Effect of myocardial ischemia and nitroglycerin on systolic time intervals in the segmental myocardium

Effects of ischemia and nitroglycerin on systolic time intervals in the segmental myocardial length were studied in anesthetized open-chest dogs. Two strain-gauges were sutured on the surface of the left ventricular wall; one was in the central area perfused by the left circumflex coronary artery (LCX) and the other was in the area perfused by the left anterior descending coronary artery. LCX was partially occluded with a screw type constrictor to the degree at which reactive hyperemia after the transient total coronary occlusion almost disappeared. After the hemodynamics stabilized nitroglycerin (20 microgram/kg) was injected into the femoral vein. In the ischemic area, contraction time was shortened and precontraction time was prolonged in association with an elongation of end-systolic and early systolic segment-length, respectively. The systolic time intervals in the ischemic segment were improved as a result of the recovery in the segment-length toward the control. The results suggest the usefulness of analyzing the segmental myocardial systolic time intervals for verifying the asynchronous contraction of the ventricle and the favourable effects of nitroglycerin on segmental myocardial function in the ischemic area.</p

Lymph Node Stromal Cell Subsets

The spatiotemporal regulation of immune responses in the lymph node (LN) depends on its sophisticated tissue architecture, consisting of several subcompartments supported by distinct fibroblastic stromal cells (FSCs). However, the intricate details of stromal structures and associated FSC subsets are not fully understood. Using several gene reporter mice, we sought to discover unrecognized stromal structures and FSCs in the LN. The four previously identified FSC subsets in the cortex are clearly distinguished by the expression pattern of reporters including PDGFRb, CCL21-ser, and CXCL12. Herein, we identified a unique FSC subset expressing both CCL21-ser and CXCL12 in the deep cortex periphery (DCP) that is characterized by preferential B cell localization. This subset was clearly different fromCXCL12highLepRhigh FSCs in themedullary cord, which harbors plasma cells. B cell localization in the DCP was controlled chiefly by CCL21-ser and, to a lesser extent, CXCL12. Moreover, the optimal development of the DCP as well as medulla requires B cells. Together, our findings suggest the presence of a unique microenvironment in the cortex-medulla boundary and offer an advanced view of the multi-layered stromal framework constructed by distinct FSC subsets in the LN

A Distinct Subset of Fibroblastic Stromal Cells Constitutes the Cortex-Medulla Boundary Subcompartment of the Lymph Node

The spatiotemporal regulation of immune responses in the lymph node (LN) depends on its sophisticated tissue architecture, consisting of several subcompartments supported by distinct fibroblastic stromal cells (FSCs). However, the intricate details of stromal structures and associated FSC subsets are not fully understood. Using several gene reporter mice, we sought to discover unrecognized stromal structures and FSCs in the LN. The four previously identified FSC subsets in the cortex are clearly distinguished by the expression pattern of reporters including PDGFRβ, CCL21-ser, and CXCL12. Herein, we identified a unique FSC subset expressing both CCL21-ser and CXCL12 in the deep cortex periphery (DCP) that is characterized by preferential B cell localization. This subset was clearly different from CXCL12highLepRhigh FSCs in the medullary cord, which harbors plasma cells. B cell localization in the DCP was controlled chiefly by CCL21-ser and, to a lesser extent, CXCL12. Moreover, the optimal development of the DCP as well as medulla requires B cells. Together, our findings suggest the presence of a unique microenvironment in the cortex-medulla boundary and offer an advanced view of the multi-layered stromal framework constructed by distinct FSC subsets in the LN

Identification of amino acids in antigen-binding site of class II HLA proteins independently associated with hepatitis B vaccine response

