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. 相似文献
Plasmonics - In this paper, we propose an ultra-broadband multi-slot cross bowtie (MSCB) nanoantenna for light absorption, whose elements compose of dual rectangles and cross bowtie and rectangular... 相似文献
The “Nanguo” pear is a typically climacteric fruit and ethylene is the main factor controlling the ripening process of climacteric fruit. Ethylene biosynthesis has been studied clearly and ACC synthase (ACS) is the rate-limited enzyme. ACO (ACC oxidase) is another important enzyme in ethylene biosynthesis. By exploring the pear genome, we identified 13 ACS genes and 11 ACO genes, respectively, and their expression patterns in fruit and other organs were investigated. Among these genes, 11 ACS and 8ACO genes were expressed in pear fruits. What’s more, 4 ACS and 3ACO genes could be induced by Ethephon and inhibited by 1-MCP treatment. This study is the first time to explore ACS and ACO genes at genome-wide level and will provide new data for research on pear fruit ripening.
CO2 fluxes from wood decomposition represent an important source of carbon from forest ecosystems to the atmosphere, which are determined by both wood traits and climate influencing the metabolic rates of decomposers. Previous studies have quantified the effects of moisture and temperature on wood decomposition, but these effects were not separated from the potential influence of wood traits. Indeed, it is not well understood how traits and climate interact to influence wood CO2 fluxes. Here, we examined the responses of CO2 fluxes from dead wood with different traits (angiosperm and gymnosperm) to 0%, 35%, and 70% rainfall reduction across seasonal temperature gradients. Our results showed that drought significantly decreased wood CO2 fluxes, but its effects varied with both taxonomical group and drought intensity. Drought‐induced reduction in wood CO2 fluxes was larger in angiosperms than gymnosperms for the 35% rainfall reduction treatment, but there was no significant difference between these groups for the 70% reduction treatment. This is because wood nitrogen density and carbon quality were significantly higher in angiosperms than gymnosperms, yielding a higher moisture sensitivity of wood decomposition. These findings were demonstrated by a significant positive interaction effect between wood nitrogen and moisture on CO2 fluxes in a structural equation model. Additionally, we ascertained that a constant temperature sensitivity of CO2 fluxes was independent of wood traits and consistent with previous estimates for extracellular enzyme kinetics. Our results highlight the key role of wood traits in regulating drought responses of wood carbon fluxes. Given that both climate and forest management might extensively modify taxonomic compositions in the future, it is critical for carbon cycle models to account for such interactions between wood traits and climate in driving dynamics of wood decomposition. 相似文献
Microsatellites are widely distributed throughout nearly all genomes which have been extensively exploited as powerful genetic markers for diverse applications due to their high polymorphisms. Their length variations are involved in gene regulation and implicated in numerous genetic diseases even in cancers. Although much effort has been devoted in microsatellite database construction, the existing microsatellite databases still had some drawbacks, such as limited number of species, unfriendly export format, missing marker development, lack of compound microsatellites and absence of gene annotation, which seriously restricted researchers to perform downstream analysis. In order to overcome the above limitations, we developed PSMD (Pan‐Species Microsatellite Database, http://big.cdu.edu.cn/psmd/ ) as a web‐based database to facilitate researchers to easily identify microsatellites, exploit reliable molecular markers and compare microsatellite distribution pattern on genome‐wide scale. In current release, PSMD comprises 678,106,741 perfect microsatellites and 43,848,943 compound microsatellites from 18,408 organisms, which covered almost all species with available genomic data. In addition to interactive browse interface, PSMD also offers a flexible filter function for users to quickly gain desired microsatellites from large data sets. PSMD allows users to export GFF3 formatted file and CSV formatted statistical file for downstream analysis. We also implemented an online tool for analysing occurrence of microsatellites with user‐defined parameters. Furthermore, Primer3 was embedded to help users to design high‐quality primers with customizable settings. To our knowledge, PSMD is the most extensive resource which is likely to be adopted by scientists engaged in biological, medical, environmental and agricultural research. 相似文献
Probiotics and Antimicrobial Proteins - This paper aims to study the effects of compound microbe-based beads on changes in the intestinal microbiota and alleviation of high-fat (HF)... 相似文献