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https://www.readbyqxmd.com/read/28550769/mk-8776-a-novel-chk1-inhibitor-exhibits-an-improved-radiosensitizing-effect-compared-to-ucn-01-by-exacerbating-radiation-induced-aberrant-mitosis
#1
Motofumi Suzuki, Tohru Yamamori, Tomoki Bo, Yuri Sakai, Osamu Inanami
Checkpoint kinase 1 (Chk1) is an evolutionarily conserved serine/threonine kinase that plays an important role in G2/M checkpoint signaling. Here, we evaluate the radiosensitizing effects of a novel selective Chk1 inhibitor MK-8776, comparing its efficacy with a first-generation Chk1 inhibitor UCN-01, and attempt to elucidate the mechanism of radiosensitization. In a clonogenic survival assay, MK-8776 demonstrated a more pronounced radiosensitizing effect than UCN-01, with lower cytotoxicity. Importantly, radiosensitization by MK-8776 can be achieved at doses as low as 2...
May 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28550201/the-influence-of-mhc-class-ii-on-b-cell-defects-induced-by-invariant-chain-cd74-n-terminal-fragments
#2
Janna Schneppenheim, Ann-Christine Loock, Susann Hüttl, Michaela Schweizer, Renate Lüllmann-Rauch, Hans-Heinrich Oberg, Philipp Arnold, Christian H K Lehmann, Diana Dudziak, Dieter Kabelitz, Ralph Lucius, Ana-Maria Lennon-Duménil, Paul Saftig, Bernd Schröder
The invariant chain (CD74) mediates assembly and targeting of MHC class II (MHCII) complexes. In endosomes, CD74 undergoes sequential degradation by different proteases, including cathepsin S (CatS) and the intramembrane protease signal peptide peptidase-like 2a (SPPL2a). In their absence, CD74 N-terminal fragments (NTFs) accumulate. In SPPL2a(-/-) B cells, such an NTF impairs endosomal trafficking and BCR signal transduction. In mice, this leads to a loss of splenic B cells beyond the transitional stage 1...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28549950/spray-stability-of-self-assembled-filaments-for-delivery
#3
Abdullah Mahmud, Takamasa Harada, Karthikan Rajagopal, David A Christian, Praful Nair, Ryan Murphy, Dennis E Discher
Filamentous viruses are common in nature and efficiently deliver - sometimes via aerosol - genetic material, viral proteins, and other factors to animals and plants. Aerosolization can be a severe physicochemical test of the stability of any filamentous assembly whether it is made from natural polymers such as viral proteins or synthetic polymers. Here, worm-like "filomicelles" that self-assemble in water from amphiphilic block copolymers were investigated as aerosolized delivery vehicles. After spraying and drying, fluorophore-loaded filomicelles that were originally ~10-20μm long could be imaged as 2-5μm long fragments that survived rehydration on natural and artificial surfaces (i...
May 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28549935/the-conserved-domain-in-morf-proteins-has-distinct-affinities-to-the-ppr-and-e-elements-in-ppr-rna-editing-factors
#4
Eszter Bayer-Császár, Sascha Haag, Anja Jörg, Franziska Glass, Barbara Härtel, Toshihiro Obata, Etienne H Meyer, Axel Brennicke, Mizuki Takenaka
In plant organelles specific nucleotide motifs at C to U RNA editing sites are recognized by the PLS-class of pentatricopeptide repeat (PPR) proteins, which are additionally characterized by a C-terminal E domain. The PPR elements bind the nucleotides in the target RNA, while the function of the E domain has remained unknown. At most sites RNA editing also requires multiple organellar RNA editing factor (MORF) proteins. To understand how these two types of proteins are involved in RNA editing complexes, we systematically analyzed their protein-protein interactions...
May 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28549925/intracellular-domain-contacts-contribute-to-ecadherin-constitutive-dimerization-in-the-plasma-membrane
#5
Deo R Singh, Fozia Ahmed, Sarvenaz Sarabipour, Kalina Hristova
Epithelial cadherin (Ecadherin) is responsible for the intercellular cohesion of epithelial tissues. It forms lateral clusters within adherens cell-cell junctions, but its association state outside these clusters is unknown. Here we use a quantitative FRET approach to show that Ecadherin forms constitutive dimers, and that these dimers exist independently of the actin cytosletelon or cytoplasmic proteins. The dimers are stabilized by inter-molecular contacts that occur along the entire length of Ecadherin, with the intracellular domains having a surprisingly strong favorable contribution...
