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nicotinic acid

Max C Richter, Susann Ludewig, Alex Winschel, Tobias Abel, Charlotte Bold, Leonie R Salzburger, Susanne Klein, Kang Han, Sascha W Weyer, Ann-Kristina Fritz, Bodo Laube, David P Wolfer, Christian J Buchholz, Martin Korte, Ulrike C Müller
Increasing evidence suggests that synaptic functions of the amyloid precursor protein (APP), which is key to Alzheimer pathogenesis, may be carried out by its secreted ectodomain (APPs). The specific roles of APPsα and APPsβ fragments, generated by non-amyloidogenic or amyloidogenic APP processing, respectively, remain however unclear. Here, we expressed APPsα or APPsβ in the adult brain of conditional double knockout mice (cDKO) lacking APP and the related APLP2. APPsα efficiently rescued deficits in spine density, synaptic plasticity (LTP and PPF), and spatial reference memory of cDKO mice...
April 16, 2018: EMBO Journal
Matthew D King, Thomas Long, Daniel L Pfalmer, Timothy L Andersen, Owen M McDougal
BACKGROUND: Conventional de novo drug design is costly and time consuming, making it accessible to only the best resourced research organizations. An emergent approach to new drug development is drug repurposing, in which compounds that have already gone through some level of clinical testing are examined for efficacy against diseases divergent than their original application. Repurposing of existing drugs circumvents the time and considerable cost of early stages of drug development, and can be accelerated by using software to screen existing chemical databases to identify suitable drug candidates...
April 16, 2018: BMC Bioinformatics
Jin-Song Gong, Qiang Zhang, Bing-Chen Gu, Ting-Ting Dong, Heng Li, Hui Li, Zhen-Ming Lu, Jin-Song Shi, Zheng-Hong Xu
The constitutively expression system for P. putida nitrilase was firstly constructed to improve the nicotinic acid production and reduce the production costs. High density culture strategy was employed to enhance the biomass and nitrilase production of recombinant strain. The total nitrilase activity reached up to 654 U·mL-1 without the induction. 541 g·L-1 nicotinic acid was accumulated via fed batch mode of substrate feeding through 290 min of conversion.
March 30, 2018: Bioresource Technology
Guillermo de la Rosa, Ligia L Corrales-García, Ximena Rodriguez-Ruiz, Estuardo López-Vera, Gerardo Corzo
The three-fingered toxin family and more precisely short-chain α-neurotoxins (also known as Type I α-neurotoxins) are crucial in defining the elapid envenomation process, but paradoxically, they are barely neutralized by current elapid snake antivenoms. This work has been focused on the primary structural identity among Type I neurotoxins in order to create a consensus short-chain α-neurotoxin with conserved characteristics. A multiple sequence alignment considering the twelve most toxic short-chain α-neurotoxins reported from the venoms of the elapid genera Acanthophis, Oxyuranus, Walterinnesia, Naja, Dendroaspis and Micrurus led us to propose a short-chain consensus α-neurotoxin, here named ScNtx...
April 6, 2018: Amino Acids
Yusuke Masuda, Nobuya Kurikawa, Tomohiro Nishizawa
BACKGROUND AND AIMS: Nicotinic acid administration causes plasma non-esterified fatty acid (NEFA) reduction and plasma lipid changes, including reduced triglyceride levels. GPR109A, which is expressed mainly in adipose tissue and has anti-lipolytic activity, was reported to be a molecular target for nicotinic acid. However, recent clinical reports have shown that most GPR109A agonists failed to induce clinically meaningful plasma lipid changes. In addition, a recent study has shown that the TG lowering effect of nicotinic acid was not diminished in Gpr109a deficient mice, which is different from the original finding...
March 24, 2018: Atherosclerosis
Yanting Zhang, Qing Chen, Junbin Ji, Lingling Zhao, Lei Zhang, Jiguo Qiu, Jian He
Nicotinic acid (NA), known as vitamin B3, is ubiquitous in nature and plays an important role in living organisms. The microbial catabolism of NA is highly diverse. However, the NA degradation by Alcaligenes faecalis strains has been poorly investigated. In this study, we report the complete genome sequence of A. faecalis JQ135 (4.08 Mbp) and several essential genes for NA degradation. This genome sequence will facilitate to elucidate the molecular metabolism of NA and advance the potential biotechnological applications of A...
April 5, 2018: Current Microbiology
Jinqin Chen, Li Liang, Huying Ning, Fengtao Cai, Zhuguo Liu, Longxiao Zhang, Liangyi Zhou, Qiuyun Dai
α-Conotoxins (α-CTxs) are small peptides composed of 11 to 20 amino acid residues with two disulfide bridges. Most of them potently and selectively target nicotinic acetylcholine receptor (nAChR) subtypes, and a few were found to inhibit the GABAB receptor (GABAB R)-coupled N-type calcium channels (Cav2.2). However, in all of α-CTxs targeting both receptors, the disulfide connectivity arrangement "C¹-C³, C²-C⁴" is present. In this work, a novel α4/7-CTx named Lt1.3 (GCCSHPACSGNNPYFC-NH₂) was cloned from the venom ducts of Conus litteratus ( C...
