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https://www.readbyqxmd.com/read/28222482/functional-reconstitution-of-the-mycobacterium-tuberculosis-long-chain-acyl-coa-carboxylase-from-multiple-acyl-coa-subunits
#1
Bernardo Bazet Lyonnet, Lautaro Diacovich, Gabriela Gago, Lucie Spina, Fabienne Bardou, Anne Lemassu, Annaïk Quémard, Hugo Gramajo
Mycobacterium tuberculosis produces a large number of structurally diverse lipids that have been implicated in the pathogenicity, persistence and antibiotic resistance of this organism. Most building blocks involved in the biosynthesis of all these lipids are generated by acyl-CoA carboxylases (ACCase) whose subunit composition and physiological roles have not yet been clearly established. A rather controversial data in the literature refers to the exact protein composition and substrate specificity of the enzyme complex that produces the long-chain α-carboxy-acyl-CoAs; one of the substrates involved in the last step of condensation mediated by the polyketide synthase Pks13 to synthesize mature mycolic acids...
February 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28221861/inhibiting-histone-deacetylase-as-a-means-to-reverse-resistance-to-angiogenesis-inhibitors-phase-i-study-of-abexinostat-plus-pazopanib-in-advanced-solid-tumor-malignancies
#2
Rahul Aggarwal, Scott Thomas, Nela Pawlowska, Imke Bartelink, Jennifer Grabowsky, Thierry Jahan, Amy Cripps, Armand Harb, Jim Leng, Anne Reinert, Ilaria Mastroserio, Thach-Giao Truong, Charles J Ryan, Pamela N Munster
Purpose This phase I trial evaluated epigenetic modulation of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor by using a histone deacetylase abexinostat in combination with pazopanib to enhance response and reverse resistance. Patients and Methods Pazopanib was administered once a day on days 1 to 28 and abexinostat was administered orally twice a day on days 1 to 5, 8 to 12, and 15 to 19 (schedule A) or on days 1 to 4, 8 to 11, and 15 to 18 (schedule B). Dose escalation (3 + 3 design) in all solid tumors was followed by dose expansion in renal cell carcinoma (RCC)...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28220956/releasing-the-cohesin-ring-a-rigid-scaffold-model-for-opening-the-dna-exit-gate-by-pds5-and-wapl
#3
Zhuqing Ouyang, Hongtao Yu
The ring-shaped ATPase machine, cohesin, regulates sister chromatid cohesion, transcription, and DNA repair by topologically entrapping DNA. Here, we propose a rigid scaffold model to explain how the cohesin regulators Pds5 and Wapl release cohesin from chromosomes. Recent studies have established the Smc3-Scc1 interface as the DNA exit gate of cohesin, revealed a requirement for ATP hydrolysis in ring opening, suggested regulation of the cohesin ATPase activity by DNA and Smc3 acetylation, and provided insights into how Pds5 and Wapl open this exit gate...
February 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28220771/expanding-the-genetic-code-of-mus-musculus
#4
Songmi Han, Aerin Yang, Soonjang Lee, Han-Woong Lee, Chan Bae Park, Hee-Sung Park
Here we report the expansion of the genetic code of Mus musculus with various unnatural amino acids including N(ɛ)-acetyl-lysine. Stable integration of transgenes encoding an engineered N(ɛ)-acetyl-lysyl-tRNA synthetase (AcKRS)/tRNA(Pyl) pair into the mouse genome enables site-specific incorporation of unnatural amino acids into a target protein in response to the amber codon. We demonstrate temporal and spatial control of protein acetylation in various organs of the transgenic mouse using a recombinant green fluorescent protein (GFPuv) as a model protein...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28220633/fatty-acid-composition-fat-deposition-lipogenic-gene-expression-and-performance-of-broiler-fed-diet-supplemented-with-different-sources-of-oil
#5
Jannatara Khatun, Teck Chwen Loh, Henny Akit, Hooi Ling Foo, Rosfarizan Mohamad
The present study assessed the effect of feeding palm oil (PO), sunflower oil (SO) and their combination on performance, fat deposition, fatty acid composition and lipogenic gene expression of broilers reared for 42 days. A total of 144 1-day-old broilers (Cobb500) were randomly allotted into four treatment diets with each having six replicates of six chicks in each replicate following a completely randomized design. Live weight gain and feed efficiency was significantly (P < 0.05) higher in birds fed with a combination of oil sources compared to controls...
