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https://www.readbyqxmd.com/read/28535436/microcystin-lr-induces-changes-in-the-gaba-neurotransmitter-system-of-zebrafish
#1
Wei Yan, Li Li, Guangyu Li, Sujuan Zhao
It has been reported that exposure to microcystins altered adult zebrafish swimming performance parameters, but the possible mechanisms of action remain unknown. Neuronal activity depends on the balance between the number of excitatory and inhibitory processes which are associated with neurotransmitters. In the present study, zebrafish embryos (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30μg/L (microcystin-LR) MCLR for 90day until reaching sexual maturity. To investigate the effects of MCLR on the neurotransmitter system, mRNA levels involved in amino acid g-aminobutyric acid (GABA) and glutamate metabolic pathways were tested using quantitative real-time PCR...
May 15, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28534874/shifting-brain-inhibitory-balance-and-connectivity-of-the-prefrontal-cortex-of-adults-with-autism-spectrum-disorder
#2
L A Ajram, J Horder, M A Mendez, A Galanopoulos, L P Brennan, R H Wichers, D M Robertson, C M Murphy, J Zinkstok, G Ivin, M Heasman, D Meek, M D Tricklebank, G J Barker, D J Lythgoe, R A E Edden, S C Williams, D G M Murphy, G M McAlonan
Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the 'responsivity' of the E-I system to pharmacologic challenge; or whether E-I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder...
May 23, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28534738/optocontrol-of-glutamate-receptor-activity-by-single-side-chain-photoisomerization
#3
Viktoria Klippenstein, Christian Hoppmann, Shixin Ye, Lei Wang, Pierre Paoletti
Engineering light-sensitivity into proteins has wide ranging applications in molecular studies and neuroscience. Commonly used tethered photoswitchable ligands, however, require solvent-accessible protein labeling, face structural constrains, and are bulky. Here, we designed a set of optocontrollable NMDA receptors by directly incorporating single photoswitchable amino acids (PSAAs) providing genetic encodability, reversibility, and site tolerance. We identified several positions within the multi-domain receptor endowing robust photomodulation...
May 23, 2017: ELife
https://www.readbyqxmd.com/read/28534512/a-viral-microrna-downregulates-metastasis-suppressor-cd82-and-induces-cell-invasion-and-angiogenesis-by-activating-the-c-met-signaling
#4
W Li, M Hu, C Wang, H Lu, F Chen, J Xu, Y Shang, F Wang, J Qin, Q Yan, B J Krueger, R Renne, S-J Gao, C Lu
Kaposi's sarcoma (KS) as the most common AIDS-associated malignancy is etiologically caused by KS-associated herpesvirus (KSHV). KS is a highly disseminated and vascularized tumor. KSHV encodes 12 pre-microRNAs that yield 25 mature microRNAs (miRNAs), but their roles in KSHV-induced tumor metastasis and angiogenesis remain largely unclear. KSHV-encoded miR-K12-6 (miR-K6) can generate two mature miRNAs, miR-K6-5p and miR-K6-3p. Recently, we have shown that miR-K6-3p induced cell migration and angiogenesis via directly targeting SH3 domain binding glutamate-rich protein (SH3BGR)...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534301/effects-of-acetyl-l-carnitine-in-diabetic-neuropathy-and-other-geriatric-disorders
#5
REVIEW
G Sergi, S Pizzato, F Piovesan, C Trevisan, N Veronese, E Manzato
A long history of diabetes mellitus and increasing age are associated with the onset of diabetic neuropathy, a painful and highly disabling complication with a prevalence peaking at 50% among elderly diabetic patients. Acetyl-L-carnitine (ALC) is a molecule derived from the acetylation of carnitine in the mitochondria that has an essential role in energy production. It has recently been proposed as a therapy to improve the symptoms of diabetic neuropathy. ALC is widely distributed in mammalian tissues, including the brain, blood-brain barrier, brain neurons, and astrocytes...
