Visual Properties of Transgenic Rats Harboring the Channelrhodopsin-2 Gene Regulated by the Thy-1.2 Promoter

Channelrhodopsin-2 (ChR2), one of the archea-type rhodopsins from green algae, is a potentially useful optogenetic tool for restoring vision in patients with photoreceptor degeneration, such as retinitis pigmentosa. If the ChR2 gene is transferred to retinal ganglion cells (RGCs), which send visual information to the brain, the RGCs may be repurposed to act as photoreceptors. In this study, by using a transgenic rat expressing ChR2 specifically in the RGCs under the regulation of a Thy-1.2 promoter, we tested the possibility that direct photoactivation of RGCs could restore effective vision. Although the contrast sensitivities of the optomotor responses of transgenic rats were similar to those observed in the wild-type rats, they were enhanced for visual stimuli of low-spatial frequency after the degeneration of native photoreceptors. This result suggests that the visual signals derived from the ChR2-expressing RGCs were reinterpreted by the brain to form behavior-related vision

Deciphering morbid curiosity: Psychological mechanisms underlying the voluntary viewing of negative images

The principle of hedonism assumes that people pursue pleasure and positive experiences; however, we often observe that people voluntarily seek negative experiences in various daily settings—sometimes interpreted as the manifestation of “morbid curiosity.” This study tested four hypotheses to appraise people’s voluntary viewing of negative images: novelty/curiosity, metacognitive miscalibration, emotional arousal, and optimal stimulation. We used a paradigm in which participants could choose whether to view a positively or negatively valenced image. The results revealed that the rate of choosing to view positive and negative images decreased when participants had already seen the images previously. This result supports the novelty/curiosity hypotheses. However, contrary to the metacognitive miscalibration, emotional arousal, and optimal stimulation hypotheses, participants overestimated their negative feelings prior to viewing negative images, individual differences in sensation-seeking did not predict people’s choice of viewing negative images, and emotional arousal did not have an inverted-U relationship with choice behavior. These findings indicate a potential mechanism underlying people’s behavior in voluntarily seeking negative information, although we still observe a large unexplained variance vis-à-vis participants’ voluntary choice of negative images

社会的排斥に対する正統性評価尺度の作成

Ostracism, the act of ignoring, exclusion and rejection, occurs across the life span and has been documented as harmful and powerful not only for the ostracized member, but also for the ostracizing member and the observers. To ostracize others, individuals vary in the extent to which they evaluate ostracism as an effective and just method to promote group solidarity and efficiency. In this study, we developed and validated the Legitimacy of Ostracism Scale (LOS) that measures one’s tendency to accept ostracizing someone from a group as a legitimate action to increase group benefits. Japanese undergraduates (n = 513) completed a questionnaire including LOS (10 items), Machiavellianism, vigilance, relational models, and prevention focus. Exploratory factor analysis indicated a single-factor structure with seven items (α = .832). Confirmatory factor analysis on 7-item LOS also indicated that the data best fit a single-factor model. As theoretically predicted, LOS was positively correlated with Machiavellianism, vigilance, orientations for authority ranking and equality matching, and prevention focus. These results demonstrate the high reliability and validity of the 7-item LOS. Further studies need to show that LOS indicates one’s actual propensity to ostracize others

Transport mechanism and affinity of [99mTc]Tc-mercaptoacetyltriglycine ([99mTc]MAG3) on the apical membrane of renal proximal tubule cells

