心拍変動解析を用いたイヌ : ヒト間の不快情動伝染に関する研究

【背景と目的】　共感性の基盤となる情動伝染は、他者の視点取得（相手の置かれている立場に立つこと）や心の理論（自身や他者の心的状態を推し量る能力）といった高次認知機能や心的機能を必要とせず、他者の情動表出を知覚することで自動的に自身の情動状態に変化を起こす現象である。この現象はヒトのみならず、社会性を有する動物種において広く存在することが明らかとなっている。情動伝染の特徴として、親和性の高い個体間でより成立しやすいこと、快情動よりも不快情動の方が成立しやすいことが挙げられる。これらのことから情動伝染が存在する意義は、危険を感知した個体の表出する情報を共有することで、危険そのものを察知した個体のみならず群れの他個体や群れそのものとしての生存価を上昇させるためにあることが示唆されているが、その進化的な起源やメカニズムには未解明な点が多い。情動伝染の進化的起源には3つの可能性が考えられる。1つ目は進化の早い段階で発生し、そのまま保存されてきた可能性、2つ目は進化の早い段階で発生したものの、種の分化に伴い種特異的になった可能性、そして3つ目は社会性のある種でそれぞれ独立して発生した可能性である。この点を検討するためには、異種間で情動伝染が成立するかを研究することが有用だろう。　イヌはヒトと3～4万年に及ぶ共生を経て、ヒトの出す様々な社会的・情動的シグナルに対する高い感受性を獲得したこと、また飼い主との間にヒトの母子間に類似した生物学的絆を形成するようになったことが行動学的、内分泌学的観点から報告されている。これらのイヌの特性は、ヒトとの間で情動伝染成立に必要な「他者の情動表出の知覚」と「高い親和性」を満たす。さらにイヌはペットとして飼育されている個体数が多いため、比較的被験対象を得やすい。これらのことから、異種間での情動伝染の有無を検討する場合、ヒト（飼い主）とイヌは適切な対象であると考えられる。そこで本研究では、異種間での情動伝染成立の有無を検証することを目的として、飼い主とイヌに着目し、2つの実験を行った。第1章では、イヌの情動変化の検出方法としての心拍変動解析の有用性について、第2章では飼い主に不快情動を惹起させ、その情動がイヌに伝染するかを行動解析ならびに心拍変動解析を用いて検証した。【方法】＜第1章：イヌの情動変化が心拍変動に与える影響＞　一般家庭で飼育されている健康なイヌを対象とした。イヌの情動状態を変化させる刺激として「ベースライン（イヌに対して何の注意も払わない飼い主と同じ実験室内にいる）」、「快刺激（飼い主によるストローク）」、「不快刺激（飼い主との分離）」をベースライン‐快刺激（または不快刺激）‐ベースライン‐不快刺激（または快刺激）‐ベースラインの順で呈示し、それぞれの刺激呈示時のイヌの行動および心拍変動をビデオカメラとイヌに装着した心電計を用いて記録した。呈示した快・不快刺激がそれぞれイヌの快・不快情動を惹起させたかを確認するために、快刺激、不快刺激とその直前のベースライン時のイヌの行動（姿勢の種類、ドアから1m以内での滞在、注視と探索、呼吸様式、鳴き声、尾振り）を解析し比較を行った。行動解析によるイヌの情動状態の確認後、イヌの快・不快情動が心拍変動に与える影響を観察するために、快刺激、不快刺激とその直前のベースライン時のイヌの心拍変動をそれぞれ比較した。心拍変動は姿勢の影響を除外するために各刺激呈示時に15秒同じ姿勢を維持している箇所を記録したデータの中から抜き出して解析した。解析は時間領域解析を行い、mean RRI（平均RR間隔）、SDNN（自律神経系全体の指標）およびRMSSD（副交感神経活性の指標）を比較に用いた。＜第2章：心拍変動解析を用いたヒト‐イヌ間の不快情動伝染の検討＞　一般家庭で飼育されている健康なイヌおよびその飼い主を対象に行った。イヌ－飼い主ペアにはそれぞれストレス下条件、コントロール条件の2回、それぞれの条件間に1週間以上の間隔を空けて参加してもらった。ストレス下条件では、実験室でヒトにストレスを負荷する方法として提唱されているTrier Social Stress Test（Kirschbaum et al., 1993）を一部改変したものを用いて飼い主に社会的ストレスを負荷した。コントロール条件では飼い主に社会的ストレスを与えなかった。ストレス下条件とコントロール条件の順番については、ペアによってカウンターバランスをとった。それぞれの条件下での飼い主およびイヌのストレスの程度を評価するために、心拍変動解析、ビデオによる行動解析を行った。飼い主に対してはそれらに加え、質問用紙による状態・特性不安検査を行いストレス負荷の程度を確認した。また心拍変動解析を用いて、微細な時系列での飼い主とイヌの同調の有無について測定するためにtime-binを15秒として飼い主とイヌのmean RRI、SDNN、RMSSDの相関分析を行った。さらにそこで得た相関係数と実験中のイヌおよび飼い主の行動や、年齢などのイヌの諸因子との間で相関分析を行った。【結果】＜第1章＞　行動解析の結果、ベースライン時と比較して、快刺激呈示時には「飼い主を注視・探索する時間」、「座位」、「立位」の姿勢をとっている時間が快刺激時に有意に増加し、「頭を床につけて臥位」、「ドアから1m以内での滞在」、「実験場所内の注視・探索」する時間が有意に減少した(すべてpHealthy dogs that lived with their owner family were studied. To change the dog\u27s emotional state, we used a positive stimulus (stroking by the owner) and a negative stimulus (separation from the owner) and we set a baseline (staying in the room with the owner but with no interaction) to compare with these emotional states. The stimulus and baseline were presented in a order of baseline-positive or negative stimulus-baseline-the opposite as the first stimulus-baseline and we recorded the changes of the electrocardiogram with a cardiography equipment and recorded the behavior with a video camera. To confirm whether the positive and negative stimuli that we exhibited elicited positive and negative emotions in dogs, the relative percentage of time that dogs spent in various behaviors (posture, standing by the door within 1m and orienting the door, attention and exploration, respiration, vocalization, tail wagging) in each situation were analyzed and compared those in positive and negative situation with those at just before baseline. After confirming dogs’ emotional state by behavioral analysis, The HRV parameters in each situation were compared with those at baseline. To exclude the influence of the change of posture on the HRV parameters, we selected 15 seconds RR intervals (RRI) period when dogs remained in the same posture at baseline and in each situation and calculated the HRV parameters; mean RRI (the average of RRI), SDNN (standard deviation of normal to normal RR intervals, that is a parameter of autonomic nerve system), and RMSSD (the root mean square of successive heartbeat interval differences, that is a parameter of parasympathetic nerve system).Healthy dogs that lived as pets and their owners participated. The dog-owner pair participated in the two different condition, in the control condition and stress condition, with and interval of more than one week. In stress condition, the owners got social stress using modified Trier Social Stress Test (Kirschbaum et al., 1993), which applies social stress for humans in the experimental situation. In control condition, the owners did not get