High-mobility group and other nonhistone substrates for nuclear histoneN-acetyltransferase

A variety of nonhistone proteins and polyamines has been studied for their substrate activity for nuclear histone N-acetyltransferase. Nonhistone chromatin high-mobility group (HMG) proteins are found to be as good a substrate for the enzyme as histones. The enzyme also acetylates spermidine and spermine. However, protamine, bovine serum albumin, and ubiquitin are not substrates. Chymotryptic peptides of histone and HMGs retained about 64% of the substrate activity, but trypsin treatment reduced the substrate activity by more than 85%. Both N-acetyltransferase activities for HMGs and histones are copurified through salt extraction, polyethylene glycol fractionation, and chromatography on DEAE-cellulose, phosphocellulose columns, and a HPLC anionic-exchange column. The highly purified nuclear histone acetyltransferase shows similar optimal pH and ping-pong kinetics for both HMGs and histones. The Km for HMG is 0.25 mg/ml. HMGs are able to accept the acetyl group from isolated acetyl-enzyme intermediate. Denatured gel analysis shows that HMG 1 and HMG 2 are the major proteins acetylated. High salt concentrations, mononucleotides, and DNA, which inhibit histone substrate activity of the enzyme, also inhibit HMG substrate activity. These observations suggest that there is a major nuclear N-acetyltransferase which is responsible for the acetylation of both histones and HMGs and perhaps also of spermine and spermidine. Thus the regulation of the structure and function of chromatin through postsynthetic acetylation can be achieved by a single nuclear N-acetyltransferase.     

Strong plastid degradation is consistent within section Chondrophyllae,the most speciose lineage of Gentiana

Recovering phylogenetic relationships in lineages experiencing intense diversification has always been a persistent challenge in evolutionary studies, including in Gentiana section Chondrophyllae sensu lato (s.l.). Indeed, this subcosmopolitan taxon encompasses more than 180 mostly annual species distributed around the world. We sequenced and assembled 22 new plastomes representing 21 species in section Chondrophyllae s.l. In addition to previously released plastome data, our study includes all main lineages within the section. We reconstructed their phylogenetic relationships based on protein‐coding genes and recombinant DNA (rDNA) cistron sequences, and then investigated plastome structural evolution as well as divergence time. Despite an admittedly humble species cover overall, we recovered a well‐supported phylogenetic tree based on plastome data, and found significant discordance between phylogenetic relationships and taxonomic treatments. Our results show that G. capitata and G. leucomelaena diverged early within the section, which is then further divided into two clades. The divergence time estimation showed that section Chondrophyllae s.l. evolved in the second half of the Oligocene. We found that section Chondrophyllae s.l. had the smallest average plastome size (128 KB) in tribe Gentianeae (Gentianaceae), with frequent gene and sequence losses such as the ndh complex and its flanking regions. In addition, we detected both expansion and contraction of the inverted repeat (IR) regions. Our study suggests that plastome degradation parallels the diversification of this group, and illustrates the strong discordance between phylogenetic relationships and taxonomic treatments, which now need to be carefully revised.     

长江中游地区农业生态效率空间关联网络演化及驱动因素

厘清农业生态效率空间关联的网络特征及驱动因素对践行绿色发展理念、实现区域协同治理具有重要意义。基于2001-2019年长江中游地区38个地级市的面板数据,采用超效率至强有效前沿最近距离(MINDS)模型测度各地级市的农业生态效率,运用引力模型对长江中游地区农业生态效率的空间关联关系进行识别,进而利用社会网络分析方法和二次指派程序(QAP)方法揭示其网络结构演化特征和驱动因素。研究表明:(1)长江中游地区农业生态效率的空间关联关系表现出复杂的网络结构形态,空间关联网络具有高通达性且等级结构趋于松散,但网络稳定性却趋于下降;(2)武汉市和长沙市在空间关联网络中居核心地位,既扮演中心行动者角色又兼具"中介"和"桥梁"功能;岳阳市、黄石市等省际边界地级市在网络中则扮演边缘行动者角色;(3)空间关联网络核心-边缘结构由"十五"时期的"大聚集、小分散"演变为"十三五"时期的"大分散、小聚集",核心区由中部聚集转变为向四周发散;(4)地理空间的邻接、地区农业产业地位、财政支出、经济发展水平的相近以及交通运输水平的差异均有助于空间关联网络的形成。     

A backbone‐dependent rotamer library with high (ϕ, ψ) coverage using metadynamics simulations

Backbone‐dependent rotamer libraries are commonly used to assign the side chain dihedral angles of amino acids when modeling protein structures. Most rotamer libraries are created by curating protein crystal structure data and using various methods to extrapolate the existing data to cover all possible backbone conformations. However, these rotamer libraries may not be suitable for modeling the structures of cyclic peptides and other constrained peptides because these molecules frequently sample backbone conformations rarely seen in the crystal structures of linear proteins. To provide backbone‐dependent side chain information beyond the α‐helix, β‐sheet, and PPII regions, we used explicit‐solvent metadynamics simulations of model dipeptides to create a new rotamer library that has high coverage in the (ϕ, ψ) space. Furthermore, this approach can be applied to build high‐coverage rotamer libraries for noncanonical amino acids. The resulting Metadynamics of Dipeptides for Rotamer Distribution (MEDFORD) rotamer library predicts the side chain conformations of high‐resolution protein crystal structures with similar accuracy (~80%) to a state‐of‐the‐art rotamer library. Our ability to test the accuracy of MEDFORD at predicting the side chain dihedral angles of amino acids in noncanonical backbone conformation is restricted by the limited structural data available for cyclic peptides. For the cyclic peptide data that are currently available, MEDFORD and the state‐of‐the‐art rotamer library perform comparably. However, the two rotamer libraries indeed make different rotamer predictions in noncanonical (ϕ, ψ) regions. For noncanonical amino acids, the MEDFORD rotamer library predicts the χ ₁ values with approximately 75% accuracy.     

