Tau Monoclonal Antibody Generation Based on Humanized Yeast Models: IMPACT ON TAU OLIGOMERIZATION AND DIAGNOSTICS*

A link between Tau phosphorylation and aggregation has been shown in different models for Alzheimer disease, including yeast. We used human Tau purified from yeast models to generate new monoclonal antibodies, of which three were further characterized. The first antibody, ADx201, binds the Tau proline-rich region independently of the phosphorylation status, whereas the second, ADx215, detects an epitope formed by the Tau N terminus when Tau is not phosphorylated at Tyr¹⁸. For the third antibody, ADx210, the binding site could not be determined because its epitope is probably conformational. All three antibodies stained tangle-like structures in different brain sections of THY-Tau22 transgenic mice and Alzheimer patients, and ADx201 and ADx210 also detected neuritic plaques in the cortex of the patient brains. In hippocampal homogenates from THY-Tau22 mice and cortex homogenates obtained from Alzheimer patients, ADx215 consistently stained specific low order Tau oligomers in diseased brain, which in size correspond to Tau dimers. ADx201 and ADx210 additionally reacted to higher order Tau oligomers and presumed prefibrillar structures in the patient samples. Our data further suggest that formation of the low order Tau oligomers marks an early disease stage that is initiated by Tau phosphorylation at N-terminal sites. Formation of higher order oligomers appears to require additional phosphorylation in the C terminus of Tau. When used to assess Tau levels in human cerebrospinal fluid, the antibodies permitted us to discriminate patients with Alzheimer disease or other dementia like vascular dementia, indicative that these antibodies hold promising diagnostic potential.     

Epidermal fatty acid‐binding protein protects nerve growth factor‐differentiated PC12 cells from lipotoxic injury

Epidermal fatty acid‐binding protein (E‐FABP/FABP5/DA11) binds and transport long‐chain fatty acids in the cytoplasm and may play a protecting role during neuronal injury. We examined whether E‐FABP protects nerve growth factor‐differentiated PC12 cells (NGFDPC12 cells) from lipotoxic injury observed after palmitic acid (C16:0; PAM) overload. NGFDPC12 cells cultures treated with PAM/bovine serum albumin at 0.3 mM/0.15 mM show PAM‐induced lipotoxicity (PAM‐LTx) and apoptosis. The apoptosis was preceded by a cellular accumulation of reactive oxygen species (ROS) and higher levels of E‐FABP. Antioxidants MCI‐186 and N‐acetyl cysteine prevented E‐FABP's induction in expression by PAM‐LTx, while tert‐butyl hydroperoxide increased ROS and E‐FABP expression. Non‐metabolized methyl ester of PAM, methyl palmitic acid (mPAM), failed to increase cellular ROS, E‐FABP gene expression, or trigger apoptosis. Treatment of NGFDPC12 cultures with siE‐FABP showed reduced E‐FABP levels correlating with higher accumulation of ROS and cell death after exposure to PAM. In contrast, increasing E‐FABP cellular levels by pre‐loading the cells with recombinant E‐FABP diminished the PAM‐induced ROS and cell death. Finally, agonists for PPARβ (GW0742) or PPARγ (GW1929) increased E‐FABP expression and enhanced the resistance of NGFDPC12 cells to PAM‐LTx. We conclude that E‐FABP protects NGFDPC12 cells from lipotoxic injury through mechanisms that involve reduction of ROS.

     

A revised classification of the genus Matrona Selys, 1853 using molecular and morphological methods (Odonata: Calopterygidae)

An extensive review of the genus Matrona is presented based on mitochondrial (COI) and nuclear (ITS) sequences from 150 samples which cover all the known taxa of this genus. The separation of two main clades (oreades group: M. oreades, M. corephaea and M. taoi; basilaris group: M. basilaris, M. nigripectus, M. cyanoptera, M. japonica and M. annina) is strongly supported. The classification of all traditional recognized species is confirmed. The Hainan population separates very well from mainland M. basilaris populations, which is also confirmed by geometric morphometric analysis of wing shape. Given the implications of the molecular analysis the genus Matrona is grouped into two subgenera: subgen. Matrona (type species M. basilaris) and D ivortia subgen. nov. (type species M. oreades). A new species, M . ( M .) mazu sp. nov. , from Hainan is described. Brief taxonomic notes on the nine recognized species of the genus are given. Lectotype designations of M. basilaris and M. nigripectus are published. © 2015 The Linnean Society of London     

Predicting the wetland distributions under climate warming in the Great Xing’an Mountains,northeastern China

