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Ryota Saito, Maiko Hoshi, Akihiro Kato, Chikako Ishikawa, Toshiya Komatsu
A number of (Z)-4-arylmethylene-1H-imidazol-5(4H)-ones, which are related to the fluorescent chromophore of the Aequorea green fluorescent protein (GFP), have been synthesized and evaluated their in vitro inhibitory activity against recombinant human aldose reductase for the first time. The GFP chromophore model 1a, with a p-hydroxy group on the 4-benzylidene and a carboxymethyl group on the N1 position, exhibited strong bioactivity with an IC50 value of 0.36 μM. This efficacy is higher than that of sorbinil, a known highly potent aldose reductase inhibitor...
October 8, 2016: European Journal of Medicinal Chemistry
Thomas J Lawton, Amy C Rosenzweig
Nature utilizes two groups of enzymes to catalyze methane conversions, methyl-coenzyme M reductases (MCRs) and methane monooxygenases (MMOs). These enzymes have been difficult to incorporate into industrial processes due to their complexity, poor stability, and lack of recombinant tractability. Despite these issues, new ways of preparing and stabilizing these enzymes have recently been discovered, and new mechanistic insight into how MCRs and MMOs break the C-H bond in nature's most inert hydrocarbon have been obtained...
October 18, 2016: Current Opinion in Chemical Biology
Maria Chatzinikolaidou, Charalampos Pontikoglou, Konstantina Terzaki, Maria Kaliva, Athanasia Kalyva, Eleni Papadaki, Maria Vamvakaki, Maria Farsari
The regeneration of bone via a tissue engineering approach involves components from the macroscopic to the nanoscopic level, including appropriate 3D scaffolds, cells and growth factors. In this study, hexagonal scaffolds of different diagonals were fabricated by Direct Laser Writing using a photopolymerizable hybrid material. The proliferation of bone marrow (BM) mesenchymal stem cells (MSCs) cultured on structures with various diagonals, 50, 100, 150 and 200μm increased significantly after 10days in culture, however without significant differences among them...
October 13, 2016: Colloids and Surfaces. B, Biointerfaces
Nathaniel J Robinson, William P Schiemann
Despite significant clinical advancements, cancer remains a leading cause of mortality throughout the world due largely to the process of metastasis and the dissemination of cancer cells from their primary tumor of origin to distant secondary sites. The clinical burden imposed by metastasis is further compounded by a paucity of information regarding the factors that mediate metastatic progression. Linear chromosomes are capped by structures known as telomeres, which dictate cellular lifespan in humans by shortening progressively during successive cell divisions...
October 18, 2016: Biochimica et Biophysica Acta
Jialin Zhang, Wenxing Liu, Weiye Chen, Cuicui Li, Meimei Xie, Zhigao Bu
From 2013 to 2015, peste des petits ruminants (PPR) broke out in more than half of the provinces of China; thus, the application and development of diagnostic methods are very important for the control of PPR. Here, an immunoperoxidase monolayer assay (IPMA) was developed to detect antibodies against PPR. However, during IPMA development, we found that Vero cells were not the appropriate choice because staining results were not easily observed. Therefore, we first established a baby hamster kidney-goat signaling lymphocyte activation molecule (BHK-SLAM) cell line that could stably express goat SLAM for at least 20 generations...
2016: PloS One
A Didier, R Dietrich, E Märtlbauer
The non-hemolytic enterotoxin complex (Nhe) is supposed to be the main virulence factor of B. cereus causing a diarrheal outcome of food poisoning. This tripartite toxin consists of the single components NheA, -B and -C all of them being necessary for maximum toxicity. In the past, research activities aiming to elucidate the mode-of-action of Nhe were mostly focused on the B- and C-component. In this study the generation of novel monoclonal antibodies (mAb) and their thorough characterization enabled the determination of key features for NheA...
2016: PloS One
Qian Lu, Jihong Wang, Junshu Jiang, Shengnan Wang, Qilan Jia, Yue Wang, Weiping Li, Qin Zhou, Li Lv, Qingwei Li
BACKGROUND: The RGD-toxin protein Lj-RGD3 is a naturally occurring 118 amino acid peptide that can be obtained from the salivary gland of the Lampetra japonica fish. This unique peptide contains 3 RGD (Arg-Gly-Asp) motifs in its primary structure. Lj-RGD3 is available in recombinant form (rLj-RGD3) and can be produced in large quantities using DNA recombination techniques. The pharmacology of the three RGD motif-containing peptides has not been studied. This study investigated the protective effects of rLj-RGD3, a novel polypeptide, against ischemia/reperfusion-induced damage to the brain caused by middle cerebral artery occlusion (MCAO) in a rat stroke model...