Endocytosis of Peptidase Inhibitor SerpinE2 promotes Myocardial Fibrosis through activating ERK1/2 and β-catenin Signaling Pathways

Cardiac fibrosis is one of the common pathological processes in many cardiovascular diseases characterized by excessive extracellular matrix deposition. SerpinE2 is a kind of protein that inhibits peptidase in extracellular matrix and up-regulated tremendously in mouse model of cardiac fibrosis induced by pressure-overloaded via transverse aortic constriction (TAC) surgery. However, its effect on cardiac fibroblasts (CFs), collagen secretion and the underlying mechanism remains unclear. In this study, DyLight® 488 green fluorescent dye or His-tagged proteins were used to label the exogenous serpinE2 protein. It was showed that extracellular serpinE2 translocated into CFs by low-density lipoprotein receptor-related protein 1 (LRP1) and urokinase plasminogen activator receptor (uPAR) of cell membrane through endocytosis. Knockdown of LRP1 or uPAR reduced the level of serpinE2 in CFs and down-regulated the collagen expression. Inhibition of the endocytosis of serpinE2 could inhibit ERK1/2 and β-catenin signaling pathways and subsequently attenuated collagen secretion. Knockdown of serpinE2 attenuates cardiac fibrosis in TAC mouse. We conclude that serpinE2 could be translocated into cardiac fibroblasts due to endocytosis through directly interact with the membrane protein LRP1 and uPAR, and this process activated the ERK1/2, β-catenin signaling pathways, consequently promoting collagen production.     

Galectin-3 critically mediates the hepatoprotection conferred by M2-like macrophages in ACLF by inhibiting pyroptosis but not necroptosis signalling

We previously documented that M2-like macrophages exert a hepatoprotective effect in acute-on-chronic liver failure (ACLF) by inhibiting necroptosis signalling. Nevertheless, the molecular mechanism behind this hepatoprotection still needs to be further dissected. Galectin-3 (GAL3) has been reported to be critically involved in the pathogenesis of multiple liver diseases, whereas the potential role of GAL3 in ACLF remains to be explored. Herein, we hypothesised that GAL3 plays a pivotal role in the hepatoprotection conferred by M2-like macrophages in ACLF by inhibiting necroptosis. To test this hypothesis, we first assessed the expression of GAL3 in control and fibrotic mice with or without acute insult. Second, loss- and gain-of-function experiments of GAL3 were performed. Third, the correlation between GAL3 and M2-like macrophage activation was analysed, and the potential role of GAL3 in M2-like macrophage-conferred hepatoprotection was confirmed. Finally, the molecular mechanism underlying GAL3-mediated hepatoprotection was dissected. GAL3 was found to be obviously upregulated in fibrotic mice with or without acute insult but not in acutely injured mice. Depletion of GAL3 aggravated hepatic damage in fibrotic mice upon insult. Conversely, adoptive transfer of GAL3 provided normal mice enhanced resistance against acute insult. The expression of GAL3 is closely correlated with M2-like macrophage activation. Through adoptive transfer and depletion experiments, M2-like macrophages were verified to act as a major source of GAL3. Importantly, GAL3 was confirmed to hold a pivotal place in the hepatoprotection conferred by M2-like macrophages through loss- and gain-of-function experiments. Unexpectedly, the depletion and adoptive transfer of GAL3 resulted in significant differences in the expression levels of pyroptosis but not necroptosis signalling molecules. Taken together, GAL3 plays a pivotal role in the hepatoprotection conferred by M2-like macrophages in ACLF by inhibiting pyroptosis but not necroptosis signalling. Our findings provide novel insights into the pathogenesis and therapy of ACLF.Subject terms: Inflammasome, Necroptosis     

Mechanisms of chromatin-based epigenetic inheritance

Multi-cellular organisms such as humans contain hundreds of cell types that share the same genetic information(DNA sequences), and yet have different cellular traits and functions. While how genetic information is passed through generations has been extensively characterized, it remains largely obscure how epigenetic information encoded by chromatin regulates the passage of certain traits, gene expression states and cell identity during mitotic cell divisions, and even through meiosis. In this r...     

扎龙湿地白鹤春季停歇地昼间行为时间分配及活动规律

在2004年4～5月,采用瞬时扫描取样法对扎龙国家级自然保护区林甸芦苇沼泽区的野生白鹤(Grusleucogeranus)在春季迁徙停歇地的昼间各种行为进行了研究。结果表明,在整个观察时期内白鹤各种行为具有较强的规律性,活动时间分配比例为:觅食31%、游走27%、静栖19%、警戒17%、修饰6%。白鹤觅食行为在一天中有两个高峰,分别为早晨和黄昏;游走行为基本上与觅食行为呈正相变化,并且几乎每个游走高峰及低潮相应地伴随着觅食的高峰和低潮;由于渔民清晨下苇塘收鱼和放牧,在5:30～6:30和6:30～7:30两个时间段警戒行为比例最高;静栖行为基本与游走及觅食行为呈负相关,对比发现,静栖行为比例低于觅食行为,与笼养鹤类的情况存在一定的差异,原因可能是食物丰富度影响了野生状态下行为的时间分配;修饰行为所占比例较小,是由于修饰行为是非主要行为,其发生是随机的。天气状况对白鹤数量变化有一定影响,阴雨和大风天气,白鹤数量明显减少,鹤群转移。与正常天气情况相比,阴雨和大风对白鹤觅食、静栖和游走行为时间分配影响显著(P阴雨=0·000<0·05,P大风=0·000<0·05),觅食时间缩短,游走行为减少,静栖时间变长。