February 21, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/28219933/akt-signalling-as-a-mediator-of-cardiac-adaptation-to-low-birth-weight
#6
Kimberley Cw Wang, Kimberley J Botting, Song Zhang, Caroline McMillen, Doug A Brooks, Janna L Morrison
Intrauterine insults, such as poor nutrition and placental insufficiency, can alter cardiomyocyte development and this can have significant long-term implications for heart health. Consequently, epidemiological studies have shown that low birth weight babies have an increased risk of death from cardiovascular disease in adult life. In addition, intrauterine growth restriction can result in increased left ventricular hypertrophy, which is the strongest predictor for poor health outcomes in cardiac patients. The mechanisms responsible for these associations are not clear, but a suboptimal intrauterine environment can program alternative expression of genes such as cardiac IGF-2/H19, IGF-2R and AT1R through either an increase or decrease in DNA methylation or histone acetylation at specific loci...
February 20, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28219012/the-tyrosinase-catalyzed-oxidation-of-the-leukoderma-inducing-agent-raspberry-ketone-produces-e-4-3-oxo-1-butenyl-1-2-benzoquinone-implications-for-melanocyte-toxicity
#7
Shosuke Ito, Maki Hinoshita, Erina Suzuki, Makoto Ojika, Kazumasa Wakamatsu
The exposure of human skin to 4-(4-hydroxyphenyl)-2-butanone (raspberry ketone, RK) is known to cause chemical/occupational leukoderma. RK has a structure closely related to 4-(4-hydroxyphenyl)-2-butanol (rhododendrol), a skin whitening agent that was found to cause leukoderma in the skin of consumers in 2013. Rhododendrol is a good substrate for tyrosinase and causes a tyrosinase-dependent cytotoxicity to melanocytes, cells that are responsible for skin pigmentation. Therefore, it is expected that RK exerts its cytotoxicity to melanocytes through the tyrosinase-catalyzed oxidation to cytotoxic o-quinones...
February 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28218781/study-on-the-effects-of-blueberry-treatment-on-histone-acetylation-modification-of-ccl4-induced-liver-disease-in-rats
#8
W Zhan, X Liao, T Tian, L Yu, X Liu, B Li, J Liu, B Han, R J Xie, Q H Ji, Q Yang
The objective of this study was to investigate the effects of blueberry treatment on histone acetylation modification of carbon tetrachloride (CCl4)-induced liver disease in rats. Laboratory rats were randomly divided into control, hepatic fibrosis, blueberry treatment, blueberry intervention, and natural recovery groups. Rats in the model groups were treated with CCl4 administered subcutaneously at 4- and 8-week intervals, and then executed. Both the 4- and 8-week treatment groups were treated with blueberry juice for 8 weeks, and then executed after 12 and 16 weeks, respectively...
February 16, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28216958/-1-h-nmr-based-serum-metabolomics-reveals-erythromycin-induced-liver-toxicity-in-albino-wistar-rats
#9
Atul Rawat, Durgesh Dubey, Anupam Guleria, Umesh Kumar, Amit K Keshari, Swati Chaturvedi, Anand Prakash, Sudipta Saha, Dinesh Kumar
INTRODUCTION: Erythromycin (ERY) is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. OBJECTIVE: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using (1)H NMR based serum metabolomics...
October 2016: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/28216620/aspirin-alleviates-cardiac-fibrosis-in-mice-by-inhibiting-autophagy
#10
Ping-Ping Liu, Hong-Hong Liu, Shu-Hong Sun, Xing-Xing Shi, Wan-Cheng Yang, Guo-Hai Su, Jing Zhao
Aspirin (ASA) is a cardioprotective drug with anti-cardiac fibrosis action in vivo. This study was aimed to clarify the anti-cardiac fibrosis action of ASA and the underlying mechanisms. Two heart injury models (injection of isoproterenol and ligation of the left anterior descending branch) were used in mice to induce cardiac fibrosis. The animals were treated with ASA (10 mg·kg(-1)·d(-1), ig) for 21 and 14 d, respectively. ASA administration significantly improved cardiac function, and ameliorated heart damage and fibrosis in the mice...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28216594/anti-hyperglycemic-activity-of-major-compounds-from-calea-ternifolia
#11
Sonia Escandón-Rivera, Araceli Pérez-Vásquez, Andrés Navarrete, Mariana Hernández, Edelmira Linares, Robert Bye, Rachel Mata
Demethylisoencecalin (1) and caleins A (4) and C (5) (3.16-31.6 mg/kg, p.o.), the major components from an infusion of Calea ternifolia controlled postprandial glucose levels during an oral sucrose tolerance test (OSTT, 3 g/kg) in normal and nicotinamide/streptozotocin (NA/STZ, 40/100 mg/kg) hyperglicemic mice. The effects were comparable to those of acarbose (5 mg/kg). During the isolation of 1, 4, and 5, four additional metabolites not previously reported for the plant, were obtained, namely 6-acetyl-5-hydroxy-2-methyl-2-hydroxymethyl-2H-chromene (3), herniarin (6), scoparone (7), and 4',7-dimethylapigenin (8)...
