Age‐related changes in the biophysical and morphological characteristics of mouse cochlear outer hair cells

Outer hair cells (OHCs) are electromotile sensory receptors that provide sound amplification within the mammalian cochlea. Although OHCs appear susceptible to ageing, the progression of the pathophysiological changes in these cells is still poorly understood. By using mouse strains with a different progression of hearing loss (C57BL/6J, C57BL/6NTac, C57BL/6NTacCdh23+ , C3H/HeJ), we have identified morphological, physiological and molecular changes in ageing OHCs (9–12 kHz cochlear region). We show that by 6 months of age, OHCs from all strains underwent a reduction in surface area, which was not a sign of degeneration. Although the ageing OHCs retained a normal basolateral membrane protein profile, they showed a reduction in the size of the K+ current and non‐linear capacitance, a readout of prestin‐dependent electromotility. Despite these changes, OHCs have a normal V m and retain the ability to amplify sound, as distortion product otoacoustic emission thresholds were not affected in aged, good‐hearing mice (C3H/HeJ, C57BL/6NTacCdh23+ ). The loss of afferent synapses was present in all strains at 15 months. The number of efferent synapses per OHCs, defined as postsynaptic SK2 puncta, was reduced in aged OHCs of all strains apart from C3H mice. Several of the identified changes occurred in aged OHCs from all mouse strains, thus representing a general trait in the pathophysiological progression of age‐related hearing loss, possibly aimed at preserving functionality. We have also shown that the mechanoelectrical transduction (MET) current from OHCs of mice harbouring the Cdh23ahl allele is reduced with age, highlighting the possibility that changes in the MET apparatus could play a role in cochlear ageing

Choice of tracers for the evaluation of spray deposits

Tracer substances, used to evaluate spraying effectiveness, ordinarily modify the surface tension of aqueous solutions. This study aimed to establish a method of using tracers to evaluate distribution and amount of spray deposits, adjusted to the surface tension of the spraying solution. The following products were tested: 0.15% Brilliant Blue, 0.15% Saturn Yellow in 0.015% Vixilperse lignosulfonate, and 0.005% sodium fluorescein, and mixtures of Brilliant Blue plus Saturn Yellow and Brilliant Blue plus sodium fluorescein at the same concentrations. Solutions were deposited on citrus leaves and stability was determined by measuring fluorescence and optical density of solutions without drying, dried in the dark and exposed to sunlight for 2, 4 and 8 h. These values were compared to those obtained directly in water. The static surface tension of the tracer solution was determined by weighing droplets formed during a period of 20 to 40 seconds. The Brilliant Blue and Saturn Yellow mixture at 0.15% was stable under all conditions tested. It was not absorbed by the leaves and maintained the same surface tension as that of water, thus permitting concentration adjustment to the same levels used for agrochemical products, and allowing the development of a qualitative method based on visual evaluation of the distribution of the pigment under ultraviolet light and of a quantitative method based on the determination of the amount of the dye deposited in the same solution. Spray deposition could be evaluated at different surface tensions of the spraying solution, simulating the effect of agrochemical formulations

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Importance of sitka spruce <i>picea sitchensis</i> seed and garden bird-feeders for siskins <i>carduelis spinus</i> and coal tits <i>periparus ater</i>

Capsule Siskins and Coal Tits were present in gardens more often in years of poor Sitka Spruce cone crops, with synchrony across the UK. Aims To examine how the relative abundances of Siskins and Coal Tits in a garden in western Scotland varied annually with the size of the spruce cone crop, and to determine whether this pattern was similar nationally. Methods A ten-year mist-netting data set from Tarbet, Argyll and Bute was used to test the hypothesis that some species utilize supplementary food in gardens more often in years with poor cone crops than in years when crops are large. Annual peaks in the relative abundances of four species (two that ate conifer seed and two that did not) in Tarbet were correlated with a Sitka Spruce masting index. BTO Garden BirdWatch data from six regions of the UK were correlated with the Tarbet data, the cone index and each other to determine the extent of synchrony. Results Both Siskins and Coal Tits were present more often in the Tarbet garden in years with poor cone crops, with relative abundances significantly negatively correlated with cone crop for both species (r = -0.739 and -0.832, respectively). Correlations between regions using BTO data showed abundances of species in gardens to be broadly similar across the UK. Independent scores of cone abundance in Kielder and Galloway were correlated. Correlations between BTO data, cone index and Tarbet garden data were mostly high and almost all in the same direction, also indicating a degree of synchrony in cone production across the UK. Conclusion Both Siskins and Coal Tits appear to be influenced by changes in cone abundance, switching to feed on supplementary food in gardens more often in years with few cones than in mast years. While such a relationship has been shown previously for Siskins, for Coal Tits this is a novel resul