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https://www.readbyqxmd.com/read/28822288/two-sides-of-the-coin-part-2-colloid-and-surface-science-meets-real-biointerfaces
#1
Barry W Ninham, Kåre Larsson, Pierandrea Lo Nostro
Part 1 revisited developments in lipid and surfactant self assembly over the past 40 years [1]. New concepts emerged. Here we explore how these developments can be used to make sense of and bring order to a range of complex biological phenomena. Together with Part 1, this contribution is a fundamental revision of intuition at the boundaries of Colloid Science and Biological interfaces from a perspective of nearly 50 years. We offer new insights on a unified treatment of self assembly of lipids, surfactants and proteins in the light of developments presented in Part 1...
August 5, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28822281/an-integrative-study-to-identify-novel-scaffolds-for-sphingosine-kinase-1-inhibitors
#2
Marcela Vettorazzi, Emilio Angelina, Santiago Lima, Tomas Gonec, Jan Otevrel, Pavlina Marvanova, Tereza Padrtova, Petr Mokry, Pavel Bobal, Lina M Acosta, Alirio Palma, Justo Cobo, Janette Bobalova, Jozef Csollei, Ivan Malik, Sergio Alvarez, Sarah Spiegel, Josef Jampilek, Ricardo D Enriz
Sphingosine kinase 1 (SphK1), the enzyme that produces the bioactive sphingolipid metabolite, sphingosine-1-phosphate, is a promising new molecular target for therapeutic intervention in cancer and inflammatory diseases. In view of its importance, the main objective of this work was to find new and more potent inhibitors for this enzyme possessing different structural scaffolds than those of the known inhibitors. Our theoretical and experimental study has allowed us to identify two new structural scaffolds (three new compounds), which could be used as starting structures for the design and then the development of new inhibitors of SphK1...
August 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28822236/synthesis-structural-studies-and-biological-activity-of-novel-cu-ii-complexes-with-thiourea-derivatives-of-4-azatricyclo-5-2-1-0-2-6-dec-8-ene-3-5-dione
#3
Aleksandra Drzewiecka-Antonik, Paweł Rejmak, Marcin T Klepka, Anna Wolska, Piotr Pietrzyk, Karolina Stępień, Giuseppina Sanna, Marta Struga
The new Cu(II) complexes of 1/2/3-(bromophenyl)-3-(1,7,8,9-tetramethyl-3,5-dioxo-4-azatricyclo[5.2.1.0(2,6)]dec-8-en-4-yl)thiourea derivatives have been synthesized. The spectroscopic studies together with density functional theory calculations of Cu(II) complexes revealed that two parent ligands coordinate to the copper cation in bidentate fashion via thiocarbonyl S and deprotonated N atoms forming rarely observed four-membered chelate ring, with nearly planar [CuN2S2] moiety. In solid state, the mononuclear complex is formed for thiourea derivative with 3-bromophenyl, whereas for Cu(II) connection with 2- and 4-bromophenyl-thioureas the formation of dinuclear complexes is observed, the latter formed by the stacking of mononuclear complexes...
August 9, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28822229/vasculogenesis-and-angiogenesis-initiation-under-normoxic-conditions-through-wnt-%C3%AE-catenin-pathway-in-gliomas
#4
Alexandre Vallée, Rémy Guillevin, Jean-Noël Vallée
The canonical Wnt/β-catenin pathway is up-regulated in gliomas and involved in proliferation, invasion, apoptosis, vasculogenesis and angiogenesis. Nuclear β-catenin accumulation correlates with malignancy. Hypoxia activates hypoxia-inducible factor (HIF)-1α by inhibiting HIF-1α prolyl hydroxylation, which promotes glycolytic energy metabolism, vasculogenesis and angiogenesis, whereas HIF-1α is degraded by the HIF prolyl hydroxylase under normoxic conditions. We focus this review on the links between the activated Wnt/β-catenin pathway and the mechanisms underlying vasculogenesis and angiogenesis through HIF-1α under normoxic conditions in gliomas...
August 19, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28822125/in-vitro-alkylation-methods-for-assessing-the-protein-redox-state
#5
Flavien Zannini, Jérémy Couturier, Olivier Keech, Nicolas Rouhier
Cysteines are important residues for protein structure, function, and regulation. Owing to their modified reactivity, some cysteines can undergo very diverse redox posttranslational modifications, including the reversible formation of disulfide bonds, a widespread protein regulatory process as well exemplified in plant chloroplasts for Calvin-Benson cycle enzymes. Both core- and peripheral-photorespiratory enzymes possess conserved cysteines, some of which have been identified as being subject to oxidative modifications...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28822058/immune-dysfunction-in-non-hodgkin-lymphoma-avenues-for-new-immunotherapy-based-strategies
#6
REVIEW
Lorenzo Falchi
PURPOSE OF THIS REVIEW: The present review focuses on key aspects of non-Hodgkin lymphoma (NHL) evasion of immune surveillance and how these can be leveraged to devise effective immunotherapy strategies. RECENT FINDINGS: In recent years, significant progress has been made in the field of cancer immunotherapy. In particular, the remarkable clinical results of anti-programmed death (PD)-1/PD-ligand (L)1 antibodies are revolutionizing the treatment approach to multiple solid and hematologic tumors...
