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https://www.readbyqxmd.com/read/28422165/structural-basis-of-inhibition-of-lipid-linked-oligosaccharide-flippase-pglk-by-a-conformational-nanobody
#1
Camilo Perez, Martin Köhler, Daniel Janser, Els Pardon, Jan Steyaert, Renato Zenobi, Kaspar P Locher
PglK is an ABC transporter that flips a lipid-linked oligosaccharide (LLO) that serves as a donor in protein N-glycosylation. Previous structures revealed two inward-facing conformations, both with very large separations of the nucleotide binding domains (NBDs), and a closed, ADP-bound state that featured an occluded cavity. To investigate additional states, we developed conformation-sensitive, single-domain camelid nanobodies (Nb) and studied their effect on PglK activity. Biochemical, structural, and mass spectrometric analyses revealed that one inhibitory Nb binds as a single copy to homodimeric PglK...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28418896/nfkb-is-essential-for-activin-induced-colorectal-cancer-migration-via-upregulation-of-pi3k-mdm2-pathway
#2
Arundhati Jana, Nancy L Krett, Grace Guzman, Ahmer Khalid, Ozkan Ozden, Jonas J Staudacher, Jessica Bauer, Seung Hyun Baik, Timothy Carroll, Cemal Yazici, Barbara Jung
Colorectal cancer (CRC) remains a common and deadly cancer due to metastatic disease. Activin and TGFB (TGFβ) signaling are growth suppressive pathways that exert non-canonical pro-metastatic effects late in CRC carcinogenesis. We have recently shown that activin downregulates p21 via ubiquitination and degradation associated with enhanced cellular migration independent of SMADs. To investigate the mechanism of metastatic activin signaling, we examined activated NFkB signaling and activin ligand expression in CRC patient samples and found a strong correlation...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417533/split-tasks-of-asymmetric-nucleotide-binding-sites-in-the-heterodimeric-abc-exporter-efrcd
#3
Lea M Hürlimann, Michael Hohl, Markus A Seeger
Many heterodimeric ATP-binding cassette (ABC) exporters evolved asymmetric ATP-binding sites containing a degenerate site incapable of ATP hydrolysis due to noncanonical substitutions in conserved sequence motifs. Recent studies revealed that nucleotide binding to the degenerate site stabilizes contacts between the nucleotide-binding domains (NBDs) of the inward-facing transporter and regulates ATP hydrolysis at the consensus site via allosteric coupling mediated by the D-loops. However, it is unclear whether nucleotide binding to the degenerate site is strictly required for substrate transport...
April 18, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28399365/tin-ii-hydrides-as-intermediates-in-rearrangements-of-tin-ii-alkyl-derivatives
#4
Shuai Wang, Madison L McCrea-Hendrick, Cory M Weinstein, Christine A Caputo, Elke Hoppe, James C Fettinger, Marilyn M Olmstead, Philip P Power
Reactions of the Sn(II) hydrides, [ArSn(µ-H)]2 (1) (Ar = AriPr4 (1a) or AriPr6 (1b), AriP4 = C6H3-2,6-(C6H3-2,6-iPr2)2, AriPr6 = C6H3-2,6- (C6H2-2,4,6-iPr3)2) with norbornene (NB) or norbornadiene (NBD) readily generate the bicyclic alkyl/alkenyl substituted stannylenes, ArSn(norbornyl) (2a or 2b) or ArSn(norbornenyl) (3a or 3b), respectively. Heating a toluene solution of 3a or 3b at reflux afforded the rearranged species, ArSn(3-tricyclo[2.2.1.02,6]heptane) (4a or 4b), in which the norbornenyl ligand is transformed into a nortricyclyl group...
April 11, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28383632/measuring-change-in-symptoms-of-neurobehavioural-disability-responsiveness-of-the-st-andrew-s-swansea-neurobehavioural-outcome-scale
#5
Nick Alderman, Claire Williams, Caroline Knight, Rodger Ll Wood
Objective: Neurobehavioural disability (NBD) after acquired brain injury (ABI) is often associated with poor outcome. The "St Andrew's-Swansea Neurobehavioural Outcome Scale" (SASNOS) was developed to measure NBD in a range of applications. Two of the "holy trinity" of psychometric properties, reliability and validity, have been comprehensively mapped, but the extent to which SASNOS meets the third, responsiveness, has not been investigated. Demonstrating responsiveness is essential in instruments employed in repeated measurement scenarios to confirm their ability to discriminate real change from error...
