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https://www.readbyqxmd.com/read/27926996/small-molecule-modulator-of-sigma-2-receptor-is-neuroprotective-and-reduces-cognitive-deficits-and-neuro-inflammation-in-experimental-models-of-alzheimer-s-disease
#1
Bitna Yi, James J Sahn, Pooneh Memar Ardestani, Andrew K Evans, Luisa Scott, Jessica Z Chan, Sangeetha Iyer, Ashley Crisp, Gabriella Zuniga, Jonathan Pierce-Shimomura, Stephen F Martin, Mehrdad Shamloo
Accumulating evidence suggests that modulating the sigma 2 receptor (Sig2R) can provide beneficial effects for neurodegenerative diseases. Herein, we report the identification of a novel class of Sig2R binding ligands and their cellular and in vivo activity in experimental models of Alzheimer's disease (AD). We report that SAS-0132 and DKR-1051, selective ligands of Sig2R, modulate intracellular Ca(2+) levels in human SK-N-SH neuroblastoma cells. The Sig2R antagonists SAS-0132 and JVW-1009 are neuroprotective in a C...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926995/frozen-but-no-accident-why-the-20-standard-amino-acids-were-selected
#2
REVIEW
Andrew J Doig
The 20 standard amino acids encoded by the Genetic Code were adopted during the RNA World, around 4 billion years ago. This amino acid set could be regarded as a frozen accident, implying that other possible structures could equally well have been chosen to use in proteins. Amino acids were not primarily selected for their ability to support catalysis, since the RNA World already had highly effective cofactors to perform reactions, such as oxidation, reduction and transfer of small molecules. Rather, they were selected to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets...
December 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27926943/the-mouse-cytomegalovirus-gene-m42-targets-surface-expression-of-the-protein-tyrosine-phosphatase-cd45-in-infected-macrophages
#3
Nadine Thiel, Kirsten A Keyser, Niels A W Lemmermann, Jennifer D Oduro, Karen Wagner, Carina Elsner, Anne Halenius, Tihana Lenac Roviš, Melanie M Brinkmann, Stipan Jonjić, Luka Cicin-Sain, Martin Messerle
The receptor-like protein tyrosine phosphatase CD45 is expressed on the surface of cells of hematopoietic origin and has a pivotal role for the function of these cells in the immune response. Here we report that following infection of macrophages with mouse cytomegalovirus (MCMV) the cell surface expression of CD45 is drastically diminished. Screening of a set of MCMV deletion mutants allowed us to identify the viral gene m42 of being responsible for CD45 down-modulation. Moreover, expression of m42 independent of viral infection upon retroviral transduction of the RAW264...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926882/effect-of-reduced-humic-acid-on-the-transport-of-ferrihydrite-nanoparticles-under-anoxic-conditions
#4
Peng Liao, Wenlu Li, Dengjun Wang, Yi Jiang, Chao Pan, John D Fortner, Songhu Yuan
Humic acid (HA) occurs ubiquitously in the subsurface environments and is well-known to play a critical role in the fate and transport of ferrihydrite nanoparticles (NPs) and NPs-associated contaminants. Under anoxic conditions, HA can readily be reduced by microorganisms or geochemical reducing species, and the mechanisms and kinetics of ferrihydrite reduction by reduced HA (HAred) are well-documented; however, the role of these redox reactions on the transport of ferrihydrite NPs is largely underestimated...
