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https://www.readbyqxmd.com/read/29220569/crocadepsins-depsipeptides-from-the-myxobacterium-chondromyces-crocatus-found-by-a-genome-mining-approach
#1
Frank Surup, Konrad Viehrig, Shwan Rachid, Alberto Plaza, Christine K Maurer, Rolf W Hartmann, Rolf Müller
Analysis of the genome sequence of the myxobacterium Chondromyces crocatus Cm c5 revealed the presence of numerous cryptic megasynthetase gene clusters, one of which we here assign to two previously unknown chlorinated metabolites by a comparative gene inactivation and secondary metabolomics approach. Structure elucidation of these compounds revealed a unique cyclic depsipeptide skeleton featuring β- and δ-amide bonds of aspartic acid and 3-methyl ornithine moieties, respectively. Insights into their biosynthesis were obtained by targeted gene inactivation and feeding experiments employing isotope-labeled precursors...
December 8, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29219809/the-cell-wall-of-the-filamentous-anoxygenic-phototrophic-bacterium-oscillochloris-trichoides
#2
Olga I Keppen, Ruslan N Ivanovsky, Galina M Streshinskaya, Natalia V Lebedeva, Alexander S Shashkov, Andrey S Dmitrenok, Denis S Grouzdev
The filamentous anoxygenic phototrophic bacterium Oscillochloris trichoides DG-6 has been studied, and it has been shown that there are no lipopolysaccharides on the cell surface. Fatty acids hydroxylated at the C3 position, amino sugars and phosphate-containing compounds characteristic of lipid A have also not been found. The genes encoding for proteins responsible for the synthesis of lipopolysaccharides and the genes for the transport system, usually localized in the outer membrane of Gram-negative bacteria, have not been detected in the genome...
December 8, 2017: Microbiology
https://www.readbyqxmd.com/read/29215586/investigation-of-polyamine-metabolism-and-homeostasis-in-pancreatic-cancers
#3
Chelsea Massaro, Jenna Thomas, Otto Phanstiel Iv
Pancreatic cancers are currently the fourth leading cause of cancer-related death and new therapies are desperately needed. The most common pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). This report describes the development of therapies, which effectively deplete PDAC cells of their required polyamine growth factors. Of all human tissues, the pancreas has the highest level of the native polyamine spermidine. To sustain their high growth rates, PDACs have altered polyamine metabolism, which is reflected in their high intracellular polyamine levels and their upregulated import of exogenous polyamines...
December 7, 2017: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29215193/metabolomics-of-tomato-xylem-sap-during-bacterial-wilt-reveals-ralstonia-solanacearum-produces-abundant-putrescine-a-metabolite-that-accelerates-wilt-disease
#4
Tiffany M Lowe-Power, Connor G Hendrich, Edda von Roepenack-Lahaye, Bin Li, Dousheng Wu, Raka Mitra, Beth L Dalsing, Patrizia Ricca, Jacinth Naidoo, David Cook, Amy Jancewicz, Patrick Masson, Bart Thomma, Thomas Lahaye, Anthony J Michael, Caitilyn Allen
Ralstonia solanacearum thrives in plant xylem vessels and causes bacterial wilt disease despite the low nutrient content of xylem sap. We found that R. solanacearum manipulates its host to increase nutrients in tomato xylem sap, enabling it to grow better in sap from infected plants than in sap from healthy plants. Untargeted GC/MS metabolomics identified 22 metabolites enriched in R. solanacearum-infected sap. Eight of these could serve as sole carbon or nitrogen sources for R. solanacearum. Putrescine, a polyamine that is not a sole carbon or nitrogen source for R...
December 7, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/29210399/an-ion-pair-receptor-comprising-urea-groups-and-n-benzyl-aza-18-crown-6-effective-recognition-and-liquid-liquid-extraction-of-kcl-salt
#5
Maciej Zakrzewski, Dominika Załubiniak, Piotr Piątek
Compound 1 was designed and prepared as a heteroditopic ion-pair receptor that contains two urea groups for anion complexation and N-benzyl-18-crown-6 for cation recognition. These ion-binding domains are assembled together by the l-ornithine scaffold. Qualitative cation coordination studies of receptor 1, supported by quantitative data received for monotopic N-(3-nitrobenzyl)-aza-18-crown-6 (3a), have shown that 1 has a strong affinity for Na+, K+ and NH4+ cations. Anion binding studies revealed that in the absence of cations coordinated to 1 (TBA salts), anions are bound with a relatively moderate strength with the selectivity: BzO- > AcO- > Cl-> NO2- > Br-...
