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Diego M Presman, Gordon L Hager
It is widely accepted that the glucocorticoid receptor (GR), a ligand-regulated transcription factor that triggers anti-inflammatory responses, binds specific response elements as a homodimer. Here, we will discuss the original primary data that established this model and contrast it with a recent report characterizing the GR-DNA complex as a tetramer.
October 20, 2016: Transcription
Jie Guang, Qiyong Peter Liu, Russell Hopson, Gerald Kagan, Weibin Li, Thomas B Monroe, Paul G Williard
A metastable, polymorphic hexameric crystal structure of lithium pinacolone enolate (LiOPin) is reported along with three preparation methods. NMR-based structural characterization implies that the lithium pinacolate hexamer deaggregates to a tetramer in toluene but retains mainly the hexameric structure in non-aromatic hydrocarbon solvents such as cyclohexane. Moreover, the presence of a small amount of lithium aldolate (LiOA) dramatically influences the aggregation state of LiOPin by forming a mixed aggregate with a 3:1 ratio (LiOPin3•LiOA)...
October 20, 2016: Journal of the American Chemical Society
Xin Tian, Zaixing Yang, Guangxin Duan, Anqing Wu, Zonglin Gu, Leili Zhang, Chunying Chen, Zhifang Chai, Cuicui Ge, Ruhong Zhou
Graphene and graphene-based nanomaterials are broadly used for various biomedical applications due to their unique physiochemical properties. However, how graphene-based nanomaterials interact with biological systems has not been thoroughly studied. This study shows that graphene oxide (GO) nanosheets retard A549 lung carcinoma cell migration through nanosheet-mediated disruption of intracellular actin filaments. After GO nanosheets treatment, A549 cells display slower migration and the structure of the intracellular actin filaments is dramatically changed...
October 20, 2016: Small
J M Greene, P Dash, S Roy, C McMurtrey, W Awad, J S Reed, K B Hammond, S Abdulhaqq, H L Wu, B J Burwitz, B F Roth, D W Morrow, J C Ford, G Xu, J Y Bae, H Crank, A W Legasse, T H Dang, H Y Greenaway, M Kurniawan, M C Gold, M J Harriff, D A Lewinsohn, B S Park, M K Axthelm, J J Stanton, S G Hansen, L J Picker, V Venturi, W Hildebrand, P G Thomas, D M Lewinsohn, E J Adams, J B Sacha
Studies on mucosal-associated invariant T cells (MAITs) in nonhuman primates (NHP), a physiologically relevant model of human immunity, are handicapped due to a lack of macaque MAIT-specific reagents. Here we show that while MR1 ligand-contact residues are conserved between human and multiple NHP species, three T-cell receptor contact-residue mutations in NHP MR1 diminish binding of human MR1 tetramers to macaque MAITs. Construction of naturally loaded macaque MR1 tetramers facilitated identification and characterization of macaque MR1-binding ligands and MAITs, both of which mirrored their human counterparts...
October 19, 2016: Mucosal Immunology
Yoshiaki Suzuki, Susumu Ohya, Hisao Yamamura, Wayne R Giles, Yuji Imaizumi
Large-conductance Ca(2+)-activated K(+) (BK) channels play essential roles in both excitable and non-excitable cells. For example, in chondrocytes, agonist-induced Ca(2+) release from intracellular store activates BK channels, and this hyperpolarizes these cells, augments Ca(2+) entry, and forms a positive feed-back mechanism for Ca(2+) signaling and stimulation-secretion coupling. In the present study, functional roles of a newly identified splice variant in the BK channel α subunit (BKαΔe2) were examined in a human chondrocyte cell line, OUMS-27, and in a HEK293 expression system...
October 7, 2016: Journal of Biological Chemistry
Atul Kumar, Petra Sýkorová, Gabriel Demo, Pavel Dobeš, Pavel Hyršl, Michaela Wimmerová
Photorhabdus luminescens is known for its symbiosis with the entomopathogenic nematode Heterorhabditis bacteriophora and its pathogenicity towards insect larvae. A hypothetical protein from P. luminescens was identified, purified from the native source and characterized as an L-fucose-binding lectin, named PLL. Glycan array and biochemical characterization data revealed PLL to be specific towards L-fucose and the disaccharide glycan 3,6-O-Me2-Glcβ1-4(2,3-O-Me2)Rhaα-O-(p-C6H4)-OCH2CH2NH2. PLL was discovered to be a homo-tetramer with an inter-subunit disulphide bridge...
