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Evelina Cardoso, Thomas Mercier, Anna Dorothea Wagner, Krisztian Homicsko, Olivier Michielin, Kim Ellefsen-Lavoie, Laurène Cagnon, Manuel Diezi, Thierry Buclin, Nicolas Widmer, Chantal Csajka, Laurent Decosterd
A sensitive and selective method of high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS) has been developed for the simultaneous quantification of six anticancer protein kinase inhibitors (PKIs), dabrafenib, trametinib, vemurafenib, cobimetinib, pazopanib, regorafenib, and two active metabolites (regorafenib-M2 and regorafenib-M5) in human plasma. Plasma protein precipitation with methanol enables the sample extraction of 100 μL aliquot of plasma. Analytes are detected by electrospray triple-stage quadrupole mass spectrometry and quantified using the calibration curves with stable isotope-labeled internal standards...
February 8, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Jocelyn F Hafer, Katherine A Boyer
BACKGROUND: Aging is associated with a loss of mobility and altered gait mechanics. Loss of function and mobility may be due to or exacerbated by low levels of physical activity in the aged. The mechanisms linking age-related changes in physiology, altered mobility and gait may be elucidated by examining movement coordination and coordination variability. RESEARCH QUESTION: The purpose of this study was to examine the impacts of age and habitual physical activity level on segment coordination and coordination variability during gait...
February 26, 2018: Gait & Posture
Michela Balconi, Laura Gatti, Maria Elide Vanutelli
Cooperation behavior is a core question of study on social neuroscience. In the present study, inter-brain functional connectivity and cognitive performance were considered during joint which was failing. The cognitive performance and the EEG (brain oscillations from delta to beta) underlying the execution of joint-actions were recorded when dyads of participants executed synchronicity game and received reinforcing negative feedbacks A pre-feedback condition (cooperation) and a control condition (individual task, T0) were provided as well as a check for possible learning effect (time series analysis)...
March 12, 2018: Consciousness and Cognition
Ambra Masuzzo, Julien Royet
Immune responses and metabolic regulation are tightly coupled in animals, but the underlying mechanistic connections are not fully understood. In this issue of Cell Host & Microbe, Lee et al. (2018) reveal how sustained ROS production in the gut depends on an upstream metabolic switch.
March 14, 2018: Cell Host & Microbe
Vitor Cabral, Karina B Xavier
Bacterial sensing is important for perceiving environmental cues and activating responses. In this issue of Cell Host & Microbe, Hertzog et al. (2018) show that group A Streptococcus can couple the ability to respond to host cues with autoinduction of a quorum sensing system, leading to killing of bacterial competitors.
March 14, 2018: Cell Host & Microbe
Li Chen, Nathchar Naowarojna, Heng Song, Shu Wang, Jianyun Wang, Zixin Deng, Changming Zhao, Pinghua Liu
Ovothiol is a histidine thiol derivative. The biosynthesis of ovothiol involves an extremely efficient trans-sulfuration strategy. The non-heme iron enzyme OvoA catalyzed oxidative coupling be-tween cysteine and histidine is one of the key steps. Besides catalyzing the oxidative coupling between cysteine and histidine, OvoA also catalyzes the oxi-dation of cysteine to cysteine sulfinic acid (cysteine dioxygenase activity). Thus far, very little mecha-nistic information is available for OvoA-catalysis. In this report, we measured the kinetic isotope effect (KIE) in OvoA-catalysis using the isotopically sensitive branching method...
March 15, 2018: Journal of the American Chemical Society
Barry M Trost, Chris Kalnmals
Herein, we report a valuable umpolung strategy that highlights the ambiphilic nature of the bis(phenylsulfonyl)methyl synthon and demonstrates its utility as a synthetic linchpin. While the bis(phenylsulfonyl)methyl group is typically introduced as an sp3 carbon nucleophile, we demonstrate that it can also function as an effective sp2 carbon electrophile in the presence of organolithium nucleophiles. Akyl- and aryllithiums couple with the central carbon of the bis(phenylsulfonyl)methyl unit to ultimately generate trisubstituted alkenes, comprising a formal sp3-sp2 and sp2-sp2 cross-coupling between organolithiums and bis(sulfones)...
