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https://www.readbyqxmd.com/read/28812276/arundic-acid-increases-expression-and-function-of-astrocytic-glutamate-transporter-eaat1-via-the-erk-akt-and-nf-%C3%AE%C2%BAb-pathways
#1
Pratap Karki, Peter Hong, James Johnson, Edward Pajarillo, Deok-Soo Son, Michael Aschner, Eunsook Y Lee
Glutamate is the major excitatory neurotransmitter in the brain, but excessive synaptic glutamate must be removed to prevent excitotoxic injury and death. Two astrocytic glutamate transporters, excitatory amino acid transporter (EAAT) 1 and 2, play a major role in eliminating excess glutamate from the synapse. Dysregulation of EAAT1 contributes to the pathogenesis of multiple neurological disorders, such as Alzheimer's disease (AD), ataxia, traumatic brain injuries, and glaucoma. In the present study, we investigated the effect of arundic acid on EAAT1 to determine its efficacy in enhancing the expression and function of EAAT1, and its possible mechanisms of action...
August 15, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28811348/a-critical-role-of-glutamine-and-asparagine-%C3%AE-nitrogen-in-nucleotide-biosynthesis-in-cancer-cells-hijacked-by-an-oncogenic-virus
#2
Ying Zhu, Tingting Li, Suzane Ramos da Silva, Jae-Jin Lee, Chun Lu, Hyungjin Eoh, Jae U Jung, Shou-Jiang Gao
While glutamine is a nonessential amino acid that can be synthesized from glucose, some cancer cells primarily depend on glutamine for their growth, proliferation, and survival. Numerous types of cancer also depend on asparagine for cell proliferation. The underlying mechanisms of the glutamine and asparagine requirement in cancer cells in different contexts remain unclear. In this study, we show that the oncogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) accelerates the glutamine metabolism of glucose-independent proliferation of cancer cells by upregulating the expression of numerous critical enzymes, including glutaminase 2 (GLS2), glutamate dehydrogenase 1 (GLUD1), and glutamic-oxaloacetic transaminase 2 (GOT2), to support cell proliferation...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28809966/template-assisted-photodimerization-of-n-unprotected-uracil-derivatives-selective-formation-of-the-cis-syn-photodimer
#3
N M Weckenmann, C Maichle-Mössmer, B J Nachtsheim
A UV light-induced photodimerization of 5-[(imidazol-1-yl)methyl]uracil using glutamate- and aspartate-derived cyclic dipeptides (2,5-diketopiperazines - DKPs) as templates was investigated. Dual salt bridge formation between imidazole side chains and carboxylic acids resulted in the preorganization of the uracil monomers and the preferential formation of the cis-syn photodimer.
August 15, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28809097/piconewton-scale-analysis-of-ras-braf-signal-transduction-with-single-molecule-force-spectroscopy
#4
Chae-Seok Lim, Cheng Wen, Yanghui Sheng, Guangfu Wang, Zhuan Zhou, Shiqiang Wang, Huaye Zhang, Anpei Ye, J Julius Zhu
Intermolecular interactions dominate the behavior of signal transduction in various physiological and pathological cell processes, yet assessing these interactions remains a challenging task. Here, this study reports a single-molecule force spectroscopic method that enables functional delineation of two interaction sites (≈35 pN and ≈90 pN) between signaling effectors Ras and BRaf in the canonical mitogen-activated protein kinase (MAPK) pathway. This analysis reveals mutations on BRaf at Q257 and A246, two sites frequently linked to cardio-faciocutaneous syndrome, result in ≈10-30 pN alterations in RasBRaf intermolecular binding force...
