Serotonergic neurons respond to nutrients and regulate the timing of steroid hormone biosynthesis in Drosophila

The temporal transition of development is flexibly coordinated in the context of the nutrient environment, and this coordination is essential for organisms to increase their survival fitness and reproductive success. Steroid hormone, a key player of the juvenile-to-adult transition, is biosynthesized in a nutrient-dependent manner; however, the underlying genetic mechanism remains unclear. Here we report that the biosynthesis of insect steroid hormone, ecdysteroid, is regulated by a subset of serotonergic neurons in Drosophila melanogaster. These neurons directly innervate the prothoracic gland (PG), an ecdysteroid-producing organ and share tracts with the stomatogastric nervous system. Interestingly, the projecting neurites morphologically respond to nutrient conditions. Moreover, reduced activity of the PG-innervating neurons or of ​serotonin signalling in the PG strongly correlates with a delayed developmental transition. Our results suggest that serotonergic neurons form a link between the external environment and the internal endocrine system by adaptively tuning the timing of steroid hormone biosynthesis

Quality and safety issues related to traditional animal medicine: role of taurine

<p>Abstract</p> <p>Background</p> <p><it>Calculus Bovis</it> (:<it>C.Bovis</it>) is one of the most precious and commonly-used medicinal materials in Japan and China. As the natural occurrence is very rare, a source of supply for <it>C. Bovis</it> is far behind the actual need and great efforts have been taken for some substitutes of natural <it>C. Bovis</it>. Unfortunately, very little information is available on the quality and/or clinical efficacy of medication based on <it>C. Bovis</it>. To ensure sustainable use of traditional therapeutic agents derived from <it>C. Bovis</it>, we felt that several issues needed to be addressed: 1) the source of the <it>C. Bovis</it> materials and quality control; 2) the role of taurine in the efficacy of <it>C. Bovis</it>.</p> <p>Methods</p> <p>Nine samples of natural <it>C. Bovis</it> and its substitutes were collected. ICP-MS was used for elemental analysis and the characterization was performed by principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA) as multivariate approaches. The efficacy of <it>C. Bovis</it> was evaluated for morphology, viability and beating pattern on cultured cardiac myocytes and/or fibroblasts.</p> <p>Results</p> <p>PCA and multi-elemental focus was effective in discriminating <it>C. Bovis</it> samples derived from different habitats. A satisfactory classification using SIMCA was obtained among Australia <it>C. Bovis</it>, other habitats and the substitutes. Australian samples had better batch uniformity than other habitats and were composed of fewer elements. We have used Australian<it> C. Bovis</it> for assessment on its bioactive compounds. Rat cardiac cells incubated with <it>C. Bovis</it> extract (0.01-0.1mg/ml) maintained normal morphology, viability and beating pattern. Cardiac myocytes and fibroblasts treated for 48 h with CA (0.5mM) or DCA (0.1mM) caused cell injury, as reflected by changes in appearance and a reduction of viability detected by the MTS assay. In cardiomyocytes, 0.5 h exposure of CA (0.5mM) markedly decreased the velocity ratio of beating, whereas the simultaneous addition of 1 mM taurine largely prevented the decrease.</p> <p>Conclusions</p> <p>The multi-elemental focus provided some references for the quality control and the efficacy of <it>C. Bovis</it>. Taurine partly attenuated the harmful actions of bile acids. It is plausible that the relationship between taurine and the bile acids contributes to therapeutic effect of <it>C. Bovis</it>.</p

Somatic insulin signaling regulates a germline starvation response in Drosophila egg chambers

AbstractEgg chambers from starved Drosophila females contain large aggregates of processing (P) bodies and cortically enriched microtubules. As this response to starvation is rapidly reversed upon re-feeding females or culturing egg chambers with exogenous bovine insulin, we examined the role of endogenous insulin signaling in mediating the starvation response. We found that systemic Drosophila insulin-like peptides (dILPs) activate the insulin pathway in follicle cells, which then regulate both microtubule and P body organization in the underlying germline cells. This organization is modulated by the motor proteins Dynein and Kinesin. Dynein activity is required for microtubule and P body organization during starvation, while Kinesin activity is required during nutrient-rich conditions. Blocking the ability of egg chambers to form P body aggregates in response to starvation correlated with reduced progeny survival. These data suggest a potential mechanism to maximize fecundity even during periods of poor nutrient availability, by mounting a protective response in immature egg chambers