August 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28821867/identification-of-the-n-terminal-transmembrane-domain-of-stard7-and-its-importance-for-mitochondrial-outer-membrane-localization-and-phosphatidylcholine-transfer
#7
Yasuhiro Horibata, Hiromi Ando, Motoyasu Satou, Hiroaki Shimizu, Satomi Mitsuhashi, Yasuo Shimizu, Masahiko Itoh, Hiroyuki Sugimoto
StarD7 facilitates phosphatidylcholine (PC) transfer to mitochondria, and is essential for mitochondrial homeostasis. However, the molecular mechanism for PC transfer by protein remains poorly understood. Herein, we describe a putative novel transmembrane (TM) domain C-terminal to the mitochondria-targeting signal (MTS) sequence at the N-terminus of StarD7. The mature form of StarD7 is integrated and/or associated onto the outer leaflet of the outer mitochondrial membrane (OMM) in HEPA-1 and HepG2 cells. A truncated form of StarD7 lacking the TM domain is distributed in the inner space of the mitochondria, and cannot reverse mitochondrial abnormalities, such as complex formation and PC content, when re-expressed in StarD7-KO HEPA-1 cells...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821836/porv-is-an-outer-membrane-shuttle-protein-for-the-type-ix-secretion-system
#8
Michelle D Glew, Paul D Veith, Dina Chen, Dhana G Gorasia, Ben Peng, Eric C Reynolds
Porphyromonas gingivalis is a keystone pathogen associated with chronic periodontitis. Major virulence factors named gingipains (cysteine proteinases, RgpA, RgpB and Kgp) are secreted via the Type IX Secretion System (T9SS). These, together with approximately 30 other proteins, are secreted to the cell surface and anchored to the outer membrane by covalent modification to anionic lipopolysaccharide (A-LPS) via the novel Gram negative sortase, PorU. PorU is localised on the cell surface and cleaves the C-terminal domain signal (CTD) of T9SS substrates and conjugates their new C-termini to A-LPS...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821815/epac1-deficient-mice-have-bleeding-phenotype-and-thrombocytes-with-decreased-gpib%C3%AE-expression
#9
Gyrid Nygaard, Lars Herfindal, Kathrine S Asrud, Ronja Bjørnstad, Reidun K Kopperud, Eystein Oveland, Frode S Berven, Lene Myhren, Erling A Hoivik, Turid Helen Felli Lunde, Marit Bakke, Stein O Døskeland, Frode Selheim
Epac1 (Exchange protein directly activated by cAMP 1) limits fluid loss from the circulation by tightening the endothelial barrier. We show here that Epac1(-/-) mice, but not Epac2(-/-) mice, have prolonged bleeding time, suggesting that Epac1 may limit fluid loss also by restraining bleeding. The Epac1(-/-) mice had deficient in vitro secondary hemostasis. Quantitative comprehensive proteomics analysis revealed that Epac1(-/-) mouse platelets (thrombocytes) had unbalanced expression of key components of the glycoprotein Ib-IX-V (GPIb-IX-V) complex, with decrease of GP1bβ and no change of GP1bα...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821720/structural-basis-for-the-broad-substrate-specificity-of-the-human-tyrosylprotein-sulfotransferase-1
#10
Shinnosuke Tanaka, Toshiaki Nishiyori, Hidetaka Kojo, Reo Otsubo, Moe Tsuruta, Katsuhisa Kurogi, Ming-Cheh Liu, Masahito Suiko, Yoichi Sakakibara, Yoshimitsu Kakuta
Tyrosylprotein sulfotransferases (TPSTs) are enzymes that catalyze post-translational tyrosine sulfation of proteins. In humans, there are only two TPST isoforms, designated TPST1 and TPST2. In a previous study, we reported the crystal structure of TPST2, which revealed the catalytic mechanism of the tyrosine sulfation reaction. However, detailed molecular mechanisms underlying how TPSTs catalyse a variety of substrate proteins with different efficiencies and how TPSTs catalyze the sulfation of multiple tyrosine residues in a substrate protein remain unresolved...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821673/unc-18-and-tomosyn-antagonistically-control-synaptic-vesicle-priming-downstream-of-unc-13-in-c-elegans
#11
Seungmee Park, Na-Ryum Bin, Bin Yu, Raymond Wong, Ewa Sitarska, Kyoko Sugita, Ke Ma, Junjie Xu, Chi-Wei Tien, Arash Algouneh, Ekaterina Turlova, Siyan Wang, Pranay Siriya, Waleed Shahid, Lorraine Kalia, Zhong-Ping Feng, Philippe P Monnier, Hong-Shuo Sun, Mei Zhen, Shangbang Gao, Josep Rizo, Shuzo Sugita
Munc18-1/UNC-18 is believed to prime SNARE-mediated membrane fusion, yet the underlying mechanisms remain enigmatic. Here, we examined how potential gain-of-function mutations of Munc18-1/UNC-18 affect locomotory behavior and synaptic transmission, and how Munc18-1-mediated priming is related to Munc13-1/UNC-13 and Tomosyn/TOM-1, positive and negative SNARE regulators, respectively. We show that a Munc18-1(P335A)/UNC-18(P334A) mutation leads to significantly increased locomotory activity and acetylcholine release in C...
