Hearing depends on the transduction of sounds into neural signals by the inner hair cells of the cochlea. Cochleae also have outer hair cells with unique electromotile properties that increase auditory sensitivity, but they are particularly susceptible to damage by intense noise exposure, ototoxic drugs, and aging. Although the outer hair cells have synapses on afferent neurons that project to the brain, the function of this neuronal circuit is unclear. Here, we created a novel mouse allele that inserts a fluorescent reporter at the C1ql1 locus which revealed gene expression in the outer hair cells and allowed creation of outer hair cell-specific C1ql1 knockout mice. We found that C1ql1 expression in outer hair cells corresponds to areas with the most sensitive frequencies of the mouse audiogram, and that it has an unexpected adolescence-onset developmental timing. No expression was observed in the inner hair cells. Since C1QL1 in the brain is made by neurons, transported anterogradely in axons, and functions in the synaptic cleft, C1QL1 may serve a similar function at the outer hair cell afferent synapse. Histological analyses revealed that C1ql1 conditional knockout cochleae may have reduced outer hair cell afferent synapse maintenance. However, auditory behavioral and physiological assays did not reveal a compelling phenotype. Nonetheless, this study identifies a potentially useful gene expressed in the cochlea and opens the door for future studies aimed at elucidating the function of C1QL1 and the function of the outer hair cell and its afferent neurons.
The ongoing pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused millions of deaths worldwide. However, most SARS‐CoV‐2 detection methods depend on time‐consuming sample preparation and large detection instruments. Herein, a method employing nonbleeding pH paper to achieve both RNA extraction and visual isothermal amplification is proposed, enabling rapid, instrument‐free SARS‐CoV‐2 detection. By taking advantage of capillary forces, pH‐paper‐based RNA extraction can be accomplished within 1 min without need for any equipment. Further, the pH paper can mediate dye‐free visual isothermal amplification detection. In less than a 46‐min sample‐to‐answer time, pH‐paper‐based extraction and visual detection (termed pH‐EVD) can consistently detect 1200 genome equivalents per microliter of SARS‐CoV‐2 in saliva, which is comparable to TaqMan probe‐based quantitative reverse transcription PCR (RT‐qPCR). Through coupling with a chemically heated incubator called a smart cup, the instrument‐free, pH‐EVD‐based SARS‐CoV‐2 detection method on 30 nasopharyngeal swab samples and 33 contrived saliva samples is clinically validated. Thus, the pH‐EVD method provides simple, rapid, reliable, low‐cost, and instrument‐free SARS‐CoV‐2 detection and has the potential to streamline onsite COVID‐19 diagnostics.
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