Social costs, limits to growth, right to growth: an approach to the global environment oriented to philosophy of law

The main Question of this paper is: how can we tackle the global warming in accordance with the economical growth especially in emerging countries? K. W. Kapp, “The Social Costs of Private Enterprise” (1950), defines the social costs as direct or indirect damages which are not compensated by the producer, but added to the third parties. An example might be the disaster of the BP plant in April 2010, in which the polluter can hardly cover all the damages so as to make the seawater clean, to regenerate the harmed natural lives and to recover the jobs and the everyday life of the residents on site. The Club of Rome, “The Limits to Growth” (1972), makes us aware of the five conditions which set the limits to growth: population, industrialization, pollution, consumption of food and natural resources, which tendentiously increase in a exponential progression. The GDP growth 10% a year means that it will be 2.59 times as large in ten years, whereas technology could resolve problematic concerning five elements at highest in arithmetical progression. Remarkable would be that the modern industrial civilization has brought social damages in form of global warming. Developed nations have not payed for it yet. All the people in the world should have right to economical growth at any rate, which would however be limited by those five conditions. Conclusion: the developed nations should give up the consumption lifestyle for the sake of equal right of every citizen in the world to reasonable standard of living

Neural Correlates of Attitude Change Following Positive and Negative Advertisements

Understanding changes in attitudes towards others is critical to understanding human behaviour. Neuropolitical studies have found that the activation of emotion-related areas in the brain is linked to resilient political preferences, and neuroeconomic research has analysed the neural correlates of social preferences that favour or oppose consideration of intrinsic rewards. This study aims to identify the neural correlates in the prefrontal cortices of changes in political attitudes toward others that are linked to social cognition. Functional magnetic resonance imaging (fMRI) experiments have presented videos from previous electoral campaigns and television commercials for major cola brands and then used the subjects' self-rated affinity toward political candidates as behavioural indicators. After viewing negative campaign videos, subjects showing stronger fMRI activation in the dorsolateral prefrontal cortex lowered their ratings of the candidate they originally supported more than did those with smaller fMRI signal changes in the same region. Subjects showing stronger activation in the medial prefrontal cortex tended to increase their ratings more than did those with less activation. The same regions were not activated by viewing negative advertisements for cola. Correlations between the self-rated values and the neural signal changes underscore the metric representation of observed decisions (i.e., whether to support or not) in the brain. This indicates that neurometric analysis may contribute to the exploration of the neural correlates of daily social behaviour

Novel method for immunofluorescence staining of mammalian eggs using non-contact alternating-current electric-field mixing of microdroplets

Recently, a new technique was developed for non-catalytically mixing microdroplets. In this method, an alternating-current (AC) electric field is used to promote the antigen-antibody reaction within the microdroplet. Previously, this technique has only been applied to histological examinations of flat structures, such as surgical specimens. In this study, we applied this technique for the first time to immunofluorescence staining of three-dimensional structures, specifically, mammalian eggs. We diluted an antibody against microtubules from 1:1,000 to 1:16,000, and compared the chromatic degree and extent of fading across dilutions. In addition, we varied the frequency of AC electricfield mixing from 5 Hz to 46 Hz and evaluated the effect on microtubule staining. Microtubules were more strongly stained after AC electric-field mixing for only 5 minutes, even when the concentration of primary antibody was 10 times lower than in conventional methods. AC electric-field mixing also alleviated microtubule fading. At all frequencies tested, AC electric-field mixing resulted in stronger microtubule staining than in controls. There was no clear difference in a microtubule staining between frequencies. These results suggest that the novel method could reduce antibody consumption and shorten immunofluorescence staining time

Activation of the pentose phosphate pathway in macrophages is crucial for granuloma formation in sarcoidosis

