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Mary J Sabulski, Sean E Pidgeon, Marcos M Pires
Agents with novel mechanisms of action are needed to complement traditional antibiotics. Towards these goals, we have exploited the surface-homing properties of vancomycin to tag the surface of Gram-positive pathogens with immune cell attractants in two unique modes. First, vancomycin was conjugated to the small molecule hapten 2,4-dinitrophenol (DNP) to promote bacterial opsonization. Second, we built on these results by improving the tagging specificity and mechanism of incorporation by coupling it to a sortase A substrate peptide...
October 1, 2017: Chemical Science
Hassan Sharifiyazdi, Abdolah Mirzaei, Zahra Ghanaatian
Follicle stimulating hormone (FSH) is released from the anterior pituitary gland and has an important role in female fertility. As FSH is a glycoprotein polypeptide hormone which cannot pass through the cell membrane, its influence on target cells must be mediated by the FSH receptor (FSHR). Accordingly, any kind of mutation in FSHR can affect reproduction in dairy cows. In this study, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for recognition of a point mutation (A/G: position -278) located in the FSHR gene in Iranian dairy cows...
November 6, 2017: Animal Reproduction Science
Tracy E Williams, Patricia B Howard
OBJECTIVE: The aims of this article were to describe the implementation of an academic-practice partnership for healthcare system workforce development and provide preliminary outcomes of the associated pilot study. BACKGROUND: The demand for cross-continuum healthcare delivery models necessitates creation of workforce development structures for advanced practice nursing. METHODS: An academic-practice partnership specified enrollment of 5 cohorts of BSN staff nurses in a 3-year DNP program...
December 2017: Journal of Nursing Administration
Karen Hande, Julia C Phillippi
No abstract text is available yet for this article.
November 13, 2017: Nurse Educator
Peter Niedbalski, Christopher R Parish, Qing Wang, Zahra Hayati, Likai Song, Andre F Martins, A Dean Sherry, Lloyd Laporca Lumata
Optimal efficiency of dissolution dynamic nuclear polarization (DNP) is essential to provide the required high sensitivity enhancements for in vitro and in vivo hyperpolarized 13C nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI). At the nexus of the DNP process are the free electrons which provide the high spin alignment that is transferred to the nuclear spins. Without changing DNP instrumental conditions, one way to improve 13C DNP efficiency is by adding trace amounts of paramagnetic additives such as lanthanide (e...
November 10, 2017: Journal of Physical Chemistry. A
Thomas Wiegand, Wei-Chih Liao, Ta Chung Ong, Alexander Däpp, Riccardo Cadalbert, Christophe Copéret, Anja Böckmann, Beat H Meier
DNP (dynamic nuclear polarization)-enhanced solid-state NMR is employed to directly detect protein-DNA and protein-ATP interactions and identify the residue type establishing the intermolecular contacts. While conventional solid-state NMR can detect protein-DNA interactions in large oligomeric protein assemblies in favorable cases, it typically suffers from low signal-to-noise ratios. We show here, for the oligomeric DnaB helicase from Helicobacter pylori complexed with ADP and single-stranded DNA, that this limitation can be overcome by using DNP-enhanced spectroscopy...
November 8, 2017: Journal of Biomolecular NMR
Rivkah Tamar Rogawski, Ivan V Sergeyev, Yinglu Zhang, Timothy Hoang Tran, Yongjun Li, Liang Tong, Ann E McDermott
We characterize the effect of specifically bound biradicals on the NMR spectra of dihydrofolate reductase (DHFR) from E. coli. Dynamic nuclear polarization methods enhance the signal-to-noise of solid state NMR experiments by transferring polarization from unpaired electrons of biradicals to nuclei. There has been recent interest in co-localizing the paramagnetic polarizing agents with the analyte of interest through covalent or non-covalent specific interactions. This experimental approach broadens the scope of dynamic nuclear polarization methods by offering the possibility of selective signal enhancements and the potential to work in a broad range of environments...
November 8, 2017: Journal of Physical Chemistry. B
Indu Jaiswal, Amita Jain, Sanjeev Kumar Verma, Pooja Singh, Surya Kant, Mastan Singh
BACKGROUND: Mycobacterium can develop drug resistance (DR) by mutation of its existing gene. However, the existence of DR without mutation shows the need to look for an alternative mechanism such as the role of efflux pumps. In this study, we examined the effect of efflux pump inhibitors on isoniazid (INH) susceptibility in clinical isolates of Mycobacterium tuberculosis (Mtb). MATERIALS AND METHODS: Resazurin microtiter assay was used to examine the effect of efflux pump inhibitors on minimum inhibitory concentration (MIC) levels of INH in eighteen Mtb clinical isolates...
