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https://www.readbyqxmd.com/read/29782488/insight-into-small-molecule-binding-to-the-neonatal-fc-receptor-by-x-ray-crystallography-and-100-khz-magic-angle-spinning-nmr
#1
Daniel Stöppler, Alex Macpherson, Susanne Smith-Penzel, Nicolas Basse, Fabien Lecomte, Hervé Deboves, Richard D Taylor, Tim Norman, John Porter, Lorna C Waters, Marta Westwood, Ben Cossins, Katharine Cain, James White, Robert Griffin, Christine Prosser, Sebastian Kelm, Amy H Sullivan, David Fox, Mark D Carr, Alistair Henry, Richard Taylor, Beat H Meier, Hartmut Oschkinat, Alastair D Lawson
Aiming at the design of an allosteric modulator of the neonatal Fc receptor (FcRn)-Immunoglobulin G (IgG) interaction, we developed a new methodology including NMR fragment screening, X-ray crystallography, and magic-angle-spinning (MAS) NMR at 100 kHz after sedimentation, exploiting very fast spinning of the nondeuterated soluble 42 kDa receptor construct to obtain resolved proton-detected 2D and 3D NMR spectra. FcRn plays a crucial role in regulation of IgG and serum albumin catabolism. It is a clinically validated drug target for the treatment of autoimmune diseases caused by pathogenic antibodies via the inhibition of its interaction with IgG...
May 21, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29780950/extreme-descemet-s-membrane-rupture-with-hydrops-in-keratoconus-clinical-and-histological-manifestations
#2
I-Ping Loh, Jennifer C Fan Gaskin, Trevor Sherwin, Charles N J McGhee
Purpose: To study the clinical and histological manifestations of an extreme Descemet's membrane rupture as a result of keratoconus. Observations: Using Periodic acid-Schiff assay to study a keratoconic cornea with an extreme rupture showed that the ruptured Descemet's membrane had retracted and folded into scrolls and ridges. The dimensions of the rupture were estimated to be 3.7mm2 , and the central cornea was extremely thinned with a thickness of only 260μm...
June 2018: American Journal of Ophthalmology Case Reports
https://www.readbyqxmd.com/read/29780657/characterizing-cellular-mechanical-phenotypes-with-mechano-node-pore-sensing
#3
Junghyun Kim, Sewoon Han, Andy Lei, Masaru Miyano, Jessica Bloom, Vasudha Srivastava, Martha M Stampfer, Zev J Gartner, Mark A LaBarge, Lydia L Sohn
The mechanical properties of cells change with their differentiation, chronological age, and malignant progression. Consequently, these properties may be useful label-free biomarkers of various functional or clinically relevant cell states. Here, we demonstrate mechano-node-pore sensing (mechano-NPS), a multi-parametric single-cell-analysis method that utilizes a four-terminal measurement of the current across a microfluidic channel to quantify simultaneously cell diameter, resistance to compressive deformation, transverse deformation under constant strain, and recovery time after deformation...
2018: Microsystems & Nanoengineering
https://www.readbyqxmd.com/read/29779368/automated-3d-printed-microfluidic-array-for-rapid-nanomaterial-enhanced-detection-of-multiple-proteins
#4
Karteek Kadimisetty, Spundana Malla, Ketki Bhalerao, Islam M Mosa, Snehasis Bhakta, Norman Lee, James F Rusling
We report here the fabrication and validation of a novel 3D printed, automated immunoarray to detect multiple proteins with ultralow detection limits. This low cost, miniature immunoarray employs electrochemiluminescent (ECL) detection measured with a CCD camera and employs touch screen control of a micropump to facilitate automated use. The miniaturized array features prefilled reservoirs to deliver sample and reagents to a paper-thin pyrolytic graphite microwell detection chip to complete sandwich immunoassays...
May 21, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29777551/a-new-method-for-quantitative-determination-of-renalase-based-on-mass-spectrometry-determination-of-a-proteotypic-peptide-labeled-with-stable-isotopes
#5
A T Kopylov, V I Fedchenko, O A Buneeva, N V Pyatakova, V G Zgoda, A E Medvedev
RATIONALE: Renalase is a recently discovered kidney secretory protein, which is considered as an important component involved in blood pressure regulation. Although altered levels of renalase have been detected in plasma and urine of patients with various kidney diseases, there is certain inconsistency of changes in the renalase levels reported by different laboratories. The latter is obviously associated with the use of ELISA as the only available approach for quantitative analysis of renalase...
