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https://www.readbyqxmd.com/read/29454056/biophysical-and-immunological-characterization-of-2-drib-modified-hsa-and-its-implications-in-diabetes-mellitus
#1
Ishrat Jahan Saifi, Km Neelofar, M R Ajmal, Sheelu Shafiq Siddiqi
Glycoxidation of protein may lead to develop diabetes. In the present study, different concentrations of 2-deoxy d-ribose (2-dRib) were used to modify human serum albumin (HSA). Nitro Blue Tetrazolium (NBT) assay results showed that yield of the fructosamine content was directly proportional to the concentration of 2-dRib. UV and fluorescence spectroscopy results showed an increment in hyperchromicity and decrease in fluorescence intensity of 2-dRib modified HSA as compared to native HSA. Further secondary structural changes were confirmed by UV-circular dichroism (UV-CD) and Fourier transform infrared spectroscopy (FT-IR)...
February 14, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29453948/noncritical-signaling-role-of-a-kinase-receptor-interaction-surface-in-the-escherichia-coli-chemosensory-core-complex
#2
Germán E Piñas, Michael D DeSantis, John S Parkinson
In E. coli chemosensory arrays, transmembrane receptors, a histidine autokinase CheA, and a scaffolding protein CheW interact to form an extended hexagonal lattice of signaling complexes. One interaction, previously assigned a crucial signaling role, occurs between chemoreceptors and the CheW-binding P5 domain of CheA. Structural studies showed a receptor helix fitting into a hydrophobic cleft at the boundary between P5 subdomains. Our work aimed to elucidate the in vivo roles of the receptor-P5 interface, employing as a model the interaction between E...
February 14, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29453713/-1-h-13-c-and-15-n-resonance-assignments-of-cw-domain-of-the-n-methyltransferase-ashh2-free-and-bound-to-the-mono-di-and-tri-methylated-histone-h3-tail-peptides
#3
Olena Dobrovolska, Maxim Bril'kov, Øyvind Ødegård-Fougner, Rein Aasland, Øyvind Halskau
The ASHH2 CW domain is responsible for recognizing the methylation state at lysine 4 of histone 3 N-terminal tails and implicated in the recruitment of the ASHH2 methyltransferase enzyme correctly to the histones. The ASHH2 CW domain binds H3 lysine motifs that can be either mono-, di-, or tri-methylated [ARTK(meX)QTAR, where X denotes the number of methylations], but binds strongest to monomethylated instances (K d values reported in the range of 1 µm to 500 nM). Hoppmann et al. published the uncomplexed NMR structure of an ASHH2 CW domain in 2011...
February 16, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29453509/critical-thresholds-for-eventual-extinction-in-randomly-disturbed-population-growth-models
#4
Scott D Peckham, Edward C Waymire, Patrick De Leenheer
This paper considers several single species growth models featuring a carrying capacity, which are subject to random disturbances that lead to instantaneous population reduction at the disturbance times. This is motivated in part by growing concerns about the impacts of climate change. Our main goal is to understand whether or not the species can persist in the long run. We consider the discrete-time stochastic process obtained by sampling the system immediately after the disturbances, and find various thresholds for several modes of convergence of this discrete process, including thresholds for the absence or existence of a positively supported invariant distribution...
February 16, 2018: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/29453386/anti-fibrotic-effects-of-cxcr4-targeting-i-body-ad-114-in-preclinical-models-of-pulmonary-fibrosis
#5
K Griffiths, D M Habiel, J Jaffar, U Binder, W G Darby, C G Hosking, A Skerra, G P Westall, C M Hogaboam, M Foley
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease that is prevalent in individuals >50 years of age, with a median survival of 3-5 years and limited therapeutic options. The disease is characterized by collagen deposition and remodeling of the lung parenchyma in a process that is thought to be driven by collagen-expressing immune and structural cells. The G-protein coupled C-X-C chemokine receptor 4, CXCR4, is a candidate therapeutic target for IPF owing to its role in the recruitment of CXCR4 + fibrocytes from the bone marrow to fibrotic lung tissue and its increased expression levels by structural cells in fibrotic lung tissue...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453292/clonal-selection-drives-protective-memory-b-cell-responses-in-controlled-human-malaria-infection
#6
Rajagopal Murugan, Lisa Buchauer, Gianna Triller, Cornelia Kreschel, Giulia Costa, Gemma Pidelaserra Martí, Katharina Imkeller, Christian E Busse, Sumana Chakravarty, B Kim Lee Sim, Stephen L Hoffman, Elena A Levashina, Peter G Kremsner, Benjamin Mordmüller, Thomas Höfer, Hedda Wardemann
Affinity maturation, the clonal selection and expansion of antigen-activated B cells expressing somatically mutated antibody variants that develop during T cell-dependent germinal center reactions, is considered pivotal for efficient development of protective B cell memory responses to infection and vaccination. Repeated antigen exposure promotes affinity maturation but each time also recruits antigen-reactive naïve B cells into the response. Here, we determined the relative impact of affinity maturation versus antigen-mediated clonal selection of naïve B cells to mount potent B cell memory responses in humans after repeated exposure to a complex pathogen, the malaria parasite Plasmodium falciparum (Pf)...