October 7, 2016: Journal of Biological Chemistry
Hirotsugu Nagase, Tomohira Takeoka, Shinya Urakawa, Akiko Morimoto-Okazawa, Atsunari Kawashima, Kota Iwahori, Shuji Takiguchi, Hiroyoshi Nishikawa, Eiichi Sato, Shimon Sakaguchi, Masaki Mori, Yuichiro Doki, Hisashi Wada
Regulatory T cells (Tregs) have an immunosuppressive role in the tumor microenvironment. Since effector Tregs (eTregs), which have highly suppressive functions, are located in a subpopulation of Foxp3(+) CD4(+) Tregs, the TCR-inducible costimulatory receptor (ICOS) was applied as a marker of eTregs that infiltrated gastric cancer tissue and the induction pathway of ICOS(+) Foxp3(+) cells was analyzed by flow cytometry and immunohistochemistry. In tumor-infiltrating lymphocytes (TILs), ICOS(+) Foxp3(+) CD4(+) T cells were abundantly observed in the late stages of gastric cancer...
October 18, 2016: International Journal of Cancer. Journal International du Cancer
Nicholas W Fischer, Aaron Prodeus, David Malkin, Jean Gariépy
Mutations in the oligomerization domain of p53 are genetically linked to cancer susceptibility in Li-Fraumeni Syndrome. These mutations typically alter the oligomeric state of p53 and impair its transcriptional activity. Activation of p53 through tetramerization is required for its tumor suppressive function by inducing transcriptional programs that lead to cell fate decisions such as cell cycle arrest or apoptosis. How p53 chooses between these cell fate outcomes remains unclear. Here, we use five oligomeric variants of p53, including two novel p53 constructs, that yield either monomeric, dimeric or tetrameric forms of p53 and demonstrate that they induce distinct cellular activities and gene expression profiles that lead to different cell fate outcomes...
October 18, 2016: Cell Cycle
Michael J Houghton, David B Collum
Enolization of O-methyl hydroxamic acids (Weinreb amides) in tetrahydrofuran solution with lithium diisopropylamide affords predominantly tetrameric enolates. Aryl substituents on the enolates promote deaggregation. The aggregation states are assigned by using the method of continuous variation in conjunction with (6)Li NMR spectroscopy. Decoalescence of the tetramer resonance below -100 °C shows considerable spectral complexity attributed to isomerism of the methoxy-based chelates. Density functional theory calculations were used to examine the consequences of the bite angle of five-membered chelates in cubic tetramers and resulting solvation numbers that were higher than anticipated...
October 17, 2016: Journal of Organic Chemistry
Michael Groszmann, Hannah L Osborn, John R Evans
Aquaporins are channel proteins that function to increase the permeability of biological membranes. In plants, aquaporins are encoded by multigene families that have undergone substantial diversification in land plants. The Plasma membrane Intrinsic Proteins (PIPs) subfamily of aquaporins are of particular interest given their potential to improve plant water relations and photosynthesis. Flowering plants have between 7 and 28 PIP genes. Their expression varies with tissue and cell type, through development and in response to a variety of factors, contributing to the dynamic and tissue specific control of permeability...
October 14, 2016: Plant, Cell & Environment
Emre Brookes, Patrice Vachette, Mattia Rocco, Javier Pérez
Size-exclusion chromatography coupled with SAXS (small-angle X-ray scattering), often performed using a flow-through capillary, should allow direct collection of monodisperse sample data. However, capillary fouling issues and non-baseline-resolved peaks can hamper its efficacy. The UltraScan solution modeler (US-SOMO) HPLC-SAXS (high-performance liquid chromatography coupled with SAXS) module provides a comprehensive framework to analyze such data, starting with a simple linear baseline correction and symmetrical Gaussian decomposition tools [Brookes, Pérez, Cardinali, Profumo, Vachette & Rocco (2013 ▸)...
