C-terminal truncation exacerbates the aggregation and cytotoxicity of α-Synuclein: A vicious cycle in Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disease which usually associates with neuroinflammation. The main pathological characteristics of PD are dopaminergic neurons death and the presence of Lewy bodies which are composed of aggregated α-synuclein (α-Syn). Truncated forms of α-Syn are found in the brain of PD patients, and account for 10–30% of total synuclein in Lewy bodies. Caspase-1, which plays an important role in neuroinflammation, cleaves full-length α-Syn (α-Syn FL) to generate a C-terminus 19-residues truncated α-Syn (α-Syn121). However, the role of truncated α-Syn in the onset and/or pathogenesis of PD is unclear. Here, we used α-Syn121 as a model to explore its aggregation, membrane disruption and cytotoxicity properties. Compared with α-Syn FL, α-Syn121 aggregated at an accelerated rate, and formed amorphous aggregates rich in random coil structures rather than β-sheet-rich linear fibrils formed by α-Syn FL. Importantly, higher cytotoxicity with lower membrane disruption capacity was found for α-Syn121 aggregates. Furthermore, α-Syn121 aggregates could activate the apoptosis signaling pathway and stimulate the caspase-1-mediated cleavage of α-Syn FL to generate α-Syn121, which as a result leading to increased levels of endogenous α-Syn121 and intracellular S129 phosphorylated α-Syn inclusions. Together, our data suggests a hidden vicious cycle in PD that α-Syn121 rapidly forms amorphous aggregates, which activate caspase-1 to cleave α-Syn FL and generate more α-Syn121, and this cycle may contribute to the onset and/or pathogenesis of PD.     

Establishment of Salt Stress Tolerant Rice Plants Through Step Up NaCl Treatment In Vitro

Establishment of salt tolerant rice plants was examined by single step or step up NaCl treatments of shoot bud clumps in vitro, and variation among in vitro salt tolerant plants were examined by rapid amplified polymorphic DNA (RAPD). Shoot bud clumps were necrotic, stubbed or dead when subjected to single step treatment with 1.5 or 2.0 % NaCl. Conversely all the clumps could grow vigorously when subjected to step up salt treatment with 0.5, 1.0, 1.5 and 2.0 % NaCl at 3 week intervals and 2 % NaCl tolerant plants were established. RAPD revealed shoot bud clumps with and without different NaCl treatments, seedlings from field and grown in vitro, and regenerants from callus were genetically close to one another. Conversely, callus cultures were genetically isolated. Growth under different salt stress conditions was not correlated with the genetic variation, suggesting that 2.0 % NaCl tolerant plants might not result from genetic mutation but were due to adaptation of plants by step up NaCl treatment in vitro.     

Nutrient co-limitation of primary producer communities

Synergistic interactions between multiple limiting resources are common, highlighting the importance of co-limitation as a constraint on primary production. Our concept of resource limitation has shifted over the past two decades from an earlier paradigm of single-resource limitation towards concepts of co-limitation by multiple resources, which are predicted by various theories. Herein, we summarise multiple-resource limitation responses in plant communities using a dataset of 641 studies that applied factorial addition of nitrogen (N) and phosphorus (P) in freshwater, marine and terrestrial systems. We found that more than half of the studies displayed some type of synergistic response to N and P addition. We found support for strict definitions of co-limitation in 28% of the studies: i.e. community biomass responded to only combined N and P addition, or to both N and P when added separately. Our results highlight the importance of interactions between N and P in regulating primary producer community biomass and point to the need for future studies that address the multiple mechanisms that could lead to different types of co-limitation.     

