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Contrast kinetics

Sarah Theiner, Márkó Grabarics, Luis Galvez, Hristo P Varbanov, Nadine S Sommerfeld, Markus Galanski, Bernhard K Keppler, Gunda Koellensperger
The potential advantage of platinum(iv) complexes as alternatives to classical platinum(ii)-based drugs relies on their kinetic stability in the body before reaching the tumor site and on their activation by reduction inside cancer cells. In this study, an analytical workflow has been developed to investigate the reductive biotransformation and kinetic inertness of platinum(iv) prodrugs comprising different ligand coordination spheres (respectively, lipophilicity and redox behavior) in whole human blood. The distribution of platinum(iv) complexes in blood pellets and plasma was determined by inductively coupled plasma-mass spectrometry (ICP-MS) after microwave digestion...
March 21, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Anne Kathrine R Junker, Leila R Hill, Amber L Thompson, Stephen Faulkner, Thomas Just Sørensen
Lanthanide based dyes and assays exploit the antenna effect, where a sensitiser-chromophore is used as a light harvesting antenna and subsequent excited state energy transfer populates the emitting lanthanide centred excited state. A rudimentary understanding of the design criteria for designing efficient dyes and assays based on the antenna effect is in place. By preparing kinetically inert lanthanide complexes based on the DO3A scaffold, we are able to study the excited state energy transfer from a 7-methoxy-coumarin antenna chromophore to europium(iii) and terbium(iii) centred excited states...
March 21, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Alexander Kreft, Peter G Jones, Daniel B Werz
D-A cyclopropanes bearing a simple cyclopropyl group as donor are shown to undergo a variety of [3+ n]-cycloaddition reactions ( n = 2-4). This behavior contrasts sharply with that of common D-A cyclopropanes with aliphatic donors. Kinetic experiments demonstrate that, in terms of donor ability, the cyclopropyl substituent lies between electron-rich and electron-neutral aryl donors.
March 20, 2018: Organic Letters
Linda K Bruetzel, Philipp Walker, Thomas Gerling, Hendrik Dietz, Jan Lipfert
Self-assembled DNA structures enable creation of specific shapes at the nm-µm scale with molecular resolution. The creation of functional DNA assemblies will likely require dynamic structures that can undergo controllable conformational changes. DNA devices based on shape complementary stacking interactions have been demonstrated to undergo reversible conformational changes triggered by changes in ionic environment or temperature. An experimentally unexplored aspect is how quickly conformational transitions of large synthetic DNA origami structures can actually occur...
March 20, 2018: Nano Letters
Rowena M Briones, Ajit K Sarmah
Detection of metformin, an antidiabetic drug and its transformation product guanylurea in various environmental matrices such as surface water and groundwater, coupled with their effects on aquatic organisms warrant an understanding of the compounds fate and behaviour in the environment. Batch studies were conducted with the aim of evaluating the sorption of these two emerging contaminants in six New Zealand agricultural soils of contrasting physico-chemical properties. Kinetic studies revealed that metformin and guanylurea sorption in Te Kowhai soil was very rapid initially achieving 90% sorption within the first 4 and 13h, respectively...
March 2, 2018: Science of the Total Environment
Jian Xiao, Si-Yang Wang, Zi-Jun Zhou, Yao Zhang, Chun-Lei Song, Yi-Yong Zhou, Xiu-Yun Cao
The over-enrichment of lake waters with nitrogen (N) and phosphorus (P) has become a serious environmental problem, but modes of change in stoichiometry and enzymatic regeneration along trophic gradients are largely unknown. Seasonal variations in the kinetics of extracellular aminopeptidase (LAP) and alkaline phosphatase (AP), together with the composition of phytoplankton and concentrations of N and P, were examined from Jun 2013 to September 2014 in a Chinese shallow lake in which two basins had contrasting trophic states...
March 1, 2018: Science of the Total Environment
Natsuki Hemmi, Yasuko Akiyama-Oda, Koichi Fujimoto, Hiroki Oda
One of the conserved traits of arthropod embryonic development is striped expression of homologs of Drosophila segment polarity genes, including hedgehog (hh). Although a diversity of stripe-forming processes is recognized among arthropod embryos, such varied stripe-forming processes have not been well characterized from cellular and quantitative perspectives. The spider Parasteatoda tepidariorum embryo, which has a hh-dependent mechanism of axis formation, offers a cell-based field where the stripes of Pt-hh (a hh homolog) expression dynamically develop in accordance with axis formation and growth, with the patterning processes varying among the regions of the field...
