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https://www.readbyqxmd.com/read/29785179/nanoformulation-of-brain-derived-neurotrophic-factor-with-target-receptor-triggered-release-in-the-central-nervous-system
#1
Yuhang Jiang, James M Fay, Chi-Duen Poon, Natasha Vinod, Yuling Zhao, Kristin Bullock, Si Qin, Devika S Manickam, Xiang Yi, William A Banks, Alexander V Kabanov
Brain-derived neurotrophic factor (BDNF) is identified as a potent neuroprotective and neuroregenerative agent for many neurological diseases. Regrettably, its delivery to the brain is hampered by poor serum stability and rapid brain clearance. Here, a novel nanoformulation is reported composed of a bio-compatible polymer, poly(ethylene glycol)- b -poly(L-glutamic acid) (PEG-PLE), that hosts the BDNF molecule in a nanoscale complex, termed here Nano-BDNF. Upon simple mixture, Nano-BDNF spontaneously forms uniform spherical particles with a core-shell structure...
February 7, 2018: Advanced Functional Materials
https://www.readbyqxmd.com/read/29784882/phenotypic-assessment-suggests-multiple-start-codons-for-hetn-an-inhibitor-of-heterocyst-differentiation-in-anabaena-sp-strain-pcc-7120
#2
Orion S Rivers, Silvia Beurmann, Allexa Dow, Loralyn M Cozy, Patrick Videau
Multicellular organisms must carefully regulate the timing, number, and location of specialized cellular development. In the filamentous cyanobacterium Anabaena sp. strain PCC 7120, nitrogen-fixing heterocysts are interspersed between vegetative cells in a periodic pattern to achieve optimal exchange of bioavailable nitrogen and reduced carbon. The spacing between heterocysts is regulated by the activity of two developmental inhibitors: PatS and HetN. PatS functions to create a de novo pattern from a homogenous field of undifferentiated cells, while HetN maintains the pattern throughout subsequent growth...
May 21, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29784860/molecular-and-functional-characterization-of-fc%C3%AE-riiib-receptor-ligand-interaction-implications-for-neutrophil-mediated-immune-mechanisms-in-malaria
#3
Piyapong Simtong, Amornrat V Romphruk, Annalena Traum, Monika Burg-Roderfeld, Gregor Bein, Konstantin Jakubowski, Andreas Dominik, Michael Theisen, Ikhlaq Hussain Kana, Ulrich J Sachs, Sentot Santoso
The Fcγ receptor IIIb (FcγRIIIb) is a low-affinity receptor of IgG and is essential in neutrophil mediated effector functions. Different allelic forms of FcγRIIIb carrying human neutrophil antigen (HNA-1a, -1b, -1c and -1d) have been identified. Here, we have generated stable transfected HEK293 cell lines expressing HNA-1aa, -1bb, and -1bc. Of these, cells expressing HNA-1bc interacted significantly stronger (2.277 versus 0.743) with human IgG than cells expressing the HNA-1aa or -1bb alloforms. The higher affinity of IgG towards the HNA-1c alloform was confirmed using neutrophils derived from German blood donors...
May 21, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29784398/use-of-%C3%AE-cyclodextrin-as-enhancer-of-ascorbic-acid-rejection-in-permselective-films-for-amperometric-biosensor-applications
#4
Patrizia Monti, Gaia Rocchitta, Salvatore Marceddu, Maria A Dettori, Davide Fabbri, Samir Jaoua, Quirico Migheli, Giovanna Delogu, Pier A Serra
Interference rejection in amperometric biosensors can be more effective introducing some modifiers during electro-deposition of permselective film. Addition of β-cyclodextrin (βCD), a cyclic oligosaccharide composed of seven glucose units, to the ortho-phenylendiamine (oPD) monomer were already demonstrated to provide an enhancement in ascorbic acid (AA) rejection. Here we evaluated the improvement in permselectivity of poly-eugenol and poly-magnolol films electro-polymerized in presence of different amounts of βCD or eugenol-βCD inclusion complex for amperometric biosensor application...
August 15, 2018: Talanta
https://www.readbyqxmd.com/read/29783774/d-amino-acid-peptide-residualizing-agents-for-protein-radioiodination-effect-of-aspartate-for-glutamate-substitution
#5
Marek Pruszynski, Choong Mo Kang, Eftychia Koumarianou, Ganesan Vaidyanathan, Michael R Zalutsky
The residualizing prosthetic agent N ε -(3-[* I]iodobenzoyl)-Lys⁵- N α -maleimido-Gly¹-d-GEEEK ([* I]IB-Mal-d-GEEEK) showed promise for the radioiodination of monoclonal antibodies (mAbs) that bind to internalizing molecular targets. Although enhanced tumor uptake was achieved in these studies, elevated kidney accumulation also was observed, particularly with low-molecular-weight, single-domain antibody fragments (sdAbs). Here, we developed an analogous agent (IB-Mal-d-GDDDK), in which glutamate residues (E) were replaced with aspartates (D) to determine whether this modification could decrease renal uptake...
