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https://www.readbyqxmd.com/read/29334372/pharmacological-blockade-of-asct2-dependent-glutamine-transport-leads-to-antitumor-efficacy-in-preclinical-models
#1
Michael L Schulte, Allie Fu, Ping Zhao, Jun Li, Ling Geng, Shannon T Smith, Jumpei Kondo, Robert J Coffey, Marc O Johnson, Jeffrey C Rathmell, Joe T Sharick, Melissa C Skala, Jarrod A Smith, Jordan Berlin, M Kay Washington, Michael L Nickels, H Charles Manning
The unique metabolic demands of cancer cells underscore potentially fruitful opportunities for drug discovery in the era of precision medicine. However, therapeutic targeting of cancer metabolism has led to surprisingly few new drugs to date. The neutral amino acid glutamine serves as a key intermediate in numerous metabolic processes leveraged by cancer cells, including biosynthesis, cell signaling, and oxidative protection. Herein we report the preclinical development of V-9302, a competitive small molecule antagonist of transmembrane glutamine flux that selectively and potently targets the amino acid transporter ASCT2...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29334321/biosynthesis-of-galactomannans-found-in-filamentous-fungi-belonging-to-pezizomycotina
#2
Takuji Oka
The galactomannans (GMs) that are produced by filamentous fungi belonging to Pezizomycotina, many of which are pathogenic for animals and plants, are polysaccharides consisting of α-(1→2)-/α-(1→6)-mannosyl and β-(1→5)-/β-(1→6)-galactofuranosyl residues. GMs are located at the outermost layer of the cell wall. When a pathogenic fungus infects a host, its cell surface must be in contact with the host. The GMs on the cell surface may be involved in the infection mechanism of a pathogenic fungus or the defense mechanism of a host...
January 15, 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29332424/salivary-metabolomics-profile-of-patients-with-recurrent-aphthous-ulcer-as-revealed-by-liquid-chromatography-tandem-mass-spectrometry
#3
Yantao Li, Daoming Wang, Chunwei Zeng, Yichen Liu, Guangyuan Huang, Zhanlong Mei
Objective We compared the salivary nontargeted metabolite profiles between patients with recurrent aphthous ulcer (RAU) and healthy individuals to investigate the metabolic alterations associated with RAU. Methods Saliva samples were collected from 45 patients with RAU and 49 healthy individuals, and the salivary metabolites were quantified using liquid chromatography-tandem mass spectrometry. The metabolomic profiles were then analyzed using multivariate and univariate statistical methods, and enrichment of the metabolites in various biological pathways was assessed...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29332207/skeletal-muscle-expression-of-p43-a-truncated-thyroid-hormone-receptor-%C3%AE-affects-lipid-composition-and-metabolism
#4
François Casas, Gilles Fouret, Jérome Lecomte, Fabienne Cortade, Laurence Pessemesse, Emilie Blanchet, Chantal Wrutniak-Cabello, Charles Coudray, Christine Feillet-Coudray
Thyroid hormone is a major regulator of metabolism and mitochondrial function. Thyroid hormone also affects reactions in almost all pathways of lipids metabolism and as such is considered as the main hormonal regulator of lipid biogenesis. The aim of this study was to explore the possible involvement of p43, a 43 Kda truncated form of the nuclear thyroid hormone receptor TRα1 which stimulates mitochondrial activity. Therefore, using mouse models overexpressing p43 in skeletal muscle (p43-Tg) or lacking p43 (p43-/-), we have investigated the lipid composition in quadriceps muscle and in mitochondria...
January 13, 2018: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29332191/genome-wide-characterization-of-differentially-expressed-genes-provides-insights-into-regulatory-network-of-heat-stress-response-in-radish-raphanus-sativus-l
#5
Ronghua Wang, Yi Mei, Liang Xu, Xianwen Zhu, Yan Wang, Jun Guo, Liwang Liu
Heat stress (HS) causes detrimental effects on plant morphology, physiology, and biochemistry that lead to drastic reduction in plant biomass production and economic yield worldwide. To date, little is known about HS-responsive genes involved in thermotolerance mechanism in radish. In this study, a total of 6600 differentially expressed genes (DEGs) from the control and Heat24 cDNA libraries of radish were isolated by high-throughput sequencing. With Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, some genes including MAPK, DREB, ERF, AP2, GST, Hsf, and Hsp were predominantly assigned in signal transductions, metabolic pathways, and biosynthesis and abiotic stress-responsive pathways...
