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https://www.readbyqxmd.com/read/28636281/aryl-and-heteroaryl-substituted-phenylalanines-as-ampa-receptor-ligands
#1
Ewa Szymańska, Paulina Chałupnik, Tommy N Johansen, Birgitte Nielsen, Ana Maria Cuñado Moral, Darryl S Pickering, Anna Więckowska, Katarzyna Kieć-Kononowicz
A series of racemic unnatural amino acids was rationally designed on the basis of recently published X-ray structures of the GluA2 LBD with bound phenylalanine-based antagonists. Twelve new diaryl- or aryl/heteroaryl-substituted phenylalanine derivatives were synthesized and evaluated in vitro in radioligand binding assays at native rat ionotropic glutamate receptors. The most interesting compound in this series, (RS)-2-amino-3-(3'-hydroxy-5-(1H-pyrazol-4-yl)-[1,1'-biphenyl]-3-yl)propanoic acid 7e, showed the binding affinity of 4...
June 21, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28636132/trpc1-and-trpc3-dependent-ca-2-signaling-in-mouse-cortical-astrocytes-affects-injury-evoked-astrogliosis-in-vivo
#2
Thabet Belkacemi, Alexander Niermann, Laura Hofmann, Ulrich Wissenbach, Lutz Birnbaumer, Petra Leidinger, Christina Backes, Eckart Meese, Andreas Keller, Xianshu Bai, Anja Scheller, Frank Kirchhoff, Stephan E Philipp, Petra Weissgerber, Veit Flockerzi, Andreas Beck
Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca(2+) . Transient receptor potential canonical (TRPC) channels may contribute to Ca(2+) influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells...
June 21, 2017: Glia
https://www.readbyqxmd.com/read/28635962/growth-of-organic-crystals-via-attachment-and-transformation-of-nanoscopic-precursors
#3
Yuan Jiang, Matthias Kellermeier, Denis Gebaue, Zihao Lu, Rose Rosenberg, Adrian Moise, Michael Przybylski, Helmut Cölfen
A key requirement for the understanding of crystal growth is to detect how new layers form and grow at the nanoscale. Multistage crystallization pathways involving liquid-like, amorphous or metastable crystalline precursors have been predicted by theoretical work and have been observed experimentally. Nevertheless, there is no clear evidence that any of these precursors can also be relevant for the growth of crystals of organic compounds. Herein, we present a new growth mode for crystals of DL-glutamic acid monohydrate that proceeds through the attachment of preformed nanoscopic species from solution, their subsequent decrease in height at the surface and final transformation into crystalline 2D nuclei that eventually build new molecular layers by further monomer incorporation...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28635550/peptide-grafted-and-self-assembled-poly-%C3%AE-glutamic-acid-phenylalanine-nanoparticles-targeting-camptothecin-to-glioma
#4
Hitesh Kulhari, Srinivasa R Telukutla, Deep Pooja, Ravi Shukla, Ramakrishna Sistla, Vipul Bansal, David J Adams
AIM: To synthesize cRGDfK peptide conjugated poly(γ-glutamic acid)-phenylalanine nanoparticles to improve the therapeutic efficacy of camptothecin (CPT) against glioblastoma multiforme. METHODS: Peptide-conjugated, drug-loaded nanoparticles (cRGDfK-conjugated camptothecin-loaded PGA-PA nanoparticles [RCPN]) were prepared and physico-chemically characterized using different techniques. Nanoparticles were evaluated for in vitro anticancer activity, cellular uptake, induction of apoptosis and wound healing cell migration against U87MG human glioblastoma cells...