Technetium-99m-labeled mercaptoacetyltriglycine ([99mTc]MAG3) is widely used for evaluation of transplanted kidneys, diagnosis of tubular necrosis, and scintigraphic studies of tubular function. [99mTc]MAG3 is a substrate for organic anion transporter (OAT)1 and OAT3 on the basolateral membrane side for renal secretion. We investigated the transport mechanism and affinity of [99mTc]MAG3 on the apical membrane of renal proximal tubule cells for renal secretion. Adenosine triphosphate-binding cassette (ABC) transporters for renal secretion of [99mTc]MAG3 were examined using ABC transporter vesicles expressing multiple drug resistance 1 (MDR1), breast cancer resistance protein (BCRP), multidrug resistance-associated protein (MRP)2, and MRP4. MK-571, a MRP inhibitor, was applied to measure the Km and Vmax of MRP2 and MRP4 in a vesicle transport assay. Single photon emission computed tomography (SPECT) was performed in normal rats and MRP2-deficient Eisai hyperbilirubinuria rats (EHBR) using [99mTc]MAG3 with and without MK-571. [99mTc]MAG3 uptake in adenosine triphosphate was significantly higher than that in adenosine monophosphate in vesicles that highly expressed MRP2 and MRP4. The affinity of [99mTc]MAG3 for MRP4 was higher than that for MRP2. Renal secretion via MRP2 and MRP4 was identified by comparing normal and EHBR rats with and without MK-571 on SPECT. [99mTc]MAG3 is transported via MRP2 and MRP4 on the apical membrane of renal proximal tubule cells. The affinity of MRP4 is higher than that of MRP2

[131I]MIBG exports via MRP transporters and inhibition of the MRP transporters improves accumulation of [131I]MIBG in neuroblastoma

NTRODUCTION: (131)I-labeled m-iodobenzylguanidine ([(131)I]MIBG) has been used to treat neuroblastoma patients, but [(131)I]MIBG may be immediately excreted from the cancer cells by the adenosine triphosphate binding cassette transporters, similar to anticancer drugs. The purpose of this study was to clarify the efflux mechanism of [(131)I]MIBG in neuroblastomas and improve accumulation by inhibition of the transporter in neuroblastomas. METHODS: [(131)I]MIBG was incubated in human embryonic kidney (HEK)293 cells expressing human organic anion transporting polypeptide (OATP)1B1, OATP1B3, OATP2B1, organic anion transporter (OAT)1 and OAT2, organic cation transporter (OCT)1 and OCT2, and sodium taurocholate cotransporting polypeptide, and in vesicles expressing P-glycoprotein (MDR1), multidrug resistance associated protein (MRP)1-4, or breast cancer resistance protein with and without MK-571 and probenecid (MRP inhibitors). Time activity curves of [(131)I]MIBG with and without MK-571 and probenecid were established using an SK-N-SH neuroblastoma cell line, and transporter expression of multiple drug resistance was measured. Biodistribution and SPECT imaging examinations were conducted using [(123)I]MIBG with and without probenecid in SK-N-SH-bearing mice. RESULTS: [(131)I]MIBG uptake was significantly higher in OAT1, OAT2, OCT1, and OCT2 than in mock cells. Uptake via OCT1 and OCT2 was little inhibited by MK-571 and probenecid. [(131)I]MIBG uptake into vesicles that highly expressed MRP1 or MRP4 was significantly higher in ATP than in AMP, and these inhibitors restored uptake to levels similar to that in AMP. Examining the time activity curves for [(131)I]MIBG in SK-N-SH cells, higher expressions of MDR1, MRP1, MRP4, and MK-571, or probenecid loading produced significantly higher uptake than in control at most incubation times. The ratios of tumors to blood or muscle in SK-N-SH-bearing mice were significantly increased by probenecid loading in comparison with normal mice. CONCLUSIONS: [(131)I]MIBG exports via MRP1 and MRP4 in neuroblastoma. The accumulation and tumor-to-blood or muscle ratios of [(131)I]MIBG are improved by inhibition of MRPs with probenecid in neuroblastoma. ADVANCES IN KNOWLEDGE: [(131)I]MIBG, widely used for treatment of neuroendocrine tumors including neuroblastoma, is excreted via MRP1 and MRP4 in neuroblastoma. IMPLICATIONS FOR PATIENT CARE: Loading with probenecid, OAT, and MRP inhibitors improves [(131)I]MIBG accumulation

Different Efflux Transporter Affinity and Metabolism of 99m Tc-2-Methoxyisobutylisonitrile and 99m Tc-Tetrofosmin for Multidrug Resistance Monitoring in Cancer.

Little is known about the affinity and stability of Tc-labeled 2-methoxyisobutylisonitrile (Tc-MIBI) and tetrofosmin (Tc-TF) for imaging of multiple drug resistance transporters in cancer. We examined the affinity of Tc-labeled compounds for these transporters and their stability