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https://www.readbyqxmd.com/read/29141223/gradients-of-rac1-nanoclusters-support-spatial-patterns-of-rac1-signaling
#1
Amanda Remorino, Simon De Beco, Fanny Cayrac, Fahima Di Federico, Gaetan Cornilleau, Alexis Gautreau, Maria Carla Parrini, Jean-Baptiste Masson, Maxime Dahan, Mathieu Coppey
Rac1 is a small RhoGTPase switch that orchestrates actin branching in space and time and protrusion/retraction cycles of the lamellipodia at the cell front during mesenchymal migration. Biosensor imaging has revealed a graded concentration of active GTP-loaded Rac1 in protruding regions of the cell. Here, using single-molecule imaging and super-resolution microscopy, we show an additional supramolecular organization of Rac1. We find that Rac1 partitions and is immobilized into nanoclusters of 50-100 molecules each...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29138401/imaging-the-transient-heat-generation-of-individual-nanostructures-with-a-mechanoresponsive-polymer
#2
Xueqin Chen, Qing Xia, Yue Cao, Qianhao Min, Jianrong Zhang, Zixuan Chen, Hong-Yuan Chen, Jun-Jie Zhu
Measuring the localized transient heat generation is critical for developing applications of nanomaterials in areas of photothermal therapy (PTT), drug delivery, optomechanics and biological processes engineering. However, accurate thermometry with high spatiotemporal resolution is still a challenge. Here we develop a thermosensitive polymer-capped gold nanorod (AuNRs@pNIPAAm), which has temperature-dependent local surface plasmon resonance spectra due to the submolecular conformational change of pNIPAAm molecules...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29137078/successful-treatment-of-ovarian-cancer-with-apatinib-combined-with-chemotherapy-a-case-report
#3
Mingzi Zhang, Zhongkai Tian, Yehong Sun
RATIONALE: The standard treatment for ovarian cancer is chemotherapy with 2 drugs (taxanes and platinum drugs). However, the traditional combination of the 2 drugs has many adverse effects (AEs) and the cancer cells will quickly become resistant to the drugs. Apatinib is a small-molecule antiangiogenic agent which has shown promising therapeutic effects against diverse tumor types, but it still remains unknown whether apatinib has an antitumor effect in patients with ovarian cancer. Herein, we present a successfully treated case of ovarian cancer using chemotherapy and apatinib, in order to demonstrate the effectiveness of this new combined regimen in ovarian cancer...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29137048/apatinib-for-the-treatment-of-pulmonary-epithelioid-hemangioendothelioma-a-case-report-and-literature-review
#4
Zhipeng Zheng, Hanying Wang, Hanliang Jiang, Enguo Chen, Jun Zhang, Xinyou Xie
RATIONALE: Pulmonary epithelioid hemangioendothelioma (P-EHE) is a rare tumor, with no established standard treatment. Overexpression of vascular endothelial growth factor receptor 2 (VEGFR-2) has been reported in some P-EHE patients. Apatinib, a new small molecule tyrosine kinase inhibitor that specifically targets VEGFR-2, has therapeutic benefits in some advanced tumors. However, its efficacy in P-EHE cases has not been reported. PATIENT CONCERNS: Herein, we presented a 44-year-old man with recurrent hemoptysis for approximately 9 years...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29133242/revisiting-in-vitro-release-test-for-topical-gel-formulations-the-effect-of-osmotic-pressure-explored-for-better-bio-relevance
#5
Soorin Jeong, Seonghee Jeong, Sungyoon Chung, Aeri Kim
Release test methods for topical dosage forms including pharmacopeial tests require a large volume of release media, with limited application for high throughput screening. In the present study, we evaluated Transwell assay to miniaturize the release test method for optimization of thermoreversible topical gel formulations. We also explored the osmotic effect on the in vitro release rates from gel formulations to understand the bio-relevance of release media. An extreme vertices type of mixture design in Minitab®16 generated eleven formulations composed of poloxamer 407, poloxamer 188, and phosphate buffered saline (PBS)...
