Molecular mechanisms of ＂off-on switch＂ of activities of human IDH1 by tumor-associated mutation R132H

人的 cytosolic NADP-IDH (IDH1 ) 最近被发现了涉及 tumorigenesis。尤其是，到目前为止识别的导出肿瘤的 IDH1 变化主要发生在 Arg132，和变化 R132H 是最流行的。这个变化损害酶的氧化 IDH 活动，但是显示把伪 - ketoglutarate (伪 K G ) 变换成 2-hydroxyglutarate 的新减小功能。这里，我们报导有或没有 isocitrate (ICT ) 的 R132H 变异的 IDH1 的结构跳了。和 mutagenesis 的结构的数据和生物化学的数据揭示一个以前未定义的起始的 ICT 有约束力的状态并且证明那项 IDH 活动要求一个 conformational 变化到一关门预先转移状态。Arg132 在催化反应起多重功能的作用；特别地， R132H 变化从起始的 ICT 有约束力的状态妨碍 conformational 变化到预先转移状态，导致 IDH 活动的缺陷。我们的结果第一次描述那有中间的符合构造，对应于一个起始的 ICT 有约束力的状态并且 R132H 变化能在这符合构造套住酶，因此使潜在地肿瘤镇压的 IDH 活动的鈥渙f f 开关鈥 ? 的分子的机制清楚些。而且，我们为获得的 伪K G 减小活动证明了 Tyr139 的必要性并且建议 Tyr139 可以由从 NADPH 在一个氢化物阴离子的转移期间在 伪K G 的 C2 原子上补偿增加的否定费用到 伪K G 起一个重要作用，它提供新卓见进 鈥渙n 开关鈥?的机制假设地由这个变化的 IDH1 的 oncogenic 减小活动。

Structural basis of immunosuppression by the therapeutic antibody daclizumab

发信号的 Interleukin-2 (IL )-2 在小径被显示出为在有机关移植的病人的免疫力的抑制有效减轻 / 消除 allograft 拒绝的堵住这的有免疫力的回答，和药的激活起一个枢轴的作用。首先人性化的 monoclonal 抗体(mAb ) daclizumab 掉进这个范畴并且对 IL-2 受体建筑群的一个关键部件显示出高特性和亲密关系，也就是 IL-2R 伪。揭示由 daclizumab 表明小径的 IL-2 的抑制的分子的机制，我们在 2.6 和 2.8 点与 IL-2R 伪 ectodomain 在免费形式并且在建筑群决定了 daclizumab Fab 的水晶结构？分辨率分别地。daclizumab Fab 当面采用类似的符合构造或 IL-2R 伪 ectodomain 的缺席。daclizumab 的抗原绑定地点主要由决定形成大断然控告的表面消沉和通常是恐水病的二个 flanking 补丁的区域(CDR ) 的五补充组成。 conformational epitope 由 IL-2R 伪 ectodomain 的几个不连续的片断组成，哪个与与 IL-2 交往的区域重叠的大部分，建议到 IL-2R 伪 的 daclizumab 的绑定将阻止 IL-2 绑定到 IL-2R 伪 和 IL-2/IL-2R 伪尾纬c 建筑群的随后的形成，因此堵住表明小径的 IL-2 。这些结果也为指向 IL-2R 伪的改进 mAb 药的设计和发展有含意。

Dynamic shaping of vectorial optical fields based on two-dimensional blazed holographic grating

We propose a vectorial optical field generation system based on two-dimensional blazed grating to high-efficiently generate structured optical fields with prescribed amplitude,phase,and polarization.In this system,an optimized blazed grating hologram is written on a spatial light modulator(SLM)and can diffract the majority of the incident light into the first-order diffractions of the x and y directions,which then serve as base vectors for synthesizing desired vector beams.Compared with the conventional cosine grating used in the previous work,the proposed two-dimensional,blazed grating has a much higher efficiency.Both computer simulation and optical experiment validate that a conversion efficiency up to 5 times that of the former work is achieved.Our method can facilitate applications of the optical field manipulation.

