Absence of Radial Spokes in Mouse Node Cilia Is Required for Rotational Movement but Confers Ultrastructural Instability as a Trade-Off

SummaryDetermination of left-right asymmetry in mouse embryos is established by a leftward fluid flow that is generated by clockwise rotation of node cilia. How node cilia achieve stable unidirectional rotation has remained unknown, however. Here we show that brief exposure to the microtubule-stabilizing drug paclitaxel (Taxol) induces randomly directed rotation and changes the ultrastructure of node cilia. In vivo observations and a computer simulation revealed that a regular 9+0 arrangement of doublet microtubules is essential for stable unidirectional rotation of node cilia. The 9+2 motile cilia of the airway, which manifest planar beating, are resistant to Taxol treatment. However, the airway cilia of mice lacking the radial spoke head protein Rsph4a undergo rotational movement instead of planar beating, are prone to microtubule rearrangement, and are sensitive to Taxol. Our results suggest that the absence of radial spokes allows node cilia to rotate unidirectionally but, as a trade-off, renders them ultrastructurally fragile

Mammalian Fat and Dachsous cadherins regulate apical membrane organization in the embryonic cerebral cortex

Compartmentalization of the plasma membrane in a cell is fundamental for its proper functions. In this study, we present evidence that mammalian Fat4 and Dachsous1 cadherins regulate the apical plasma membrane organization in the embryonic cerebral cortex. In neural progenitor cells of the cortex, Fat4 and Dachsous1 were concentrated together in a cell–cell contact area positioned more apically than the adherens junction (AJ). These molecules interacted in a heterophilic fashion, affecting their respective protein levels. We further found that Fat4 associated and colocalized with the Pals1 complex. Ultrastructurally, the apical junctions of the progenitor cells comprised the AJ and a stretch of plasma membrane apposition extending apically from the AJ, which positionally corresponded to the Fat4–Dachsous1-positive zone. Depletion of Fat4 or Pals1 abolished this membrane apposition. These results highlight the importance of the Fat4–Dachsous1–Pals1 complex in organizing the apical membrane architecture of neural progenitor cells

血液透析患者の栄養状態ならびに栄養摂取状況が生活の質(QOL)に及ぼす影響

血液透析患者において透析治療を長期に継続していく上で種々の透析合併症の予防のため適切な食事療法の実践が重要である｡厳格な食事療法は生活の質(QOL)や栄養状態の低下に繋がる可能性もある｡本研究では､外来血液透析患者70名を対象に栄養摂取状況と栄養状態及び QOL について評価､解析を行った｡その結果､約30%の患者が栄養状態にﾘｽｸありと判定された｡栄養状態と食事摂取量には相関は認められなかったが､栄養状態が低下した群では､豆類の摂取量が少なかった｡透析患者の栄養状態と QOL を詳細に解析すると女性は栄養状態が低下しても包括的尺度(SF-36)､腎疾患特異的尺度ともに比較的維持されていたが､男性は栄養状態の悪化により有意な低下が認められた｡SF-36 では身体的健康度だけでなく､精神的健康度も悪化していた｡男性患者にはより早期からの栄養面での管理と指導が重要であり､またきめ細やかなｹｱや周囲の人々からの精神的な支えや理解が大切である｡For patients undergoing long-term hemodialysis treatment, appropriate nutrition therapy is important to prevent complications. However, strict dietary regimens sometimes reduce the Quality of Life(QOL)and nutritional status. In this study, we examined and analyzed the nutrient intake, nutritional status, and QOL of 70 outpatients undergoing hemodialysis. As the results, approximately 30% of the subjects were judged to have nutritional problems. Although no association was observed between the nutritional status and amount of food intake, the consumption of bean products was lower in subjects with a reduced nutritional status. Analysis of the nutritional status and QOL of the dialysis patients showed that female subjects had favorable scores on the Short-Form 36(SF-36)Health Survey and Kidney Disease Quality of Life(KDQOL)despite a reduction in the nutritional status; however, a significant score reduction was observed in male subjects in association with the deterioration of their nutritional status. The results of SF-36 showed not only physical, but also mental health deteriorations. For male patients, early dietary interventions and guidance, as well as thoughtful care, emotional support, and understanding from people around them are essential

Homeostatic Epithelial Renewal in the Gut Is Required for Dampening a Fatal Systemic Wound Response in Drosophila

Effective defense responses involve the entire organism. To maintain body homeostasis after tissue damage, a systemic wound response is induced in which the response of each tissue is tightly orchestrated to avoid incomplete recovery or an excessive, damaging response. Here, we provide evidence that in the systemic response to wounding, an apoptotic caspase pathway is activated downstream of reactive oxygen species in the midgut enterocytes (ECs), cells distant from the wound site, in Drosophila. We show that a caspase-pathway mutant has defects in homeostatic gut cell renewal and that inhibiting caspase activity in fly ECs results in the production of systemic lethal factors after wounding. Our results indicate that wounding remotely controls caspase activity in ECs, which activates the tissue stem cell regeneration pathway in the gut to dampen the dangerous systemic wound reaction

Inheritance of a Nuclear PIWI from Pluripotent Stem Cells by Somatic Descendants Ensures Differentiation by Silencing Transposons in Planarian

Differentiation of pluripotent stem cells (PSCs) requires transposon silencing throughout the process. PIWIs, best known as key factors in germline transposon silencing, are also known to act in somatic differentiation of planarian PSCs (neoblasts). However, how PIWIs control the latter process remains elusive. Here, using Dugesia japonica, we show that a nuclear PIWI, DjPiwiB, was bound to PIWI-interacting RNAs (generally key mediators of PIWI-dependent transposon silencing), and was detected in not only neoblasts but also their descendant somatic cells, which do not express piwi. In contrast, cytoplasmic DjPiwiA and DjPiwiC were detected only in neoblasts, in accord with their transcription there. DjPiwiB was indispensable for regeneration, but dispensable for transposon silencing in neoblasts. However, transposons were derepressed at the onset of differentiation in DjPiwiB-knockdown planarians. Thus, DjPiwiB appears to be inherited by descendant somatic cells of neoblasts to ensure transposon silencing in those cells, which are unable to produce PIWI proteins