November 10, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29130504/mass-spectrometry-based-metabolomics-targeting-the-crosstalk-between-gut-microbiota-and-brain-in-neurodegenerative-disorders
#6
REVIEW
Hemi Luan, Xian Wang, Zongwei Cai
Metabolomics seeks to take a "snapshot" in a time of the levels, activities, regulation and interactions of all small molecule metabolites in response to a biological system with genetic or environmental changes. The emerging development in mass spectrometry technologies has shown promise in the discovery and quantitation of neuroactive small molecule metabolites associated with gut microbiota and brain. Significant progress has been made recently in the characterization of intermediate role of small molecule metabolites linked to neural development and neurodegenerative disorder, showing its potential in understanding the crosstalk between gut microbiota and the host brain...
November 12, 2017: Mass Spectrometry Reviews
https://www.readbyqxmd.com/read/29130205/visualizing-rna-in-live-bacterial-cells-using-fluorophore-and-quencher-binding-aptamers
#7
Murat Sunbul, Ankita Arora, Andres Jäschke
To elucidate the roles, dynamics, and regulation of RNAs, it is vital to be able to visualize the RNA of interest (ROI) in living cells noninvasively. Here, we describe a novel live-cell RNA imaging method using fluorophore- and quencher-binding aptamers, which can be genetically fused to the ROI. In this method, new membrane permeable and nonfluorescent fluorophore-quencher conjugates were utilized, and we showed that their fluorescence increases dramatically upon binding to fluorophore- or quencher-binding aptamers...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29128531/the-hierarchical-response-of-human-corneal-collagen-to-load
#8
J S Bell, S Hayes, C Whitford, J Sanchez-Weatherby, O Shebanova, C Vergari, C P Winlove, N Terrill, T Sorensen, A Elsheikh, K M Meek
Fibrillar collagen in the human cornea is integral to its function as a transparent lens of precise curvature, and its arrangement is now well-characterised in the literature. While there has been considerable effort to incorporate fibrillar architecture into mechanical models of the cornea, the mechanical response of corneal collagen to small applied loads is not well understood. In this study the fibrillar and molecular response to tensile load was quantified using small and wide angle X-ray scattering (SAXS/WAXS), and digital image correlation (DIC) photography was used to calculate the local strain field that gave rise to the hierarchical changes...
November 8, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29120599/facile-c-f-bond-formation-through-a-concerted-nucleophilic-aromatic-substitution-mediated-by-the-phenofluor-reagent
#9
Constanze N Neumann, Tobias Ritter
Late-stage fluorination reactions aim to reduce the synthetic limitations of conventional organofluorine chemistry with respect to substrate scope and functional group tolerance. C-F bond formation is commonly thermodynamically favorable but almost universally associated with high kinetic barriers. Apart from PhenoFluor chemistry, most modern aromatic fluorination methods reported to date rely on the use of transition metal catalysts, with C-F bonds often formed through reductive elimination. Reductive elimination chemistry to make C-X bonds becomes increasingly challenging when moving to higher atomic numbers in the periodic table from C-C to C-F, in part because of higher metal-X bond dissociation energies...
November 9, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29114581/building-block-architecture-of-botulinum-toxin-complex-conformational-changes-provide-insights-into-the-hemagglutination-ability-of-the-complex
#10
Tomonori Suzuki, Yoshimasa Sagane, Takashi Matsumoto, Kimiko Hasegawa, Akihito Yamano, Koichi Niwa, Toshihiro Watanabe
Clostridium botulinum produces the botulinum neurotoxin (BoNT). Previously, we provided evidence for the "building-block" model of botulinum toxin complex (TC). In this model, a single BoNT is associated with a single nontoxic nonhemagglutinin (NTNHA), yielding M-TC; three HA-70 molecules are attached and form M-TC/HA-70, and one to three "arms" of the HA-33/HA-17 trimer (two HA-33 and one HA-17) further bind to M-TC/HA-70 via HA-17 and HA-70 binding, yielding one-, two-, and three-arm L-TC. Of all TCs, only the three-arm L-TC caused hemagglutination...