November 2017: Lung India: Official Organ of Indian Chest Society
Teobaldo Cuya, Leonardo Baptista, Tanos Celmar Costa França
Components of ginger (Zingiber officinale) extracts have been described as potential new drug candidates against Alzheimer disease (AD), able to interact with several molecular targets related to the AD treatment. However, there are very few theoretical studies in literature on the possible mechanisms of action by which these compounds can work as potential anti-AD drugs. For this reason, we performed here docking, molecular dynamic simulations and mmpbsa calculations on 4 components of ginger extracts former reported as active inhibitors of human acetylcholinesterase (HssAChE), and compared our results to the known HssAChE inhibitor and commercial drug in use against AD, donepezil (DNP)...
November 3, 2017: Journal of Biomolecular Structure & Dynamics
Sheetal K Jain, Guinevere Mathies, Robert G Griffin
Dynamic nuclear polarization (DNP) is theoretically able to enhance the signal in nuclear magnetic resonance (NMR) experiments by a factor γe/γn, where γ's are the gyromagnetic ratios of an electron and a nuclear spin. However, DNP enhancements currently achieved in high-field, high-resolution biomolecular magic-angle spinning NMR are well below this limit because the continuous-wave DNP mechanisms employed in these experiments scale as ω0(-n) where n ∼ 1-2. In pulsed DNP methods, such as nuclear orientation via electron spin-locking (NOVEL), the DNP efficiency is independent of the strength of the main magnetic field...
October 28, 2017: Journal of Chemical Physics
Injeong Cho, Hyun-Ok Song, Jeong Hoon Cho
The uncoupling protein 4 (ucp-4) gene is involved in agedependent neurodegeneration in C. elegans. Therefore, we aimed to investigate the mechanism underlying the association between mitochondrial uncoupling and neurodegeneration by examining the effects of uncoupling agents and ucp-4 overexpression in C. elegans. Treatment with either DNP or CCCP improved neuronal defects in wild type during aging.Uncoupling agents also restored neuronal phenotypes of ucp-4 mutants to those exhibited by wild type, while ucp-4 overexpression attenuated the severity of age-dependent neurodegeneration...
October 27, 2017: Molecules and Cells
Alexander J Leeder, Lynda J Brown, Johanna Becker-Baldus, Michaela Mehler, Clemens Glaubitz, Richard C D Brown
Three all-trans retinals containing multiple (13) C labels have been synthesised to enable DNP enhanced solid-state MAS NMR studies of novel microbial retinylidene membrane proteins including proteorhodpsin and channelrhodopsin. The synthetic aproaches allowed specific introduction of (13) C labels in ring substituents and at different positions in the polyene chain to probe structural features such as ring orientation and interaction of the chromophore with the protein in the ground state and in photointermediates...
October 28, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
Song Chen, Hongmei Li, Peng Hou
An imidazo [1,5-α]pyridine-based fluorescent probe MIPY-DNP with a large Stokes shift (173 nm) for the sensing of thiophenols in aqueous medium has been developed. This probe with 2,4-dinitrophenyl ether as a highly thiophenol-selective group was constructed based on the combination of PET and ESIPT mechanisms. Upon the treatment with thiophenols, MIPY-DNP produced a remarkable fluorescence enhancement (209-fold) at 478 nm. The detect limit for thiophenols was calculated to be as low as 5.6 nM. Importantly, the practical utility of MIPY-DNP for the selective detection of thiophenols has been successfully demonstrated in both real water samples and living cells...
November 15, 2017: Analytica Chimica Acta
David Guarin, Sina Marhabaie, Alberto Rosso, Daniel Abergel, Geoffrey Bodenhausen, Konstantin L Ivanov, Dennis Kurzbach
Dynamic nuclear polarization (DNP) embraces a family of methods to increase signal intensities in nuclear magnetic resonance (NMR) spectroscopy. Despite extensive theoretical work that allows one to distinguish at least five distinct mechanisms, it remains challenging to determine the relative weights of the processes that are responsible for DNP in state-of-the-art experiments operating with stable organic radicals like nitroxides at high magnetic fields and low temperatures. Specifically, determining experimental conditions where DNP involves thermal mixing, which denotes a spontaneous heat exchange between different spin reservoirs, remains challenging...