May 20, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29781607/preparation-of-pga-pae-micelles-for-enhanced-anti-tumor-efficacy-of-cisplatin
#6
Yazhou Chen, Li Zhang, Yingjie Liu, Shiming Tan, Ruidan Qu, Zirong Wu, Yue Zhou, Jing Huang
Poly-γ-L-glutamic acid (PGA) is an outstanding drug carrier candidate owning to its excellent biodegradability and biocompatibility. PGA carrier may shield toxic drugs from the body and enable the delivery of poorly soluble or unstable drugs thereby minimize the side effects and improve drug efficacy. However, the limitation of PGA as a drug carrier is low drug loading efficiency (DLE), which is usually below 30%. In this study, we reported a chemical modification method using L-phenylalanine ethyl ester (PAE)...
May 21, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29780670/unfolding-of-%C3%AE-helical-20-residue-poly-glutamic-acid-analyzed-by-multiple-runs-of-canonical-molecular-dynamics-simulations
#7
Naoki Ogasawara, Kota Kasahara, Ryosuke Iwai, Takuya Takahashi
Elucidating the molecular mechanism of helix-coil transitions of short peptides is a long-standing conundrum in physical chemistry. Although the helix-coil transitions of poly-glutamic acid (PGA) have been extensively studied, the molecular details of its unfolding process still remain unclear. We performed all-atom canonical molecular dynamics simulations for a 20-residue PGA, over a total of 19 μs, in order to investigate its helix-unfolding processes in atomic resolution. Among the 28 simulations, starting with the α-helical conformation, all showed an unfolding process triggered by the unwinding of terminal residues, rather than by kinking and unwinding of the middle region of the chain...
2018: PeerJ
https://www.readbyqxmd.com/read/29779945/moderate-uv-exposure-enhances-learning-and-memory-by-promoting-a-novel-glutamate-biosynthetic-pathway-in-the-brain
#8
Hongying Zhu, Ning Wang, Lei Yao, Qi Chen, Ran Zhang, Junchao Qian, Yiwen Hou, Weiwei Guo, Sijia Fan, Siling Liu, Qiaoyun Zhao, Feng Du, Xin Zuo, Yujun Guo, Yan Xu, Jiali Li, Tian Xue, Kai Zhong, Xiaoyuan Song, Guangming Huang, Wei Xiong
Sunlight exposure is known to affect mood, learning, and cognition. However, the molecular and cellular mechanisms remain elusive. Here, we show that moderate UV exposure elevated blood urocanic acid (UCA), which then crossed the blood-brain barrier. Single-cell mass spectrometry and isotopic labeling revealed a novel intra-neuronal metabolic pathway converting UCA to glutamate (GLU) after UV exposure. This UV-triggered GLU synthesis promoted its packaging into synaptic vesicles and its release at glutamatergic terminals in the motor cortex and hippocampus...
May 7, 2018: Cell
https://www.readbyqxmd.com/read/29778944/activation-and-blockade-of-basolateral-amygdala-5-ht-6-receptor-produce-anxiolytic-like-behaviors-in-an-experimental-model-of-parkinson-s-disease
#9
Yi-Na Sun, Lu Yao, Li-Bo Li, Yong Wang, Cheng-Xue Du, Yuan Guo, Jian Liu
Although the basolateral amygdala (BLA) and serotonin6 (5-HT6 ) receptor are involved in modulation of anxiety, their roles in Parkinson' disease (PD)-related anxiety are still unknown. Thus we perform this study to examine the involvement of BLA 5-HT6 receptor on anxiety in unilateral 6-hydroxydopamine-induced PD rats. The lesion of the medial forebrain bundle (MFB) induced anxiety-like behaviors, and decreased the basal firing rate of BLA glutamate neurons and dopamine (DA) levels in tissues of the medial prefrontal cortex (mPFC), amygdala and ventral part of hippocampus (vHip) in rats...