May 22, 2017: Aging Clinical and Experimental Research
https://www.readbyqxmd.com/read/28534263/n-acetylaspartylglutamate-inhibits-heroin-self-administration-and-heroin-seeking-behaviors-induced-by-cue-or-priming-in-rats
#6
Huaqiang Zhu, Miaojun Lai, Weisheng Chen, Disen Mei, Fuqiang Zhang, Huifeng Liu, Wenhua Zhou
Activation of presynaptic group II metabotropic glutamate receptors (mGluR2/3) inhibits drug reward and drug-seeking behavior, but the role of N-acetylaspartylglutamate (NAAG), an agonist of endogenous mGluR2/3, in heroin reward and heroin-seeking behavior remained unclear. Here, we aimed to explore the effects of exogenous NAAG on heroin self-administration and heroin-seeking behavior. First, rats were trained to self-administer heroin under a fixed ratio 1 (FR1) schedule for 10 days, then received NAAG (50 or 100 μg/10 μL in each nostril) in the absence or presence of LY341495 (1 mg/kg, i...
May 22, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28534111/overexpression-of-ppc-or-deletion-of-mdh-for-improving-production-of-%C3%AE-aminobutyric-acid-in-recombinant-corynebacterium-glutamicum
#7
Feng Shi, Ming Zhang, Yongfu Li
L-Glutamate decarboxylase (GAD) transforms L-glutamate into γ-aminobutyric acid (GABA). Corynebacterium glutamicum that expresses exogenous GAD gene(s) can synthesize GABA from its own produced L-glutamate. To enhance GABA production in recombinant C. glutamicum strain SH, metabolic engineering strategies were used to improve the supply of the GABA precursor, L-glutamate. Five new strains were constructed here. First, the ppc gene was coexpressed with two GAD genes (gadB1 and gadB2). Then, the mdh gene was deleted in C...
June 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28533442/the-role-of-shed-prp-c-in-the-neuropathogenesis-of-hiv-infection
#8
Bezawit W Megra, Eliseo A Eugenin, Joan W Berman
HIV-1 enters the CNS soon after peripheral infection and causes chronic neuroinflammation and neuronal damage that leads to cognitive impairment in 40-70% of HIV-infected people. The nonpathogenic cellular isoform of the human prion protein (PrP(c)) is an adhesion molecule constitutively expressed in the CNS. Previously, our laboratory showed that shed PrP(c) (sPrP(c)) is increased in the cerebrospinal fluid of HIV-infected people with cognitive deficits as compared with infected people with no impairment. In this article, we demonstrate that CCL2 and TNF-α, inflammatory mediators that are elevated in the CNS of HIV-infected people, increase shedding of PrP(c) from human astrocytes by increasing the active form of the metalloprotease ADAM10...
May 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28533401/evolutionary-steps-involving-counterion-displacement-in-a-tunicate-opsin
#9
Keiichi Kojima, Takahiro Yamashita, Yasushi Imamoto, Takehiro G Kusakabe, Motoyuki Tsuda, Yoshinori Shichida
Ci-opsin1 is a visible light-sensitive opsin present in the larval ocellus of an ascidian, Ciona intestinalis This invertebrate opsin belongs to the vertebrate visual and nonvisual opsin groups in the opsin phylogenetic tree. Ci-opsin1 contains candidate counterions (glutamic acid residues) at positions 113 and 181; the former is a newly acquired position in the vertebrate visual opsin lineage, whereas the latter is an ancestral position widely conserved among invertebrate opsins. Here, we show that Glu113 and Glu181 in Ci-opsin1 act synergistically as counterions, which imparts molecular properties to Ci-opsin1 intermediate between those of vertebrate- and invertebrate-type opsins...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533177/immunohistochemical-comparison-of-astrocytic-mglur5-upregulation-in-infraorbital-nerve-versus-sciatic-nerve-ligated-rat
#10
Benoit Michot, Ronald Deumens, Emmanuel Hermans
The differential pharmacological responsiveness of cephalic and extra-cephalic neuropathic pain has been proposed to relate to distinct mechanisms that may involve neuroinflammatory reactions mediated by glial cells. Astrocytes are particularly important for neuronal sensitization in neuropathic pain, in part through modulation of glutamatergic transmission. Because the metabotropic glutamate receptor 5 (mGluR5) is involved in the astrocytic regulation of the glutamatergic system, we investigated modifications of its expression in models of cephalic versus extra-cephalic neuropathic pain...