March 15, 2018: Chemistry: a European Journal
Rafał Podgórski, David Aebisher, Monika Stompor, Dominika Podgórska, Artur Mazur
The aim of this paper is a straightforward presentation of the steroidogenesis process and the most common type of congenital adrenal hyperplasia (CAH) - 21-hydroxylase deficiency - as well as the analytical diagnostic methods that are used to recognize this disease. CAH is a family of common autosomal recessive disorders characterized by impaired adrenal cortisol biosynthesis with associated androgen excess due to a deficiency of one or more enzymes in the steroidogenesis process within the adrenal cortex...
March 15, 2018: Acta Biochimica Polonica
Kai Sun, Deqiang Yang, Sihao Liu, Tianming Yang
In this paper, a wide-band low cross polarization antenna with a structure of microstrip line coupling to slot line as the balun is proposed. The radiation part of the antenna is fed by two pairs of parallel transmission line via a transition from a slot line which is coupled by a microstrip line. Because it is fed by parallel transmission lines, which is balanced-fed structure, the antenna can achieve an improved low cross-polarization performance. The height of the antenna is 0.146λ0 (λ0 is the wavelength of lowest frequency)...
2018: PloS One
Miguel R Lugo, Bronwyn Lyons, Cristina Lento, Derek J Wilson, A Rod Merrill
Scabin is a mono-ADP-ribosyltransferase enzyme and is a putative virulence factor produced by the plant pathogen, Streptomyces scabies. Previously, crystal structures of Scabin were solved in the presence and absence of substrate analogues and inhibitors. Herein, experimental (hydrogen-deuterium exchange), simulated (molecular dynamics), and theoretical (Gaussian Network Modeling) approaches were systematically applied to study the dynamics of apo-Scabin in the context of a Scabin·NAD+·DNA model. MD simulations revealed that the apo-Scabin solution conformation correlates well with the X-ray crystal structure, beyond the conformation of the exposed, mobile regions...
2018: PloS One
Dilyana Filipova, Margit Henry, Tamara Rotshteyn, Anna Brunn, Mariana Carstov, Martina Deckert, Jürgen Hescheler, Agapios Sachinidis, Gabriele Pfitzer, Symeon Papadopoulos
In skeletal muscle the coordinated actions of two mechanically coupled Ca2+ channels-the 1,4-dihydropyridine receptor (Cav1.1) and the type 1 ryanodine receptor (RYR1)-underlie the molecular mechanism of rapid cytosolic [Ca2+] increase leading to contraction. While both [Ca2+]i and contractile activity have been implicated in the regulation of myogenesis, less is known about potential specific roles of Cav1.1 and RYR1 in skeletal muscle development. In this study, we analyzed the histology and the transcriptomic changes occurring at E14...
2018: PloS One
Qiang Lu, Guanghui Liu, Chuanli Xiao, Chuanzhen Hu, Shiwu Zhang, Ronald X Xu, Kaiqin Chu, Qianming Xu, Zachary J Smith
In this paper we report the development of a cost-effective, modular, open source, and fully automated slide-scanning microscope, composed entirely of easily available off-the-shelf parts, and capable of bright field and fluorescence modes. The automated X-Y stage is composed of two low-cost micrometer stages coupled to stepper motors operated in open-loop mode. The microscope is composed of a low-cost CMOS sensor and low-cost board lenses placed in a 4f configuration. The system has approximately 1 micron resolution, limited by the f/# of available board lenses...
2018: PloS One
LaDonya Jackson, Wael Eldahshan, Susan C Fagan, Adviye Ergul
For many years, modulators of the renin angiotensin system (RAS) have been trusted by clinicians for the control of essential hypertension. It was recently demonstrated that these modulators have other pleiotropic properties independent of their hypotensive effects, such as enhancement of cognition. Within the brain, different components of the RAS have been extensively studied in the context of neuroprotection and cognition. Interestingly, a crosstalk between the RAS and other systems such as cholinergic, dopaminergic and adrenergic systems have been demonstrated...
March 15, 2018: International Journal of Molecular Sciences
Robert D Johnson, Patrizia Camelliti
The heart is a complex organ composed of multiple cell types, including cardiomyocytes and different non-myocyte populations, all working closely together to determine the hearts properties and maintain normal cardiac function. Connexins are abundantly expressed proteins that form plasma membrane hemichannels and gap junctions between cells. Gap junctions are intracellular channels that allow for communication between cells, and in the heart they play a crucial role in cardiac conduction by coupling adjacent cardiomyocytes...