December 1, 2016: Water Research
https://www.readbyqxmd.com/read/27926847/probing-lipid-bilayers-under-ionic-imbalance
#5
Jiaqi Lin, Alfredo Alexander-Katz
Biological membranes are normally under a resting transmembrane potential (TMP), which originates from the ionic imbalance between extracellular fluids and cytosols, and serves as electric power storage for cells. In cell electroporation, the ionic imbalance builds up a high TMP, resulting in the poration of cell membranes. However, the relationship between ionic imbalance and TMP is not clearly understood, and little is known about the effect of ionic imbalance on the structure and dynamics of biological membranes...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926836/probing-small-molecule-binding-to-unfolded-polyprotein-based-on-its-elasticity-and-refolding
#6
Ricksen S Winardhi, Qingnan Tang, Jin Chen, Mingxi Yao, Jie Yan
Unfolded protein, a disordered structure found before folding of newly synthesized protein or after protein denaturation, is a substrate for binding by many cellular factors such as heat-stable proteins, chaperones, and many small molecules. However, it is challenging to directly probe such interactions in physiological solution conditions because proteins are largely in their folded state. In this work we probed small molecule binding to mechanically unfolded polyprotein using sodium dodecyl sulfate (SDS) as an example...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926736/structure-of-cc-chemokine-receptor-2-with-orthosteric-and-allosteric-antagonists
#7
Yi Zheng, Ling Qin, Natalia V Ortiz Zacarías, Henk de Vries, Gye Won Han, Martin Gustavsson, Marta Dabros, Chunxia Zhao, Robert J Cherney, Percy Carter, Dean Stamos, Ruben Abagyan, Vadim Cherezov, Raymond C Stevens, Adriaan P IJzerman, Laura H Heitman, Andrew Tebben, Irina Kufareva, Tracy M Handel
CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27926729/intracellular-allosteric-antagonism-of-the-ccr9-receptor
#8
Christine Oswald, Mathieu Rappas, James Kean, Andrew S Doré, James C Errey, Kirstie Bennett, Francesca Deflorian, John A Christopher, Ali Jazayeri, Jonathan S Mason, Miles Congreve, Robert M Cooke, Fiona H Marshall
Chemokines and their G-protein-coupled receptors play a diverse role in immune defence by controlling the migration, activation and survival of immune cells. They are also involved in viral entry, tumour growth and metastasis and hence are important drug targets in a wide range of diseases. Despite very significant efforts by the pharmaceutical industry to develop drugs, with over 50 small-molecule drugs directed at the family entering clinical development, only two compounds have reached the market: maraviroc (CCR5) for HIV infection and plerixafor (CXCR4) for stem-cell mobilization...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27926530/the-association-between-serum-uric-acid-and-glaucoma-severity-in-primary-angle-closure-glaucoma-a-retrospective-case-control-study
#9
Shengjie Li, Mingxi Shao, Binghua Tang, Aiping Zhang, Wenjun Cao, Xinghuai Sun
Uric acid (UA) is a major antioxidant molecule and has been hypothesized to have a protective effect on the central nervous system against oxidative damage. We prospectively investigated the serum concentration of UA in primary angle closure glaucoma (PACG), and explored the association between serum concentration of UA and the severity of PACG. Using a retrospective case-control study design, 886 PACG subjects and 994 control subjects who attended the Eye & ENT Hospital of Fudan University, were eligible for this study...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926522/il-10-expression-defines-an-immunosuppressive-dendritic-cell-population-induced-by-antitumor-therapeutic-vaccination
#10
Diana Llopiz, Marta Ruiz, Stefany Infante, Lorea Villanueva, Leyre Silva, Sandra Hervas-Stubbs, Diego Alignani, Elizabeth Guruceaga, Juan J Lasarte, Pablo Sarobe
Vaccination induces immunostimulatory signals that are often accompanied by regulatory mechanisms such as IL-10, which control T-cell activation and inhibit vaccine-dependent antitumor therapeutic effect. Here we characterized IL-10-producing cells in different tumor models treated with therapeutic vaccines. Although several cell subsets produced IL-10 irrespective of treatment, an early vaccine-dependent induction of IL-10 was detected in dendritic cells (DC). IL-10 production defined a DC population characterized by a poorly mature phenotype, lower expression of T-cell stimulating molecules and upregulation of PD-L1...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925755/collective-molecular-superrotation-a-model-for-extremely-flexible-molecules-applied-to-protonated-methane
#11
Hanno Schmiedt, Per Jensen, Stephan Schlemmer
The concept of molecular structure is traditionally considered to be virtually fundamental. However, it breaks down in extremely flexible molecules, whose dynamics are governed by large-amplitude motions. For the dynamics of molecules with free internal rotations, we therefore propose a five-dimensional rigid rotor model, with states characterized by two generalized angular momentum quantum numbers and a rotational constant B. The quantum numbers characterize a 5D angular-momentum vector, super-j, which describes collective rotations that involve both the internal and the overall rotation...