November 1, 2017: Journal of Physical Chemistry Letters
Jean-Francois Nierengarten, Iwona Nierengarten, Eric Meichsner, Michel Holler, Pauline Pieper, Robert Deschenaux, Béatrice Delavaux-Nicot
A pillar[5]arene-containing rotaxane building block bearing exchangeable stoppers has been prepared in multi-gram scale quantities with high yields from the reaction of 2,4-dinitrophenol (DNP) with the inclusion complex resulting from the association of dodecanedioyl chloride with 1,4-diethoxypillar[5]arene. Stopper exchange reactions have been achieved by treatment of the resulting DNP diester with various amines through an addition-elimination mechanism preventing the unthreading of the axle component during the reaction and thus preserving the [2]rotaxane structures...
October 26, 2017: Chemistry: a European Journal
J A Jarvis, I Haies, M Lelli, A J Rossini, I Kuprov, M Carravetta, P T F Williamson
The quadrupolar interaction experienced by the spin-1 (14)N nucleus is known to be extremely sensitive to local structure and dynamics. Furthermore, the (14)N isotope is 99.6% naturally abundant, making it an attractive target for characterisation of nitrogen-rich biological molecules by solid-state NMR. In this study, dynamic nuclear polarization (DNP) is used in conjunction with indirect (14)N detected solid-state NMR experiments to simultaneously characterise the quadrupolar interaction at multiple (14)N sites in the backbone of the microcrystalline protein, GB3...
November 7, 2017: Chemical Communications: Chem Comm
Roberta Spadaccini, Hundeep Kaur, Johanna Becker-Baldus, Clemens Glaubitz
MsbA, a homodimeric ABC exporter, translocates its native substrate lipid A as well as a range of smaller, amphiphilic substrates across the membrane. Magic angle sample spinning (MAS) NMR, in combination with dynamic nuclear polarization (DNP) for signal enhancement, has been used to probe two specific sites in transmembrane helices 4 and 6 of full length MsbA embedded in lipid bilayers. Significant chemical shift changes in both sites were observed in the vanadate-trapped state compared to apo state MsbA...
October 22, 2017: Biochimica et Biophysica Acta
Stef Smeets, Zachariah J Berkson, Dan Xie, Stacey I Zones, Wei Wan, Xiaodong Zou, Ming-Feng Hsieh, Bradley F Chmelka, Lynne B McCusker, Christian Baerlocher
The structure of the calcined form of the high-silica zeolite SSZ-70 has been elucidated by combining synchrotron X-ray powder diffraction (XRPD), high resolution transmission electron microscopy (HRTEM), and two-dimensional (2D) dynamic nuclear polarization (DNP)-enhanced NMR techniques. The framework structure of SSZ-70 is a polytype of MWW and can be viewed as a disordered ABC-type stacking of MWW-layers. HRTEM and XRPD simulations show that the stacking sequence is almost random, with each layer being shifted by ±1/3 along the <110> direction with respect to the previous one...
October 25, 2017: Journal of the American Chemical Society
M J Moure, Y Zhuo, G J Boons, J H Prestegard
The synthesis of perdeuterated and (13)C enriched myo-inositol is presented. Myo-inositol and its derivatives are of interest as substrates for enzymes producing phosphorylated species with regulatory functions in many organisms. Its utility in monitoring real-time phosphorylation by myo-inositol-3-kinase is illustrated using dynamic nuclear polarization (DNP) to enhance NMR observation.
November 16, 2017: Chemical Communications: Chem Comm
Abdou Tchoukoua, Takuma Suzuki, Nanang Rudianto Ariefta, Takuya Koseki, Yusuke Okawa, Ken-Ichi Kimura, Yoshihito Shiono
A new eremophilane sesquiterpene, 13,13-dimethoxyintegric acid (1), together with known compound integric acid (2) have been isolated from a fungus, Xylaria sp. V-27, obtained from a dead branch. The structure of 1 was established by means of spectroscopic analyses. 1 and 2 promoted growth restoring activity against the mutant yeast strain (Saccharomyces cerevisiae (zds1Δ erg3Δ pdr1Δ pdr3Δ)) and inhibited degranulation of rat basophilic leukemia RBL-2H3 cells stimulated by immnunoglobulin G + 2,4-dinitrophenylated-bovine serum albumin (IgE+DNP-BSA), thapsigargin and A23187...
October 25, 2017: Journal of Antibiotics
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