Consecutive Aryne Generation Strategy for the Synthesis of 1,3-Diarylpyrazoles.

An efficient method for the synthesis of diverse 1,3-diarylpyrazoles via consecutive aryne generation has been developed. The bisaryne precursors bearing o-iodo- and o-silylaryl triflate moieties were prepared by sequential Suzuki-Miyaura and Chan-Lam-Evans cross-coupling reactions. The selective generation of the first aryne triggered by a silylmethyl Grignard reagent followed by the second aryne generation mediated by a fluoride ion allowed for the synthesis of diverse multisubstituted 1,3-diarylpyrazoles in a modular synthetic manner with various arynophiles.

YPC-21661 and YPC-22026, novel small molecules, inhibit ZNF143 activity in vitro and in vivo.

Zinc-finger protein 143 (ZNF143) is a transcription factor that is involved in anticancer drug resistance and cancer cell survival. In the present study, we identified a novel small molecule N-(5-bromo-2-methoxyphenyl)-3-(pyridine-3-yl) propiolamide (YPC-21661) that inhibited ZNF143 promoter activity and down-regulated the expression of the ZNF143-regulated genes, RAD51, PLK1, and Survivin, by inhibiting the binding of ZNF143 to DNA. In addition, YPC-21661 was cytotoxic and induced apoptosis in the human colon cancer cell line, HCT116 and human prostate cancer cell line, PC-3. 2-(pyridine-3-ylethynyl)-5-(2-(trifluoromethoxy)phenyl)-1,3,4-oxadiazole (YPC-22026), a metabolically stable derivative of YPC-21661, induced tumor regression accompanied by the suppression of ZNF143-regulated genes in a mouse xenograft model. The present study revealed that the inhibition of ZNF143 activity by small molecules induced tumor regression in vitro and in vivo; therefore, ZNF143 is a promising target of cancer therapeutics.

Cobalt-catalyzed regioselective dehydrohalogenation of alkyl halides with dimethylphenylsilylmethylmagnesium chloride.

Cobalt-catalyzed reactions of haloalkanes with dimethylphenylsilylmethylmagnesium chloride result in highly regioselective dehydrohalogenation. The reaction does not follow the conventional E2 elimination mechanism but includes beta-hydride elimination from the corresponding alkylcobalt intermediate. The interesting reaction mechanism of the cobalt-catalyzed dehydrohalogenation offered unique transformations that are otherwise difficult to attain.

Effects of facial expression on shared attention mechanisms.

We investigated the effects of facial expression on shared attention mechanisms. A female or male facial stimulus with one of 3 facial expressions (happiness, neutral, or anger) was presented at the center of a display. This facial stimulus gazed toward a subject, or toward the left or right side of the display. After the facial stimulus was offset, a target appeared on the left or right side of the display and the reaction time to the target was measured. In the statistical analysis by ANOVA, there was a significant main effect of congruity between the target position and the gaze direction in both the female and male facial cues, indicating that gaze direction significantly affected reaction time. When the female facial cues were presented, the reaction times for the congruent target position to the gaze direction were significantly shorter in the happy than other facial expressions. However, there were no significant differences in reaction time when the facial stimuli were presented in an inverted orientation. The results demonstrated that facial expression significantly affected shared attention mechanisms.

Cobalt-catalyzed addition of styrylboronic acids to 2-vinylpyridine derivatives.

Treatment of 2-vinyl nitrogen-containing heteroaromatic compounds with styrylboronic acid in the presence of a cobalt catalyst and a base results in an addition reaction to afford the corresponding 4-phenyl-3-butenyl heteroarenes. The adjacent nitrogen atom is essential for the promotion of the reaction because the nitrogen accelerates the addition of the styryl cobalt species, generated by transmetalation, onto the vinyl group. The reaction represents a rare example of cobalt catalysis in the reactions of organoboronic acids.

Cobalt-catalyzed isomerization of 1-alkenes to (E)-2-alkenes with dimethylphenylsilylmethylmagnesium chloride and its application to the stereoselective synthesis of (E)-alkenylsilanes.