March 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29111150/small-molecule-delivery-to-solid-tumors-with-chitosan-coated-plga-particles-a-lesson-learned-from-comparative-imaging
#11
Jinho Park, Yihua Pei, Hyesun Hyun, Mark A Castanares, David S Collins, Yoon Yeo
For polymeric nanoparticles (NPs) to deliver more drugs to tumors than free drug solution, it is critical that the NPs establish interactions with tumor cells and avoid removal from the tumors. Since traditional polyethylene glycol (PEG) surface layer interferes with the cell-NP interaction in tumors, we used a water-soluble and blood-compatible chitosan derivative called zwitterionic chitosan (ZWC) as an alternative surface coating for poly(lactic-co-glycolic acid) (PLGA) NPs. The ZWC-coated PLGA NPs showed pH-dependent surface charge profiles and differential cellular interactions according to the pH of the medium...
October 27, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29109777/improved-tumor-targeting-and-longer-retention-time-of-nir-fluorescent-probes-using-bioorthogonal-chemistry
#12
Xianghan Zhang, Bo Wang, Na Zhao, Zuhong Tian, Yunpeng Dai, Yongzhan Nie, Jie Tian, Zhongliang Wang, Xiaoyuan Chen
The traditional labeling method for targeted NIR fluorescence probes requires directly covalent-bonded conjugation of targeting domains and fluorophores in vitro. Although this strategy works well, it is not sufficient for detecting or treating cancers in vivo, due to steric hindrance effects that relatively large fluorophore molecules exert on the configurations and physiological functions of specific targeting domains. The copper-free, "click-chemistry"-assisted assembly of small molecules in living systems may enhance tumor accumulation of fluorescence probes by improving the binding affinities of the targeting factors...
2017: Theranostics
https://www.readbyqxmd.com/read/29109279/ultrafast-25-fs-relaxation-in-highly-excited-states-of-methyl-azide-mediated-by-strong-nonadiabatic-coupling
#13
William K Peters, David E Couch, Benoit Mignolet, Xuetao Shi, Quynh L Nguyen, Ryan C Fortenberry, H Bernhard Schlegel, Françoise Remacle, Henry C Kapteyn, Margaret M Murnane, Wen Li
Highly excited electronic states are challenging to explore experimentally and theoretically-due to the large density of states and the fact that small structural changes lead to large changes in electronic character with associated strong nonadiabatic dynamics. They can play a key role in astrophysical and ionospheric chemistry, as well as the detonation chemistry of high-energy density materials. Here, we implement ultrafast vacuum-UV (VUV)-driven electron-ion coincidence imaging spectroscopy to directly probe the reaction pathways of highly excited states of energetic molecules-in this case, methyl azide...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29108275/functional-imaging-in-combination-with-mutation-status-aids-prediction-of-response-to-inhibiting-b-cell-receptor-signaling-in-lymphoma
#14
Laura Jacobs, Stefan Habringer, Jolanta Slawska, Katharina Huber, Elke Hauf, Zhoulei Li, Yosef Refaeli, Markus Schwaiger, Martina Rudelius, Axel Walch, Ulrich Keller
Aberrant B-cell receptor (BCR) signaling is known to contribute to malignant transformation. Two small molecule inhibitors targeting BCR pathway signaling include ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, and idelalisib, a specific Phosphatidylinositol-4,5-bisphosphate 3-kinase delta (PI3Kδ) inhibitor, both of which have been approved for use in haematological malignancies. Despite the identification of various diffuse large B-cell lymphoma (DLBCL) subtypes, mutation status alone is not sufficient to predict patient response and therapeutic resistance can arise...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29105856/rapid-iododeboronation-with-and-without-gold-catalysis-application-to-radiolabelling-of-arenes
#15
Stacey Webster, Kerry M O'Rourke, Conor Fletcher, Sally Pimlott, Andrew Sutherland, Ai-Lan Lee
Radiopharmaceuticals incorporating radioactive iodine in combination with SPECT imaging play a key role in nuclear medicine, with applications in drug development and disease diagnosis. Despite this importance, there are relatively few general methods for incorporating radioiodine into small molecules. Here we describe a rapid, air- and moisture-stable ipso-iododeboronation procedure using NIS, in the non-toxic and green solvent dimethyl carbonate. The fast reaction and mild conditions of the gold-catalysed method led to the development of a highly efficient process for radiolabelling of arenes, which constitutes the first example of an application of homogenous gold catalysis to selective radiosynthesis...