August 15, 2017: Small
https://www.readbyqxmd.com/read/28808393/evaluation-of-the-antidiabetic-properties-of-s-1708-mulberry-variety
#5
Brijesh Ranjan, Randhir Kumar, Neeraj Verma, Swati Mittal, Pranab Lal Pakrasi, R Venkatesh Kumar
BACKGROUND: Diabetes is a metabolic disease prevalent worldwide in all age group of people. The source of diabetes is due to an oxidation process that can produce free radicals. An increase in oxidative free radicals in the body is reported to be one of the several causes of diabetes. The best remedy to combat oxidative stress is the use of antioxidants, which inhibit and scavenge free radicals. AIM: This study has been undertaken to evaluate the antioxidant activity and antidiabetic effect of mulberry leaf extract in diabetic mice...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28807674/phenylglycine-analogs-are-inhibitors-of-the-neutral-amino-acid-transporters-asct1-and-asct2-and-enhance-nmda-receptor-mediated-ltp-in-rat-visual-cortex-slices
#6
Alan C Foster, Natalie Rangel-Diaz, Ursula Staubli, Jia-Ying Yang, Mahmud Penjwini, Veena Viswanath, Yong-Xin Li
The N-methyl-d-aspartate receptor (NMDA) co-agonist d-serine is a substrate for the neutral amino acid transporters ASCT1 (SLC1A4) and ASCT2 (SLC1A5). We identified l-phenylglycine (PG) and its analogs as inhibitors of ASCT1 and ASCT2. PG analogs were shown to be non-substrate inhibitors of ASCT1 and ASCT2 with a range of activities relative to other amino acid transport systems, including sodium-dependent glutamate transporters, the sodium-independent d-serine transporter asc-1 and system L. L-4-chloroPG was the most potent and selective ASCT1/2 inhibitor identified...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28806601/influence-of-sublethal-doses-of-acetamiprid-and-halosulfuron-methyl-on-metabolites-of-zebra-fish-brachydanio-rerio
#7
Hong Zhang, Lijuan Zhao
Acetamiprid, a neonicotinoid pesticide, is reported to have adverse sublethal effects on non-target beneficial organisms. Halosulfuron-methyl (HM), one of the most widely used herbicides in agriculture, has high ecotoxicity to aquatic plants and animals. In this study, a GC-MS-based metabolomics approach was used to investigate the toxicity of acetamiprid and HM. The Automated Mass Spectral Deconvolution and Identification System (AMDIS) software program and the retention index method were used to identify 51 metabolites in zebra fish (Brachydanio rerio)...
August 4, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28804999/diversity-of-astroglial-responses-across-human-neurodegenerative-disorders-and-brain-aging
#8
Isidro Ferrer
Astrogliopathy refers to alterations of astrocytes occurring in diseases of the nervous system, and it implies the involvement of astrocytes as key elements in the pathogenesis and pathology of diseases and injuries of the central nervous system. Reactive astrocytosis refers to the response of astrocytes to different insults to the nervous system, whereas astrocytopathy indicates hypertrophy, atrophy/degeneration and loss of function and pathological remodeling occurring as a primary cause of a disease or as a factor contributing to the development and progression of a particular disease...
September 2017: Brain Pathology
https://www.readbyqxmd.com/read/28804802/improvement-of-glycerol-catabolism-in-bacillus-licheniformis-for-production-of-poly-%C3%AE-glutamic-acid
#9
Yangyang Zhan, Chengjun Zhu, Bojie Sheng, Dongbo Cai, Qin Wang, Zhiyou Wen, Shouwen Chen
Bacillus licheniformis WX-02 is a well-studied strain to produce poly-γ-glutamic acid (γ-PGA) with numerous applications. This study is to improve WX-02 strain's capability of assimilating glycerol, a major byproduct of biofuels industries, through metabolic manipulation. Through gene knockout, the GlpK pathway was identified as the sole functional glycerol catabolism pathway, while the DhaK pathway was inactive for this strain under either aerobic or anaerobic conditions. The enhancement of glycerol utilization was attempted by substituting the native glpFK promoter with the constitutive promoter (P43), ytzE promoter (PytzE), and bacABC operon promoter (PbacA), respectively...
August 13, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28804274/non-invasive-urinary-metabolomic-profiling-discriminates-prostate-cancer-from-benign-prostatic-hyperplasia
#10
Clara Pérez-Rambla, Leonor Puchades-Carrasco, María García-Flores, José Rubio-Briones, José Antonio López-Guerrero, Antonio Pineda-Lucena
INTRODUCTION: Prostate cancer (PCa) is one of the most common malignancies in men worldwide. Serum prostate specific antigen (PSA) level has been extensively used as a biomarker to detect PCa. However, PSA is not cancer-specific and various non-malignant conditions, including benign prostatic hyperplasia (BPH), can cause a rise in PSA blood levels, thus leading to many false positive results. OBJECTIVES: In this study, we evaluated the potential of urinary metabolomic profiling for discriminating PCa from BPH...