Thrombin Stimulates Synthesis of Macrophage Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating Factor and Granulocyte Colony-Stimulating Factor by Human Proximal Tubular Epithelial Cells in Culture

Background/Aims: Colony-stimulating factors (CSFs) are well-known hematopoietic growth factors. Although recent studies revealed that CSFs are involved in many inflammatory conditions, the local production of CSFs and its regulation in the kidney is not well elucidated. Therefore, using cultured human proximal tubular epithelial cells (PTEC), we examined the effect of thrombin on CSFs production, since thrombin has been suggested to play an important role in tubulointerstitial injury. Methods: PTEC were incubated with thrombin (0.5–5.0 U/ml) and the effects on the production of macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF) were measured in the cell supernatant by enzyme-linked immunosorbent assay, and the expressions of mRNA were analyzed by quantitative real-time reverse transcription polymerase chain reaction. Using argatroban, a direct thrombin inhibitor, we also examined the specific effect of thrombin. Results: Thrombin 5.0 U/ml significantly stimulated the production of M-CSF (p Conclusion: We demonstrated that thrombin significantly increased the production of CSFs by PTEC. These data suggest that the local production of CSFs in the tubulointerstitium may affect tubulointerstitial lesions in kidney injury

Effect of Surface Pre-Reacted Glass Ionomer Containing Dental Sealant on the Inhibition of Enamel Demineralization.

The effect of a surface pre-reacted glass ionomer (S-PRG)-containing sealant on the demineralization inhibition and remineralization of intact enamel adjacent to the sealant material was investigated. BeautiSealant (BTS, S-PRG sealant, Shofu), Teeth Mate F-12.0 (TMF, fluoride-releasing sealant, Kuraray Noritake Dental), and an experimental silica-filler sealant were investigated. After pH cycling for 10 days, the enamel surface adjacent to the sealant material was observed using confocal laser microscopy and scanning electron microscopy. The polymerized sealant disks were immersed in a demineralized solution (pH: 4.3) to measure pH change. The enamel specimens with polymerized sealant disks were additionally immersed in demineralized solution, followed by energy-dispersive X-ray spectroscopy. The demineralized area of BTS was significantly smaller than that of TMF and SS (p &lt; 0.05). The surfaces adjacent to the sealant of TMF and SS were demineralized, while the surface of BTS was comparatively intact. An increase in pH values were observed in the BTS and TMF groups. Enamel surfaces presented an inhibition of demineralization for BTS and TMF, but not for SS. Fluoride uptake from the polymerized sealant was greater for BTS than for TMF. The S-PRG-containing sealant showed a buffering ability, demineralization inhibition, promotion of remineralization, and it can be advised for clinical applications

Investigation of the molecular causes underlying physical abnormalities in Diamond‐Blackfan anemia patients with RPL5 haploinsufficiency

Diamond-Blackfan anemia (DBA) is a genetic disorder caused by mutations in genes encoding ribosomal proteins and characterized by erythroid aplasia and various physical abnormalities. Although accumulating evidence suggests that defective ribosome biogenesis leads to p53-mediated apoptosis in erythroid progenitor cells, little is known regarding the underlying causes of the physical abnormalities. In this study, we established induced pluripotent stem cells from a DBA patient with RPL5 haploinsufficiency. These cells retained the ability to differentiate into osteoblasts and chondrocytes. However, RPL5 haploinsufficiency impaired the production of mucins and increased apoptosis in differentiated chondrocytes. Increased expression of the pro-apoptotic genes BAX and CASP9 further indicated that RPL5 haploinsufficiency triggered p53-mediated apoptosis in chondrocytes. MDM2, the primary negative regulator of p53, plays a crucial role in erythroid aplasia in DBA patient. We found the phosphorylation level of MDM2 was significantly decreased in RPL5 haploinsufficient chondrocytes. In stark contrast, we found no evidence that RPL5 haploinsufficiency impaired osteogenesis. Collectively, our data support a model in which RPL5 haploinsufficiency specifically induces p53-mediated apoptosis in chondrocytes through MDM2 inhibition, which leads to physical abnormalities in DBA patients