December 6, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29209135/first-case-of-cross-auxiliary-double-domino-donor-liver-transplantation
#6
Zhi-Jun Zhu, Lin Wei, Wei Qu, Li-Ying Sun, Ying Liu, Zhi-Gui Zeng, Liang Zhang, En-Hui He, Hai-Ming Zhang, Ji-Dong Jia, Zhong-Tao Zhang
We report a case of double domino liver transplantation in a 32-year-old woman who was diagnosed with familial amyloid polyneuropathy (FAP) and liver dysfunction. A two-stage surgical plan was designed, and one domino graft was implanted during each stage. During the first stage, an auxiliary domino liver transplantation was conducted using a domino graft from a 4-year-old female child with Wilson's disease. After removing the right lobe of the FAP patient's liver, the graft was rotated 90 degrees counterclockwise and placed along the right side of the inferior vena cava (IVC)...
November 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29190951/multi-omics-analysis-reveals-that-ornithine-decarboxylase-contributes-to-erlotinib-resistance-in-pancreatic-cancer-cells
#7
Won-Jun Jang, Boyeon Choi, Sang-Hoon Song, Naeun Lee, Dong-Joon Kim, Sooyeun Lee, Chul-Ho Jeong
Molecular and metabolic alterations in cancer cells are one of the leading causes of acquired resistance to chemotherapeutics. In this study, we explored an experimental strategy to identify which of these alterations can induce erlotinib resistance in human pancreatic cancer. Using genetically matched erlotinib-sensitive (BxPC-3) and erlotinib-resistant (BxPC-3ER) pancreatic cancer cells, we conducted a multi-omics analysis of metabolomes and transcriptomes in these cells. Untargeted and targeted metabolomic analyses revealed significant changes in metabolic pathways involved in the regulation of polyamines, amino acids, and fatty acids...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29187192/comprehensive-metabolic-profiling-of-chronic-low-grade-inflammation-among-generally-healthy-individuals
#8
Maik Pietzner, Anne Kaul, Ann-Kristin Henning, Gabi Kastenmüller, Anna Artati, Markus M Lerch, Jerzy Adamski, Matthias Nauck, Nele Friedrich
BACKGROUND: Inflammation occurs as an immediate protective response of the immune system to a harmful stimulus, whether locally confined or systemic. In contrast, a persisting, i.e., chronic, inflammatory state, even at a low-grade, is a well-known risk factor in the development of common diseases like diabetes or atherosclerosis. In clinical practice, laboratory markers like high-sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen, are used to reveal inflammatory processes...
November 30, 2017: BMC Medicine
https://www.readbyqxmd.com/read/29180053/unique-properties-of-arginase-purified-from-camel-liver-cytosol
#9
Tahany M Maharem, Walid E Zahran, Rasha E Hassan, Mohamed M Abdel Fattah
Arginase (ARG) is an enzyme involved in urea cycle, where it catalyzes the hydrolysis of L-arginine into L-ornithine and urea. Since there is no information about the isolation and purification of ARG from camel liver, this investigation was designed to purify and characterize ARG from camel liver and compare its molecular and kinetic properties with that reported from other species. Camel liver arginase (CL-ARG) was purified to homogeneity using heat denaturation followed by ammonium sulphate precipitation with a combination of DEAE-cellulose, SP-Sepharose and Sephadex G 100-120 chromatography columns...
