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     

邻苯二甲酸对萝卜种子萌发、幼苗叶片膜脂过氧化及渗透调节物质的影响

华北地区是我国玉米的主产区,玉米秸秆还田不仅可有效改善土壤理化性状、提高土壤生物有效性,还会在腐解过程中释放出目前公认的化感物质——酚酸类物质,邻苯二甲酸是玉米秸秆腐解液中的主要酚酸类物质。从玉米秸秆还田过程中主要腐解产物(邻苯二甲酸)对蔬菜作物的化感效应角度进行了研究,为量化秸秆还田量及构建粮-菜轮作制度探寻化感效应依据。试验以萝卜为蔬菜材料,通过配置4个浓度(0.05、0.5、1.0、2.0 mmol/L)的邻苯二甲酸溶液,模拟玉米秸秆还田条件,以清水为对照,研究主要腐解产物邻苯二甲酸对萝卜种子萌发、幼苗生长、膜脂过氧化作用及渗透调节物质的影响。结果表明:(1)萝卜不同生育期对邻苯二甲酸化感效应的响应程度不同。在0.05-1 mmol/L浓度范围内,邻苯二甲酸处理促进了萝卜种子萌发,但随着处理浓度的增大,促进作用减弱;浓度达到2 mmol/L时对萝卜种子萌发具有抑制效果。(2)邻苯二甲酸0.05mmol/L处理,促进了萝卜幼苗干鲜物质积累,幼苗根系生长,其中根系长度和根系表面积分别比对照提高42.03%、38.36%,显著高于清水对照;植株体内超氧化物歧化酶(Superoxide dismutase, SOD)活性增大,过氧化物酶(Peroxidase, POD)、过氧化氢酶(Catalase, CAT)活性降低,膜脂过氧化产物丙二醛(Malonaldehyde, MDA)含量与对照无显著差异。(3)当邻苯二甲酸浓度超过0.5 mmol/L时,萝卜幼苗脂质过氧化伤害加剧,体内MDA含量急剧增加,代谢与生理功能出现紊乱,正常生长及干鲜物质积累受到显著抑制。邻苯二甲酸浓度达到2 mmol/L时,叶片数较对照降低了36.51%;根系长度、根系表面积及根尖数降幅分别为64.46%、40.20%、41.28%。(4)对于渗透调节物质的影响,邻苯二甲酸处理促进了萝卜幼苗叶片可溶性糖含量的增加,但随着处理浓度的升高其促进作用逐渐减弱;可溶性蛋白含量随着邻苯二甲酸处理浓度的升高表现出逐渐减少的趋势,分别较对照降低了12.82%、14.88%、21.58%、24.73%。因此,华北地区实施玉米-萝卜轮作模式,从化感效应角度研究玉米秸秆量化还田,应将土壤中邻苯二甲酸浓度控制在0.5 mmol/L范围以内,以防止邻苯二甲酸浓度过高对萝卜幼苗生长的抑制作用。     

川西米亚罗林区不同海拔岷江冷杉生长对气候变化的响应

为分析青藏高原东缘半湿润区树木生长与气候关系随海拔变化的规律,于川西米亚罗林区分别在高、中、低海拔选取3个采样点,共采集132棵岷江冷杉年轮样芯,建立了最长达170a(1842-2011年)3个海拔高度的差值年表.岷江冷杉年轮指数与气候因子的相关分析表明:随海拔高度降低,温度与生长的负相关呈增加趋势.高海拔岷江冷杉径向生长与前—年冬季最低温呈显著正相关,中低海拔与当年春季均温、最高温和年均最高温呈显著负相关.低海拔岷江冷杉与当年4月降水呈显著正相关,随海拔升高降水与岷江冷杉生长的相关性降低.中低海拔岷江冷杉年表与4、5月帕尔默干旱指数(P DSI)呈显著正相关,表明在中低海拔存在春季干旱胁迫,抑制了岷江冷杉的生长.另外,大龄树木比小龄树木对气候变化的响应更敏感.     

