Dopamine D_1 Receptors and Nonlinear Probability Weighting in Risky Choice

Misestimating risk could lead to disadvantaged choices such as initiation of drug use (or gambling) and transition to regular drug use (or gambling). Although the normative theory in decision-making under risks assumes that people typically take the probability-weighted expectation over possible utilities, experimental studies of choices among risks suggest that outcome probabilities are transformed nonlinearly into subjective decision weights by a nonlinear weighting function that overweights low probabilities and underweights high probabilities. Recent studies have revealed the neurocognitive mechanism of decision-making under risk. However, the role of modulatory neurotransmission in this process remains unclear. Using positron emission tomography, we directly investigated whether dopamine D_1 and D_2 receptors in the brain are associated with transformation of probabilities into decision weights in healthy volunteers. The binding of striatal D_1 receptors is negatively correlated with the degree of nonlinearity of weighting function. Individuals with lower striatal D_1 receptor density showed more pronounced overestimation of low probabilities and underestimation of high probabilities. This finding should contribute to a better understanding of the molecular mechanism of risky choice, and extreme or impaired decision-making observed in drug and gambling addiction

Effect of Zn substitution for Cu on Ca2−x_{2-x}Nax_{x}CuO2_{2}Cl2_{2} near the hole concentration of 1/8 per Cu

A weakening of superconductivity upon substitution of Cu by Zn (0.5~1 %) is observed in a high-T_c cuprate, Ca_{2-x}Na_xCuO2Cl2, near the hole concentration of 1/8 per Cu. The superconducting transition temperature and its volume fraction, estimated by magnetic susceptibility, exhibit a sizable anomaly for x=0.12~0.14, where the slowing down of Cu spin fluctuations below 5 K is demonstrated by muon spin relaxation experiments. These observations are in close resemblance to other typical cuprates including YBa2Cu3O_{7-d}, and Bi2Sr2Ca_{1-x}Y_xCu2O_{8+d}, providing further evidence that Zn-induced "stripe" correlation is a universal feature of high-T_c cuprate superconductors common to that of La_{2-x}A_{x}CuO4 (A=Ba, Sr).Comment: 4 pages, 3 figure

Japanese multicenter database of healthy controls for [¹²³I]FP-CIT SPECT

Purpose: The aim of this multicenter trial was to generate a [¹²³I]FP-CIT SPECT database of healthy controls from the common SPECT systems available in Japan. Methods: This study included 510 sets of SPECT data from 256 healthy controls (116 men and 140 women; age range, 30–83 years) acquired from eight different centers. Images were reconstructed without attenuation or scatter correction (NOACNOSC), with only attenuation correction using the Chang method (ChangACNOSC) or X-ray CT (CTACNOSC), and with both scatter and attenuation correction using the Chang method (ChangACSC) or X-ray CT (CTACSC). These SPECT images were analyzed using the Southampton method. The outcome measure was the specific binding ratio (SBR) in the striatum. These striatal SBRs were calibrated from prior experiments using a striatal phantom. Results: The original SBRs gradually decreased in the order of ChangACSC, CTACSC, ChangACNOSC, CTACNOSC, and NOACNOSC. The SBRs for NOACNOSC were 46% lower than those for ChangACSC. In contrast, the calibrated SBRs were almost equal under no scatter correction (NOSC) conditions. A significant effect of age was found, with an SBR decline rate of 6.3% per decade. In the 30–39 age group, SBRs were 12.2% higher in women than in men, but this increase declined with age and was absent in the 70–79 age group. Conclusions: This study provided a large-scale quantitative database of [¹²³I]FP-CIT SPECT scans from different scanners in healthy controls across a wide age range and with balanced sex representation. The phantom calibration effectively harmonizes SPECT data from different SPECT systems under NOSC conditions. The data collected in this study may serve as a reference database

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Optimization Method for Operation Schedule of Microgrids Considering Uncertainty in Available Data

Operation scheduling in electric power grids is one of the most practical optimization problems as it sets a target for the efficient management of the electric power supply and demand. Advancement of a method to solve this issue is crucially required, especially in microgrids. This is because the operational capability of microgrids is generally lower than that of conventional bulk power grids, and therefore, it is extremely important to develop an appropriate, coordinated operation schedule of the microgrid components. Although various techniques have been developed to solve the problem, there is no established solution. The authors propose a problem framework and a solution method that finds the optimal operation schedule of the microgrid components considering the uncertainty in the available data. In the authors’ proposal, the objective function of the target problem is formulated as the expected cost of the microgrid’s operations. Since the risk of imbalance in the power supply and demand is evaluated as a part of the objective function, the necessary operational reserve power is automatically calculated. The usefulness of the proposed problem framework and its solution method was verified through numerical simulations and the results are discussed

Changes in Dopamine Synthesis after Risperidone Administration in Patients with Schizophrenia: A Positron Emission Tomography Study with [11C]DOPA

The 8th NeuroReceptor Mapping Congress (NRM2010