Proteins on the cell surface and secreted proteins are modified with sugar chains that generate and modulate biological complexity and diversity. Sugar chains not only contribute physically to the conformation and solubility of proteins, but also exert various functions via sugar-binding proteins that reside on the cell surface or in organelles of the secretory pathway. However, some glycosidases and lectins are found in the cytosol or nucleus. Recent studies of cytosolic sugar–related molecules have revealed that sugar chains on proteins in (...) the cytosol act as signals of adverse cellular conditions. In this review, we summarize recent reports that cytosolic sugar chains can trigger ubiquitination, followed by proteasomal and autophagic degradation to maintain cellular homeostasis. In addition, we discuss the functions of sugar-binding proteins revealed to date, along with possibilities not yet explored. The cytosolic N-glycans that normally reside on the cell surface or in organelles serves as a signal for the presence of unwanted proteins or organelles. Here, we review the monitoring system for cytosolic glycans including glycosidases and lectin in the cytosol. (shrink)

Cells utilize diverse organelles to maintain homeostasis and to respond to extracellular stimuli. Recently, multifaceted aspects of organelle stress caused by various factors have been emerging. The endosome is an essential organelle, functioning as the central hub for membrane trafficking in cooperation with the ubiquitin system. However, knowledge regarding endosomal stress, which refers to organelle stress of the endosome, is currently limited. We recently revealed ubiquitin‐mediated endosomal stress of early endosomes (EEs) and its responsive signaling pathways. These findings shed light (...) on the relevance of ubiquitin‐mediated endosomal stress to physiological and pathological processes. Here, we present a hypothesis that ubiquitin‐mediated endosomal stress may have significant roles in biological contexts and that ubiquitin‐specific protease 8 is a key regulator of ubiquitin clearance from EEs. (shrink)

The core aims of the Global Health Impact Project include incentivizing pharmaceutical companies for socially conscious production and promoting socially conscious consumption among consumers. Its backbone is a metric that computes the amount of illness burden alleviated by a pharmaceutical drug. This essay aims to assess the connection between values and numbers in the Global Health Impact Project. Specifically, I concentrate on two issues, the anonymity of illness burden and the distribution of health benefits. The former issue asks whether we (...) should treat the illness burden of every person the same. The latter issue asks among whom health benefits should be fairly distributed. Examination of these issues begs for clarification of some of the key concepts of the Global Health Impact Project, such as the definition of essential medicines and the significance of national borders. Although this essay focuses on the two particular metric issues in the Global Health Impact Project, its core argument is applicable to other metrics for ethically motivated initiatives—to construct a metric for an ethically motivated initiative, it is not only important to articulate underlying concepts and values, but it is also important to operationalize them, so they are consistently reflected in the metric. (shrink)

ObjectivesThe purpose of the current study was to examine whether a self-report measure identifies prenatal substance use and predicts resulting adverse birth outcomes in a large cohort using electronic medical records.MethodsPregnant patients who were admitted between 2014 and 2015 at Christiana Care Health System and delivered singleton birth were included in the analyses. Participant demographic information, pregnancy comorbidities, self-reported substance use, and birth outcomes were retrieved from electronic medical records. Detailed descriptive analyses of prenatal substance use were conducted, and logistic (...) models were evaluated for the associations between substance use and each birth outcome.ResultsThe average maternal age was 30 years, 37% receiving Medicaid. Over 58% were White, 26% were Black, and 13% were Hispanic. Cigarette smoking only showed the highest prevalence among substance u... (shrink)

Lysosomal positioning is an important factor in regulating cellular responses, including autophagy. Because proteins encoded by disease‐responsible genes are involved in lysosomal trafficking, proper intracellular lysosomal trafficking is thought to be essential for cellular homeostasis. In the past few years, the mechanisms of lysosomal trafficking have been elucidated with a focus on adapter proteins linking motor proteins to lysosomes. Here, we outline recent findings on the mechanisms of lysosomal trafficking by focusing on adapter protein c‐Jun NH2‐terminal kinase‐interacting protein (JIP) 4, (...) which plays a central role in this process, and other JIP4 functions and JIP family proteins. Additionally, we discuss neuronal diseases associated with aberrance in the JIP family protein. Accumulating evidence suggests that chemical manipulation of lysosomal positioning may be a therapeutic approach for these neuronal diseases. (shrink)

In studies publishing identifying personal information, obtaining consent is regarded as necessary, as it is impossible to ensure complete anonymity. However, current journal practices around specific points to consider when obtaining consent, the contents of consent forms and how consent forms are managed have not yet been fully examined. This study was conducted to identify potential issues surrounding consent to publish identifying personal information.

