Mapping the ultrafast vibrational dynamics of all- trans and 13- cis retinal isomerization in Anabaena Sensory Rhodopsin

International audienceDiscrepancies in the isomerization dynamics and quantum yields of the trans and cis retinal protonated Schiff base is a well-known issue in the context of retinal photochemistry. Anabaena Sensory Rhodopsin (ASR) is a microbial retinal protein that comprises a retinal chromophore in two ground state (GS) conformations: all-trans, 15-anti (AT) and 13-cis, 15-syn (13C). In this work, we apply impulsive vibrational spectroscopic techniques (DFWM, pump-DFWM and pump-IVS) to ASR to shed more light on how the structural changes take place in the excited state within the same protein environment. Our findings point to distinct features in the ground state structural conformations as well as to drastically different evolutions in the excited state manifold. The ground state vibrational spectra show stronger Raman activity of the C14-H out-of-plane wag (at about 805 cm-1) for 13C than for AT isomer, which hints at a pre-distortion of the 13C in the ground state. Evolution of the Raman frequency after interaction with actinic pulse shows a blue shift for the C=C stretching and CH3 rocking mode for both isomers. For AT, however, the blue shift is not instantaneous as observed for the 13C isomer, rather it takes more than 200 fs to reach the maximum frequency shift. This frequency blue shift is rationalized by a decrease of the effective conjugation length during the isomerization reaction, which further confirms a slower formation of the twisted state for the AT isomer and corroborates the presence of a barrier in the excited state trajectory previously predicted by quantum chemical calculations

Meteor Radar Study of Ionospheric Wind at Kyoto

This paper describes the results of meteor radar observations which have been carried out at Kyoto University since December, 1977. The radar, a coherent pulse doppler radar with a transmitting frequency of 31.57 MHz and a nominal peak power of 10 kW, is able to detect wind fields at meteor regions of 80-110 km. The solar semidiurnal tide generally dominates the wind oscillations at these heights, while a diurnal tide of comparable magnitude reveals itself in a less regular manner. Some anomalies in the amplitude and phase characteristics of the tides are shown, which might be related to a possible interaction with winds and waves, or to some disturbed conditions in the earth's atmosphere. Also planetary scale waves such as quasi-2-day oscillations and resonantly magnified gravity-mode waves have also been found there. Hence, the meteor radar, together with its cooperation with other observations, will helps us understand the dynamical process of atmospheric waves on a global scale

The effect of modifiable healthy practices on higher-level functional capacity decline among Japanese community dwellers

This study aimed to clarify the effects of the accumulation of 8 modifiable practices related to health, including smoking, alcohol drinking, physical activity, sleeping hours, body mass index, dietary diversity, ikigai (life worth living), and health checkup status, on higher-level functional capacity decline among Japanese community dwellers. Data were derived from the National Institute for Longevity Sciences - Longitudinal Study of Aging. Subjects comprised 1269 men and women aged 40 to 79 years at baseline (1997–2000) who participated in a follow-up postal survey (2013). Higher-level functional capacity was measured using the Tokyo Metropolitan Institute of Gerontology Index of Competence (total score and 3 subscales: instrumental self-maintenance, intellectual activity, and social role). The odds ratio (OR) and 95% confidence interval (CI) for a decline in higher-level functional capacity in the follow-up study according to the total number of healthy practices were analyzed using the lowest category as a reference. Multivariate adjusted ORs (95% CIs) for the total score of higher-level functional capacity, which declined according to the total number of healthy practices (0–4, 5–6, 7–8 groups) were 1.00 (reference), 0.63 (0.44–0.92), and 0.54 (0.31–0.94). For the score of social role decline, multivariate adjusted ORs (95% CIs) were 1.00 (reference), 0.62 (0.40–0.97), and 0.46 (0.23–0.90), respectively (P for trend = 0.04). Having more modifiable healthy practices, especially in social roles, may protect against a decline in higher-level functional capacity among middle-aged and elderly community dwellers in Japan

Transformed diffuse large B-cell lymphoma from marginal zone lymphoma in the anterior mediastinum: A case report and review of the literature

Marginal zone lymphoma (MZL) arising from the anterior mediastinum is rare. In the majority of reported cases, the tumor was incidentally discovered, reflecting its indolent clinical features. We present a 38-year-old woman who had no medical history, and presented with a bulky anterior mediastinal tumor complicated by life-threatening compression of the vasculature and bronchi. Biopsy specimens of the neoplasm suggested transformed diffuse large B-cell lymphoma (DLBCL) from MZL. To our best knowledge, this is the first case report of anterior mediastinum MZL associated with an aggressive clinical course and life-threatening complications likely due to transformation to DLBCL

