ticipant's ability to successfully shift these patterns. Because neural variability is common in individuals poststroke, this illustrates a potential clinical benefit of this procedure.Purpose The purpose of this study was to examine the aging effects on the categorical perception (CP) of Mandarin lexical Tones 1-4 and Tones 1-2 in noise. It also investigated whether listeners' categorical tone perception in noise correlated with their general tone identification of 20 natural vowel-plus-tone signals in noise. Method Twelve younger and 12 older listeners with normal hearing were recruited in both tone identification and discrimination tasks in a CP paradigm where fundamental frequency contours of target stimuli varied systematically from the flat tone (Tone 1) to the rising/falling tones (Tones 2/4). Both tasks were conducted in quiet and noise with signal-to-noise ratios set at -5 and -10 dB, respectively, and general tone identification of natural speech signals was also tested in noise conditions. Results Compared with younger listeners, older listeners had shallower identification slopes and smaller discrimination peakedness in Tones 1-2/4 perception in all listening conditions, except for Tones 1-4 perception in quiet where no group differences were found. Meanwhile, noise affected Tones 1-2/4 perception The signal-to-noise ratio condition at -10 dB brought shallower slope in Tones 1-2/4 identification and less peakedness in Tones 1-4 discrimination for both listener groups. Older listeners' CP in noise, the identification slopes in particular, positively correlated with their general tone identification in noise, but such correlations were partially missing for younger listeners. Conclusions Both aging and the presence of speech-shaped noise significantly reduced the CP of Mandarin Tones 1-2/4. Listeners' Mandarin tone recognition may be related to their CP of Mandarin tones.Two types of voltage-dependent inward currents were evoked by depolarization in murine antral smooth muscle cells (SMCs) bathed in Ca2+-containing physiological solution high-voltage-activated (HVA) and low-voltage-activated (LVA) inward currents. We examined whether the LVA current was due to 1) T-type Ca2+ channels, 2) Ca2+-activated Cl-channels, 3) nonselective cation channels (NSCC), or 4) voltage-dependent K+ channels. Replacement of external Ca2+ (2 mM) with equimolar Ba2+ increased the amplitude of the HVA current but blocked the LVA current. Nicardipine blocked the HVA current, and in the presence of nicardipine, T-type Ca2+ blockers failed to block LVA current. A Cl- channel antagonist had little effect on LVA current. Cation-free external solution completely abolished both HVA and LVA currents. Addition of Ca2+ to the solution restored only HVA currents. Addition of K+ (5 mM) to otherwise cation-free solution induced LVA current that reversed at -20 mV. These data suggest that LVA current is not due to T-type Ca2+ channels, Ca2+-activated Cl- channels, or NSCC. A-type K+ (KA) currents and delayed rectifying K+ (KDR) currents can be resolved in antral SMCs dialyzed with a solution containing 140 mM K+. When cells were exposed to high K+ external solution and dialyzed with Cs+-rich solution in the presence of nicardipine, LVA current was evoked and reversed at positive potentials. LVA currents were blocked by K+ channel blockers, 4-aminopyridine, and tetraethylammonium. In conclusion, LVA inward currents can be generated by K+ influx via KA channels in murine antral SMCs when cells were dialyzed with Cs+-rich solution.Intestinal Tuft cells sense luminal contents to influence the mucosal immune response against eukaryotic infection. Paneth cells secrete antimicrobial proteins as part of the mucosal protective barrier. Defects in Tuft and Paneth cells occur commonly in various gut mucosal disorders. MicroRNA-195 (miR-195) regulates the stability and translation of target mRNAs and is involved in many aspects of cell processes and pathologies. Here, we reported the posttranscriptional mechanisms by which miR-195 regulates Tuft and Paneth cell function in the small intestinal epithelium. Mucosal tissues from intestinal epithelial tissue-specific miR-195 transgenic (miR195-Tg) mice had reduced numbers of double cortin-like kinase 1 (DCLK1)-positive (Tuft) and lysozyme-positive (Paneth) cells, compared with tissues from control mice, but there were no effects on Goblet cells and enterocytes. Intestinal organoids expressing higher miR-195 levels from miR195-Tg mice also exhibited fewer Tuft and Paneth cells. Transgenic expression of miR-195 in mice failed to alter growth of the small intestinal mucosa but increased vulnerability of the gut barrier in response to lipopolysaccharide (LPS). Studies aimed at investigating the mechanism underlying regulation of Tuft cells revealed that miR-195 directly interacted with the Dclk1 mRNA via its 3'-untranslated region and inhibited DCLK1 translation. Interestingly, the RNA-binding protein HuR competed with miR-195 for binding Dclk1 mRNA and increased DCLK1 expression. These results indicate that miR-195 suppresses the function of Tuft and Paneth cells in the small intestinal epithelium and further demonstrate that increased miR-195 disrupts Tuft cell function by inhibiting DCLK1 translation via interaction with HuR.Vascular smooth muscle (VSM) cell phenotypic expression and autophagic state are dynamic responses to stress. Vascular pathologies, such as hypoxemia and ischemic injury, induce a synthetic VSM phenotype and autophagic flux resulting in a loss of vascular integrity and VSM cell death respectfully. Both clinical pilot and experimental stroke studies demonstrate that sphingosine-1-phosphate receptor (S1PR) modulation improves stroke outcome; however, specific mechanisms associated with a beneficial outcome at the level of the cerebrovasculature have not been clearly elucidated. We hypothesized that ozanimod, a selective S1PR type 1 ligand, will attenuate VSM synthetic phenotypic expression and autophagic flux in primary human brain VSM cells following acute hypoxia plus glucose deprivation (HGD; in vitro ischemic-like injury) exposure.  https://www.selleckchem.com/products/ipi-549.html  Cells were treated with ozanimod and exposed to normoxia or HGD. Crystal violet staining, standard immunoblotting, and immunocytochemical labeling techniques assessed cellular morphology, vacuolization, phenotype, and autophagic state.