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Jake Cosme, Hongbo Guo, Sina Hadipour-Lakmehsari, Andrew Emili, Anthony O Gramolini
Cardiac fibroblasts (CF) represent a major subpopulation of cells in the developing and adult heart. Cardiomyocyte (CM) and CF intercellular communication occurs through paracrine interactions and modulate myocyte development and stress response. Detailed proteomic analysis of the CF secretome in normal and stressed conditions may offer insights into the role of CF in heart development and disease. Primary neonatal mouse CF were isolated and cultured for 24h in 21% (normoxic) or 2% (hypoxic) O2. Conditioned media was separated to obtain EXO and EXO-depleted secretome fractions...
June 22, 2017: Journal of Proteome Research
Prasanta Ghorai, Abhisek Midya, Sanjay Maity
A unified dynamic kinetic spiroketalization/ enantioselective oxa-Michael addition cascade of an aromatic ketone tethered to an alkoxyboronate and an enone moiety has been developed using cinchona alkaloid based amino-thiourea/-squaramide organocatalysts to provide isobenzofuran based benzannulated spiroketals with high diastereoselectivities and excellent enantioselectivities. Further, a dynamic kinetic peroxy-hemiacetalization/dynamic kinetic spiroketalization/ enantioselective oxa-Michael addition cascade of above substrates provides the corresponding exo-peroxy benzannulated spiroketals with outstanding enantio- and diastereo-selectivities...
June 22, 2017: Chemistry: a European Journal
Jaap E Borger, Maarten K Jongkind, Andreas W Ehlers, Martin Lutz, J Chris Slootweg, Koop Lammertsma
The development of selective functionalization strategies of white phosphorus (P4) is important to avoid the current chlorinated intermediates. The use of transition metals (TMs) could lead to catalytic procedures, but these are severely hampered by the high reactivity and unpredictable nature of the tetrahedron. Herein, we report selective first steps by reacting P4 with a metal anion [Cp*Fe(CO)2](-) (Cp*=C5(CH3)5), which, in the presence of bulky Lewis acids (LA; B(C6F5)3 or BPh3), leads to unique TM-substituted LA-stabilized bicyclo[1...
June 2017: ChemistryOpen
Jun Luo, Xiuji Cui, Lu Gao, Jianming Hu
The hepatitis B virus (HBV) covalently closed circular (CCC) DNA functions as the only viral template capable of coding for all the viral RNA species and is thus essential to initiate and sustain viral replication. CCC DNA is converted, in a multi-step and ill-understood process, from a relaxed circular (RC) DNA, in which neither of the two DNA strands is covalently closed. To detect putative intermediates during RC to CCC DNA conversion, two 3' exonucleases Exo I and Exo III, in combination were used to degrade all DNA strands with a free 3' end, which would nevertheless preserve closed circular DNA, either single-stranded (SS) or double-stranded (DS)...
June 21, 2017: Journal of Virology
Joo Ern Ang, Akos Pal, Yasmin J Asad, Alan T Henley, Melanie Valenti, Gary Box, Alexis de Haven Brandon, Victoria Revell, Debra J Skene, Miro Venturi, Ruediger Rueger, Valerie Meresse, Suzanne A Eccles, Johann S de Bono, Stanley B Kaye, Paul Workman, Udai Banerji, Florence I Raynaud
<p>MAPK pathway activation is frequently observed in human malignancies, including melanoma, and is associated with sensitivity to MEK inhibition and changes in cellular metabolism. Using quantitative mass spectrometry-based metabolomics, we identified in preclinical models 21 plasma metabolites including amino acids, propionylcarnitine, phosphatidylcholines and sphingomyelins that were significantly altered in two B-RAF mutant melanoma xenografts and that were reversed following a single dose of the potent and selective MEK inhibitor RO4987655...
June 21, 2017: Molecular Cancer Therapeutics
Siti Nor Syairah Anis, Mohamad Suffian Mohamad Annuar, Khanom Simarani
In vivo and in vitro depolymerizations of intracellular medium-chain-length poly-3-hydroxyalkanoates (mcl-PHA) in Pseudomonas putida Bet001 grown on lauric acid was studied. Both processes were studied under optimum conditions for mcl-PHA depolymerization viz. 0.2 M Tris-HCl buffer, pH 9, ionic strength (I) = 0.2 M at 30 °C. For in vitro depolymerization studies, cell-free system was obtained from lysing bacterial cells suspension by ultrasonication at optimum conditions (frequency 37 kHz, 30% of power output, <25 (°)C for 120 minutes)...
June 21, 2017: Preparative Biochemistry & Biotechnology
Susie Vrobel
This paper focusses on the notions of time and timelessness in Eastern and Western thought traditions. The Introduction addresses the Eastern differentiation between the mind, which does not operate in a successive manner and is therefore not caught in time, and the time-laden successively operating mind and brain. I also describe how Jiddu Krishnamurti reconciles the two through insight, an event which restructures the brain and culminates in an eternal Now. In the following sections, I draw analogies to Western notions of timelessness and insight...
