3,803 research outputs found
Variable domain N-linked glycosylation and negative surface charge are key features of monoclonal ACPA: implications for B-cell selection
Autoreactive B cells have a central role in the pathogenesis of rheumatoid
arthritis (RA), and recent findings have proposed that anti-citrullinated
protein autoantibodies (ACPA) may be directly pathogenic. Herein, we
demonstrate the frequency of variable-region glycosylation in single-cell
cloned mAbs. A total of 14 ACPA mAbs were evaluated for predicted N-linked
glycosylation motifs in silico and compared to 452 highly-mutated mAbs from RA
patients and controls. Variable region N-linked motifs (N-X-S/T) were
strikingly prevalent within ACPA (100%) compared to somatically hypermutated
(SHM) RA bone marrow plasma cells (21%), and synovial plasma cells from
seropositive (39%) and seronegative RA (7%). When normalized for SHM, ACPA
still had significantly higher frequency of N-linked motifs compared to all
studied mAbs including highly-mutated HIV broadly-neutralizing and
malaria-associated mAbs. The Fab glycans of ACPA-mAbs were highly sialylated,
contributed to altered charge, but did not influence antigen binding. The
analysis revealed evidence of unusual B-cell selection pressure and
SHM-mediated decreased in surface charge and isoelectric point in ACPA. It is
still unknown how these distinct features of anti-citrulline immunity may have
an impact on pathogenesis. However, it is evident that they offer selective
advantages for ACPA+ B cells, possibly also through non-antigen driven
mechanisms
Increasing the quantum efficiency of InAs/GaAs QD arrays for solar cells grown by MOVPE without using strain-balance technology
Research into the formation of InAs quantum dots (QDs) in GaAs using the metalorganic vapor phase epitaxy technique ispresented. This technique is deemed to be cheaper than the more often used and studied molecular beam epitaxy. The bestconditions for obtaining a high photoluminescence response, indicating a good material quality, have been found among awide range of possibilities. Solar cells with an excellent quantum ef?ciency have been obtained, with a sub-bandgapphoto-response of 0.07 mA/cm2per QD layer, the highest achieved so far with the InAs/GaAs system, proving the potentialof this technology to be able to increase the ef?ciency of lattice-matched multi-junction solar cells and contributing to abetter understanding of QD technology toward the achievement of practical intermediate-band solar cells
Introducing MINA-The Molecularly Imprinted Nanoparticles Assay
A new ELISAâ (enzymeâlinked immunosorbent assay)âlike assay is demonstrated in which no elements of biological origin are used for molecular recognition or signaling. Composite imprinted nanoparticles that contain a catalytic core and which are synthesized by using a solidâphase approach can simultaneously act as recognition/signaling elements, and be used with minimal modifications to standard assay protocols. This assay provides a new route towards replacement of unstable biomolecules in immunoassays
Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting
Acknowledgements The iHARP database was funded by unrestricted grants from Mundipharma International Ltd and Research in Real-Life Ltd; these analyses were funded by an unrestricted grant from Teva Pharmaceuticals. Mundipharma and Teva played no role in study conduct or analysis and did not modify or approve the manuscript. The authors wish to direct a special appreciation to all the participants of the iHARP group who contributed data to this study and to Mundipharma, sponsors of the iHARP group. In addition, we thank Julie von Ziegenweidt for assistance with data extraction and Anna Gilchrist and Valerie L. Ashton, PhD, for editorial assistance. Elizabeth V. Hillyer, DVM, provided editorial and writing support, funded by Research in Real-Life, Ltd.Peer reviewedPublisher PD
Transcriptional silencing of the Dickkopfs-3 (Dkk-3) gene by CpG hypermethylation in acute lymphoblastic leukaemia
Dkk-3 is a newly characterised mortalisation-related gene and an antagonist of the Wnt oncogenic signalling pathway whose
expression is decreased in a variety of cancer cell lines, suggesting that the Dkk-3 gene, located at chromosome 11p15.1, functions as
a tumour suppressor gene. Although 11p15 is a âhot spotâ for methylation in acute lymphoblastic leukaemia (ALL), the role of Dkk-3
abnormalities has never been evaluated in this disease. We analysed CpG island methylation of the Dkk-3 promoter in six ALL cell
lines and 183 ALL patients. We observed Dkk-3 hypermethylation in all cell lines and in cells from 33% (60/183) of ALL patients.
Moreover, Dkk-3 methylation was associated with decreased Dkk-3 mRNA expression and this expression was restored after
exposure to the demethylating agent 5-AzaC. Clinical features did not differ between hypermethylated and unmethylated patients.
Estimated disease-free survival (DFS) and overall survival at 10 and 11 years, respectively, were 49.8 and 45.6% for normal patients
and 10.5 and 15.1% for hypermethylated patients (PŒ0.001 and 0.09). Multivariate analysis demonstrated that Dkk-3 methylation
was an independent prognostic factor predicting DFS (PŒ0.0009). Our data suggest that Dkk-3 methylation occurs at an early stage
in ALL pathogenesis and probably influences the clinical behaviour of the disease
Raise the anchor! Synthesis, X-ray and NMR characterization of 1,3,5-triazinanes with an axial tert-butyl group
N-t-Bu-Nâ,Nââ-disulfonamide-1,3,5-triazinanes were synthesized and characterized by X-ray single crystal structure analysis. In the course of the X-ray structure elucidation, the first solid experimental evidence of the axial position of the tert-butyl group in unconstrained hexahydro-1,3,5-triazacyclohexanes was obtained. Dynamic low-temperature NMR analysis allowed to fully investigate a rare case of crystallization-driven unanchoring of the tert-butyl group in the chair conformation of saturated sixmembered cycles. DFT calculations show that the use of explicit solvent molecules is necessary to explain the equatorial position of the t-Bu group in solution. Otherwise, the axial conformer is the thermodynamically stable isomer.Fil: Kletskov, Alexey V.. University of Russia; RusiaFil: Zatykina, Anastasya D.. University of Russia; RusiaFil: Grudova, Mariya V.. University of Russia; RusiaFil: Sinelshchikova, Anna A.. Academy of Sciences; RusiaFil: Grigoriev, Mikhail. Academy of Sciences; RusiaFil: Zaytsev, Vladimir P.. University of Russia; RusiaFil: Gil, Diego Mauricio. Universidad Nacional de TucumĂĄn. Instituto de BiotecnologĂa FarmacĂ©utica y Alimentaria. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - TucumĂĄn. Instituto de BiotecnologĂa FarmacĂ©utica y Alimentaria; Argentina. Universidad Nacional de TucumĂĄn. Facultad de BioquĂmica, QuĂmica y Farmacia. Instituto de QuĂmica OrgĂĄnica; ArgentinaFil: Novikov, Roman A.. Academy of Sciences; RusiaFil: Zubkov, Fedor Ivanovich. University of Russia; RusiaFil: Frontera, Antonio. Universidad de las Islas Baleares; Españ
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