Mitochondrial Na ϩ /Ca 2ϩ -Exchanger Blocker CGP37157 Protects against Chromaffin Cell Death Elicited by Veratridine

ABSTRACT Mitochondrial calcium (Ca 2ϩ ) dyshomeostasis constitutes a critical step in the metabolic crossroads leading to cell death. Therefore, we have studied here whether 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP37157; CGP), a blocker of the mitochondrial Na . This drastic cytoprotective effect of CGP could be explained in part through its regulatory actions on the mNCX. In general, it is accepted that a dysregulation of the mechanism that fine tunes the transient or more sustained levels of the cytosolic Ca 2ϩ concentrations ([Ca 2ϩ ] c ), leads to excitotoxic neuronal death ABBREVIATIONS: mNCX, mitochondrial Na ϩ /Ca 2ϩ -exchanger; DMSO, dimethyl sulfoxide; FPL64176, FPL, 2,5-dimethyl-4-[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylic acid methyl ester; 30 K ϩ /FPL, 30 mM K ϩ /0.3 M FPL; MTT formazan, 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan, thiazolyl blue formazan; CGP37157, 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one; TTX, tetrodotoxin citrate, octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethan o-10aH- [1,3] dioxocino [6,5-d]pyrimidin

Neuron 83, this issue

found in this control experiment: an offset in the motion coherence of the real stimulus biases the monkeys' choices and confidence ratings just like microstimulation did. In an elegant control experiment, Fetsch et al. (2014) sought to break the system apart. Instead of using low currents to stimulate a small patch of neurons with similar preferred orientations, the authors now injected a large amount of current that recruited a wider population of neurons including disparate preferred motion directions. This widespread activation resulted in a large increase in the number of sure bet choices, indicating that monkeys experienced noisy motion information and less confident decisions. The result illustrates at least two important issues. First, it demonstrates that monkeys are capable of reporting a large decrease in confidence and, second, it shows that the behavioral consequences of microstimulation are exquisitely dependent on the selectivity of the stimulated neurons. Large stimulation currents, instead of injecting additional information, indiscriminately recruit neuronal populations whose contributions can mask subtle sensory representations. The results reported by Fetsch et al. (2014) demonstrate that the mechanisms that read sensory evidence have access to the additional information added by microstimulation at the level of MT/MST. Future experiments should be aimed to identify the downstream neuronal circuits that read this evidence to decide whether to choose a safe bet or to risk for a larger reward. Importantly, these circuits must have learned, during behavioral training, the association between the amount of accumulated evidence and the likelihood that a given answer will be correct. What are the neuronal correlates of this learning? The answer will likely include the orchestrating functions of the frontal cortices, and also the modulatory effects of subcortical projection systems (de Lafuente and Romo, 2011; Schultz, 2013)

Measurements of branching fractions and CP-violating charge asymmetries in multibody charmless BB decays reconstructed in 2019-2020 Belle II data

We report on measurements of branching fractions ($\mathcal{B}$) and CP-violating charge asymmetries ($\mathcal{A}_{\rm CP}$) of multibody charmless $B$ decays reconstructed by the Belle II experiment at the SuperKEKB electron-positron collider. We use a sample of collisions collected in 2019 and 2020 at the $\Upsilon(4S)$ resonance and corresponding to $62.8$ fb$^{-1}$ of integrated luminosity. We use simulation to determine optimized event selections. The $\Delta E$ and $M_{\rm bc}$ distributions of the resulting samples are fit to determine signal yields of approximately 690, 840, and 380 decays for the channels $B^+ \to K^+K^-K^+$, $B^+ \to K^+\pi^-\pi^+$, and $B^0 \to K^+\pi^-\pi^0$, respectively. These yields are corrected for efficiencies determined from simulation and control data samples to obtain $\mathcal{B}(B^+ \to K^+K^-K^+) = [35.8 \pm 1.6(\rm stat) \pm 1.4 (\rm syst)]\times 10^{-6}$, $\mathcal{B}(B^+ \to K^+\pi^-\pi^+) = [67.0 \pm 3.3 (\rm stat)\pm 2.3 (\rm syst)]\times 10^{-6}$, $\mathcal{B}(B^0 \to K^+\pi^-\pi^0) = [38.1 \pm 3.5 (\rm stat)\pm 3.9 (\rm syst)]\times 10^{-6}$, $\mathcal{A}_{\rm CP}(B^+ \to K^+K^-K^+) = -0.103 \pm 0.042(\rm stat) \pm 0.020 (\rm syst)$, $\mathcal{A}_{\rm CP}(B^+ \to K^+\pi^-\pi^+) = -0.010 \pm 0.050 (\rm stat)\pm 0.021(\rm syst)$, and $\mathcal{A}_{\rm CP}(B^0 \to K^+\pi^-\pi^0) = 0.207 \pm 0.088 (\rm stat)\pm 0.011(\rm syst)$. Results are consistent with previous measurements and demonstrate detector performance comparable with the best Belle results