Effect of Preoperative Carbohydrate and Amino Acid Infusion on Postoperative Counter-Regulatory Hormone in Patients Undergoing Elective Thoracoscopic Esophagectomy

Compared with the conventional open surgery, thoracoscopic esophagectomy results in decreased thorax destruction, fewer postoperative complications, and shorter hospitalisation. However, preoperative fasting causes hyperglycemia, prompting attempts to improve postoperative hyperglycemia by preoperatively administering carbohydrate orally or intravenously. Herein, we examined the effect of preoperative carbohydrate and amino acid infusion on counter-regulatory hormone levels in patients undergoing elective thoracoscopic esophagectomy. The glucose and amino acid (GA) group (n=12) were infused with a low concentration of sugar accelerant and amino acid, and the control (GAF) group (n=12) was infused with a sugar-free extracellular fluid, until entering the operating room. We evaluated plasma catecholamine 3 fractions, cortisol, and glucose, as well as 3-methylhistidine in the urine. Adrenaline levels were significantly higher in the GAF group (263.0±201.8µIU/ml) than in the GA group (114.7±127.0µIU/ml) at the end of the surgery (P=0.042), and at postoperative day (POD) 1 (200.8±137.4 vs. 80.5±64.3µIU/ml; P=0.013). The noradrenalin level was also significantly higher in the GAF group (517.9±523.6µIU/ml) than in the GA group (254.3±205.4µIU/ml) at POD1 (P=0.028), as was the cortisol level (20.0±10.6µIU/ml vs. 10.2±8.0µIU/ml; P=0.015). No significant differences were observed between the two groups in levels of blood glucose or 3-methylhistidine in the urine. Preoperative glucose-amino acid administration improved catabolism suppression in this study

ノウコウソク ノ チリョウ セイセキ ワ ナゼ コウジョウ シナイ ノカ : 10ネンカン ノ ヤマガタケン ノウソッチュウ トウロク データ カラ ノ ヨゴ フリョウ インシ ノ ケントウ

　We studied ten years of stroke data registered with the Yamagata Society on Treatment for Cerebral Stroke（YSTCS）. The subjects included 16,407 cases of acute-phase cerebral infarction that were registered with the YSTCS during the ten years between 2002 and 2011. The cases were divided into two groups: the early phase group（2002-2006）and the late phase group（2007-2011）.　The clinical diagnoses included atherothrombotic cerebral infarction（AT）（n=7,196; 43.9%）, cardiogenic cerebral embolism（CE）（n=4,011; 24.4%）, and lacunar infarction（LI）（n=4,703; 28.7%）. The average age of the early phase group was 72.7±11.43 years, while that of the late phase group was 75.0±11.35 years; the difference was statistically significant. The proportion of CE cases increased in the late phase, while that of LI decreased. This phenomenon was more marked in cases involving patients of ≥80 years of age. In both the early and late phase groups, the AT and CE cases showed a significantly high proportion of poor outcomes. However, when age adjustment was implemented in the late phase group, the treatment outcomes improved across all clinical entities. A multiple logistic regression analysis revealed a significant association between old age, female sex, severe symptoms at onset, CE, a previous history of stroke, and a poor prognosis.　It is clear that developments in medicine have not kept pace with the advancement in the age at onset. The improvement of the outcomes of treatment for cerebral infarction requires further developments in acute-phase therapies and the primary prevention of cardiogenic cerebral embolism, many cases of which are severe

Analysis of the Evidence-practice Gap to Facilitate Proper Medical Care for the Elderly: Investigation, using Databases, of Utilization Measures for National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB)

As Japan becomes a super-aging society, presentation of the best ways to provide medical care for the elderly, and the direction of that care, are important national issues. Elderly people have multi-morbidity with numerous medical conditions and use many medical resources for complex treatment patterns. This increases the likelihood of inappropriate medical practices and an evidence-practice gap. The present study aimed to: derive findings that are applicable to policy from an elucidation of the actual state of medical care for the elderly; establish a foundation for the utilization of National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), and present measures for the utilization of existing databases in parallel with NDB validation. Cross-sectional and retrospective cohort studies were conducted using the NDB built by the Ministry of Health, Labor and Welfare of Japan, private health insurance claims databases, and the Kyoto University Hospital database (including related hospitals). Medical practices (drug prescription, interventional procedures, testing) related to four issues—potential inappropriate medication, cancer therapy, chronic kidney disease treatment, and end-of-life care—will be described. The relationships between these issues and clinical outcomes (death, initiation of dialysis and other adverse events) will be evaluated, if possible

STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes

STING炎症シグナルの終結分子機構 --新規細胞内分解システムの発見--. 京都大学プレスリリース. 2023-03-14.Stimulator of interferon genes (STING) is essential for the type I interferon response against a variety of DNA pathogens. Upon emergence of cytosolic DNA, STING translocates from the endoplasmic reticulum to the Golgi where STING activates the downstream kinase TBK1, then to lysosome through recycling endosomes (REs) for its degradation. Although the molecular machinery of STING activation is extensively studied and defined, the one underlying STING degradation and inactivation has not yet been fully elucidated. Here we show that STING is degraded by the endosomal sorting complexes required for transport (ESCRT)-driven microautophagy. Airyscan super-resolution microscopy and correlative light/electron microscopy suggest that STING-positive vesicles of an RE origin are directly encapsulated into Lamp1-positive compartments. Screening of mammalian Vps genes, the yeast homologues of which regulate Golgi-to-vacuole transport, shows that ESCRT proteins are essential for the STING encapsulation into Lamp1-positive compartments. Knockdown of Tsg101 and Vps4, components of ESCRT, results in the accumulation of STING vesicles in the cytosol, leading to the sustained type I interferon response. Knockdown of Tsg101 in human primary T cells leads to an increase the expression of interferon-stimulated genes. STING undergoes K63-linked ubiquitination at lysine 288 during its transit through the Golgi/REs, and this ubiquitination is required for STING degradation. Our results reveal a molecular mechanism that prevents hyperactivation of innate immune signalling, which operates at REs

Evaluation of Surgical Stress Associated with Video-assisted Thoracic Surgery for Esophageal Cancer According to Interleukin-6 Variation in Pleural Cavity Lavage Fluid

Esophagectomy for esophageal cancer is one of the most invasive gastrointestinal surgeries. In 1996, we introduced video-assisted thoracic surgery for esophageal cancer (VATS-E) to reduce surgical stress. In 2010, we started employing artificial pneumothorax (AP) using carbon dioxide gas in VATS-E to further reduce surgical stress. In this study, we evaluated interleukin-6 (IL-6) levels in pleural cavity lavage fluid (PLF) of patients undergoing VATS-E with or without AP, and examined the effect of AP on VATS-E-induced stress. This non-randomized study included patients who underwent VATS-E with or without AP at Showa University Hospital between 2009 and 2013 and from whom PLF could be collected. IL-6 concentrations in PLF were examined before and after the thoracic part of the operation. We compared IL-6 variation, defined as the difference between IL-6 concentrations in PLF before and after the thoracic part of the operation, between patients for whom AP was used and those for whom it was not used. A total of 52 patients were included in the study; 26 underwent VATS-E with AP (group AP), and 26 underwent VATS-E without AP (group NP). IL-6 concentrations in PLF were significantly elevated immediately after the thoracic part of the operation in both groups. IL-6 variation in PLF correlated with both thoracic operative time and blood loss, which were considered practical parameters of surgical stress, and was significantly lower in group AP than in group NP. In conclusion, IL-6 variation in PLF is a useful and sensitive maker of surgical stress during VATS-E. VATS-E with AP is less invasive than VATS-E without AP because AP lowers the perioperative systemic inflammatory response to thoracic surgery

Smaller Hippocampal Volume and Degraded Peripheral Hearing Among Japanese Community Dwellers

A growing body of literature has demonstrated that dementia and hearing loss are interrelated. Recent interest in dementia research has expanded to brain imaging analyses with auditory function. The aim of this study was to investigate the link between hearing ability, which was assessed using pure-tone audiometry, and the volume of brain regions, specifically the hippocampus, entorhinal cortex, Heschl’s gyrus, and total gray matter, using Freesurfer software and T1-weighted brain magnetic resonance imaging. The data for 2082 samples (age range = 40–89 years) were extracted from a population-based cohort of community dwellers. Hearing-impaired individuals showed significantly smaller hippocampal volumes compared with their non-hearing-impaired counterparts for all auditory frequency ranges. In addition, a correlational analysis showed a significant dose-response relationship for hearing ability and hippocampal volume after adjusting for potential confounding factors so that the more degraded the peripheral hearing was, the smaller the hippocampal volume was. This association was consistent through the auditory frequency range. The volume of the entorhinal cortex, right Heschl’s gyrus and total gray matter did not correlate with hearing level at any frequency. The volume of the left Heschl’s gyrus showed a significant relationship with the hearing levels for some auditory frequencies. The current results suggested that the presence of hearing loss after middle age could be a modifier of hippocampal atrophy