Theoretical study on ultrafast intersystem crossing of chromium(III) acetylacetonate

In the relaxation process from the ^4T_[2g] state of chromium(III) acetylacetonate, Cr^III(acac)_3, ultrafast intersystem crossing (ISC) competes with vibrational relaxation (VR). This contradicts the conventional cascade model, where ISC rates are slower than VR ones. We hence investigate the relaxation process with quantum chemical calculations and excited-state wavepacket simulations to obtain clues about the origins of the ultrafast ISC. It is found that a potential energy curve of the ^4T_[2g] state crosses those of the ^2T_[1g] states near the Franck–Condon region and their spin–orbit couplings are strong. Consequently, ultrafast ISC between these states is observed in the wavepacket simulation

Approaches to Identify Inhibitors of Melanin Biosynthesis via the Quality Control of Tyrosinase

Tyrosinase, a copper-containing glycoprotein, is the rate-limiting enzyme critical for melanin biosynthesis in specialized organelles termed melanosomes that are produced only by melanocytic cells. Inhibitors of tyrosinase activity have long been sought as therapeutic means to treat cutaneous hyperpigmentary disorders. Multiple potential approaches exist that could control pigmentation via the regulation of tyrosinase activity, for example: the transcription of its messenger RNA, its maturation via glycosylation, its trafficking to melanosomes, as well as modulation of its catalytic activity and/or stability. However, relatively little attention has been paid to regulating pigmentation via the stability of tyrosinase, which depends on its processing and maturation in the endoplasmic reticulum and Golgi, its delivery to melanosomes and its degradation via the ubiquitin-proteasome pathway and/or the endosomal/lysosomal system. Recently, it has been shown that carbohydrate modification, molecular chaperone engagement, and ubiquitylation all play pivotal roles in regulating the degradation/stability of tyrosinase. While such processes affect virtually all proteins, such effects on tyrosinase have immediate and dramatic consequences on pigmentation. In this review, we classify melanogenic inhibitory factors in terms of their modulation of tyrosinase function and we summarize current understanding of how the quality control of tyrosinase processing impacts its stability and melanogenic activity

Long-term maintenance of human induced pluripotent stem cells by automated cell culture system.

自動培養装置によるヒトiPS細胞の長期間培養に成功 . 京都大学プレスリリース. 2015-11-27.Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem (iPS) cells, are regarded as new sources for cell replacement therapy. These cells can unlimitedly expand under undifferentiated conditions and be differentiated into multiple cell types. Automated culture systems enable the large-scale production of cells. In addition to reducing the time and effort of researchers, an automated culture system improves the reproducibility of cell cultures. In the present study, we newly designed a fully automated cell culture system for human iPS maintenance. Using an automated culture system, hiPS cells maintained their undifferentiated state for 60 days. Automatically prepared hiPS cells had a potency of differentiation into three germ layer cells including dopaminergic neurons and pancreatic cells

A Case of Vaginal Varices that Caused Massive Bleeding after Vaginal Delivery

Article信州医学雑誌 64(1):35-39 (2016)journal articl

Le corpus PhoDiFLE : un corpus commun de français langue étrangère pour une étude phonétique des productions de locuteurs de langues maternelles plurielles

PhoDiFLE est un corpus créé pour permettre la comparaison entre des productions phonétiques de français natifs et d’apprenants, à des fins didactiques. Nous présentons ici les questionnements qui ont guidé notre réflexion dans la réalisation de ce corpus. À travers une démarche mixte (guidée par corpus et fondée sur corpus), nous nous intéressons aux écarts de réalisations avec la « norme », selon l’origine des locuteurs. Des analyses acoustiques et perceptives conduisent à la création d’outils intégrés de formalisation, de représentation, de remédiation et d’évaluation selon la langue d’origine de chaque apprenant.The PhoDiFLE corpus has been developed to enable researchers, especially those concerned with remedial phonetics, to compare French native speakers and foreign learners utterances in French. This article examines the issues that had to be dealt with while creating this corpus. Our approach combines corpus-driven and corpus-based studies and focuses on the phonetic variants across native and non-native speakers. Acoustic and perceptual analyses allow to compare their productions. This corpus will finally result in the making of tools aiming to formalise, represent, correct and assess the variants observed in learners of French as a Second Language

The somatic mutations in Interferon-γ signal molecules in human uterine leiomyosarcoma

Human uterine leiomyosarcoma (U-LMS) is neoplastic malignancy that typically arises in tissues of mesenchymal origin. The identification of novel molecular mechanism leading to human U-LMS formation and the establishment of new therapies has been hampered by several critical points. We earlier reported that mice with a homozygous deficiency for proteasome beta subunit 9 (Psmb9)/β1i, an interferon (IFN)-γ inducible factor, spontaneously develop U-LMS. The use of research findings of the experiment with mouse model has been successful in increasing our knowledge and understanding of how alterations, in relevant oncogenic, tumour suppressive, and signaling pathways directly impact sarcomagenesis. The IFN-γ pathway is important for control of tumour growth and invasion and has been implicated in several malignant tumours. In this study, experiments with human tissues revealed a defective expression of PSMB9/β1i in human U-LMS that was traced to the IFN-γ pathway and the specific effect of somatic mutations of JANUS KINASE (JAK) 1 molecule or promoter region on the locus cording PSMB9/β1i gene. Understanding the molecular mechanisms of human U-LMS may lead to identification of new diagnostic candidates or therapeutic targets against human U-LMS

The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis

C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with beta 2-glycoprotein I (beta 2GPI), implicating oxLDL/P2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/beta 2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/R2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and beta 2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of adierosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/beta 2GPI complexes correlated with total cholesterol and hemoglobin Al c. Thus, the generation of CRP/oxLDL/beta 2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/R2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis

Beneficial effect of branched-chain amino acid supplementation on glycemic control in chronic hepatitis C patients with insulin resistance: Implications for type 2 diabetes

Branched-chain amino acids (BCAAs) improve disorders of albumin metabolism, quality of life, subjective symptoms, and prognosis in patients with chronic hepatitis. However, it remains unclear whether they improve insulin resistance. We examined the effects of BCAAs on glucose tolerance and insulin sensitivity in patients with chronic hepatitis C and insulin resistance. Individuals with a definitive diagnosis of chronic hepatitis C and insulin resistance were eligible for participation. Eligible participants were randomly assigned to the BCAA group or a control group. Participants were then crossed over to the other treatment for a further 12 weeks. Baseline clinical features, laboratory markers, fatty acid levels, and insulin sensitivity, assessed with oral glucose tolerance tests and a hyperinsulinemic euglycemic clamp, were also examined before and 12 and 24 weeks after the beginning of the study. Of the 27 patients who completed the study, 14 began in the BCAA group and 13 began as controls. There were no significant differences in glucose metabolism parameters or lipid profiles between the groups. HbA1c values were improved in 10 patients and worsened or remained unchanged in 17 patients. The only predictive variable for change in HbA1c was the baseline Matsuda index: the lower the index, the greater the improvement in HbA1c values. BCAA therapy did not have adverse effects on glucose tolerance or insulin sensitivity in patients with chronic hepatitis C and insulin resistance. Moreover, it had a therapeutic effect on HbA1c values in patients with marked peripheral (primarily muscle) insulin resistance. © 2012 Elsevier Inc