March 15, 2018: Developmental Biology
Meysam Amidfar, Gislaine Z Réus, Joao Quevedo, Yong-Ku Kim
A developing body of evidence indicates that disturbed glutamate neurotransmission especially through N-methyl-d-aspartate (NMDA) is central to the pathophysiology of major depressive disorder (MDD) and NMDA receptor antagonists have shown therapeutic potential in the MDD treatment. Memantine is an uncompetitive NMDA receptor antagonist, approved for treatment of Alzheimer's disease (AD) that in contrast to other NMDA receptor antagonists at therapeutic doses does not induce highly undesirable side effects...
March 15, 2018: European Journal of Pharmacology
Facundo Marconi, María Laura Umpiérrez, David Gonzalez, Sonia Rodríguez Giordano, Paula Rodriguez
The biotransformation of (4R)-(-)-carvone by Mentha pulegium (pennyroyal) leaves and its endophytic bacteria was performed in order to search for novel biocatalysts with enoate reductase activity. The obtained results clearly indicated that endophytes play an important role in the biotransformation of (4R)-(-)-carvone with pennyroyal plant tissues. The best activity was associated to the endophytic bacteria Pseudomonas proteolytica FM18Mci1 and Bacillus sp. FM18civ1. Enoate reductase activity for the reduction of (4R)-(-)-carvone and (4S)-(+)-carvone as model substrates was evaluated for each strain...
March 17, 2018: World Journal of Microbiology & Biotechnology
Dirk van den Brand, Cornelia Veelken, Leon Massuger, Roland Brock
Drug delivery into tumors and metastases is a major challenge in the eradication of cancers such as epithelial ovarian carcinoma. Cationic cell-penetrating peptides (CPPs) are a promising group of delivery vehicles to mediate cellular entry of molecules that otherwise poorly enter cells. However, little is known about their penetration behavior in tissues. Here, we investigated penetration of cationic CPPs in 3D ovarian cancer spheroids and patient-derived 3D tumor explants. Penetration kinetics and distribution after long-term incubation were imaged by confocal microscopy...
March 14, 2018: Biochimica et Biophysica Acta
Frans Vinberg, Igor V Peshenko, Jeannie Chen, Alexander M Dizhoor, Vladimir J Kefalov
Light adaptation of photoreceptor cells is mediated by Ca2+-dependent mechanisms. In darkness, Ca2+ influx through cGMP-gated channels into the outer segment of photoreceptors is balanced by Ca2+ extrusion via Na+/Ca2+, K+ exchangers (NCKXs). Light activates a G protein signaling cascade, which closes cGMP-gated channels and decreases Ca2+ levels in photoreceptor outer segment because of continuing Ca2+ extrusion by NCKXs. Guanylate Cyclase Activating Proteins (GCAPs) then upregulate cGMP synthesis by activating retinal membrane guanylate cyclases (RetGCs) in low Ca2+...
March 16, 2018: Journal of Biological Chemistry
Saugata Patra, Dibyendu Das, R Rajesh, Mithun K Mitra
It is known from grand canonical simulations of a system of hard rods on two-dimensional lattices that an orientationally ordered nematic phase exists only when the length of the rods is at least seven. However, a recent microcanonical simulation with diffusion kinetics, conserving both total density and zero nematic order, reported the existence of a nematically phase-segregated steady state with interfaces in the diagonal direction for rods of length six [Phys. Rev. E 95, 052130 (2017)2470-004510.1103/PhysRevE...
February 2018: Physical Review. E
Ja Hye Myung, Michael J Eblan, Joseph M Caster, Sinjung Park, Michael J Poellmann, Kyle Wang, Joel E Tepper, Kevin A Tam, Seth M Miller, Colette Shen, Ronald C Chen, Tian Zhang, Bhishamjit Chera, Andrew Z Wang, Seungpyo Hong
PURPOSE: We aimed to examine the effects of multivalent binding and biomimetic cell rolling on the sensitivity and specificity of circulating tumor cell (CTC) capture. We also investigated the clinical significance of CTCs and their kinetic profiles in cancer patients undergoing radiotherapy (RT) treatment. EXPERIMENTAL DESIGN: Patients with histologically confirmed primary carcinoma undergoing RT, with or without chemotherapy, were eligible for enrollment. Peripheral blood was collected prospectively at up to 5 time points, including prior to RT, at the first week, mid-point and final week of treatment, as well as 4 to 12 weeks after completion of RT...
March 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
David B Medeiros, Leonardo Perez de Souza, Werner C Antunes, Wagner L Araújo, Danilo M Daloso, Alisdair R Fernie
Sucrose has long been thought to play an osmolytic role in stomatal opening. However, recent evidence supports the idea that the role of sucrose in this process is primarily energetic. Here we used a combination of stomatal aperture assays coupled with kinetic [U-13 C]-sucrose isotope labelling experiments to confirm that sucrose is degraded during light-induced stomatal opening and to define the fate of the C released from sucrose breakdown. We additionally show that addition of sucrose in the medium did not enhance light-induced stomatal opening...
