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https://www.readbyqxmd.com/read/28453292/discovery-of-mixed-pharmacology-melanocortin-3-agonists-and-melanocortin-4-receptor-tetrapeptide-antagonist-compounds-tacos-based-on-the-sequence-ac-xaa-1-arg-pi-dphe-xaa-4-nh2
#1
Skye R Doering, Katie T Freeman, Sathya M Schnell, Erica M Haslach, Marvin Louie Servanez Dirain, Ginamari Ginamarie Debevec, Phaedra Geer, Radleigh G Santos, Marc A Giulianotti, Clemencia Pinilla, Jon R Appel, Robert C Speth, Richard A Houghten, Carrie Haskell-Luevano
The centrally expressed melanocortin-3 and -4 receptors (MC3R/MC4R) have been studied as possible targets for weight management therapies, with a preponderance of studies focusing on the MC4R. Herein, a novel tetrapeptide scaffold [Ac-Xaa1-Arg-(pI)DPhe-Xaa4-NH2] is reported. The scaffold was derived from results obtained from a MC3R mixture-based positional scanning campaign. From these results, a set of 48 tetrapeptides were designed and pharmacologically characterized at the mouse melanocortin-1, -3, -4, and -5 receptors...
April 28, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28449103/novel-degenerative-and-developmental-defects-in-a-zebrafish-model-of-mucolipidosis-type-iv
#2
Huiqing Li, Wuhong Pei, Sivia Vergarajauregui, Patricia M Zerfas, Nina Raben, Shawn M Burgess, Rosa Puertollano
Mucolipidosis type IV (MLIV) is a lysosomal storage disease characterized by neurologic and ophthalmologic abnormalities. There is currently no effective treatment. MLIV is caused by mutations in MCOLN1, a lysosomal cation channel from the transient receptor potential (TRP) family. In this study we used genome editing to knockout the two mcoln1 genes present in Dario rerio (zebrafish). Our model successfully reproduced the retinal and neuromuscular defects observed in MLIV patients, indicating that this model is suitable for studying the disease pathogenesis...
April 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28448473/transcriptomic-analysis-of-calcium-remodeling-in-colorectal-cancer
#3
Enrique Pérez-Riesgo, Lucía G Gutiérrez, Daniel Ubierna, Alberto Acedo, Mary P Moyer, Lucía Núñez, Carlos Villalobos
Colorectal cancer (CRC) cells undergo the remodeling of intracellular Ca(2+) homeostasis, which contributes to cancer hallmarks such as enhanced proliferation, invasion and survival. Ca(2+) remodeling includes critical changes in store-operated Ca(2+) entry (SOCE) and Ca(2+) store content. Some changes have been investigated at the molecular level. However, since nearly 100 genes are involved in intracellular Ca(2+) transport, a comprehensive view of Ca(2+) remodeling in CRC is lacking. We have used Next Generation Sequencing (NGS) to investigate differences in expression of 77 selected gene transcripts involved in intracellular Ca(2+) transport in CRC...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28445957/peripheral-kynurenine-tryptophan-ratio-is-not-a-reliable-marker-of-systemic-indoleamine-2-3-dioxygenase-a-lesson-drawn-from-patients-on-hemodialysis
#4
Yuanhan Chen, Zhen Xie, Chenggen Xiao, Min Zhang, Zhilian Li, Jianteng Xie, Yusheng Zhang, Xingchen Zhao, Pengfei Zeng, Liyi Mo, Xinling Liang, Wei Shi
Indoleamine 2,3-dioxygenase (IDO) has emerged as a pivotal enzyme for mediating immune tolerance. Because IDO metabolizes tryptophan into kynurenine, the plasma kynurenine/tryptophan (Kyn/Trp) ratio has been widely used as a marker of systemic IDO. Here, we evaluated the clinical value of using the plasma Kyn/Trp ratio to estimate cell-mediated immune responses to tuberculin skin testing and risk of new bacterial infection. We also compared the Kyn/Trp ratio to a novel IDO marker, the IDO median fluorescence index (MFI) of peripheral blood mononuclear cells, which was determined by flow cytometry...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445290/efficacy-of-quadriceps-vastus-medialis-dry-needling-in-a-rehabilitation-protocol-after-surgical-reconstruction-of-complete-anterior-cruciate-ligament-rupture
#5
Jorge Velázquez-Saornil, Beatriz Ruíz-Ruíz, David Rodríguez-Sanz, Carlos Romero-Morales, Daniel López-López, Cesar Calvo-Lobo