February 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28216155/forced-fog1-expression-in-erythroleukemia-cells-induction-of-erythroid-genes-and-repression-of-myelo-lymphoid-transcription-factor-pu-1
#12
Tohru Fujiwara, Katsuyuki Sasaki, Kei Saito, Shunsuke Hatta, Satoshi Ichikawa, Masahiro Kobayashi, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Hideo Harigae
The transcription factor GATA-1-interacting protein Friend of GATA-1 (FOG1) is essential for proper transcriptional activation and repression of GATA-1 target genes; yet, the mechanisms by which FOG1 exerts its activating and repressing functions remain unknown. Forced FOG1 expression in human K562 erythroleukemia cells induced the expression of erythroid genes (SLC4A1, globins) but repressed that of GATA-2 and PU.1. A quantitative chromatin immunoprecipitation (ChIP) analysis demonstrated increased GATA-1 chromatin occupancy at both FOG1-activated as well as FOG1-repressed gene loci...
February 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28216063/the-nad-precursor-nicotinic-acid-improves-genomic-integrity-in-human-peripheral-blood-mononuclear-cells-after-x-irradiation
#13
Kathrin Weidele, Sascha Beneke, Alexander Bürkle
NAD(+) is an essential cofactor for enzymes catalyzing redox-reactions as well as an electron carrier in energy metabolism. Aside from this, NAD(+) consuming enzymes like poly(ADP-ribose) polymerases and sirtuins are important regulators involved in chromatin-restructuring processes during repair and epigenetics/transcriptional adaption. In order to replenish cellular NAD(+) levels after cleavage, synthesis starts from precursors such as nicotinamide, nicotinamide riboside or nicotinic acid to match the need for this essential molecule...
February 13, 2017: DNA Repair
https://www.readbyqxmd.com/read/28216050/vancomycin-induces-reactive-oxygen-species-dependent-apoptosis-via-mitochondrial-cardiolipin-peroxidation-in-renal-tubular-epithelial-cells
#14
Yuya Sakamoto, Takahisa Yano, Yuki Hanada, Aki Takeshita, Fumika Inagaki, Satohiro Masuda, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo
Vancomycin (VCM) is a first-line antibiotic for serious infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is one of the most complaint in VCM therapy. We previously reported that VCM induced apoptosis in a porcine proximal tubular epithelial cell line (LLC-PK1), in which mitochondrial complex I may generate superoxide, leading to cell death. In the present study, VCM caused production of mitochondrial reactive oxygen species and peroxidation of the mitochondrial phospholipid cardiolipin that was reversed by administration of the mitochondrial uncoupler carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP)...
February 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28215637/polyglycolic-acid-sheet-attached-with-fibrin-glue-can-facilitate-faster-epithelialization-of-the-mastoid-cavity-after-canal-wall-down-tympanoplasty
#15
Taisuke Kobayashi, Kiyofumi Gyo, Masahiro Komori, Masamitsu Hyodo
OBJECTIVE: This study retrospectively investigated whether polyglycolic acid (PGA) sheet attached to the bone surface using fibrin glue facilitate faster epithelialization of the mastoid bowl after canal wall-down (CWD) tympanoplasty compared to a simple dressing using poly-N-acetyl-glucosamine (Kichin) sheet. MATERIALS AND METHODS: After completion of the CWD tympanoplasty, PGA sheet (n=16, PGA group) with fibrin glue or Kichin sheet (n=38, Kichin group) were placed on the bone surface of the mastoid bowl...