October 1, 2016: Journal of Applied Crystallography
Theyencheri Narayanan, Dhammika Weerakkody, Alexander G Karabadzhak, Michael Anderson, Oleg A Andreev, Yana K Reshetnyak
The pH (Low) Insertion Peptides (pHLIP® peptides) find application in studies of membrane-associated folding, since spontaneous insertion of these peptides is conveniently triggered by varying pH. Also, pHLIP® peptides have medical utility, since they can target acidic diseased tissues, such as tumors, and deliver therapeutic cargo molecules across membrane or target nanoparticles to cancer cells. Here we employed small angle X-ray scattering (SAXS) to investigate WT pHLIP® peptide oligomeric state in solution at high concentrations and monitor changes in liposome structure upon peptide insertion into bilayer...
October 11, 2016: Journal of Physical Chemistry. B
Katrina Brendle, Ulrike Schwarz, Patrick Jäger, Patrick Weis, Manfred M Kappes
We have combined ion mobility mass spectrometry with quantum chemical calculations to investigate the gas phase structures of multiply negatively charged oligomers of meso-tetra(4-sulfonatophenyl)metalloporphyrins comprising the divalent metal centers Zn(II), Cu(II) and Pd(II). Sets of candidate structures were obtained by geometry optimizations based on calculations at both the semiempirical PM7and DFT levels. The corresponding theoretical cross sections were calculated with the projection approximation and also with the trajectory method...
October 11, 2016: Journal of Physical Chemistry. A
Vinayak Singh, Stefano Donini, Angela Pacitto, Claudia Sala, Ruben C Hartkoorn, Neeraj Dhar, Gyorgy Keri, David B Ascher, Guillaume Mondésert, Anthony Vocat, Andréanne Lupien, Raphael Sommer, Hélène Vermet, Sophie Lagrange, Joe Buechler, Digby F Warner, John D McKinney, Janos Pato, Stewart T Cole, Tom L Blundell, Menico Rizzi, Valerie Mizrahi
VCC234718, a molecule with growth inhibitory activity against Mycobacterium tuberculosis (Mtb), was identified by phenotypic screening of a 15344-compound library. Sequencing of a VCC234718-resistant mutant identified a Y487C substitution in the inosine monophosphate dehydrogenase, GuaB2, which was subsequently validated to be the primary molecular target of VCC234718 in Mtb. VCC234718 inhibits Mtb GuaB2 with a Ki of 100 nM and is uncompetitive with respect to IMP and NAD(+). This compound binds at the NAD(+) site, after IMP has bound, and makes direct interactions with IMP; therefore, the inhibitor is by definition uncompetitive...
September 8, 2016: ACS Infectious Diseases
Michiel C van Aalderen, Ester B M Remmerswaal, Kirstin M Heutinck, Anja Ten Brinke, Mariet C W Feltkamp, Neelke C van der Weerd, Karlijn A M I van der Pant, Frederike J Bemelman, René A W van Lier, Ineke J M Ten Berge
Polyomavirus BK (BKPyV) frequently reactivates in immunosuppressed renal transplant recipients (RTRs) and may lead to graft loss due to BKPyV-induced interstitial nephritis (BKVN). Little is known on the differentiation of CD8+ T cells targeting BKPyV in RTRs. Here we investigated whether BKPyV-specific CD8+ T cell differentiation differs in RTRs with varying degrees of BKPyV reactivation and/or BKVN. Using combinatorial encoding with tetramers carrying BKPyV major capsid protein (VP1) and large T antigen protein (LTAG) epitopes, we investigated CD8+ T cell responses to BKPyV in longitudinally obtained PBMC samples from 46 HLA-A02-positive RTRs and 20 healthy adults...