social stress. The order of condition was counterbalanced by pairs. To evaluate the owners’ and dogs’ anxiety levels in each condition, we measured 5 minutes HRV parameters and 10 minutes behavioral analysis. In addition, owners asked to fill out the questionnaire (State-and Trait anxiety Inventory). Furthermore, RRI of dogs and owners were sampled as 15 seconds time-bins and calculated HRV parameters, mean RRI, SDNN, and RMSSD. We performed correlation analysis for these parameters between dogs and their owners to observing HRV synchronization between dogs and their owners. We also performed correlation analysis for correlation coefficients between dogs and their owners and various factors, like dog’s age and the percentage of behavior of dogs or owners in the experiment.ResultsAs a result of behavioral analysis, in positive situation, the time of “attention and exploration to their owner”, “sit”, and “stand” significantly increased. On the other hand, the time of “ lie down with their head on the floor”, “stand by the door within 1m with orienting the door” and “attention and exploration to the experimental room” significantly decreased (pFrom questionnaire, state-anxiety tended to increase in stress condition compared with in control condition (p=0.061). Trait-anxiety was not different between two conditions. As the result of the behavioral analysis, only “attention to their owners” of dogs increased longer in the stress condition (pFrom behavioral analysis, positive emotional state in dogs was elicited by “stroking by their owners” as positive stimulus. Negative emotional state in dogs was elicited by “separation from their owner” as negative stimulus. Each stimulus exhibited in the experiment was appropriate for eliciting each emotion in dogs. The result of HRV parameters were also different between in positive and in negative situation. SDNN decreased in positive situation. Some studies report that a decrease of SDNN is associated with stress in parallel with elevated heart rate (HR) or decreased RMSSD, on the other hand, there are a report that a decrease of SDNN in parallel with increased RMSSD in positive situation. We suggest that the decrease of SDNN not in parallel with a decreased HR or RMSSD is the indicator of low arousal positive emotional state like stroking. A decrease of RMSSD in negative situation is a same result that reported in previous studies in other animals. Therefore in dogs the decrease of RMSSD is a indicator of negative emotional state. Although the stimuli that elicited dogs’ emotion in chapter 1 were limited, it is obvious that emotional states reflects the HRV parameters in dogs and the response changed according to the emotional states.The result of questionnaire shows that the owners tended to feel mild stress in stress condition. The result of behavioral analysis indicated that dogs were attracted to their owners who showed some reactions in stress condition. Frans de Waal claims that “preconcern”, one is attracted to other when one perceives other that shows its emotional states like distress, occurs prior to empathy or sympathy in primates. We considered that increasing time of attention to the owners in stress condition, which may have occurred due to preconcern. 5 minutes and 15 seconds time-bin HRV analysis showed no evidence that suggests emotional contagion between dogs and their owners. However, in stress condition, there are significant correlation between correlation coefficients of HRV and dogs’ age and rearing period. Also, correlation tendencies were found between correlation coefficients of HRV and dogs’ posture, time of attention to the owner in the experiment in stress condition. From these results, emotional contagion exists between dogs and their owners when the owners feel stress, and it was suggested a trend that there are some factors, such as the time period being together, that may be effecting the establishment of emotional contagion. Conclusion.From the above mentioned results, we suggest that emotional contagion occurred at early stage of the evolution and saved. However, there is a report that dogs and humans coevolved for more than 30,000 years, therefore the results in this study may be supported by that special relations. To clarify this point, it is necessary to investigate whether emotional contagion exists in other interspecies in the future.博士(獣医学)麻布大学この博士論文は内容の要約のみの公開（または一部非公開）になっていま