March 31, 2018: Marine Drugs
Wei-Ni Ma, Ming-Mei Zhou, Xiao-Jun Gou, Le Zhao, Fang Cen, Ying Xu, Hong-Yi Shen
The urinary metabolomic study based on gas chromatography-mass spectrometry (GC-MS) had been developed to investigate the possible antidepressant mechanism of chlorogenic acid (CGA) in a rat model of sleep deprivation (SD). According to pattern recognition analysis, there was a clear separation among big platform group (BP), sleep deprivation group (SD), and the CGA (model + CGA), and CGA group was much closer to the BP group by showing a tendency of recovering towards BP group. Thirty-six significantly changed metabolites related to antidepressant by CGA were identified and used to explore the potential mechanism...
2018: International Journal of Genomics
Vytautas Petkevičius, Justas Vaitekūnas, Jonita Stankevičiūtė, Renata Gasparavičiūtė, Rolandas Meškys
Microbial degradation of 2-hydroxypyridine usually results in the formation of a blue pigment (nicotine blue). In contrast, the Burkholderia sp. MAK1 bacterium utilizes 2-hydroxypyridine without the accumulation of nicotine blue. This scarcely investigated degradation pathway presumably employs a 2-hydroxypyridine 5-monooxygenase, an elusive enzyme that has been hypothesized, but has yet to be identified or characterised. The isolation of a mutant strain of Burkholderia sp. MAK1ΔP5 that is unable to utilize 2-hydroxypyridine has led to the identification of a gene cluster (designated hpd ), which is responsible for the degradation of 2-hydroxypyridine...
March 30, 2018: Applied and Environmental Microbiology
Denis S Kudryavtsev, Ekaterina N Spirova, Irina V Shelukhina, Lina V Son, Yana V Makarova, Natalia K Utkina, Igor E Kasheverov, Victor I Tsetlin
Diverse ligands of the muscle nicotinic acetylcholine receptor (nAChR) are used as muscle relaxants during surgery. Although a plethora of such molecules exists in the market, there is still a need for new drugs with rapid on/off-set, increased selectivity, and so forth. We found that pyrroloiminoquinone alkaloid Makaluvamine G (MG) inhibits several subtypes of nicotinic receptors and ionotropic γ-aminobutiric acid receptors, showing a higher affinity and moderate selectivity toward muscle nAChR. The action of MG on the latter was studied by a combination of electrophysiology, radioligand assay, fluorescent microscopy, and computer modeling...
March 28, 2018: Marine Drugs
Stuart A Forman
General anesthetics are known to act in part by binding to and altering the function of pentameric ligand-gated ion channels such as nicotinic acetylcholine and γ-aminobutyric acid type A receptors. Combining heterologous expression of the subunits that assemble to form these ion channels, mutagenesis techniques and voltage-clamp electrophysiology have enabled a variety of "structure-function" approaches to questions of where anesthetic binds to these ion channels and how they enhance or inhibit channel function...
2018: Methods in Enzymology
Manita Guragain, Jamie Jennings-Gee, Natalia Cattelan, Mary Finger, Matt S Conover, Thomas Hollis, Rajendar Deora
Many of the pathogenic species of the genus Bordetella have an absolute requirement for nicotinic acid (NA) for laboratory growth. These gram negative bacteria also harbor a gene cluster homologous to the nic cluster of Pseudomonas putida which is involved in aerobic degradation of NA and its transcriptional control. We report here that BpsR, a negative regulator of biofilm formation and Bps polysaccharide production, controls the growth of B. bronchiseptica by repressing the expression of nic genes. The severe growth defect of the Δ bpsR strain in Stainer Scholte media was restored by supplementation with NA which also functioned as an inducer of nic genes at low micromolar concentrations that are usually present in animals and humans...
March 26, 2018: Journal of Bacteriology
Jeffrey J Kelu, Sarah E Webb, Antony Galione, Andrew L Miller
During the development of the early spinal circuitry in zebrafish, spontaneous Ca2+ transients in the primary motor neurons (PMNs) are reported to transform from being slow and uncorrelated, to being rapid, synchronized and patterned. In this study, we demonstrated that in intact zebrafish, Ca2+ release +via two-pore channel type 2 (TPC2) from acidic stores/endolysosomes is required for the establishment of synchronized activity in the PMNs. Using the SAIGFF213A;UAS:GCaMP7a double-transgenic zebrafish line, Ca2+ transients were visualized in the caudal PMNs (CaPs)...
