Pdz adaptors: Their regulation of epithelial transporters and involvement in human diseases

金沢大学医薬保健研究域薬学系Homeostasis in the body is at least partially maintained by mechanisms that control membrane permeability, and thereby serve to control the uptake of essential substances (e.g., nutrients) and the efflux of unwanted substances (e.g., xenobiotics and metabolites) in epithelial cells. Various transporters play fundamental roles in such bidirectional transport, but little is known about how they are organized on plasma membranes. Protein-protein interactions may play a key role: several transporters in epithelial cells interact with the so-called adaptor proteins, which are membrane anchored and interact with both transporters and other membranous proteins. Although most of the evidences for transporter-adaptor interaction has been obtained in vitro, recent studies suggest that adaptor-mediated transporter regulation does occur in vivo and could be relevant to human diseases. Thus, protein-protein interaction is not only associated with the formation of macromolecular complexes but is also involved in various cellular events, and may provide transporters with additional functionality by forming transporter networks on plasma membranes. Interactions between xenobiotic transporters and PSD95/Dlg/ZO1 (PDZ) adaptors were previously reviewed by Kato and Tsuji (2006. Eur J Pharm Sci 27:487-500); the present review focuses on the latest findings about PDZ adaptors as regulators of transporter networks and their potential role in human diseases. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci © 2011 Wiley-Liss, Inc

超吸水性ポリマー球状塞栓物質の高張食塩水を用いた膨潤抑制法の開発

PURPOSE: To analyze size changes of superabsorbent polymer (SAP) microspheres with the reduced expansion technique, and to evaluate pharmacological advantages of transarterial chemoembolization using cisplatin-loaded SAP microspheres with the reduced expansion technique. MATERIALS AND METHODS: In an in vitro study, diluted contrast materials containing different concentrations of sodium ions were examined to expand SAP microspheres and determined the reduced expansion technique. Size distributions of cisplatin-loaded SAP microspheres were analyzed. In an in vivo study, TACE was performed using cisplatin-loaded SAP microspheres with the reduced expansion and control techniques in 18 VX2 rabbits. RESULTS: The degree of expansion was reduced to the greatest extent by using a mixture of non-ionic contrast material and 10% NaCl at a 4:1 ratio. The mean diameter of the reduced expansion of cisplatin-loaded SAP microspheres was 188.4 μm, while that of the control expansion was 404.9 μm. The plasma platinum concentrations of the reduced expansion group at 5 min after TACE were significantly higher than those of the control expansion group (2.19 ± 0.77 vs. 0.75 ± 0.08 μg/mL, P = .01). The tumor platinum concentrations of the reduced expansion group at 1 h were significantly higher than those of the control expansion group (10.76 ± 2.57 vs. 1.57 ± 0.14 μg/g, P = .044). CONCLUSION: The expanding level of SAP microspheres can be reduced by using hypertonic saline. Cisplatin-loaded SAP microspheres with the reduced expansion technique have the advantages of achieving higher cisplatin tissue concentration in TACE for liver tumors.博士（医学）・甲第709号・令和元年6月26日© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2018This is a post-peer-review, pre-copyedit version of an article published in Cardiovascular and interventional radiology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00270-018-1990-4

Prospective Study on the Association between Harm Avoidance and Postpartum Depressive State in a Maternal Cohort of Japanese Women

BACKGROUND: Recent studies have displayed increased interest in examining the relationship between personality traits and the onset, treatment response patterns, and relapse of depression. This study aimed to examine whether or not harm avoidance (HA) was a risk factor for postpartum depression measured by the Edinburgh Postnatal Depression Scale (EPDS) and the state dependency of HA. METHODS: Pregnant women (n=460; mean age 31.9±4.2 years) who participated in a prenatal program completed the EPDS as a measure of depressive state and the Temperament and Character Inventory (TCI) as a measure of HA during three periods: early pregnancy (T1), late pregnancy (around 36 weeks), and 1 month postpartum (T2). Changes in EPDS and HA scores from T1 to T2 were compared between the non depressive (ND) group and the postpartum depressive (PD) group. RESULTS: There was no significant difference in the level of HA between the ND and PD groups at T1. In the ND group, EPDS and HA scores did not change significantly from T1 to T2. In the PD group, both scores increased significantly from T1 to T2 (EPDS, p<0.0001; HA, p<0.048). In the ND and PD groups, a significant positive correlation was observed in changes in EPDS and HA scores from T1 to T2 (r=0.31, p=0.002). CONCLUSIONS: These results suggest that HA cannot be considered a risk factor for the development of postpartum depression measured by EPDS. Furthermore, HA may be state dependent

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Etude comparée des verbes de perception visuelle en français et en japonais

