信任节点机制下的异构多智能体系统安全一致性控制

本文研究了一类由一阶二阶智能体组成的异构系统安全一致性分析与设计问题.首先从拓扑结构角度,通过设立信任节点机制,显著提升了系统网络拓扑的稳健性.然后,针对邻居中敌对节点的攻击行为,分别设计了一阶二阶智能体的控制策略,并给出了系统实现安全一致性目标的充分条件.最后,通过仿真实例验证了理论结果的有效性.

Solution structure of the RNA recognition domain of METTL3-METTL14 N^6-methyladenosine methyltransferase

N^6-methyladenosine(m6A),a ubiquitous RNA modification,is installed by METTL3-METTL14 complex.The structure of the heterodimeric complex between the methyltransferase domains(MTDs)of METTL3 and METTL14 has been previously determined.However,the MTDs alone possess no enzymatic activity.Here we present the solution structure for the zinc finger domain(ZFD)of METTL3,the inclusion of which fulfills the methyltransferase activity of METTL3-METTL14.We show that the ZFD specifically binds to an RNA containing 5'-GGACU-3'consensus sequence,but does not to one without.The ZFD thus serves as the target recognition domain,a structural feature previously shown for DNA methyltransferases,and cooperates with the MTDs of METTL3-METTL14 for catalysis.However,the interaction between the ZFD and the specific RNA is extremely weak,with the binding affinity at several hundred micromolar under physiological conditions.The ZFD contains two CCCH-type zinc fingers connected by an anti-parallel P-sheet.Mutational analysis and NMR titrations have mapped the functional interface to a contiguous surface.As a division of labor,the RNA-binding interface comprises basic residues from zinc finger 1 and hydrophobic residues fromβ-sheet and zinc finger 2.Further we show that the linker between the ZFD and MTD of METTL3 is flexible but partially folded,which may permit the cooperation between the two domains during catalysis.Together,the structural characterization of METTL3 ZFD paves the way to elucidate the atomic details of the entire process of RNA m6A modification.

Structural Insights into N^6-methyladenosine (m^6A) Modification in the Transcriptome

More than 100 types of chemical modifications in RNA have been well documented. Recently, several modifications, such as N6-methyladenosine （m^6A）, have been detected in mRNA, opening the window into the realm of epitranscriptomies. The m^6A modification is the most abundant modification in mRNA and non-coding RNA （ncRNA）. At the molecular level, m^6A affects almost all aspects of mRNA metabolism, including splicing, translation, and stability, as well as microRNA （miRNA） maturation, playing essential roles in a range of cellular processes. The m^6A modification is regulated by three classes of proteins generally referred to as the ＂writer＂ （adenosine methyltransferase）, ＂eraser＂ （m^6A demethylating enzyme）, and ＂reader＂ （m^6A-binding protein）. The m^6A modification is reversibly installed and removed by writers and erasers, respectively. Readers, which are members of the YT521-B homology （YTH） family proteins, selectively bind to RNA and affect its fate in an m^6A-dependent manner. In this review, we summarize the structures of the functional proteins that modulate the m^6A modification, and provide our insights into the m^6A-mediated gene regulation.

Synthesis, Characterization and Electrochemical Properties of 4,5-Diazafluoren-9-yl or Fluoren-9-yl Terminated Homobimetallic Ruthenium and Osmium Allenylidene, AlkynyI-Allenylidene Complexes

A variety of rigid ruthenium and osmium allenylidene, ruthenium alkynyl-allenylidene complexes have been prepared. These allenylidene complexes were derived from 9-ethynyl-9-fluorenol and 9-hydroxy-9-ethynyl-4,5-diazafluorene in the presence of cis-OsCl2（dppm）2 and cis-RuCl2（dppe）2. The respective products have been fully characterized by 1H, 13C, 31P NMR spectrometry, IR spectrometry, elemental analysis, and UV/Vis spectrophotometry. Moreover, electrochemical studies reveal that the dinuclear complexes display a quasi-reversible redox behavior and a moderate electronic communication between the two metal centers in 8a. UV–vis studies show a remarkable absorption in the region （λmax = 300-700 nm） for these complexes.

The novel SLC40A1(T419I)variant results in a loss-of-function phenotype and may provide insights into the mechanism of large granular lymphocytic leukemia and pure red cell aplasia

Variants in the solute carrier family 40 member 1(SLC40A1)gene are the molecular basis of ferroportin disease,which is an autosomal dominant hereditary hemochromatosis.Here,we present a patient with pure red cell aplasia(PRCA)and large granular lymphocytic leukemia(LGLL)associated with an extremely high levels of serum ferritin and iron overload syndrome.Whole exon sequencing revealed a novel heterozygous variant in SLC40A1(p.T419I),which was found in his daughter as well.A series of functional studies in vitro of the T419I variant in ferroportin were conducted and the results revealed a reduced capacity of iron export from cells without changes in protein localization and its sensitivity to hepcidin.Intracellular iron storage in mutated cells was significantly higher than that of wild-type.These findings suggest that the novel variant p.T419I can cause the classical form of ferroportin disease and an elevated intracellular iron level indicates a potential novel pathogenic mechanism underlying PRCA and LGLL.