Base excision repair but not DNA double‐strand break repair is impaired in aged human adipose‐derived stem cells

The decline in DNA repair capacity contributes to the age‐associated decrease in genome integrity in somatic cells of different species. However, due to the lack of clinical samples and appropriate tools for studying DNA repair, whether and how age‐associated changes in DNA repair result in a loss of genome integrity of human adult stem cells remains incompletely characterized. Here, we isolated 20 eyelid adipose‐derived stem cell (ADSC) lines from healthy individuals (young: 10 donors with ages ranging 17–25 years; old: 10 donors with ages ranging 50–59 years). Using these cell lines, we systematically compared the efficiency of base excision repair (BER) and two DNA double‐strand break (DSB) repair pathways—nonhomologous end joining (NHEJ) and homologous recombination (HR)—between the young and old groups. Surprisingly, we found that the efficiency of BER but not NHEJ or HR is impaired in aged human ADSCs, which is in contrast to previous findings that DSB repair declines with age in human fibroblasts. We also demonstrated that BER efficiency is negatively associated with tail moment, which reflects a loss of genome integrity in human ADSCs. Mechanistic studies indicated that at the protein level XRCC1, but not other BER factors, exhibited age‐associated decline. Overexpression of XRCC1 reversed the decline of BER efficiency and genome integrity, indicating that XRCC1 is a potential therapeutic target for stabilizing genomes in aged ADSCs.     

Tau inhibits PKA by nuclear proteasome‐dependent PKAR2α elevation with suppressed CREB/GluA1 phosphorylation

Intraneuronal accumulation of wild‐type tau plays a key role in Alzheimer's disease, while the mechanisms underlying tauopathy and memory impairment remain unclear. Here, we report that overexpressing full‐length wild‐type human tau (hTau) in mouse hippocampus induces learning and memory deficits with remarkably reduced levels of multiple synapse‐ and memory‐associated proteins. Overexpressing hTau inhibits the activity of protein kinase A (PKA) and decreases the phosphorylation level of cAMP‐response element binding protein (CREB), GluA1, and TrkB with reduced BDNF mRNA and protein levels both in vitro and in vivo. Simultaneously, overexpressing hTau increased PKAR2α (an inhibitory subunit of PKA) in nuclear fraction and inactivated proteasome activity. With an increased association of PKAR2α with PA28γ (a nuclear proteasome activator), the formation of PA28γ‐20S proteasome complex remarkably decreased in the nuclear fraction, followed by a reduced interaction of PKAR2α with 20S proteasome. Both downregulating PKAR2α by shRNA and upregulating proteasome by expressing PA28γ rescued hTau‐induced PKA inhibition and CREB dephosphorylation, and upregulating PKA improved hTau‐induced cognitive deficits in mice. Together, these data reveal that intracellular tau accumulation induces synapse and memory impairments by inhibiting PKA/CREB/BDNF/TrkB and PKA/GluA1 signaling, and deficit of PA28γ‐20S proteasome complex formation contributes to PKAR2α elevation and PKA inhibition.     

Mutation of the chloroplast‐localized phosphate transporter OsPHT2;1 reduces flavonoid accumulation and UV tolerance in rice

Phosphorus (P) is an essential macronutrient required for plant development and production. The mechanisms regulating phosphate (Pi) uptake are well established, but the function of chloroplast Pi homeostasis is poorly understood in Oryza sativa (rice). PHT2;1 is one of the transporters/translocators mediating Pi import into chloroplasts. In this study, to gain insight into the role of OsPHT2;1‐mediated stroma Pi, we analyzed OsPHT2;1 function in Pi utilization and photoprotection. Our results showed that OsPHT2;1 was induced by Pi starvation and light exposure. Cell‐based assays showed that OsPHT2;1 localized to the chloroplast envelope and functioned as a low‐affinity Pi transporter. The ospht2;1 had reduced Pi accumulation, plant growth and photosynthetic rates. Metabolite profiling revealed that 52.6% of the decreased metabolites in ospht2;1 plants were flavonoids, which was further confirmed by 40% lower content of total flavonoids compared with the wild type. As a consequence, ospht2;1 plants were more sensitive to UV‐B irradiation. Moreover, the content of phenylalanine, the precursor of flavonoids, was also reduced, and was largely associated with the repressed expression of ADT1/MTR1. Furthermore, the ospht2;1 plants showed decreased grain yields at relatively high levels of UV‐B irradiance. In summary, OsPHT2;1 functions as a chloroplast‐localized low‐affinity Pi transporter that mediates UV tolerance and rice yields at different latitudes.     