May 23, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28549867/integrated-testing-strategies-can-be-optimal-for-chemical-risk-classification
#6
Marko Raseta, Jon Pitchford, James Cussens, John Doe
There is an urgent need to refine strategies for testing the safety of chemical compounds. This need arises both from the financial and ethical costs of animal tests, but also from the opportunities presented by new in-vitro and in-silico alternatives. Here we explore the mathematical theory underpinning the formulation of optimal testing strategies in toxicology. We show how the costs and imprecisions of the various tests, and the variability in exposures and responses of individuals, can be assembled rationally to form a Markov Decision Problem...
May 23, 2017: Mathematical Biosciences
https://www.readbyqxmd.com/read/28549650/effect-of-picalm-rs3851179-polymorphism-on-the-default-mode-network-function-in-mild-cognitive-impairment
#7
Ding-Ming Sun, Hai-Feng Chen, Qi-Long Zuo, Fan Su, Feng Bai, Chun-Feng Liu
Alterations in default mode network (DMN) functional connectivity (FC) might accompany the dysfunction of Alzheimer's disease (AD). Indeed, episodic memory impairment is a hallmark of AD, and mild cognitive impairment (MCI) has been associated with a high risk for AD. Phosphatidylinositol-binding clathrin assembly protein (PICALM) (rs3851179) has been associated with AD; in particular, the A allele may serve a protective role, while the G allele serves as a strong genetic risk factor. Therefore, the identification of genetic polymorphisms associated with the DMN is required in MCI subjects...
May 23, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28549454/genomic-adaptation-to-agricultural-environments-cabbage-white-butterflies-pieris-rapae-as-a-case-study
#8
Kristin L Sikkink, Megan E Kobiela, Emilie C Snell-Rood
BACKGROUND: Agricultural environments have long presented an opportunity to study evolution in action, and genomic approaches are opening doors for testing hypotheses about adaptation to crops, pesticides, and fertilizers. Here, we begin to develop the cabbage white butterfly (Pieris rapae) as a system to test questions about adaptation to novel, agricultural environments. We focus on a population in the north central United States as a unique case study: here, canola, a host plant, has been grown during the entire flight period of the butterfly over the last three decades...
May 26, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28549295/structural-characterization-of-astaxanthin-aggregates-as-revealed-by-analysis-and-simulation-of-optical-spectra
#9
Liping Lu, Taoping Hu, Zhigang Xu
Carotenoids can self-assemble in hydrated polar solvents to form J- or H-type aggregates, inducing dramatic changes in photophysical properties. Here, we measured absorption and emission spectra of astaxanthin in ethanol-water solution using ultraviolet-visible and fluorescence spectrometers. Two types of aggregates were distinguished in mixed solution at different water contents by absorption spectra. After addition of water, all probed samples immediately formed H-aggregates with maximum blue shift of 31nm...
May 15, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28549266/self-cascade-reaction-catalyzed-by-cuo-nanoparticle-based-dual-functional-enzyme-mimics
#10
Ai-Ling Hu, Hao-Hua Deng, Xiao-Qing Zheng, Yan-Yu Wu, Xiu-Ling Lin, Ai-Lin Liu, Xing-Hua Xia, Hua-Ping Peng, Wei Chen, Guo-Lin Hong
It is desirable but challenging to assemble various biomimetic properties into a functional catalytic cascade system. In this work, cupric oxide nanoparticles were investigated as oxidase mimics for the aerobic oxidation of cysteine to cystine with the generation of hydrogen peroxide. Coupling this property with the peroxidase-like activity of CuO nanoparticles, we constructed a self-organized cascade reaction system based on a single-component nanozyme, which includes the oxidation of cysteine to yield cystine and hydrogen peroxide and the hydrogen peroxide-mediated oxidation of terephthalic acid to produce a fluorescence change...
