Aims: Cigarette smoke (CS) in active smokers and second-hand smoke exposure exacerbate respiratory disorders such as asthma and chronic bronchitis. While women are known to experience a more asthmatic response to CS than emphysema in men, there is limited information on the mechanisms of CS-induced airway dysfunction. We hypothesize that CS interferes with a normal (protective) bronchodilatory role of estrogens, thus worsening airway contractility. Methods: We tested effects of cigarette smoke extract (CSE) on 17β-estradiol (E₂) signaling in enzymatically-dissociated bronchial airway smooth muscle (ASM) obtained from lung samples of non-smoking female patients undergoing thoracic surgery. Results: In fura-2 loaded ASM cells, CSE increased intracellular calcium ([Ca²⁺]_i) responses to 10µM histamine. Acute exposure to physiological concentrations of E₂ decreased [Ca²⁺]_i responses. However, in 24h exposed CSE cells, although expression of estrogen receptors was increased, the effect of E₂ on [Ca²⁺]_i was blunted. Acute E₂ exposure also decreased store-operated Ca²⁺ entry and inhibited stromal interaction molecule 1 (STIM1) phosphorylation: effects blunted by CSE. Acute exposure to E₂ increased cAMP, but less so in 24h CSE-exposed cells. 24h CSE exposure increased S-nitrosylation of ERα. Furthermore, 24h CSE-exposed bronchial rings showed increased bronchoconstrictor agonist responses that were not reduced as effectively by E₂ compared to non-CSE controls. Conclusion: These data suggest that CS induces dysregulation of estrogen signaling in ASM, which could contribute to increased airway contractility in women exposed to CS.

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One factor affecting the qualia of music perception is the major/minor mode distinction. Major modes are perceived as more arousing, happier, positive, brighter, and less awkward than minor modes. This difference in emotionality of modes is also affected by pitch direction, with ascending pitch associated with positive affect and decreasing pitch with negative affect. The present study examined whether pitch direction influenced the identification of major versus minor musical modes. In six experiments, participants were familiarized with ascending and descending major and minor modes. We then played ascending and descending scales or simple eight-note melodies and asked listeners to identify the mode (major or minor). Identification of mode was moderated by pitch direction: major modes were identified more accurately when played with ascending pitch, and minor modes were identified better when played with descending pitch. Additionally, we replicated the difference in emotional affect between major and minor modes. The crossover pattern in mode identification may result from dual activation of positive and negative constructs, under specific combinations of mode and pitch direction.Keywords Music perception . Musical mode . Pitch direction Previous studies have examined the role that musical structure, such as tempo (fast versus slow), mode (major versus minor), consonance/dissonance, and pitch direction (ascending versus descending), has on tone discrimination, perceived

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