January 13, 2018: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/29332168/efficient-crispr-cas9-based-genome-editing-in-carrot-cells
#6
Magdalena Klimek-Chodacka, Tomasz Oleszkiewicz, Levi G Lowder, Yiping Qi, Rafal Baranski
The first report presenting successful and efficient carrot genome editing using CRISPR/Cas9 system. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas9) is a powerful genome editing tool that has been widely adopted in model organisms recently, but has not been used in carrot-a model species for in vitro culture studies and an important health-promoting crop grown worldwide. In this study, for the first time, we report application of the CRISPR/Cas9 system for efficient targeted mutagenesis of the carrot genome...
January 13, 2018: Plant Cell Reports
https://www.readbyqxmd.com/read/29331924/gene-expression-patterns-regulating-the-seed-metabolism-in-relation-to-deterioration-ageing-of-primed-mung-bean-vigna-radiata-l-seeds
#7
Satyendra Nath Sharma, Ankita Maheshwari, Chitra Sharma, Nidhi Shukla
We are proposing mechanisms to account for the loss of viability (seed deterioration/ageing) and enhancement in seed quality (post-storage priming treatment). In order to understand the regulatory mechanism of these traits, we conducted controlled deterioration (CD) test for up to 8 d using primed mung bean seeds and examined how CD effects the expression of many genes, regulating the seed metabolism in relation to CD and priming. Germination declined progressively with increased duration of CD, and the priming treatment completely/partially reversed the inhibition depending on the duration of CD...
January 5, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29331904/anthocyanins-in-perilla-plants-and-dried-leaves
#8
Yumi Fujiwara, Miya Kono, Airi Ito, Michiho Ito
High-quality perilla leaves are purple on upper and lower surfaces and have a good aroma. The Japanese Pharmacopoeia specifies the content of essential oils in perilla leaves but not that of anthocyanins. Several reports have described the chemical species of anthocyanins in red perilla, but a complete analysis of anthocyanins in perilla has not been reported. In this study, the anthocyanins in the leaves of cultivated and wild species of perilla and those in commercially available perilla herbs were studied...
January 11, 2018: Phytochemistry
https://www.readbyqxmd.com/read/29331889/l-ascorbic-acid-metabolism-in-an-ascorbate-rich-kiwifruit-actinidia-eriantha-benth-cv-white-during-postharvest
#9
Zhen-Ye Jiang, Yu Zhong, Jian Zheng, Maratab Ali, Guo-Dong Liu, Xiao-Lin Zheng
Kiwifruit (Actinidia eriantha Benth.) 'White', a novel cultivar with higher L-ascorbic acid (AsA) level, is registered in China. Changes in AsA, related metabolites, enzymatic activity, and gene expression associated with AsA biosynthesis and recycling process were investigated in this paper. The results indicated that AsA biosynthesis through L-galactose pathway supplemented by D-galacturonic acid pathway and AsA recycling collectively contributed to accumulating and remaining higher AsA level in kiwifruit cv...
January 6, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29331744/urinary-metabolomics-study-the-mechanism-of-taohong-siwu-decoction-intervention-in-acute-blood-stasis-model-rats-based-on-liquid-chromatography-coupled-to-quadrupole-time-of-flight-mass-spectrometry
#10
Xiaosong Zhang, Pengling Li, Yongli Hua, Peng Ji, Wanling Yao, Qi Ma, Ziwen Yuan, Yanqiao Wen, Chaoxue Yang, Yanming Wei
Taohong Siwu Decoction (TSD) is a classic prescription in traditional Chinese medicine and is widely used to promote blood circulation to remove blood stasis. However, the effect mechanisms are not yet well understood. Here, a urinary metabolomic approach based on liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC/Q-TOF-MS) was conducted to explore the changes in the endogenous metabolites and to assess the integral efficacy of TSD on acute blood stasis model rats. Then, parameters for hemorheology and coagulation functions were detected...