May 19, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28549256/assembly-and-inhibitory-activity-of-monovalent-mannosides-terminated-with-aromatic-methyl-esters-the-effect-of-naphthyl-groups
#11
Hussein Al-Mughaid, Raed M Al-Zoubi, Maha Khazaaleh, T Bruce Grindley
A series of monovalent α-D-mannoside ligands terminated with aromatic methyl esters have been synthesized in excellent yields using the Cu(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition ("click chemistry"). These mannosides were designed to have a unique aglycone moiety (tail) that combines a triazole ring attached to aromatic methyl esters via a six carbon alkyl chain. The mannose unit of these ligands was linked at the ortho, meta, and para positions of substituted methyl benzoates and 1-, 3-, and 6-substituted methyl 2-napthaoates...
March 29, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28549217/surface-enhanced-raman-scattering-active-gold-nanoparticles-with-enzyme-mimicking-activities-for-measuring-glucose-and-lactate-in-living-tissues
#12
Yihui Hu, Hanjun Cheng, Xiaozhi Zhao, Jiangjiexing Wu, Faheem Muhammad, Shichao Lin, Jian He, Liqi Zhou, Chengping Zhang, Yu Deng, Peng Wang, Zhengyang Zhou, Shuming Nie, Hui Wei
Gold nanoparticles (AuNPs) with simultaneous plasmonic and biocatalytic properties provide a promising approach to developing versatile bioassays. However, the combination of AuNPs' intrinsic enzyme mimicking properties with their surface-enhanced Ra-man scattering (SERS) activities has yet to be explored. Here we designed a peroxidase mimicking nanozyme by in situ growing AuNPs into a highly porous and thermally stable metal-organic framework (MOF) called MIL-101. The obtained AuNPs@MIL-101 nanozymes acted as the peroxidase mimics to oxidize Raman inactive reporter leucomalachite green (LMG) into the active malachite green (MG) with hydrogen peroxide, and simultaneously as the SERS substrates to enhance the Raman signals of the as-produced MG...
May 26, 2017: ACS Nano
https://www.readbyqxmd.com/read/28549198/de-novo-transcriptome-assembly-of-sugarcane-leaves-submitted-to-prolonged-water-deficit-stress
#13
A A Belesini, F M S Carvalho, B R Telles, G M de Castro, P F Giachetto, J S Vantini, S D Carlin, J O Cazetta, D G Pinheiro, M I T Ferro
Sugarcane production is strongly influenced by drought, which is a limiting factor for agricultural productivity in the world. In this study, the gene expression profiles obtained by de novo assembly of the leaf transcriptome of two sugarcane cultivars that differ in their physiological response to water deficit were evaluated by the RNA-Seq method: drought-tolerant cultivar (SP81-3250) and drought-sensitive cultivar (RB855453). For this purpose, plants were grown in a greenhouse for 60 days and were then submitted to three treatments: control (-0...
May 25, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28549068/oligodendroglial-myelination-requires-astrocyte-derived-lipids
#14
Nutabi Camargo, Andrea Goudriaan, Anne-Lieke F van Deijk, Willem M Otte, Jos F Brouwers, Hans Lodder, David H Gutmann, Klaus-Armin Nave, Rick M Dijkhuizen, Huibert D Mansvelder, Roman Chrast, August B Smit, Mark H G Verheijen
In the vertebrate nervous system, myelination of axons for rapid impulse propagation requires the synthesis of large amounts of lipids and proteins by oligodendrocytes and Schwann cells. Myelin membranes are thought to be cell-autonomously assembled by these axon-associated glial cells. Here, we report the surprising finding that in normal brain development, a substantial fraction of the lipids incorporated into central nervous system (CNS) myelin are contributed by astrocytes. The oligodendrocyte-specific inactivation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), an essential coactivator of the transcription factor SREBP and thus of lipid biosynthesis, resulted in significantly retarded CNS myelination; however, myelin appeared normal at 3 months of age...