区域生态文明建设水平综合评估指标

2007年中国政府提出"生态文明"建设以来,已批准了三批52个生态文明建设试点。生态系统与社会经济发展的复杂性要求科学、客观地评估区域生态文明建设,以便科学地决策和行动。区域生态文明建设是一个复合的过程,其核心在于社会-经济-自然复合生态系统各组分的和谐进步。因此,基于生态系统服务(ES)、生态足迹(EF)和人均GDP3个指标,以及这3个指标所代表的资源禀赋、人类对自然生态系统的占用、经济增长之间的线性逻辑关系,构建综合性相对指数;并以此对2010年中国大陆各省(市、直辖市)的生态文明建设水平进行了综合评估,其中,海南省的生态文明建设指数最大,为0.5091,北京市的指数最小,为0.0377;最后,分析了2010年中国大陆各省(市、区)生态文明建设的生态压力和生态效率,北京、天津和上海3个直辖市处于低资源禀赋高资源消费状况,全国大多数省(市、区)处于低消耗和低产出的阶段,经济增长尚有较大的潜力。     

中国陆地生态系统碳源/汇整合分析

国家尺度陆地生态系统碳收支及其循环过程的研究对于提升地球系统科学与全球变化科学的科技创新能力、提高我国参与应对全球气候变化国际行动和维护国家利益的话语权、保障国家生态安全和改进生态系统管理都具有重要意义。近年来,我国已经在气候变化与陆地生态系统碳循环领域开展了大量的研究工作,主要包括国家清查、生态系统模型模拟、大气反演等手段。然而,由于大尺度陆地生态系统碳源/汇的估算存在很大的不确定性,目前尚未形成国家尺度的陆地生态系统碳源/汇的整合分析。通过搜集已发表的关于中国陆地生态系统及其组分碳源/汇的59篇文献,整合国家清查、生态系统模型模拟、大气反演3种研究手段,分析中国陆地生态系统碳源/汇大小以及时间尺度上的动态变化。结果表明,在1960s-2010s期间中国陆地生态系统碳汇整体呈上升趋势,平均为（0.213±0.030）Pg C/a,其中森林、草地、农田和灌木生态系统碳汇分别为（0.101±0.023）Pg C/a、（0.032±0.007）Pg C/a、（0.043±0.010）Pg C/a和（0.028±0.010）Pg C/a。森林生态系统中的植被碳汇远大于土壤碳汇,然而这种格局在草地和农田生态系统却相反,而且1960s-2010s期间中国主要植被类型的生态系统碳汇总体上随时间呈增加趋势。融合多源数据（地面观测、激光雷达、卫星遥感等）、多尺度数据（样地尺度、站点尺度、区域尺度）以及多手段数据（联网观测、森林清查、模型模拟）,有助于全面准确地评估中国陆地生态系统碳源/汇及其对气候变化的响应。     

斑点叉尾鮰源普通变形杆菌的分离、鉴定及药敏特性

【目的】对患病斑点叉尾鮰进行病原菌分离、鉴定及药敏实验,为斑点叉尾鮰肠道坏死病的防控提供参考。【方法】从患病斑点叉尾鮰病灶、肝、脾和肾分离纯化病原菌,经理化特性测定及16S rRNA基因序列分析对其进行鉴定,开展人工感染试验,并利用纸片扩散法进行药敏特性分析。【结果】分离菌株k1为本次引发斑点叉尾鮰病害的致病菌,其对斑点叉尾鮰的LD50为2.82×10~5 CFU/g。菌株k1理化特性与普通变形杆菌Proteus vulgaris基本一致,16S rRNA基因序列与普通变形杆菌相似性最高,综合判定分离菌株为普通变形杆菌。分离菌株k1对环丙沙星、头孢唑林及头孢拉定等12种抗生素高度敏感,对苯唑西林、阿莫西林及痢特灵等7种抗生素耐药。【结论】分离菌株k1是斑点叉尾鮰病原菌,养殖时可选用庆大霉素及氟苯尼考等药物进行防控。     

Age‐related memory vulnerability to interfering stimuli is caused by gradual loss of MAPK‐dependent protection in Drosophila

Age‐related memory impairment (AMI) is a common phenomenon across species. Vulnerability to interfering stimuli has been proposed to be an important cause of AMI. However, the molecular mechanisms underlying this vulnerability‐related AMI remain unknown. Here we show that learning‐activated MAPK signals are gradually lost with age, leading to vulnerability‐related AMI in Drosophila. Young flies (2‐ or 3‐day‐old) exhibited a significant increase in phosphorylated MAPK levels within 15 min after learning, whereas aged flies (25‐day‐old) did not. Compared to 3‐day‐old flies, significant 1 h memory impairments were observed in 15‐, 20‐, and 30‐day‐old flies, but not in 10‐day‐old flies. However, with post‐learning interfering stimuli such as cooling or electric stimuli, 10‐day‐old flies had worse memory performance at 1 h than 3‐day‐old flies, showing a premature AMI phenomenon. Increasing learning‐activated MAPK signals through acute transgene expression in mushroom body (MB) neurons restored physiological trace of 1 h memory in a pair of MB output neurons in aged flies. Decreasing such signals in young flies mimicked the impairment of 1 h memory trace in aged flies. Restoring learning‐activated MAPK signals in MB neurons in aged flies significantly suppressed AMI even with interfering stimuli. Thus, our data suggest that age‐related loss of learning‐activated neuronal MAPK signals causes memory vulnerability to interfering stimuli, thereby leading to AMI.     