May 18, 2018: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29776548/a-label-free-electrochemical-biosensor-for-direct-detection-of-rack-1-by-using-disposable-low-cost-and-reproducible-ito-based-electrode
#6
Hakan Törer, Elif Burcu Aydın, Mustafa Kemal Sezgintürk
In this study we designed an ultrasensitive electrochemical immunosensor for RACK 1 detection using 11-cyanoundecyltrimethoxysilane (11-CUTMS) as a immobilization matrix to immobilize biorecognition element. The used silane agent (11-CUTMS) provides a favorable platform for efficient loading of anti-RACK 1 antibody. The effective loading of the biorecognition element on the 11-CUTMS matrix was monitored by scanning electron microscopy (SEM), atomic force microscopy (AFM) images and fourier transform infrared spectroscopy (FTIR) spectra...
September 18, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29774041/report-on-the-current-inventory-of-the-toolbox-for-plant-cell-wall-analysis-proteinaceous-and-small-molecular-probes
#7
REVIEW
Maja G Rydahl, Aleksander R Hansen, Stjepan K Kračun, Jozef Mravec
Plant cell walls are highly complex structures composed of diverse classes of polysaccharides, proteoglycans, and polyphenolics, which have numerous roles throughout the life of a plant. Significant research efforts aim to understand the biology of this cellular organelle and to facilitate cell-wall-based industrial applications. To accomplish this, researchers need to be provided with a variety of sensitive and specific detection methods for separate cell wall components, and their various molecular characteristics in vitro as well as in situ ...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29773891/assessing-the-feasibility-of-neutralizing-osteopontin-with-various-therapeutic-antibody-modalities
#8
Vahid Farrokhi, Jeffrey R Chabot, Hendrik Neubert, Zhiyong Yang
Osteopontin is a secreted glycophosphoprotein that is highly implicated in many physiological and pathological processes such as biomineralization, cell-mediated immunity, inflammation, fibrosis, cell survival, tumorigenesis and metastasis. Antibodies against osteopontin have been actively pursued as potential therapeutics for various diseases by pharmaceutical companies and academic laboratories. Many studies have demonstrated the efficacy of osteopontin inhibition in a variety of preclinical models of diseases such as rheumatoid arthritis, cancer, nonalcoholic steatohepatitis, but clinical utility has not yet been demonstrated...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773326/tremelimumab-combined-with-durvalumab-in-patients-with-mesothelioma-nibit-meso-1-an-open-label-non-randomised-phase-2-study
#9
Luana Calabrò, Aldo Morra, Diana Giannarelli, Giovanni Amato, Armida D'Incecco, Alessia Covre, Arthur Lewis, Marlon C Rebelatto, Riccardo Danielli, Maresa Altomonte, Anna Maria Di Giacomo, Michele Maio
BACKGROUND: Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study. We aimed to investigate the efficacy and safety of first-line or second-line tremelimumab combined with durvalumab, an anti-PD-L1 monoclonal antibody, in patients with malignant mesothelioma. METHODS: In this open-label, non-randomised, phase 2 trial, patients with unresectable pleural or peritoneal mesothelioma received intravenous tremelimumab (1 mg/kg bodyweight) and durvalumab (20 mg/kg bodyweight) every 4 weeks for four doses, followed by maintenance intravenous durvalumab at the same dose and schedule for nine doses...
May 14, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29772383/a-signal-decreased-electrochemical-immunosensor-for-the-sensitive-detection-of-lag-3-protein-based-on-a-hollow-nanobox-mofs-aupt-alloy
#10
Wei Xu, Zhen Qin, Yutong Hao, Qiang He, Shuai Chen, Zhongshuang Zhang, Dan Peng, Haiyan Wen, Jun Chen, Jingfu Qiu, Chaorui Li
In this work, hollow nanobox metal-organic framework (HNM) nanocomposites were synthesised and utilised for the first time in a signal decreased electrochemical immunosensor for the ultrasensitive quantitative determination of lymphocyte activation gene-3 (LAG-3) protein, which is a newly discovered biomarker. With the aid of signal materials, namely, SiO2 -tagged anti-LAG-3 antibody (SiO2 -Ab2 ) and the biotin-streptavidin system, the sensor can achieve signal amplification. Encapsulation of tin dioxide-functionalised reduced graphene oxide (rGO-SnO2 ) and gold and platinum alloys (AuPt alloys) onto the surface of hollow nanobox metal-organic frameworks (MOFs) was performed to prepare rGO-SnO2 /hollow nanobox-MOFs/AuPt alloys (rGO-SnO2 /HNMs/AuPt) as the matrix...