Crystallographic texture- and grain boundary density-independent improvement of corrosion resistance in austenitic 316L stainless steel fabricated via laser powder bed fusion

Improvement of corrosion resistance of austenitic 316L stainless steel via laser powder bed fusion (LPBF) is currently a prominent research topic; however, the effects of crystallographic texture and the related grain boundary density on the corrosion resistance of LPBF-fabricated parts have not been elucidated. For biomedical applications, crystallographic texture control from a single crystalline-like to randomly oriented polycrystalline microstructure is highly attractive for optimizing the mechanical properties (particularly the Young's modulus) of implants. An investigation of the impacts of crystallographic planes and grain boundaries exposed to the biological environment on corrosion behavior is necessary. 316L stainless steels with different crystallographic textures and grain boundary densities were successfully fabricated via LPBF. The corrosion resistances of the LPBF-fabricated specimens were comprehensively assessed by anodic polarization, dissolution, and crevice corrosion repassivation tests. The LPBF-fabricated specimens showed extremely high pitting potentials in the physiological saline compared with the commercially available counterparts, and importantly, excellent pitting corrosion resistance was observed irrespective of the crystallographic planes and grain boundary density exposed. Moreover, the LPBF-fabricated specimens did not show metastable pitting corrosion even in an accelerated test using an acid solution. The repassivation behavior of the specimens was not affected by LPBF. Such a drastic improvement in the corrosion resistances of the LPBF-fabricated specimens might be attributed to suppression of inclusion coarsening owing to the rapid cooling rate during solidification in LPBF. By using LPBF, the desired crystallographic texture can be introduced based on the desired mechanical properties without concern for corrosiveness.Tsutsumi Y., Ishimoto T., Oishi T., et al. Crystallographic texture- and grain boundary density-independent improvement of corrosion resistance in austenitic 316L stainless steel fabricated via laser powder bed fusion. Additive Manufacturing, 45, 102066. https://doi.org/10.1016/j.addma.2021.102066

