NEDDylation regulates RAD18 ubiquitination and localization in response to oxidative DNA damage

Genome integrity is important for cell growth, development and proliferation. The E3 ligase RAD18 plays a vital role in the DNA damage response (DDR) to maintain genome integrity. Recent studies reveal that RAD18 has non-ubiquitinated and mono-ubiquitinated form in normal cells. However, whether RAD18 undergoes other post-translational modification remains to be investigated. Here we show that RAD18 is a target of NEDD8, an ubiquitin-like protein. In response to hydrogen peroxide (H₂O₂)-induced oxidative stress, RAD18 NEDDylation increases significantly, while its ubiquitination decreases. Moreover, NEDD8 overexpression or deNEDDylase NEDP1 deletion further antagonizes RAD18 ubiquitination. In addition, treatment with MLN4924, an inhibitor of NEDD8-activating Enzyme, reduces the interaction between PCNA and RAD18, which blocks the localization of RAD18 to form foci, and thus inhibiting polymerase η recruitment after oxidative stress. Together, our study demonstrates that RAD18 NEDDylation regulates its localization and involves in the DDR pathway by modulating RAD18 ubiquitination.     

<Emphasis Type="Italic">CaMi</Emphasis>, a root-knot nematode resistance gene from hot pepper (<Emphasis Type="Italic">Capsium annuum</Emphasis> L.) confers nematode resistance in tomato

Several root-knot nematode (Meloidogyne spp.) resistance genes have been discovered in different pepper (Capsium annuum L.) lines; however, none of them has yet been cloned. In this study, a candidate root-knot nematode resistance gene (designated as CaMi) was isolated from the resistant pepper line PR 205 by degenerate PCR amplification combined with the RACE technique. Expression profiling analysis revealed that this gene was highly expressed in roots, leaves, and flowers and expressed at a lower level in stems and was not detectable in fruits. To verify the function of CaMi, a sense vector containing the genomic DNA spanning the full coding region of CaMi was constructed and transferred into root-knot nematode susceptible tomato plants. Sixteen transgenic plants carrying one to five copies of T-DNA inserts were generated from two nematode susceptible tomato cultivars. RT-PCR analysis revealed that the expression levels of CaMi gene varied in different transgenic plants. Nematode assays showed that the resistance to root-knot nematodes was significantly improved in some transgenic lines compared to untransformed susceptible plants, and that the resistance was inheritable. Ultrastructure analysis showed that nematodes led to the formation of galls or root knots in the susceptible lines while in the resistant transgenic plants, the CaMi gene triggered a hypersensitive response (HR) as well as many necrotic cells around nematodes. Rugang Chen and Hanxia Li are contributed equally to this work.     

The physiologic complexity of beat-to-beat blood pressure is associated with age-related alterations in blood pressure regulation

The fluctuations in resting-state beat-to-beat blood pressure (BP) are physiologically complex, and the degree of such BP complexity is believed to reflect the multiscale regulation of this critical physiologic process. Hypertension (HTN), one common age-related condition, is associated with altered BP regulation and diminished system responsiveness to perturbations such as orthostatic change. We thus aimed to characterize the impact of HTN on resting-state BP complexity, as well as the relationship between BP complexity and both adaptive capacity and underlying vascular characteristics. We recruited 392 participants (age: 60–91 years), including 144 that were normotensive and 248 with HTN (140 controlled- and 108 uncontrolled-HTN). Participants completed a 10-min continuous finger BP recording during supine rest, then underwent measures of lying-to-standing BP change, arterial stiffness (i.e., brachial-ankle pulse wave velocity), and endothelial function (i.e., flow-mediated vasodilation). The complexity of supine beat-to-beat systolic (SBP) and diastolic (DBP) BP was quantified using multiscale entropy. Thirty participants with HTN (16 controlled-HTN and 14 uncontrolled-HTN) exhibited orthostatic hypotension. SBP and DBP complexity was greatest in normotensive participants, lower in those with controlled-HTN, and lowest in those in uncontrolled-HTN (p < 0.0005). Lower SBP and DBP complexity correlated with greater lying-to-standing decrease in SBP and DBP level (β = −0.33 to −0.19, p < 0.01), greater arterial stiffness (β = −0.35 to −0.18, p < 0.01), and worse endothelial function (β = 0.17–0.22, p < 0.01), both across all participants and within the control- and uncontrolled-HTN groups. These results suggest that in older adults, BP complexity may capture the integrity of multiple interacting physiologic mechanisms that regulate BP and are important to cardiovascular health.     