June 21, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28634390/increased-glutamate-in-somatosensory-cortex-in-functional-dyspepsia
#5
Arthur D P Mak, Georg Northoff, David K W Yeung, Winnie C W Chu, Steve C N Hui, Cynthia Cheung, Jessica Ching, Linda Lam, Sing Lee, Justin Wu
Functional Dyspepsia-Post-prandial Distress Syndrome (FD-PDS) was associated with mood-related increases in resting activity and lowered activation threshold in the somatosensory cortex (SSC), insula and perigenual anterior cingulate cortex(pgACC) in functional imaging studies. The underlying cortical neurochemical changes are unknown. We performed proton Magnetic Resonance Spectroscopy (1H-MRS) on 17 consecutive tertiary clinic-recruited psychotropic-naïve Rome III FD-PDS female and 17 age-sex matched healthy controls...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634070/high-and-low-concentration-of-17%C3%AE-estradiol-protect-cerebellar-granule-neurons-in-different-time-windows
#6
Irene B Sørvik, Ragnhild E Paulsen
17α-estradiol is a hormonally inactive isomer of 17β-estradiol, but with similar potency as neuroprotector. However, we have previously reported that pretreatment with high concentration (10 μM) of both estrogens abolishes their neuroprotection in rat cerebellar granule neurons. Here, we have examined neuroprotective properties of 17α-estradiol against glutamate-induced excitotoxicity in chicken cerebellar granule neurons using low (1 nM) and high concentration.17α-Estradiol, 1 nM, was neuroprotective when glutamate was administered after a pretreatment period of 24 h, but not when coadministered with glutamate...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28633367/cortical-glutamate-in-migraine
#7
Ronald Zielman, Jannie P Wijnen, Andrew Webb, Gerrit L J Onderwater, Itamar Ronen, Michel D Ferrari, Hermien E Kan, Gisela M Terwindt, Mark C Kruit
Cortical hyperexcitability due to enhanced glutamatergic activity has been implicated in migraine pathophysiology but direct evidence is lacking. Here we assessed glutamate levels and intracellular mobility of glutamate in the visual cortex of migraineurs in-between attacks. We included 50 migraineurs (23 with aura and 27 without aura) and 24 age- and gender-matched non-headache controls. We used proton magnetic resonance spectroscopy (1H-MRS) and diffusion weighted spectroscopy at 7 T with a single volume of interest (2 × 2 × 3 cm) located in the primary and secondary visual cortex...
June 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28632336/serious-life-events-and-the-risk-of-latent-autoimmune-diabetes-in-adults-lada-and-type-2-diabetes
#8
B Rasouli, T Andersson, P-O Carlsson, R Hjort, J E Löfvenborg, M Martinell, L Groop, T Tuomi, S Carlsson
AIM: It has been suggested that experiencing serious life events may promote Type 1 diabetes in children. Studies in adults are lacking, as are studies on the interaction of life events with genetic factors. We aimed to investigate life events and the risk of latent autoimmune diabetes in adults (LADA) and Type 2 diabetes while taking into account HLA genotype. METHODS: Analysis was based on 425 incident cases of LADA, 1417 incident cases of Type 2 diabetes and 1702 population-based controls recruited in Sweden between 2010 and 2016...
June 20, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28631873/roles-of-afadin-in-functional-differentiations-of-hippocampal-mossy-fiber-synapse
#9
Xiaoqi Geng, Tomohiko Maruo, Kenji Mandai, Irwan Supriyanto, Muneaki Miyata, Shotaro Sakakibara, Akira Mizoguchi, Yoshimi Takai, Masahiro Mori
A hippocampal mossy fiber synapse has a complex structure and is implicated in learning and memory. In this synapse, the mossy fiber boutons attach to the dendritic shaft by puncta adherentia junctions and wrap around a multiply-branched spine, forming synaptic junctions. We have recently shown using transmission electron microscopy, immunoelectron microscopy and serial block face-scanning electron microscopy that atypical puncta adherentia junctions are formed in the afadin-deficient mossy fiber synapse and that the complexity of postsynaptic spines and mossy fiber boutons, the number of spine heads, the area of postsynaptic densities and the density of synaptic vesicles docked to active zones are decreased in the afadin-deficient synapse...
June 20, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28631864/ceftriaxone-reduces-l-dopa-induced-dyskinesia-severity-in-6-hydroxydopamine-parkinson-s-disease-model
#10
Tanya Chotibut, Samantha Meadows, Ella A Kasanga, Tamara McInnis, Mark A Cantu, Christopher Bishop, Michael F Salvatore
BACKGROUND: Increased extracellular glutamate may contribute to l-dopa induced dyskinesia, a debilitating side effect faced by Parkinson's disease patients 5 to 10 years after l-dopa treatment. Therapeutic strategies targeting postsynaptic glutamate receptors to mitigate dyskinesia may have limited success because of significant side effects. Increasing glutamate uptake may be another approach to attenuate excess glutamatergic neurotransmission to mitigate dyskinesia severity or prolong the time prior to onset...