March 22, 2018: Developmental Biology
P C White, J Hirschfeld, M R Milward, P R Cooper, H J Wright, J B Matthews, I L C Chapple
BACKGROUND AND OBJECTIVE: Cigarette smoking is a major risk factor for periodontitis, and smoking perturbs neutrophil reactive oxygen species production. This study tested the hypothesis that cigarette smoke extract (CSE) and its components/metabolites nicotine, cotinine and thiocyanate (SCN-), may influence neutrophil functions. MATERIAL AND METHODS: Chemotaxis was assessed in neutrophils pre-treated with CSE using real-time video microscopy. Neutrophil extracellular trap (NET) release in response to CSE, nicotine, cotinine, SCN- as well as to phorbol 12-myristate-13-acetate and hypochlorous acid following pre-treatment with CSE, nicotine, cotinine or SCN- was assessed using fluorescence-based assays...
March 25, 2018: Journal of Periodontal Research
Heidi C O'Neill, Charles R Wageman, Sarah E Sherman, Sharon R Grady, Michael J Marks, Jerry A Stitzel
A single nucleotide polymorphism (SNP) in CHRNA5 (rs16969968, change from an aspartic acid (D) to asparagine (N) at position 398 of the human α5 nicotinic acetylcholine receptor subunit) has been associated with increased risk for nicotine dependence. Consequently, carriers of the risk variant may be at elevated risk for in utero nicotine exposure. To assess whether this gene-environment interaction might impact nicotine intake in developmental nicotine-exposed offspring, we utilized a mouse expressing this human SNP...
March 24, 2018: Genes, Brain, and Behavior
Shakeeb A Wazea, Walaa Wadie, Ashraf K Bahgat, Hanan S El-Abhar
Vagal stimulation controls systemic inflammation and modulates the immune response in different inflammatory conditions, including inflammatory bowel diseases (IBD). The released acetylcholine binds to alpha-7 nicotinic acetylcholine receptor (α7 nAChR) to suppress pro-inflammatory cytokines. This provides a new range of potential therapeutic approaches for controlling inflammatory responses. The present study aimed to assess whether galantamine (Galan) anti-inflammatory action involves α7 nAChR in a 2,4,6-trinitrobenzene sulfonic acid (TNBS) model of colitis and to estimate its possible molecular pathways...
March 23, 2018: Scientific Reports
Maju Mathew Koola
Cognitive impairments due to electroconvulsive therapy (ECT), traumatic brain injury (TBI), and neurologic and psychiatric disorders are prevalent. Cholinergic and glutamatergic pathways, α-7 nicotinic acetylcholine (α-7nACh) receptor, and N-methyl-d-aspartate (NMDA) receptor are potential pathophysiologic mechanisms in all of these conditions. Galantamine not only is an acetylcholinesterase inhibitor but has a dual mode of action as a α-7nACh receptor modulator as well. Memantine is a noncompetitive NMDA receptor antagonist...
March 1, 2018: Primary Care Companion to CNS Disorders
Giulia Donvito, Fabiana Piscitelli, Pretal Muldoon, Asti Jackson, Rosa Maria Vitale, Enrico D'Aniello, Catia Giordano, Bogna M Ignatowska-Jankowska, Mohammed A Mustafa, Francesca Guida, Gavin N Petrie, Linda Parker, Reem Smoum, Laura Sim-Selley, Sabatino Maione, Aron H Lichtman, M Imad Damaj, Vincenzo Di Marzo, Raphael Mechoulam
Cigarette smokers with brain damage involving the insular cortex display cessation of tobacco smoking, suggesting that this region may contribute to nicotine addiction. In the present study, we speculated that molecules in the insular cortex that are sensitive to experimental traumatic brain injury (TBI) in mice might provide leads to ameliorate nicotine addiction. Using targeted lipidomics, we found that TBI elicited substantial increases of a largely uncharacterized lipid, N-acyl-glycine, N-oleoyl-glycine (OlGly), in the insular cortex of mice...
March 19, 2018: Neuropharmacology
Xianhua Liu, Ruiheng Yang, Bo Dai, Honghao Zhang, Jinxue Wang, Ning Ma
BACKGROUND: Studies indicate that nicotinic acid and related compounds may decrease phosphorus concentrations effectively by reducing the absorption in the gastrointestinal tract. However, the efficacy and safety of oral niacin treatments have only been investigated in a limited number of small-scale studies. METHODS: We performed this meta-analysis by pooling 12 qualified relevant preclinical and clinical trials to evaluate the association of nicotinic acid (and its related compounds) treatment and hyperphosphatemia among dialysis patients...
March 2018: Medicine (Baltimore)
Kateryna Zhalnina, Katherine B Louie, Zhao Hao, Nasim Mansoori, Ulisses Nunes da Rocha, Shengjing Shi, Heejung Cho, Ulas Karaoz, Dominique Loqué, Benjamin P Bowen, Mary K Firestone, Trent R Northen, Eoin L Brodie
Like all higher organisms, plants have evolved in the context of a microbial world, shaping both their evolution and their contemporary ecology. Interactions between plant roots and soil microorganisms are critical for plant fitness in natural environments. Given this co-evolution and the pivotal importance of plant-microbial interactions, it has been hypothesized, and a growing body of literature suggests, that plants may regulate the composition of their rhizosphere to promote the growth of microorganisms that improve plant fitness in a given ecosystem...
April 2018: Nature Microbiology
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