细菌测试片的冷水可凝凝固剂初步研究和应用

微生物测试片具有携带方便、不用配制培养基的优点, 为一种新型的检测工具。测试片的技术关键是冷水可凝胶, 本文通过研究新的冷水可凝凝固剂(HKG)的保水性能、pH、强度、微生物利用及降解和抑菌效果, 再组装成细菌菌落总数测试片, 进行特异性和食品样品效果检验, 并与倾注平板法比对, 评价其作为微生物测试片凝固剂的可行性。结果显示HKG对16种微生物均无抑菌作用, pH为中性, 强度为340.31 g/cm2 ? 48.71 g/cm2; 具有良好的保水性能; HKG在短时期(5 d)内不支持微生物生长, 不被分解利用, 在测试片和倾注培养法中5种测试菌株均可达相同的灵敏度(P = 0.438 > 0.05), 各菌株菌落数(P = 0.442 > 0.05)和食品样品菌落数(P = 0.718 > 0.05)比较在统计学上无显著差异。结果表明, HKG能较好地应用于细菌测试片计数, 并能提高检测效率。     

荷斯坦奶牛脊柱畸形综合征的研究进展

荷斯坦奶牛脊柱畸形综合征是近年新发现的一种常染色体隐性遗传病,该病对纯合子胎儿是致死性的。当荷斯坦牛的育种核心群中携带者达到一定比例,脊柱畸形综合征就会对奶业造成巨大损失。文章综述了脊柱畸形综合征的主要症状和影响、致病基因及检测方法的研究进展以及我国潜在的荷斯坦奶牛脊柱畸形综合征携带者的状况。     

A pathway for protons in nitric oxide reductase from Paracoccus denitrificans

Nitric oxide reductase (NOR) from P. denitrificans is a membrane-bound protein complex that catalyses the reduction of NO to N₂O (2NO + 2e⁻ + 2H⁺ → N₂O + H₂O) as part of the denitrification process. Even though NO reduction is a highly exergonic reaction, and NOR belongs to the superfamily of O₂-reducing, proton-pumping heme-copper oxidases (HCuOs), previous measurements have indicated that the reaction catalyzed by NOR is non-electrogenic, i.e. not contributing to the proton electrochemical gradient. Since electrons are provided by donors in the periplasm, this non-electrogenicity implies that the substrate protons are also taken up from the periplasm. Here, using direct measurements in liposome-reconstituted NOR during reduction of both NO and the alternative substrate O₂, we demonstrate that protons are indeed consumed from the ‘outside’. First, multiple turnover reduction of O₂ resulted in an increase in pH on the outside of the NOR-vesicles. Second, comparison of electrical potential generation in NOR-liposomes during oxidation of the reduced enzyme by either NO or O₂ shows that the proton transfer signals are very similar for the two substrates proving the usefulness of O₂ as a model substrate for these studies. Last, optical measurements during single-turnover oxidation by O₂ show electron transfer coupled to proton uptake from outside the NOR-liposomes with a τ = 15 ms, similar to results obtained for net proton uptake in solubilised NOR [U. Flock, N.J. Watmough, P. Ädelroth, Electron/proton coupling in bacterial nitric oxide reductase during reduction of oxygen, Biochemistry 44 (2005) 10711-10719]. NOR must thus contain a proton transfer pathway leading from the periplasmic surface into the active site. Using homology modeling with the structures of HCuOs as templates, we constructed a 3D model of the NorB catalytic subunit from P. denitrificans in order to search for such a pathway. A plausible pathway, consisting of conserved protonatable residues, is suggested.     

温室番茄蒸腾量与其影响因子的相关分析及模型模拟

采用盆栽方法,研究不同灌溉量处理下温室番茄日蒸腾量与单株总叶面积、土壤相对含水量、空气温度、空气相对湿度、太阳辐射等因子的相关关系,并建立日蒸腾量的回归模型.结果表明:番茄日蒸腾量与单株总叶面积、土壤相对含水量、空气温度、空气相对湿度和太阳辐射等因子呈显著的线性关系,各因子之间存在复杂的相互作用;土壤水分状况是番茄蒸腾量的主要决策因子,决策系数为27.4％;日最低空气相对湿度是主要限制因子,决策系数为-119.7％;番茄日蒸腾量预测值和实测值的回归系数平方值(R2)为0.81,回归估计标准误差(RMSE)和相对误差(RE)分别为68.52 g和19.4％.根据通径分析筛选主要影响因子建立的番茄日蒸腾量回归模型能够较好地模拟温室番茄日蒸腾量.     

Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course

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