Non-HDL-C and CVD

Aims: We aimed to investigate the association between non-high-density lipoprotein cholesterol (non-HDL-C) levels and the risk of cardiovascular disease (CVD) and its subtypes. Methods: In this contemporary cohort study, we analyzed the data of 63,814 Japanese employees aged ≥ 30 years, without known CVD in 2012 and who were followed up for up to 8 years. The non-HDL-C level was divided into 5 groups: ＜110, 110-129, 130-149, 150-169, and ≥ 170 mg/dL. The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for CVD and its subtypes associated with each non-HDL-C group, considering 130-149 mg/dL as the reference group. Results: During the study period, 271 participants developed CVD, including 78 myocardial infarctions and 193 strokes (102 ischemic strokes, 89 hemorrhagic strokes, and 2 unknowns). A U-shaped association between non-HDL-C and stroke was observed. In the analysis of stroke subtypes, the multivariable-adjusted HR (95% CI) for hemorrhagic stroke was 2.61 (1.19–5.72), 2.02 (0.95–4.29), 2.10 (1.01–4.36), and 1.98 (0.96-4.08), while that for ischemic stroke was 1.54 (0.77-3.07), 0.91 (0.46-1.80), 0.73 (0.38-1.41), and 1.50 (0.87-2.56) in the ＜110, 110-129, 150-169, and ≥ 170 mg/dL groups, respectively. Individuals with elevated non-HDL-C levels had a higher risk of myocardial infarction. Conclusions: High non-HDL-C levels were associated with an increased risk of myocardial infarction. Moreover, high and low non-HDL-C levels were associated with a high risk of stroke and its subtypes among Japanese workers

Accelerator and Reactor Neutrino Oscillation Experiments in a Simple Three-Generation Framework

We present a new approach to the analysis of neutrino oscillation experiments, in the one mass-scale limit of the three-generation scheme. In this framework we reanalyze and recombine the most constraining accelerator and reactor data, in order to draw precise bounds in the new parameter space. We consider our graphical representations as particularly suited to show the interplay among the different oscillation channels. Within the same framework, the discovery potential of future short and long baseline experiments is also investigated, in the light of both the recent signal from the LSND experiment and the atmospheric neutrino anomaly.Comment: uuencoded compressed tar file. Figures (13) available by ftp to ftp://eku.sns.ias.edu/pub/lisi/ (192.16.204.30). Submitted to Physical Review

Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy

The expression of several cancer stem cell (CSC)-related markers has been confirmed in non-small cell lung cancer (NSCLC). The aim of this study was to clarify the clinical role of CSC-related markers in patients with NSCLC undergoing induction chemoradiotherapy (CRT). Fifty patients with clinically diagnosed N2 or N3 NSCLC who underwent induction CRT with docetaxel and cisplatin concurrently with thoracic radiation followed by surgery were examined in this study. The expressions of CSC related markers (CD133, ALDH1, ABCG2, and Bmi-1) were examined using immunohistochemical staining in surgically resected specimens. Among the 50 patients, 20 patients had no residual tumor cells in the resected specimen when examined pathologically; CSC-related marker expressions and their correlation to survival were evaluated in the other 30 patients. After a median follow-up period of 72 months, the 5-year overall survival rate of the patients with CD133-positive or ALDH1-positive specimens was significantly worse than that of the patients with both CD133-negative and ALDH1-negative expressions (449% vs. 90.0%, respectively; P=0.042). In a multivariate analysis. CD133 and ALDH1 negativity (P=0.047) and cN2-3 single station metastasis (P=0.03) were significant independent prognostic factors for prolonged survival. The expressions of CSC-related markers after CRT were significantly correlated with a poor prognosis in patients with NSCLC. The development of therapeutic strategies including adjuvant therapy that take CSC-related marker positivity into consideration is likely to be a key factor in further improvements of the prognosis of patients undergoing trimodality therapy

Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities

We developed a simple algorithm, i-Score (inhibitory-Score), to predict active siRNAs by applying a linear regression model to 2431 siRNAs. Our algorithm is exclusively comprised of nucleotide (nt) preferences at each position, and no other parameters are taken into account. Using a validation dataset comprised of 419 siRNAs, we found that the prediction accuracy of i-Score is as good as those of s-Biopredsi, ThermoComposition21 and DSIR, which employ a neural network model or more parameters in a linear regression model. Reynolds and Katoh also predict active siRNAs efficiently, but the numbers of siRNAs predicted to be active are less than one-eighth of that of i-Score. We additionally found that exclusion of thermostable siRNAs, whose whole stacking energy (ΔG) is less than −34.6 kcal/mol, improves the prediction accuracy in i-Score, s-Biopredsi, ThermoComposition21 and DSIR. We also developed a universal target vector, pSELL, with which we can assay an siRNA activity of any sequence in either the sense or antisense direction. We assayed 86 siRNAs in HEK293 cells using pSELL, and validated applicability of i-Score and the whole ΔG value in designing siRNAs

