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https://www.readbyqxmd.com/read/28222358/tyrosine-kinase-inhibition-is-an-important-factor-for-gene-expression-of-crth2-in-human-eosinophils-and-lymphocytes-a-novel-mechanism-for-explaining-eosinophils-recruitment-by-the-neuro-immune-axis-in-allergic-rhinitis
#1
A E El-Shazly, P Roncarati, M Lejeune, P P Lefebvre, P Delvenne
We recently shown a novel neuro-immune competition between vasoactive intestinal peptide (VIP) and PGD2 for CRTH2 receptor, and that genistein augmented VIP and PGD2-induced eosinophil chemotaxis. However, there are neither studies on the CRTH2 gene expression in allergic rhinitis (AR) nor in the effect of tyrosine kinase inhibitors in CRTH2 gene regulation. Our Objectives were to study the gene expression modulation of CRTH2 receptor in AR patients and the effect of tyrosine kinase inhibitors (TKIs) on CRTH2 gene modulation...
February 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28221926/evaluation-of-selected-nutrients-and-contaminants-in-distillers-grains-from-ethanol-production-in-texas
#2
Kyung-Min Lee, Timothy J Herrman, Lynn Post
This article contains the results of the evaluation of distillers grain (DG) coproducts from different ethanol plants around the United States and supplemented in animal diets in Texas, based on samples analyzed from 2008 to 2014. The samples were assessed for concentration, occurrence, and prevalence of selected nutrients and contaminants. Protein and sulfur contents of DG were largely different between maize and sorghum coproducts, as well as wet distillers grain with solubles (WDGS) and dried distillers grain with solubles (DDGS), indicating a significant effect of grain feedstock and dry grind process stream on DG composition and quality...
September 2016: Journal of Food Protection
https://www.readbyqxmd.com/read/28221788/substituted-2-aminopyrimidines-selective-for-%C3%AE-7-nicotinic-acetylcholine-receptor-activation-and-association-with-acetylcholine-binding-proteins
#3
Katarzyna Kaczanowska, Gisela Andrea Camacho Hernandez, Larissa Bendiks, Larissa Kohs, Jose Manuel Cornejo Bravo, Michal Harel, M G Finn, Palmer Taylor
Through studies with ligand binding to the acetylcholine binding protein (AChBP), we previously identified a series of 4,6 substituted 2-aminopyrimidines that associate with this soluble surrogate of the nicotinic acetylcholine receptor (nAChR) in a cooperative fashion, not seen for classical nicotinic agonists and antagonists. To examine receptor interactions of this structural family on ligand-gated ion channels, we employed HEK cells transfected with cDNA's encoding three requisite receptor subtypes: α7-nAChR, α4β2-nAChR and a serotonin receptor (5-HT3AR), along with a fluorescent reporter...
February 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28221782/the-cation-%C3%AF-interaction-enables-a-halo-tag-fluorogenic-probe-for-fast-no-wash-live-cell-imaging-and-gel-free-protein-quantification
#4
Yu Liu, Kun Miao, Noah P Dunham, Hongbin Liu, Matthew Fares, Amie K Boal, Xiaosong Li, Xin Zhang
Design of fluorogenic probes for Halo-tag is highly desirable but challenging. Previous work achieved this goal by controlling the chemical switch of spirolactones upon the covalent conju-gation between Halo-tag and probes or by incorporating a 'channel dye' into the substrate bind-ing tunnel of Halo-tag. In this work, we have developed a novel class of Halo-tag fluorogenic probes that are derived from solvatochromic fluorophores. The optimal probe, harboring a ben-zothiadiazole scaffold, exhibits a 1000-fold fluorescence enhancement upon reaction with Halo-tag...
February 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28221363/premature-primary-tooth-eruption-in-cognitive-motor-delayed-adnp-mutated-children
#5
I Gozes, A Van Dijck, G Hacohen-Kleiman, I Grigg, G Karmon, E Giladi, M Eger, Y Gabet, M Pasmanik-Chor, E Cappuyns, O Elpeleg, R F Kooy, S Bedrosian-Sermone
A major flaw in autism spectrum disorder (ASD) management is late diagnosis. Activity-dependent neuroprotective protein (ADNP) is a most frequent de novo mutated ASD-related gene. Functionally, ADNP protects nerve cells against electrical blockade. In mice, complete Adnp deficiency results in dysregulation of over 400 genes and failure to form a brain. Adnp haploinsufficiency results in cognitive and social deficiencies coupled to sex- and age-dependent deficits in the key microtubule and ion channel pathways...