April 5, 2017: Archives of Clinical Neuropsychology: the Official Journal of the National Academy of Neuropsychologists
https://www.readbyqxmd.com/read/28358164/thiolysis-of-nbd-based-dyes-for-colorimetric-and-fluorescence-detection-of-h2s-and-biothiols-design-and-biological-applications
#6
REVIEW
Long Yi, Zhen Xi
Hydrogen sulfide (H2S) is an important endogenous signaling molecule with multiple biological functions. The development of colorimetric and fluorescent probes for the visualization of H2S is useful for studying H2S biology. This review details up-to-date research on H2S probes based on thiolysis reactions of NBD (7-nitro-1,2,3-benzoxadiazole) amines or ethers (thioethers). The reactivity and selectivity of NBD-based dyes are discussed. The design principles of NBD-based probes are highlighted. The advantages and disadvantages of NBD-based probes are compared, and their biological applications are discussed...
March 30, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28358005/structural-intermediates-and-directionality-of-the-swiveling-motion-of-pyruvate-phosphate-dikinase
#7
Alexander Minges, Daniel Ciupka, Christian Winkler, Astrid Höppner, Holger Gohlke, Georg Groth
Pyruvate phosphate dikinase (PPDK) is a vital enzyme in cellular energy metabolism catalyzing the ATP- and Pi-dependent formation of phosphoenolpyruvate from pyruvate in C4 -plants, but the reverse reaction forming ATP in bacteria and protozoa. The multi-domain enzyme is considered an efficient molecular machine that performs one of the largest single domain movements in proteins. However, a comprehensive understanding of the proposed swiveling domain motion has been limited by not knowing structural intermediates or molecular dynamics of the catalytic process...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28356133/abdominal-massage-for-neurogenic-bowel-dysfunction-in-people-with-multiple-sclerosis-amber-abdominal-massage-for-bowel-dysfunction-effectiveness-research-study-protocol-for-a-randomised-controlled-trial
#8
Doreen McClurg, Kirsteen Goodman, Suzanne Hagen, Fional Harris, Sean Treweek, Anton Emmanuel, Christine Norton, Maureen Coggrave, Selina Doran, John Norrie, Peter Donnan, Helen Mason, Sarkis Manoukian
BACKGROUND: Multiple sclerosis (MS) is a life-long condition primarily affecting younger adults. Neurogenic bowel dysfunction (NBD) occurs in 50-80% of these patients and is the term used to describe constipation and faecal incontinence, which often co-exist. Data from a pilot study suggested feasibility of using abdominal massage for the relief of constipation, but the effectiveness remains uncertain. METHODS/DESIGN: This is a multi-centred patient randomised superiority trial comparing an experimental strategy of once daily abdominal massage for 6 weeks against a control strategy of no massage in people with MS who have stated that their constipation is bothersome...
March 29, 2017: Trials
https://www.readbyqxmd.com/read/28315324/nucleolin-protects-macrophages-from-oxldl-induced-foam-cell-formation-through-up-regulating-abca1-expression
#9
Yuanbin Li, Bimei Jiang, Pengfei Liang, Zhongyi Tong, Meidong Liu, Qinglan Lv, Yanjuan Liu, Xuanyou Liu, Yuting Tang, Xianzhong Xiao
Our recent studies have indicated that nucleolin, as a multifunctional RNA-binding protein, exerts protective effects in the myocardial cells and endothelial cells under the condition of oxidative stress. However, the function of nucleolin and its potential mechanism in macrophage-derived foam cell formation remain largely unexplored. ApoE-/- mice were fed with a high-fat diet (HFD) for 10-24 weeks. Protein expression was measured by western blotting or immunofluorescence, and gene expression at the mRNA level was detected by qRT-PCR...
April 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28306394/measuring-discourse-coherence-in-anomic-aphasia-using-rhetorical-structure-theory
#10
Anthony Pak-Hin Kong, Anastasia Linnik, Sam-Po Law, Waisa Wai-Man Shum
PURPOSE: The existing body of work regarding discourse coherence in aphasia has provided mixed results, leaving the question of coherence being impaired or intact as a result of brain injury unanswered. In this study, discourse coherence in non-brain-damaged (NBD) speakers and speakers with anomic aphasia was investigated quantitatively and qualitatively. METHOD: Fifteen native speakers of Cantonese with anomic aphasia and 15 NBD participants produced 60 language samples...