February 16, 2018: Science Immunology
https://www.readbyqxmd.com/read/29453264/bacterial-community-shift-and-coexisting-coexcluding-patterns-revealed-by-network-analysis-in-a-bioreduced-uranium-contaminated-site-after-reoxidation
#7
Bing Li, Wei-Min Wu, David B Watson, Erick Cardenas, Yuanqing Chao, D H Phillips, Tonia Mehlhorn, Kenneth Lowe, Shelly D Kelly, Pengsong Li, Huchun Tao, James M Tiedje, Craig S Criddle, Tong Zhang
A site in Oak Ridge, Tennessee, USA, has sediments that contain >3% iron oxides and is contaminated with uranium (U). The U(VI) was bioreduced to U(IV) and immobilized in situ through intermittent injections of ethanol. Then it was allowed to reoxidize via the invasion of low-pH (3.6-4.0), high-nitrate (up to 200 mM) groundwater back into the reduced zone for 1,383 days. To examine the biogeochemical response, high-throughput sequencing and network analysis were applied to characterize bacterial population shifts, as well as co-occurrence and co-exclusion patterns among microbial communities...
February 16, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29453052/ac-lvffark-nh-2-conjugation-to-%C3%AE-cyclodextrin-exhibits-significantly-enhanced-performance-on-inhibiting-amyloid-%C3%AE-protein-fibrillogenesis-and-cytotoxicity
#8
Huan Zhang, Xiaoyan Dong, Fufeng Liu, Jie Zheng, Yan Sun
Inhibition of amyloid β-protein (Aβ) aggregation is of significance for the potential treatment of Alzheimer's disease. We have herein conjugated heptapeptide Ac-LVFFARK-NH 2 (LK7) to β-cyclodextrin (βCyD) and studied the inhibitory effect of the LK7-βCyD conjugate on Aβ aggregation. The conjugation significantly improved the peptide solubility and suppressed the self-assembly propensity. This led to 30% increase of the binding affinity of LK7 for Aβ in the conjugate due to increased hydrophobic interactions...
February 11, 2018: Biophysical Chemistry
https://www.readbyqxmd.com/read/29452744/emerging-concepts-in-diagnosis-and-treatment-of-syncope-by-pacing
#9
REVIEW
Richard Sutton, Jean-Claude Deharo, Michele Brignole, Mohamed H Hamdan
Neuroendocrine syncope is a newly proposed term to embody both syncope of reflex and adenosine-related etiology. Recent publications on tilt testing have revealed the presence of a hypotensive tendency in some patients, even in the face of severe cardioinhibition. This new understanding may allow better selection of older reflex syncope patients, documented by ECG loop recorder, for successful pacing where tilt testing is ideally negative for a good result in terms of few syncope recurrences and prompts a less aggressive management policy when hypotensive medication is required...
February 13, 2018: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29452613/the-role-of-plasma-membrane-calcium-atpases-pmcas-in-neurodegenerative-disorders
#10
REVIEW
Parvana Hajieva, Marius W Baeken, Bernd Moosmann
Selective degeneration of differentiated neurons in the brain is the unifying feature of neurodegenerative disorders such as Parkinson's disease (PD) or Alzheimer's disease (AD). A broad spectrum of evidence indicates that initially subtle, but temporally early calcium dysregulation may be central to the selective neuronal vulnerability observed in these slowly progressing, chronic disorders. Moreover, it has long been evident that excitotoxicity and its major toxic effector mechanism, neuronal calcium overload, play a decisive role in the propagation of secondary neuronal death after acute brain injury from trauma or ischemia...
