Palmitate increases Nur77 expression by modulating ZBP89 and Sp1 binding to the Nur77 proximal promoter in pancreatic β-cells

Nur77 is a stress sensor in pancreatic β-cells, which negatively regulates glucose-stimulated insulin secretion. We recently showed that a lipotoxic shock caused by exposure of β-cells to the saturated fatty acid palmitate strongly increases Nur77 expression. Here, using dual luciferase reporter assays and Nur77 promoter deletion constructs, we identified a regulatory cassette between −1534 and −1512 bp upstream from the translational start site mediating Nur77 promoter activation in response to palmitate exposure. Chromatin immunoprecipitation, transient transfection and siRNA-mediated knockdown assays revealed that palmitate induced Nur77 promoter activation involves Sp1 recruitment and ZBP89 release from the gene promoter.     

近二十年来罗布泊地区生态环境研究综述

随着近期我国"一带一路"生态文明建设以及生态文明建设的提出与实施,生态类型丰富但自然环境脆弱的西北地区再度引发学界关注。历史上罗布泊地区作为陆上丝绸之路交通重要节点,在中外文明交往与民族融合进程中发挥着重大作用,但如今罗布泊干涸以及罗布泊地区生态环境恶化的现实促使学界对该区域的生态环境演变历史进行反思。为进一步了解当前罗布泊地区生态环境研究的整体概况、热点议题及学术前沿趋势,从自然环境与人文环境两大方面对近二十年来罗布泊地区生态环境研究做出阶段性总结,以期为后续深入探讨区域生态环境变化与社会文明演进互动提供参考。     

The dynamics of parental care in Choughs(Pyrrhocorax pyrrhocorax)

Summary The dynamics of parental investment throughout the nestling stage and the factors affecting it were studied in the Chough(Pyrrhocorax pyrrhocorax), a species whose patterns of apportioning parental care are largely unknown. The occurrence of important trade-offs between the sexes, among the different activities of parental care and between parents' survival and current offspring survival were estimated. The parental contributions of both sexes were assessed mainly in terms of food provisioning rate and nest attendance time. Only the female brooded young nestlings while the two sexes contributed equally in food deliveries and nest sanitation. Nestling age greatly affected nest attendance time. The female spent a long time brooding in the first 10 days after hatching. Both sexes increased attendance towards the end of the nestling stage. Conversely, feeding rate and feeding rate per nestling remained approximately constant throughout the nestling period. Nestlings in smaller broods received more feeding visits than those in larger broods. The shape of the per-nestling feeding rate curve was concave-up, supporting Nur's (1984) trade-offs model rather than the Lack-Gibb hypothesis. Maintaining a high feeding frequency in broods already above the modal value might be disadvantageous, implying few benefits and large energy costs (i.e. the reduction of the parents' residual reproductive value). Female brooding time in relation to brood size showed the same decreasing concave-up trend line. Short-term trade-offs proved to be important determinants of the dynamics of parental care. Specifically, the distance from the feeding areas greatly affected the delivery rate: pairs spent a disproportionately longer time foraging in more distant patches than in closer ones. Diurnal variations and changes owing to weather conditions were also examined.

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Die Dynamik elterlicher Investition bei der Alpenkrähe(Pyrrhocorax pyrrhocorax)

Zusammenfassung Der elterliche Aufwand und die geschlechtliche Verteilung des Brutaufwandes bei Alpenkrähen ist weitgehend unbekannt. Ziel der Arbeit war es deshalb, die verschiedenen Aktivitäten der elterlichen Brutversorgung und deren Konsequenzen für die Überlebensverhältnisse der Eltern und des Nachwuchses näher zu untersuchen. Die Fütterung der Brut und die Anwesenheit und Betreuung am Nest standen im Mittelpunkt. Während nur das Weibchen brütete, teilten sich die Eltern die Jungenaufzucht und die Pflege des Nestes etwa gleichmäßig, wobei das Nestlingsalter einen erheblichen Einfluß auf die Nestversorgung hatte. In den ersten 10 Tagen huderte das Weibchen intensiv. Beide Eltern steigerten ihre Brutpflege zum Ende der Nestlingszeit. Dagegen blieben die Fütterungsrate und die Anzahl Fütterungen je Nestling über die gesamte Nestlingszeit in etwa konstant. Junge in kleineren Bruten erhielten mehr Fütterungen als solche in großen. Der Verlauf der Abhängigkeit der Fütterungen je Nestling von der Brutgröße stützt mehr die Hypothese von Nur (1984) als die von Lack und Gibb. Die Aufrechterhaltung einer hohen Fütterungsrate auch bei großen Bruten dürfte nachteilig sein, da sie nur wenig Nutzen bei einem hohen Aufwand (Beeinträchtigung der späteren Brutmöglichkeiten) bringt. Der Huderaufwand des Weibchens zeigt in etwa denselben Zusammenhang mit der Brutgröße. Kurzzeitige elterliche Entscheidungen scheinen eine wichtige Rolle in der Regulation der elterlichen Brutpflege zu spielen. Dabei kommt gerade der räumlichen Lage der Nahrungsplätze eine große Bedeutung zu: an weiter entfernt gelegenen Nahrungsplätzen verbrachten die Eltern unverhältnismäßig mehr Zeit als an nahen Futterplätzen. Daneben haben die Tageszeit und das Wetter einen Einfluß auf die elterliche Brutfürsorge der Alpenkrähen.