February 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28221136/an-essential-dual-function-complex-mediates-erythrocyte-invasion-and-channel-mediated-nutrient-uptake-in-malaria-parasites
#6
Daisuke Ito, Marc A Schureck, Sanjay A Desai
Malaria parasites evade immune detection by growth and replication within erythrocytes. After erythrocyte invasion, the intracellular pathogen must increase host cell uptake of nutrients from plasma. Here, we report that the parasite-encoded RhopH complex contributes to both invasion and channel-mediated nutrient uptake. As rhoph2 and rhoph3 gene knockouts were not viable in the human P. falciparum pathogen, we used conditional knockdowns to determine that the encoded proteins are essential and to identify their stage-specific functions...
February 21, 2017: ELife
https://www.readbyqxmd.com/read/28220989/global-and-local-mechanisms-sustain-axonal-proteostasis-of-transmembrane-proteins
#7
REVIEW
Víctor Hugo Cornejo, Alejandro Luarte, Andrés Couve
The control of neuronal protein homeostasis or proteostasis is tightly regulated both spatially and temporally, assuring accurate and integrated responses to external or intrinsic stimuli. Local or autonomous responses in dendritic and axonal compartments are crucial to sustain function during development, physiology and in response to damage or disease. Axons are responsible for generating and propagating electrical impulses in neurons, and the establishment and maintenance of their molecular composition are subject to extreme constraints exerted by length and size...
February 21, 2017: Traffic
https://www.readbyqxmd.com/read/28220887/mass-spectrometric-analysis-of-trpm6-and-trpm7-phosphorylation-reveals-regulatory-mechanisms-of-the-channel-kinases
#8
Na Cai, Zhiyong Bai, Vikas Nanda, Loren W Runnels
TRPM7 and TRPM6 were the first identified bifunctional channels to contain their own kinase domains, but how these channel-kinases are regulated is poorly understood. Previous studies identified numerous phosphorylation sites on TRPM7, but very little is known about TRPM6 phosphorylation or sites on TRPM7 transphosphorylated by TRPM6. Our mass spectrometric analysis of homomeric and heteromeric TRPM7 and TRPM6 channels identified phosphorylation sites on both proteins, as well as several prominent sites on TRPM7 that are commonly modified through autophosphorylation and transphosphorylation by TRPM6...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220370/the-effect-of-candesartan-on-pentraxin-3-plasma-levels-as-marker-of-endothelial-dysfunction-in-patients-with-essential-arterial-hypertension
#9
V Buda, M Andor, C Cristescu, M Voicu, F Cochera, P Tuduce, L Petrescu, M C Tomescu
BACKGROUND: In the last decades, the studies performed on the field of endothelial dysfunction confirmed the fact that the starting point of this pathology is the inflammation. Several inflammatory biomarkers had been discovered and studied, ones showing systemic inflammation, and others being more specific biomarkers and showing the local inflammation. Pentraxin-3 (PTX3) is a new inflammatory biomarker, from the same family as high-selectivity C-reactive protein (hs-CRP), but it is a more specific biomarker, due to its local production: the endothelial cells and not the liver like in the case of hs-CRP...
February 21, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28219986/functional-analysis-of-the-transmembrane-and-cytoplasmic-domains-of-pcdh15a-in-zebrafish-hair-cells
#10
Reo Maeda, Itallia V Pacentine, Timothy Erickson, Teresa Nicolson
Protocadherin 15 (PCDH15) is required for mechanotransduction in sensory hair cells as a component of the tip link. Isoforms of PCDH15 differ in their cytoplasmic domains (CD1, CD2, and CD3), but share the extracellular and transmembrane (TMD) domains, as well as an intracellular domain known as the common region (CR). In heterologous expression systems, both the TMD and CR of PCDH15 have been shown to interact with members of the mechanotransduction complex. The in vivo significance of these protein-protein interaction domains of PCDH15 in hair cells has not been determined...
February 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28219978/a-mutation-in-the-g-protein-gene-gnb2-causes-familial-sinus-node-and-atrioventricular-conduction-dysfunction
#11
Birgit Stallmeyer, Johanna Kuß, Stefan Kotthoff, Sven Zumhagen, Kirsty S Vowinkel, Susanne Rinne, Lina A Matschke, Corinna Friedrich, Ellen Schulze-Bahr, Stephan Rust, Guiscard Seebohm, Niels Decher, Eric Schulze-Bahr
Rationale: Familial sinus node and atrioventricular (AV) conduction dysfunction is a rare disorder that leads to paroxysmal dizziness, fatigue and syncope due to a temporarily or permanent reduced heart rate. To date, only a few genes for familial sinus and/or AV conduction dysfunction are known and the majority of cases remain etiologically unresolved. Objective: We aim to identify the disease gene in a large three-generation family (n=25) with autosomal dominant sinus node dysfunction (SND) and AV block (AVB) and to characterise the mutation-related pathomechanisms in familial SND+AVB...