February 16, 2017: Auris, Nasus, Larynx
https://www.readbyqxmd.com/read/28215142/small-molecule-modulation-of-hdac6-activity-the-propitious-therapeutic-strategy-to-vanquish-neurodegenerative-disorders
#16
Shabir Ahmad Ganai
Histone deacetylases (HDACs) are epigenetic enzymes creating the transcriptionally inactive state of chromatin by erasing acetyl moiety from histone and non-histone substrates. HDAC6 modulates several biological pathways in dividing cells as well as in post-mitotic neurons, and has been implicated in the pathophysiology of neurodegeneration. The distinct cellular functions and survival in these cells are reliant on HDAC6-mediated processes including intracellular trafficking, chaperone-mediated stress responses, anti-oxidation and protein degradation...
February 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28214900/mir-21-regulates-tnf-%C3%AE-induced-cd40-expression-via-the-sirt1-nf-%C3%AE%C2%BAb-pathway-in-renal-inner-medullary-collecting-duct-cells
#17
Qinqin Lin, Yuanwen Geng, Meng Zhao, Shuaishuai Lin, Qing Zhu, Zhenjun Tian
BACKGROUND/AIMS: Recent studies have indicated that microRNA-21 (miR-21) is involved in the inflammatory response in relation to renal disease. Sirtuin1 (SIRT1) exerts renoprotective properties by counteracting inflammation. The activation of CD40 triggers inflammation that participates in renal inflammation and injury. The relationship between miR-21, SIRT1 and CD40, however, remains elusive. METHODS: Immunohistochemistry, small-interfering RNA (siRNA) transfection, quantitative real-time PCR and western blotting were applied to assess the morphological, functional and molecular mechanisms in primary cultured renal inner medullary collecting duct (IMCD) cells...
January 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214842/inhibition-of-methylglyoxal-induced-ages-rage-expression-contributes-to-dermal-protection-by-n-acetyl-l-cysteine
#18
Chun-Tao Yang, Fu-Hui Meng, Li Chen, Xiang Li, Lai-Jian Cen, Yu-Hua Wen, Cai-Chen Li, Hui Zhang
BACKGROUND/AIM: Accumulation of advanced glycation end products (AGEs) is a major cause of diabetes mellitus (DM) skin complications. Methylglyoxal (MGO), a reactive dicarbonyl compound, is a crucial intermediate of AGEs generation. N-acetyl-L-cysteine (NAC), an active ingredient of some medicines, can induce endogenous GSH and hydrogen sulfide generation, and set off a condensation reaction with MGO. However, there is rare evidence to show NAC can alleviate DM-induced skin injury through inhibition of AGEs generation or toxicity...
13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214753/structural-and-functional-insights-into-corrinoid-iron-sulfur-protein-from-human-pathogen-clostridium-difficile
#19
Yaozhu Wei, Xiaofei Zhu, Sixue Zhang, Xiangshi Tan
The human pathogen Clostridium difficile infection (CDI) is one of the most important healthcare-associated infections. The Wood-Ljungdahl pathway, which is responsible for Acetyl-CoA biosynthesis, is essential for the survival of the pathogen and is absent in humans. The key proteins and enzymes involved in the pathway are attractive targets for the treatment of CDI. Corrinoid iron-sulfur protein (CoFeSP) is a key protein and acts as a methyl transformer in the Wood-Ljungdahl pathway. In this study, CoFeSP from Clostridium difficile (CoFeSPCd) was cloned, expressed in E...
February 13, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28214243/synthetic-metabolic-bypass-for-a-metabolic-toggle-switch-enhances-acetyl-coa-supply-for-isopropanol-production-by-escherichia-coli
#20
Yuki Soma, Taiki Yamaji, Fumio Matsuda, Taizo Hanai
Almost all synthetic pathways for biofuel production are designed to require endogenous metabolites in glycolysis, such as phosphoenolpyruvate, pyruvate, and acetyl-CoA. However, such metabolites are also required for bacterial cell growth. To reduce the metabolic imbalance between cell growth and target chemical production, we previously constructed a metabolic toggle switch (MTS) as a conditional flux redirection tool controlling metabolic flux of TCA cycle toward isopropanol production. This approach succeeded to improve the isopropanol production titer and yield while ensuring sufficient cell growth...
February 14, 2017: Journal of Bioscience and Bioengineering
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