As I have pointed out in a series of papers, which appeared about fifteen years ago in the Revue de l'histoire des religions, there are numerous resemblances between the ancient myths of the Indo-Europeans, on the one hand, and those of Japan, on the other. These resemblances, relating both to the fundamental structures of the two mythological systems and to a number of curious details, constitute an assemblage which seems too conspicuous to be regarded as either accidental or the result (...) of a similitude of human mentalities, manifesting itself, so it seems, through the creation of a great many similar myths and legends throughout the length and breadth of the surface of our planet. (shrink)

This paper provides a detailed comparison between discourse representation theory and dependent type semantics, two frameworks for discourse semantics. Although it is often stated that DRT and those frameworks based on dependent types are mutually exchangeable, we argue that they differ with respect to variable handling, more specifically, how substitution and other operations on variables are defined. This manifests itself in two recalcitrant problems posed for DRT; namely, the overwrite problem and the duplication problem. We will see that these problems (...) still pose a challenge for various extended compositional systems based on DRT, while they do not arise in a framework of DTS where substitution and other operations are defined in the standard type-theoretic manner without stipulating any additional constraints. We also compare the notions of contexts underlying these two kinds of frameworks, namely, contexts represented as assignment functions and contexts represented as proof terms, and see what different predictions they make for some linguistic examples. (shrink)

新資料から、現代にも通ずる日本独自の豊かな死生観を探求した、江戸後期を代表する思想家としての新たな篤胤像を描き出す意欲作。.

The history of the documentation of health inequality is long. The way in which health inequality has customarily been documented is by comparing differences in the average health across groups, for example, by sex or gender, income, education, occupation, or geographic region. In the controversial World Health Report 2000, researchers at the World Health Organization criticized this traditional practice and proposed to measure health inequality across individuals irrespective of individuals’ group affiliation. They defended its proposal on the moral grounds without (...) clear explanation. In this paper I ask: is health inequality across individuals of moral concern, and, if so, why? Clarification of these questions is crucial for meaningful interpretation of health inequality measured across individuals. Only if there was something morally problematic in health inequality across individuals, its reduction would be good news. Specifically, in this paper I provide three arguments for the moral significance of health inequality across individuals: (a) health is special, (b) health equity plays an important and unique role in the general pursuit of justice, and (c) health inequality is an indicator of general injustice in society. I then discuss three key questions to examine the validity of these arguments: (i) how special is health?, (ii) how good is health as an indicator?, and (iii) what do we mean by injustice? I conclude that health inequality across individuals is of moral interest with the arguments (b) and (c). (shrink)

Emerging parallel to long-standing, academic and policy inquiries on personal responsibility for health is the empirical assessment of lay persons’ views. Yet, previous studies rarely explored personal responsibility for health among lay persons as dynamic societal values. We sought to explore lay persons’ views on personal responsibility for health using the Fairness Dialogues, a method for lay persons to deliberate equity issues in health and health care through a small group dialogue using a hypothetical scenario. We conducted two 2-h Fairness (...) Dialogues sessions (n = 15 in total) in Nova Scotia, Canada. We analyzed data using thematic analysis. Our analysis showed that personal choice played an important role in participants’ thinking about health. Underlying the concept of personal choice was considerations of freedom and societal debt. In participants’ minds, personal and social responsibilities co-existed and they were unwilling to determine health care priority based on personal responsibility. The Fairness Dialogues is a promising deliberative method to explore lay persons’ views as dynamic values to be developed through group dialogues as opposed to static, already-formed values waiting to be elicited. (shrink)

