The quantitative characterization of coal spontaneous combustion and the accurate determination of the dangerous degree are hot and difficult in the field of coal mine safety. In the paper, the ...experimental test analysis of Huangling No. 2 coal was carried out by a self-designed and built kilogram-level coal spontaneous combustion experimental device, and the macro featured parameters were obtained and analyzed, such as temperature field, index gas, weight, oxygen consumption rate and exothermic intensity, and spontaneous combustion limit parameters. The results show that the experimental spontaneous combustion period of Huangling No.2 coal is 34 days. When the coal temperature was below the critical temperature of 74.59 °C, the oxidation of coal samples was relatively slow, and the oxygen consumption and the production rate of gas products did not change much. After the coal temperature exceeded the critical temperature, the oxygen consumption rate and exothermic intensity increased faster and the oxidation accelerated. After reaching the dry cracking temperature of 104.93 °C, the oxidation degree accelerated sharply. CO starts to appear at the beginning of the experiment, and the increase of CO gas concentration during the heating process is exponential and can be used as an index gas. Under the temperature condition of 40 °C, the floating coal of 0.7 m needs 25.83% oxygen concentration, and the maximum air leakage intensity of the coal is negative, and no spontaneous combustion will occur. The test data and calculation results of the experiment are important for the prediction and forecast of natural fires and the determination of the risk of spontaneous combustion on site.
The tolerances and limitations in design and manufacturing of both electrical motors and inverters lead to parasitic resistances in the phases. Therefore, the phase resistances are asymmetric, which ...causes an asymmetry among the phase currents and a resulting increase in torque ripple. This paper proposes a novel scheme for torque ripple minimization using online estimation of unbalanced stator resistances of a permanent-magnet synchronous motor. The identifiability of the stator resistances in a nonlinear model is investigated by employing a sensitivity analysis. The phase resistances are estimated by recursive least squares in the rotating reference frame in real time. Using the estimated resistances, torque ripple reduction is achieved by a compensation scheme in the stationary reference frame. The effectiveness of the proposed scheme is verified in both simulation and test-bench experiments. Results with and without consideration of magnetic saturation are compared.
Structure of nucleosome-bound human BAF complex He, Shuang; Wu, Zihan; Tian, Yuan ...
Science (American Association for the Advancement of Science),
02/2020, Letnik:
367, Številka:
6480
Journal Article
Recenzirano
Mammalian SWI/SNF family chromatin remodelers, BRG1/BRM-associated factor (BAF) and polybromo-associated BAF (PBAF), regulate chromatin structure and transcription, and their mutations are linked to ...cancers. The 3.7-angstrom-resolution cryo-electron microscopy structure of human BAF bound to the nucleosome reveals that the nucleosome is sandwiched by the base and the adenosine triphosphatase (ATPase) modules, which are bridged by the actin-related protein (ARP) module. The ATPase motor is positioned proximal to nucleosomal DNA and, upon ATP hydrolysis, engages with and pumps DNA along the nucleosome. The C-terminal α helix of SMARCB1, enriched in positively charged residues frequently mutated in cancers, mediates interactions with an acidic patch of the nucleosome. AT-rich interactive domain-containing protein 1A (ARID1A) and the SWI/SNF complex subunit SMARCC serve as a structural core and scaffold in the base module organization, respectively. Our study provides structural insights into subunit organization and nucleosome recognition of human BAF complex.
Dear Editor, N6-methyladenosine （m6A） has been demonstrated to be ubiquitous in several types of eukaryotic RNAs, including messenger RNA （mRNA）, transfer RNA （tRNA）, ribosomal RNA （rRNA）, long ...non-coding RNA （lncRNA）, and small nuclear RNA （snRNA） 1. The recent discoveries of RNA m6A methyltransferase complex METTL3/METTL14/WTAP and demethylases FTO and ALKBH5 prove the reversibility of m6A modification 2-6. This modification plays important roles in various biological processes, including circadian rhythms 7,
DNA-dependent protein kinase （DNA-PK） is a serine/threonine protein kinase complex composed of a catalytic subunit （DNA-PKcs） and KU70/80 heterodimer bound to DNA. DNA-PK holoenzyme plays a critical ...role in non-homologous end joining （NHEJ）, the major DNA repair pathway. Here, we determined cryo-electron microscopy structure of human DNA-PK holoenzyme at 6.6 A resolution. In the complex structure, DNA-PKcs, KU70, KU80 and DNA duplex form a 650-kDa heterotetramer with 1：1：1：1 stoichiometry. The N-terminal α-solenoid （-2 800 residues） of DNA-PKcs adopts a double-ring fold and connects the catalytic core domain of DNA-PKcs and KU70/80-DNA. DNA-PKcs and KU70/80 together form a DNA-binding tunnel, which cradles -30-bp DNA and prevents sliding in- ward of DNA-PKcs along with DNA duplex, suggesting a mechanism by which the broken DNA end is protected from unnecessary processing. Structural and biochemical analyses indicate that KU70/80 and DNA coordinately induce conformational changes of DNA-PKcs and allosterically stimulate its kinase activity. We propose a model for activa- tion of DNA-PKcs in which allosteric signals are generated upon DNA-PK holoenzyme formation and transmitted to the kinase domain through N-terminal HEAT repeats and FAT domain of DNA-PKcs. Our studies suggest a mecha- nism for recognition and protection of broken DNA ends and provide a structural basis for understanding the activa- tion of DNA-PKcs and DNA-PK-mediated NHEJ pathway.
