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An increasing number of pathogenic variants in presynaptic proteins involved in the synaptic vesicle cycle are being discovered in neurodevelopmental disorders. The clinical features of these synaptic vesicle cycle disorders are diverse, but the most prevalent phenotypes include intellectual disability, epilepsy, movement disorders, cerebral visual impairment, and psychiatric symptoms (Verhage and Sørensen, 2020; Bonnycastle et al., 2021; John et al., 2021; Melland et al., 2021). Among this growing list of synaptic vesicle cycle disorders, the most frequent is STXBP1 encephalopathy caused by de novo heterozygous pathogenic variants in syntaxin-binding protein 1 (STXBP1, also known as MUNC18-1; Verhage and Sørensen, 2020; John et al., 2021). STXBP1 is an essential protein for presynaptic neurotransmitter release. Its haploinsufficiency is the main disease mechanism and impairs both excitatory and inhibitory neurotransmitter release. However, the disease pathogenesis and cellular origins of the broad spectrum of neurological phenotypes are poorly understood. Here we generate cell type-specific Stxbp1 haploinsufficient male and female mice and show that Stxbp1 haploinsufficiency in GABAergic/glycinergic neurons causes developmental delay, epilepsy, and motor, cognitive, and psychiatric deficits, recapitulating majority of the phenotypes observed in the constitutive Stxbp1 haploinsufficient mice and STXBP1 encephalopathy. In contrast, Stxbp1 haploinsufficiency in glutamatergic neurons results in a small subset of cognitive and seizure phenotypes distinct from those caused by Stxbp1 haploinsufficiency in GABAergic/glycinergic neurons. Thus, the contrasting roles of excitatory and inhibitory signaling reveal GABAergic/glycinergic dysfunction as a key disease mechanism of STXBP1 encephalopathy and suggest the possibility to selectively modulate disease phenotypes by targeting specific neurotransmitter systems. [ABSTRACT FROM AUTHOR]

The Geostationary Environmental Monitoring Spectrometer (GEMS) is a UV-visible spectrometer onboard the GEO-KOMPSAT-2B satellite launched into geostationary orbit in February 2020. To evaluate GEMS NO2 column data, comparison was carried out using NO2 vertical column density (VCD) measured using direct-sunlight observations by the Pandora spectrometer system at four sites in Seosan, South Korea, during November 2020 to January 2021. Correlation coefficients between GEMS and Pandora NO2 data at four sites ranged from 0.35 to 0.48, with root mean square errors (RMSEs) from 4.7 × 1015 molec. cm-2 to 5.5 × 1015 molec. cm-2 for cloud fraction (CF) < 0.7. Higher correlation coefficients of 0.62-0.78 with lower RMSEs from 3.3 × 1015 molec. cm-2 to 4.3 × 1015 molec. cm-2 were found with CF < 0.3, indicating the higher sensitivity of GEMS to atmospheric NO2 in less-cloudy conditions. Overall, GEMS NO2 column data tend to be lower than those of Pandora due to differences in representative spatial coverage, with a large negative bias under high-CF conditions. With correction for horizontal representativeness in Pandora measurement coverage, the correlation coefficients range from 0.69 to 0.81 with RMSEs from 3.2 × 1015 molec. cm-2 to 4.9 × 1015 molec. cm-2 were achieved for CF < 0.3, showing the better correlation with the correction than that without the correction. [ABSTRACT FROM AUTHOR]

According to the dual entitlement principle, consumers find it fair for firms to price asymmetrically to cost changes--that is, for firms to increase prices when costs increase but maintain prices when costs decrease. However, a meta-analysis reveals asymmetric pricing is less prevalent in collectivistic (vs. individualistic) countries (study 1). We propose a fairness-based explanation, demonstrating that interdependent consumers in collectivistic cultures perceive asymmetric pricing to be less fair than do independent consumers in individualistic cultures (studies 2, 4, and 5). We attribute this cultural variation to culture-specific relationship norms. Specifically, we argue that while the practice of asymmetric pricing is consistent with the exchange norms among independent consumers that emphasize self-interest pursuit, it is inconsistent with the communal norms among interdependent consumers mandating firm benevolence. Supporting this argument, we find that (a) directly manipulating communal (vs. exchange) norms yields similar differences in fairness perceptions that mimic those due to culture (study 3), (b) the cultural differences are mediated by the communal mandate for firm benevolence (study 4), and (c) the cultural differences are mitigated when a firm frames asymmetric pricing as benevolent (study 5). We conclude by discussing the theoretical and managerial implications of these findings. [ABSTRACT FROM AUTHOR]

* PURPOSE: To evaluate the therapeutic effect of intravitreal bevacizumab injection for symptomatic retinal arterial macroaneurysm. * DESIGN: Retrospective interventional case series. * METHODS: The study included 23 patients (23 eyes)with symptomatic retinal arterial macroaneurysm. They were categorized according to treatment method into 2 groups: an intravitreal bevacizumab-treated group (11 eyes) and an untreated group (12 eyes). Bevacizumab was injected at the initial visit, followed by as-needed monthly reinjection. Best-corrected visual acuity (BCVA) and central macular thickness were documented and analyzed between groups. * RESULTS: The mean follow-up period for all subjects was 10.83 ± 4.6 months. The mean number of injections for the treated group was 1.42 ± 0.69.Themean logarithm of the minimal angle of resolution (logMAR) of BCVA improved from baseline at the last follow-up by 0.26 in the bevacizumab-treated group (P = .02) and by 0.34 in the untreated group (P=.005). Average central macular thickness decreased from 384.4 ± 150.1 mm to 265 ± 112.5 mm in the bevacizumab-treated group (P = .0002) and from 413.2 ± 155.2 mm to 236.3 ± 103.5 mm in the untreated group (P = .008). The BCVA was significantly improved from baseline after 1 month in the bevacizumab-treated group (P = .02) and after 3 months in the untreated group (P = .01). However, there was no statistically significant difference in BCVA improvement or central macular thickness improvement achieved at the final visit. * CONCLUSIONS: Intravitreal bevacizumab injection likely hastens resolution of macular edema and hemorrhage secondary to retinal arterial macroaneurysm. Intravitreal bevacizumab injection could be an effective treatment option for symptomatic retinal arterial macroaneurysm. [ABSTRACT FROM AUTHOR]