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https://www.readbyqxmd.com/read/29232769/antiparkinsonian-and-antidyskinetic-profiles-of-two-novel-potent-and-selective-nociceptin-orphanin-fq-receptor-agonists
#1
Ludovico Arcuri, Salvatore Novello, Martina Frassineti, Daniela Mercatelli, Clarissa Anna Pisanò, Ilaria Morella, Stefania Fasano, Blair V Journigan, Michael E Meyer, Willma E Polgar, Riccardo Brambilla, Nurulain T Zaveri, Michele Morari
BACKGROUND AND PURPOSE: We previously showed that Nociceptin/orphanin FQ opioid peptide (NOP) receptor agonists attenuate the expression of levodopa-induced dyskinesia in animal models of Parkinson's disease. We now investigate the efficacy of two novel, potent and chemically distinct NOP receptor agonists, AT-390 and AT-403, to improve parkinsonian disabilities and attenuate dyskinesia development and expression. EXPERIMENTAL APPROACH: Binding affinity and functional efficacy of AT-390 and AT-403 at the opioid receptors were determined in radioligand displacement assays and in GTPγS binding assay respectively, conducted in Chinese hamster ovary cells...
December 12, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29232711/dependence-of-prevalence-of-contiguous-pathways-in-proteins-on-structural-complexity
#2
Kelly M Thayer, Jesse C Galganov, Avram J Stein
Allostery is a regulatory mechanism in proteins where an effector molecule binds distal from an active site to modulate its activity. Allosteric signaling may occur via a continuous path of residues linking the active and allosteric sites, which has been suggested by large conformational changes evident in crystal structures. An alternate possibility is that the signal occurs in the realm of ensemble dynamics via an energy landscape change. While the latter was first proposed on theoretical grounds, increasing evidence suggests that such a control mechanism is plausible...
2017: PloS One
https://www.readbyqxmd.com/read/29232705/etv2-mir-130a-jarid2-cascade-regulates-vascular-patterning-during-embryogenesis
#3
Bhairab N Singh, Naoyuki Tahara, Yasuhiko Kawakami, Satyabrata Das, Naoko Koyano-Nakagawa, Wuming Gong, Mary G Garry, Daniel J Garry
Remodeling of the primitive vasculature is necessary for the formation of a complex branched vascular architecture. However, the factors that modulate these processes are incompletely defined. Previously, we defined the role of microRNAs (miRNAs) in endothelial specification. In the present study, we further examined the Etv2-Cre mediated ablation of DicerL/L and characterized the perturbed vascular patterning in the embryo proper and yolk-sac. We mechanistically defined an important role for miR-130a, an Etv2 downstream target, in the mediation of vascular patterning and angiogenesis in vitro and in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/29232700/sygl-1-and-lst-1-link-niche-signaling-to-puf-rna-repression-for-stem-cell-maintenance-in-caenorhabditis-elegans
#4
Heaji Shin, Kimberly A Haupt, Aaron M Kershner, Peggy Kroll-Conner, Marvin Wickens, Judith Kimble
Central questions in regenerative biology include how stem cells are maintained and how they transition from self-renewal to differentiation. Germline stem cells (GSCs) in Caenorhabditis elegans provide a tractable in vivo model to address these questions. In this system, Notch signaling and PUF RNA binding proteins, FBF-1 and FBF-2 (collectively FBF), maintain a pool of GSCs in a naïve state. An open question has been how Notch signaling modulates FBF activity to promote stem cell self-renewal. Here we report that two Notch targets, SYGL-1 and LST-1, link niche signaling to FBF...
December 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29232670/some-galeomorph-sharks-express-a-mammalian-microglia-specific-protein-in-radial-ependymoglia-of-the-telencephalon
#5
Skirmantas Janušonis
Ionized calcium-binding adapter molecule 1 (Iba1), also known as allograft inflammatory factor 1 (AIF-1), is a highly conserved cytoplasmic scaffold protein. Studies strongly suggest that Iba1 is associated with immune-like reactions in all Metazoa. In the mammalian brain, it is abundantly expressed in microglial cells and is used as a reliable marker for this cell type. The present study used multiple-label microscopy and Western blotting to examine Iba1 expression in the telencephalon of 2 galeomorph shark species, the swellshark (Cephaloscyllium ventriosum) and the horn shark (Heterodontus francisci), a member of an ancient extant order...