May 2017: PLoS Biology
https://www.readbyqxmd.com/read/28548926/preclinical-study-of-cc223-as-a-potential-anti-ovarian-cancer-agent
#15
Zhenzhen Jin, Huanfu Niu, Xuenan Wang, Lei Zhang, Qin Wang, Aijun Yang
Aberrant activation of mTOR contributes to ovarian cancer progression. CC223 is a novel and potent mTOR kinase inhibitor. The current study tested its activity against human ovarian cancer cells. We showed that CC223, at nM concentrations, inhibited survival and proliferation of established/primary human ovarian cancer cells. Further, significant apoptosis activation was observed in CC223-treated ovarian cancer cells. CC223 disrupted assembly of mTOR complex 1 (mTORC1) and mTORC2 in SKOV3 cells. Meanwhile, activation of mTORC1 and mTORC2 was almost completely blocked by CC223...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548881/constraints-drivers-and-implications-of-influenza-a-virus-reassortment
#16
Anice C Lowen
Influenza A viruses are constantly changing. This change accounts for seasonal epidemics, infrequent pandemics, and zoonotic outbreaks. A major mechanism underlying the genetic diversification of influenza A virus is reassortment of intact gene segments between coinfecting viruses. This exchange is possible because of the segmented nature of the viral genome. Here, I first consider the constraints and drivers acting on influenza A virus reassortment, including the likelihood of coinfection at the host and cellular levels, mixing and assembly of heterologous gene segments within coinfected cells, and the fitness associated with reassortant genotypes...
May 26, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28548856/decorated-cyclopentadienes-from-acetylene-and-ketones-in-just-two-steps
#17
Elena Yu Schmidt, Ivan A Bidusenko, Igor' A Ushakov, Alexander V Vashchenko, Boris A Trofimov
The products of the one-pot assembly of acetylene and ketones in the KOH/DMSO system, 7-methylene-6,8-dioxabicyclo[3.2.1]octanes, undergo an acid-catalyzed (CF3COOH, room temperature) rearrangement to rarely substituted cyclopentadienes in good-to-excellent yields. The mechanism of the rearrangement has been supported by the isolation and corresponding transformations of two intermediates.
May 26, 2017: Organic Letters
https://www.readbyqxmd.com/read/28548841/light-absorption-by-brown-carbon-in-the-southeastern-united-states-is-ph-dependent
#18
Sabrina M Phillips, Aleia D Bellcross, Geoffrey D Smith
Light-absorbing organic material, or "brown carbon" (BrC), can significantly influence the effect that aerosols have on climate. Here, we investigate how changing pH affects the absorption spectra of water-soluble BrC from ambient particulate matter smaller than 2.5 μm collected in Athens, Georgia, in the spring and fall of 2016, including samples from nearby wildfires. We find that absorption increases 10% per pH unit from pH 2 to pH 12 with a broad, featureless tail at visible wavelengths, where the largest fractional increase is also observed...
May 26, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28548819/tuning-the-properties-of-polymer-capsules-for-cellular-interactions
#19
Huanli Sun, Jiwei Cui, Yi Ju, Xi Chen, Edgar H H Wong, Jenny Tran, Greg G Qiao, Frank Caruso
Particle-cell interactions are governed by, among other factors, the composition and surface properties of the particles. Herein, we report the preparation of various polymer capsules with different compositions and properties via atom transfer radical polymerization mediated continuous assembly of polymers (CAPATRP), where the cellular interactions of these capsules, particularly fouling and specific targeting, are examined by flow cytometry and deconvolution microscopy. Acrylated eight-arm poly(ethylene glycol) (8-PEG) and poly(N-(2-hydroxypropyl)-methacrylamide) (PHPMA) as well as methacrylated hyaluronic acid (HA), poly(glutamic acid) (PGA), and poly(methacrylic acid) (PMA) are used as macro-cross-linkers to obtain a range of polymer capsules with different compositions (PEG, PHPMA, HA, PGA, and PMA)...
May 26, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28548666/zinc-and-the-iron-donor-frataxin-regulate-oligomerization-of-the-scaffold-protein-to-form-new-fe-s-cluster-assembly-centers
#20
B K Galeano, W Ranatunga, O Gakh, D Y Smith, J R Thompson, G Isaya
Early studies of the bacterial Fe-S cluster assembly system provided structural details for how the scaffold protein and the cysteine desulfurase interact. This work and additional work on the yeast and human systems elucidated a conserved mechanism for sulfur donation but did not provide any conclusive insights into the mechanism for iron delivery from the iron donor, frataxin, to the scaffold. We previously showed that oligomerization is a mechanism by which yeast frataxin (Yfh1) can promote assembly of the core machinery for Fe-S cluster synthesis both in vitro and in cells, in such a manner that the scaffold protein, Isu1, can bind to Yfh1 independent of the presence of the cysteine desulfurase, Nfs1...
May 26, 2017: Metallomics: Integrated Biometal Science
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