2016: PloS One
Lasse van Wijlick, René Geissen, Jessica S Hilbig, Quentin Lagadec, Pilar D Cantero, Eugen Pfeifer, Mateusz Juchimiuk, Sven Kluge, Stephan Wickert, Paula Alepuz, Joachim F Ernst
In eukaryotes, Dom34 upregulates translation by securing levels of activatable ribosomal subunits. We found that in the yeast Saccharomyces cerevisiae and the human fungal pathogen Candida albicans, Dom34 interacts genetically with Pmt1, a major isoform of protein O-mannosyltransferase. In C. albicans, lack of Dom34 exacerbated defective phenotypes of pmt1 mutants, while they were ameliorated by Dom34 overproduction that enhanced Pmt1 protein but not PMT1 transcript levels. Translational effects of Dom34 required the 5'-UTR of the PMT1 transcript, which bound recombinant Dom34 directly at a CA/AC-rich sequence and regulated in vitro translation...
October 2016: PLoS Genetics
Philippe Lefrançois, Beth Rockmill, Pingxing Xie, G Shirleen Roeder, Michael Snyder
During meiosis, chromosomes undergo a homology search in order to locate their homolog to form stable pairs and exchange genetic material. Early in prophase, chromosomes associate in mostly non-homologous pairs, tethered only at their centromeres. This phenomenon, conserved through higher eukaryotes, is termed centromere coupling in budding yeast. Both initiation of recombination and the presence of homologs are dispensable for centromere coupling (occurring in spo11 mutants and haploids induced to undergo meiosis) but the presence of the synaptonemal complex (SC) protein Zip1 is required...
October 2016: PLoS Genetics
Kerry A Geiler-Samerotte, Yuan O Zhu, Benjamin E Goulet, David W Hall, Mark L Siegal
The protein-folding chaperone Hsp90 has been proposed to buffer the phenotypic effects of mutations. The potential for Hsp90 and other putative buffers to increase robustness to mutation has had major impact on disease models, quantitative genetics, and evolutionary theory. But Hsp90 sometimes contradicts expectations for a buffer by potentiating rapid phenotypic changes that would otherwise not occur. Here, we quantify Hsp90's ability to buffer or potentiate (i.e., diminish or enhance) the effects of genetic variation on single-cell morphological features in budding yeast...
October 2016: PLoS Biology
Huilin Ou, Wei Yao, Nanping Wu, Frederick X C Wang, Tianhao Weng, Chengcong Han, Xiangyun Lu, Dongshan Yu, Haibo Wu, Linfang Cheng, Honglin Chen, Hangping Yao, Lanjuan Li
Developing a safe and effective H7N9 influenza vaccine was initiated in early spring 2013, following human infections with a novel avian influenza A (H7N9) virus. In this study, a candidate H7N9 vaccine seed strain is produced using reverse genetics, with HA and NA derived from a human H7N9 virus and the remaining genes from the PR8 backbone virus which grows well in eggs. We verified that the virulence and transmissibility of the recombinant H7N9 vaccine seed strain were decreased as compared to wild-type H7N9 virus, to levels comparable with PR8...
October 19, 2016: Oncotarget
Yoshikane Nonagase, Kimio Yonesaka, Hisato Kawakami, Satomi Watanabe, Koji Haratani, Takayuki Takahama, Naoki Takegawa, Hiroto Ueda, Junko Tanizaki, Hidetoshi Hayashi, Takeshi Yoshida, Masayuki Takeda, Yasutaka Chiba, Takao Tamura, Kazuhiko Nakagawa, Junji Tsurutani
BACKGROUND: Overexpression of heregulin, a HER3 ligand, is one mechanism that confers resistance to the anti-HER2 agents trastuzumab and lapatinib. We investigated the impact of heregulin expression on the efficacy of HER2-targeted therapeutic agents, including trastuzumab, trastuzumab emtansine (T-DM1) and lapatinib, in vitro and in vivo and evaluated the heregulin messenger RNA (mRNA) levels in specimens from patients with HER2-positive breast or gastric cancer. RESULTS: Cell proliferation and apoptosis assays demonstrated that heregulin conferred robust resistance to lapatinib and trastuzumab via HER3-Akt pathway activation followed by survivin overexpression; however, heregulin conferred minimal or no resistance to T-DM1 and paclitaxel...
October 19, 2016: Oncotarget
Daniela Rupp, Leonie Flückiger, Marcus Adolph, Tais Gorkhover, Maria Krikunova, Jan Philippe Müller, Maria Müller, Tim Oelze, Yevheniy Ovcharenko, Benjamin Röben, Mario Sauppe, Sebastian Schorb, David Wolter, Rolf Mitzner, Michael Wöstmann, Sebastian Roling, Marion Harmand, Rolf Treusch, Mathias Arbeiter, Thomas Fennel, Christoph Bostedt, Thomas Möller
We studied the nanoplasma formation and explosion dynamics of single large xenon clusters in ultrashort, intense x-ray free-electron laser pulses via ion spectroscopy. The simultaneous measurement of single-shot diffraction images enabled a single-cluster analysis that is free from any averaging over the cluster size and laser intensity distributions. The measured charge state-resolved ion energy spectra show narrow distributions with peak positions that scale linearly with final ion charge state. These two distinct signatures are attributed to highly efficient recombination that eventually leads to the dominant formation of neutral atoms in the cluster...