November 25, 2016: Physical Review Letters
https://www.readbyqxmd.com/read/27925690/purification-and-characterization-of-a-platelet-aggregation-inhibitor-and-anticoagulant-cc-5_ntase-cd-73-like-from-cerastes-cerastes-venom
#12
Samah Saoud, Fatah Chérifi, Traki Benhassine, Fatima Laraba-Djebari
The present study is the first attempt to report the characterization of a nucleotidase from Cerastes cerastes venom. A 70 kDa 5'-nucleotidase (Cc-5'NTase) was purified to homogeneity. The amino acid sequence of Cc-5'NTase displayed high homology with many nucleotidases. Its activity was optimal at pH 7 with a specific hydrolytic activity toward mono-, di-, and triphosphate adenylated nucleotides. Cc-5'NTase preferentially hydrolyzed ADP and obeyed Michaelis-Menten kinetics. Among the metals and inhibitors tested, Ni(2+) and Mg(2+) completely potentiated enzyme activity, whereas EGTA, PMSF, iodoacetamide, vanillic acid, vanillyl mandelic acid, and 1,10-phenanthroline partially abolished its activity...
December 7, 2016: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/27925683/inorganic-polyphosphate-a-key-modulator-of-inflammation
#13
REVIEW
Seyed Mahdi Hassanian, Amir Avan, Abdolreza Ardeshirylajimi
Inorganic polyphosphate (PolyP) is a molecule with prothrombotic and proinflammatory properties in blood. PolyP activates the NF-κB signaling pathway, increases the expression of cell surface adhesion molecules and disrupts the vascular barrier integrity of endothelial cells. PolyP-induced NF-κB activation and vascular hyperpermeability are regulated by the mTORC1 and mTORC2 pathways, respectively. Through interaction with RAGE and P2Y1 receptors, PolyP dramatically amplifies the proinflammatory responses of nuclear proteins...
December 7, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27925618/the-comparative-landscape-of-duplications-in-heliconius-melpomene-and-heliconius-cydno
#14
A Pinharanda, S H Martin, S L Barker, J W Davey, C D Jiggins
Gene duplications can facilitate adaptation and may lead to interpopulation divergence, causing reproductive isolation. We used whole-genome resequencing data from 34 butterflies to detect duplications in two Heliconius species, Heliconius cydno and Heliconius melpomene. Taking advantage of three distinctive signals of duplication in short-read sequencing data, we identified 744 duplicated loci in H. cydno and H. melpomene and evaluated the accuracy of our approach using single-molecule sequencing. We have found that duplications overlap genes significantly less than expected at random in H...
December 7, 2016: Heredity
https://www.readbyqxmd.com/read/27925611/differential-expression-of-bcl-2-in-the-cochlea-and-auditory-cortex-of-a-mouse-model-of-age-related-hearing-loss
#15
Qiuhong Huang, Hao Xiong, Haidi Yang, Yongkang Ou, Zhigang Zhang, Suijun Chen, Yongyi Ye, Yiqing Zheng
Bcl-2, the first gene shown to be involved in apoptosis, is a potent regulator of cell survival and known to have protective effects against a variety of age-related diseases. However, the possible relationship between hearing and Bcl-2 expression in the cochlea or auditory cortex of C57BL/6 mice, a mouse model of age-related hearing loss, is still unknown. Using RT-PCR, immunohistochemistry, and Western blot analysis, our results show that Bcl-2 is strongly expressed in the inner hair cells and spiral ganglion neurons of young mice...
