In 1789, there was an Ainu uprising against Wajin (Japanese) in the Kunashiri and Menashi districts of eastern Ezo. The uprising was quickly quelled in what is often referred to as the Battle of ...Kunashiri-Menashi. A year later, Matsumae domain, assigned by the Tokugawa shogunate to govern Ezo, completed Ishū retsuzō, a set of portraits of twelve Ainu chiefs who collaborated with the domain in suppressing the uprising. The paintings, executed by Kakizaki Hakyō (1764–1826), were intended not just to honor the chiefs’ deeds but also to represent Confucian ideals. This was a time when the shogunate was campaigning to revive Confucianism. It duly commissioned a work of similar style and purpose, namely the Kenjō no sōji, a set of wall panels for the Shishinden Hall in the imperial palace in Kyoto featuring thirty-two Chinese sages. Was the contemporaneous creation of these two sets of paintings a mere coincidence? Ishū retsuzō was first taken to Kyoto, where it was viewed by Confucian scholars, court nobles, and the emperor himself. The visually striking portraits enjoyed a quiet popularity among intellectuals and daimyo in Kyoto and Edo. Toward the end of the Edo period, part of the Ishū retsuzō was included in publications by Ezo explorer Matsuura Takeshirō. Contrary to the original intent of the work, it was used to introduce the “customs” of the Ainu, and was even introduced to Europe as such.
Background
Indigo Naturalis (IN) is used as a traditional herbal medicine for ulcerative colitis (UC). However, the mechanisms of action of IN have not been clarified. We aimed to evaluate the ...efficacy of IN for ameliorating colonic inflammation. We further investigated the mechanisms of action of IN.
Methods
Colitis severity was assessed in dextran sodium sulfate-induced colitis and trinitrobenzene sulfonic acid-induced colitis models with or without the oral administration of IN or indigo, which is a known major component of IN. Colonic lamina propria (LP) mononuclear cells isolated from IN-treated mice were analyzed with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and flow cytometry. LP and splenic mononuclear cells cultured in vitro with IN or indigo were also analyzed. The role of the candidate receptor for indigo, the aryl hydrocarbon receptor (AhR), was analyzed using
Ahr
-deficient mice.
Results
Colitis severity was significantly ameliorated in the IN and indigo treatment groups compared with the control group. The mRNA expression levels of interleukin (
Il
)-
10
and
Il-22
in the LP lymphocytes were increased by IN treatment. The treatment of splenocytes with IN or indigo increased the expression of anti-inflammatory cytokines and resulted in the expansion of IL-10-producing CD4
+
T cells and IL-22-producing CD3
−
RORγt
+
cells, but not CD4
+
Foxp3
+
regulatory T cells. The amelioration of colitis by IN or indigo was abrogated in
Ahr
-deficient mice, in association with diminished regulatory cytokine production.
Conclusions
IN and indigo ameliorated murine colitis through AhR signaling activation, suggesting that AhR could be a promising therapeutic target for UC.
The heat shock response is important for the viability of all living organisms. It involves the induction of heat shock proteins whose expression is mainly regulated by heat shock factor 1 (HSF1). ...Medaka (Oryzias latipes) is a teleost fish with an XX/XY sex determination system. High water temperature (HT) inhibits the female-type proliferation of germ cells and induces the masculinisation of XX medaka in some cases during gonadal sex differentiation. Here, we investigated the roles of HSF1 on the proliferation of germ cells using HSF1 knockout medaka. Loss of HSF1 function under HT completely inhibited the female-type proliferation of germ cells, induced the expression of the anti-Mullerian hormone receptor type 2 (amhr2) and apoptosis-related genes, and suppressed that of the dead end (dnd) and heat shock protein-related genes. Moreover, the loss of HSF1 and AMHR2 function under HT recovered female-type proliferation in germ cells, while loss of HSF1 function under HT induced gonadal somatic cell apoptosis during early sex differentiation. These results strongly suggest that HSF1 under the HT protects the female-type proliferation of germ cells by inhibiting amhr2 expression in gonadal somatic cells. These findings provide new insights into the molecular mechanisms underlying environmental sex determination.
G-protein-coupled receptor 52 (GPR52) is an orphan Gs-coupled G-protein-coupled receptor. GPR52 inhibits dopamine D2 receptor signaling and activates dopamine D1/N-methyl-d-aspartate receptors via ...intracellular cAMP accumulation, and therefore, GPR52 agonists may have potential as a novel class of antipsychotics. A series of GPR52 agonists with a bicyclic core was designed to fix the conformation of the phenethyl ether moiety of compounds 2a and 2b. 3-2-(3-Chloro-5-fluorobenzyl)-1-benzothiophen-7-yl-N-(2-methoxyethyl)benzamide 7m showed potent activity (pEC50 = 7.53 ± 0.08) and good pharmacokinetic properties. Compound 7m significantly suppressed methamphetamine-induced hyperactivity in mice after oral administration of 3 mg/kg without disturbance of motor function.
