Prospective and retrospective values integrated in frontal cortex drive predictive choice

予測に基づいて行動を選ぶ脳の回路の発見 --2次運動野が担う予測的な行動選択--. 京都大学プレスリリース. 2023-01-30.Animals must flexibly estimate the value of their actions (action-value) to successfully adapt to a changing environment. The brain is thought to estimate action-values from two different sources, namely the action-outcome history (retrospective value) and the knowledge of the environment (prospective value), but how different estimates of action-values are reconciled to make a choice is not well understood. Here we found that as mice learn the state-transition structure of a decision-making task, retrospective and prospective values become jointly encoded in the preparatory activity of neurons in ALM. Suppressing this preparatory activity in expert mice returned their behavior to a naïve state. These results reveal the neural circuit that injects structural knowledge into action selection to promote predictive decision-making

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Association of autosomal‐recessive‐type distal renal tubular acidosis and Glanzmann thrombasthenia as a consequence of runs of homozygosity

Abstract We report the case of a Filipino girl with autosomal‐recessive‐type distal renal tubular acidosis and Glanzmann thrombasthenia caused by homozygous variants in the genes SLC4A1 and ITGA2B within the long homozygous DNA region on chromosome 17q21.31. This haplotype may be retained among individuals of Filipino descent

Annealed ZnO/Al2O3 Core-Shell Nanowire as a Platform to Capture RNA in Blood Plasma

RNA analytical platforms gained extensive attention recently for RNA-based molecular analysis. However, the major challenge for analyzing RNAs is their low concentration in blood plasma samples, hindering the use of RNAs for diagnostics. Platforms that can enrich RNAs are essential to enhance molecular detection. Here, we developed the annealed ZnO/Al2O3 core-shell nanowire device as a platform to capture RNAs. We showed that the annealed ZnO/Al2O3 core-shell nanowire could capture RNAs with high efficiency compared to that of other circulating nucleic acids, including genomic DNA (gDNA) and cell-free DNA (cfDNA). Moreover, the nanowire was considered to be biocompatible with blood plasma samples due to the crystalline structure of the Al2O3 shell which serves as a protective layer to prevent nanowire degradation. Our developed device has the potential to be a platform for RNA-based extraction and detection

Significance of gene mutations in the Wnt signaling pathway in traditional serrated adenomas of the colon and rectum.

Recent studies have shown that colorectal serrated lesions, which include sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs), are precursors of colorectal cancer. However, the molecular mechanisms underlying the carcinogenesis, particularly in TSAs, remain largely uncharacterized. To clarify their molecular and clinicopathological characteristics, we performed mutation and methylation analyses of cancer-associated genes in 78 serrated lesions, including TSAs, SSAs and microvesicular hyperplastic polyps. Target exon sequence analysis was performed with 39 genes, including genes known to be frequently mutated in colorectal cancers and/or serrated lesions. We also used bisulfite pyrosequencing to assess the methylation status of various cancer-associated genes and marker genes of the CpG island methylator phenotype (CIMP). The prevalence of mutations in genes associated with Wnt signaling was significantly higher in TSAs than SSAs (65% vs. 28%, p < 0.01). Among those, RNF43 mutations were observed in 38% of TSAs and 17% of SSAs. In immunohistochemical studies of 39 serrated lesions, the prevalence of abnormal nuclear β-catenin accumulation was significantly higher in TSAs (57%) than SSAs (8%) (P = 0.01). SMOC1 methylation was detected in 54% of TSAs but in no SSAs (p < 0.01). Additionally, SMOC1 methylation was more prevalent among TSAs with KRAS mutation (82%) than with BRAF mutation (38%, p = 0.03). Lesions with CIMP-high or RNF43 mutations were detected only in TSAs with BRAF mutation, suggesting two distinct carcinogenic pathways in TSAs. Mutations in genes associated with Wnt signaling play a greater role in the carcinogenesis of TSAs than SSAs

Novel Photosensitizer β-Mannose-Conjugated Chlorin e6 as a Potent Anticancer Agent for Human Glioblastoma U251 Cells

A photosensitizer is a molecular drug for photodynamic diagnosis and photodynamic therapy (PDT) against cancer. Many studies have developed photosensitizers, but improvements in their cost, efficacy, and side effects are needed for better PDT of patients. In the present study, we developed a novel photosensitizer &beta;-mannose-conjugated chlorin e6 (&beta;-M-Ce6) and investigated its PDT effects in human glioblastoma U251 cells. U251 cells were incubated with &beta;-M-Ce6, followed by laser irradiation. Cell viability was determined using the Cell Counting Kit-8 assay. The PDT effects of &beta;-M-Ce6 were compared with those of talaporfin sodium (TS) and our previously reported photosensitizer &beta;-glucose-conjugated chlorin e6 (&beta;-G-Ce6). Cellular uptake of each photosensitizer and subcellular distribution were analyzed by fluorescence microscopy. &beta;-M-Ce6 showed 1000&times; more potent PDT effects than those of TS, and these were similar to those of &beta;-G-Ce6. &beta;-M-Ce6 accumulation in U251 cells was much faster than TS accumulation and distributed to several organelles such as the Golgi apparatus, mitochondria, and lysosomes. This rapid cellular uptake was inhibited by low temperature, which suggested that &beta;-M-Ce6 uptake uses biological machinery. &beta;-M-Ce6 showed potent PDT anti-cancer effects compared with clinically approved TS, which is a possible candidate as a next generation photosensitizer in cancer therapy