Treatment of 1-alkenes with dimethylphenylsilylmethylmagnesium chloride in the presence of a cobalt-NHC complex in dioxane at 50 degrees C or higher provides the corresponding (E)-2-alkenes selectively. The isomerization is applicable to the stereoselective synthesis of (E)-crotylsilanes and (E)-1-propenylsilanes from the corresponding homoallylsilanes and allylsilanes, respectively.

A study of the effect of the femoral head diameter on prosthetic hip joint dislocation using a hip-joint motion simulator.

Prosthetic hip joint dislocation phenomenon is generated by the hip joint simulator and the effect of the femoral head diameter is studied under the same condition which is similar to the condition in daily activities. Impedance control is applied to control the hip joint motion and the joint contact force simultaneously in order to take into account the constraint caused by surrounding tendons, muscles, and a joint capsule of the hip joint. The experimental results show that the hip joint dislocation phenomenon is generated by the simulator and the obtained results about the effect of the femoral head size agree with those of the other research.

Spatial firing properties of lateral septal neurons.

The present study describes the spatial firing properties of neurons in the lateral septum (LS). LS neuronal activity was recorded in rats as they performed a spatial navigation task in an open field. In this task, the rat acquired an intracranial self-stimulation reward when it entered a certain place, a location that varied randomly from trial to trial. Of 193 neurons recorded in the LS, 81 showed place-related activity. The majority of the tested neurons changed place-related activity when spatial relations between environmental cues were altered by rotating intrafield (proximal) cues. The comparison of place activities between LS place-related neurons recorded in the present study and hippocampal place cells recorded in our previous study, using identical behavioral and recording procedures, revealed that spatial parameters (spatial information content, coherence, and cluster size) were smaller in the LS than in the hippocampus. Of the 193 LS neurons, 86 were influenced by intracranial self-stimulation rewards; 31 of these 86 were also place-related. These results, together with previous anatomical and behavioral observations, suggest that the spatial information sent from the hippocampus to the LS is modulated by and interacts with signals related to reward in the LS.

Dopamine D1 receptors involved in locomotor activity and accumbens neural responses to prediction of reward associated with place.

Predicting reward is essential in learning approach behaviors. Dopaminergic activity has been implicated in reward, movement, and cognitive processes, all essential elements in learning. The nucleus accumbens (NAc) receives converging inputs from corticolimbic information-processing areas and from mesolimbic dopamine neurons originating in the ventral tegmental area. Previously, we reported that in mice, a dopamine D2 receptor knockout (D2R-KO) eliminated the prereward inhibitory response, increased place-field size of NAc neurons, and reduced locomotor activity without marked change in intracranial self-stimulation (ICSS) behavior. The present study investigated the specific contribution of dopamine D1 receptor (D1R) in mediating reward, locomotor activity, and spatial associative processes and in regulating NAc neural responses. In contrast to D2R-KO animals, here we find D1R-KO in mice selectively eliminated the prereward excitatory response and decreased place-field size of NAc neurons. Furthermore, D1R-KO impaired ICSS behavior, seriously reduced locomotor activity, and retarded acquisition of a place learning task. Thus, the present results suggest that D1R may be an important determinant in brain stimulation reward (ICSS) and participates in coding for a type of reward prediction of NAc neurons and in spatial learning.

Altered accumbens neural response to prediction of reward associated with place in dopamine D2 receptor knockout mice.

Midbrain dopaminergic activity seems to be important in forming the prediction of future events such as rewards. The nucleus accumbens (NAc) plays an important role in the integration of reward with motor function, and it receives dense dopamine innervation and extensive limbic and cortical afferents. Here, we examined the specific role of the dopamine D2 receptor (D2R) in mediating associative learning, locomotor activity, and regulating NAc neural responses by using D2R-knockout (KO) mice and their wild-type littermates. D2R-KO mice displayed reduced locomotor activity and slower acquisition of a place-learning task. D2R-KO eliminated the prereward inhibitory response of neurons in the NAc. In contrast, an increased number of neurons in D2R-KO mice displayed place-related activity. These results provide evidence that D2R in the NAc participates in coding for a specific type of neural response to incentive contingencies and partly in spatial learning.