BACKGROUND: Several new rehabilitation modalities have been proposed after anterior cruciate ligament (ACL) reconstruction. Among these, trigger point dry needling (TrP-DN) might be useful in the treatment of myofascial pain syndrome associated with ACL reconstruction to reduce pain intensity, increase knee flexion range and modify the mechanical properties of the quadriceps muscle during late-stage rehabilitation. To date, this is the first randomized clinical trial to support the use of TrP-DN in the early rehabilitation process after ACL reconstruction...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28442765/the-gpr139-reference-agonists-1a-and-7c-and-tryptophan-and-phenylalanine-share-a-common-binding-site
#6
Anne Cathrine Nøhr, Willem Jespers, Mohamed A Shehata, Leonard Floryan, Vignir Isberg, Kirsten Bayer Andersen, Johan Åqvist, Hugo Gutiérrez-de-Terán, Hans Bräuner-Osborne, David E Gloriam
GPR139 is an orphan G protein-coupled receptor expressed in the brain, in particular in the habenula, hypothalamus and striatum. It has therefore been suggested that GPR139 is a possible target for metabolic disorders and Parkinson's disease. Several surrogate agonist series have been published for GPR139. Two series published by Shi et al. and Dvorak et al. included agonists 1a and 7c respectively, with potencies in the ten-nanomolar range. Furthermore, Isberg et al. and Liu et al. have previously shown that tryptophan (Trp) and phenylalanine (Phe) can activate GPR139 in the hundred-micromolar range...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28440188/trp-channels-as-novel-targets-for-endogenous-ligands-focus-on-endocannabinoids-and-nociceptive-signalling
#7
Maksim V Storozhuk, Alexander V Zholos
The endocannabinoid system is gaining steadily increasing research interest as its important role in the regulation of many fundamental physiological processes becomes more and more evident. One area which received particularly significant attention concerns targeting the endocannabinoid system as a useful strategy in pain control, especially in refractory, difficult to treat cases of chronic pain. Apart from the classical targets of cannabinoids, the CB1 and CB2 receptors, several members of the large TRP family of Ca2+-permeable cation channels have been designated as "ionotropic cannabinoid receptors" to highlight their role in cannabinoid signalling...
April 24, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28437833/transient-receptor-potential-trp-channels-and-exercise-associated-muscle-cramping-eamc-a-tale-of-multiple-complexities
#8
EDITORIAL
M P Schwellnus, M D Hoffman
No abstract text is available yet for this article.
April 24, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28435101/interaction-of-glucocorticoids-and-progesterone-derivatives-with-human-serum-albumin
#9
Rola Abboud, Mohammad Akil, Catherine Charcosset, Hélène Greige-Gerges
Glucocorticoids (GCs) and progesterone derivatives (PGDs) are steroid hormones with well-known biological activities. Their interaction with human serum albumin (HSA) may control their distribution. Their binding to albumin is poorly studied in literature. This paper deals with the interaction of a series of GCs (cortisol, cortisone, prednisolone, prednisone, 6-methylprednisolone and 9-fluorocortisol acetate) and PGDs (progesterone, hydroxylated PGDs, methylated PGDs and dydrogesterone) with HSA solution (pH 7...
April 20, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28432632/tryptophan-fluorescence-yields-and-lifetimes-as-a-probe-of-conformational-changes-in-human-glucokinase
#10
Bogumil Zelent, Chris Bialas, Ignacy Gryczynski, Pan Chen, Rahul Chib, Karina Lewerissa, Maria G Corradini, Richard D Ludescher, Jane M Vanderkooi, Franz M Matschinsky
Five variants of glucokinase (ATP-D-hexose-6-phosphotransferase, EC 2.7.1.1) including wild type and single Trp mutants with the Trp residue at positions 65, 99, 167 and 257 were prepared. The fluorescence of Trp in all locations studied showed intensity changes when glucose bound, indicating that conformational change occurs globally over the entire protein. While the fluorescence quantum yield changes upon glucose binding, the enzyme's absorption spectra, emission spectra and fluorescence lifetimes change very little...