Impact of the spatial coherence on self-interference digital holography

Owing to the unique feature that the signal and reference waves of self-interference digital holography(SIDH)contain the same spatial information from the same point of object,compared with conventional digital holography,the SIDH has the special spatial coherence properties.We present a statistical optics approach to analyzing the formation of cross-correlation image in SIDH.Our study reveals that the spatial coherence of illumination light can greatly influence the imaging characteristics of SIDH,and the impact extent of the spatial coherence depends substantially on the recording distance of hologram.The theoretical conclusions are supported well by numerical simulation and optical experiments.

Manipulating propagation and evolution of polarization singularities in composite Bessel-like fields

Structured optical fields embedded with polarization singularities(PSs)have attracted extensive attention due to their capability to retain topological invariance during propagation.Many advances in PS research have been made over the past 20 years in the areas of mathematical description,generation and detection technologies,propagation dynamics,and applications.However,one of the most crucial and difficult tasks continues to be manipulating PSs with multiple degrees of freedom,especially in three-dimensional(3D)tailored optical fields.We propose and demonstrate the longitudinal PS lines obtained by superimposing Bessel-like modes with orthogonal polarization states on composite vector optical fields(VOFs).The embedded PSs in the fields can be manipulated to propagate robustly along arbitrary trajectories,or to annihilate,revive,and transform each other at on-demand positions in 3D space,allowing complex PS’topological morphology and intensity patterns to be flexibly customized.Our findings could spur further research into singular optics and help with applications such as micromanipulation,microstructure fabrication,and optical encryption.

Caenorhabditis elegans NMAD-1 functions as a demethylase for actin

Dear Editor,DNA N^(6)-methyladenine(6mA)modifi-cation,which was found in bacteria,archaea,viruses,and eukaryotes ranging from unicellular protists,fungi,and ciliates to multicellular plants and animals,has been proposed to be potentially associated with some important biological processes such as gene expression regulation and oncogenic pathways(Wion and Casadesus,2006;Boulias and Greer,2022).Yet,recent studies highlighted the arguments on the rarity,source,and origin of 6mA in invertebrates and vertebrates(Boulias and Greer,2022).

High efficiency generation of tunable ellipse perfect vector beams

We present a highly efficient method of generating and shaping ellipse perfect vector beams (EPVBs) with a prescribed ellipse intensity profile and continuously variant linear polarization state. The scheme is based on the coaxial superposition of two orthogonally polarized ellipse laser beams of controllable phase vortex serving as the base vector components. The phase-only computer-generated hologram is specifically designed by means of a modified iteration algorithm involving a complex amplitude constraint, which is able to generate an EPVB with high diffraction efficiency in the vector optical field generator. We experimentally demonstrate that the efficiency of generating the EPVB has a notable improvement from 1.83% in the conventional complex amplitude modulation based technique to 11.1% in our method. We also discuss and demonstrate the simultaneous shaping of multiple EPVBs with independent tunable ellipticity and polarization vortex in both transversal (2D) and axial (3D) focusing structures, proving potentials in a variety of polarization-mediated applications such as trapping and transportation of particles in more complex geometric circumstances.

某全地形车车架模态相关性分析

车架是全地形车的关键部件.本文首先对某全地形车车架进行有限元模态分析,再通过对其进行实验模态分析,对前述有限元模型和结果进行了验证;而后利用频率和振型相关性准则对上述两种结果进行了相关性分析,进一步验证了数值仿真的正确性,为今后的分析工作打好了基础.

Structure of human lysine methyltransferase Smyd2 reveals insights into the substrate divergence in Smyd proteins

The SET-and myeloid-Nervy-DEAF-1(MYND)-domain containing(Smyd)lysine methyltransferases 1–3 share relatively high sequence similarity but exhibit divergence in the substrate specificity.Here we report the crystal structure of the full-length human Smyd2 in complex with S-adenosyl-L-homocysteine(AdoHcy).Although the Smyd1–3 enzymes are similar in the overall structure,detailed comparisons demonstrate that they differ substantially in the potential substrate-binding site.The binding site of Smyd3 consists mainly of a deep and narrow pocket,while those of Smyd1 and Smyd2 consist of a comparable pocket and a long groove.In addition,Smyd2,which has lysine methyltransferase activity on histone H3-lysine 36,exhibits substantial differences in the wall of the substrate-binding pocket compared with those of Smyd1 and Smyd3 which have activity specifically on histone H3-lysine 4.The differences in the substrate-binding site might account for the observed divergence in the specificity and methylation state of the substrates.Further modeling study of Smyd2 in complex with a p53 peptide indicates that mono-methylation of p53-Lys372 might result in steric conflict of the methyl group with the surrounding residues of Smyd2,providing a structural explanation for the inhibitory effect of the SET7/9-mediated mono-methylation of p53-Lys372 on the Smyd2-mediated methylation of p53-Lys370.