May 17, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29778792/valproic-acid-attenuates-manganese-induced-reduction-in-expression-of-glt-1-and-glast-with-concomitant-changes-in-murine-dopaminergic-neurotoxicity
#10
James Johnson, Edward Pajarillo, Pratap Karki, Judong Kim, Deok-Soo Son, Michael Aschner, Eunsook Lee
Exposure to elevated levels of manganese (Mn) causes manganism, a neurological disorder with similar characteristics to those of Parkinson's disease (PD). Valproic acid (VPA), an antiepileptic, is known to inhibit histone deacetylases and exert neuroprotective effects in many experimental models of neurological disorders. In the present study, we investigated if VPA attenuated Mn-induced dopaminergic neurotoxicity and the possible mechanisms involved in VPA's neuroprotection, focusing on modulation of astrocytic glutamate transporters (glutamate aspartate transporter, GLAST and glutamate transporter 1, GLT-1) and histone acetylation in H4 astrocyte culture and mouse models...
May 17, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29778688/molecular-basis-of-diseases-caused-by-the-mtdna-mutation-m-8969g-a-in-the-subunit-a-of-atp-synthase
#11
Natalia Skoczeń, Alain Dautant, Krystyna Binko, François Godard, Marine Bouhier, Xin Su, Jean-Paul Lasserre, Marie-France Giraud, Déborah Tribouillard-Tanvier, Huimei Chen, Jean-Paul di Rago, Roza Kucharczyk
The ATP synthase which provides aerobic eukaryotes with ATP, organizes into a membrane-extrinsic catalytic domain, where ATP is generated, and a membrane-embedded FO domain that shuttles protons across the membrane. We previously identified a mutation in the mitochondrial MT-ATP6 gene (m.8969G>A) in a 14-year-old Chinese female who developed an isolated nephropathy followed by brain and muscle problems. This mutation replaces a highly conserved serine residue into asparagine at amino acid position 148 of the membrane-embedded subunit a of ATP synthase...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29778094/substrate-sustained-release-based-high-efficacy-biosynthesis-of-gaba-by-lactobacillus-brevis-ncl912
#12
Qiong Wang, Xiaohua Liu, Jinheng Fu, Shuixing Wang, Yuanhong Chen, Kunpeng Chang, Haixing Li
BACKGROUND: Gamma-aminobutyric acid (GABA) plays a significant role in the food and drug industries. Our previous study established an efficient fed-batch fermentation process for Lactobacillus brevis NCL912 production of GABA from monosodium L-glutamate; however, monosodium L-glutamate may not be an ideal substrate, as it can result in the rapid increase of pH due to decarboxylation. Thus, in this study, L-glutamic acid was proposed as a substrate. To evaluate its potential, key components of the fermentation medium affecting GABA synthesis were re-screened and re-optimized to enhance GABA production from L...
May 19, 2018: Microbial Cell Factories
https://www.readbyqxmd.com/read/29777762/astrocyte-elevated-gene-1-is-a-novel-regulator-of-astrogliosis-and-excitatory-amino-acid-transporter-2-via-interplaying-with-nuclear-factor-%C3%AE%C2%BAb-signaling-in-astrocytes-from-amyotrophic-lateral-sclerosis-mouse-model-with-hsod1-g93a-mutation
#13
Xiang Yin, Shuyu Wang, Yan Qi, Xudong Wang, Hongquan Jiang, Tianhang Wang, Yueqing Yang, Ying Wang, Chunting Zhang, Honglin Feng
AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1G93A -positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling...
May 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29777624/characterisation-of-a-putative-glutamate-5-kinase-from-leishmania-donovani
#14
Natasha Sienkiewicz, Han B Ong, Alan H Fairlamb
Previous metabolic studies have demonstrated that leishmania parasites are able to synthesise proline from glutamic acid and threonine from aspartic acid. The first committed step in both biosynthetic pathways involves an amino acid kinase, either a glutamate 5-kinase (EC 2.7.2.11) or an aspartokinase (EC 2.7.2.4). Bioinformatic analysis of multiple leishmania genomes identifies a single amino-acid-kinase gene (LdBPK 262740.1) variously annotated as either a putative glutamate or aspartate kinase. To establish the catalytic function of this Leishmania donovani gene product, we have determined the physical and kinetic properties of the recombinant enzyme purified from Escherichia coli...
May 19, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29776930/modifying-the-lantibiotic-mutacin-1140-for-increased-yield-activity-and-stability
#15
Mengxin Geng, Leif Smith
Mutacin 1140 belongs to the epidermin family of type AI lantibiotics. This family has a broad spectrum of activity against Gram-positive bacteria. The binding of mutacin 1140 to lipid II leads to the inhibition of cell wall synthesis. Pharmacokinetic experiments on type AI lantibiotics are generally discouraging for clinical applications due to their short half-life. The unprotected dehydrated and protease susceptible residues outside of the lanthionine rings may play a role in their short half-life in physiological settings...