April 22, 2017: Journal of Fluorescence
https://www.readbyqxmd.com/read/28432033/lipids-as-central-modulators-of-sensory-trp-channels
#11
REVIEW
Maria Grazia Ciardo, Antonio Ferrer-Montiel
The transient receptor potential (TRP) ion channel family is involved in a diversity of physiological processes including sensory and homeostatic functions, as well as muscle contraction and vasomotor control. Their dysfunction contributes to the etiology of several diseases, being validated as therapeutic targets. These ion channels may be activated by physical or chemical stimuli and their function is highly influenced by signaling molecules activated by extracellular signals. Notably, as integral membrane proteins, lipid molecules also modulate their membrane location and function either by direct interaction with the channel structure or by modulating the physico-chemical properties of the cellular membrane...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28431284/mitovirus-uga-trp-codon-usage-parallels-that-of-host-mitochondria
#12
Max L Nibert
Mitoviruses replicate in mitochondria of their host fungi. They have small RNA genomes that encompass a single ORF encoding the viral RdRp. Since UGA codons encode Trp in fungal mitochondria, the RdRp ORF of a typical mitovirus includes multiple UGA codons. In some mitoviruses, however, the ORF has no such codons, suggesting that these particular viruses may be under selective pressure to exclude them. In this report, new evidence is presented that host fungi whose mitoviruses have no or few UGA codons are distinctive in also having no or few UGA codons in their core mitochondrial genes...
April 18, 2017: Virology
https://www.readbyqxmd.com/read/28430359/sulfur-containing-gaseous-signal-molecules-ion-channels-and-cardiovascular-diseases
#13
REVIEW
Wen Yu, Hongfang Jin, Chaoshu Tang, Junbao Du, Zhiren Zhang
Sulfur-containing gaseous signal molecules including hydrogen sulfide (H2 S) and sulfur dioxide (SO2 ) were previously recognized as toxic gases. However, extensive studies have revealed that they can be generated in the cardiovascular system via a sulfur-containing amino acid metabolic pathway, playing an important part in cardiovascular physiology and pathophysiology. Ion channels are pore-forming membrane proteins present in the membrane of all biological cells; functions include establishing a resting membrane potential and controlling action potentials and other electrical signals by conducting ions across the cell membrane...
April 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28429191/melanogenesis-inhibition-in-mice-using-a-low-fluence-1064-nm-q-switched-neodymium-doped-yttrium-aluminum-garnet-laser-a-pilot-study
#14
Jae-Hui Nam, Joon Hong Min, Wang-Kyun Kim, Sunmin Yim, Won-Serk Kim
A low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum garnet laser, or laser toning, has yielded favorable outcomes in various benign pigmented disorders. However, the exact mechanism of action of laser toning has not been fully elucidated. We sought to determine the inhibitory effect of laser toning on melanogenesis and to assess how laser passes influence the outcomes. To produce perceptible pigmentation, nine HRM-2 melanin-possessing hairless mice were treated with ultraviolet (UV) B radiation on the dorsal skin...
April 20, 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/28425165/melanogenesis-inhibitory-and-cytotoxic-activities-of-limonoids-alkaloids-and-phenolic-compounds-from-phellodendron-amurense-bark
#15
Toshihiro Akihisa, Satoru Yokokawa, Eri Ogihara, Masahiro Matsumoto, Jie Zhang, Takashi Kikuchi, Kazuo Koike, Masahiko Abe
Four limonoids, 1-4, five alkaloids, 5-9, and four phenolic compounds, 10-13, were isolated from a MeOH extract of the bark of Phellodendron amurense (Rutaceae). Among these, compound 13 was a new, and its structure was established as rel-(1R,2R,3R)-5-hydroxy-3-(4-hydroxy-3-methoxyphenyl)-6-methoxy-1-(methoxycarbonylmethyl)indane-2-carboxylic acid methyl ester (γ-di(methyl ferulate)) based on the spectrometric analysis. Upon evaluation of compounds 1-13 against the melanogenesis in the B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH), four compounds, limonin (1), noroxyhydrastinine (6), haplopine (7), and 4-methoxy-N-methyl-2-quiolone (8), exhibited potent melanogenesis-inhibitory activities with almost no toxicity to the cells...