December 8, 2016: Audiology & Neuro-otology
https://www.readbyqxmd.com/read/27925481/mitochondrial-ros-uncoupled-from-atp-synthesis-determine-endothelial-activation-for-both-physiological-recruitment-of-patrolling-cells-and-pathological-recruitment-of-inflammatory-cells
#16
Xinyuan Li, Pu Fang, William Y Yang, Kylie Chan, Muriel Lavallee, Keman Xu, Tracy Gao, Hong Wang, Xiaofeng Yang
Mitochondrial reactive oxygen species (mtROS) are signaling molecules, which drive inflammatory cytokine production and T cell activation. In addition, cardiovascular diseases, cancers, and autoimmune diseases all share a common feature of increased mtROS level. Both mtROS and ATP are produced as a result of electron transport chain activity, but it remains enigmatic whether mtROS could be generated independently from ATP synthesis. A recent study shed light on this important question and found that, during endothelial cell (EC) activation, mtROS could be upregulated in a proton leak-coupled, but ATP synthesis-uncoupled manner...
November 5, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27925477/relevance-of-meniscal-cell-regional-phenotype-to-tissue-engineering
#17
Shawn P Grogan, Chantal Pauli, Martin K Lotz, Darryl D D'Lima
PURPOSE: Meniscus contains heterogeneous populations of cells that have not been fully characterized. Cell phenotype is often lost during culture; however, culture expansion is typically required for tissue engineering. We examined and compared cell surface molecule expression levels on human meniscus cells from the vascular and avascular regions and articular chondrocytes while documenting changes during culture-induced dedifferentiation. MATERIALS AND METHODS: Expression of 16 different surface molecules were examined by flow cytometry after monolayer culture for 24 h, 1 week, and 2 weeks...
December 7, 2016: Connective Tissue Research
https://www.readbyqxmd.com/read/27925474/fiber-development-and-matrix-production-in-tissue-engineered-menisci-using-bovine-mesenchymal-stem-cells-and-fibrochondrocytes
#18
Mary Clare McCorry, Lawrence J Bonassar
Mesenchymal stem cells (MSCs) have been investigated with promising results for meniscus healing and tissue engineering. While MSCs are known to contribute to ECM production, less is known about how MSCs produce and align large organized fibers for application to tissue engineering the meniscus. The goal of this study was to investigate the capability of MSCs to produce and organize extracellular matrix molecules compared to meniscal fibrochondrocytes (FCCs). Bovine FCCs and MSCs were encapsulated in an anatomically accurate collagen meniscus using mono-culture and co-culture of each cell type...
December 7, 2016: Connective Tissue Research
https://www.readbyqxmd.com/read/27925454/rap1a-promotes-ovarian-cancer-metastasis-via-activation-of-erk-p38-and-notch-signaling
#19
Lili Lu, Jingshu Wang, Yougen Wu, Ping Wan, Gong Yang
As one of the Ras-associated proteins, Rap1A has been linked to cancer initiation and development. However, the precise function of Rap1A in ovarian cancer is still not understood. Here, we show that Rap1A promotes ovarian cancer tumorigenesis and metastasis via stimulating cell proliferation, migration and invasion both in vivo and in vitro. Mechanistic study showed that Rap1A activates extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and Notch pathways, leading to the enhanced expression of several epithelial-mesenchymal transition (EMT) markers such as slug, zeb1, vimentin, fibronectin, and MMP9...
December 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27925439/surface-faceting-and-reconstruction-of-ceria-nanoparticles
#20
Chengwu Yang, Xiaojuan Yu, Stefan Heißler, Alexei Nefedov, Sara Colussi, Jordi Llorca, Alessandro Trovarelli, Yuemin Wang, Christof Wöll
The surface atomic arrangement of metal oxides determines their physical and chemical properties, and the ability to control and optimize structural parameters is of crucial importance for many applications, in particular in heterogeneous catalysis and photocatalysis. Whereas the structures of macroscopic single crystals can be determined with established methods, for nanoparticles (NPs), this is a challenging task. Herein, we describe the use of CO as a probe molecule to determine the structure of the surfaces exposed by rod-shaped ceria NPs...
December 7, 2016: Angewandte Chemie
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