January 2, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29331688/coproheme-decarboxylases-phylogenetic-prediction-versus-biochemical-experiments
#11
Vera Pfanzagl, Laurenz Holcik, Daniel Maresch, Giulia Gorgone, Hanna Michlits, Paul G Furtmüller, Stefan Hofbauer
Coproheme decarboxylases (ChdCs) are enzymes responsible for the catalysis of the terminal step in the coproporphyrin-dependent heme biosynthesis pathway. Phylogenetic analyses confirm that the gene encoding for ChdCs is widespread throughout the bacterial world. It is found in monoderm bacteria (Firmicutes, Actinobacteria), diderm bacteria (e. g. Nitrospirae) and also in Archaea. In order to test phylogenetic prediction ChdC representatives from all clades were expressed and examined for their coproheme decarboxylase activity...
January 10, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29331508/compartmentalized-crosstalk-of-cftr-and-tmem16a-ano1-through-epac1-and-adcy1
#12
Joana Lérias, Madalena Pinto, Roberta Benedetto, Rainer Schreiber, Margarida Amaral, Massimo Aureli, Karl Kunzelmann
Airway epithelial cells express both Ca2+ activated TMEM16A/ANO1 and cAMP activated CFTR anion channels. Previous work suggested a significant crosstalk of intracellular Ca2+ and cAMP signaling pathways, leading to activation of both chloride channels. We demonstrate that in airway epithelial cells, stimulation of purinergic or muscarinic G-protein coupled receptors (GPCRs) activates TMEM16A and CFTR. Additional expression of Gq/11 and phospholipase C coupled GPCRs strongly enhanced the crosstalk between Ca2+- and cAMP-dependent signaling...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29331423/thymidylate-synthase-prompts-metastatic-progression-through-the-dtmp-associated-emt-process-in-pancreatic-ductal-adenocarcinoma
#13
Muxing Kang, Wen Zheng, Qing Chen, Wenjie Qin, Pengping Li, Shifei Huang, Yizhao Zhou, Lantian Wang, Haolei Cai, Wenjie Lu, Biao Jiang, Qingqu Guo, Jian Chen, Dylan Wan, Jianyu Rao, Yulian Wu
As a fundamental metabolic enzyme, anti-Thymidylate synthase (TS) strategy has been shown to be an effective therapy for human cancers. However, the genuine effects of TS in pancreatic ductal adenocarcinoma (PDA) are still conflicting. We systemically assessed the prognostic value and whether TS associated with malignant progression in PDA. Protein and mRNA expression level of TS were evaluated in en bloc PDA samples, the prognostic effect of TS expressed in cytoplasm or cytonuclear was determined separately in the first time...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29331350/construction-of-pogoduet-an-inducible-bicistronic-vector-for-synthesis-of-recombinant-proteins-in-corynebacterium-glutamicum
#14
Oliver Goldbeck, Gerd M Seibold
The Gram-positive Corynebacterium glutamicum is widely known for its application in the industrial production of amino acids and as a non-pathogenic model organism for cell wall biosynthesis in the group of CMN bacteria. For biotechnological and physiological studies often co-expression of recombinant genes is required, however for C. glutamicum no vector for the independent co-expression of two genes was described. We here created the novel expression vector pOGOduet for C. glutamicum, which carries the ColE1 replicon of E...
January 10, 2018: Plasmid
https://www.readbyqxmd.com/read/29331336/udp-sugar-accumulation-drives-hyaluronan-synthesis-in-breast-cancer
#15
Sanna Oikari, Tiia Kettunen, Satu Tiainen, Jukka Häyrinen, Amro Masarwah, Mazen Sudah, Anna Sutela, Ritva Vanninen, Markku Tammi, Päivi Auvinen
Increased uptake of glucose, a general hallmark of malignant tumors, leads to an accumulation of intermediate metabolites of glycolysis. We investigated whether the high supply of these intermediates promotes their flow into UDP-sugars, and consequently into hyaluronan, a tumor-promoting matrix molecule. We quantified UDP-N-Acetylglucosamine (UDP-GlcNAc) and UDP-glucuronic acid (UDP-GlcUA) in human breast cancer biopsies, the levels of enzymes contributing to their synthesis, and their association with the hyaluronan accumulation in the tumor...