August 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821630/il-17a-deficiency-mitigates-bleomycin-induced-complement-activation-during-lung-fibrosis
#12
Ellyse Cipolla, Amanda J Fisher, Hongmei Gu, Elizabeth A Mickler, Manisha Agarwal, Carol A Wilke, Kevin K Kim, Bethany B Moore, Ragini Vittal
Interleukin 17A (IL-17A) and complement (C') activation have each been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We have reported that IL-17A induces epithelial injury via TGF-β in murine bronchiolitis obliterans; that TGF-β and the C' cascade present signaling interactions in mediating epithelial injury; and that the blockade of C' receptors mitigates lung fibrosis. In the present study, we investigated the role of IL-17A in regulating C' in lung fibrosis. Microarray analyses of mRNA isolated from primary normal human small airway epithelial cells indicated that IL-17A (100 ng/ml; 24 h; n = 5 donor lungs) induces C' components (C' factor B, C3, and GPCR kinase isoform 5), cytokines (IL8, -6, and -1B), and cytokine ligands (CXCL1, -2, -3, -5, -6, and -16)...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821623/proteolytic-cleavage-by-the-imp-complex-or-oct1-peptidase-controls-the-localization-of-the-yeast-peroxiredoxin-prx1-to-distinct-mitochondrial-compartments
#13
Fernando Gomes, Flavio Romero Palma, Mario H Barros, Eduardo T Tsuchida, Helena G Turano, Thiago G P Alegria, Marilene Demasi, Luis E S Netto
Yeast Prx1 is a mitochondrial 1-Cys peroxiredoxin that catalyzes the reduction of endogenously generated H2O2 Prx1 is synthesized on cytosolic ribosomes as a preprotein with a cleavable N-terminal presequence that is the mitochondrial targeting signal, but the mechanisms underlying Prx1 distribution to distinct mitochondrial subcompartments are unknown. Here, we provide direct evidence of the following dual mitochondrial localization of Prx1: a soluble form in the intermembrane space and a form in the matrix weakly associated with the inner mitochondrial membrane...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821601/high-sensitivity-quantitative-proteomics-using-automated-multidimensional-nano-flow-chromatography-and-accumulated-ion-monitoring-on-quadrupole-orbitrap-linear-ion-trap-mass-spectrometer
#14
Paolo Cifani, Alex Kentsis
Quantitative proteomics using high-resolution and accuracy mass spectrometry promises to transform our understanding of biological systems and disease. Recent development of parallel reaction monitoring (PRM) using hybrid instruments substantially improved the specificity of targeted mass spectrometry. Combined with high-efficiency ion trapping, this approach also provided significant improvements in sensitivity. Here, we investigated the effects of ion isolation and accumulation on the sensitivity and quantitative accuracy of targeted proteomics using the recently developed hybrid quadrupole-Orbitrap-linear ion trap mass spectrometer...
August 18, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28821575/ldl-switches-the-lrp6-internalization-route-from-flotillin-dependent-to-clathrin-dependent-in-hepatic-cells
#15
Hideki Yamamoto, Daisuke Umeda, Shinji Matsumoto, Akira Kikuchi
Low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) was originally identified as a coreceptor of the Wnt signaling pathway and has been shown to be involved in LDL transport. In polarized hepatocytes, many apical proteins are sorted to the basolateral membrane and then internalized and transported to the apical bile canalicular membrane-a process known as transcytosis. Herein, we show that LRP6 is transcytosed to the apical membrane of polarized hepatic HepG2 cells via a flotillin-dependent manner in the absence of LDL...