January 10, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29452367/variant-in-human-pofut1-reduces-enzymatic-activity-and-likely-causes-a-recessive-microcephaly-global-developmental-delay-with-cardiac-and-vascular-features
#11
Hideyuki Takeuchi, Derek Wong, Michael Schneider, Hudson H Freeze, Megumi Takeuchi, Steven J Berardinelli, Atsuko Ito, Hane Lee, Stanley F Nelson, Robert S Haltiwanger
Protein O-fucosyltransferase-1 (POFUT1) adds O-fucose monosaccharides to epidermal growth factor-like (EGF) repeats found on approximately 100 mammalian proteins, including Notch receptors. Haploinsufficiency of POFUT1 has been linked to adult-onset Dowling Degos Disease (DDD) with hyperpigmentation defects. Homozygous deletion of mouse Pofut1 results in embryonic lethality with severe Notch-like phenotypes including defects in somitogenesis, cardiogenesis, vasculogenesis, and neurogenesis, but the extent to which POFUT1 is required for normal human development is not yet understood...
February 14, 2018: Glycobiology
https://www.readbyqxmd.com/read/29452354/alpha-synuclein-inhibits-snx3-retromer-mediated-retrograde-recycling-of-iron-transporters-in-s-cerevisiae-and-c-elegans-models-of-parkinson-s-disease
#12
Dhaval Patel, Chuan Xu, Sureshbabu Nagarajan, Zhengchang Liu, Wayne O Hemphill, Runhua Shi, Vladimir N Uversky, Guy A Caldwell, Kim A Caldwell, Stephan N Witt
We probed the role of alpha-synuclein (α-syn) in modulating sorting nexin 3 (Snx3)-retromer-mediated recycling of iron transporters in Saccharomyces cerevisiae and Caenorhabditis elegans. In yeast, the membrane-bound heterodimer Fet3/Ftr1 is the high affinity iron importer. Fet3 is a membrane-bound multicopper ferroxidase, whose ferroxidase domain is orthologous to human ceruloplasmin (Cp), that oxidizes external Fe+2 to Fe+3; the Fe+3 ions then channel through the Ftr1 permease into the cell. When the concentration of external iron is low (< 1 µM), Fet3/Ftr1 is maintained on the plasma membrane by retrograde endocytic-recycling; whereas, when the concentration of external iron is high (> 10 µM), Fet3/Ftr1 is endocytosed and shunted to the vacuole for degradation...
February 14, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29452175/replacement-treatment-during-extinction-training-with-the-atypical-dopamine-uptake-inhibitor-jhw-007-reduces-relapse-to-methamphetamine-seeking
#13
Ashlea F Dassanayake, Juan J Canales
There are currently no approved medications to effectively counteract the effects of methamphetamine (METH), reduce its abuse and prolong abstinence from it. Data accumulated in recent years have shown that a range of N-substituted benztropine (BZT) analogues possesses psychopharmacological features consistent with those of a potential replacement or "substitute" treatment for stimulant addiction. On the other hand, the evidence that antidepressant therapy may effectively prevent relapse to stimulant seeking is controversial...
February 13, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29451701/phase-1b-study-of-pasireotide-everolimus-and-selective-internal-radioembolization-therapy-for-unresectable-neuroendocrine-tumors-with-hepatic-metastases
#14
Hyun S Kim, Walid L Shaib, Chao Zhang, Ganji Purnachandra Nagaraju, Christina Wu, Olatunji B Alese, Zhengjia Chen, Edith Brutcher, Meredith Renfroe, Bassel F El-Rayes
BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2...
February 16, 2018: Cancer
https://www.readbyqxmd.com/read/29451581/tautomerism-and-electronic-spectroscopy-of-protonated-1-and-2-aminonaphthalene
#15
Jennifer A Noble, Michel Broquier, Gilles Grégoire, Satchin Soorkia, Gustavo Pino, Ernesto Marceca, Claude Dedonder-Lardeux, Christophe Jouvet
Experimental and theoretical investigations of the excited states of protonated 1- and 2-aminonaphthalene are presented. The electronic spectra are obtained by laser induced photofragmentation of the ions captured in a cold ion trap. Using ab initio calculations, the electronic spectra can be assigned to different tautomers which have the proton on the amino group or on the naphthalene moiety. It is shown that the tautomer distribution can be varied by changing the electrospray source conditions, favoring either the most stable form in solution (amino protonation) or that in the gas phase (aromatic ring protonation)...