January 10, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29331089/modification-of-chrysanthemum-odour-and-taste-with-chrysanthemol-synthase-induces-strong-dual-resistance-against-cotton-aphids
#16
Hao Hu, Jinjin Li, Thierry Delatte, Jacques Vervoort, Liping Gao, Francel Verstappen, Wei Xiong, Jianping Gan, Maarten A Jongsma, Caiyun Wang
Aphids are pests of chrysanthemum that employ plant volatiles to select host plants and ingest cell contents to probe host quality before engaging in prolonged feeding and reproduction. Changes in volatile and non-volatile metabolite profiles can disrupt aphid-plant interactions and provide new methods of pest control. Chrysanthemol synthase (CHS) from Tanacetum cinerariifolium, represents the first committed step in the biosynthesis of pyrethrin ester insecticides, but no biological role for the chrysanthemol product alone has yet been documented...
January 13, 2018: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/29330614/effect-of-ancymidol-on-cell-wall-metabolism-in-growing-maize-cells
#17
J Mabel Hernández-Altamirano, Asier Largo-Gosens, Romina Martínez-Rubio, Diego Pereda, Jesús M Álvarez, José L Acebes, Antonio Encina, Penélope García-Angulo
Ancymidol inhibits the incorporation of cellulose into cell walls of maize cell cultures in a gibberellin-independent manner, impairing cell growth; the reduction in the cellulose content is compensated with xylans. Ancymidol is a plant growth retardant which impairs gibberellin biosynthesis. It has been reported to inhibit cellulose synthesis by tobacco cells, based on its cell-malforming effects. To ascertain the putative role of ancymidol as a cellulose biosynthesis inhibitor, we conducted a biochemical study of its effect on cell growth and cell wall metabolism in maize cultured cells...
January 12, 2018: Planta
https://www.readbyqxmd.com/read/29330556/evolution-of-the-phosphatidylcholine-biosynthesis-pathways-in-green-algae-combinatorial-diversity-of-methyltransferases
#18
Takashi Hirashima, Masakazu Toyoshima, Takashi Moriyama, Naoki Sato
Phosphatidylcholine (PC) is one of the most common phospholipids in eukaryotes, although some green algae such as Chlamydomonas reinhardtii are known to lack PC. Recently, we detected PC in four species in the genus Chlamydomonas: C. applanata NIES-2202, C. asymmetrica NIES-2207, C. debaryana NIES-2212, and C. sphaeroides NIES-2242. To reveal the PC biosynthesis pathways in green algae and the evolutionary scenario involved in their diversity, we analyzed the PC biosynthesis genes in these four algae using draft genome sequences...
January 12, 2018: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/29330550/a-metabolomics-pilot-study-on-desmoid-tumors-and-novel-drug-candidates
#19
Kelly A Mercier, Mushriq Al-Jazrawe, Raymond Poon, Zachery Acuff, Benjamin Alman
Desmoid tumors (aggressive fibromatosis) are locally invasive soft tissue tumors that lack the ability to metastasize. There are no directed therapies or standard treatment plan, and chemotherapeutics, radiation, and surgery often have temporary effects. The majority of desmoid tumors are related to T41A and S45F mutations of the beta-catenin encoding gene (CTNNB1). Using broad spectrum metabolomics, differences were investigated between paired normal fibroblast and desmoid tumor cells from affected patients...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330547/recessive-loss-of-function-pign-alleles-including-an-intragenic-deletion-with-founder-effect-in-la-r%C3%A3-union-island-in-patients-with-fryns-syndrome
#20
Jean-Luc Alessandri, Christopher T Gordon, Marie-Line Jacquemont, Nicolas Gruchy, Norbert F Ajeawung, Guillaume Benoist, Myriam Oufadem, Asma Chebil, Yannis Duffourd, Coralie Dumont, Marion Gérard, Paul Kuentz, Thibaud Jouan, Francesca Filippini, Thi Tuyet Mai Nguyen, Olivier Alibeu, Christine Bole-Feysot, Patrick Nitschké, Asma Omarjee, Duksha Ramful, Hanitra Randrianaivo, Bérénice Doray, Laurence Faivre, Jeanne Amiel, Philippe M Campeau, Julien Thevenon
Fryns syndrome (FS) is a multiple malformations syndrome with major features of congenital diaphragmatic hernia, pulmonary hypoplasia, craniofacial dysmorphic features, distal digit hypoplasia, and a range of other lower frequency malformations. FS is typically lethal in the fetal or neonatal period. Inheritance is presumed autosomal recessive. Although no major genetic cause has been identified for FS, biallelic truncating variants in PIGN, encoding a component of the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway, have been identified in a limited number of cases with a phenotype compatible with FS...
January 12, 2018: European Journal of Human Genetics: EJHG
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