November 6, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29102609/dash-and-recruit-mechanism-drives-membrane-curvature-recognition-by-the-small-bacterial-protein-spovm
#16
Edward Y Kim, Erin R Tyndall, Kerwyn Casey Huang, Fang Tian, Kumaran S Ramamurthi
In Bacillus subtilis, sporulation requires that the 26-amino acid protein SpoVM embeds specifically into the forespore membrane, a structure with convex curvature. How this nanometer-sized protein can detect curves on a micrometer scale is not well understood. Here, we report that SpoVM exploits a "dash-and-recruit" mechanism to preferentially accumulate on the forespore. Using time-resolved imaging and flow cytometry, we observe that SpoVM exhibits a faster adsorption rate onto membranes of higher convex curvature...
October 31, 2017: Cell Systems
https://www.readbyqxmd.com/read/29101869/mesoporous-silica-for-drug-delivery-interactions-with-model-fluorescent-lipid-vesicles-and-live-cells
#17
Munmun Bardhan, Anupa Majumdar, Sayantan Jana, Tapas Ghosh, Uttam Pal, Snehasikta Swarnakar, Dulal Senapati
Formulated mesoporous silica nanoparticle (MSN) systems offer the best possible drug delivery system through the release of drug molecules from the accessible pores. In the present investigation, steady state and time resolved fluorescence techniques along with the fluorescence imaging were applied to investigate the interactions of dye loaded MSN with fluorescent unilamellar vesicles and live cells. Here 1,2-dimyristoyl-sn-glycero-3-phospocholine (DMPC) was used to prepare Small Unilamellar Vesicles (SUVs) as the model membrane with fluorescent 1,6-diphenyl-1,3,5-hexatriene (DPH) molecule incorporated inside the lipid bilayer...
November 1, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29101783/one-pot-preparation-of-hydrophilic-manganese-oxide-nanoparticles-as-t1-nano-contrast-agent-for-molecular-magnetic-resonance-imaging-of-renal-carcinoma-in-vitro-and-in-vivo
#18
Jingjing Li, Chen Wu, Pingfu Hou, Min Zhang, Kai Xu
Magnetic resonance imaging (MRI) contrast agents have become a necessary part for clinical practice to improve the sensitivity for the diagnosis of small lesions and injuries. Among them, manganese oxide nanoparticle (MnO NPs)-based MRI contrast agent attracts more and more attention because of their better performance in the detection of brain disease and positive enhancement in T1-weighted image. However, the relatively low r1 relaxivity and complex synthetic route hampered their wider applications. In this work, we proposed a one-pot approach to prepare hydrophilic MnO NPs via a polyol-like method with poly (ethylene glycol) (PEG) as both a solvent and surfactant...
October 27, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29095596/1-6-diphenyl-1-3-5-hexatriene-dph-as-a-novel-matrix-for-maldi-ms-imaging-of-fatty-acids-phospholipids-and-sulfatides-in-brain-tissues
#19
Hanadi Ibrahim, Kristina Jurcic, Jasmine S-H Wang, Shawn Narain Whitehead, Ken K-C Yeung
1,6-Diphenyl-1,3,5-hexatriene (DPH) is a commonly-used fluorescence probe for studying cell membrane-lipids due to its affinity towards the acyl chains in the phospholipid bilayers. In this work, we investigated its use in matrix-assisted laser desorption/ionization (MALDI) as a new matrix for mass spectrometry imaging (MSI) of mouse and rat brain tissue. DPH exhibits very minimal matrix-induced background signals for the analysis of small molecules (below m/z of 1000). In the negative ion mode, DPH permits the highly sensitive detection of small fatty acids (m/z 200 to 350) as well as a variety of large lipids up to m/z of 1000, including lyso-phospholipid, phosphatidic acid (PA), phosphoethanolamine (PE), phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidylinositol (PI), and sulfatides (ST)...
November 2, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29091994/quantifying-biological-samples-using-linear-poisson-independent-component-analysis-for-maldi-tof-mass-spectra
#20
S Deepaisarn, P D Tar, N A Thacker, A Seepujak, A W McMahon
Motivation: Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI) facilitates the analysis of large organic molecules. However, the complexity of biological samples and MALDI data acquisition leads to high levels of variation, making reliable quantification of samples difficult. We present a new analysis approach that we believe is well-suited to the properties of MALDI mass spectra, based upon an Independent Component Analysis derived for Poisson sampled data...
October 28, 2017: Bioinformatics
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