June 20, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28631555/grik3-a-novel-oncogenic-protein-related-to-tumor-tnm-stage-lymph-node-metastasis-and-poor-prognosis-of-gc
#11
Baocheng Gong, Yuan Li, Zhenguo Cheng, Pengliang Wang, Lei Luo, Hanwei Huang, Shijie Duan, Funan Liu
Glutamate receptor, ionotropic, kainate 3 (GRIK3), as a member of the glutamate kainate receptor family, mainly participated in neuroactive ligand receptor interaction pathway. Other members of GRIK family were previously reported to regulate cellular migration, transformation, and proliferation in tumor. However, the mechanism of GRIK3 in tumor is still unclear. Therefore, the purpose of our study was to reveal the expression and clinical significance of GRIK3 in gastric cancer (GC). First, we performed the expression analysis and survival analysis of GRIK3 using The Cancer Genome Atlas (TCGA) database, and the results showed that the GRIK3 expressed differentially between gastric cancer tissues and the adjacent normal tissues and that higher expression of GRIK3 was associated with poor survival outcomes...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631520/striatal-changes-underlie-mpep-mediated-suppression-of-the-acquisition-and-expression-of-pramipexole-induced-place-preference-in-an-alpha-synuclein-rat-model-of-parkinson-s-disease
#12
Simon Loiodice, Portia McGhan, Vitalina Gryshkova, Renaud Fleurance, David Dardou, Aziz Hafidi, Andre Nogueira da Costa, Franck Durif
Impulsive-compulsive disorders in Parkinson's disease patients have been described as behavioural or substance addictions including pathological gambling or compulsive medication use of dopamine replacement therapy. A substantial gap remains in the understanding of these disorders. We previously demonstrated that the rewarding effect of the D2/D3 agonist pramipexole was enhanced after repeated exposure to L-dopa and alpha-synuclein mediated dopaminergic nigral loss with specific transcriptional signatures suggesting a key involvement of the glutamatergic pathway...
June 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28631282/biosynthesis-of-complex-indole-alkaloids-elucidation-of-the-concise-pathway-of-okaramines
#13
Chen-Yu Lai, Hsiao-Ching Lin, I-Wen Lo, Ranuka T Hewage, Yi-Chen Chen, Chien-Ting Chen, Chi-Fang Lee, Steven Lin, Man-Cheng Tang
The okaramines are a class of complex indole alkaloids isolated from Penicillium and Aspergillus species. Their potent insecticidal activity arises from selectively activating glutamate-gated chloride channels (GluCls) in invertebrates, not affecting human ligand-gated anion channels. Okaramines B (1) and D (2) contain a polycyclic skeleton, including an azocine ring and an unprecedented 2-dimethyl-3-methyl-azetidine ring. Due to their complex scaffold, okaramines have inspired many total synthesis efforts, but the enzymology of the okaramine biosynthetic pathway remains unexplored...
June 20, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28631172/glutamine-a-major-player-in-nitrogen-catabolite-repression-in-the-yeast-dekkera-bruxellensis
#14
Danielli Batista Bezerra Cajueiro, Denise Castro Parente, Fernanda Cristina Bezerra Leite, Marcos Antonio de Morais Junior, Will de Barros Pita
In the present work we studied the expression of genes from nitrogen central metabolism in the yeast Dekkera bruxellensis and under regulation by the Nitrogen Catabolite Repression mechanism (NCR). These analyses could shed some light on the biological mechanisms involved in the adaptation and survival of this yeast in the sugarcane fermentation process for ethanol production. Nitrogen sources (N-sources) in the form of ammonium, nitrate, glutamate or glutamine were investigated with or without the addition of methionine sulfoximine, which inhibits the activity of the enzyme glutamine synthetase and releases cells from NCR...
