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https://www.readbyqxmd.com/read/28441529/mps1-regulates-kinetochore-microtubule-attachment-stability-via-the-ska-complex-to-ensure-error-free-chromosome-segregation
#1
John Maciejowski, Hauke Drechsler, Kathrin Grundner-Culemann, Edward R Ballister, Jose-Antonio Rodriguez-Rodriguez, Veronica Rodriguez-Bravo, Mathew J K Jones, Emily Foley, Michael A Lampson, Henrik Daub, Andrew D McAinsh, Prasad V Jallepalli
The spindle assembly checkpoint kinase Mps1 not only inhibits anaphase but also corrects erroneous attachments that could lead to missegregation and aneuploidy. However, Mps1's error correction-relevant substrates are unknown. Using a chemically tuned kinetochore-targeting assay, we show that Mps1 destabilizes microtubule attachments (K fibers) epistatically to Aurora B, the other major error-correcting kinase. Through quantitative proteomics, we identify multiple sites of Mps1-regulated phosphorylation at the outer kinetochore...
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28441491/a-naturally-occurring-isoform-specific-probe-for-highly-selective-and-sensitive-detection-of-human-cytochrome-p450-3a5
#2
Jing-Jing Wu, Yun-Feng Cao, Liang Feng, Yu-Qi He, James Y Hong, Tong-Yi Dou, Ping Wang, Da-Cheng Hao, Guang-Bo Ge, Ling Yang
Cytochrome P450 (CYP) 3A5 characterized with polymorphic and extensive expression in multiple tissues is the most important P450 enzyme among the minor CYP3A isoforms. However, a selective and sensitive probe for CYP3A5 remains unavailable. In this study, we identified and characterized a naturally-occurring lignan 12 (Schisantherin E) as an isoform-specific probe for selective detection of CYP3A5 activity in complex biological samples. With thorough characterization including LC-MS and NMR, we found that 12 can be metabolized by CYP3A5 to generate a major metabolite 2-O-demethylated 12...
April 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28437613/evaluating-the-role-of-multidrug-resistance-protein-3-mdr3-inhibition-in-predicting-drug-induced-liver-injury-using-125-pharmaceuticals
#3
Michael D Aleo, Falgun Shah, Kan He, Paul D Bonin, A David Rodrigues
The role of bile salt export protein (BSEP) inhibition in drug-induced liver injury (DILI) has been investigated widely, while inhibition of the canalicular multidrug resistant protein 3 (MDR3) has received less attention. This transporter plays a pivotal role in secretion of phospholipids into bile and functions coordinately with BSEP to mediate the formation of bile acid-containing biliary micelles. Therefore, inhibition of MDR3 in human hepatocytes was examined across 125 drugs (70 of Most- and 55 of No-DILI-concern)...
April 24, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28435103/magnetization-transfer-contrast-and-chemical-exchange-saturation-transfer-mri-features-and-analysis-of-the-field-dependent-saturation-spectrum
#4
Peter C M van Zijl, Wilfred W Lam, Jiadi Xu, Linda Knutsson, Greg J Stanisz
Magnetization Transfer Contrast (MTC) and Chemical Exchange Saturation Transfer (CEST) experiments measure the transfer of magnetization from molecular protons to the solvent water protons, an effect that becomes apparent as an MRI signal loss ("saturation"). This allows molecular information to be accessed with the enhanced sensitivity of MRI. In analogy to Magnetic Resonance Spectroscopy (MRS), these saturation data are presented as a function of the chemical shift of participating proton groups, e.g. OH, NH, NH2, which is called a Z-spectrum...
April 20, 2017: NeuroImage
https://www.readbyqxmd.com/read/28416470/block-ionomer-micellar-nanoparticles-from-double-hydrophilic-copolymers-classifications-and-promises-for-delivery-of-cancer-chemotherapeutics
#5
REVIEW
S S Abolmaali, A M Tamaddon, M Salmanpour, S Mohammadi, R Dinarvand
A class of double hydrophilic copolymers comprising ionic and nonionic water-soluble blocks, which are also called block ionomers, represent an interesting type of polymer assembly forming stable, homogeneous core-corona dispersions. They exhibit the solution behavior of normal polyelectrolytes, whereas assembly into micelle, vesicle or disk morphology happens by an external stimulus (pH, temperature or ionic strength) or complex formation with metal ions, ionic surfactants, polyelectrolytes, etc. Temperature, pH, redox or salt sensitivity affords a unique opportunity to control the triggered release of payloads accommodated through electrostatic interaction, coordination or chemical conjugation...