2017: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/28803850/association-of-exposure-to-manganese-and-iron-with-striatal-and-thalamic-gaba-and-other-neurometabolites-neuroimaging-results-from-the-weldox-ii-study
#11
Swaantje Casjens, Urike Dydak, Shalmali Dharmadhikari, Anne Lotz, Martin Lehnert, Clara Quetscher, Christoph Stewig, Benjamin Glaubitz, Tobias Schmidt-Wilcke, David Edmondson, Chien-Lin Yeh, Tobias Weiss, Christoph van Thriel, Lennard Herrmann, Siegfried Muhlack, Dirk Woitalla, Michael Aschner, Thomas Brüning, Beate Pesch
OBJECTIVE: Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. MATERIAL AND METHODS: GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites...
August 10, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28802275/response-of-methylocystis-sp-strain-sc2-to-salt-stress-physiology-global-transcriptome-and-amino-acid-profiles
#12
Dongfei Han, Hannes Link, Werner Liesack
Soil microorganisms have to rapidly respond to salt-induced osmotic stress. Type II methanotrophs of the genus Methylocystis are widely distributed in upland soils, but are known to have a low salt tolerance. Here, we tested the ability of Methylocystis sp. strain SC2 to adapt to increased salinity. When exposed to 0.75% NaCl, methane oxidation was completely inhibited for 2.25 h and fully recovered within 6 h. Growth was inhibited for 23.5 h and then fully recovered. Its transcriptome was profiled after 0 min (control), 45 min (early response) and 14 h (late response) of stress exposure...
August 11, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28802074/altered-amino-acid-concentrations-in-nafld-impact-of-obesity-and-insulin-resistance
#13
Melania Gaggini, Fabrizia Carli, Chiara Rosso, Emma Buzzigoli, Milena Marietti, Veronica Della Latta, Demetrio Ciociaro, Maria Lorena Abate, Roberto Gambino, Maurizio Cassader, Elisabetta Bugianesi, Amalia Gastaldelli
Plasma concentrations of amino acids (AA), in particular branched chain (BCAA), are often found increased in non-alcoholic fatty liver disease (NAFLD). However, if this is due to increased muscular protein catabolism, obesity and/or increased insulin resistance (IR) or impaired tissue metabolism is not known. Thus, we evaluated a) if subjects with NAFLD non-obese (NAFLD-NO), compared to obese (NAFLD-Ob) display altered plasma AA compared to controls (CT); b) if AA concentrations are associated to IR and liver histology...
August 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28800966/reconstruction-of-a-metabolic-regulatory-network-in-escherichia-coli-for-purposeful-switching-from-cell-growth-mode-to-production-mode-in-direct-gaba-fermentation-from-glucose
#14
Yuki Soma, Yuri Fujiwara, Takuya Nakagawa, Keigo Tsuruno, Taizo Hanai
γ-aminobutyric acid (GABA) is a drug and functional food additive and is used as a monomer for producing the biodegradable plastic, polyamide 4. Recently, direct GABA fermentation from glucose has been developed as an alternative to glutamate-based whole cell bioconversion. Although total productivity in fermentation is determined by the specific productivity and cell amount responsible for GABA production, the optimal metabolic state for GABA production conflicts with that for bacterial cell growth. Herein, we demonstrated metabolic state switching from the cell growth mode based on the metabolic pathways of the wild type strain to a GABA production mode based on a synthetic metabolic pathway in Escherichia coli through rewriting of the metabolic regulatory network and pathway engineering...
August 8, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28800112/low-concentration-tributyltin-decreases-glur2-expression-via-nuclear-respiratory-factor-1-inhibition
#15
Keishi Ishida, Kaori Aoki, Tomoko Takishita, Masatsugu Miyara, Shuichiro Sakamoto, Seigo Sanoh, Tomoki Kimura, Yasunari Kanda, Shigeru Ohta, Yaichiro Kotake
Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 (GluR2) expression in cortical neurons and enhances neuronal vulnerability to glutamate. However, the mechanism of this TBT-induced GluR2 decrease remains unknown...