The 1.3-MDa transcription factor IID (TFIID) is required for preinitiation complex (PIC) assembly and RNA polymerase II (Pol II)-mediated transcription initiation on almost all genes. The 26-subunit ...Mediator stimulates transcription and cyclin-dependent kinase 7 (CDK7)-mediated phosphorylation of Pol II C-terminal domain (CTD). We determined the structures of human Mediator in the Tail module-extended (at near-atomic resolution) and Tail-bent conformations and structures of TFIID-based PIC-Mediator (76 polypeptides, ~4.1 MDa) in four distinct conformations. PIC-Mediator assembly induces concerted reorganization (Head-tilting and Middle-down) of Mediator and creates a Head-Middle sandwich, which stabilizes two CTD segments and brings CTD to CDK7 for phosphorylation, suggesting a CTD-gating mechanism favorable for phosphorylation. The TFIID-based PIC architecture modulates Mediator organization and TFIIH stabilization, underscoring the significance of TFIID in orchestrating PIC-Mediator assembly.
The 5'-end capping of nascent pre-mRNA represents the initial step in RNA processing, with evidence demonstrating that guanosine addition and 2'-O-ribose methylation occur in tandem with early steps ...of transcription by RNA polymerase II, especially at the pausing stage. Here, we determine the cryo-EM structures of the paused elongation complex in complex with RNGTT, as well as the paused elongation complex in complex with RNGTT and CMTR1. Our findings show the simultaneous presence of RNGTT and the NELF complex bound to RNA polymerase II. The NELF complex exhibits two conformations, one of which shows a notable rearrangement of NELF-A/D compared to that of the paused elongation complex. Moreover, CMTR1 aligns adjacent to RNGTT on the RNA polymerase II stalk. Our structures indicate that RNGTT and CMTR1 directly bind the paused elongation complex, illuminating the mechanism by which 5'-end capping of pre-mRNA during transcriptional pausing.
The 14-subunit metazoan-specific Integrator contains an endonuclease that cleaves nascent RNA transcripts. Here, we identified a complex containing Integrator and protein phosphatase 2A core enzyme ...(PP2A-AC), termed INTAC. The 3.5-angstrom-resolution structure reveals that nine human Integrator subunits and PP2A-AC assemble into a cruciform-shaped central scaffold formed by the backbone and shoulder modules, with the phosphatase and endonuclease modules flanking the opposite sides. As a noncanonical PP2A holoenzyme, the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 and thus regulates transcription. Our study extends the function of PP2A to transcriptional regulation and reveals how dual enzymatic activities-RNA cleavage and RNA polymerase II dephosphorylation-are structurally and functionally integrated into the INTAC complex.
Histone demethylases play important roles in various biological processes in a manner dependent on their demethylase activities. However, little is known about their demethylase-independent ...activities. Here, we report that LSD2, a well-known histone H3K4me1/me2 demethylase, possesses an unexpected E3 ubiquitin ligase activity. LSD2 directly ubiquitylates and promotes proteasome-dependent degradation of O-GlcNAc transferase (OGT), and inhibits A549 lung cancer cell growth in a manner dependent on its E3 ligase activity, but not demethylase activity. The depletion of LSD2 stabilizes OGT and promotes colony formation of 293T cells. LSD2 regulates distinct groups of target genes through histone demethylase and E3 ligase activities, respectively. Such regulation suggests a mechanism through which LSD2 suppresses tumorigenesis by promoting the degradation of OGT and other substrates yet to be discovered. Our study reveals an antigrowth function of LSD2 dependent on its E3 ligase activity and establishes a connection between histone demethylase and ubiquitin-dependent pathway.
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•The histone demethylase LSD2 possesses unexpected E3 ubiquitin ligase activity•LSD2 targets OGT for polyubiquitylation in vitro and in vivo•LSD2 inhibits lung cancer cell A549 growth by promoting OGT degradation•LSD2 regulates distinct groups of target genes
Yang et al. found that the histone demethylase LSD2 possesses unexpected E3 ubiquitin ligase activity. LSD2 inhibits lung cancer cell growth through promoting ubiquitylation and degradation of OGT. The study defines a function of LSD2 and establishes a connection between histone demethylase and ubiquitin-dependent pathway.
Mammalian TIP60 is a multi-functional enzyme with histone acetylation and histone dimer exchange activities. It plays roles in diverse cellular processes including transcription, DNA repair, cell ...cycle control, and embryonic development. Here we report the cryo-electron microscopy structures of the human TIP60 complex with the core subcomplex and TRRAP module refined to 3.2-Å resolution. The structures show that EP400 acts as a backbone integrating the motor module, the ARP module, and the TRRAP module. The RUVBL1-RUVBL2 hexamer serves as a rigid core for the assembly of EP400 ATPase and YL1 in the motor module. In the ARP module, an ACTL6A-ACTB heterodimer and an extra ACTL6A make hydrophobic contacts with EP400 HSA helix, buttressed by network interactions among DMAP1, EPC1, and EP400. The ARP module stably associates with the motor module but is flexibly tethered to the TRRAP module, exhibiting a unique feature of human TIP60. The architecture of the nucleosome-bound human TIP60 reveals an unengaged nucleosome that is located between the core subcomplex and the TRRAP module. Our work illustrates the molecular architecture of human TIP60 and provides architectural insights into how this complex is bound by the nucleosome.Mammalian TIP60 is a multi-functional enzyme with histone acetylation and histone dimer exchange activities. Here, the authors determined the cryo-EM structures of human TIP60 complex and an architecture of the nucleosome-bound human TIP60.
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