几丁质合成抑制剂在白蚁防治中的研究进展

昆虫生长调节剂是一类新型的第三代杀虫剂,能阻碍或干扰昆虫正常的生长发育,活性高,残毒小,对环境污染少,大量应用于农、林、卫生害虫防治.其中,应用比较广泛的是几丁质合成抑制剂,能阻碍白蚁新表皮的形成,抑制白蚁的蜕皮而致死.目前,几丁质合成抑制剂如氟铃脲、杀铃脲、除虫脲、氟啶脲等已应用于白蚁群体防治,对白蚁有显著的控制作用,是目前砒剂和灭蚁灵较理想的替代物.     

SARS-CoV-2 spike protein interacts with and activates TLR41

Dear Editor, Accumulating clinical data suggest the main causes of death by COVID-19 include respiratory failure and the onset of sepsis.1 Importantly,sepsis ha...     

副珠蜡蚧阔柄跳小蜂的寄生影响因子

副珠蜡蚧阔柄跳小蜂Metaphycus parasaissetiae是橡副珠蜡蚧Parasaissetia nigra成虫的重要内寄生蜂。寄生蜂的寄生效果受多种因素影响,就温度、光周期、寄主成虫日龄、雌蜂日龄及交配等因子对副珠蜡蚧阔柄跳小蜂的寄生率、每头寄主的出蜂量及后代雌性率的影响进行研究,以期探明几种因子对该蜂寄生效果的影响。结果表明:温度为27—30℃时寄生率最高为91.7%,出蜂量以27℃最高为7.5头,雌性率以24℃条件最高为72.1%,其次27℃为62.6%,说明24—30℃是寄生效果较好的适温范围;光周期对副珠蜡蚧阔柄跳小蜂的影响明显,光暗比为12 h∶12 h条件下,其寄生率、出蜂量、后代雌性率均最大,分别为70.6%、5.3头、68.3%;副珠蜡蚧阔柄跳小蜂寄生用20—21日龄橡副珠蜡蚧成虫的寄生率、出蜂量及后代雌性率均为最高,分别为87.0%、5.6头、51.2%,说明20—21日龄的橡副珠蜡蚧成虫是副珠蜡蚧阔柄跳小蜂最适合寄生的阶段;雌蜂日龄对寄生效果的影响明显,3日龄的出蜂量最多为5.6头,4日龄的小蜂寄生率最高为81.7%,5日龄的雌性率最大为55.2%;交配是另一影响寄生效果及性比的重要因子,已交配的寄生率及出蜂量显著高于未交配的,分别为91.7%、7.5头,交配的雌性率为62.1%,而未交配所育后代均为雄蜂。综合以上结果分析,可考虑选用20—21日龄橡副珠蜡蚧成虫、充分交配的3—6日龄小蜂、温度27℃及光周期L∶D=12∶12作为室内扩繁副珠蜡蚧阔柄跳小蜂的理想条件组合。     

FGF21 promotes ischaemic angiogenesis and endothelial progenitor cells function under diabetic conditions in an AMPK/NAD+-dependent manner

Diabetic vascular complications are closely associated with long-term vascular dysfunction and poor neovascularization. Endothelial progenitor cells (EPCs) play pivotal roles in maintaining vascular homeostasis and triggering angiogenesis, and EPC dysfunction contributes to defective angiogenesis and resultant diabetic vascular complications. Fibroblast growth factor 21 (FGF21) has received substantial attention as a potential therapeutic agent for diabetes via regulating glucose and lipid metabolism. However, the effects of FGF21 on diabetic vascular complications remain unclear. In the present study, the in vivo results showed that FGF21 efficiently improved blood perfusion and ischaemic angiogenesis in both type 1 and type 2 diabetic mice, and these effects were accompanied by enhanced EPC mobilization and infiltration into ischaemic muscle tissues and increases in plasma stromal cell–derived factor-1 concentration. The in vitro results revealed that FGF21 directly prevented EPC damage induced by high glucose, and the mechanistic studies demonstrated that nicotinamide adenine dinucleotide (NAD⁺) was dramatically decreased in EPCs challenged with high glucose, whereas FGF21 treatment significantly increased NAD⁺ content in an AMPK-dependent manner, resulting in improved angiogenic capability of EPCs. These results indicate that FGF21 promotes ischaemic angiogenesis and the angiogenic ability of EPCs under diabetic conditions by activating the AMPK/NAD⁺ pathway.