May 19, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28533163/grin2b-gain-of-function-mutations-are-sensitive-to-radiprodil-a-negative-allosteric-modulator-of-glun2b-containing-nmda-receptors
#11
Brice Mullier, Christian Wolff, Zara Amanda Sands, Philippe Ghisdal, Pierandrea Muglia, Rafal Marian Kaminski, Véronique Marie André
De novo gain of function mutations in GRIN2B encoding the GluN2B subunit of the N-methyl-D-aspartate (NMDA) receptor have been linked with epileptic encephalopathies, including infantile spasms. We investigated the effects of radiprodil, a selective GluN2B negative allosteric modulator and other non-selective NMDA receptor inhibitors on glutamate currents mediated by NMDA receptors containing mutated GluN2B subunits. The experiments were performed in Xenopus oocytes co-injected with the following human mRNAs: GRIN1/GRIN2B, GRIN1/GRIN2B-R540H, GRIN1/GRIN2B-N615I and GRIN1/GRIN2B-V618G...
May 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28533144/discovery-of-two-p-superfamily-conotoxins-lt9a-and-lt9b-with-different-modifications-on-voltage-sensitive-sodium-channels
#12
Lei Wang, Junliang Liu, Zhenghua Ren, Yu Chen, Anlong Xu
In this work, two P-superfamily conotoxins, lt9a and lt9b, were purified and characterized from the crude venom of Conus litteratus. The amino acid sequences of lt9a and lt9b were determined by the Edman degradation method. It has been suggested that both lt9a and lt9b are produced from the precursor encoded by the gene Lt9.1. During the conotoxin maturation process, different post-translational modifications occurred between lt9a and lt9b. Conotoxin lt9b was predicted to have two prolines that underwent hydroxylation and one glutamate that underwent carboxylation, while lt9a had no hydroxyproline and carboxyglutamate residue...
May 19, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28533117/activation-induced-changes-in-gaba-functional-mrs-at-7-t-with-mega-slaser
#13
Chen Chen, Hilmar P Sigurdsson, Sophia E Pépés, Dorothee P Auer, Peter G Morris, Paul S Morgan, Penny A Gowland, Stephen R Jackson
Functional magnetic resonance spectroscopy (fMRS) has been used to assess the dynamic metabolic responses of the brain to a physiological stimulus non-invasively. However, only limited information on the dynamic functional response of γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain, is available. We aimed to measure the activation-induced changes in GABA unambiguously using a spectral editing method, instead of the conventional direct detection techniques used in previous fMRS studies...
May 19, 2017: NeuroImage
https://www.readbyqxmd.com/read/28533113/a-novel-serine-racemase-inhibitor-suppresses-neuronal-over-activation-in-vivo
#14
Hisashi Mori, Ryogo Wada, Satoyuki Takahara, Yoshikazu Horino, Hironori Izumi, Tetsuya Ishimoto, Tomoyuki Yoshida, Mineyuki Mizuguchi, Takayuki Obita, Hiroaki Gouda, Shuichi Hirono, Naoki Toyooka
Serine racemase (SRR) is an enzyme that produces d-serine from l-serine. d-Serine acts as an endogenous coagonist of NMDA-type glutamate receptors (NMDARs), which regulate many physiological functions. Over-activation of NMDARs induces excitotoxicity, which is observed in many neurodegenerative disorders and epilepsy states. In our previous works on the generation of SRR gene knockout (Srr-KO) mice and its protective effects against NMDA- and Aβ peptide-induced neurodegeneration, we hypothesized that the regulation of NMDARs' over-activation by inhibition of SRR activity is one such therapeutic strategy to combat these disease states...
May 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28532451/enhancing-poly-%C3%AE-glutamic-acid-production-in-bacillus-amyloliquefaciens-by-introducing-the-glutamate-synthesis-features-from-corynebacterium-glutamicum
#15
Jun Feng, Yufen Quan, Yanyan Gu, Fenghong Liu, Xiaozhong Huang, Haosheng Shen, Yulei Dang, Mingfeng Cao, Weixia Gao, Xiaoyun Lu, Yi Wang, Cunjiang Song, Shufang Wang
BACKGROUND: Poly-γ-glutamic acid (γ-PGA) is a valuable polymer with glutamate as its sole precursor. Enhancement of the intracellular glutamate synthesis is a very important strategy for the improvement of γ-PGA production, especially for those glutamate-independent γ-PGA producing strains. Corynebacterium glutamicum has long been used for industrial glutamate production and it exhibits some unique features for glutamate synthesis; therefore introduction of these metabolic characters into the γ-PGA producing strain might lead to increased intracellular glutamate availability, and thus ultimate γ-PGA production...