Background & aimsGenetic factors in class II human leukocyte antigen (HLA) have been reported to be associated with inter-individual variation in hepatitis B virus (HBV) vaccine response. However, the mechanism underlying the associations remains elusive. In particular, the broad linkage disequilibrium in HLA region complicates the localization of the independent effects of genetic variants. Thus, the present study aimed to identify the most probable causal variations in class II HLA loci involved in the immune response to HBV vaccine.MethodsWe performed a case-control study to assess whether HLA-DRB1, -DQB1, and -DPB1 4-digit alleles were associated with the response to primary HBV vaccination in 574 healthy Japanese students. To identify causative variants, we next assessed independently associated amino acid variants in these loci using conditional logistic regression analysis. Furthermore, to clarify the functional effects of these variants on HLA proteins, we performed computational structural studies.ResultsHLA-DRB1∗01:01, HLA-DRB1∗08:03, HLA-DQB1∗05:01, and HLA-DPB1∗04:02 were significantly associated with sufficient response, whereas HLA-DPB1∗05:01 was associated with poor response. We then identified amino acids independently associated with sufficient response, namely, leucine at position 26 of HLA-DRβ1 and glycine-glycine-proline-methionine at positions 84–87 of HLA-DPβ1. These amino acids were located in antigen-binding pocket 4 of HLA-DR and pocket 1 of HLA-DP, respectively, which are important structures for selective binding of antigenic peptides. In addition, the detected variations in HLA-DP protein were responsible for the differences in the electrostatic potentials of the pocket, which can explain in part the sufficient/poor vaccine responses.ConclusionHLA-DRβ1 position 26 and HLA-DPβ1 positions 84–87 are independently associated with anti-HBs production against HBV vaccine. Our results suggest that HBsAg presentation through these HLA pocket structures plays an important role in the inter-individual variability of HBV vaccination

Laser-driven multi-MeV high-purity proton acceleration via anisotropic ambipolar expansion of micron-scale hydrogen clusters

強力なレーザーを使ってエネルギーがそろった純度100％の陽子ビーム発生に成功 --レーザー駆動陽子ビーム加速器の実現へ向けて大きく前進--. 京都大学プレスリリース. 2022-10-13.Multi-MeV high-purity proton acceleration by using a hydrogen cluster target irradiated with repetitive, relativistic intensity laser pulses has been demonstrated. Statistical analysis of hundreds of data sets highlights the existence of markedly high energy protons produced from the laser-irradiated clusters with micron-scale diameters. The spatial distribution of the accelerated protons is found to be anisotropic, where the higher energy protons are preferentially accelerated along the laser propagation direction due to the relativistic effect. These features are supported by three-dimensional (3D) particle-in-cell (PIC) simulations, which show that directional, higher energy protons are generated via the anisotropic ambipolar expansion of the micron-scale clusters. The number of protons accelerating along the laser propagation direction is found to be as high as 1.6 ±0.3 × 10⁹/MeV/sr/shot with an energy of 2.8 ±1.9 MeV, indicating that laser-driven proton acceleration using the micron-scale hydrogen clusters is promising as a compact, repetitive, multi-MeV high-purity proton source for various applications

microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity

褐色脂肪細胞の燃焼を促す新たなメカニズムを解明 --体の熱産生にマイクロRNA-33が関与--. 京都大学プレスリリース. 2021-02-17.Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33−/− mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33f/f dopamine-β-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)A receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33f/f DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress

フェムト秒レーザーと金属表面の相互作用により誘起されるレーザーナノアブレーション

京都大学0048新制・課程博士博士(理学)甲第18539号理博第4015号新制||理||1579(附属図書館)31439京都大学大学院理学研究科物理学・宇宙物理学専攻(主査)教授 阪部 周二, 教授 田中 貴浩, 准教授 橋田 昌樹学位規則第4条第1項該当Doctor of ScienceKyoto UniversityDGA

Simple formula for the interspaces of periodic grating structures self-organized on metal surfaces by femtosecond laser ablation

Self-organized grating structures formed on Mo and Ti metal surfaces irradiated with femtosecond laser pulses at wavelengths of 800 and 400 nm are investigated by electron microscopy. We observe the formation of the self-organized grating structures on the metals irradiated with 400-nm laser pulses at low laser fluence in narrow fluence ranges. The interspaces of the grating structure depend on the wavelength and fluence of the laser. We find that the dependence of the grating interspaces on laser fluence can be explained by a simple formula for induction of a surface-plasma wave through the parametric decay of laser light