Discovery of naked charm particles and lifetime differences among charm species using nuclear emulsion techniques innovated in Japan

This is a historical review of the discovery of naked charm particles and lifetime differences among charm species. These discoveries in the field of cosmic-ray physics were made by the innovation of nuclear emulsion techniques in Japan. A pair of naked charm particles was discovered in 1971 in a cosmic-ray interaction, three years prior to the discovery of the hidden charm particle, J/Ψ, in western countries. Lifetime differences between charged and neutral charm particles were pointed out in 1975, which were later re-confirmed by the collaborative Experiment E531 at Fermilab. Japanese physicists led by K.Niu made essential contributions to it with improved emulsion techniques, complemented by electronic detectors. This review also discusses the discovery of artificially produced naked charm particles by us in an accelerator experiment at Fermilab in 1975 and of multiple-pair productions of charm particles in a single interaction in 1987 by the collaborative Experiment WA75 at CERN

Testing violations of special and general relativity through the energy dependence of nu_mu<--->nu_tau oscillations in the Super-Kamiokande atmospheric neutrino experiment

The atmospheric neutrino data collected by the Super-Kamiokande experiment span about four decades in neutrino energy E, and are thus appropriate to probe the energy dependence of the oscillation wavelength \lambda associated to nu_munu_tau flavor transitions, when these are assumed to explain the data. Such dependence takes the form \lambda^{-1}\propto E^n in a wide class of theoretical models, including ``standard'' oscillations due to neutrino mass and mixing (n=-1), energy-independent oscillations (n=0), and violations of the equivalence principle or of Lorentz invariance (n=1). We study first how the theoretical zenith distributions of sub-GeV, multi-GeV, and upward-going muon events change for different integer values of n. Then we perform a detailed analysis of the Super-Kamiokande data by treating the energy exponent n as a free parameter, with unconstrained scale factors for both the amplitude and the phase of nu_munu_tau oscillations. We find a best-fit range n=-0.9 \pm 0.4 at 90% C.L., which confirms the standard scenario (n=-1) as the dominant oscillation mechanism, and strongly constrains possible concurrent exotic processes (n \neq -1). In particular, we work out the interesting case of leading standard oscillations plus subleading terms induced by violations of special or general relativity principles, and obtain extremely stringent upper bounds on the amplitude of such violations in the (nu_mu,nu_tau) sector.Comment: 13 pages (RevTeX) + 6 figures (PostScript, color). Requires epsfig.st

Whole Genome Sequencing and Complete Genetic Analysis Reveals Novel Pathways to Glycopeptide Resistance in Staphylococcus aureus

The precise mechanisms leading to the emergence of low-level glycopeptide resistance in Staphylococcus aureus are poorly understood. In this study, we used whole genome deep sequencing to detect differences between two isogenic strains: a parental strain and a stable derivative selected stepwise for survival on 4 µg/ml teicoplanin, but which grows at higher drug concentrations (MIC 8 µg/ml). We uncovered only three single nucleotide changes in the selected strain. Nonsense mutations occurred in stp1, encoding a serine/threonine phosphatase, and in yjbH, encoding a post-transcriptional negative regulator of the redox/thiol stress sensor and global transcriptional regulator, Spx. A missense mutation (G45R) occurred in the histidine kinase sensor of cell wall stress, VraS. Using genetic methods, all single, pairwise combinations, and a fully reconstructed triple mutant were evaluated for their contribution to low-level glycopeptide resistance. We found a synergistic cooperation between dual phospho-signalling systems and a subtle contribution from YjbH, suggesting the activation of oxidative stress defences via Spx. To our knowledge, this is the first genetic demonstration of multiple sensor and stress pathways contributing simultaneously to glycopeptide resistance development. The multifactorial nature of glycopeptide resistance in this strain suggests a complex reprogramming of cell physiology to survive in the face of drug challenge