     

Transgenic mice in apoptosis research

Transgenic mice have proved to be a valuable tool in various aspects of apoptosis research. They are particularly useful for studying apoptosis-related gene products in primary cells which may lead to different effects from similar experiments using immortalized cell lines. They allow the impact of these gene products on multi-faceted physiological processes to be identified. Transgenic mice have been generated expressing molecules ranging from Bcl-2 and Bcl-2 family members to CD95, superoxide dismutase and rhodopsin. This review details some of the insights revealed from such studies in diverse areas ranging from lymphoid development to neurodegeneration and effects on intracellular signalling.     

Nur77 nuclear import and its NBRE-binding activity in thymic lymphoma cells are regulated by different mechanisms sensitive to FK506 or HA1004

Thymic lymphoma cells restore their sensitivity to ionomycin-induced apoptosis when treated with FK506 or HA1004. In apoptosis-resistant cells, ionomycin-induced Nur77 strongly binds DNA during the first 2 h of response, in contrast to lymphoma cells treated with ionomycin together with FK506 or HA1004, which undergo massive apoptosis. We show that Nur77 could discriminate between calcium signals sensitive to FK506 and those sensitive to HA1004, as the inhibitors differentially regulate the kinetics of Nur77 nuclear import, and FK506, unlike HA1004, inhibits Nur77 DNA-binding activity. In the presence of HA1004, NBRE binding by Nur77 protein increases with time (6 h vs 2 h), whereas the final outcome of both inhibitors is apoptosis of thymic lymphoma cells.     

罗布麻资源利用与罗布麻植物分类问题

叙述了有关罗布麻分类的简要历史,讨论了我国罗布麻的植物分类问题,从植物分类学的依据和生产实践的需要考虑,应将我国罗布麻植物划分为1属2种,即罗布麻属（Apocynum L．）和罗布红麻（A．venetum L．）及罗布白麻（A．hendersonii Hook．f．）2种。     

Nur77 在缺氧/ 复氧诱导的心肌细胞凋亡中的作用及其机制的研究

目的:观察Nur77通过线粒体转位对缺氧/复氧(H/R)诱导的心肌细胞凋亡的影响。方法:原代培养l-2天SD大鼠心肌细胞,建立H/R模型。随机分为正常对照组、H/R组、Nur77组,采用免疫荧光检测横纹肌肌动蛋白(α-actin)鉴定心肌细胞;采用TUNEL染色法及Caspase-3酶活性检测心肌细胞凋亡情况;采用Western blot检测细胞核及线粒体Nur77蛋白表达、线粒体及胞浆Omi/HtrA2蛋白表达。结果:H/R组细胞核中Nur77蛋白表达明显低于正常对照组;而在线粒体中则相反。Nur77组线粒体中的Omi/HtrA2蛋白表达明显低于正常对照组;而在胞浆中则相反。结论:在心肌细胞H/R损伤时,Nur77线粒体转位促使Omi/HtrA2蛋白从线粒体释放入胞浆,从而导致心肌细胞凋亡。     

Nuclear Receptor Nur77 Facilitates Melanoma Cell Survival under Metabolic Stress by Protecting Fatty Acid Oxidation

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Natural products as modulators of the nuclear receptors and metabolic sensors LXR,FXR and RXR

Nuclear receptors (NRs) represent attractive targets for the treatment of metabolic syndrome-related diseases. In addition, natural products are an interesting pool of potential ligands since they have been refined under evolutionary pressure to interact with proteins or other biological targets.This review aims to briefly summarize current basic knowledge regarding the liver X (LXR) and farnesoid X receptors (FXR) that form permissive heterodimers with retinoid X receptors (RXR). Natural product-based ligands for these receptors are summarized and the potential of LXR, FXR and RXR as targets in precision medicine is discussed.