March 17, 2017: International Journal of Speech-language Pathology
https://www.readbyqxmd.com/read/28293837/treatment-of-plants-with-gaseous-ethylene-and-gaseous-inhibitors-of-ethylene-action
#11
Mark L Tucker, Joonyup Kim, Chi-Kuang Wen
The gaseous nature of ethylene affects not only its role in plant biology but also how you treat plants with the hormone. In many ways, it simplifies the treatment problem. Other hormones have to be made up in solution and applied to some part of the plant hoping the hormone will be taken up into the plant and translocated throughout the plant at the desired concentration. Because all plant cells are connected by an intercellular gas space the ethylene concentration you treat with is relatively quickly reached throughout the plant...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28286085/hspa5-gene-encoding-hsp70-chaperone-bip-in-the-endoplasmic-reticulum
#12
REVIEW
Jie Wang, Jessica Lee, David Liem, Peipei Ping
The HSPA5 gene (Ensembl ID: ENSG00000044574 (WTSI/EMBL-EBI, 2015)) encodes the binding immunoglobulin protein (BiP), an Hsp70 family chaperone localized in the ER lumen. As a highly conserved molecular chaperone, BiP assists in a wide range of folding processes via its two structural domains, a nucleotide-binding domain (NBD) and substrate-binding domain (SBD). BiP is also an essential component of the translocation machinery for protein import into the ER, a regulator for Ca(2+) homeostasis in the ER, as well as a facilitator of ER-associated protein degradation (ERAD) via retrograde transportation of aberrant proteins across the ER membrane...
March 7, 2017: Gene
https://www.readbyqxmd.com/read/28267925/the-influence-of-metal-ions-on-the-dynamics-of-supported-phospholipid-langmuir-films
#13
Stephen M Baumler, Gary J Blanchard
The translational diffusion dynamics of the zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) at a planar phosphorylated support surface containing metal ions (Mg(2+), Ca(2+), Ba(2+), Ni(2+), Zn(2+), Cd(2+), Zr(4+)) was investigated using X-ray photoelectron spectroscopy (XPS) and fluorescence recovery after photobleaching (FRAP). Fluorescence recovery curves yielded diffusion constants on the order of 2-5 μm(2)/s for the chromophore-tagged 12:0 NBD-Lyso-PC. Ionic interactions between the zwitterionic headgroup and metal ions were found to play a secondary role in mediating lipid fluidity...
March 13, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28266845/synthesis-antiviral-potency-in-vitro-admet-and-x-ray-structure-of-potent-cd4-mimics-as-entry-inhibitors-that-target-the-phe43-cavity-of-hiv-1-gp120
#14
Francesca Curreli, Young Do Kwon, Dmitry S Belov, Ranjith R Ramesh, Alexander V Kurkin, Andrea Altieri, Peter D Kwong, Asim K Debnath
In our attempt to optimize the lead HIV-1 entry antagonist, NBD-11021, we present in this study the rational design and synthesis of 60 new analogues and determination of their antiviral activity in a single-cycle and a multicycle infection assay to derive a comprehensive structure-activity relationship (SAR). Two of these compounds, NBD-14088 and NBD-14107, showed significant improvement in antiviral activity compared to the lead entry antagonist in a single-cycle assay against a large panel of Env-pseudotyped viruses...
April 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28240893/how-intrinsic-dynamics-mediates-the-allosteric-mechanism-in-the-abc-transporter-nucleotide-binding-domain-dimer
#15
Peter M Jones, Anthony M George
A protein's architecture facilitates specific motions-intrinsic dynamic modes-that are employed to effect function. Here we used molecular dynamics (MD) simulations to investigate the dynamics of the MJ0796 ABC transporter nucleotide-binding domain (NBD). ABC transporter NBDs form a rotationally symmetric dimer whereby two equivalent active sites are formed at their interface; in complex with a dimer of transmembrane domains they hydrolyze ATP to energize translocation of substrates across cellular membranes...