Perceptual grouping has traditionally been thought to be governed by innate, universal principles. However, recent work has found differences in Japanese and English speakers' non-linguistic perceptual grouping, implicating language in non-linguistic perceptual processes (Iversen, Patel, & Ohgushi, 2008). Two experiments test Japanese- and English-learning infants of 5-6 and 7-8 months of age to explore the development of grouping preferences. At 5-6 months, neither the Japanese nor the English infants revealed any systematic perceptual biases. However, by 7-8 months, the same age (...) as when linguistic phrasal grouping develops, infants developed non-linguistic grouping preferences consistent with their language's structure (and the grouping biases found in adulthood). These results reveal an early difference in non-linguistic perception between infants growing up in different language environments. The possibility that infants' linguistic phrasal grouping is bootstrapped by abstract perceptual principles is discussed. (shrink)

Tracheostomy with invasive ventilation may be required for the survival of patients at advanced stages of amyotrophic lateral sclerosis. In Japan it has been shown that a proactive approach toward TIV may prolong the survival of ALS patients by over 10 years by preventing the lethal respiratory failure that generally occurs within 3-5 years of the onset of the disease. Measures to prolong life expectancy without foregoing quality of life have produced better results in Japan than in other developed countries. (...) This ‘Japanese bias’ has been attributed to socio-cultural and religious factors as well as to the availability of material resources in Japan. In this article, we use the concepts of onozukara in kadō and amae to illuminate features of patient care that may contribute to this ‘Japanese bias’. (shrink)

The promised open space of cyber-interaction has its dark side hidden behind its brilliant rhetoric. The danger emerges within the very center of developing this technology (cyber-evolution). That is a more fundamental danger than this dark side seems to have. The possible replacement of our primary reality with virtual reality might erode the significance of our existential reality. This means also that the virtual reality might lose its own ground to be constructed. In order to clarify this fundamental problem at (...) issue I show some results from a questionnaire done on younger generation. The results seem to suggest possible way of facing this problem. (shrink)

本書は、人間的営みとしての学びの広さ・深さ・自由さを確認していく。人間の成長、人間形成という視点から、学びの実践を通して「学び」の人間学的原理、学ぶ主体にとっての意味を考察。個人の具体的な経験を通して 、多様な学びのあり方を提示。日本人の学び方、教え方の伝統や特徴とその問題について考察。.

Kei Yoshida critically assesses five different theoretical approaches to cultural interpretivism and conclusions on rationality. This book reveals the need for a cogent solution to the problem of rationality and urges social scientists to interpret symbolic systems' or agents’ intentions as well as explain the consequences of human actions.

儒教・仏教という知的伝統と、西洋哲学という新たな知が出会った明治。近代化と伝統の間で花開く新たな知の深層を明らかにする!

Although there are many historical and philosophical analyses of evolutionary developmental biology (EvoDevo), its development in the 1980s, when many individual or collective attempts to synthesize evolution and development were made, has not been examined in detail. This article focuses on some interdisciplinary studies during the 1980s and argues that they had important characteristics that previous historical and philosophical work has not recognized. First, we clarify how each set of studies from the 1980s integrated the results or approaches from different (...) biological fields, such as paleontology, developmental genetics, comparative morphology, experimental embryology, theoretical developmental biology, and population genetics. Second, after close examination we show that the interdisciplinary studies during the 1980s adopted different and conflicting views of genes, such as developmental-genetic, epigenetic, or population-genetic ones. We conclude that EvoDevo in the 1980s was a motley aggregation of various kinds of local integration. Finally, we discuss the implications of our analysis by comparing these early EvoDevo studies with those of the Modern Synthesis and with the present state of EvoDevo. (shrink)

ABSTRACTExperiences that contradict one's core concepts elicit intense emotions. Such schema incongruence can elicit awe, wherein experiences that are too vast...

江戸の豊穣な知性とコミュニケーションから生まれた平田篤胤の思想を、同時代のなかで読み解き、平田学派の書物をめぐる人々の様相、また書物そのものの動きを追う「書物の社会史」という視点から、史料をもって描き 出す。.