小拟南芥MKK基因家族全基因组鉴定及进化和表达分析

丝裂原活化蛋白激酶激酶(mitogen-activated protein kinase kinase,MAPKK或MKK)是丝裂原活化蛋白激酶(mitogen-activatedproteinkinase,MAPK)级联的重要组成部分,在植物的生长发育和胁迫应答过程中发挥重要作用。目前,已在多种植物中鉴定了MKK基因家族,但在十字花科植物小拟南芥(Arabidopsis pumila)中MKK基因家族的系统鉴定与分析尚未见报道。为了探索小拟南芥MKK基因家族的进化和功能,本研究通过全基因组分析鉴定了小拟南芥中16个MKK基因,散布于小拟南芥的10条染色体上。基于系统发育分析和多重序列比对,将这些基因分为5个亚族:A亚族(5个)、B亚族(2个)、C亚族(4个)、D亚族(3个)和E亚族(2个)。分子进化和共线性分析表明小拟南芥中存在7对复制基因,分别是ApMKK1-1/1-2、ApMKK2-1/2-2、ApMKK3-1/3-2、ApMKK4-1/4-2、ApMKK5-1/5-2、ApMKK9-1/9-2和ApMKK10-1/10-2,其中ApMKK1-1/1-2在复制事件之后发生了加速进化。结合ApMKKs启动子区的顺式元件分布和ApMKKs在成熟叶片、茎、花和果实以及盐胁迫下的表达模式,结果发现复制基因的表达具有组织特异性和功能多样性。部分复制基因在组织中的表达模式存在差异,但在盐胁迫下的表达模式却基本相同。本研究结果为解析MKK介导的小拟南芥发育过程和非生物胁迫信号转导通路的复杂机制奠定了基础。

小鼠耳芥MAPKKK基因家族全基因组鉴定及进化与表达

丝裂原活化蛋白激酶激酶激酶(Mitogen-activated protein kinase kinase kinases,MAPKKKs)是MAPK级联的重要组成部分,在发育过程和胁迫反应中发挥重要功能。小鼠耳芥(Arabidopsis pumila)是生活在新疆荒漠中的十字花科短命植物,具有很好的耐盐能力。为了探索小鼠耳芥MAPKKK基因家族的进化和功能,本研究通过全基因组分析从小鼠耳芥基因组中鉴定了143个ApMAPKKK基因,分属3个亚族:ZIK(20个)、MEKK(36个)和RAF(87个)。共线性分析表明小鼠耳芥与拟南芥和琴叶拟南芥分别存在74和72个共线性基因,说明该家族在小鼠耳芥基因组中发生了明显的扩张;进化分析表明存在64对复制基因对,Ka/Ks均小于1,以纯化选择为主。利用RNA-seq数据分析ApMAPKKK在盐胁迫和不同组织中的表达特征,结果表明在250 mmol/L NaCl胁迫下,大多数ApMAPKKK基因上调表达,其中ApMAPKKK18-1/2和ApMAPKKK17-1/2显著上调表达;而在8个组织中,ApMAPKKK主要呈现6种表达模式;部分复制基因在盐胁迫和组织中的表达模式存在差异。本研究结果为进一步解析小鼠耳芥MAPKKK基因家族成员响应非生物胁迫信号转导通路的复杂机制奠定了基础。

Effect of SARS-CoV-2 infection in early pregnancy on placental development

Dear Editor,Since the COVID-19 pandemic, the potential risks associated with maternal SARS-CoV-2 infection and its effect on fetal development have been a subject of considerable public concern. Previous studies have shown that SARS-CoV-2 infection during pregnancy may increase the incidence of adverse outcomes.

cGAS guards against chromosome endto-end fusions during mitosis and facilitates replicative senescence

As a sensor of cytosolic DNA, the role of cyclic GMP-AMP synthase (cGAS) in innate immune response is well established, yet how its functions in different biological conditions remain to be elucidated. Here, we identify cGAS as an essential regulator in inhibiting mitotic DNA double-strand break (DSB) repair and protecting short telomeres from end-to-end fusion independent of the canonical cGAS-STING pathway. cGAS associates with telomeric/subtelomeric DNA during mitosis when TRF1/TRF2/POT1 are deficient on telomeres. Depletion of cGAS leads to mitotic chromosome end-to-end fusions predominantly occurring between short telomeres. Mechanistically, cGAS interacts with CDK1 and positions them to chromosome ends. Thus, CDK1 inhibits mitotic non-homologous end joining (NHEJ) by blocking the recruitment of RNF8. cGAS-deficient human primary cells are defective in entering replicative senescence and display chromosome end-to-end fusions, genome instability and prolonged growth arrest. Altogether, cGAS safeguards genome stability by controlling mitotic DSB repair to inhibit mitotic chromosome end-to-end fusions, thus facilitating replicative senescence.

