Binding with nucleic acids or glycosaminoglycans converts soluble protein oligomers to amyloid

Ample evidence suggests that almost all polypeptides can either adopt a native structure (folded or intrinsically disordered) or form misfolded amyloid fibrils. Soluble protein oligomers exist as an intermediate between these two states, and their cytotoxicity has been implicated in the pathology of multiple human diseases. However, the mechanism by which soluble protein oligomers develop into insoluble amyloid fibrils is not clear, and investigation of this important issue is hindered by the unavailability of stable protein oligomers. Here, we have obtained stabilized protein oligomers generated from common native proteins. These oligomers exert strong cytotoxicity and display a common conformational structure shared with known protein oligomers. They are soluble and remain stable in solution. Intriguingly, the stabilized protein oligomers interact preferentially with both nucleic acids and glycosaminoglycans (GAG), which facilitates their rapid conversion into insoluble amyloid. Concomitantly, binding with nucleic acids or GAG strongly diminished the cytotoxicity of the protein oligomers. EGCG, a small molecule that was previously shown to directly bind to protein oligomers, effectively inhibits the conversion to amyloid. These results indicate that stabilized oligomers of common proteins display characteristics similar to those of disease-associated protein oligomers and represent immediate precursors of less toxic amyloid fibrils. Amyloid conversion is potently expedited by certain physiological factors, such as nucleic acids and GAGs. These findings concur with reports of cofactor involvement with disease-associated amyloid and shed light on potential means to interfere with the pathogenic properties of misfolded proteins.     

RGD-independent cell adhesion via a tissue transglutaminase-fibronectin matrix promotes fibronectin fibril deposition and requires syndecan-4/2 and {alpha}5{beta}1 integrin co-signaling

Fibronectin (FN) deposition mediated by fibroblasts is an important process in matrix remodeling and wound healing. By monitoring the deposition of soluble biotinylated FN, we show that the stress-induced TG-FN matrix, a matrix complex of tissue transglutaminase (TG2) with its high affinity binding partner FN, can increase both exogenous and cellular FN deposition and also restore it when cell adhesion is interrupted via the presence of RGD-containing peptides. This mechanism does not require the transamidase activity of TG2 but is activated through an RGD-independent adhesion process requiring a heterocomplex of TG2 and FN and is mediated by a syndecan-4 and β1 integrin co-signaling pathway. By using α5 null cells, β1 integrin functional blocking antibody, and a α5β1 integrin targeting peptide A5-1, we demonstrate that the α5 and β1 integrins are essential for TG-FN to compensate RGD-induced loss of cell adhesion and FN deposition. The importance of syndecan-2 in this process was shown using targeting siRNAs, which abolished the compensation effect of TG-FN on the RGD-induced loss of cell adhesion, resulting in disruption of actin skeleton formation and FN deposition. Unlike syndecan-4, syndecan-2 does not interact directly with TG2 but acts as a downstream effector in regulating actin cytoskeleton organization through the ROCK pathway. We demonstrate that PKCα is likely to be the important link between syndecan-4 and syndecan-2 signaling and that TG2 is the functional component of the TG-FN heterocomplex in mediating cell adhesion via its direct interaction with heparan sulfate chains.     

Optimizing Seed Water Content:Relevance to Storage Stability and Molecular Mobility

This research was conducted to determine the optimum moisture content (MC) that gave maximum longevity to seeds. Three species were used to represent seeds with different dry matter reserves, which gives them different sorption properties: maize (Zea mays L.), elm (Ulmus pumila L.) and safflower (Carthamus tinctorius L.). The seeds of elm, safflower, and maize embryos with MC ranging from 0.00– 0.15 g H2O/g dry weight (DW) were stored at 35 °C for different periods of time. The results showed that the optim...     

Astrocytes Express N-Methyl-D-Aspartate Receptor Subunits in Development,Ischemia and Post-Ischemia

The expression of the N-methyl-D-aspartate receptor (NMDA-R) in astrocytes is controversial. The receptor is commonly considered neuron-specific. We showed that astrocytes in primary cultures differentially expressed mRNA of NMDA-R subunits, NR1, NR2A and NR2B, in development, ischemia and post-ischemia. One-week-old cultures expressed detectable NR1 mRNA, which fell significantly at 2 weeks and became barely detectable at 4 weeks. NR2A and NR2B mRNA were both significantly up-regulated from 1 to 2 weeks. In 4 weeks, 2 h of ischemia caused a significant up-regulation of NR1 and NR2B mRNA; while 6 h caused down-regulation of NR2A mRNA. Under 3 h of post-ischemia, only NR1 mRNA was increased. Ischemia induced the expression of major NMDA-R effecter, nitric oxide synthase 1, which was unaffected by AMPA-R antagonist CNQX, but dose-dependently inhibited by NMDA-R specific antagonist MK-801. These findings reflected that astrocyte could express inducible functional NMDA receptors without the presence of neurons.     

Morphological and molecular characterization of Aspidisca hongkongensis spec. nov. (Ciliophora,Euplotida) from the South China Sea

The morphology and infraciliature of a new ciliate, Aspidisca hongkongensis spec. nov., a large marine form isolated from the coastal waters near Hong Kong, were investigated. It differs from the congeners by the combination of cell size (about 90×60 μm in vivo), 9–11 conspicuous dorsal ridges, one fine and seven strong frontoventral cirri, six membranelles in anterior portion of adoral zone, and 17–23 membranelles in posterior portion of adoral zone. The comparison with similar congeners clearly supports the distinction of this new species based on morphological and small subunit (SSU) rRNA gene sequence studies. The SSU rRNA gene sequence similarity within the genus is about 75.3–92.1% which indicates that this is a distinct form. Phylogenetic trees based on SSU rRNA gene information show that A. hongkongensis groups with A. leptaspis.     