December 13, 2017: Brain, Behavior and Evolution
https://www.readbyqxmd.com/read/29232612/aliphatic-hydrocarbons-recovered-in-vegetables-from-soils-based-on-their-in-situ-distribution-in-various-soil-humus-fractions-using-a-successive-extraction-method
#6
Juan Zhang, Shu-Kai Fan, Ming-Hua Zhang, Michael L Grieneisen, Jian-Feng Zhang
Aliphatic hydrocarbons (AHs) are major petroleum contaminants in the environment. In this study, the AHs bound to various soil endogenetic humus fractions were separated through successive extraction. Most of the AHs (46.1%) in soils were adsorbed onto/into humic acids (HA) and a small quantity of AHs (9.6%) were organic solvent extractable. AHs in B. chinensis were also analyzed since their potential risks to the residents through ingestion. AHs from C21 to C34, so called high molecular weight AHs (HMWAHs), were dominant AHs in B...
December 6, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29232602/cooperative-protein-unfolding-a-statistical-mechanical-model-for-the-action-of-denaturants
#7
J Seelig
Knowledge of protein stability is of utmost importance in various fields of biotechnology. Protein stability can be assessed in solution by increasing the concentration of denaturant and recording the structural changes with spectroscopic or thermodynamic methods. The standard interpretation of the experimental data is to assume a 2-state equilibrium between completely folded and completely unfolded protein molecules. Here we propose a cooperative model based on the statistical-mechanical Zimm-Bragg theory...
December 5, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/29232588/bioactive-products-from-singlet-oxygen-photooxygenation-of-cannabinoids
#8
Ahmed Galal Osman, Khaled M Elokely, Vivek K Yadav, Paulo Carvalho, Mohamed Radwan, Desmond Slade, Waseem Gul, Shabana Khan, Olivia R Dale, Afeef S Husni, Michael L Klein, Stephen J Cutler, Samir A Ross, Mahmoud A ElSohly
Photooxygenation of Δ8 tetrahydrocannabinol (Δ8-THC), Δ9 tetrahydrocannabinol (Δ9-THC), Δ9 tetrahydrocannabinolic acid (Δ9-THCA) and some derivatives (acetate, tosylate and methyl ether) yielded 24 oxygenated derivatives, 18 of which were new and 6 were previously reported, including allyl alcohols, ethers, quinones, hydroperoxides, and epoxides. Testing these compounds for their modulatory effect on cannabinoid receptors CB1 and CB2 led to the identification of 7 and 21 as CB1 partial agonists with Ki values of 0...
November 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232587/discovery-of-naphtho-1-2-d-oxazole-derivatives-as-potential-anti-hcv-agents-through-inducing-heme-oxygenase-1-expression
#9
Chih-Hua Tseng, Chun-Kuang Lin, Yeh-Long Chen, Chin-Kai Tseng, Jar-Yu Lee, Jin-Ching Lee
A number of naphtho[1,2-d]oxazole derivatives were synthesized and evaluated for their anti-HCV virus activity. Among them, compound 18 was the most active, exhibited approximately 21-folds more active anti-HCV activity (IC50 of 0.63 μM) than that of ribavirin (IC50 = 13.16 μM). Compound 18 was less cytotoxic than ribavirin, and the selective index (SI) of 18 is approximately 28-folds higher than that of ribavirin (229.10 v.s. 8.08). By using heme oxygenase-1 (HO-1) promoter-based assay and western blotting, compound 18 could induce HO-1 promoter activity, and protein expression...
December 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232585/synthesis-of-new-triterpenic-monomers-and-dimers-as-potential-antiproliferative-agents-and-their-molecular-docking-studies
#10
Aasim Saeed, Hidayat Hussain, Umair Shamraiz, Najeeb Ur Rehman, Husain Yar Khan, Amin Badshah, Lucie Heller, René Csuk, Majid Ali, Ajmal Khan, Ahmed Al-Harrasi
In the current investigation, new monomers of myrrhanone B and lupeolic acid were prepared via reaction of triterpenic acids with linkers in the presence of K2CO3. In addition, new bis-myrrhanone B homodimers, myrrhanone B-myrrhanol B heterodimers, and bis-myrrhanone β-boswellic acids heterodimer were prepared. Evaluation of these compounds on the proliferation of four different human cancer cell lines, viz., FaDu (pharynx carcinoma), A2780 (ovarian carcinoma), HT29 (colon adenocarcinoma) and A375 (malignant melanoma) has been performed...
