Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation

Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation, we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8(+) sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large-pore ion channels to specifically block nociceptors, substantially reduced ovalbumin- or house-dust-mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce the release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4(+) and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma

A Next-Generation Liquid Xenon Observatory for Dark Matter and Neutrino Physics

The nature of dark matter and properties of neutrinos are among the mostpressing issues in contemporary particle physics. The dual-phase xenontime-projection chamber is the leading technology to cover the availableparameter space for Weakly Interacting Massive Particles (WIMPs), whilefeaturing extensive sensitivity to many alternative dark matter candidates.These detectors can also study neutrinos through neutrinoless double-beta decayand through a variety of astrophysical sources. A next-generation xenon-baseddetector will therefore be a true multi-purpose observatory to significantlyadvance particle physics, nuclear physics, astrophysics, solar physics, andcosmology. This review article presents the science cases for such a detector.<br

Computerized respiratory sounds can differentiate smokers and non-smokers

Cigarette smoking is often associated with the development of several respiratory diseases however, if diagnosed early, the changes in the lung tissue caused by smoking may be reversible. Computerised respiratory sounds have shown to be sensitive to detect changes within the lung tissue before any other measure, however it is unknown if it is able to detect changes in the lungs of healthy smokers. This study investigated the differences between computerised respiratory sounds of healthy smokers and non-smokers. Healthy smokers and non-smokers were recruited from a university campus. Respiratory sounds were recorded simultaneously at 6 chest locations (right and left anterior, lateral and posterior) using air-coupled electret microphones. Airflow (1.0–1.5 l/s) was recorded with a pneumotachograph. Breathing phases were detected using airflow signals and respiratory sounds with validated algorithms. Forty-four participants were enrolled: 18 smokers (mean age 26.2, SD = 7 years; mean FEV1 % predicted 104.7, SD = 9) and 26 non-smokers (mean age 25.9, SD = 3.7 years; mean FEV1 % predicted 96.8, SD = 20.2). Smokers presented significantly higher frequency at maximum sound intensity during inspiration [(M = 117, SD = 16.2 Hz vs. M = 106.4, SD = 21.6 Hz; t(43) = −2.62, p = 0.0081, d z = 0.55)], lower expiratory sound intensities (maximum intensity: [(M = 48.2, SD = 3.8 dB vs. M = 50.9, SD = 3.2 dB; t(43) = 2.68, p = 0.001, d z = −0.78)]; mean intensity: [(M = 31.2, SD = 3.6 dB vs. M = 33.7,SD = 3 dB; t(43) = 2.42, p = 0.001, d z = 0.75)] and higher number of inspiratory crackles (median [interquartile range] 2.2 [1.7–3.7] vs. 1.5 [1.2–2.2], p = 0.081, U = 110, r = −0.41) than non-smokers. Significant differences between computerised respiratory sounds of smokers and non-smokers have been found. Changes in respiratory sounds are often the earliest sign of disease. Thus, computerised respiratory sounds might be a promising measure to early detect smoking related respiratory diseases

A next-generation liquid xenon observatory for dark matter and neutrino physics

The nature of dark matter and properties of neutrinos are among the most pressing issues in contemporary particle physics. The dual-phase xenon time-projection chamber is the leading technology to cover the available parameter space for weakly interacting massive particles, while featuring extensive sensitivity to many alternative dark matter candidates. These detectors can also study neutrinos through neutrinoless double-beta decay and through a variety of astrophysical sources. A next-generation xenon-based detector will therefore be a true multi-purpose observatory to significantly advance particle physics, nuclear physics, astrophysics, solar physics, and cosmology. This review article presents the science cases for such a detector