The goal of my study is to precise the semantic and syntactic roles of the diverse and polysemic visual verbs in French and in Japanese. I will show the common (and the differencing) characteristics that can be observed between the two very differnet languages. My postulate is that both the way a speaker can grasp a phenomenon and the congnitive sytsem are particular to the society whose language it is, be it Franch or Japanese. Throught the case of visual perception, I will show that how the speaker builds a relation between the subject, the verb, and the object is differnet depending on the language. To do so, I will base my analysis on a corpus of authentic utterances.In the first chapter, I will study the Japanese verbs miru and mieru wich are often contrasted together. From the secon chapter on, I will focus on analyzing the French verbs, starting with voir. In my research, I will proceed to the detailed description of five construction : N0+voir, N0+voir+N1, N0+voir+que+, N0+voir+N1+attribue and se voir. I will deal with the first three aforementioned construction first. I will propose and analysis of the infinitive clause followed by the analysis of the two types of attributive clauses (relative and participial) in the third chapter. I will deal with pronominal verb se voir and the substitution between se voir and se faire in the fourth chapter. In the last chapter I will compare the meaning and the way the verbs voir and regarder function according to the type of N0 and N1. I will try to bring to the surface the commonalities and the differences between these two languages, genetically much different : how the speaker grasps a phenomenon and their cognitive system are certainly specific to each language and the society where this language is spoken.L'objectif de notre étude est de préciser les rôles syntaxiques et sémantiques de verbes visuels, polysémiques et variés dans les deux langues que sont le japonais et le français. Nous montrerons leurs points communs (et ceux de désaccord) observables, partant du postulat selon lequel la façon de saisir un phénomène et le système cognitif sont bien propres à la société qui possède la langue, le japonais ou le français : à travers le cas de la perception visuelle, nous étudierons la façon de construire la relation entre le sujet, le verbe et l'objet afin d'apporter des arguments à ce postulat. Pour ce faire, nous nous appuierons sur l'analyse d'un corpus d'énoncés attestés. Dans un premier chapitre, nous étudierons les verbes japonais miru et mieru qui sont souvent traités de manière contrastive. Nous nous concentrons, à partir du deuxième chapitre, sur l'étude des verbes français, et en premier lieu, sur le verbe voir. Dans notre travail, nous procéderons à la description fine de cinq construction : N0+vois, N0+voir+N1, N0+voir+que, N0+voir+N1+attribut et se voir. Nous nous concentrons d'abord sur les trois premières constructions mentionnées. Nous proposerons une analyse de la proposition infinitive et ensuite des deux types de propositions attributives (relative et participiale) dans le troisième chapitre. Nous nous occuperons du verbe pronominal se voir et de la substitution entre se voir et se faire dans le quatrième chapitre. Dans le dernier chapitre, nous comparerons la signification et le fonctionnement des deux verbes, voir et regarder, selon la nature de N0 et de N1. Nous essayerons de faire émerger les points communs et les divergences entre ces deux langues génétiquement bien différentes : la façon de saisir un phénomène et le système cognitif sont certainement propres à chaque langue et à la société où cette langue évolue

Visual verbs : a comparative study between French and Japanese

L'objectif de notre étude est de préciser les rôles syntaxiques et sémantiques de verbes visuels, polysémiques et variés dans les deux langues que sont le japonais et le français. Nous montrerons leurs points communs (et ceux de désaccord) observables, partant du postulat selon lequel la façon de saisir un phénomène et le système cognitif sont bien propres à la société qui possède la langue, le japonais ou le français : à travers le cas de la perception visuelle, nous étudierons la façon de construire la relation entre le sujet, le verbe et l'objet afin d'apporter des arguments à ce postulat. Pour ce faire, nous nous appuierons sur l'analyse d'un corpus d'énoncés attestés. Dans un premier chapitre, nous étudierons les verbes japonais miru et mieru qui sont souvent traités de manière contrastive. Nous nous concentrons, à partir du deuxième chapitre, sur l'étude des verbes français, et en premier lieu, sur le verbe voir. Dans notre travail, nous procéderons à la description fine de cinq construction : N0+vois, N0+voir+N1, N0+voir+que, N0+voir+N1+attribut et se voir. Nous nous concentrons d'abord sur les trois premières constructions mentionnées. Nous proposerons une analyse de la proposition infinitive et ensuite des deux types de propositions attributives (relative et participiale) dans le troisième chapitre. Nous nous occuperons du verbe pronominal se voir et de la substitution entre se voir et se faire dans le quatrième chapitre. Dans le dernier chapitre, nous comparerons la signification et le fonctionnement des deux verbes, voir et regarder, selon la nature de N0 et de N1. Nous essayerons de faire émerger les points communs et les divergences entre ces deux langues génétiquement bien différentes : la façon de saisir un phénomène et le système cognitif sont certainement propres à chaque langue et à la société où cette langue évolue.The goal of my study is to precise the semantic and syntactic roles of the diverse and polysemic visual verbs in French and in Japanese. I will show the common (and the differencing) characteristics that can be observed between the two very differnet languages. My postulate is that both the way a speaker can grasp a phenomenon and the congnitive sytsem are particular to the society whose language it is, be it Franch or Japanese. Throught the case of visual perception, I will show that how the speaker builds a relation between the subject, the verb, and the object is differnet depending on the language. To do so, I will base my analysis on a corpus of authentic utterances.In the first chapter, I will study the Japanese verbs miru and mieru wich are often contrasted together. From the secon chapter on, I will focus on analyzing the French verbs, starting with voir. In my research, I will proceed to the detailed description of five construction : N0+voir, N0+voir+N1, N0+voir+que+, N0+voir+N1+attribue and se voir. I will deal with the first three aforementioned construction first. I will propose and analysis of the infinitive clause followed by the analysis of the two types of attributive clauses (relative and participial) in the third chapter. I will deal with pronominal verb se voir and the substitution between se voir and se faire in the fourth chapter. In the last chapter I will compare the meaning and the way the verbs voir and regarder function according to the type of N0 and N1. I will try to bring to the surface the commonalities and the differences between these two languages, genetically much different : how the speaker grasps a phenomenon and their cognitive system are certainly specific to each language and the society where this language is spoken

L’expression de la perception visuelle : regard franco-japonais

International audienc

パリ第13大学 Aude GREZKA 氏講演の記録

International audienc

凝結表現の記述のための方法論的ツールの開発

International audienceFrozen expressions are both very complex and widespread language phenomena. The questions are: how to represent them and how to identify them? We propose a model which is able of accounting grammatical, semantic and meta linguistic informations of a given expression. To illustrate this description we propose two scenarios: translation and language learner tutor. Associated with these scenarios, two prototypes will be presented