February 16, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29451567/stable-small-specific-low-valency-quantum-dots-for-single-molecule-imaging
#16
Jungmin Lee, Xinyi Feng, Ou Chen, Moungi G Bawendi, Jun Huang
We have developed a strategy for synthesizing immediately activable, water-soluble, compact (∼10-12 nm hydrodynamic diameter) quantum dots with a small number of stable and controllable conjugation handles for long distance delivery and subsequent biomolecule conjugation. Upon covalent conjugation with engineered monovalent streptavidin, the sample results in a population consisting of low-valency quantum dots. Alternatively, we have synthesized quantum dots with a small number of biotin molecules that can self-assemble with engineered divalent streptavidin via high-affinity biotin-streptavidin interactions...
February 16, 2018: Nanoscale
https://www.readbyqxmd.com/read/29451404/optimizing-nbe-pk-pd-assays-using-the-gyrolab-affinity-software-conveniently-within-the-bioanalyst-s-existing-workflow
#17
Maria Myzithras, Tammy Bigwarfe, Erica Waltz, Hua Li, Jennifer Ahlberg, Irina Rybina, Sarah Low, Cynthia Hess Kenny, John Miglietta, Rachel Kroe-Barrett
AIM: The fully automated microfluidics-based Gyrolab is a popular instrument for the bioanalysis of protein therapeutics; requiring minimal sample and reagent volumes. Gyros offers affinity software for determining binding affinity in solution using a high-throughput method and miniaturized reactions. RESULTS: Using this affinity software, multiple CTGF-targeting reagents were characterized on the Gyrolab after <100% target coverage was seen in a cynomolgus pharmacokinetic/PD study dosed with anti-CTGF antibodies...
February 16, 2018: Bioanalysis
https://www.readbyqxmd.com/read/29451391/the-future-of-lc-ms-for-pharmaceutical-analysis-an-interview-with-jun-qu
#18
Jun Qu
Jun Qu speaks to Sankeetha Nadarajah, Editor of Bioanalysis: Jun Qu is the group leader of the proteomics and pharmaceutical analysis lab of SUNY-Buffalo (NY, USA) and a Professor in the Department of Pharmaceutical Sciences. His research is focused on the study of Clinical and Pharmaceutical Proteomics and Pharmaceutical Analysis using LC-MS-based strategies. His research programs include high-resolution and large-scale expression profiling of pathological proteomes, for the discovery of novel disease/therapeutics biomarkers using gel-free proteomic methods; sensitive identification, localization and quantification of post-translational modifications in tissue proteomes such as these in myocardium, using novel anti-PTM affinity capture and alternating Collision-induced dissociation/Electron transfer dissociation to obtain abundant PTM information; targeted investigation of marker proteins that are of high interests for clinical and pharmaceutical study, using highly sensitive nano-LC/SRM-based methods; and highly sensitive and accurate investigation of the PK of biotherapeutics using LC-MS...
February 16, 2018: Bioanalysis
https://www.readbyqxmd.com/read/29451388/a-dual-inhibitor-of-staphylococcus-aureus-virulence-and-biofilm-attenuates-expression-of-major-toxins-and-adhesins
#19
Barbara Hofbauer, Jan Vomacka, Matthias Stahl, Vadim S Korotkov, Megan C Jennings, William Wuest, Stephan A Sieber
Staphylococcus aureus is a major bacterial pathogen that invades and damages host tissue by the expression of devastating toxins. We here performed a phenotypic screen of 35 molecules that were structurally inspired by previous hydroxyamide-based S. aureus virulence inhibitors compiled from commercial sources or designed and synthesized de novo. One of the most potent compounds, AV73, did not only reduce hemolytic alpha-hemolysin production in S. aureus but also impeded in vitro biofilm formation. The effect of AV73 on bacterial proteomes and extracellular protein levels were analyzed by quantitative proteomics and revealed a significant down-regulation of major virulence and biofilm promoting proteins...
February 16, 2018: Biochemistry
https://www.readbyqxmd.com/read/29451362/simultaneous-multiple-ms-binding-assays-for-the-dopamine-norepinephrine-and-serotonin-transporters
#20
Patrick Neiens, Angela De Simone, Georg Höfner, Klaus T Wanner
In this work, we present label-free, mass-spectrometry-based binding assays (MS Binding Assays), targeting the human dopamine, norepinephrine, and serotonin transporters (hDAT, hNET, and hSERT) in simultaneous binding experiments. Using a validated LC-ESI-MS/MS method for quantification of the selective dopamine transporter inhibitor (R,R)-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin-3-ol ((R,R)-D-84), the selective norepinephrine transporter inhibitor (S,S)-reboxetine, and the selective serotonin reuptake inhibitor (S)-citalopram, binding affinities at the three monoamine transporters could be characterized simultaneously in a single binding experiment...
February 16, 2018: ChemMedChem
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