April 14, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28411469/primary-hepatocytes-from-arctic-char-salvelinus-alpinus-as-a-relevant-arctic-in-vitro-model-for-screening-contaminants-and-environmental-extracts
#6
Karina Petersen, Maria T Hultman, Knut Erik Tollefsen
Contaminants find their way to the Arctic through long-range atmospheric transport, transport via ocean currents, and through increased anthropogenic activity. Some of the typical pollutants reaching the Arctic (PAHs, PCBs) are known to induce cytochrome P450 1a (CYP1A) protein expression and ethoxyresorufin-O-deethylase (EROD) activity through the aryl hydrocarbon receptor (AhR). In addition, some endocrine disrupting chemicals (EDCs) such as estrogen mimics (xenoestrogens) have been documented in Arctic areas and they may interfere with natural sexual development and reproduction...
April 2, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28405963/multidimensional-investigation-of-bedrock-heterogeneity-unconformities-at-a-dnapl-impacted-site
#7
Colby M Steelman, Jessica R Meyer, Beth L Parker
Organic solvent (i.e., dense nonaqueous phase liquid, DNAPL) migration in the subsurface is known to be extremely sensitive to geologic heterogeneity. There is often a focus on heterogeneity that results from changing depositional conditions over short spatial scales. Similar or even more extreme spatial heterogeneity can result postdeposition due to erosional processes. This study applies a synergistic approach based on a combination of high-resolution lithologic logs of continuous cores, borehole geophysical logs, surface electrical resistivity, and seismic refraction tomography models to assess spatial heterogeneity in a shallow bedrock sequence subject to multiple unconformities and contaminated with a mixture of organic chemicals...
April 12, 2017: Ground Water
https://www.readbyqxmd.com/read/28401767/expanded-target-chemical-analysis-reveals-extensive-mixed-organic-contaminant-exposure-in-u-s-streams
#8
Paul M Bradley, Celeste A Journey, Kristin M Romanok, Larry B Barber, Herbert T Buxton, William T Foreman, Edward T Furlong, Susan T Glassmeyer, Michelle L Hladik, Luke R Iwanowicz, Daniel K Jones, Dana W Kolpin, Kathryn M Kuivila, Keith A Loftin, Marc A Mills, Michael T Meyer, James L Orlando, Timothy J Reilly, Kelly L Smalling, Daniel L Villeneuve
Surface water from 38 streams nationwide was assessed using 14 target-organic methods (719 compounds). Designed-bioactive anthropogenic contaminants (biocides, pharmaceuticals) comprised 57% of 406 organics detected at least once. The 10 most-frequently detected anthropogenic-organics included eight pesticides (desulfinylfipronil, AMPA, chlorpyrifos, dieldrin, metolachlor, atrazine, CIAT, glyphosate) and two pharmaceuticals (caffeine, metformin) with detection frequencies ranging 66-84% of all sites. Detected contaminant concentrations varied from less than 1 ng L(-1) to greater than 10 μg L(-1), with 77 and 278 having median detected concentrations greater than 100 ng L(-1) and 10 ng L(-1), respectively...
April 12, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28401081/zinc-in-pancreatic-islet-biology-insulin-sensitivity-and-diabetes
#9
REVIEW
Wolfgang Maret
About 20 chemical elements are nutritionally essential for humans with defined molecular functions. Several essential and nonessential biometals are either functional nutrients with antidiabetic actions or can be diabetogenic. A key question remains whether changes in the metabolism of biometals and biominerals are a consequence of diabetes or are involved in its etiology. Exploration of the roles of zinc (Zn) in this regard is most revealing because 80 years of scientific discoveries link zinc and diabetes...
March 2017: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/28399373/extended-ensemble-approach-to-transferable-potentials-for-low-resolution-coarse-grained-models-of-ionomers
#10
Joseph F Rudzinski, Keran Lu, Scott T Milner, Janna K Maranas, William G Noid
We develop an extended ensemble method for constructing transferable, low-resolution coarse-grained (CG) models of polyethylene-oxide (PEO)-based ionomer chains with varying composition at multiple temperatures. In particular, we consider ionomer chains consisting of 4 isophthalate groups, which may be neutral or sulfonated, that are linked by 13 PEO repeat units. The CG models represent each isophthalate group with a single CG site and also explicitly represent the diffusing sodium counterions but do not explicitly represent the PEO backbone...