March 29, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28237038/local-targeting-nf-%C3%AE%C2%BAb-in-the-lung-tissue-of-tb-infected-mice-diminishes-the-level-of-pathology
#16
Galena Shepelkova, Vladimir Evstifeev, Tatiana Kondratieva, Irina Bocharova, Mikhail Averbakh, Alexander Apt
Mice of the genetically TB-susceptible strain I/St were infected with ∼100 CFU of Mycobacterium tuberculosis strain H37Rv, and after week 3 post-infection treated by inhalations of the NBD peptide selectively blocking NF-κB activation pathway. This therapy resulted in a pronounced attenuation of lung pathology and down-regulation of the expression of several genes encoding major inflammatory molecules, but did not diminish the level of mycobacterial multiplication in the lungs.
March 2017: Tuberculosis
https://www.readbyqxmd.com/read/28224327/effects-of-in-vivo-and-in-vitro-administration-of-neuro-behcet-s-disease-igg
#17
Ece Erdağ, Ceren Şahin, Cem İsmail Küçükali, Sinem Bireller, Melike Küçükerden, Murat Kürtüncü, Recai Türkoğlu, Bedia Cakmakoglu, Erdem Tüzün, Feyza Arıcıoğlu
Antibodies directed against membrane antigens of neuronal axonal processes (neuropil) have been recently identified in neuro-Behcet's disease (NBD) patients. To delineate the potential pathogenic action of these antibodies, pooled sera from seven NBD patients with neuropil antibodies and seven healthy controls were divided into purified IgG and IgG-depleted serum (IgG-DS) fractions and each fraction was administered into lateral ventricles of rats. NBD IgG-injected rats showed reduced locomotor activity in the open field test as compared to NBD IgG-DS, healthy control IgG, healthy control IgG-DS and PBS injected rats (n = 10 for each group)...
February 21, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28213514/peripheral-membrane-interactions-boost-the-engagement-by-an-anti-hiv-1-broadly-neutralizing-antibody
#18
Edurne Rujas, José M M Caaveiro, Sara Insausti, Miguel García-Porras, Kouhei Tsumoto, José L Nieva
The 4E10 antibody displays an extreme breadth of HIV-1 neutralization and therefore constitutes a suitable model system for structure-guided vaccine design and immunotherapeutics against AIDS. In this regard, the relevance of autoreactivity with membrane lipids for the biological function of this antibody is still a subject of controversy. To address this dispute, herein we have compared the membrane partitioning ability of the 4E10 antibody and several of its variants, which were mutated at the region of the paratope surface in contact with the membrane interface...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28183182/a-redox-active-fluorescent-ph-indicator-for-detecting-plasmodium-falciparum-strains-with-reduced-responsiveness-to-quinoline-antimalarial-drugs
#19
Mouhamad Jida, Cecilia P Sanchez, Karène Urgin, Katharina Ehrhardt, Saravanan Mounien, Aurelia Geyer, Mourad Elhabiri, Michael Lanzer, Elisabeth Davioud-Charvet
Mutational changes in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) have been associated with differential responses to a wide spectrum of biologically active compounds including current and former quinoline and quinoline-like antimalarial drugs. PfCRT confers altered drug responsiveness by acting as a transport system, expelling drugs from the parasite's digestive vacuole where these drugs exert, at least part of, their antiplasmodial activity. To preserve the efficacy of these invaluable drugs, novel functional tools are required for epidemiological surveys of parasite strains carrying mutant PfCRT variants and for drug development programs aimed at inhibiting or circumventing the action of PfCRT...
February 10, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28115930/transanal-irrigation-for-refractory-chronic-idiopathic-constipation-patients-perceive-a-safe-and-effective-therapy
#20
Kevin J Etherson, Ian Minty, Iain M Bain, Jeremy Cundall, Yan Yiannakou
Background. Transanal irrigation (TAI) can successfully treat neurogenic bowel dysfunction (NBD), but patient perception of its use in chronic idiopathic constipation (CIC) is unknown. Objective. To evaluate patient perceptions of the efficacy and safety of TAI for CIC and whether there are predictive factors of perceived treatment response. Methods. Prospective data collection of baseline physiology and symptom severity; retrospective evaluation of efficacy and safety perceptions using a snapshot survey. All patients fulfilling the Rome III criteria for functional constipation with chronic idiopathic aetiology were included...
2017: Gastroenterology Research and Practice
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