February 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28219928/mitochondria-control-store-operated-ca-2-entry-through-na-and-redox-signals
#12
Tsipi Ben-Kasus Nissim, Xuexin Zhang, Assaf Elazar, Soumitra Roy, Judith A Stolwijk, Yandong Zhou, Rajender K Motiani, Maxime Gueguinou, Nadine Hempel, Michal Hershfinkel, Donald L Gill, Mohamed Trebak, Israel Sekler
Mitochondria exert important control over plasma membrane (PM) Orai1 channels mediating store-operated Ca(2+) entry (SOCE). Although the sensing of endoplasmic reticulum (ER) Ca(2+) stores by STIM proteins and coupling to Orai1 channels is well understood, how mitochondria communicate with Orai1 channels to regulate SOCE activation remains elusive. Here, we reveal that SOCE is accompanied by a rise in cytosolic Na(+) that is critical in activating the mitochondrial Na(+)/Ca(2+) exchanger (NCLX) causing enhanced mitochondrial Na(+) uptake and Ca(2+) efflux...
February 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28219792/conjugative-type-iv-secretion-in-gram-positive-pathogens-trag-a-lytic-transglycosylase-and-endopeptidase-interacts-with-translocation-channel-protein-tram
#13
Verena Kohler, Ines Probst, Andreas Aufschnaiter, Sabrina Büttner, Lisa Schaden, Gerald Rechberger, Günther Koraimann, Elisabeth Grohmann, Walter Keller
Conjugative transfer plays a major role in the transmission of antibiotic resistance in bacteria. pIP501 is a Gram-positive conjugative model plasmid with the broadest transfer host-range known so far and is frequently found in Enterococcus faecalis and Enterococcus faecium clinical isolates. The pIP501 type IV secretion system is encoded by 15 transfer genes. In this work, we focus on the VirB1-like protein TraG, a modular peptidoglycan metabolizing enzyme, and the VirB8-homolog TraM, a potential member of the translocation channel...
February 17, 2017: Plasmid
https://www.readbyqxmd.com/read/28219789/acetazolamide-lowers-intracranial-pressure-and-modulates-the-cerebrospinal-fluid-secretion-pathway-in-healthy-rats
#14
Maria Uldall, Hannah Botfield, Inger Jansen-Olesen, Alexandra Sinclair, Rigmor Jensen
Acetazolamide is one of the most widely used drugs for lowering intracranial pressure (ICP) and is believed to reduce cerebrospinal fluid (CSF) secretion via its action on the choroid plexus (CP). In the CP the main driving force for CSF secretion is primarily active transport of Na(+) ions facilitated by the Na/K ATPase. Transmembrane water channels, known as aquaporins (AQP), are also present in the CP and play an important role in the movement of water. In the present study, we investigated the effect of a single dose acetazolamide on the activity of the Na/K ATPase and ICP...
February 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28218740/maresin1-stimulates-alveolar-fluid-clearance-through-the-alveolar-epithelial-sodium-channel-na-k-atpase-via-the-alx-pi3k-nedd4-2-pathway
#15
Jun-Li Zhang, Xiao-Jun Zhuo, Jing Lin, Ling-Chun Luo, Wei-Yang Ying, Xiang Xie, Hua-Wei Zhang, Jing-Xiang Yang, Dan Li, Fang Gao Smith, Sheng-Wei Jin
Maresin1 (MaR1) is a new docosahexaenoic acid-derived pro-resolving agent that promotes the resolution of inflammation. In this study, we sought to investigate the effect and underlining mechanisms of MaR1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. MaR1 was injected intravenously or administered by instillation (200 ng/kg) 8 h after LPS (14 mg/kg) administration and AFC was measured in live rats. In primary rat alveolar type II epithelial cells, MaR1 (100 nM) was added to the culture medium with lipopolysaccharide for 6 h...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28218252/dissecting-the-molecular-organization-of-the-translocon-associated-protein-complex
#16
Stefan Pfeffer, Johanna Dudek, Miroslava Schaffer, Bobby G Ng, Sahradha Albert, Jürgen M Plitzko, Wolfgang Baumeister, Richard Zimmermann, Hudson H Freeze, Benjamin D Engel, Friedrich Förster
In eukaryotic cells, one-third of all proteins must be transported across or inserted into the endoplasmic reticulum (ER) membrane by the ER protein translocon. The translocon-associated protein (TRAP) complex is an integral component of the translocon, assisting the Sec61 protein-conducting channel by regulating signal sequence and transmembrane helix insertion in a substrate-dependent manner. Here we use cryo-electron tomography (CET) to study the structure of the native translocon in evolutionarily divergent organisms and disease-linked TRAP mutant fibroblasts from human patients...