August 18, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28821568/lrrk2-promotes-the-activation-of-nlrc4-inflammasome-during-salmonella-typhimurium-infection
#16
Weiwei Liu, Xia'nan Liu, Yu Li, Junjie Zhao, Zhenshan Liu, Zhuqin Hu, Ying Wang, Yufeng Yao, Aaron W Miller, Bing Su, Mark R Cookson, Xiaoxia Li, Zizhen Kang
Although genetic polymorphisms in the LRRK2 gene are associated with a variety of diseases, the physiological function of LRRK2 remains poorly understood. In this study, we report a crucial role for LRRK2 in the activation of the NLRC4 inflammasome during host defense against Salmonella enteric serovar Typhimurium infection. LRRK2 deficiency reduced caspase-1 activation and IL-1β secretion in response to NLRC4 inflammasome activators in macrophages. Lrrk2(-/-) mice exhibited impaired clearance of pathogens after acute S...
August 18, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28821545/heterologous-production-of-thermophile-thermochromatium-tepidum-photosynthetic-reaction-centre-and-light-harvesting-1-complexes-in-the-mesophile-rhodobacter-sphaeroides-and-thermal-stabilities-of-a-hybrid-core-complex
#17
D Jun, V Huang, J T Beatty
The photosynthetic complexes of the thermophile Thermochromatium tepidum are of considerable interest in biohybrid solar cell applications because of the capability of thermophilic proteins to tolerate elevated temperatures. Synthetic operons encoding reaction centre (RC) and light harvesting 1 (LH1) pigment-protein complexes of T. tepidum were expressed in the mesophile Rhodobacter sphaeroides The T. tepidum RC (TRC) was assembled, and functional with the addition of menadione to populate the QA pocket. The production of the T...
August 18, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28821532/cross-phenotype-association-mapping-of-the-mhc-identifies-genetic-variants-that-differentiate-psoriatic-arthritis-from-psoriasis
#18
John Bowes, James Ashcroft, Nick Dand, Farideh Jalali-Najafabadi, Eftychia Bellou, Pauline Ho, Helena Marzo-Ortega, Philip S Helliwell, Marie Feletar, Anthony W Ryan, David J Kane, Eleanor Korendowych, Michael A Simpson, Jonathan Packham, Ross McManus, Matthew A Brown, Catherine H Smith, Jonathan N Barker, Neil McHugh, Oliver FitzGerald, Richard B Warren, Anne Barton
OBJECTIVES: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis, with a strong heritable component, affecting patients with psoriasis. Here we attempt to identify genetic variants within the major histocompatibility complex (MHC) that differentiate patients with PsA from patients with cutaneous psoriasis alone (PsC). METHODS: 2808 patients with PsC, 1945 patients with PsA and 8920 population controls were genotyped. We imputed SNPs, amino acids and classical HLA alleles across the MHC and tested for association with PsA compared to population controls and the PsC patient group...
August 18, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28821492/use-of-the-low-frequency-high-frequency-ratio-of-heart-rate-variability-to-predict-short-term-deterioration-in-emergency-department-patients-with-sepsis
#19
Douglas P Barnaby, Shannon M Fernando, Kevin J Ferrick, Christophe L Herry, Andrew J E Seely, Polly E Bijur, E John Gallagher
OBJECTIVE: To examine the ability of the low-frequency/high-frequency (LF/HF) ratio of heart rate variability (HRV) analysis to identify patients with sepsis at risk of early deterioration. METHODS: This is a prospective observational cohort study of patients with sepsis presenting to the Montefiore Medical Center ED from December 2014 through September 2015. On presentation, a single ECG Holter recording was obtained and analysed to obtain the LF/HF ratio of HRV...
August 18, 2017: Emergency Medicine Journal: EMJ
https://www.readbyqxmd.com/read/28821449/daphnauranins-a-and-b-two-new-antifeedants-isolated-from-daphne-aurantiaca-roots
#20
Sheng-Zhuo Huang, Qing-Yun Ma, Fan-Dong Kong, Zhi-Kai Guo, Qi Wang, Hao-Fu Dai, Yu-Qing Liu, Jun Zhou, You-Xing Zhao
Daphnauranins A (1) and B (2), two sesquiterpenoids were isolated from the roots of Daphne aurantiaca Diels. One is an unprecedented 5/7 oxacycloheptane ring system, the other is a sesquiterpene-lignan complex. Their structures were elucidated by comprehensive spectroscopic methods including MS and NMR. Their absolute configurations were further confirmed by the quantum ECD calculations. Daphnauranins A and B showed anti-insect activities against male fruit fly with anti-feeding rate up to 46.2±7.1 and 44...
August 15, 2017: Fitoterapia
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