Enhanced tensile ductility of tungsten microwires via high-density dislocations and reduced grain boundaries

Despite being strong with many outstanding physical properties,tungsten is inherently brittle at room temperature,restricting its structural and functional applications at small scales.Here,a facile strategy has been adopted,to introduce high-density dislocations while reducing grain boundaries,through electron backscatter diffraction(EBSD)-guided microfabrication of cold-drawn bulk tungsten wires.The designed tungsten microwire attains an ultralarge uniform tensile elongation of~10.6%,while retains a high yield strength of~2.4 GPa.in situ TEM tensile testing reveals that the large uniform elongation of tungsten microwires originates from the motion of pre-existing high-density dislocations,while the subsequent ductile fracture is attributed to crack-tip plasticity and the inhibition of grain boundary cracking.This work demonstrates the application potential of tungsten microcomponents with superior ductility and workability for micro/nanoscale mechanical,electronic,and energy systems.

FULL-DISCRETE FINITE ELEMENT METHOD FOR STOCHASTIC HYPERBOLIC EQUATION

This paper is concerned with the finite element method for the stochastic wave equation and the stochastic elastic equation driven by space-time white noise. For simplicity~ we rewrite the two types of stochastic hyperbolic equations into a unified form. We convert the stochastic hyperbolic equation into a regularized equation by discretizing the white noise and then consider the full-discrete finite element method for the regularized equation. We derive the modeling error by using “Green＇s method” and the finite element approximation error by using the error estimates of the deterministic equation. Some numerical examples are presented to verify the theoretical results.

Therapeutic potential of C1632 by inhibition of SARS-CoV-2 replication and viral-induced inflammation through upregulating let-7

Dear Editor,The COVID-19 pandemic caused by SARS-CoV-2 has led to acute respiratory distress syndrome(ARDS)with a high rate of death.An excessive inflammatory response,caused by virus infection,is associated with severe clinical manifestations that may lead to death of patients.1 Therefore,the blockage of virus replication and suppression of hyper-inflammatory response are beneficial for COVID-19 treatment.However,the drug targeting both virus and hyper-inflammation,as far as we know,is not available yet.

位错驱动下ZnS单晶半导体的非凡光-机-电学特性

Dislocations,which are topological line defects within a crystal lattice,play a dominant role in crystal plasticity and thus affect various mechanical,electronic,magnetic and optical properties of crystals.These dislocations also play a crucial role in the structural hardening and material processing[1].In general,mechanical stress is believed to be the fundamental driving force for the movement of dislocations in a crystal.

Inhibition of p53 and/or AKT as a new therapeutic approach specifically targeting ALT cancers

While the majority of all human cancers court teract telomere shortening by expressing telomerase,-15%of all cancers maintain telomere length by a telomerase?independent mechanism known as alternative lengthening of telomeres(ALT).Here,we show that high load of intrinsic DNA damage is present in ALT cancer cells,leading to apoptosis stress by activating p53-independent,but JNK/c-IVIyc-dependent apoptotic pathway.Notably,ALT cells expressing wild-type p53 show much lower apoptosis than p53-deficient ALT cells.Mechanistically,we find that intrinsic DNA damage in ALT cells induces low level of p53 that is insufficient to initiate the transcription of apoptosis-related genes,but is sufficient to stimulate the expression of key components of mTORC2(mTOR and Rictor),which in turn leads to phosphorylation of AKT.Activated AKT(p-AKT)thereby stimulates downstream anti-apoptotic events.Therefore,p53 and AKT are the key factors that suppress sponta?neous apoptosis in ALT cells.Indeed,inhibition of p53 or AKT selectively induces rapid death of ALT cells in vitro,and p53 inhibitor severely suppresses the growth of ALT-cell xenograft tumors in mice.These findings reveal a previously unrecognized function of p53 in antiapoptosis and identify that the inhibition of p53 or AKT has a potential as therapeutics for specifically targeting ALT cancers.

Interaction of {11■2} twin variants in hexagonal close-packed titanium

As multiple{11■2}twin variants are often formed during deformation in hexagonal close-packed (hcp)titanium, the twin-twin interaction structure has a profound influence on mechanical properties. In this paper, the twin-twin interaction structures of the{11■2}contraction twin in cold-rolled commercial purity titanium were studied by using electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM). Formation of the{11■2}twin variants was found to deviate the rank of Schmid factor,and the non-Schmid behavior was explained by the high-angle grain boundary nucleation mechanism.All the observed twin-twin pairs manifested a quilted-looking structure, which consists of the incoming twins being arrested by the obstacle twins. Furthermore, the quilted-looking{11■2}twin-twin boundary was revealed by TEM and high resolution TEM observations. De-twinning, lattice rotation and curved twin boundary were observed in the obstacle twin due to the twin-twin reaction with the impinging twin. A twin-twin interaction mechanism for the{11■2}twin variants was proposed in terms of the dislocation dissociation, which will enrich the understanding for the propagation of twins and twinning-induced hardening in hcp metals and alloys.

