neurons into Area X could influence these processes. As an entry point into addressing this possibility, we investigated the maturation and connectivity within the song circuit and behavioral activation of newly generated Area X neurons...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28638277/titanium-dioxide-nanoparticles-as-radiosensitisers-an-in-vitro-and-phantom-based-study
#15
Esho Qasho Youkhana, Bryce Feltis, Anton Blencowe, Moshi Geso
Objective: Radiosensitisation caused by titanium dioxide nanoparticles (TiO2-NPs) is investigated using phantoms (PRESAGE(®) dosimeters) and in vitro using two types of cell lines, cultured human keratinocyte (HaCaT) and prostate cancer (DU145) cells. Methods: Anatase TiO2-NPs were synthesised, characterised and functionalised to allow dispersion in culture-medium for in vitro studies and halocarbons (PRESAGE(®) chemical compositions). PRESAGE(®) dosimeters were scanned with spectrophotometer to determine the radiation dose enhancement...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28638171/3d-printed-abdominal-aortic-aneurysm-phantom-for-image-guided-surgical-planning-with-a-patient-specific-fenestrated-endovascular-graft-system
#16
Karen M Meess, Richard L Izzo, Maciej L Dryjski, Richard E Curl, Linda M Harris, Michael Springer, Adnan H Siddiqui, Stephen Rudin, Ciprian N Ionita
Following new trends in precision medicine, Juxatarenal Abdominal Aortic Aneurysm (JAAA) treatment has been enabled by using patient-specific fenestrated endovascular grafts. The X-ray guided procedure requires precise orientation of multiple modular endografts within the arteries confirmed via radiopaque markers. Patient-specific 3D printed phantoms could familiarize physicians with complex procedures and new devices in a risk-free simulation environment to avoid periprocedural complications and improve training...
February 11, 2017: Proceedings of SPIE
https://www.readbyqxmd.com/read/28638099/brilliant-x-rays-using-a-two-stage-plasma-insertion-device
#17
J A Holloway, P A Norreys, A G R Thomas, R Bartolini, R Bingham, J Nydell, R M G M Trines, R Walker, M Wing
Particle accelerators have made an enormous impact in all fields of natural sciences, from elementary particle physics, to the imaging of proteins and the development of new pharmaceuticals. Modern light sources have advanced many fields by providing extraordinarily bright, short X-ray pulses. Here we present a novel numerical study, demonstrating that existing third generation light sources can significantly enhance the brightness and photon energy of their X-ray pulses by undulating their beams within plasma wakefields...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638059/cis-regulatory-evolution-in-prokaryotes-revealed-by-interspecific-archaeal-hybrids
#18
Carlo G Artieri, Adit Naor, Israela Turgeman-Grott, Yiqi Zhou, Ryan York, Uri Gophna, Hunter B Fraser
The study of allele-specific expression (ASE) in interspecific hybrids has played a central role in our understanding of a wide range of phenomena, including genomic imprinting, X-chromosome inactivation, and cis-regulatory evolution. However across the hundreds of studies of hybrid ASE, all have been restricted to sexually reproducing eukaryotes, leaving a major gap in our understanding of the genomic patterns of cis-regulatory evolution in prokaryotes. Here we introduce a method to generate stable hybrids between two species of halophilic archaea, and measure genome-wide ASE in these hybrids with RNA-seq...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28636361/a-machine-learning-assisted-approach-for-discovering-novel-inhibitors-targeting-bromodomain-containing-protein-4
#19
Jing Xing, Wenchao Lu, Rongfeng Liu, Yulan Wang, Yiqian Xie, Hao Zhang, Zhe Shi, Hao Jiang, Yu-Chih Liu, Kaixian Chen, Hualiang Jiang, Cheng Luo, Mingyue Zheng
Bromodomain-containing protein 4 (BRD4) is implicated in the pathogenesis of a number of different cancers, inflammatory diseases and heart failure. Much effort has been dedicated toward discovering novel scaffold BRD4 inhibitors (BRD4is) with different selectivity profiles and potential anti-resistance properties. Structure-based drug design (SBDD) and virtual screening (VS) are the most frequently used approaches. Here, we demonstrate a novel, structure-based VS approach that uses machine-learning algorithms trained on the priori structure and activity knowledge to predict the likelihood that a compound is a BRD4i based on its binding pattern with BRD4...
June 21, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28636313/iodine-iii-reagents-in-radical-chemistry
#20
Xi Wang, Armido Studer
The chemistry of hypervalent iodine(III) compounds has gained great interest over the past 30 years. Hypervalent iodine(III) compounds show valuable ionic reactivity due to their high electrophilicity but also express radical reactivity as single electron oxidants for carbon and heteroatom radical generation. Looking at ionic chemistry, these iodine(III) reagents can act as electrophiles to efficiently construct C-CF3, X-CF3 (X = heteroatom), C-Rf (Rf = perfluoroalkyl), X-Rf, C-N3, C-CN, S-CN, and C-X bonds...
June 21, 2017: Accounts of Chemical Research
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