April 20, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28424587/interactions-of-the-mechanosensitive-channels-with-extracellular-matrix-integrins-and-cytoskeletal-network-in-osmosensation
#16
REVIEW
Runsheng Jiao, Dan Cui, Stephani C Wang, Dongyang Li, Yu-Feng Wang
Life is maintained in a sea water-like internal environment. The homeostasis of this environment is dependent on osmosensory system translation of hydromineral information into osmotic regulatory machinery at system, tissue and cell levels. In the osmosensation, hydromineral information can be converted into cellular reactions through osmoreceptors, which changes thirst and drinking, secretion of antidiuretic vasopressin (VP), reabsorption of water and salt in the kidneys at systemic level as well as cellular metabolic activity and survival status at tissue level...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28423490/reappraisal-of-xrcc1-arg194trp-polymorphism-and-glioma-risk-a-cumulative-meta-analysis
#17
Jun-Ti Lu, Ai-Ping Deng, Juan Song, Li Zhang, Jie Luo
The association between XRCC1 Arg194Trp polymorphism and glioma risk were inconsistent from published meta-analyses and epidemiological studies. Hence, we performed this updated and cumulative meta-analysis to reappraisal this relationship. PubMed, Embase, CBM (Chinese Biomedical Database), and CNKI (China National Knowledge Internet) databases were comprehensively searched up to August 13, 2016 (updated on December 22, 2016). After study selection and data extraction from eligible studies, the association was evaluated by odds ratios (ORs) and its 95% confidence intervals (95%CIs) using Comprehensive Meta-Analysis software...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422479/on-demand-gas-to-liquid-process-to-fabricate-thermoresponsive-antimicrobial-nanocomposites-and-coatings
#18
Bijay Kumar Poudel, Jae Hong Park, Jeong Hoon Byeon
Antimicrobial material is emerging as a major component of the mitigation strategy against microbial growth on abiotic surfaces. In this work, a newly designed process is proposed to fabricate thermoresponsive antimicrobial nanocomposites (TANs) and coatings (TACs) as an on-demand system. Thermoresponsive polymer (TRP)-incorporated silver (Ag) nanocomposites with silica nanoparticles (SNPs) or carbon nanotubes (CNTs; Ag-SNP@TRP or Ag-CNT@TRP) were produced by a single-pass gas-to-liquid process. The SNPs or CNTs were first produced by spark ablation and successively injected for dispersal in a liquid cell containing polydimethylsiloxane, poly(N-isopropylacrylamide), and silver nitrate under ultrasound irradiation...
April 26, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28422069/protein-stability-and-unfolding-following-glycine-radical-formation
#19
Michael C Owen, Imre G Csizmadia, Béla Viskolcz, Birgit Strodel
Glycine (Gly) residues are particularly susceptible to hydrogen abstraction; which results in the formation of the capto-dative stabilized Cα-centered Gly radical (GLR) on the protein backbone. We examined the effect of GLR formation on the structure of the Trp cage; tryptophan zipper; and the villin headpiece; three fast-folding and stable miniproteins; using all-atom (OPLS-AA) molecular dynamics simulations. Radicalization changes the conformation of the GLR residue and affects both neighboring residues but did not affect the stability of the Trp zipper...
April 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28421413/substrate-induced-conformational-changes-of-the-tyrocidine-synthetase-1-adenylation-domain-probed-by-intrinsic-trp-fluorescence
#20
Matilda Šprung, Barbara Soldo, Stjepan Orhanović, Viljemka Bučević-Popović
Nonribosomal peptide synthetases (NRPS) are multifunctional proteins that catalyze the synthesis of the peptide products with enormous biological potential. The process of biosynthesis starts with the adenylation (A) domain, which during the catalytic cycle undergoes extensive structural rearrangements. In this paper, we present the first study of the tyrocidine synthetase 1 A-domain (TycA-A) fluorescence properties. The TycA-A protein contains five potentially fluorescent Trp residues at positions 227, 301, 323, 376 and 406...
April 18, 2017: Protein Journal
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