August 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28798756/aerial-warfare-a-volatile-dialogue-between-the-plant-pathogen-verticillium-longisporum-and-its-antagonist-paenibacillus-polymyxa
#16
Daria Rybakova, Ute Rack-Wetzlinger, Tomislav Cernava, Angelika Schaefer, Maria Schmuck, Gabriele Berg
Verticillium wilt caused by Verticillium spp. results in severe yield losses in a broad range of crops. Verticillium outbreaks are challenging to control, and exacerbated by increases in soil temperatures and drought associated with global warming. Employing natural antagonists as biocontrol agents offers a promising approach to addressing this challenge. Paenibacillus polymyxa Sb3-1 was proven to reduce the growth of Verticillium longisporum during in vitro experiments and was shown to promote the growth of oilseed rape seedlings infested with V...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28797970/the-interaction-of-clozapine-loaded-nanocapsules-with-the-hcmec-d3-cells-in-vitro-model-of-blood-brain-barrier
#17
Sylwia Łukasiewicz, Ewa Błasiak, Krzysztof Szczepanowicz, Krzysztof Guzik, Małgorzata Bzowska, Piotr Warszyński, Marta Dziedzicka-Wasylewska
Despite progress in the development of novel pharmacological compounds, their efficacy in the treatment of neuropathologies is not satisfactory. One strategy to achieve safe and efficient brain targeting therapy is to design nanocarriers capable of transporting antipsychotic drugs through the BBB (without affecting the normal functions of the barrier) in a defined part of the brain. Here we investigate the interaction of clozapine-loaded polymeric Nano capsules (CLO-NCs) with hCMEC/D3 (human cerebral microvascular endothelial cells, D3 clone) cells that constitutes an in vitro model of the blood brain barrier (BBB)...
July 25, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28797105/regulation-of-hepatic-stellate-cell-proliferation-and-activation-by-glutamine-metabolism
#18
Jiang Li, Mohammed Ghazwani, Ke Liu, Yixian Huang, Na Chang, Jie Fan, Fengtian He, Liying Li, Shizhong Bu, Wen Xie, Xiaochao Ma, Song Li
Liver fibrosis is the excessive accumulation of extracellular matrix proteins, which is mainly caused by accumulation of activated hepatic stellate cells (HSCs). The mechanisms of activation and proliferation of HSCs, two key events after liver damage, have been studied for many years. Here we report a novel pathway to control HSCs by regulating glutamine metabolism. We demonstrated that the proliferation of HSCs is critically dependent on glutamine that is used to generate α-ketoglutarate (α-KG) and non-essential amino acid (NEAA)...
2017: PloS One
https://www.readbyqxmd.com/read/28796499/studies-on-the-biochemical-formation-pathway-of-the-amino-acid-l-theanine-in-tea-camellia-sinensis-and-other-plants
#19
Sihua Cheng, Xiumin Fu, Xiaoqin Wang, Yinyin Liao, Lanting Zeng, Fang Dong, Ziyin Yang
Tea (Camellia sinensis) is the most widely consumed beverage aside from water. The flavor of tea is conferred by certain metabolites, especially l-theanine, in C. sinensis. To determine why more l-theanine accumulates in C. sinensis than in other plants, we compare l-theanine contents between C. sinensis and other plant species (Camellia nitidissima, Camellia japonica, Zea mays, Arabidopsis thaliana, and Solanum lycopersicum) and use a stable isotope labeling approach to elucidate its biosynthetic route. We quantify relevant intermediates and metabolites by mass spectrometry...
August 10, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28795601/poly-glutamic-dendrimer-based-conjugates-for-cancer-vaccination-a-computational-design-for-targeted-delivery-of-antigens
#20
L I F Moura, N Martinho, L C Silva, T S Barata, S Brocchini, H F Florindo, M Zloh
Computational techniques are useful to predict interaction models and molecular properties for the design of drug delivery systems, such as dendrimers. This work evaluated the impact of surface modifications of mannosamine-conjugated multifunctional poly(glutamic acid) (PG)-dendrimers as nanocarriers of the tumour associated antigens (TAA) MART-1, gp100:44 and gp100:209. Molecular dynamics simulations and docking studies were performed. Nitrobenzoxadiazole (NBD)-PG-G4-dendrimer displayed 64 carboxylic groups, however, the Frontier Molecular Orbital Theory study evidenced that only 32 of those were available to form covalent bonds...
August 10, 2017: Journal of Drug Targeting
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