June 17, 2017: Progress in Biophysics and Molecular Biology
Fernando Lopez, David F Fernández, Moises Gulías, Jose L Mascareñas
A catalytic, versatile and atom-economical C-H functionalization process that provides a wide variety of cyclic systems featuring methyl-substituted quaternary stereocenters is described. The method relies on the use of a cationic Ir(I)-bisphosphine catalyst, which promotes a carboxamide-assisted activation of an olefinic C(sp2)-H bond followed by exo-cyclization to a tethered 1,1-disubstituted alkene. The extension of the method to aromatic and heteroaromatic C-H bonds, as well as developments on an enantioselective variant, are also described...
June 20, 2017: Angewandte Chemie
Wei He, Junpeng Zhuang, Zhanhui Yang, Jiaxi Xu
The [2 + 2] cycloadditions of thioketenes and imines are named as thio-Staudinger cycloadditions. The diastereoselectivity in thio-Staudinger cycloaddtions of alkyl/alkenyl/aryl-substituted thioketenes is rationalized. The steric effects of the thioketenes play an extremely important role in deciding the diastereoselectivity (cis/trans selectivity) through controlling exo- and endo-attack and subsequent ring closure. The conclusion is further supported by our additional experimental and calculational results...
June 20, 2017: Organic & Biomolecular Chemistry
Samy Cecioni, David J Vocadlo
Tunable Förster resonance energy transfer (FRET)-quenched substrates are useful for monitoring the activity of various enzymes within their relevant physiological environments. Development of FRET-quenched substrates for exo-glycosidases, however, has been hindered by their constrained pocket-shaped active sites. Here we report the design of a new class of substrate that overcomes this problem. These Bis-Acetal-Based Substrates (BABS) bear a hemiacetal aglycon leaving group that tethers fluorochromes in close proximity, also positioning them distant from the active site pocket...
June 20, 2017: Journal of the American Chemical Society
Oleksandr Plashkevych, Ram Shankar Upadhayaya, Jyoti Chattopadhyaya
In light of the impressive gene-silencing properties of carba-LNA modified oligo DNA and RNA, both in antisense RNA and siRNA approaches, which have been confirmed as proof-of-concept for biochemical applications in post-transcriptional gene silencing, we envision the true potential of carba-LNA modifications to be revealed soon. Herein we provide detailed protocols for synthesis of carba-LNA-A, -G, -(5-Me) C, and -T nucleosides on a medium/large scale (gram scale), as well as important guidelines for incorporation of these modified carba-LNAs into DNA or RNA oligonucleotides...
June 19, 2017: Current Protocols in Nucleic Acid Chemistry
Bing Xu, Zhan-Ming Zhang, Bing Liu, Shan Xu, Lu-Jia Zhou, Junliang Zhang
The employment of β,β-disubstituted enones as dipolarophiles poses a considerable challenge due to their steric hindrance and low reactivity. A copper-catalyzed asymmetric exo-selective dipolar cycloaddition of β-trifluoromethyl β,β-disubstituted enones with azomethine ylides was developed, which provides an efficient access to valuable pyrrolidines bearing a trifluoromethylated all-carbon quaternary stereocenter. Up to quantitative yields with up to >20 : 1 dr and 99% ee were delivered. A broad substrate scope, good functional group tolerance, high stereoselectivity, as well as diverse synthetically valuable transformations of the products make this approach highly attractive...
June 19, 2017: Chemical Communications: Chem Comm
Jie Zhou, Zhoukun Li, Jiale Wu, Lifeng Li, Ding Li, Xianfeng Ye, Xue Luo, Yan Huang, Zhongli Cui, Hui Cao
A novel β-(1,3)-glucanase gene designated lamC, cloned from Corallococcus sp. EGB, contains a fascin-like module and a glycoside hydrolase family 16 (GH16) catalytic module. LamC displays broad hydrolytic activity toward various polysaccharides. Analysis of the hydrolytic products revealed that LamC is an exo-acting enzyme on β-(1,3)- and β-(1,6)-linked glucan substrates and an endo-acting enzyme on β-(1,4)-linked glucan and xylan substrates. Site-directed mutagenesis of conserved catalytic Glu residues (E304A and E309A) demonstrated that these activities were derived from the same active site...