November 24, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29171503/-prevention-and-treatment-of-hepatic-encephalopathy
#10
Yu P Sivolap
Hepatic encephalopathy is a common neuropsychiatric complication of serious liver diseases and serves as a marker for worsening of their course and increasing the risk of death. The principal pathogenesis factors of hepatic encephalopathy is the excessive formation of ammonia and its accumulation by astrocytes. A key role in the prevention and treatment of hepatic encephalopathy is played by drugs that prevent hyperammonemia and promote the removal of ammonia from the body, namely lactulose, rifaximin and L-ornithine-L-aspartate...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29170487/lysine-possesses-the-optimal-chain-length-for-histone-lysine-methyltransferase-catalysis
#11
Abbas H K Al Temimi, Y Vijayendar Reddy, Paul B White, Hong Guo, Ping Qian, Jasmin Mecinović
Histone lysine methyltransferases (KMTs) represent an important class of epigenetic enzymes that play essential roles in regulation of gene expression in humans. Members of the KMT family catalyze the transfer of the methyl group from S-adenosylmethionine (SAM) to lysine residues in histone tails and core histones. Here we report combined MALDI-TOF MS experiments, NMR analyses and quantum mechanical/molecular dynamics studies on human KMT-catalyzed methylation of the most related shorter and longer lysine analogues, namely ornithine and homolysine, in model histone peptides...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29168171/the-arginine-metabolome-in-acute-lymphoblastic-leukemia-can-be-targeted-by-the-peg-recombinant-arginase-i-bct-100
#12
Carmela De Santo, Sarah Booth, Ashley Vardon, Antony Cousins, Vanessa Tubb, Tracey Perry, Boris Noyvert, Andrew Beggs, Margaret Ng, Christina Halsey, Pamela Kearns, Paul Cheng, Francis Mussai
Arginine is a semi-essential amino acid that plays a key role in cell survival and proliferation in normal and malignant cells. BCT-100, a pegylated recombinant human arginase, can deplete arginine and starve malignant cells of the amino acid. Acute Lymphoblastic Leukemia is the most common cancer of childhood, yet for patients with high risk or relapsed disease prognosis remains poor. We show that BCT-100 is cytotoxic to ALL blasts from patients in vitro by necrosis, and is synergistic in combination with dexamethasone...
November 23, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29163826/hdac-inhibitors-enhance-neratinib-activity-and-when-combined-enhance-the-actions-of-an-anti-pd-1-immunomodulatory-antibody-in-vivo
#13
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Paul Dent
Patients whose NSCLC tumors become afatinib resistant presently have few effective therapeutic options to extend their survival. Afatinib resistant NSCLC cells were sensitive to clinically relevant concentrations of the irreversible pan-HER inhibitor neratinib, but not by the first generation ERBB1/2/4 inhibitor lapatinib. In multiple afatinib resistant NSCLC clones, HDAC inhibitors reduced the expression of ERBB1/3/4, but activated c-SRC, which resulted in higher total levels of ERBB1/3 phosphorylation. Neratinib also rapidly reduced the expression of ERBB1/2/3/4, c-MET and of mutant K-/N-RAS; K-RAS co-localized with phosphorylated ATG13 and with cathepsin B in vesicles...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155067/contrasting-roles-of-fungal-siderophores-in-maintaining-iron-homeostasis-in-epichlo%C3%A3-festucae
#14
Natasha T Forester, Geoffrey A Lane, Melle Steringa, Iain L Lamont, Linda J Johnson
The symbiosis between Epichloë festucae and its host perennial ryegrass (Lolium perenne) is a model system for mutualistic interactions in which the fungal endophyte grows between plant shoot cells and acquires host nutrients to survive. E. festucae synthesises the siderophore epichloënin A (EA) via SidN, a non-ribosomal peptide synthetase (NRPS). EA is involved in the acquisition of iron, an essential micronutrient, as part of the process of maintaining a stable symbiotic interaction. Here, we mutated a different NRPS gene sidC and showed that it is required for production of a second siderophore ferricrocin (FC)...
November 15, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/29153651/enhanced-l-ornithine-production-by-systematic-manipulation-of-l-ornithine-metabolism-in-engineered-corynebacterium-glutamicum-s9114
#15
Bin Zhang, Li-Quan Ren, Miao Yu, Ying Zhou, Bang-Ce Ye
l-Ornithine is a non-protein amino acid with extensive applications in medicine and the food industry. Currently, l-ornithine is produced by microbial fermentation; however, this process needs to be further improved in terms of l-ornithine productivity and cost reduction. In this study, overexpression of LysE was observed to increase l-ornithine production in engineered Corynebacterium glutamicum S9114. To overcome the drawbacks of using a plasmid to express LysE, Ptac, a strong promoter, was inserted in the upstream region of lysE on the chromosome...