October 7, 2016: Physical Review Letters
Juris Ulmanis, Stephan Häfner, Rico Pires, Eva D Kuhnle, Yujun Wang, Chris H Greene, Matthias Weidemüller
We investigate theoretically and experimentally the heteronuclear Efimov scenario for a three-body system that consists of two bosons and one distinguishable particle with positive intraspecies scattering lengths. The three-body parameter at the three-body scattering threshold and the scaling factor between consecutive Efimov resonances are found to be controlled by the scattering length between the two bosons, approximately independent of short-range physics. We observe two excited-state Efimov resonances in the three-body recombination spectra of an ultracold mixture of fermionic ^{6}Li and bosonic ^{133}Cs atoms close to a Li-Cs Feshbach resonance, where the Cs-Cs interaction is positive...
October 7, 2016: Physical Review Letters
Tao Peng, Howard C Hang
Over the past years, fluorescent proteins (e.g., green fluorescent proteins) have been widely utilized to visualize recombinant protein expression and localization in live cells. Although powerful, fluorescent protein tags are limited by their relatively large sizes and potential perturbation to protein function. Alternatively, site-specific labeling of proteins with small-molecule organic fluorophores using bioorthogonal chemistry may provide a more precise and less perturbing method. This approach involves site-specific incorporation of unnatural amino acids (UAAs) into proteins via genetic code expansion, followed by bioorthogonal chemical labeling with small organic fluorophores in living cells...
October 21, 2016: Journal of the American Chemical Society
Guanchao Yin, Min Song, Shengkai Duan, Phillip Manley, Dieter Greiner, Christian A Kaufmann, Martina Schmid
Ultrathin Cu(In,Ga)Se2 (CIGSe) solar cells pose challenges of incomplete absorption and back contact recombination. In this work, we applied the simple collodial nanosphere lithography and fabricated 2D SiO2 nanomeshes (NMs), which simultaneously benefit ultrathin CIGSe solar cells electrically and optically. Electrically, the NMs are capable of passivating the back contact recombination, and increasing the minimum bandgap of absorbers. Optically, the parasitic absorption in Mo as a main optical loss is reduced...
October 21, 2016: ACS Applied Materials & Interfaces
Ashton A Connor, Robert E Denroche, Gun Ho Jang, Lee Timms, Sangeetha N Kalimuthu, Iris Selander, Treasa McPherson, Gavin W Wilson, Michelle A Chan-Seng-Yue, Ivan Borozan, Vincent Ferretti, Robert C Grant, Ilinca M Lungu, Eithne Costello, William Greenhalf, Daniel Palmer, Paula Ghaneh, John P Neoptolemos, Markus Buchler, Gloria Petersen, Sarah Thayer, Michael A Hollingsworth, Alana Sherker, Daniel Durocher, Neesha Dhani, David Hedley, Stefano Serra, Aaron Pollett, Michael H A Roehrl, Prashant Bavi, John M S Bartlett, Sean Cleary, Julie M Wilson, Ludmil B Alexandrov, Malcolm Moore, Bradly G Wouters, John D McPherson, Faiyaz Notta, Lincoln D Stein, Steven Gallinger
Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium...
October 20, 2016: JAMA Oncology
Alexandre Darmon, Michael Benzaquen, Simon Čopar, Olivier Dauchot, Teresa Lopez-Leon
We investigate experimentally and numerically the defect configurations emerging when a cholesteric liquid crystal is confined to a spherical shell. We uncover a rich scenario of defect configurations, some of them non-existent in nematic shells, where new types of defects are stabilized by the helical ordering of the liquid crystal. In contrast to nematic shells, here defects are not simple singular points or lines, but have a large structured core. Specifically, we observe five different types of cholesteric shells...
October 21, 2016: Soft Matter
Wei Huang, Jiyuan Wu, Huiqin Yang, Yin Xiong, Rui Jiang, Tianpen Cui, Duyun Ye
Abnormal features of the systemic lupus erythematosus (SLE)-derived neutrophils, promoted aberrant immune response, have inspired new studies of the induction of autoimmunity and the development of organ damage in SLE. In this study, we explore the effect of milk fat globule-EGF factor 8 (MFG-E8) on the aberrant nitrification features in pristane-induced lupus. SLE patients and mice with pristane-induced lupus develop autoantibodies associated with MFG-E8 overproduction. However, the deletion of MFG-E8 leads to uncontrolled early pulmonary and peritoneal inflammation and tissue damage in mice with pristane-induced lupus...
October 21, 2016: Cell Death and Differentiation
James K Utterback, Amanda N Grennell, Molly B Wilker, Orion M Pearce, Joel D Eaves, Gordana Dukovic
In CdS nanocrystals, photoexcited holes rapidly become trapped at the particle surface. The dynamics of these trapped holes have profound consequences for the photophysics and photochemistry of these materials. Using a combination of transient absorption spectroscopy and theoretical modelling, we demonstrate that trapped holes in CdS nanorods are mobile and execute a random walk at room temperature. In CdS nanorods of non-uniform width, we observe the recombination of spatially separated electrons and trapped holes, which exhibits a t(-1/2) power-law decay at long times...
November 2016: Nature Chemistry
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