A protein–protein interaction map reveals that the Coxiella burnetii effector CirB inhibits host proteasome activity

Coxiella burnetii is the etiological agent of the zoonotic disease Q fever, which is featured by its ability to replicate in acid vacuoles resembling the lysosomal network. One key virulence determinant of C. burnetii is the Dot/Icm system that transfers more than 150 effector proteins into host cells. These effectors function to construct the lysosome-like compartment permissive for bacterial replication, but the functions of most of these effectors remain elusive. In this study, we used an affinity tag purification mass spectrometry (AP-MS) approach to generate a C. burnetii-human protein-protein interaction (PPI) map involving 53 C. burnetii effectors and 3480 host proteins. This PPI map revealed that the C. burnetii effector CBU0425 (designated CirB) interacts with most subunits of the 20S core proteasome. We found that ectopically expressed CirB inhibits hydrolytic activity of the proteasome. In addition, overexpression of CirB in C. burnetii caused dramatic inhibition of proteasome activity in host cells, while knocking down CirB expression alleviated such inhibitory effects. Moreover, we showed that a region of CirB that spans residues 91–120 binds to the proteasome subunit PSMB5 (beta 5). Finally, PSMB5 knockdown promotes C. burnetii virulence, highlighting the importance of proteasome activity modulation during the course of C. burnetii infection.     

化感物质对枯草芽孢杆菌(Bacillus subtilis)在厌氧条件下的生长及反硝化作用的影响

研究由秸秆腐解产生的化感物质 :阿魏酸 ( t-FA)、对羟基苯甲酸 ( p-HA)和苯甲酸 ( BA)在不同浓度下对厌氧培养的枯草芽孢杆菌 ( Bacillussubtilis)的生长及其反硝化活性的影响。结果表明 ,3种浓度的阿魏酸 ( 5.1 5、2 .58、0 .2 6mmol/L)均表现出对枯草芽孢杆菌的生长有抑制作用。对羟基苯甲酸 ( 0 .3 6、3 .62、7.2 4 mmol/L )对生长影响不明显。 8.1 9mmol/L和 4 .0 9mmol/L的苯甲酸有一定的刺激作用 ,而 0 .4 1 mmol/L的苯甲酸与对照无差别。实验表明枯草芽孢秆菌不仅能转化 NO- 3生成 NO- 2 ,而且还能转化 NO- 2 生成 N2 O。 3种化感物质对 NO- 3的转化均表现抑制作用 ,其抑制作用强弱依次为阿魏酸 >对羟基苯甲酸 >苯甲酸。高浓度的抑制作用强于低浓度。阿魏酸在 5.1 5mmol/L和 2 .58mmol/L浓度下 ,其抑制作用的差异显著性分别为 P<0 .0 1 ,P<0 .0 5。 NO- 2 的生成与 NO- 3的减少相互有关联 ,第 3天测定时 ,各处理中NO- 3急剧减少 ,而 NO- 2 急剧增加。在阿魏酸、苯甲酸处理中的 NO- 2 积累高峰在第 3天、第 4天 ,然后下降。而在对羟基苯甲酸的处理中 NO- 2 的积累一直上升 ,在第 6天的观察中仍未出现下降趋势。 3种化感物质均能抑制 N2 O的生成 ,至于在田间的抑制效果尚需进一步试验     

Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis

Depression is a serious public-health issue. Recent reports have suggested higher susceptibility to viral infections in depressive patients. However, how depression affects antiviral innate immune signaling remains unknown. Here, we revealed a reduction in expression of Abelson helper integration site 1 (AHI1) in the peripheral blood mononuclear cells (PBMCs) and macrophages from the patients with major depressive disorder (MDD), which leads to attenuated antiviral immune response. We found that depression-related arginine vasopressin (AVP) induces reduction of AHI1 in macrophages. Further studies demonstrated that AHI1 is a critical stabilizer of basal type-I-interferon (IFN-I) signaling. Mechanistically, AHI1 recruits OTUD1 to deubiquitinate and stabilize Tyk2, while AHI1 reduction downregulates Tyk2 and IFN-I signaling activity in macrophages from both MDD patients and depression model mice. Interestingly, we identified a clinical analgesic meptazinol that effectively stimulates AHI1 expression, thus enhancing IFN-I antiviral defense in depression model mice. Our study promotes the understanding of the signaling mechanisms of depression-mediated antiviral immune dysfunction, and reveals meptazinol as an enhancer of antiviral innate immunity in depressive patients.Subject terms: Innate immunity, Ubiquitylation, Cell signalling     