December 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232581/homo-and-heteroleptic-pt-ii-complexes-of-onn-donor-hydrazone-and-4-picoline-a-synthetic-structural-and-detailed-mechanistic-anticancer-investigation
#11
Faiz-Ur Rahman, Muhammad Zeeshan Bhatti, Amjad Ali, Hong-Quan Duong, Yao Zhang, Bo Yang, Satish Koppireddi, Yuejian Lin, Hui Wang, Zhan-Ting Li, Dan-Wei Zhang
Two series of homoleptic Pt(II)(hydrazone)Cl (C1a-C5a) and heteroleptic Pt(II)(hydrazone)(4-picoline). BF4 (C1b-C5b) complexes were prepared and characterized by 1H, 13C, 19F NMR and HR ESI-MS. Structure of C2b was confirmed by single crystal X-ray analysis. These complexes were studied for their in vitro anticancer activities in human multiple cancer cells including breast (MCF-7), liver (HepG2), lung (H460), colon (HCT116) and cervical (Hela) cancers. C1a-C5a and C1b-C5b showed considerable anticancer effect...
November 26, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232521/an-immunoglobulin-fc-fused-peptide-without-c-terminal-arg-or-lys-residue-augments-neuropilin-1-dependent-tumor-vascular-permeability
#12
Du-San Baek, Jeong-Ho Kim, Ye-Jin Kim, Yong-Sung Kim
Neuropilin-1 (NRP1), which functions as a co-receptor for vascular endothelial growth factor (VEGF) and is implicated in vascular permeability and tumorigenesis, has been targeted by peptides that specifically bind to the VEGF-binding region on NRP1. Like natural VEGF ligands, all known peptides with NRP1-binding activity bind only through a carboxy (C)-terminal R/K-x-x-R/K sequence motif (x stands for any amino acids); this strict requirement is called the C-end rule (CendR). Here, we report immunoglobulin Fc-fused NRP1-specific peptides deviating from CendR...
December 12, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29232504/a-genetic-toolbox-for-modulating-the-expression-of-heterologous-genes-in-the-cyanobacterium-synechocystis-sp-pcc-6803
#13
Bo Wang, Carrie Eckert, Pin-Ching Maness, Jianping Yu
Cyanobacteria, genetic models for photosynthesis research for decades, have recently become attractive hosts for producing renewable fuels and chemicals, owing to their genetic tractability, relatively fast growth, and their ability to utilize sunlight, fix carbon dioxide and, in some cases, fix nitrogen. Despite significant advances, there is still an urgent demand for synthetic biology tools in order to effectively manipulate genetic circuits in cyanobacteria. In this study, we have compared a total of 17 natural and chimeric promoters, focusing on expression of the ethylene-forming enzyme (EFE) in the cyanobacterium Synechocystis sp...
December 12, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29232494/reconstructing-relational-information
#14
Kevin M Horecka, Michael Dulas, Hillary Schwarb, Heather Lucas, Melissa Duff, Neal J Cohen
Hippocampal involvement in learning and remembering relational information has an extensive history, often focusing specifically on spatial information. In humans, spatial reconstruction (SR) paradigms are a powerful tool for evaluating an individuals' spatial-relational memory. In SR tasks, participants study locations of items in space and subsequently reconstruct the studied display after a short delay. Previous work has revealed that patients with hippocampal damage are impaired both in overall placement accuracy as well as on a specific measure of relational memory efficacy, "swaps" (i...
December 12, 2017: Hippocampus
https://www.readbyqxmd.com/read/29232483/epitope-resolved-detection-of-peanut-specific-ige-antibodies-by-spr-imaging
#15
Min Shen, Amit Joshi, Raghu Vannam, Chandra Dixit, Robert Hamilton, Challa V Kumar, James F Rusling, Mark Wayne Peczuh
Peanut allergy can be life-threatening and is mediated by allergen-specific immunoglobulin E (IgE) antibodies. Investigation of IgE antibody binding to allergenic epitopes identifies specific interactions underlying the allergic response. Here we report a surface plasmon resonance imaging (SPRi) immunoassay for differentiating IgE antibodies by epitope resolved detection. IgE antibodies are first captured by magnetic beads bearing IgE ε-chain specific antibodies and then introduced to an SPRi array immobilized with epitopes from the major peanut allergen glycoprotein Arachis hypogaea h2 (Ara h2)...