MIXED FINITE ELEMENT METHODS FOR FRACTIONAL.NAVIER-STOKES EQUATIONS

This paper gives the detailed numerical analysis of mixed finite element method for fractional Navier-Stokes equations.The proposed method is based on the mixed finite element method in space and a finite difference scheme in time.The stability analyses of semi-discretization scheme and fully discrete scheme are discussed in detail.Furthermore,We give the convergence analysis for both semidiscrete and flly discrete schemes and then prove that the numerical solution converges the exact one with order O(h2+k),where h and k:respectively denote the space step size and the time step size.Finally,numerical examples are presented to demonstrate the effectiveness of our numerical methods.

β-Catenin Deletion in Regional Neural Progenitors Leads to Congenital Hydrocephalus in Mice

Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality;however,the underlying cellular and molecular mechanisms remain largely unknown.Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited.Here,we describe a new mouse model of congenital hydrocephalus through knockout ofβ-catenin in Nkx2.1-expressing regional neural progenitors.Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood.Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis afterβ-catenin knockout.Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages.Thus,knockout ofβ-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.

High elasticity of CsPbBr_(3) perovskite nanowires for flexible electronics

Due to the enhanced ambient structural stability and excellent optoelectronic properties, all-inorganic metal halide perovskite nanowires have become one of the most attractive candidates for flexible electronics, photovoltaics and optoelectronics. Their elastic property and mechanical robustness become the key factors for device applications under realistic service conditions with various mechanical loadings. Here, we demonstrate that high tensile elastic strain (∼ 4% to ∼ 5.1%) can be achieved in vapor-liquid-solid-grown single-crystalline CsPbBr_(3) nanowires through in situ scanning electron microscope (SEM) buckling experiments. Such high flexural elasticity can be attributed to the structural defect-scarce, smooth surface, single-crystallinity and nanomechanical size effect of CsPbBr_(3) nanowires. The mechanical reliability of CsPbBr_(3) nanowire-based flexible photodetectors was examined by cyclic bending tests, with no noticeable performance deterioration observed after 5,000 cycles. The above results suggest great application potential for using all-inorganic perovskite nanowires in flexible electronics and energy harvesting systems.

Formation mechanism of hydride precipitation in commercially pure titanium

Since titanium has high affinity for hydrogen and reacts reversibly with hydrogen,the precipitation of titanium hydrides in titanium and its alloys cannot be ignored.Two most common hydride precipitates in α-Ti matrix areγ-hydride and δ-hydride,however their mechanisms for precipitation are still unclear.In the present study,we find that both γ-hydride and δ-hydride phases with different specific orientations were randomly precipitated in the as-received hot forged commercially pure Ti.In addition,a large amount of the titanium hydrides can be introduced into Ti matrix with selective precipitation by using electrochemical treatment.Cs-corrected scanning transmission electron microscopy is used to study the precipitation mechanisms of the two hydrides.It is revealed that the γ-hydride and δ-hydride precipitations are both formed through slip+shuffle mechanisms involving a unit of two layers of titanium atoms,but the difference is that the γ-hydride is formed by prismatic slip corresponding to hydrogen occupying the octahedral sites of α-Ti,while the δ-hydride is formed by basal slip corresponding to hydrogen occupying the tetrahedral sites ofα-Ti.

A tribute to Professor Yong Zhao

Professor Yong Zhao was the Dean of School of Life Sciences at Sun Yat-sen University and a renowned biologist whose studies focused on the role of telomeres and telom-erase in cancer and aging.Dr.Zhao's postdoctoral mentor Professor Woodring E.Wright(1949-2019)of University of Texas Southwestern Medical Center(UTSW)once remarked,“It will be hard for anyone else in my lab to match up to the superb performance of Yong Zhao.”

Correction to:Inhibition of p53 and/or AKT as a new therapeutic approach specifically targeting ALT cancers

Figure 4.AKT is phosphorylated in p53>dependent manner in ALT cells.(A)Western blot determination of total and phosphorylated AKT(S473)in p53-positive(VA13,U20S)and p53-defective(SAOS2,SKLU-1)ALT cells.(B)Knockdown of p53 in U20S or moderate expression of p53 in SAOS2 induces down or up-regulation of p-AKT,respectively.(C)Knockdown of ATM or ATR by siRNA decreases abundance of p53,phosphorylated p53 and p-AKT.(D)Quantitative-PCR determination of the level of ATR or ATM in U20S cells transfected with siRNA to ATR or ATM,respectively.Scramble siRNA(Si-Ctl)was used as control.Data represent the mean±SEM,n=3-4.(E)ATM(KU60019)or ATR(VE-821)inhibitor decreases abundance of p-AKT in U20S cells.U20S cells were treated with indicated concentration of KU60019 or VE-821 for 24 h.(F)The expression of wt-p53,but not mutant p53(p53-s269e)defective of transcription activity,increases the level of p-AKT.(G)PFTa.an inhibitor of p53 transcription activity,suppresses the phosphorylation of AKT.U20S cells were treated with indicated concentration of PFTa for 24 h.