Nutrient removal in wetlands with different macrophyte structures in eastern Lake Taihu,China

A natural wetland of about 12 000 m² along the east coast of Lake Taihu was separated into five subzones with different macrophyte structures to investigate their nutrient removal dynamics. Wastewater was continuously pumped into the wetland from July 2008 to June 2009 at an average rate of 22 m³/h. Neighboring natural wetland with high density of macrophyte was chosen as a comparison site. The removal of TN, TDN, TP, and TDP in the experimental wetlands as a whole was about 79.3, 54.5, 4.5, and 3.4 kg, respectively. The decrease of nitrogen concentration was more pronounced in winter (January–March) 2009, representing a respective reduction of 46.4%, 48.0%, and 47.9% in TN, TDN, and NH₄–N concentration. Results reveal a higher nutrient removal potential in wetland dominated by Typha orientalis Presl, Zizania latifolia Turcz, and Hemarthria sibirica under high nutrient load. However, areas dominated by Zizania latifolia Turcz, Nelumbo nucifera Gaertn, and Ceratophyllum demersum L. had better purification performance when the above-water-surface macrophytes were harvested frequently. Dissolved oxygen, pH, and oxidation–reduction potential decreased with the increase of the percentage of Zizania latifolia Turcz-dominated macrophytes. High nutrient concentration in the comparison site and net increase of NH₄–N in Z1 indicate the possibility of water re-pollution by intense macrophyte decomposition. Furthermore, results suggest that harvesting macrophytes has potential ability in nitrogen, especially ammonium nitrogen removal, and hence could be considered in wetland construction for lake restoration.     

5-Arylamino-1,2,4-triazin-6(1H)-one CRF1 receptor antagonists

A series of 5-arylamino-1,2,4-triazin-6(1H)-ones was synthesized and evaluated as antagonists at the corticotropin releasing factor receptor. Formation of CYP-mediated oxidative reactive metabolites previously observed in a related N³-phenylpyrazinone structure was minimized by incorporation of the additional ring nitrogen found in the triazinones.     

黄土高原植被物候变化及其对季节性气候变化的响应

受气候变化影响,全球范围内植被物候发生了显著变化,而目前针对不同植被分区类型下（荒漠草原区、典型草原区、森林草原区、落叶栎林区、落叶栎林亚区）植被物候变化及其对季节性气候变化响应的研究尚少。因此基于MODIS遥感归一化差值植被指数（MODIS NDVI：MOD13Q1）数据、中国植被区划数据及135个气象站点插值数据,利用Sen''s斜率估计、Hurst指数和高阶偏相关分析等方法,研究黄土高原2001-2018年植被物侯变化及其对季节性气候变化的响应。结果表明：（1）黄土高原植被生长季始期（SOS,Start of Growing Season）主要集中在第96-144天,子植被分区由西北向东南方向,逐渐呈现提前趋势,71.0%的像元植被SOS整体提前0-2 d/10a （α=0.05）,且在未来一段时间66%的像元植被SOS继续呈现提前趋势;植被生长季末期（EOS,End of Growing Season）主要集中在第288-304天,各子植被分区植被EOS变化基本保持一致,87.6％的像元植被EOS整体延迟0-3 d/10a （α=0.05）,且在未来一段时间有80%的像元植被EOS继续呈现推迟趋势。（2）黄土高原植被SOS主要受各季节温度的影响;当年春季降水导致植被SOS提前,主要分布在黄土高原中部;上年夏季和上年秋季降水增加会导致植被SOS推迟;当年春季、上年秋季和年初冬季的温度升高均会导致植被SOS提前;各子植被分区植被SOS对不同季节降水的响应存在差异,而对不同季节温度的响应具有一致性。（3）黄土高原植被EOS主要受各季节降水和秋季温度的影响;不同季节降水增加均会导致大部分植被EOS推迟;当年秋季温度导致整体区域植被EOS推迟,且各子植被区植被EOS对当年秋季温度响应具有一致性。该研究可为大尺度植被物候影响因素提供新的认识,也为植被适应未来气候变化提供借鉴。     

Madecassoside attenuates inflammatory response on collagen-induced arthritis in DBA/1 mice

Madecassoside (MA), a triterpenoid product isolated from Centella asiatica, has been described to exhibit antioxidant and anti-inflammatory activities. The present study was undertaken to determine whether madecassoside (MA) is efficacious against collagen-induced arthritis (CIA) in mice and its possible mechanisms. DBA/1J mice were immunized with bovine type II collagen and treated with MA (3, 10 and 30 mg/kg d, i.g.) from days 21 to 42 after immunization. Arthritis was evaluated by hind paw swelling, polyarthritis index, and histological examination. In vitro proliferation of spleen cells was examined using 3-[4,5-dimethylthylthiazol-2-yl]-2, 5-diphenyltetrazoliumbromide (MTT) assay. Plasma levels of cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) and the expression of prostaglandin E₂ (PGE₂), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in synovial tissues were also determined. The results showed that comparing with untreated CIA mice, treated with MA dose-dependently suppressed the clinical arthritis score and joints tissues pathological damage, reduced the proliferation of spleen cells, plasma levels of TNF-α and IL-6, synovial tissues PGE₂ production and COX-2 protein expression, however, the expression of COX-1 in symovial tissues did not change and the plasma levels of IL-10 were increased. These results suggest that MA can effectively alleviate inflammatory response on CIA, and anti-inflammatory effects of MA can be attributed, at least partially, to the inhibition of pro-inflammatory mediators, including COX-2 expression, PGE₂ production, TNF-α and IL-6 levels and the up-regulation anti-inflammatory molecule IL-10.