April 24, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28378767/the-need-to-compare-assessing-the-level-of-agreement-of-three-high-throughput-assays-against-plasmodium-falciparum-mature-gametocytes
#11
Leonardo Lucantoni, Sasdekumar Loganathan, Vicky M Avery
Whole-cell High-Throughput Screening (HTS) is a key tool for the discovery of much needed malaria transmission blocking drugs. Discrepancies in the reported outcomes from various HTS Plasmodium falciparum gametocytocidal assays hinder the direct comparison of data and ultimately the interpretation of the transmission blocking potential of hits. To dissect the underlying determinants of such discrepancies and assess the impact that assay-specific factors have on transmission-blocking predictivity, a 39-compound subset from the Medicines for Malaria Venture Malaria Box was tested in parallel against three distinct mature stage gametocytocidal assays, under strictly controlled parasitological, chemical, temporal and analytical conditions resembling the standard membrane feeding assay (SMFA)...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28371759/broadband-quantitative-nqr-for-authentication-of-vitamins-and-dietary-supplements
#12
Cheng Chen, Fengchao Zhang, Swarup Bhunia, Soumyajit Mandal
We describe hardware, pulse sequences, and algorithms for nuclear quadrupole resonance (NQR) spectroscopy of medicines and dietary supplements. Medicine and food safety is a pressing problem that has drawn more and more attention. NQR is an ideal technique for authenticating these substances because it is a non-invasive method for chemical identification. We have recently developed a broadband NQR front-end that can excite and detect (14)N NQR signals over a wide frequency range; its operating frequency can be rapidly set by software, while sensitivity is comparable to conventional narrowband front-ends over the entire range...
May 2017: Journal of Magnetic Resonance
https://www.readbyqxmd.com/read/28371754/extending-the-distributed-lag-model-framework-to-handle-chemical-mixtures
#13
Ghalib A Bello, Manish Arora, Christine Austin, Megan K Horton, Robert O Wright, Chris Gennings
Distributed Lag Models (DLMs) are used in environmental health studies to analyze the time-delayed effect of an exposure on an outcome of interest. Given the increasing need for analytical tools for evaluation of the effects of exposure to multi-pollutant mixtures, this study attempts to extend the classical DLM framework to accommodate and evaluate multiple longitudinally observed exposures. We introduce 2 techniques for quantifying the time-varying mixture effect of multiple exposures on an outcome of interest...
March 31, 2017: Environmental Research
https://www.readbyqxmd.com/read/28371153/multiplexed-nucleic-acid-hybridization-assays-using-single-fret-pair-distance-tuning
#14
Xue Qiu, Jiajia Guo, Zongwen Jin, Igor L Medintz, Niko Hildebrandt
Multiplexed photoluminescence (PL) detection plays an important role in chemical and biological sensing. Here, it is shown that time-gated (TG) detection of a single terbium-donor-based Förster resonance energy transfer (FRET) pair can be used to selectively quantify low nanomolar concentrations of multiple DNAs or microRNAs in a single sample. This study demonstrates the applicability of single-TG-FRET-pair multiplexing for molecular (Tb-to-dye) and nanoparticle (Tb-to-quantum-dot) biosensing. Both systems use acceptor-sensitization and donor-quenching for quantifying biomolecular recognition and modification of the donor-acceptor distance for tuning the PL decays...
April 3, 2017: Small
https://www.readbyqxmd.com/read/28370680/rapid-and-sensitive-determination-of-multiple-endocrine-disrupting-chemicals-by-ultrasound-assisted-in-situ-derivatization-dispersive-liquid-liquid-microextraction-coupled-with-uhplc-ms-ms
#15
Na Wei, Zhenjia Zheng, Yuhua Wang, Yanduo Tao, Yun Shao, Shuyun Zhu, Jinmao You, Xian-En Zhao
RATIONALE: Endocrine disrupting chemicals (EDCs) in environment samples and food stuffs are an increasing serious public health issue due to their potency to interfere and deregulate several aspects of the endocrine system. Because of their extremely low abundance, it remains a challenging task to develop a sensitive detection method. METHODS: 4'-Carbonyl chloride rosamine (CCR) was used as a derivatization reagent for EDCs for the first time. A new ultrasound-assisted in situ derivatization-dispersive liquid-liquid microextraction (UA-DLLME with in situ derivatization) method for multiple EDCs including five estrogens, two alkylphenols, eight bisphenols, seven parabens and triclosan coupled with ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) has been developed and validated...