May 18, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29775942/toxicological-effects-on-earthworms-eisenia-fetida-exposed-to-sub-lethal-concentrations-of-bde-47-and-bde-209-from-a-metabolic-point
#16
Ruoyu Liang, Juan Chen, Yajuan Shi, Yonglong Lu, Suriyanarayanan Sarvajayakesavalu, Xiangbo Xu, Xiaoqi Zheng, Kifayatullah Khan, Chao Su
Earthworms improve the soil fertility and they are also sensitive to soil contaminants. Earthworms (Eisenia fetida), standard reference species, were usually chosen to culture and handle for toxicity tests. Metabolic responses in earthworms exposed to 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) and decabromodiphenyl ether (BDE-209) were inhibitory and interfered with basal metabolism. In this study, 1 H-NMR based metabolomics was used to identify sensitive biomarkers and explore metabolic responses of earthworms under sub-lethal BDE-47 and BDE-209 concentrations for 14 days...
May 15, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29775570/rapid-non-classical-effects-of-steroids-on-the-membrane-receptor-dynamics-and-downstream-signaling-in-neurons
#17
REVIEW
Klaudia Barabás, Soma Godó, Ferenc Lengyel, Dávid Ernszt, József Pál, István M Ábrahám
Although rapid effects of steroid hormones on membrane receptors and intracellular signaling molecules have been extensively studied in neurons, we are only beginning to understand the molecular mechanisms behind these non-classical steroid actions. Single molecule tracking (SMT) studies on live cells demonstrated that surface trafficking of membrane receptors determines their ligand binding properties and downstream signaling events. Recent findings suggest that one of the underlying mechanisms of non-classical steroid actions is the alteration of receptor movements on the membrane surface...
May 15, 2018: Hormones and Behavior
https://www.readbyqxmd.com/read/29775221/reagent-induced-asymmetric-induction-in-addition-reaction-of-reduced-glutathione-onto-bis-mannich-chalcones
#18
Aline Bernardes, Giulio D C D'Oliveira, Aneta Silezin, Mónika Kuzma, Szilárd Molnár, Caridad Noda Pérez, Pál Perjési
The stereochemistry of non-enzyme catalyzed nucleophilic addition of GSH to 4'-hydroxychalcone 1 and its bis-Mannich derivative 2 was investigated at different pH values (pH 3.2, 6.1, 7.4, and 8.0). The stereochemical outcome of the reactions was evaluated by HPLC-UV-Vis method. Under strongly acidic conditions (pH 3.2), an unexpected diastereoselective addition of GSH onto the bis-Mannich derivative 2 was observed. Such a selectivity could not be observed in the similar reaction of 2 with N-acetylcysteine...
May 18, 2018: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29773477/selenium-bioaccumulation-and-associated-nutraceutical-properties-in-calocybe-indica-mushroom-cultivated-on-se-enriched-wheat-straw
#19
Himanshi Rathore, Abhishek Sharma, Shalinee Prasad, Satyawati Sharma
Calocybe indica was cultivated on wheat straw enriched with various concentrations of sodium selenite (Na2 SeO3 ), (2.5-40 μg/ml). The content of selenium (Se) in fruit bodies increased linearly by increasing the amount of Na2 SeO3 , although the biomass yield inhibited above 5 μg/ml. The fruit bodies accumulated inorganic Se into organic forms by integrating the Se into proteins (56%-68%), polysaccharides (22%-29%), and nucleic acids (1.4%-2.7%). Maximum protein content (25.31 g/100 g) was observed in fruit bodies harvested from the substrate enriched with 10 μg/ml Se...
May 15, 2018: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/29772516/acidic-amino-acids-a-new-type-of-enzyme-mimics-with-application-to-biosensing-and-evaluating-of-antioxidant-behaviour
#20
Ying Shi, Li Liu, Yuanyuan Yu, Yijuan Long, Huzhi Zheng
Nanomaterials have triggered tremendous interest to mimick peroxidase but rarely attention has been paid to small molecules. Herein we first found that acidic amino acids including l-glutamic acid (L-Glu) and l-aspartic acid (L-Asp) exhibited an intrinsic peroxidase-like activity, endowing acidic amino acids with the capability of catalysing the oxidation of the peroxidase substrates 3,3',5,5'-tetramethylbenzidine (TMB) to produce color reaction in the presence of H2 O2 . Reaction mechanism was further investigated by means of electron spin resonance spectroscopy (ESR), enzyme kinetics assay and quantum theoretical calculations, to verify and provide a good deal of insight into the catalytic process...
May 8, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
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