Among the many intervention programs for children with autism spectrum disorder (ASD), the Early Start Denver Model (ESDM) is one of the few approaches that has succeeded in demonstrating clinical ...efficacy in randomized control trials. Here, we inves-tigate the clinical efficacy of ESDM intervention in young children with ASD in a community setting within Japan.
All subjects were children with ASD who received ESDM intervention during the study period. Each ESDM session lasted 75 min and occurred once per week for at least 12 weeks. The outcome measures consisted of the Kyoto Scale of Psychological Develop-ment (K-test), Aberrant Behavior Checklist-Japanese version (ABC-J), and the Clinical Global Impression-Severity scale (CGI-S).
Twenty-seven subjects (29.4±6.4 months old) received ESDM intervention that lasted for 8.0±2.6 months on average. The score on Language and Social developmental quotient on the K-test increased significantly after the intervention. The total scores on the ABC-J and CGI-S significantly decreased after completion of the ESDM intervention.
Our results suggest that ESDM intervention could reduce the severity of distinct clinical features of ASD, such as impair-ments in social interaction and communication assessed by the K-test, and maladaptive behavior rated by the ABC-J and CGI-S. We be-lieve that the ESDM adapted to each institution might become one of the standard options for children with ASD in Japan.
Background
Patients with inflammatory bowel disease (IBD) often exhibit vitamin K deficiency. Vitamin K has been shown to inhibit inflammation via interleukin (IL)-6 suppression. This study aimed to ...evaluate the effect of vitamin K in a murine model of colitis.
Methods
Colitis was induced using dextran sulfate sodium (DSS) in mice fed either a vitamin K-deficient (K-def) or a vitamin K-supplemented (K-sup) diet. The clinical and histological severity of colitis was assessed, and levels of cytokine production from the spleen and colonic lamina propria were measured by enzyme-linked immunosorbent assay and quantitative real-time reverse transcription polymerase chain reaction. Cytokine expression levels in CD4
+
, CD11b
+
, and CD19
+
cells in the presence and absence of vitamin K menatetrenone (MK-4) were measured in vitro and apoptosis was determined by caspase 3/7 activity and Annexin V staining.
Results
DSS administration resulted in significantly more severe body weight loss, shorter colon length, and higher histological scores in mice fed a K-def diet than those fed a K-sup diet. IL-6 expression in lamina propria mononuclear cells was significantly higher in the K-def group than in the K-sup group. IL-6 expression was significantly decreased in the presence of MK-4 in CD19
+
cells, but not in the CD4
+
and CD11b
+
subpopulations. Apoptotic cell population in CD19
+
cells was increased in the presence of MK-4 in vitro and in vivo.
Conclusions
Vitamin K exerts a protective effect against DSS colitis; this effect is associated with IL-6 downregulation. Vitamin K could be a potential treatment target for IBD.
In vertebrate germ cell differentiation, gonadal somatic cells and germ cells are closely related. By analyzing this relationship, it has recently been reported in mammals that primordial germ cells ...(PGCs), induced from pluripotent stem cells and germline stem cells, can differentiate into functional gametes when co-cultured
with fetal gonadal somatic cells. In some fish species, differentiation into functional sperm by reaggregation or co-culture of gonadal somatic cells and germ cells has also been reported; however, the relationship between gonadal somatic cells and germ cells in these species is not well-understood. Here, we report the transcriptional regulation of Müllerian inhibiting substance (MIS) and the establishment of a gonadal somatic cell line using
transgenic fish, in medaka (
)-a fish model which offers many advantages for molecular genetics. MIS is a glycoprotein belonging to the transforming growth factor β superfamily. In medaka,
mRNA is expressed in gonadal somatic cells of both sexes before sex differentiation, and MIS regulates the proliferation of germ cells during this period. Using luciferase assays, we found that steroidogenic factor 1 (SF1) and liver receptor homolog 1 (LRH1) activate medaka
gene transcription, probably by binding to the
promoter. We also report that
transgenic medaka emit GFP fluorescence specific to gonadal somatic cells in the gonads. By fusing Sertoli cells from transgenic medaka with a cell line derived from medaka hepatoma cancer, we produced a hybridoma cell line that expresses gonadal somatic cell-specific markers, including Sertoli and Leydig cell markers. Moreover, embryonic PGCs co-cultured with the established hybridoma, as feeder cells, proliferated and formed significant colonies after 1 week. PGCs cultured for 3 weeks expressed a germ cell marker
, as well as the meiotic markers
and
. Thus, we here provide the first evidence in teleosts that we have successfully established a gonadal somatic cell-derived hybridoma that can induce both the proliferation and meiosis of germ cells.
PDF