May 8, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29772250/development-and-validation-of-a-novel-semi-homogenous-clinical-assay-for-quantitation-of-ranibizumab-in-human-serum
#11
John Lowe, Eric Wakshull, Theresa Shek, Anan Chuntharapai, Rebecca Elliott, Jeriza Rusit, Mauricio Maia
Ranibizumab (Lucentis®), a humanized antigen-binding fragment (Fab) monoclonal antibody that blocks VEGF-A activity is currently approved for the treatment of several retinal degenerative diseases. The assessment of drug pharmacokinetics (PK) is essential for evaluating exposure as it relates to drug safety and efficacy. For drugs administered intravitreally, systemic drug levels during the course of clinical studies are typically 100 to 1000-fold lower than those of similar therapeutics dosed intravenously, posing a significant bioanalytical challenge for PK measurements...
May 14, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29772060/nucleocytoplasmic-shuttling-the-ins-and-outs-of-quantitative-imaging
#12
Chris Molenaar, Kate L Weeks
Nucleocytoplasmic protein shuttling is integral to the transmission of signals between the nucleus and the cytoplasm. The nuclear/cytoplasmic distribution of proteins of interest can be determined via fluorescence microscopy, following labelling of the target protein with fluorophore-conjugated antibodies (immunofluorescence) or by tagging the target protein with an autofluorescent protein, such as green fluorescent protein (GFP). The latter enables live cell imaging, a powerful approach that precludes many of the artefacts associated with indirect immunofluorescence in fixed cells...
May 17, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29772044/a-phase-1-open-label-dose-escalation-trial-to-investigate-safety-and-tolerability-of-single-intravitreous-injections-of-icon-1-targeting-tissue-factor-in-wet-amd
#13
John A Wells, Christine R Gonzales, Brian B Berger, Victor H Gonzalez, Brian D Sippy, Gabriela Burian
BACKGROUND AND OBJECTIVE: This phase 1 study evaluated the safety and tolerability of single intravitreous injections (IVIs) of ICON-1 (Iconic Therapeutics, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD). ICON-1 is a modified factor VIIa protein linked with the Fc portion of a human immunoglobulin G1. The molecule binds tissue factor overexpressed on choroidal neovascularization (CNV) in AMD. PATIENTS AND METHODS: Open-label, interventional, dose-escalation trial in 18 patients with CNV due to AMD, with six patients per dose cohort...
May 1, 2018: Ophthalmic Surgery, Lasers & Imaging Retina
https://www.readbyqxmd.com/read/29771118/escherichia-coli-fiber-sensors-using-concentrated-dielectrophoretic-force-with-optical-defocusing-method
#14
Yi-Hsin Tai, Chia-Wei Lee, Dao-Ming Chang, Yu-Sheng Lai, Ding-Wei Huang, Pei-Kuen Wei
A sensitive tapered optical fiber tip combined with dielectrophoretic (DEP) trapping was used to rapid and label-free detection of bacteria in water. The angular spectrum of optical field at the fiber tip was changed with surrounding refractive index (RI). By measuring far-field intensity change at the defocus plane, the intensity sensitivity was up to 95,200 %/RIU (RI unit) and the detection limit was 2.1 × 10-6 RIU at 0.2% intensity stability. By applying an AC voltage to a Ti/Al coated fiber tip and an indium-tin-oxide glass, the DEP force effectively trapped the Escherichia coli (E...
May 17, 2018: ACS Sensors
https://www.readbyqxmd.com/read/29768499/a-fixable-probe-for-visualizing-flagella-and-plasma-membranes-of-the-african-trypanosome
#15
Justin Wiedeman, Kojo Mensa-Wilmot
The protozoan Trypanosoma brucei sp. cause diseases in humans and animals. Studies of T. brucei cell biology have revealed unique features, such as major endocytic events being limited to a single region, and mitochondrial genome segregation mediated via basal bodies. Further understanding of trypanosome cell biology can be facilitated with super-resolution fluorescence microscopy. Lack of a plasma membrane probe for fixed trypanosomes remains a persistent problem in need of a working solution. Herein, we report protocols developed using mCLING in super-resolution structured illumination fluorescence microscopy (SR-SIM)...
