心理学的レジリエンスは認知課題時のデフォルトモードネットワーク内の機能的結合性の動的変化と相関する

京都大学新制・課程博士博士(医学)甲第23069号医博第4696号新制||医||1049(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 髙橋 良輔, 教授 林 康紀, 教授 渡邉 大学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Origin of diverse phosphorylation patterns in the ERBB system

シグナル伝達による多様な細胞応答の起源 --実験と理論の融合による反応特性の決定. 京都大学プレスリリース. 2022-01-21.Intercellular signals induce various cellular responses, including growth, proliferation, and differentiation, via the dynamic processes of signal transduction pathways. For cell fate decisions, ligand-binding induces the phosphorylation of ERBB receptors, which in turn activate downstream molecules. The ERBB family includes four subtypes, which diverged through two gene duplications from a common ancestor. Differences in the expression patterns of the subtypes have been reported between different organs in the human body. However, how these different expression properties influence the diverse phosphorylation levels of ERBB proteins is not well understood. Here we study the origin of the phosphorylation responses by experimental and mathematical analyses. The experimental measurements clarified that the phosphorylation levels heavily depend on the ERBB expression profiles. We developed a mathematical model consisting of the four subtypes as monomers, homodimers, and heterodimers and estimated the rate constants governing the phosphorylation responses from the experimental data. To understand the origin of the diversity, we analyzed the effects of the expression levels and reaction rates of the ERBB subtypes on the diversity. The difference in phosphorylation rates between ERBB subtypes showed a much greater contribution to the diversity than did the dimerization rates. This result implies that divergent evolution in phosphorylation reactions rather than in dimerization reactions after whole genome duplications was essential for increasing the diversity of the phosphorylation responses

Map-guided surgery for atrial fibrillation

BackgroundAlthough current surgical procedures result in a high success rate for atrial fibrillation, they are not guided by electrophysiologic findings in individual patients and thus might include unnecessary incisions in some patients or be inappropriate for other patients. We sought to determine whether intraoperative mapping is beneficial for the surgical treatment of atrial fibrillation.MethodsA 256-channel 3-dimensional dynamic mapping system with custom-made epicardial patch electrodes was used to examine the atrial activation during atrial fibrillation and to determine the optimal procedure in 37 patients with continuous and 9 patients with intermittent atrial fibrillation intraoperatively.ResultsSurgical intervention for atrial fibrillation was not indicated in 3 patients in whom the atrial electrograms had a low voltage over a broad area. Concurrent, multiple, and repetitive activations arising from the pulmonary veins or left atrial appendage were observed in all patients. A simple left atrial procedure consisting of pulmonary vein isolation and left atrial incisions without any right atrial incisions was performed in 8 patients in whom the right atrial activation was passive, and all (100%) were cured of atrial fibrillation. The radial procedure was performed in the remaining 35 patients, and 31 (89%) of the patients were cured of atrial fibrillation. In this subset of patients, 10 exhibited reentrant or focal activation in the posterior left atrium between the right and left pulmonary veins and required an additional linear ablation on the posterior left atrium. The total amount of postoperative bleeding after the simple left atrial procedure was significantly less than after the radial procedure (378 ± 135 vs 711 ± 364 mL, P = .03). The right and left atrial transport functions were well preserved after both the radial and simple left atrial procedures.ConclusionIntraoperative mapping facilitates determining the optimal procedure for atrial fibrillation in each patient

Psychological resilience is correlated with dynamic changes in functional connectivity within the default mode network during a cognitive task

Resilience is a dynamic process that enables organisms to cope with demanding environments. Resting-state functional MRI (fMRI) studies have demonstrated a negative correlation between resilience and functional connectivities (FCs) within the default mode network (DMN). Considering the on-demand recruitment process of resilience, dynamic changes in FCs during cognitive load increases may reflect essential aspects of resilience. We compared DMN FC changes in resting and task states and their association with resilience. Eighty-nine healthy volunteers completed the Connor–Davidson Resilience Scale (CD-RISC) and an fMRI with an auditory oddball task. The fMRI time series was divided into resting and task periods. We focused on FC changes between the latter half of the resting period and the former half of the task phase (switching), and between the former and latter half of the task phase (sustaining). FCs within the ventral DMN significantly increased during “switching” and decreased during “sustaining”. For FCs between the retrosplenial/posterior cingulate and the parahippocampal cortex, increased FC during switching was negatively correlated with CD-RISC scores. In individuals with higher resilience, ventral DMN connectivities were more stable and homeostatic in the face of cognitive demand. The dynamic profile of DMN FCs may represent a novel biomarker of resilience