The small nonstructural protein NP1 of human bocavirus 1 directly interacts with Ku70 and RPA70 and facilitates viral DNA replication

Human bocavirus 1 (HBoV1), a member of the genus Bocaparvovirus of the family Parvoviridae, causes acute respiratory tract infections in young children. Well-differentiated pseudostratified human airway epithelium cultured at an air-liquid interface (HAE-ALI) is an ideal in vitro culture model to study HBoV1 infection. Unique to other parvoviruses, bocaparvoviruses express a small nonstructured protein NP1 of ~25 kDa from an open reading frame (ORF) in the center of the viral genome. NP1 plays an important role in viral DNA replication and pre-mRNA processing. In this study, we performed an affinity purification assay to identify HBoV1 NP1-inteacting proteins. We identified that Ku70 and RPA70 directly interact with the NP1 at a high binding affinity, characterized with an equilibrium dissociation constant (K_D) of 95 nM and 122 nM, respectively. Furthermore, we mapped the key NP1-interacting domains of Ku70 at aa266-439 and of RPA70 at aa181-422. Following a dominant negative strategy, we revealed that the interactions of Ku70 and RPA70 with NP1 play a significant role in HBoV1 DNA replication not only in an in vitro viral DNA replication assay but also in HBoV1-infected HAE-ALI cultures. Collectively, our study revealed a novel mechanism by which HBoV1 NP1 enhances viral DNA replication through its direct interactions with Ku70 and RPA70.     

传染性支气管炎病毒N蛋白CTL表位与BF2*15鸡MHC I基序的相互作用

【目的】近年来鸡传染性支气管炎病毒在国内鸡群呈现流行趋势,尤其是变异毒株的出现,加剧了对鸡群的危害。鸡主要组织相容复合体蛋白(MHC I)通过特定的基序结合抗原表位多肽,进而识别感染病毒的细胞并引起免疫反应,达到清除病毒的效果。鉴定BF2*15鸡主要组织相容复合体(MHC I)的结合基序。【方法】采用同源建模、分子动力学和分子对接等计算方法,构建了传染性支气管炎病毒(IBV)N蛋白表位多肽和鸡MHC I BF2*15之间的复合物结构,来探索BF2*15识别抗原表位多肽的潜在结合基序。【结果】通过对该复合物的相互作用关系分析,鉴定出BF2*15鸡主要组织相容复合体(MHC I)的一条潜在结合基序"x-Arg-xx-x-Arg"。【结论】解释了传染性支气管炎病毒N蛋白CTL表位与BF2*15鸡MHC I基序的相互作用原理,该研究结果对了解传染性支气管炎病毒免疫机制以及基于特定基序筛选和设计通用疫苗具有借鉴意义。     

The connecting cilium inner scaffold provides a structural foundation that protects against retinal degeneration

Inherited retinal degeneration due to loss of photoreceptor cells is a leading cause of human blindness. These cells possess a photosensitive outer segment linked to the cell body through the connecting cilium (CC). While structural defects of the CC have been associated with retinal degeneration, its nanoscale molecular composition, assembly, and function are barely known. Here, using expansion microscopy and electron microscopy, we reveal the molecular architecture of the CC and demonstrate that microtubules are linked together by a CC inner scaffold containing POC5, CENTRIN, and FAM161A. Dissecting CC inner scaffold assembly during photoreceptor development in mouse revealed that it acts as a structural zipper, progressively bridging microtubule doublets and straightening the CC. Furthermore, we show that Fam161a disruption in mouse leads to specific CC inner scaffold loss and triggers microtubule doublet spreading, prior to outer segment collapse and photoreceptor degeneration, suggesting a molecular mechanism for a subtype of retinitis pigmentosa.

Inherited retinal degeneration due to loss of photoreceptor cells is a leading cause of human blindness. Ultrastructure expansion microscopy on mouse retina reveals the presence of a novel structure inside the photoreceptor connecting cilium, the inner scaffold, that protects the outer segment against degeneration.