February 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28217951/cytotoxic-effect-of-zinc-oxide-nanoparticles-on-murine-photoreceptor-cells-via-potassium-channel-block-and-na-k-atpase-inhibition
#17
Chao Chen, Wenjuan Bu, Hongyan Ding, Qin Li, Dabo Wang, Hongsheng Bi, Dadong Guo
OBJECTIVE: Zinc oxide (ZnO) nanoparticles can exhibit toxicity towards organisms and oxidative stress is often hypothesized to be one of the most important factors. Nevertheless, the detailed mechanism of toxicity-induced by ZnO nanoparticles has not been completely addressed. The present study aimed to investigate the toxic effects of ZnO nanoparticles on the expression and activity of Na(+) /K(+) -ATPase and on potassium channel block. MATERIALS AND METHODS: In the present study, we explored the cytotoxic effect of ZnO nanoparticles on murine photoreceptor cells using lactate dehydrogenase (LDH) release assay, reactive oxygen species (ROS) determination, mitochondrial membrane potential (Δφm) measurement, delayed rectifier potassium current recordings and Na(+) /K(+) -ATPase expression and activity monitoring...
February 19, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28217261/affinity-of-rimantadine-enantiomers-against-influenza-a-m2-protein-revisited
#18
Antonios Drakopoulos, Christina Tzitzoglaki, Chulong Ma, Kathrin Freudenberger, Anja Hoffmann, Yanmei Hu, Günter Gauglitz, Michaela Schmidtke, Jun Wang, Antonios Kolocouris
Recent findings from solid state NMR (ssNMR) studies suggested that the (R)-enantiomer of rimantadine binds to the full M2 protein with higher affinity than the (S)-enantiomer. Intrigued by these findings, we applied functional assays, such as antiviral assay and electrophysiology (EP), to evaluate the binding affinity of rimantadine enantiomers to the M2 protein channel. Unexpectedly, no significant difference was found between the two enantiomers. Our experimental data based on the full M2 protein function were further supported by alchemical free energy calculations and isothermal titration calorimetry (ITC) allowing an evaluation of the binding affinity of rimantadine enantiomers to the M2TM pore...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28217227/cardiac-conduction-defects-and-brugada-syndrome-a-family-with-overlap-syndrome-carrying-a-nonsense-scn5a-mutation
#19
Hisaaki Aoki, Yoshihide Nakamura, Seiko Ohno, Takeru Makiyama, Minoru Horie
BACKGROUND: Phenotypes often differ even within family members carrying the same SCN5A mutation. We aimed to evaluate the genetic modifiers in a family with Brugada syndrome (BrS) and sick sinus syndrome (SSS) with an SCN5A mutation that causes the truncated alpha-subunit of cardiac Na channel protein. METHODS: To detect the genetic modifiers, we performed targeted panel sequencing of the coding region of 46 genes that are related to primary arrhythmia syndrome, by using a bench-top, next generation sequencer...
February 2017: Journal of Arrhythmia
https://www.readbyqxmd.com/read/28216314/visual-working-memory-requires-permissive-and-instructive-no-cgmp-signaling-at-presynapses-in-the-drosophila-central-brain
#20
Sara Kuntz, Burkhard Poeck, Roland Strauss
The gaseous second messenger nitric oxide (NO) has been shown to regulate memory formation by activating retrograde signaling cascades from post- to presynapse that involve cyclic guanosine monophosphate (cGMP) production to induce synaptic plasticity and transcriptional changes. In this study, we analyzed the role of NO in the formation of a visual working memory that lasts only a few seconds. This memory is encoded in a subset of ring neurons that form the ellipsoid body in the Drosophila brain. Using genetic and pharmacological manipulations, we show that NO signaling is required for cGMP-mediated CREB activation, leading to the expression of competence factors like the synaptic homer protein...
February 8, 2017: Current Biology: CB
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