November 8, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/29150896/stereospecific-control-of-peptide-gas-phase-ion-chemistry-with-cis-and-trans-cyclo-ornithine-residues
#16
Aleš Marek, Huong T H Nguyen, Břetislav Brož, František Tureček
We report non-chiral amino acid residues cis- and trans-1,4-diaminocyclohexane-1-carboxylic acid (cyclo-ornithine, cO) that exhibit unprecedented stereospecific control of backbone dissociations of singly charged peptide cations and hydrogen-rich cation radicals produced by electron-transfer dissociation (ETD). Upon collision-induced dissociation (CID) in the slow heating regime, peptide cations containing trans-cO residues undergo facile backbone cleavages of amide bonds C-terminal to trans-cO. In contrast, peptides with cis-cO residues undergo dissociations at several amide bonds along the peptide ion backbone...
November 18, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/29147966/polyamine-concentration-is-increased-in-thoracic-ascending-aorta-of-patients-with-bicuspid-aortic-valve
#17
Amalia Forte, Mario Grossi, Ciro Bancone, Marilena Cipollaro, Marisa De Feo, Per Hellstrand, Lo Persson, Bengt-Olof Nilsson, Alessandro Della Corte
Polyamines are cationic molecules synthesized via a highly regulated pathway, obtained from the diet or produced by the gut microbiota. They are involved in general molecular and cellular phenomena that play a role also in vascular disease. Bicuspid aortic valve (BAV) is a congenital malformation associated to a greater risk of thoracic ascending aorta (TAA) aneurysm, whose pathogenesis is not yet well understood. We focused on differential analysis of key members of polyamine pathway and on polyamine concentration in non-dilated TAA samples from patients with either stenotic tricuspid aortic valve (TAV) or BAV (diameter ≤ 45 mm), vs...
November 17, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/29135983/arginase-expression-modulates-nitric-oxide-production-in-leishmania-leishmania-amazonensis
#18
Stephanie Maia Acuña, Juliana Ide Aoki, Maria Fernanda Laranjeira-Silva, Ricardo Andrade Zampieri, Juliane Cristina Ribeiro Fernandes, Sandra Marcia Muxel, Lucile Maria Floeter-Winter
BACKGROUND: Arginase is an enzyme that converts L-arginine to urea and L-ornithine, an essential substrate for the polyamine pathway supporting Leishmania (Leishmania) amazonensis replication and its survival in the mammalian host. L-arginine is also the substrate of macrophage nitric oxide synthase 2 (NOS2) to produce nitric oxide (NO) that kills the parasite. This competition can define the fate of Leishmania infection. METHODOLOGY/PRINCIPAL FINDINGS: The transcriptomic profiling identified a family of oxidoreductases in L...
2017: PloS One
https://www.readbyqxmd.com/read/29135915/evaluation-of-polyamine-transport-inhibitors-in-a-drosophila-epithelial-model-suggests-the-existence-of-multiple-transport-systems
#19
Minpei Wang, Otto Phanstiel, Laurence von Kalm
Increased polyamine biosynthesis activity and an active polyamine transport system are characteristics of many cancer cell lines and polyamine depletion has been shown to be a viable anticancer strategy. Polyamine levels can be depleted by difluoromethylornithine (DFMO), an inhibitor of the key polyamine biosynthesis enzyme ornithine decarboxylase (ODC). However, malignant cells frequently circumvent DFMO therapy by up-regulating polyamine import. Therefore, there is a need to develop compounds that inhibit polyamine transport...
November 14, 2017: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29126478/optimization-of-gc-tof-ms-analysis-conditions-for-assessing-host-gut-microbiota-metabolic-interactions-chinese-rhubarb-alters-fecal-aromatic-amino-acids-and-phenol-metabolism
#20
Shan Yin, Pan Guo, Dafu Hai, Li Xu, Jiale Shu, Wenjin Zhang, Muhammad Idrees Khan, Irwin J Kurland, Yunping Qiu, Yumin Liu
In this paper, an optimized method based on gas chromatography/time-of-flight mass spectrometry (GC-TOFMS) platform has been developed for the analysis of gut microbial-host related co-metabolites in fecal samples. The optimization was performed with proportion of chloroform (C), methanol (M) and water (W) for the extraction of specific metabolic pathways of interest. Loading Bi-plots from the PLS regression model revealed that high concentration of chloroform emphasized the extraction of short chain fatty acids and TCA intermediates, while the higher concentration of methanol emphasized indole and phenyl derivatives...
December 1, 2017: Analytica Chimica Acta
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