血清sST2在心力衰竭诊断、预后中的应用价值

心力衰竭(心衰)的发病率正随着人口老龄化的加速而显著上升,目前仍然是一个重大的公共健康问题。尽管近年来在心衰治疗方面取得了显著成效,但患者的生存率依旧很低,预后差,确诊心衰后5年内死亡率高达50%。如果能够对心衰进行快速有效的诊断并按危险程度进行合理分层,将为临床医生制定治疗方案提供重要的参考依据。生物标志物在心衰的诊断、疗效评估及预后判断方面都具有重要的意义。心力衰竭是一种复杂的疾病,涉及多种生理病理过程。心力衰竭时,神经内分泌系统被激活,同时伴随着血容量和心室壁压力增加,心室肌细胞分泌NT-proBNP/BNP,因此,其可作为心衰诊断和预后生物标志物。然而血浆中NT-proBNP/BNP易受到年龄、性别、体型、左室肥大、心动过速、右心室过载、低氧血症、肾脏功能等诸多因素影响。sST2作为一种新型心力衰竭标志物,近年来备受关注,它不仅能够反映心肌纤维化程度并预测是否发生心室重构,且不受年龄、性别、肾功能等因素的影响,同时具有更低的参考变化值和个体指数,更适合用于连续监测和指导治疗,是评价心力衰竭的理想指标之一。文中对近年来sST2在心衰诊断和预后方面的研究进展进行总结归纳,并对其发展趋势进行展望。     

水稻粒长QTL定位与主效基因的遗传分析

该研究利用短粒普通野生稻矮杆突变体和长粒栽培稻品种KJ01组配杂交组合F_1,构建分离群体F_2;并对该群体粒长进行性状遗传分析,利用平均分布于水稻的12条染色体上的132对多态分子标记对该群体进行QTL定位及主效QTLs遗传分析,为进一步克隆新的主效粒长基因奠定基础,并为水稻粒形育种提供理论依据。结果表明:(1)所构建的水稻杂交组合分离群体F_2的粒长性状为多基因控制的数量性状。(2)对543株F_2分离群体进行QTL连锁分析,构建了控制水稻粒长的连锁遗传图谱,总长为1 713.94 cM,共检测出24个QTLs,只有3个表现为加性遗传效应,其余位点均表现为遗传负效应。(3)检测到的3个主效QTLs分别位于3号染色体的分子标记PSM379～RID24455、RID24455～RM15689和RM571～RM16238之间,且三者对表型的贡献率分别为54.85%、31.02%和7.62%。(4)在标记PSM379～RID24455之间已克隆到的粒长基因为该研究新发现的主效QTL位点。     

“2020年后全球生物多样性框架”进展及展望

“2020年后全球生物多样性框架”是当前《生物多样性公约》谈判的焦点议题之一。本文阐述了框架制定的背景, 介绍了“2020年后全球生物多样性框架”不限成员名额工作组(Open Ended Working Group, OEWG),的谈判过程, 综合分析了缔约方在各有关磋商进程中的观点, 以及目前缔约方对框架各个要素的共识和分歧, 评估了框架的制定进展, 并就框架的设计提出四点展望: (1)阐明转型变革的具体实施路径; (2)平衡反映公约三大目标; (3)加强与其他全球治理进程的协同; (4)强化框架对全球及缔约方履约进展的评估和审查。最后提出对我国的建议: (1)及时更新国家生物多样性战略与行动计划(National Biodiversity Strategies and Action Plans, NBSAP); (2)加强国内生物多样性工作的协调; (3)继续加强生态环境执法和责任机制。为缔约方更好参与框架制定进程, 深入了解框架及其磋商进展提供参考, 并为下一步框架制定提供参考。