China＇s Approach to Its Exchange Rate Mechanism： Adaptability of BBC Rules

China’s recent declaration of principles on its exchange rate mechanism has made it veryclear that any move should be on China’s own initiative; such a move should be sustainableand under control. China has adopted gradualism in the exchange rate reform process. OnJuly 21st, 2005, China changed Renminbi (RMB) parity (appreciation) by 2 percent, signalingthe exchange market reform process. This paper is to study the past history of the crawling-peg of RMB on the US dollar with a view of its future reform. The flexibility provided by thecrawling-peg still fits well with China’s status quo. However, the flexible mechanism shouldfollow the trend of China’s economic development with well-timed parity changes. Theextent of the fluctuation band rests upon China’s ability to maintain its currency stability tocounter future speculation and shocks. Only when the market mechanism is restored inChina can an equilibrium RMB exchange rate be reached.

Entanglement and nonlocality in a coupled-cavity system

No instrument is able to measure directly the quantum entanglement of a system. However, both theory and experiment, following the well-known Bell inequality, reveal the existence of the entanglement phenomenon in quantum mechanics. To examine the characterization of quantum entanglement, here we present a two-site cavity system, in which each cavity contains a Λ-type three-level atom and the two sites are identical and coupled with each other. We investigate and calculate the bipartite entanglement entropy of the system for the ground states. For photons of different types, corresponding to the two ground states of the atom, we investigate the correlations and violation of the Bell inequality.

Curvilinear Poincaré vector beams

We develop a method for completely shaping optical vector beams with controllable amplitude, phase, and polarization gradients along three-dimensional freestyle trajectories. We design theoretically and demonstrate experimentally curvilinear Poincaré vector beams that exhibit high intensity gradients and accurate state of polarization prescribed along the beam trajectory.

Molecular basis for the functions of dominantly active Y35N and inactive D60K Rheb mutants in mTORC1 signaling

Dear Editor,Mammalian target of rapamycin complex 1(mTORC1)serves as a central regulator of cell growth and proliferation by integrating signals from growth factors,nutrients,energy status,and cellular stress(Saxton and Sabatini,2017).A small GTPase,called Ras homolog enriched in brain(Rheb),is a positive regulator of mTORC1.Like other small GTPases,the function of Rheb is dictated by its guanine nucleotide binding states:it is active in the GTP-bound form and inactive in the GDP-bound form(Aspuria and Tamanoi,2004).

Crystal Structures of Arabidopsis thaliana Nudix Hydrolase NUDT7 Reveal a Previously Unobserved Conformation

Dear Editor,Nudix hydrolases are a superfamily of phylogenetically widespread enzymes that catalyze the hydrolysis of nucleoside diphosphate linked to another moiety X （NDP-X） to yield nucleoside monophosphate and P-X. Within the superfamily, at least four families are classified based on their substrate specificities： the Mutt family hydrolases, the ADPR pyrophosphatases, the NADH hydrolases, and the adenosine-（p）n-adenosine hydrolases （Bessman et al., 1996; Gabelii et al., 2001）. Arabidopsis thaliana contains 27 Nudix enzymes whose biological functions are not well understood except for NUDT7 （Ogawa et al., 2005）. NUDT7 belongs to the fibroblast growth factor type Nudix enzyme （FGFTNE） family and shares low sequence identity with other Nudix enzymes with known structures （Gunawardana et al., 2009）. The functional roles of NUDT7 in oxidative stress response and defense response have been demonstrated by genetic studies （Ge et al., 2007; Wang et al., 2013）. It has hydrolase activities toward ADPR and NADH; however, whether ADPR is a physiological substrate of NUDT7 remains obscure （Ge et al., 2007; Wang et al., 2013）.