Mechanical deflection of the sensory hair bundles of receptor cells in the inner ear causes ion channels located at the tips of the bundle to open, thereby initiating the perception of sound. ...Although some protein constituents of the transduction apparatus are known, the mechanically gated transduction channels have not been identified in higher vertebrates. Here, we investigate TRP (transient receptor potential) ion channels as candidates and find one, TRPA1 (also known as ANKTM1), that meets criteria for the transduction channel. The appearance of TRPA1 messenger RNA expression in hair cell epithelia coincides developmentally with the onset of mechanosensitivity. Antibodies to TRPA1 label hair bundles, especially at their tips, and tip labelling disappears when the transduction apparatus is chemically disrupted. Inhibition of TRPA1 protein expression in zebrafish and mouse inner ears inhibits receptor cell function, as assessed with electrical recording and with accumulation of a channel-permeant fluorescent dye. TRPA1 is probably a component of the transduction channel itself.
The nitrocellulose (NC) membrane based lateral flow immunoassay device (LFID) is one of the most important and widely used biosensor platforms for point-of-care (PoC) diagnostics. However, the ...analytical performance of LFID has limitations and its optimization is restricted to the bioassay chemistry, the membrane porosity, and the choice of biolabel system. These bottom neck technical issues resulted from the fact that the conventional LFID design principle has not evolved for many years, which limited the LFID for advanced biosensor applications. Here we introduce a new dimension for LFID design and optimization based on geometric flow control (GFC) of NC membranes, leading to highly sensitive GFC-LFID. This novel approach enables comprehensive flow control via different membrane geometric features such as the width (
w
) and the length (
l
) of a constriction, as well as its input angle (
θ
1
) and output angle (
θ
2
). The GFC-LFID
(
w
=0.5 mm, l=7 mm,
θ
1
= 60
°
,
θ
2
= 45
°) attained a 10-fold increase in sensitivity for detection of interleukin-6 (IL-6), compared with conventional LFID, whereas reducing by 10-fold the antibody consumption. The GFC-LFID detects IL-6 over a linear range of 0.1–10 ng/mL with a limit of detection (LoD) of 29 pg/mL, which even outperforms some commercial IL-6 LFIDs. Such significant improvement is attained by pure geometric control of the NC membrane, without additives, that only relaying on a simple high throughput laser ablation procedure suitable for integration on regular large-scale manufacturing of GFC-LFIDs. Our new development on GFC-LFID with the combination of facile scalable fabrication process, tailored flow control, improved analytical performance, and reduced antibodies consumption is likely to have a significant impact on new design concept for the LFID industry.
Abstract
We present an interim analysis of a registered clinical study (NCT04800133) to establish immunobridging with various antibody and cellular immunity markers and to compare the immunogenicity ...and reactogenicity of 2-dose BNT162b2 and CoronaVac in healthy adolescents as primary objectives. One-dose BNT162b2, recommended in some localities for risk reduction of myocarditis, is also assessed. Antibodies and T cell immune responses are non-inferior or similar in adolescents receiving 2 doses of BNT162b2 (BB,
N
= 116) and CoronaVac (CC,
N
= 123) versus adults after 2 doses of the same vaccine (BB,
N
= 147; CC,
N
= 141) but not in adolescents after 1-dose BNT162b2 (B,
N
= 116). CC induces SARS-CoV-2 N and N C-terminal domain seropositivity in a higher proportion of adolescents than adults. Adverse reactions are mostly mild for both vaccines and more frequent for BNT162b2. We find higher S, neutralising, avidity and Fc receptor-binding antibody responses in adolescents receiving BB than CC, and a similar induction of strong S-specific T cells by the 2 vaccines, in addition to N- and M-specific T cells induced by CoronaVac but not BNT162b2, possibly implying differential durability and cross-variant protection by BNT162b2 and CoronaVac, the 2 most used SARS-CoV-2 vaccines worldwide. Our results support the use of both vaccines in adolescents.
To clarify the clinical features of delayed calcification of hydrogel intraocular lenses (IOLs) based on observation of a large case series.
Ophthalmology department of 2 university teaching ...hospitals, Hong Kong, China.