October 2016: PLoS Pathogens
Kristen Zuraski, Daniel Thomas Kwasniewski, Amit Kumar Samanta, Hanna Reisler
The vibrational predissociation of the HCl-(H2O)3 tetramer, the largest HCl-(H2O)n cluster for which HCl is not predicted to be ionized, is reported. This work focuses on the predissociation pathway giving rise to H2O + HCl-(H2O)2 following IR laser excitation of the H-bonded OH stretch fundamental. H2O fragments are monitored state-selectively by 2+1 resonance enhanced multiphoton ionization (REMPI) combined with time-of-flight mass spectrometry (TOF-MS). Velocity map images of H2O in selected rotational levels are used to determine translational energy distributions from which the internal energy distributions in the pair-correlated cofragments are derived...
October 10, 2016: Journal of Physical Chemistry Letters
Anirban Pradhan, Pierre Dechambenoit, Harald Bock, Fabien Durola
Taking advantage of an unexpected regioselectivity of intramolecular Scholl reactions on penta-phenylene compounds that favors distorted [5]helicenes over their flat couterparts, a new synthetic approach to twisted graphene nanoribbons has been designed, based on side-fused di-tert-butyl-[5]helicene fragments. Both syntheses of small monomers and dimers have been achieved and their structures have been studied. An iterative synthetic strategy has been developed for the formation of longer flexible precursors, relying on the step-by-step elongation of mono-functionalized oligomeric chains...
October 10, 2016: Chemistry: a European Journal
Sourav Roy, Anik Bhattacharyya, Sourav Purkait, Antonio Bauzá, Antonio Frontera, Shouvik Chattopadhyay
Two new hetero-tetranuclear nickel(ii)/cadmium(ii) complexes, a cubane [(CH3CO2)2Ni2(L(1))2Cd2(NCS)2] (1) and a linear tetramer [(DMSO)2NiL(2)Cd(NCS)(μ1,3-SCN)Ni(DMSO)L(2)Cd(NCS)2] (2) {where H2L(1) = N,N'-bis(3-methoxysalicylidene)propane-1,3-diamine and H2L(2) = N,N'-bis(3-ethoxysalicylidene)propane-1,3-diamine are potential octadentate compartmental Schiff bases}, were synthesized and characterized. The structures of both complexes were confirmed by single crystal X-ray diffraction studies. Complex 1 contained a Ni2Cd2O4 cubane core, whereas complex 2 featured an end-to-end thiocyanate-bridged tetranuclear moiety...
September 27, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Masashi Satoh, Ken-Ichi Namba, Nobuyoshi Kitaichi, Noriko Endo, Hirokuni Kitamei, Daiju Iwata, Shigeaki Ohno, Susumu Ishida, Kazunori Onoé, Hiroshi Watarai, Masaru Taniguchi, Tatsuro Ishibashi, Joan Stein-Streilein, Koh-Hei Sonoda, Luc Van Kaer, Kazuya Iwabuchi
Experimental autoimmune uveoretinitis (EAU) represents an experimental model for human endogenous uveitis, which is caused by Th1/Th17 cell-mediated inflammation. Natural killer T (NKT) cells recognize lipid antigens and produce large amounts of cytokines upon activation. To examine the role of NKT cells in the development of uveitis, EAU was elicited by immunization with a peptide from the human interphotoreceptor retinoid-binding protein (hIRBP1-20) in complete Freund's adjuvant and histopathology scores were evaluated in C57BL/6 (WT) and NKT cell-deficient mice...
October 5, 2016: Experimental Eye Research
John J Chen, Joseph C Genereux, Eul Hyun Suh, Vincent F Vartabedian, Bibiana Rius, Song Qu, Maria T A Dendle, Jeffery W Kelly, R Luke Wiseman
Transthyretin (TTR) is a tetrameric serum protein associated with multiple systemic amyloid diseases. In these disorders, TTR aggregates in extracellular environments through a mechanism involving rate-limiting dissociation of the tetramer to monomers, which then misfold and aggregate into soluble oligomers and amyloid fibrils that induce toxicity in distal tissues. Using an assay established herein, we show that highly destabilized, aggregation-prone TTR variants are secreted as both native tetramers and non-native conformations that accumulate as high-molecular-weight oligomers...
October 20, 2016: Cell Chemical Biology
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