March 15, 2018: Plant Journal: for Cell and Molecular Biology
Kambiz Rahbar, Ali Afshar-Oromieh, Martin Bögemann, Stefan Wagner, Michael Schäfers, Lars Stegger, Matthias Weckesser
PURPOSE: PSMA-targeted PET in patients with prostate cancer (PCa) has a significant impact on treatment decisions. By far the most frequently used PSMA ligand is68 Ga-labelled PSMA-11. However, due to the availability of larger amounts of activity,18 F-labelled PSMA ligands are of major interest. The aim of the present study was to evaluate the biodistribution and performance of the novel18 F-labelled ligand PSMA-1007 at two different time points. METHODS: This retrospective analysis included 40 consecutive patients (mean age 68...
March 14, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Valentin Blanchard, Stephane Ramin-Mangata, Stephanie Billon-Crossouard, Audrey Aguesse, Manon Durand, Kevin Chemello, Brice Nativel, Laurent Flet, Maud Chetiveaux, David Jacobi, Jean-Marie Bard, Khadija Ouguerram, Gilles Lambert, Michel Krempf, Mikael Croyal
Human apolipoprotein E (apoE) exhibits three major isoforms (apoE2, apoE3, and apoE4) corresponding to polymorphism in the APOE gene. Total plasma apoE concentrations are closely related to these isoforms but the underlying mechanisms are unknown. We aimed to describe the kinetics of apoE individual isoforms to explore the mechanisms for variable total apoE plasma concentrations. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to discriminate between isoforms by identifying specific peptide sequences in subjects (3 E2/E3, 3 E3/E3 and 3 E3/E4 phenotypes) who received a primed constant infusion of2 H3 -leucine for 14 hours...
March 14, 2018: Journal of Lipid Research
J Vincent Edwards, Krystal Fontenot, Falk Liebner, Nicole Doyle Nee Pircher, Alfred D French, Brian D Condon
Nanocellulose has high specific surface area, hydration properties, and ease of derivatization to prepare protease sensors. A Human Neutrophil Elastase sensor designed with a nanocellulose aerogel transducer surface derived from cotton is compared with cotton filter paper, and nanocrystalline cellulose versions of the sensor. X-ray crystallography was employed along with Michaelis-Menten enzyme kinetics, and circular dichroism to contrast the structure/function relations of the peptide-cellulose conjugate conformation to enzyme/substrate binding and turnover rates...
March 13, 2018: International Journal of Molecular Sciences
Yi Zhao, Marcus J C Long, Yiran Wang, Sheng Zhang, Yimon Aye
Posttranslational modifications (PTMs) are the lingua franca of cellular communication. Most PTMs are enzyme-orchestrated. However, the reemergence of electrophilic drugs has ushered mining of unconventional/non-enzyme-catalyzed electrophile-signaling pathways. Despite the latest impetus toward harnessing kinetically and functionally privileged cysteines for electrophilic drug design, identifying these sensors remains challenging. Herein, we designed "G-REX"-a technique that allows controlled release of reactive electrophiles in vivo...
February 28, 2018: ACS Central Science
Zhu Liang, Wei Bu, Karl J Schweighofer, David J Walwark, Jeffrey S Harvey, Glenn R Hanlon, Daniel Amoanu, Cem Erol, Ilan Benjamin, Mark L Schlossman
During solvent extraction, amphiphilic extractants assist the transport of metal ions across the liquid-liquid interface between an aqueous ionic solution and an organic solvent. Investigations of the role of the interface in ion transport challenge our ability to probe fast molecular processes at liquid-liquid interfaces on nanometer-length scales. Recent development of a thermal switch for solvent extraction has addressed this challenge, which has led to the characterization by X-ray surface scattering of interfacial intermediate states in the extraction process...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ulrich Hohmann, Julia Santiago, Joël Nicolet, Vilde Olsson, Fabio M Spiga, Ludwig A Hothorn, Melinka A Butenko, Michael Hothorn
Plant-unique membrane receptor kinases with leucine-rich repeat ectodomains (LRR-RKs) can sense small molecule, peptide, and protein ligands. Many LRR-RKs require SERK-family coreceptor kinases for high-affinity ligand binding and receptor activation. How one coreceptor can contribute to the specific binding of distinct ligands and activation of different LRR-RKs is poorly understood. Here we quantitatively analyze the contribution of SERK3 to ligand binding and activation of the brassinosteroid receptor BRI1 and the peptide hormone receptor HAESA...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
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