Identification of Ornithine-lactam Converted from Arginine in Streptomyces incarnatus NRRL8089

Sinefungin is a nucleoside antibiotic, in which a molecule of L-ornithine is linked to the 5' end of adenosine through a C-C bond. The antibiotic was isolated from the culture broth of Streptomyces incarnatus. For the purpose of detecting intermediate of sinefungin biosynthesis, resting cell suspensions were incubated with supplemental L-arginine, and L-ornithine. 50mM Arginine was converted to a compound X that has low polarity. 50mM ornithine was not converted and remained in reaction solution. Compound X was purified using HPLC, and analyzed using (1)H-NMR and FAB-MS. These analyses showed that a compound X is "ornithine-lactam" (Mw＝114), which has a structure of circularized ornithine. These results indicated that S. incarnatus has an enzyme that converts arginine to ornithine-lactam. Such an enzyme has never been reported, and suggested that it may be relevant to sinefungin biosynthesis.シネフンギンは抗真菌，抗マラリア活性を有する核酸系抗生物質であり，放線菌 S. incarnatus により生合成される．シネフンギンはアデノシンとオルニチンがＣﾝＣ結合した構造であり，無細胞抽出液での取り込み実験からＬﾝアルギニンと ATP から生合成されると推測される．Ｌﾝアルギニン，Ｌﾝオルニチンを S. incarnatus の休止菌体反応系への投与を行いシネフンギン中間体の探索を行った．その結果50ﾋアルギニンは24時間以内に低極性化合物へと変換された．一方50ﾋオルニチンは変換されず反応液中に残存した．HPLC で化合物を精製し，1HﾝNMR，FABﾝMS での分析の結果オルニチン環状モノペプチド，「オルニチンラクタム」（分子量114）であることを明らかにした．この結果は S. incarnatus がアルギニンからオルニチンラクタムへの変換酵素を有する事を示唆する．このような酵素の報告例はこれまでになく，ニ次代謝酵素であることが示唆され，シネフンギン生合成との関連性に興味が持たれる

Phosphoinositide-dependent regulation of VAN3 ARF-GAP localization and activity essential for vascular tissue continuity in plants

ACAP-type ARF GTPase activating proteins (ARF-GAPs) regulate multiple cellular processes, including endocytosis, secretion, phagocytosis, cell adhesion and cell migration. However, the regulation of ACAP functions by other cellular proteins is poorly understood. We have reported previously that a plant ACAP, VAN3, plays a pivotal role in plant venation continuity. Here, we report on newly identified VAN3 regulators: the CVP2 (cotyledon vascular pattern 2) 5 PTase, which is considered to degrade IP3 and also to produce PtdIns(4) P from PtdIns(4,5) P-2; and a PH domain-containing protein, VAB (VAN3 binding protein). Combinational mutations of both CVP2 and its closest homologue CVL1 (CVP2 like 1) phenocopied the strong allele of van3 mutants, showing severe vascular continuity. The phenotype of double mutants between van3, cvp2 and vab suggested that VAN3, CVP2 and VAB function in vascular pattern formation in the same pathway. Localization analysis revealed that both CVP2 and VAB colocalize with VAN3 in the trans-Golgi network (TGN), supporting their functions in the same pathway. The subcellular localization of VAN3 was dependent on its PH domain, and mislocalization of VAN3 was induced in cvp2 or vab mutants. These results suggest that CVP2 and VAB cooperatively regulate the subcellular localization of VAN3 through the interaction between its PH domain and phosphoinositides and/or inositol phosphates. In addition, PtdIns(4) P, to which VAN3 binds preferentially, enhanced the ARF-GAP activity of VAN3, whereas IP3 inhibited it. These results suggest the existence of PtdIns(4) P and/or IP3-dependent subcellular targeting and regulation of VAN3 ACAP activity that governs plant vascular tissue continuity

Animal Models of Middle Ear Cholesteatoma

Middle ear acquired cholesteatoma is a pathological condition associated with otitis media, which may be associated with temporal bone resorption, otorrhea and hearing loss, and occasionally various other complications. Cholesteatoma is characterized by the enhanced proliferation of epithelial cells with aberrant morphologic characteristics. Unfortunately, our understanding of the mechanism underlying its pathogenesis is limited. To investigate its pathogenesis, different animal models have been used. This paper provides a brief overview of the current status of research in the field of pathogenesis of middle ear acquired cholesteatoma, four types of animal models previously reported on, up-to-date cholesteatoma research using these animal models, our current studies of the local hybrid ear model, and the future prospect of new animal models of middle ear cholesteatoma

Continuous perfusion of pulmonary arteries during total cardiopulmonary bypass favorably affects levels of circulating adhesion molecules and lung function

AbstractObjectives: Lung injury is a serious complication of cardiopulmonary bypass in infants with congenital heart disease and pulmonary hypertension. Cessation of blood flow in the pulmonary arteries during cardiopulmonary bypass is known to provoke lung dysfunction. We assessed the effect of continuous pulmonary perfusion on circulating adhesion molecules and on lung function. Methods: Fourteen infants with congenital heart disease and pulmonary hypertension were enrolled in the study. During total cardiopulmonary bypass, 8 patients underwent continuous perfusion of the pulmonary arteries (perfusion group), and the remaining 6 patients did not (control group). Plasma levels of circulating intercellular adhesion molecule 1, soluble granule membrane protein 140, and sialyl Lewisx and PaO2/fraction of inspired oxygen ratios were measured before commencement and serially for 24 hours after termination of bypass. Results: Plasma levels of circulating intercellular adhesion molecule 1 decreased significantly at the termination of bypass in both groups but returned to prebypass levels immediately in the control group, whereas in the perfusion group the values remained significantly less than those before bypass. Plasma levels of soluble granule membrane protein 140 in the control group were significantly higher at 6 and 12 hours after bypass than levels before bypass, whereas in the perfusion group the values remained at the prebypass level throughout the postbypass period. Trends of plasma levels of sialyl Lewisx were alike in both groups. PaO2/fraction of inspired oxygen ratios in the control group decreased significantly from 6 hours after bypass, whereas values in the perfusion group remained at the prebypass value throughout the postbypass period. Conclusions: This study suggests that in infants having congenital heart disease and pulmonary hypertension, continuous pulmonary perfusion during total cardiopulmonary bypass minimizes ischemic insult and neutrophil-endothelial interaction mediated by adhesion molecules in the pulmonary microvessels.J Thorac Cardiovasc Surg 2001;122:242-

Explaining a century of Swiss regional development by deep learning and SHAP values

We use a graph convolutional neural network (GCN) for regional development prediction with population, railway network density, and road network density of each municipality as development indicators. By structuring the long-term time series data from 2833 municipalities in Switzerland during the years 1910–2000 as graphs over time, the GCN model interprets the indicators as node features and produces an acceptable prediction accuracy on their future values. Moreover, SHapley Additive exPlanations (SHAPs) are used to make the results of this approach explainable. We develop an algorithm to obtain SHAP values for the GCN and a sensitivity indicator to quantify the marginal contributions of the node features. This explainable GCN with SHAP decomposes the indicator into the contribution by the previous status of the municipality itself and the influence from other municipalities. We show that this provides valuable insights into understanding the history of regional development. Specifically, the results demonstrate that the impacts of geographical and economic constraints and urban sprawl on regional development vary significantly between municipalities and that the constraints are more important in the early 20th century. The model is able to include more information and can be applied to other regions and countries