December 12, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29232414/influence-of-trp-flipping-on-carbohydrate-binding-in-lectins-an-example-on-aleuria-aurantia-lectin-aal
#16
Josef Houser, Stanislav Kozmon, Deepti Mishra, Sushil K Mishra, Patrick R Romano, Michaela Wimmerová, Jaroslav Koča
Protein-carbohydrate interactions are very often mediated by the stacking CH-π interactions involving the side chains of aromatic amino acids such as tryptophan (Trp), tyrosine (Tyr) or phenylalanine (Phe). Especially suitable for stacking is the Trp residue. Analysis of the PDB database shows Trp stacking for 265 carbohydrate or carbohydrate like ligands in 5 208 Trp containing motives. An appropriate model system to study such an interaction is the AAL lectin family where the stacking interactions play a crucial role and are thought to be a driving force for carbohydrate binding...
2017: PloS One
https://www.readbyqxmd.com/read/29232376/che1-aatf-interacts-with-subunits-of-the-histone-acetyltransferase-core-module-of-saga-complexes
#17
Gizem Caliskan, Ikbal C Baris, Ferhan Ayaydin, Melanie J Dobson, Muge Senarisoy, Imre M Boros, Zeki Topcu, Sevil Zencir
General Control Non-derepressible 5 (GCN5) and Alteration/Deficiency in Activation 2 and 3 proteins (ADA2 and ADA3, respectively) are subunits of the Histone AcetylTransferase (HAT) module of SAGA- and ATAC-type co-activators. We previously reported four new interacting partners of human ADA3 identified by screening a human fetal brain cDNA library using yeast two hybrid technology. One of these partners was Apoptosis-Antagonizing Transcription Factor (AATF), also known as Che-1, an RNA polymerase II-binding protein with a number of roles in different cellular processes including regulation of transcription, cell proliferation, cell cycle control, DNA damage responses and apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/29232315/beneficial-effects-of-exercise-pretreatment-in-a-sporadic-alzheimer-s-rat-model
#18
Chongyun Wu, Luodan Yang, Donovan Tucker, Yan Dong, Ling Zhu, Rui Duan, Timon Cheng-Yi Liu, Quanguang Zhang
PURPOSE: This study aimed to examine the effects of swimming exercise pretreatment on a streptozotocin (STZ)-induced sporadic Alzheimer's disease rat model and provide an initial understanding of related molecular mechanisms. METHODS: Male 2.5-month-old Sprague-Dawley rats were divided into the following 4 groups: a) control, b) swim + vehicle, c) STZ without swim, and d) swim + STZ. The Barnes Maze task and Novel Object Recognition test were used to measure hippocampus-dependent spatial learning and working memory, respectively...
December 11, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/29232169/dietary-nonheme-iron-is-equally-bioavailable-from-ferritin-or-ferrous-sulfate-in-thalassemia-intermedia
#19
Monica Khurana, Ellen B Fung, Elliott P Vichinsky, Elizabeth C Theil
Transfusion-independent patients with thalassemia intermedia (TI) develop fatal iron overload from excessive iron absorption triggered by ineffective erythropoiesis. More information about iron pharmacokinetics and nonheme, dietary iron absorption in such patients is needed to optimize management. To obtain more information, different forms of supplemental nonheme iron sources (ferritin and ferrous sulfate) were compared in 4 TI (hemoglobin <9 g/dL) and 6 control (hemoglobin 12-16 g/dL) patients. Serial serum iron concentrations were measured during the 24 hours following consumption of 1 mg/kg of elemental iron as ferritin or ferrous sulfate...
December 12, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29232160/microrna-145-antagonism-reverses-tgf-%C3%AE-inhibition-of-f508del-cftr-correction-in-airway-epithelia
#20
Farruk Lutful Kabir, Namasivayam Ambalavanan, Gang Liu, Peng Li, George M Solomon, Charitharth V Lal, Marina Mazur, Brian Halloran, Tomasz Szul, William T Gerthoffer, Steven M Rowe, William T Harris
INTRODUCTION: microRNAs (miRNAs) destabilize mRNA transcripts and inhibit protein translation. miR-145 is of particular interest in cystic fibrosis (CF) as it has a direct binding site in the 3'-untranslated region of CFTR and is upregulated by the CF genetic modifier TGF-β. HYPOTHESIS: miR-145 mediates TGF-β inhibition of CFTR synthesis and function in airway epithelia. METHODS: Primary human CF (F508del homozygous) and non-CF airway epithelial cells (AECs) were grown to terminal differentiation at air-liquid interface on permeable supports...
December 12, 2017: American Journal of Respiratory and Critical Care Medicine
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