SWAT模型对景观格局变化的敏感性分析——以丹江口库区老灌河流域为例

景观的空间配置与类型组成能够对流域的产流、产沙及非点源污染产生影响。在以往SWAT模型研究中,往往默认水文模型考虑了该影响。为分析SWAT模型对不同景观格局变化的敏感性,根据老灌河流域2000年土地利用在各子流域的组成,模拟研究区更为破碎、复杂的景观空间配置,通过设置多套试验参数,利用SWAT模型生成基于不同景观格局的模拟结果。结果表明,SWAT模型不能反映除坡度和面积变化之外的景观水平下各斑块之间因景观空间格局改变对流域产流、产沙以及非点源污染的影响;模型通过其他参数的调整,弥补了模型分析数据的不足,使实测数据与模型部分结果高度吻合。这表明,一个能够反映流域部分水文特征的SWAT模型,未必是对研究区真实情形的模拟,而是各个参数间平衡的结果。因此,在利用SWAT模型分析模拟景观变化时,不应默认模型能够模拟景观空间格局改变对流域水文过程的影响,同时研究者可以通过划分坡度带,提高模型对不同坡度土地利用的敏感性。     

Exercise increases the release of NAMPT in extracellular vesicles and alters NAD + activity in recipient cells

Aging is associated with a loss of metabolic homeostasis, with cofactors such as nicotinamide adenine dinucleotide (NAD⁺) declining over time. The decrease in NAD⁺ production has been linked to the age‐related loss of circulating extracellular nicotinamide phosphoribosyltransferase (eNAMPT), the rate‐limiting enzyme in the NAD⁺ biosynthetic pathway. eNAMPT is found almost exclusively in extracellular vesicles (EVs), providing a mechanism for the distribution of the enzyme in different tissues. Currently, the physiological cause for the release of eNAMPT is unknown, and how it may be affected by age and physical exercise. Here, we show that release of small EVs into the bloodstream is stimulated following moderate intensity exercise in humans. Exercise also increased the eNAMPT content in EVs, most prominently in young individuals with higher aerobic fitness. Both mature fit and young unfit individuals exhibited a limited increase in EV‐eNAMPT release following exercise, indicating that this mechanism is related to both the age and physical fitness of a person. Notably, unfit mature individuals were unable to increase the release of eNAMPT in EVs after exercise, suggesting that lower fitness levels and aging attenuate this important signalling mechanism in the body. EVs isolated from exercising humans containing eNAMPT were able to alter the abundance of NAD⁺ and SIRT1 activity in recipient cells compared to pre‐exercise EVs, indicating a pathway for inter‐tissue signalling promoted through exercise. Our results suggest a mechanism to limit age‐related NAD⁺ decline, through the systemic delivery of eNAMPT via EVs released during exercise.     

格网尺度下典型旅游城市生态服务价值估算和时空分异特征——以三亚为例

以典型旅游城市三亚市为案例地,利用2006-2018年4期Landsat遥感影像数据,借助ENVI、ArcGIS平台定量识别土地利用演变特征,在1km×1km格网尺度下估算旅游地生态系统服务价值,并结合空间探索性数据分析揭示生态系统服务价值时空分异特征及其与旅游地发展的时空耦合关系。结果表明：（1）2006-2018年间,三亚市生态系统服务价值总量呈逐年下降趋势,由6.73×10⁹元降至5.76×10⁹元,累计减少9.78×10⁸元;（2）空间格局上,三亚市呈"南低北高"空间分异格局,2006-2018年增值区域连片分布于崖州区、天涯区、吉阳区南部区域,且呈逐年减少趋势,减值区域集聚于天涯区东北部、海棠区;（3）空间集聚上,生态系统服务价值截面各年份均呈显著空间正相关且相关性先降后增。高高集聚区位于天涯区北部区域,低低集聚区分布于沿海、海湾地区;（4）旅游发展与生态系统服务价值时空演化特征关联性较强。三亚市天涯区北部林地生态环境良好,生态系统服务价值略有下降但绝对数值稳定,是生态系统服务价值主要来源;旅游发展较为迅速的三亚湾、崖州湾以及海棠湾,相对增值区域较多,但绝对生态系统服务价值损失显著,严重滞后于其他区域。     