May 22, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28532421/glutamate-excitotoxicity-induced-by-orally-administered-propionic-acid-a-short-chain-fatty-acid-can-be-ameliorated-by-bee-pollen
#16
Afaf El-Ansary, Huda S Al-Salem, Alqahtani Asma, Abeer Al-Dbass
BACKGROUND: Rodent models may guide investigations towards identifying either environmental neuro-toxicants or drugs with neuro-therapeutic effects. This work aims to study the therapeutic effects of bee pollen on brain glutamate excitotoxicity and the impaired glutamine-glutamate- gamma amino butyric acid (GABA) circuit induced by propionic acid (PPA), a short chain fatty acid, in rat pups. METHODS: Twenty-four young male Western Albino rats 3-4 weeks of age, and 45-60 g body weight were enrolled in the present study...
May 22, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28532126/poly-%C3%AE-glutamic-acid-coated-lipoplexes-loaded-with-doxorubicin-for-enhancing-the-antitumor-activity-against-liver-tumors
#17
Na Qi, Bo Tang, Guang Liu, Xingsi Liang
The study was to develop poly-γ-glutamic acid (γ-PGA)-coated Doxorubicin (Dox) lipoplexes that enhance the antitumor activity against liver tumors. γ-PGA-coated lipoplexes were performed by electrostatistically attracting to the surface of cationic charge liposomes with anionic γ-PGA. With the increasing of γ-PGA concentration, the particle size of γ-PGA-coated Dox lipoplexes slightly increased, the zeta potential from positive shifted to negative, and the entrapment efficiency (EE) were no significant change...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28530802/discovery-of-n-5-fluoropyridin-2-yl-6-methyl-4-pyrimidin-5-yloxy-picolinamide-vu0424238-a-novel-negative-allosteric-modulator-of-metabotropic-glutamate-receptor-subtype-5-selected-for-clinical-evaluation
#18
Andrew S Felts, Alice L Rodriguez, Anna L Blobaum, Ryan D Morrison, Brittney S Bates, Analisa Thompson Gray, Jerri M Rook, Mohammed N Tantawy, Frank W Byers, Sichen Chang, Daryl F Venable, Vincent B Luscombe, Gilles D Tamagnan, Colleen M Niswender, J Scott Daniels, Carrie K Jones, P Jeffrey Conn, Craig W Lindsley, Kyle A Emmitte
Preclinical evidence in support of the potential utility of mGlu5 NAMs for the treatment of a variety of psychiatric and neurodegenerative disorders is extensive, and multiple such molecules have entered clinical trials. Despite some promising results from clinical studies, no small molecule mGlu5 NAM has yet to reach market. Here we present the discovery and evaluation of N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (27, VU0424238), a compound selected for clinical evaluation. Compound 27 is more than 900-fold selective for mGlu5 versus the other mGlu receptors, and binding studies established a Ki value of 4...
May 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28529157/protective-treatments-and-their-target-retinal-ganglion-cells-in-diabetic-retinopathy
#19
REVIEW
Jing Zhang, Rong Liu, Hong-Yu Kuang, Xin-Yuan Gao, Hao-Ling Liu
Diabetic retinopathy(DR)is one of the complications of diabetes which could cause severe vision loss. Retinal ganglion cell(RGC)injury has been confirmed prior to micro-vascular damage. Over the past few decades, a number of animal and clinical studies have confirmed that RGC impairment leads to an early deterioration of vision in DR. Inhibition of aldose reductase (AR), advanced glycation end product (AGE), oxidative stress, glutamate toxicity, and an inflammatory response may play important roles in protecting RGCs in DR...
May 18, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28528500/using-poly-glutamic-acid-as-soil-washing-agent-to-remediate-heavy-metal-contaminated-soils
#20
Zong-Han Yang, Cheng-Di Dong, Chiu-Wen Chen, Yih-Terng Sheu, Chih-Ming Kao
The extraction efficiency of heavy metals from soils using three forms of gamma poly-glutamic acid (γ-PGA) as the washing agents was investigated. Controlling factors including agent concentrations, extraction time, pH, and liquid to soil ratio were evaluated to determine the optimum operational conditions. The distribution of heavy metal species in soils before and after extraction processes was analyzed. Up to 46 and 74% of heavy metal removal efficiencies were achieved with one round and a sequential extraction process using H-bonding form of γ-PGA (200 mM) with washing time of 40 min, liquid to solid ratio of 10 to 1, and pH of 6...
May 20, 2017: Environmental Science and Pollution Research International
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