The Crystal Structure of Monovalent Streptavidin.

The strong interaction between streptavidin (SA) and biotin is widely utilized in biotechnological applications. A SA variant, monovalent SA, was developed with a single and high affinity biotin-binding site within the intact tetramer. However, its structural characterization remains undetermined. Here, we seek to determine the crystal structure of monovalent SA at 1.7-Å resolution. We show that, in contrast to its 'close-state' in the only wild-type subunit, the L3,4 loops of three Dead SA subunits are free from crystal packing and remain in an 'open state', stabilized by a consistent H-bonding network involving S52. This H-bonding network also applies to the previously reported open state of the wild-type apo-SA. These results suggest that specific substitutions (N23A/S27D/S45A) at biotin-binding sites stabilize the open state of SA L3,4 loop, thereby further reducing biotin-binding affinity. The general features of the 'open state' SA among different SA variants may facilitate its rational design. The structural information of monovalent SA will be valuable for its applications across a wide range of biotechnological areas

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

The role of Notch pathway in tumorigenesis is highly variable. It can be tumor suppressive or pro-oncogenic, typically depending on the cellular context. Squamous cell carcinoma (SCC) is a cancer of the squamous cell, which can occur in diverse human tissues. SCCs are one of the most frequent human malignancies for which the pathologic mechanisms remain elusive. Recent genomic analysis of diverse SCCs identified marked levels of mutations in NOTCH1, implicating Notch signaling pathways in the pathogenesis of SCCs. In this review, evidences highlighting NOTCH's role in different types of SCCs are summarized. Moreover, based on accumulating structural information of the NOTCH receptor, the functional consequences of NOTCH1 gene mutations identified from diverse SCCs are analyzed, emphasizing loss of function of Notch in these cancers. Finally, we discuss the convergent view on an intriguing possibility that Notch may function as tumor suppressor in SCCs across different tissues. These mechanistic insights into Notch signaling pathways will help to guide the research of SCCs and development of therapeutic strategies for these cancers

Structural Evolution and Optoelectronic Applications of Multilayer Silicene

Despite the recent progress on two-dimensional multilayer materials (2DMM) with weak interlayer interactions, the investigation on 2DMM with strong interlayer interactions is far from its sufficiency. Here we report on first-principles calculations that clarify the structural evolution and optoelectronic properties of such a 2DMM, multilayer silicene. With our newly developed global optimization algorithm, we discover the existence of rich dynamically stable multilayer silicene phases, the stability of which is closely related to the extent of sp3 hybridization that can be evaluated by the average bonds and effective bond angles. The stable Si(111) surface structures are obtained when the silicene thickness gets up to four, showing the critical thickness for the structural evolution. We also find that the multilayer silicene with pi-bonded surfaces present outstanding optoelectronic properties for the solar cells and optical fiber communications due to the incorporation of sp2-type bonds in the sp3-type bonds dominated system. This study is helpful to complete the picture of structure and related property evolution of 2DMM with strong interlayer interactions.Comment: 4 figure

Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair.

Contrary to the long-held belief that DNA methylation of terminally differentiated cells is permanent and essentially immutable, post-mitotic neurons exhibit extensive DNA demethylation. The cellular function of active DNA demethylation in neurons, however, remains largely unknown. Tet family proteins oxidize 5-methylcytosine to initiate active DNA demethylation through the base-excision repair (BER) pathway. We found that synaptic activity bi-directionally regulates neuronal Tet3 expression. Functionally, knockdown of Tet or inhibition of BER in hippocampal neurons elevated excitatory glutamatergic synaptic transmission, whereas overexpressing Tet3 or Tet1 catalytic domain decreased it. Furthermore, dysregulation of Tet3 signaling prevented homeostatic synaptic plasticity. Mechanistically, Tet3 dictated neuronal surface GluR1 levels. RNA-seq analyses further revealed a pivotal role of Tet3 in regulating gene expression in response to global synaptic activity changes. Thus, Tet3 serves as a synaptic activity sensor to epigenetically regulate fundamental properties and meta-plasticity of neurons via active DNA demethylation

Evolutionary Stages and Disk Properties of Young Stellar Objects in the Perseus Cloud

We investigated the evolutionary stages and disk properties of 211 Young stellar objects (YSOs) across the Perseus cloud by modeling the broadband optical to mid-infrared (IR) spectral energy distribution (SED). By exploring the relationships among the turnoff wave bands lambda_turnoff (longward of which significant IR excesses above the stellar photosphere are observed), the excess spectral index alpha_excess at lambda <~ 24 microns, and the disk inner radius R_in (from SED modeling) for YSOs of different evolutionary stages, we found that the median and standard deviation of alpha_excess of YSOs with optically thick disks tend to increase with lambda_turnoff, especially at lambda_turnoff >= 5.8 microns, whereas the median fractional dust luminosities L_dust/L_star tend to decrease with lambda_turnoff. This points to an inside-out disk clearing of small dust grains. Moreover, a positive correlation between alpha_excess and R_in was found at alpha_excess > ~0 and R_in > ~10 $\times$ the dust sublimation radius R_sub, irrespective of lambda_turnoff, L_dust/L_star and disk flaring. This suggests that the outer disk flaring either does not evolve synchronously with the inside-out disk clearing or has little influence on alpha_excess shortward of 24 microns. About 23% of our YSO disks are classified as transitional disks, which have lambda_turnoff >= 5.8 microns and L_dust/L_star >10^(-3). The transitional disks and full disks occupy distinctly different regions on the L_dust/L_star vs. alpha_excess diagram. Taking L_dust/L_star as an approximate discriminator of disks with (>0.1) and without (<0.1) considerable accretion activity, we found that 65% and 35% of the transitional disks may be consistent with being dominantly cleared by photoevaporation and dynamical interaction respectively. [abridged]Comment: 31 pages, 13 figures, 2 tables. To appear in a special issue of RAA on LAMOST science