The wetland ecosystem is particularly vulnerable to hydrological and climate changes. The Great Xing’an Mountain is such a region in China that has a large area of wetlands with rare human disturbance. The predictions of the global circulation model CGCM3 (the third-generation coupled global climate model from the Canadian Centre for Climate Modeling and Analysis) indicated that the temperature in The Great Xing’an Mountain will rise by 2–4°C over the next 100 years. This paper predicts the potential distributions of wetlands in this area under the current and warming climate conditions. This predication was performed by the Random Forests model, with 18 environmental variables, which will reflect the climate and topography conditions. The model has been proven to have a great prediction ability. The wetland distributions are primarily topography-driven in the Great Xing’an Mountains. Mean annual temperature, warmness index, and potential evapotranspiration ratio are the most important climatic factors in wetland distributions. The model predictions for three future climate scenarios show that the wetland area tends to decrease, and higher emission will also cause more drastic shrinkage of wetland distributions. About 30% of the wetland area will disappear by 2050. The area will decrease 62.47, 76.90, and 85.83%, respectively, under CGCM3-B1, CGCM3-A1B, and CGCM3-A2 by 2100. As for spatial allocation, wetlands may begin to disappear from the sides to the center and south to north under a warming climate. Under CGCM3-B1, the loss of wetlands may mainly occur in the south hills with flatter terrain, and some may occur in the north hills and intermontane plains. Under CGCM3-A1B, severe vanish of wetlands is predicted. Under CGCM3-A2, only a small area of wetlands may remain in the north of the high mountains.     

Identification of curcumin derivatives as human glyoxalase I inhibitors: A combination of biological evaluation, molecular docking, 3D-QSAR and molecular dynamics simulation studies

Several recent developments suggest that the human glyoxalase I (GLO I) is a potential target for anti-tumor drug development. In present study, a series of curcumin derivatives with high inhibitory activity against human GLO I were discovered. Inhibition constant (K(i)) values of compounds 8, 9, 10, 11 and 13 to GLO I are 4.600μM, 2.600μM, 3.200μM, 3.600μM and 3.600μM, respectively. To elucidate the structural features of potent inhibitors, docking-based three-dimensional structure-activity relationship (3D-QSAR) analyses were performed. Satisfactory agreement between experiment and theory suggests that comparative molecular similarity index analysis (CoMSIA) modeling exhibit much better correlation and predictive power. The cross-validated q(2) value is 0.638 while no-validation r(2) value is 0.930. Integrated with docking-based 3D-QSAR CoMSIA modeling, molecular surface property (electrostatic and steric) mapping and molecular dynamics simulation, a set of receptor-ligand binding models and bio-affinity predictive models for rational design of more potent inhibitors of GLO I are established.     

The response of peatlands to climate warming: A review

Peatlands hold a large portion of the Earth’s terrestrial organic carbon and serve as important pools in the global carbon cycle. Due to their strong feedbacks, peatlands are one of the most important ecosystems with respect to climate warming. This paper reviews the effects of climate warming on peatland ecosystems. Climate warming will shift the point in time when vascular peatland plants flower and reach maximum biomass to an earlier date. Flower production for some plants will increase, but how the phenology of peatland bryophytes will react is still unknown. Climate warming may increase productivity of peatlands, especially ombrotrophic Sphagnum bogs, but in the long run the negative effects from decreased water availability may prevail. Climate warming will change the basic characteristics of peatlands: their wetness and the related cold environment and nutrient shortage. By increased mineralization and nitrogen and phosphorus availability, climate warming will facilitate the growth of vascular plants. This will suppress endangered plant species (which usually grow in low-productive, phosphorus-limited habitats) and lead to a change in vegetation composition and a decrease in peatland biodiversity. Climate warming will change the competitive balance between bryophytes and between Sphagnum and vascular plants. Climate warming in the Late Pleistocene facilitated the initiation of peatland formation, but most current experiments show an obvious tendency for climate warming to drive many peatlands to regressive succession with a shift in dominance from Sphagnum to vascular plants. This change in vegetation will increase the flux of CH₄ and possibly also CO₂. The effect of accelerated peat decay as a result of climate warming will vary between types of peatlands. Since climate warming will generally enhance peat respiration more than net primary production, more and more peatlands will become carbon sources rather than carbon sinks, which will aggravate climate warming by positive feedback. Finally, this paper addresses some problems with current manipulative experimental studies on peatland response to climate warming and makes suggestions for further studies.     

大兴安岭呼中林区虫害与火干扰交互作用的长期模拟

虫害和林火是森林生态系统的两种主要干扰类型,各种干扰在大时空尺度上存在一定的交互作用.本文采用空间直观景观模型LANDIS模拟虫害和林火在300年内的交互作用.结果表明:虫害干扰降低了细可燃物载量,提高了模拟前期(0～100 a)和中期(100～200 a)的粗可燃物载量,降低了模拟前期和中期的林火频率,不同干扰预案模拟后期(200～300 a)火烧频率的结果比较接近;虫害干扰降低了模拟前期和后期的火烧强度,增加了模拟中期的火烧强度,提高了模拟中期的森林火险等级,降低了模拟前期和后期的火险等级.人类灭火可增加虫害的发生面积,因此建议森林管理部门采取适当的防虫措施,不可只注重灭火,可以采取可燃物去除和计划火烧等方式管理林火,促进森林生态系统的可持续发展.