March 15, 2018: International Journal of Molecular Sciences
Felix A Blyakhman, Nikita A Buznikov, Tatyana F Sklyar, Alexander P Safronov, Elizaveta V Golubeva, Andrey V Svalov, Sergey Yu Sokolov, Grigory Yu Melnikov, Iñaki Orue, Galina V Kurlyandskaya
Hydrogels are biomimetic materials widely used in the area of biomedical engineering and biosensing. Ferrogels (FG) are magnetic composites capable of functioning as magnetic field sensitive transformers and field assisted drug deliverers. FG can be prepared by incorporating magnetic nanoparticles (MNPs) into chemically crosslinked hydrogels. The properties of biomimetic ferrogels for multifunctional biosensor applications can be set up by synthesis. The properties of these biomimetic ferrogels can be thoroughly controlled in a physical experiment environment which is much less demanding than biotests...
March 15, 2018: Sensors
Biyun Ling, Chunrong Peng, Ren Ren, Zhaozhi Chu, Zhouwei Zhang, Hucheng Lei, Shanhong Xia
One of the major concerns in the development of three-dimensional (3D) electric field sensors (EFSs) is their susceptibility to cross-axis coupling interference. The output signal for each sensing axis of a 3D EFS is often coupled by electric field components from the two other orthogonal sensing axes. In this paper, a one-dimensional (1D) electric field sensor chip (EFSC) with low cross-axis coupling interference is presented. It is designed to be symmetrical, forming a pair of in-plane symmetrically-located sensing structures...
March 15, 2018: Sensors
Md Nahid Pervez, Faizan Shafiq, Zahid Sarwar, Muhammad Munib Jilani, Yingjie Cai
In this study, the influence and optimization of the factors of a non-formaldehyde resin finishing process on cotton fabric using a Taguchi-based grey relational analysis were experimentally investigated. An L27 orthogonal array was selected for five parameters and three levels by applying Taguchi's design of experiments. The Taguchi technique was coupled with a grey relational analysis to obtain a grey relational grade for evaluating multiple responses, i.e., crease recovery angle (CRA), tearing strength (TE), and whiteness index (WI)...
March 15, 2018: Materials
Daniela Sorriento, Gaetano Santulli, Michele Ciccarelli, Angela Serena Maione, Maddalena Illario, Bruno Trimarco, Guido Iaccarino
We have recently demonstrated that the amino-terminal domain of G protein coupled receptor kinase (GRK) type 5, (GRK5-NT) inhibits NFκB activity in cardiac cells leading to a significant amelioration of LVH. Since GRK5-NT is known to bind calmodulin, this study aimed to evaluate the functional role of GRK5-NT in the regulation of calcium-calmodulin-dependent transcription factors. We found that the overexpression of GRK5-NT in cardiomyoblasts significantly reduced the activation and the nuclear translocation of NFAT and its cofactor GATA-4 in response to phenylephrine (PE)...
March 15, 2018: International Journal of Molecular Sciences
Annalisa Trenti, Serena Tedesco, Carlotta Boscaro, Lucia Trevisi, Chiara Bolego, Andrea Cignarella
Estrogen plays an important role in the regulation of cardiovascular physiology and the immune system by inducing direct effects on multiple cell types including immune and vascular cells. Sex steroid hormones are implicated in cardiovascular protection, including endothelial healing in case of arterial injury and collateral vessel formation in ischemic tissue. Estrogen can exert potent modulation effects at all levels of the innate and adaptive immune systems. Their action is mediated by interaction with classical estrogen receptors (ERs), ERα and ERβ, as well as the more recently identified G-protein coupled receptor 30/G-protein estrogen receptor 1 (GPER1), via both genomic and non-genomic mechanisms...
March 15, 2018: International Journal of Molecular Sciences
Do-Hwan Lim, Seungjae Lee, Jee Yun Han, Min-Seok Choi, Jae-Sang Hong, Youngmo Seong, Young-Soo Kwon, Young Sik Lee
The steroid hormone ecdysone has a central role in the developmental transitions of insects through its control of responsive protein-coding and microRNA (miRNA) gene expression. However, the complete regulatory network controlling the expression of these genes remains to be elucidated. In this study, we performed cross-linking immunoprecipitation coupled with deep sequencing of endogenous Argonaute 1 (Ago1) protein, the core effector of the miRNA pathway, in Drosophila S2 cells. We found that regulatory interactions between miRNAs and their cognate targets were substantially altered by Ago1 in response to ecdysone signaling...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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