KdV limit for the Vlasov-Poisson-Landau system

Two fundamental models in plasma physics are given by the Vlasov-Poisson-Landau system and the compressible Euler-Poisson system which both capture the complex dynamics of plasmas under the self-consistent electric field interactions at the kinetic and fluid levels, respectively. Although there have been extensive studies on the long wave limit of the Euler-Poisson system towards Korteweg-de Vries equations, few results on this topic are known for the Vlasov-Poisson-Landau system due to the complexity of the system and its underlying multiscale feature. In this article, we derive and justify the Korteweg-de Vries equations from the Vlasov-Poisson-Landau system modelling the motion of ions under the Maxwell-Boltzmann relation. Specifically, under the Gardner-Morikawa transformation $$(t,x,v)\to (\delta^{\frac{3}{2}}t,\delta^{\frac{1}{2}}(x-\sqrt{\frac{8}{3}}t),v)$$ with $\varepsilon^{\frac{2}{3}}\leq \delta\leq \varepsilon^{\frac{2}{5}}$ and $\varepsilon>0$ being the Knudsen number, we construct smooth solutions of the rescaled Vlasov-Poisson-Landau system over an arbitrary finite time interval that can converge uniformly to smooth solutions of the Korteweg-de Vries equations as $\delta\to 0$. Moreover, the explicit rate of convergence in $\delta$ is also obtained. The proof is obtained by an appropriately chosen scaling and the intricate weighted energy method through the micro-macro decomposition around local Maxwellians.Comment: 68 pages. All comments are welcome. arXiv admin note: text overlap with arXiv:2212.0765

Asymptotics toward viscous contact waves for solutions of the Landau equation

In the paper, we are concerned with the large time asymptotics toward the viscous contact waves for solutions of the Landau equation with physically realistic Coulomb interactions. Precisely, for the corresponding Cauchy problem in the spatially one-dimensional setting, we construct the unique global-in-time solution near a local Maxwellian whose fluid quantities are the viscous contact waves in the sense of hydrodynamics and also prove that the solution tends toward such local Maxwellian in large time. The result is proved by elaborate energy estimates and seems the first one on the dynamical stability of contact waves for the Landau equation. One key point of the proof is to introduce a new time-velocity weight function that includes an exponential factor of the form $\exp (q(t)\langle \xi\rangle^2)$ with $$q(t):=q_1-q_2\int_0^tq_3(s)\,ds,$$ where $q_1$ and $q_2$ are given positive constants and $q_3(\cdot)$ is defined by the energy dissipation rate of the solution itself. The time derivative of such weight function is able to induce an extra quartic dissipation term for treating the large-velocity growth in the nonlinear estimates due to degeneration of the linearized Landau operator in the Coulomb case. Note that in our problem the explicit time-decay of solutions around contact waves is unavailable but no longer needed under the crucial use of the above weight function, which is different from the situation in [11, 14].Comment: 60 pages. Comments are most welcome. Slight modifications have been made to simplify some estimates using the conservation of mas

国际社会应共同努力建立基于新规则的新秩序

In its nature, world history is an evolutionary cycle of non-rules, non-order to rules and order. The Peace of Westphalia began the international order aiming to resolve disputes through multinational meetings. However, the fragile world order and the code of international relations failed to prevent World War Ⅰ. Although a new system of multinational mechanisms, formed after World War I, reformed the international community, it did not stop World War Ⅱ from breaking out. After World War Ⅱ, a new system of international organizations represented by the United Nations and new norms of international relations centered on the Charter of the United Nations were established. Despite its undeniable role in the world order and the norms of international relations, the so-called Yalta System, still has its flaws. After the end of the Cold War, the necessity of a new world political, economic and security order is rising. The theory and practice of global governance is in need of upgrading. However, due to complicated historical and realistic reasons, the process of building up a new order based on new rules would be long and tortuous. Key Words: International Order, Power Relations, Charter of the United Nations, Global Governance世界历史归根到底，就是从无规则无秩序到有规则有秩序，再到建立新规则新秩序无限发展历程。威斯特伐利亚条约的诞生，标志着以多边会议为争端解决机制的国际秩序开始形成，但粗陋而孱弱的世界秩序和国际关系准则并没能阻止第一次世界大战的爆发。一战后形成的一系列新型多边合作机制曾使国际社会欢欣鼓舞，但这套体制和规则仍未能阻止二战的爆发。国际社会于二战结束之际，建立起以联合国为代表的新的国际组织体系和联合国宪章为核心的新型国际关系准则。这套名为雅尔塔体系的世界秩序和国际关系规则虽然发挥了不可否认的历史作用，但许多方面仍不尽如人意。冷战结束后，世界呼唤新的政治经济秩序、安全格局，全球治理从理论到实践都亟待更新。但由于极其复杂的历史和现实原因，建立基于新规则的新秩序，将是一个漫长而曲折的历史过程。 【关键词】国际秩序，大国关系，联合国宪章，全球治