The Rare Anaphylaxis-Associated FcγRIIa3 Exhibits Distinct Characteristics From the Canonical FcγRIIa1

FcγRIIa is an activating FcγR, unique to humans and non-human primates. It induces antibody-dependent proinflammatory responses and exists predominantly as FcγRIIa1. A unique splice variant, we designated FcγRIIa3, has been reported to be associated with anaphylactic reactions to intravenous immunoglobulins (IVIg) therapy. We aim to define the functional consequences of this FcγRIIa variant associated with adverse responses to IVIg therapy and evaluate the frequency of associated SNPs. FcγRIIa forms from macaque and human PBMCs were investigated for IgG-subclass specificity, biochemistry, membrane localization, and functional activity. Disease-associated SNPs were analyzed by sequencing genomic DNA from 224 individuals with immunodeficiency or autoimmune disease. FcγRIIa3 was identified in macaque and human PBMC. The FcγRIIa3 is distinguished from the canonical FcγRIIa1 by a unique 19-amino acid cytoplasmic insertion and these two FcγRIIa forms responded distinctly to antibody ligation. Whereas FcγRIIa1 was rapidly internalized, FcγRIIa3 was retained longer at the membrane, inducing greater calcium mobilization and cell degranulation. Four FCGR2A SNPs were identified including the previously reported intronic SNP associated with anaphylaxis, but in only 1 of 224 individuals. The unique cytoplasmic element of FcγRIIa3 delays internalization and is associated with enhanced cellular activation. The frequency of the immunodeficiency-associated SNP varies between disease populations but interestingly occurred at a lower frequency than previously reported. None-the-less enhanced FcγRIIa3 function may promote a proinflammatory environment and predispose to pathological inflammatory responses

Refractive index profile of a multi-step fibre using differential interference contrast microscopy

A method to extract quantitative phase data from differential interference contrast (DIC) microscopic images is presented. This method in conjunction with the inverse Abel transform is used to obtain an accurate refractive index profile of a calibrated multi-step optical fibre (National Physical Laboratory). Results of the refractive index profile are compared with that determined by the calibration process

A pi-phase-shifted fiber Bragg grating fabricated using a single phase mask

A fiber Bragg grating at twice the Bragg wavelength was fabricated by a standard phase mask technique and its two peaks/dips are attributed to the interleaved refractive index modulations along the fiber core that produced a pi-phase-shifted grating

Modified organosilica core-shell nanoparticles for stable pH sensing in biological solutions

Continuous monitoring using nanoparticle-based sensors has been successfully employed in complex biological systems, yet the sensors still suffer from poor long-term stability partially because of the scaffold materials chosen to date. Organosilica core-shell nanoparticles containing a mixture of covalently incorporated pH-sensitive (shell) and pH-insensitive (core) fluorophores is presented as a continuous pH sensor for application in biological media. In contrast to previous studies focusing on similar materials, we sought to investigate the sensor characteristics (dynamic range, sensitivity, response time, stability) as a function of material properties. The ratio of the fluorescence intensities at specific wavelengths was found to be highly sensitive to pH over a physiologically relevant range (4.5-8) with a response time o

Quantitative investigation of the refractive-index modulation within the core of a fiber Bragg grating

A comparison is made between the modeled and experimentally determined microscopic images of a type I Bragg grating produced in the core of an optical fiber using the ultraviolet irradiation of a phase mask. The simulated image of the refractive-index distribution, which assumes a linear relationship between the irradiation intensity and the refractive-index change, is in good agreement with the measured image

Modified Organosilica Core–Shell Nanoparticles for Stable pH Sensing in Biological Solutions

Continuous monitoring using nanoparticle-based sensors has been successfully employed in complex biological systems, yet the sensors still suffer from poor long-term stability partially because of the scaffold materials chosen to date. Organosilica core–shell nanoparticles containing a mixture of covalently incorporated pH-sensitive (shell) and pH-insensitive (core) fluorophores is presented as a continuous pH sensor for application in biological media. In contrast to previous studies focusing on similar materials, we sought to investigate the sensor characteristics (dynamic range, sensitivity, response time, stability) as a function of material properties. The ratio of the fluorescence intensities at specific wavelengths was found to be highly sensitive to pH over a physiologically relevant range (4.5–8) with a response time of <100 ms, significantly faster than that of previously reported response times using silica-based particles. Particles produced stable, pH-specific signals when stored at room temperature for more than 80 days. Finally, we demonstrated that the nanosensors successfully monitored the pH of a bacterial culture over 15 h and that pH changes in the skin of mouse cadavers could also be observed via in vivo fluorescence imaging following subcutaneous injection. The understanding gained from linking sensor characteristics and material properties will inform the next generation of optical nanosensors for continuous-monitoring applications