2018: PloS One
https://www.readbyqxmd.com/read/29768445/nogo-receptor-1-is-expressed-by-nearly-all-retinal-ganglion-cells
#16
Alexander M Solomon, Teleza Westbrook, Greg D Field, Aaron W McGee
A variety of conditions ranging from glaucoma to blunt force trauma lead to optic nerve atrophy. Identifying signaling pathways for stimulating axon growth in the optic nerve may lead to treatments for these pathologies. Inhibiting signaling by the nogo-66 receptor 1 (NgR1) promotes the re-extension of axons following a crush injury to the optic nerve, and while NgR1 mRNA and protein expression are observed in the retinal ganglion cell (RGC) layer and inner nuclear layer, which retinal cell types express NgR1 remains unknown...
2018: PloS One
https://www.readbyqxmd.com/read/29767428/photonic-crystal-enhanced-fluorescence-immunoassay-on-diatom-biosilica
#17
Kenneth Squire, Xianming Kong, Paul LeDuff, Gregory L Rorrer, Alan X Wang
Fluorescence biosensing is one of the most established biosensing methods, particularly fluorescence spectroscopy and microscopy. These are two highly sensitive techniques but require high grade electronics and optics to achieve the desired sensitivity. Efforts have been made to implement these methods using consumer grade electronics and simple optical setups for applications such as point-of-care diagnostics, but the sensitivity inherently suffers. Sensing substrates, capable of enhancing fluorescence are thus needed to achieve high sensitivity for such applications...
May 16, 2018: Journal of Biophotonics
https://www.readbyqxmd.com/read/29767232/free%C3%A2-floating-cancer-cells-in-lymph-node-sinuses-of-hilar-lymph-node%C3%A2-positive-patients-with-non%C3%A2-small-cell-lung-cancer
#18
Yusuke Nakamura, Masaya Mukai, Shinichiro Hiraiwa, Kyoko Kishima, Tomoko Sugiyama, Takuma Tajiri, Shunsuke Yamada, Masayuki Iwazaki
Previous studies demonstrated that free‑floating cancer cells (FFCCs) in the lymph node sinuses were of prognostic significance for colorectal and gastric cancer. The present study investigated the clinical significance of detecting FFCCs using Fast Red staining for cytokeratin in stage I/II non‑small cell lung cancer (NSCLC) patients and hilar lymph node positive NSCLC patients who underwent curative resection. Between 2002 and 2011, a total of 164 patients (including 22 hilar lymph node positive patients) were investigated...
May 14, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29766635/efficacy-and-safety-of-mk-1293-insulin-glargine-compared-with-originator-insulin-glargine-lantus-in-type-1-diabetes-a-randomized-open-label-clinical-trial
#19
Philip D Home, Raymond L H Lam, Wendy L Carofano, Gregory T Golm, Roy Eldor, Michael F Crutchlow, Michael C Marcos, Julio Rosenstock, Priscilla A Hollander, Baptist Gallwitz
AIMS: Comparison of the efficacy and safety of MK-1293 insulin glargine (Mk-Gla; 100 U/ml) with originator insulin glargine, Lantus (Sa-Gla) in people with type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: This phase 3, randomized, active-controlled, open-label, 52-week study enrolled 508 people with T1DM (HbA1c ≤ 11.0%; 97 mmol/mol) taking basal and prandial insulin. Participants were randomized 1:1 to once-daily Mk-Gla (n=245) or Sa-Gla (n=263). Dose titration of basal insulin was by a pre-breakfast plasma glucose dosing algorithm...
May 15, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29765647/controlled-fluorescence-quenching-by-antibody-conjugated-graphene-oxide-to-measure-tau-protein
#20
Ao Huang, Luning Zhang, Weiwei Li, Zeyu Ma, Shi Shuo, Tianming Yao
We report an ultrasensitive immunoassay for tau protein-a key marker of Alzheimer's disease. This sensing platform relies on graphene oxide (GO) surfaces conjugated with anti-human tau antibody to provide quantitative binding sites for the tau protein. The GO quenches standard fluorescein isothiocyanate labelled tau (tau-FITC) when tau protein and tau-FITC are both present and compete for the binding sites. This change in fluorescence signal can be used to quantitate tau protein. In contrast with traditional enzyme-linked immunosorbent assay (ELISA), our method does not require enzyme-linked secondary antibodies for protein recognition nor does it require an enzyme substrate for optical signal generation...
April 2018: Royal Society Open Science
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