June 19, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/28630648/comparative-metabolic-profiling-of-the-lipid-producing-green-microalga-chlorella-reveals-that-nitrogen-and-carbon-metabolic-pathways-contribute-to-lipid-metabolism
#15
Hui Chen, Yanli Zheng, Jiao Zhan, Chenliu He, Qiang Wang
Microalgae are a promising feedstock for biofuel production. Microalgal metabolic pathways are heavily influenced by environmental factors. For instance, lipid metabolism can be induced by nitrogen-limiting conditions. However, the underlying mechanisms of lipid biosynthesis are unclear. In this study, we analyzed the global metabolic profiles of three genetically closely related Chlorella strains (C1, C2, and C3) with significant differences in lipid productivity to identify the contributions of key metabolic pathways to lipid metabolism...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28630145/activity-dependent-trafficking-of-lysosomes-in-dendrites-and-dendritic-spines
#16
Marisa S Goo, Laura Sancho, Natalia Slepak, Daniela Boassa, Thomas J Deerinck, Mark H Ellisman, Brenda L Bloodgood, Gentry N Patrick
In neurons, lysosomes, which degrade membrane and cytoplasmic components, are thought to primarily reside in somatic and axonal compartments, but there is little understanding of their distribution and function in dendrites. Here, we used conventional and two-photon imaging and electron microscopy to show that lysosomes traffic bidirectionally in dendrites and are present in dendritic spines. We find that lysosome inhibition alters their mobility and also decreases dendritic spine number. Furthermore, perturbing microtubule and actin cytoskeletal dynamics has an inverse relationship on the distribution and motility of lysosomes in dendrites...
June 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28630042/the-glutamate-cystine-antiporter-slc7a11-xct-enhances-cancer-cell-dependency-on-glucose-by-exporting-glutamate
#17
Pranavi Koppula, Yilei Zhang, Jiejun Shi, Wei Li, Boyi Gan
Cancer cells with specific genetic alterations may be highly dependent on certain nutrients for survival, which can inform therapeutic strategies to target these cancer-specific metabolic vulnerabilities. The glutamate/cystine antiporter solute carrier family 7 member 11 (SLC7A11, also called xCT) is overexpressed in several cancers. Contrasting the established pro-survival roles of SLC7A11 under other stress conditions, here we report an unexpected finding that SLC7A11 overexpression enhances cancer cell dependency on glucose and renders cancer cells more sensitive to glucose starvation-induced cell death, and conversely, that SLC7A11 deficiency by either knockdown or pharmacological inhibition promotes cancer cell survival upon glucose starvation...
June 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28629983/self-assembly-nanostructure-controlled-sustained-release-activity-and-stability-of-peptide-drugs
#18
Xi-Rui Zhou, Yimeng Cao, Qiang Zhang, Xi-Bo Tian, He Dong, Long Chen, Shi-Zhong Luo
Peptides are considered as a new generation of drugs due to their high structural and functional diversity. However, the development of peptide drugs is always limited by their poor stability and short circulation time. Carriers are applied for peptide drug delivery, but there may be problems like poor loading efficiency and undesired xenobiotic toxicity. Peptide self-assembly is an effective approach to improve the stability and control the release of peptide drugs. In this study, two self-assembling anticancer peptides are designed by appending a pair of glutamic acid and asparagine to either the N-terminus or the C-terminus of a lytic peptide...
June 16, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28629846/hippocampal-gr-and-cb1-mediated-mglur5-differentially-produces-susceptibility-and-resilience-to-acute-and-chronic-mild-stress-in-rats
#19
Hongli Sun, Rujuan Su, Xiaoxiao Zhang, Jun Wen, Dan Yao, Xinru Gao, Zhongliang Zhu, Hui Li
The molecular mechanism of individual response of susceptibility and resilience under psychological stress remains controversial and unclear. The present study aimed to explore the relationship of metabotropic glutamate receptor 5 (mGluR5) with glucocorticoid receptor (GR) or cannabinoid receptor (CB1) and further indicate the molecular mechanism of susceptibility and resilience to acute stress (AS) and chronic mild stress (CMS). Sucrose preference test and open field test were used to evaluate the response of susceptibility and resilience under stress in rats...
June 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28629519/erythropoietin-endogenous-protection-of-ischemic-brain
#20
Robert T Mallet, Myoung-Gwi Ryou
The human brain requires uninterrupted delivery of blood-borne oxygen and nutrients to sustain its function. Focal ischemia, particularly, ischemic stroke, and global ischemia imposed by cardiac arrest disrupt the brain's fuel supply. The resultant ATP depletion initiates a complex injury cascade encompassing intracellular Ca(2+) overload, glutamate excitotoxicity, oxido-nitrosative stress, extracellular matrix degradation, and inflammation, culminating in neuronal and astroglial necrosis and apoptosis, neurocognitive deficits, and even death...
2017: Vitamins and Hormones
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