June 16, 2017: Applied and Environmental Microbiology
Ahmad Pourrashidi Boshrabadi, Mohammadali Surakiazad, Kourosh Karimi Yarandi, Abbas Amirjamshidi
INTRODUCTION: Extraskeletal osteosarcoma (ExOS) is a rare and well-known entity. Three to 4% of ExOSs occur in the head and neck region but anecdotally in the central nervous system (CNS). Primary intracranial osteosarcoma (PIOS) can originate from the skull, brain parenchyma, or meninges. CASE PRESENTATION: A 3-year-old boy with history of head trauma 2 weeks before admission is presented harboring an ExOS in the left temporoparietal region. He was operated with the impression of intraventricular meningioma but turned to be a PIOS without any sources in his skeleton...
June 16, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
Lei Xu, Xin Shen, Bingzhi Li, Chunhong Zhu, Xuemin Zhou
Adenosine is an endogenous nucleotide pivotally involved in nucleic acid and energy metabolism. Its excessive existence may indicate tumorigenesis, typically lung cancer. Encouraged by its significance as the clinical biomarker, sensitive assay methods towards adenosine have been popularized, with high cost and tedious procedures as the inevitable defects. Herein, we report a label-free aptamer-based exonuclease III (Exo III) amplification colorimetric aptasensor for the highly sensitive and cost-effective detection of adenosine...
August 8, 2017: Analytica Chimica Acta
Sanjay Basak, Arnab Sarkar, Santosh Mathapati, Asim K Duttaroy
Adequate placental angiogenesis is critical for the establishment of the placental circulation and thus for normal feto-placental growth and development. Fatty acid-binding protein-4 (FABP4) plays a pro-angiogenic role in endothelial cells; however, very little information is available in placental first trimester trophoblast cells. Here we report that exogenously added FABP4 (exo-FABP4) stimulated tube formation (as a measure of in vitro angiogenesis) in HTR8/SVneo trophoblastic cells. HTR-8/SVneo cells were incubated in the presence of exogenously added FABP4 at different concentrations and time points...
June 15, 2017: Molecular and Cellular Biochemistry
Ulrike Erb, Kun Zhao, Zhe Wang, Li Xiao, Margot Zöller
Exosomes (Exo), powerful intercellular communicators, are recovered in all body fluids, suggesting suitability for diagnosis and prognosis. Easy in vitro manipulation recommends Exo as drug vehicles. Aiming to consolidate diagnostic and therapeutic potential of Exo, we evaluated recovery and fate of tumor (TEX) and exogenous Exo in syngeneic and xenogeneic mice bearing a murine or a human pancreatic adenocarcinoma. A significant increase in serum (S)-TEX was observed 2 weeks after tumor cell application. Instead, S-TEX declined within 3-6 days after tumor excision...
June 12, 2017: Cancer Letters
Mikail E Abbasov, Brandi M Hudson, Dean J Tantillo, Daniel Romo
Chiral α,β-unsaturated acylammonium salts are novel dienophiles enabling enantioselective Diels-Alder-lactonization (DAL) organocascades leading to cis- and trans-fused, bicyclic γ- and δ-lactones from readily prepared dienes, commodity acid chlorides, and a chiral isothiourea organocatalyst under mild conditions. We describe extensions of stereodivergent DAL organocascades to other racemic dienes bearing pendant secondary and tertiary alcohols, and application to a formal synthesis of (+)-dihydrocompactin is described...
February 1, 2017: Chemical Science
Léo Arnoux, Sebastien Fromentin, Dario Farotto, Mathieu Beraneck, Joseph McIntyre, Michele Tagliabue
To perform goal-oriented hand movement humans combine multiple sensory signals (e.g. vision and proprioception) that can be encoded in various reference frames (body-centered and/or exo-centered). In a previous study we showed that when aligning a hand to a remembered target orientation the brain encodes both target and response in visual space when the target is sensed by one hand and the response is performed by the other, even though both are sensed only through proprioception. Here we ask whether such visual encoding is due i) to the necessity of transferring sensory information across the brain hemispheres or ii) to the necessity, due to the arms' anatomical mirror symmetry, of transforming the joint signals of one limb into the reference frame of the other...
June 14, 2017: Journal of Neurophysiology
Yue He, Chengqiu Wang, Qiyang Zhao, Yaohai Zhang, Aihua Chen, Junxiao Pang, Qi Fang, Yongliang Cui, Bining Jiao
Herein, we are presenting an approach that utilizes the λ exonuclease (λ exo) cleavage reaction in combination with the formation of G-quadruplex, thereby providing a label-free fluorometric tool for simply and accurately determining alkaline phosphatase (ALP) activity and inhibition. A hairpin probe (HP) with 5'-phosphoryl termini and 3'-end containing a G-rich region, is designed. Taking advantage of the efficient enzyme reactions, namely the λ exo cleavage reaction, the G-rich DNA fragment is released from HP and folds into a stable G-quadruplex in the presence of potassium ions, thus greatly enhance the fluorescence of N-methyl mesoporphyrin IX (NMM) (a specific G-quadruplex binder)...
September 1, 2017: Talanta
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