肉芽腫形成に特異的な代謝経路の発見 --ペントースリン酸回路の制御による新規治療--. 京都大学プレスリリース. 2023-12-01.More than skin-deep: Kyoto researchers discover metabolic pathway specific to granuloma formation in patients. 京都大学プレスリリース. 2023-12-07.Sarcoidosis is a disease of unknown etiology in which granulomas form throughout the body and is typically treated with glucocorticoids, but there are no approved steroid-sparing alternatives. Here, we investigated the mechanism of granuloma formation using single-cell RNA-Seq in sarcoidosis patients. We observed that the percentages of triggering receptor expressed on myeloid cells 2–positive (TREM2-positive) macrophages expressing angiotensin-converting enzyme (ACE) and lysozyme, diagnostic makers of sarcoidosis, were increased in cutaneous sarcoidosis granulomas. Macrophages in the sarcoidosis lesion were hypermetabolic, especially in the pentose phosphate pathway (PPP). Expression of the PPP enzymes, such as fructose-1, 6-bisphosphatase 1 (FBP1), was elevated in both systemic granuloma lesions and serum of sarcoidosis patients. Granuloma formation was attenuated by the PPP inhibitors in in vitro giant cell and in vivo murine granuloma models. These results suggest that the PPP may be a promising target for developing therapeutics for sarcoidosis

Mutations in SERPINB7, Encoding a Member of the Serine Protease Inhibitor Superfamily, Cause Nagashima-type Palmoplantar Keratosis

“Nagashima-type” palmoplantar keratosis (NPPK) is an autosomal recessive nonsyndromic diffuse palmoplantar keratosis characterized by well-demarcated diffuse hyperkeratosis with redness, expanding on to the dorsal surfaces of the palms and feet and the Achilles tendon area. Hyperkeratosis in NPPK is mild and nonprogressive, differentiating NPPK clinically from Mal de Meleda. We performed whole-exome and/or Sanger sequencing analyses of 13 unrelated NPPK individuals and identified biallelic putative loss-of-function mutations in SERPINB7, which encodes a cytoplasmic member of the serine protease inhibitor superfamily. We identified a major causative mutation of c.796C>T (p.Arg266∗) as a founder mutation in Japanese and Chinese populations. SERPINB7 was specifically present in the cytoplasm of the stratum granulosum and the stratum corneum (SC) of the epidermis. All of the identified mutants are predicted to cause premature termination upstream of the reactive site, which inhibits the proteases, suggesting a complete loss of the protease inhibitory activity of SERPINB7 in NPPK skin. On exposure of NPPK lesional skin to water, we observed a whitish spongy change in the SC, suggesting enhanced water permeation into the SC due to overactivation of proteases and a resultant loss of integrity of the SC structure. These findings provide an important framework for developing pathogenesis-based therapies for NPPK

Novel inhibitor for prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis and details of substrate-recognition mechanism.

A new inhibitor, H-Ala-Ile-pyrrolidin-2-yl boronic acid, was developed as an inhibitor against prolyl tripeptidyl aminopeptidase with a K(i) value of 88.1 nM. The structure of the prolyl tripeptidyl aminopeptidase complexed with the inhibitor (enzyme-inhibitor complex) was determined at 2.2 A resolution. The inhibitor was bound to the active site through a covalent bond between Ser603 and the boron atom of the inhibitor. This structure should closely mimic the structure of the reaction intermediate between the enzyme and substrate. We previously proposed that two glutamate residues, Glu205 and Glu636, are involved in the recognition of substrates. In order to clarify the function of these glutamate residues in substrate recognition, three mutant enzymes, E205A, E205Q, and E636A were generated by site-directed mutagenesis. The E205A mutant was expressed as an inclusion body. The E205Q mutant was expressed in soluble form, but no activity was detected. Here, the structures of the E636A mutant and its complex with the inhibitor were determined. The inhibitor was located at almost the same position as in the wild-type enzyme-inhibitor complex. The amino group of the inhibitor interacted with Glu205 and the main-chain carbonyl group of Gln203. In addition, a water molecule in the place of Glu636 of the wild-type enzyme interacted with the amino group of the inhibitor. This water molecule was located near the position of Glu636 in the wild-type and formed a hydrogen bond with Gln203. The k(cat)/K(M) values of the E636A mutant toward the two substrates used were smaller than those of the wild-type by two orders of magnitude. The K(i) value of our inhibitor for the E636A mutant was 48.8 microM, which was 554-fold higher than that against the wild-type enzyme. Consequently, it was concluded that Glu205 and Glu636 are significant residues for the N-terminal recognition of a substrate

Attentat, Terror, Gerechtigkeit

Attentat, Terror, Gerechtigkeit : eine vergleichende Studie zu B. Savinko J. Osaragi, K. Takahashi und A. Camus. - Würzburg : Ergon-Verl., 2002. - 263 S. - (Spektrum Philosophie ; 23). - Zugl.: Augsburg, Univ., Diss., 200

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