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Acetylcholine regulates intestinal epithelial secretion via muscarinic Gq-coupled receptors but its role in cell differentiation is unclear. Here, the authors show that Prox1-positive endocrine cells are sensors for the cholinergic intestinal niche and can trigger increased differentiation of enteroendocrine DCLK1-positive tuft cells.

Myocardial ischemia–reperfusion injury stabilizes the hypoxia-inducible factor HIF2-alpha. Here, the authors show that HIF2-alpha protects the heart from injury via induction of the epidermal growth factor amphiregulin, and that amphiregulin administration is cardioprotective in mice.

The complex three-way interaction between airflow, tissue, and sound, for asymmetric vocal fold vibration, is not well understood. Current modeling efforts are not able to explain clinical observations where drastic differences in sound production are often observed, with no noticeable differences in the vocal fold kinematics. To advance this understanding, an acoustical model for voiced sound generation in the presence of asymmetric intraglottal flows is developed. The source model operates in conjunction with a wave reflection analog propagation scheme and an asymmetric flow description within the glottis. To enable comparison with prior work, the source model is evaluated using a well-studied two-mass vocal fold model. The proposed source model is evaluated through acoustic measures of interest, including radiated sound pressure level, maximum flow declination rate, and spectral tilt, and also via its effects on the vocal fold dynamics. The influence of the model, in comparison to the standard symmetric Bernoulli flow description, results in an increased transfer of energy from the fluid to the vocal folds, increased radiated sound pressure level and maximum flow declination rate, and decreased spectral tilt. These differences are most pronounced for asymmetric vocal fold configurations that mimic unilateral paresis and paralysis, where minor kinematic changes can result in significant acoustic and aerodynamic differences. The results illustrate that fluid effects arising from asymmetric glottal flow can play an important role in the acoustics of pathological voiced speech.

The netrin family of secreted proteins provides migrational cues in the developing central nervous system. Recently, netrins have also been shown to regulate diverse processes beyond their functions in the brain, incluing the ochrestration of inflammatory events. Particularly netrin-1 has been implicated in dampening hypoxia-induced inflammation. Here, we hypothesized an anti-inflammatory role of endogenous netrin-1 in acute kidney injury (AKI). As homozygous deletion of netrin-1 is lethal, we studied mice with partial netrin-1 deletion (Ntn-1(+/-) mice) as a genetic model. In fact, Ntn-1(+/-) mice showed attenuated Ntn-1 levels at baseline and following ischemic AKI. Functional studies of AKI induced by 30 min of renal ischemia and reperfusion revealed enhanced kidney dysfunction in Ntn-1(+/-) mice as assessed by measurements of glomerular filtration, urine flow rate, urine electrolytes, serum creatinine and creatinine clearance. Consistent with these findings, histological studies indicated a more severe degree kidney injury. Similarly, elevations of renal and systemic inflammatory markers were enhanced in mice with partial netrin-1 deficiency. Finally, treatment of Ntn-1(+/-) mice with exogenous netrin-1 restored a normal phenotype during AKI. Taking together, these studies implicate endogenous netrin-1 in attenuating renal inflammation during AKI.