A bacterial effector counteracts host autophagy by promoting degradation of an autophagy component

Beyond its role in cellular homeostasis, autophagy plays anti‐ and promicrobial roles in host–microbe interactions, both in animals and plants. One prominent role of antimicrobial autophagy is to degrade intracellular pathogens or microbial molecules, in a process termed xenophagy. Consequently, microbes evolved mechanisms to hijack or modulate autophagy to escape elimination. Although well‐described in animals, the extent to which xenophagy contributes to plant–bacteria interactions remains unknown. Here, we provide evidence that Xanthomonas campestris pv. vesicatoria (Xcv) suppresses host autophagy by utilizing type‐III effector XopL. XopL interacts with and degrades the autophagy component SH3P2 via its E3 ligase activity to promote infection. Intriguingly, XopL is targeted for degradation by defense‐related selective autophagy mediated by NBR1/Joka2, revealing a complex antagonistic interplay between XopL and the host autophagy machinery. Our results implicate plant antimicrobial autophagy in the depletion of a bacterial virulence factor and unravel an unprecedented pathogen strategy to counteract defense‐related autophagy in plant–bacteria interactions.     

超抗原SEA增强小鼠对HBV DNA 疫苗的免疫反应

观察超抗原SEA(D227A)的真核表达载体(pmSEA),对HBVDNA疫苗诱导Balbc小鼠(H2d)免疫应答的调节作用。肌内注射空载体pcDNA3、HBVDNA疫苗加pmSEA佐剂(pHBVS2S+pmSEA)或不加佐剂(pHBVS2S);ELISA法测定血清抗HBs;ELISPOT检测分泌IFNγ的脾淋巴细胞;4h51Cr释放法检测小鼠脾细胞CTL活性。HBVDNA佐剂组免疫小鼠抗HBsAg抗体滴度明显高于不加佐剂组,其IgG1IgG2a的比例不同于多肽免疫组,二者分别为0.282与10。HBVDNA佐剂组均能增强IgG1和IgG2a的产生,是不加佐剂组的1.36、1.73倍。佐剂组小鼠脾淋巴细胞IFNγ的分泌量是不加佐剂组2～3倍。CTL细胞杀伤活性(E:T=100)佐剂组与不加佐剂组分别为:69.77%±7.5%、42.81%±7.7%,差异显著(P<0.05)。HBVDNA疫苗具有较强的免疫原性,能够诱导机体产生特异性的抗体及CTL反应;pmSEA佐剂能够提高小鼠对DNA疫苗的免疫应答,有望成为DNA疫苗的免疫佐剂。     

盐渍化胁迫下油葵对土壤原油污染的适应性及其改良措施

为了探究植物在盐渍化胁迫下对原油污染的适应性及改良措施,本研究以油葵作为研究对象,进行了原油-氯化钠-脱硫石膏盆栽正交试验和煤渣-沸石-脱硫石膏-锯沫盆栽正交试验.结果表明: 在盐渍化条件下,随着原油浓度的增大,油葵幼苗株高相对生长率(RGR)、地上生物量RGR、根氮磷比均显著减小,超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性呈先增加后显著降低的趋势;随着锯沫体积分数的加大,油葵株高RGR和地上生物量RGR均显著增加,SOD活性逐渐降低,说明锯沫在改良盐渍化原油污染土壤方面比煤渣、沸石和脱硫石膏效果显著.在盐渍化条件下,原油污染能够降低油葵幼苗的生长率,锯沫对改良原油污染有较好的效果.