March 31, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28370322/interlaboratory-evaluation-of-a-multiplexed-high-information-content-in-vitro-genotoxicity-assay
#16
Steven M Bryce, Derek T Bernacki, Jeffrey C Bemis, Richard A Spellman, Maria E Engel, Maik Schuler, Elisabeth Lorge, Pekka T Heikkinen, Ulrike Hemmann, Véronique Thybaud, Sabrina Wilde, Nina Queisser, Andreas Sutter, Andreas Zeller, Melanie Guérard, David Kirkland, Stephen D Dertinger
We previously described a multiplexed in vitro genotoxicity assay based on flow cytometric analysis of detergent-liberated nuclei that are simultaneously stained with propidium iodide and labeled with fluorescent antibodies against p53, γH2AX, and phospho-histone H3. Inclusion of a known number of microspheres provides absolute nuclei counts. The work described herein was undertaken to evaluate the interlaboratory transferability of this assay, commercially known as MultiFlow(®) DNA Damage Kit-p53, γH2AX, Phospho-Histone H3...
April 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28368054/crispr-cas9-mediated-efficient-genome-editing-via-blastospore-based-transformation-in-entomopathogenic-fungus-beauveria-bassiana
#17
Jingjing Chen, Yiling Lai, Lili Wang, Suzhen Zhai, Gen Zou, Zhihua Zhou, Chunlai Cui, Sibao Wang
Beauveria bassiana is an environmentally friendly alternative to chemical insecticides against various agricultural insect pests and vectors of human diseases. However, its application has been limited due to slow kill and sensitivity to abiotic stresses. Understanding of the molecular pathogenesis and physiological characteristics would facilitate improvement of the fungal performance. Loss-of-function mutagenesis is the most powerful tool to characterize gene functions, but it is hampered by the low rate of homologous recombination and the limited availability of selectable markers...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28349691/synergetic-sers-enhancement-in-a-metal-like-metal-double-shell-structure-for-sensitive-and-stable-application
#18
Rongcheng Ban, Yingjian Yu, Meng Zhang, Jun Yin, Binbin Xu, De-Yin Wu, Min Wu, Zhigang Zhang, Huiling Tai, Jing Li, Junyong Kang
Because of either thermal/chemical instability or high optical loss in noble metal nanostructures, searching for alternative plasmonic materials is becoming more and more urgent, considering the practical biosensing applications under various extreme conditions. In this work, titanium nitride (TiN), a low-loss metal-like material with both excellent thermal and excellent chemical stabilities, was proposed to composite with Ag hollow nanosphere (HNS) nanostructures as an effective surface-enhanced Raman scattering (SERS) substrate to realize both highly sensitive and highly stable molecular detection...
April 6, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28343395/investigation-of-the-spectroscopic-information-of-functional-groups-related-to-carbohydrate-in-different-morphological-fractions-of-corn-stover-and-their-relationship-to-nutrient-supply-and-biodegradation-characteristics
#19
Hangshu Xin, Xue Ding, Liyang Zhang, Xiaofan Wang, Yonggen Zhang, Fang Sun
The objectives of this study were to investigate 1) nutritive values and biodegradation characteristics and 2) mid-IR spectroscopic features within the regions associated with carbohydrate functional groups (including cellulosic component (CELC); structural carbohydrate (STCHO) and total carbohydrate (CHO)) in different morphological fractions of corn stover. Furthermore, correlation and regression analyses were also applied to find out the relationship between nutritional values and spectroscopic parameters...
March 25, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28336905/a-nanostructured-matrices-assessment-to-study-drug-distribution-in-solid-tumor-tissues-by-mass-spectrometry-imaging
#20
Silvia Giordano, Valentina Pifferi, Lavinia Morosi, Melinda Morelli, Luigi Falciola, Giuseppe Cappelletti, Sonja Visentin, Simonetta A Licandro, Roberta Frapolli, Massimo Zucchetti, Roberta Pastorelli, Laura Brunelli, Maurizio D'Incalci, Enrico Davoli
The imaging of drugs inside tissues is pivotal in oncology to assess whether a drug reaches all cells in an adequate enough concentration to eradicate the tumor. Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) is one of the most promising imaging techniques that enables the simultaneous visualization of multiple compounds inside tissues. The choice of a suitable matrix constitutes a critical aspect during the development of a MALDI-MSI protocol since the matrix ionization efficiency changes depending on the analyte structure and its physico-chemical properties...
March 21, 2017: Nanomaterials
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