The first 44 patients with a known diagnosis of calcified IOL were recruited. Medical and ophthalmic histories were obtained. Surgical details, surgical complications, and visual acuity before and after IOL implantation were also retrieved. Patients then had a visual acuity test, a slitlamp examination of the features of the IOL calcification, and a fundus examination for clarity of view.
Forty-six eyes of 44 patients had IOL calcification. All had a Hydroview IOL. The onset was from 4 to 26 months after surgery. Ninety-three percent of eyes had generalized IOL calcification, and 96% had forceps marks on the IOL. Mean visual acuity deteriorated from 0.4 at 3 months to 0.13 at 19 months. Visual loss was more severe in patients with diabetes mellitus or ischemic heart disease and in those in which the IOL calcified earlier after implantation.
All cases of IOL calcification were delayed in onset. The presence of forceps marks may provide a clue to the pathogenesis. Bilateral but asymmetric involvement in 2 patients suggests that the IOL was involved in the pathogenesis. Affected patients lost an average of 2.8 Snellen lines of visual acuity. Some eyes progressed more rapidly; however, the modulating factors remain unknown.
The CUHK Hong Kong Quality of Life Index, which aims to assess and monitor the quality of life in Hong Kong, is a composite index incorporating both objective and subjective measures. This index, ...developed by the Faculty of Social Science of The Chinese University of Hong Kong, employs data collected in representative sample surveys and official statistics. A wide range of life domains is covered and the year 2002 is taken as the base year of the study. Index scores demonstrate that in general the quality of life in Hong Kong has improved slightly in 2003; scores of the composite index and the three sub-indices on sectorial performance are somewhat higher than those of the previous year. It is noteworthy that Hong Kong has made noticeable progress and performs as well as many economically advanced societies in certain life domains; yet, the well-being of the people relies on further improvement in others.
To define the physiological role of IP(3)3-kinase(A) in vivo, we have generated a mouse strain with a null mutation of the IP(3)3-kinase(A) locus by gene targeting. Homozygous mutant mice were fully ...viable, fertile, apparently normal, and did not show any morphological anomaly in brain sections. In the mutant brain, the IP4 level was significantly decreased whereas the IP3 level did not change, demonstrating a major role of IP(3)3-kinase(A) in the generation of IP4. Nevertheless, no significant difference was detected in the hippocampal neuronal cells of the wild-type and the mutant mice in the kinetics of Ca2+ regulation after glutamate stimulation. Electrophysiological analyses carried out in hippocampal slices showed that the mutation significantly enhanced the LTP in the hippocampal CA1 region, but had no effect on the LTP in dentate gyrus (DG). No difference was noted, however, between the mutant and the wild-type mice in the Morris water maze task. Our results indicate that IP(3)3-kinase(A) may play an important role in the regulation of LTP in hippocampal CA1 region through the generation of IP4, but the enhanced LTP in the hippocampal CA1 does not affect spatial learning and memory.
Two doses of inactivated SARS-CoV-2 vaccine CoronaVac cannot elicit high efficacy against symptomatic COVID-19, especially against the Omicron variant, but that can be improved by a third dose in ...adults. The use of a third dose of CoronaVac in adolescents may be supported by immunobridging studies in the absence of efficacy data.
With an immunobridging design, our study (NCT04800133) tested the non-inferiority of the binding and neutralizing antibodies and T cell responses induced by a third dose of CoronaVac in healthy adolescents (N=94, median age 14.2 years, 56% male) compared to adults (N=153, median age 48.1 years, 44% male). Responses against wild-type (WT) and BA.1 SARS-CoV-2 were compared in adolescents. Safety and reactogenicity were also monitored.
A homologous third dose of CoronaVac further enhanced antibody response in adolescents compared to just 2 doses. Adolescents mounted non-inferior antibody and T cell responses compared to adults. Although S IgG and neutralizing antibody responses to BA.1 were lower than to WT, they remained detectable in 96% and 86% of adolescents. T cell responses to peptide pools spanning only the mutations of BA.1 S, N and M in adolescents were preserved, increased, and halved compared to WT respectively. No safety concerns were identified.
The primary vaccination series of inactivated SARS-CoV-2 vaccines for adolescents should include 3 doses for improved humoral immunogenicity.
PDF