育児中の助産師学生に関する研究

国際助産師連盟（以下ICM）では1年6ヶ月以上の教育を推奨している。これに対して日本では保健師助産師看護師法学校指定規則において1年以上の教育課程を必須としている。1年間でICM が提唱する教育内容を取得するには過密スケジュールが予測される。 　日本では1年制の助産師養成課程においてはほぼ30単位以上の単位履修をもって修了となり、指定規則の28単位より多くの単位取得にて卒業する1）。このように1年課程ではカリキュラムの過密状態が前提であるため、クリアできるのは学生の強い動機などが要因となっていると推測する。 　また助産学実習では看護学実習とは異なり、分娩介助等の実践が単位取得の必須要件であり、学生は時間を問わず厳しい実習状況下におかれる。このため身体的にも精神的にも強さが要求される。田中ら2）は、助産学実習は対象者との関わりが多い、学生に求められる能力が高い、学生としての責任が重い、実習体制などが看護学生の実習とは異なることを指摘している。従って学生はこれまで体験した実習よりも厳しい状況下におかれる。 　助産学実習はウェイトの大きいものであり、保健師助産師看護師学校養成所指定規則で助産学実習は11単位を必須とされている。助産学実習以外の講義においても、学生にとって学習内容が濃厚で課題が多く、1年課程であるために過密スケジュールとなることが前提となる。 　大学専攻科、別科又は専修学校など助産師養成の1年課程は、学費の負担が少ない、看護大学の卒業生のほか、看護師などの臨床経験者、社会人経験者などが入学できるメリットがあると考える。高野ら3）による社会人経験のある新人看護師を対象とした報告や、高橋4）の社会人経験者の実態などの報告、渡邉ら5）の社会人経験がある看護学生に対する教育側からの困難感などの報告があるものの、助産師学生を対象とした報告はみられないため、追究する意義があると考える。 　中島ら6）は、助産学教育の質的向上を図るためには、学生の特性を踏まえた教育法の開発や教育的支援を強化する必要性を指摘している。このため学生の特性として、育児経験者、臨床経験者、社会人経験者などを対象とし、その背景を踏まえた教育を検討することが期待される。 　そこで今回本研究では、育児中の助産師学生の1年間の学生生活の実態に焦点をあて、今後の教育側の対応への検討に資する目的で半構成的面接を行い、質的帰納的に分析したので報告する。 In order to contribute to midwifery education, semi-structured interviews for eight midwifery students who were also raising children were conducted, regarding the motivation for enrolling on the course, their challenges after enrolling, impact on their child/children, and relationship with other younger students. The results were analyzed inductively and qualitatively. As for the motivation and preparation for the enrollment, two categories:‘ long-held aspiration’‘, midwives seen in many situations’, and ‘desperate to pass the exam’ were identified. As for the challenges faced after enrollment, three categories:‘ hardship of studying that exceeded the expectation’,‘ thoughts about the child that are always in mind’, and‘ life as a student which cannot stand without support of others’ were identified. As for the feelings towards their child/children, three categories:‘ life changing that involves others’,‘ situations where, like it or not, study has to come first, not the child’, and‘ a parent who tries to convince herself that the child is understanding and appreciative’ were identified. In addition, as for the future image of themselves at the time of graduating, three categories:‘ re-acknowledgment of the work of a midwife’,‘ midwives who had become the occupational model either positively or negatively’, and‘ hopes and worries about using the obtained qualification’were identified. 　All the interviewees had childbearing experience, and their motivation of choosing the vocation came from their own childbirth experience, whether it was a positive one or a negative one. After enrolling on the course, they were worn out trying to balance the household and childcare chores and the study, involving their family members, trying to convince themselves that the child was understanding and appreciative, and trying their best to balance the child-rearing and studying while feeling guilty. 　Their priority in finding work is that it should be somewhere easily commutable, putting childcare arrangements first in their consideration. It is expected that they will re-acknowledge the serious responsibility and the breadth of the work through onsite practice and other experiences, find various midwifery role models that they had not known at the time of the enrollment, and form an occupational identity after graduation