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1.
Phys Rev Lett ; 131(14): 145003, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37862653

RESUMO

We propose exploiting the superluminal plasma wake for coherent Cherenkov radiation by injecting a relativistic electron beam (REB) into a plasma with a slowly varying density up-ramp. Using three-dimensional particle-in-cell and far-field time-domain radiation simulations, we show that an isolated subcycle pulse is coherently emitted towards the Cherenkov angle by bubble-sheath electrons successively at the rear of the REB-induced superluminal plasma wake. A theoretical model based on a superluminal current dipole has been developed to interpret such coherent radiation, and agrees well with the simulation results. This radiation has ultrashort attosecond-scale duration and high intensity, and exhibits excellent directionality with ultralow angular divergence and stable carrier envelope phase. Its intensity increases with the square of the propagation length and its central frequency can be easily tuned over a wide range, from the far infrared to the ultraviolet.

2.
Nat Commun ; 14(1): 5782, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723172

RESUMO

In laser-driven inertial confinement fusion, driving pressure boosting and smoothing are major challenges. A proposed hybrid-drive (HD) scheme can offer such ideal HD pressure performing stable implosion and nonstagnation ignition. Here we report that in the hemispherical and planar ablator targets installed in the semicylindrical hohlraum scaled down from the spherical hohlraum of the designed ignition target, under indirect-drive (ID) laser energies of ~43-50 kJ, the peak radiation temperature of 200 ± 6 eV is achieved. And using only direct-drive (DD) laser energies of 3.6-4.0 kJ at an intensity of 1.8 × 1015 W/cm2, in the hemispherical and planar targets the boosted HD pressures reach 3.8-4.0 and 3.5-3.6 times the radiation ablation pressure respectively. In all the above experiments, significant HD pressure smoothing and the important phenomenon of how a symmetric strong HD shock suppresses the asymmetric ID shock pre-compressed fuel are demonstrated. The backscattering and hot-electron energy fractions both of which are about one-third of that in the DD scheme are also measured.

3.
Zhonghua Xin Xue Guan Bing Za Zhi ; 51(9): 977-983, 2023 Sep 24.
Artigo em Chinês | MEDLINE | ID: mdl-37709715

RESUMO

Objective: To investigate the impact of COVID-19 on treatment of patients with acute ST segment elevation myocardial infarction(STEMI) undergoing primary percutaneous coronary intervention(PPCI). Methods: This was a multicenter retrospective study. STEMI patients undergoing PPCI from January 1, 2019 to December 31, 2021 were selected, based on the data of Xinnaolvsetongdao App. Clinical data and treatment time indicators, including symptom to first medical contact (S-FMC), symptom to door (StoD), first medical contact to ECG (FMC-ECG), first medical contact to guide wire (FMC-W), door to balloon (DtoB) and total ischemic time in 2019, 2020 and 2021 were compared. STEMI patients aged<60 years were sub-grouped as the young and middle-aged group, and STEMI patients aged≥60 years were sub-grouped as the elderly group. Results: A total of 7 435 (3 305 in 2019, 1 796 in 2020 and 2 334 in 2021) STEMI patients aged (59.6±12.6) years undergoing PPCI were included in this analysis. There were 5 990 males. For STEMI patients with PPCI in 2019, 2020 and 2021, FMC-ECG was 3 (1, 5) min, 3(1, 7) min and 4 (1, 7) min. FMC-W was 73 (56, 87) min, 78 (62, 95) min and 77 (62, 87) min. DtoB was 73 (56, 85) min, 78 (62, 95) min and 77 (62, 86) min. Total ischemic time was 189 (130, 273) min, 196 (138, 295) min and 209 (143, 276) min. FMC-ECG, FMC-W, DtoB and total ischemic time were longer in 2020 and 2021 than in 2019 (all P<0.05). The proportions of patients with FMC-ECG≤10 min (88.4% (1 588/1 796) vs. 92.7% (3 064/3 305), P<0.05), FMC-W≤120 min (87.9% (1 579/1796) vs. 91.7% (3 030/3 305), P<0.05) and DtoB≤90 min (72.3% (1 298/1 796) vs. 80.8% (2 672/3 305), P<0.05) were lower in 2020 than in 2019, whereas no differences were observed in the proportions of patients with FMC-ECG≤10 min (91.3% (2 131/2 334) vs. 92.7% (3 064/3 305), P=0.054), FMC-W≤120 min (92.0% (2 148/2 334) vs. 91.7% (3 030/3 305), P=0.635) and DtoB≤90 min (80.0% (1 867/2 334) vs. 80.8% (2 672/3 305), P=0.424) in 2021 compared with 2019. In the subgroup analysis, the proportions of patients with FMC-ECG≤10 min, FMC-W≤120 min and DtoB≤90 min were lower in the elderly group than in young and middle-aged group in 2019 (all P<0.05). The proportions of patients with FMC-W≤120 min and DtoB≤90 min were lower in the elderly group than in young and middle-aged group in 2021(all P<0.05). No differences were observed in the proportions of patients with FMC-ECG≤10 min, FMC-W≤120 min and DtoB≤90 min between the two group in 2020 (all P>0.05). Conclusions: Affected by the COVID-19, there is a reduction in the number of PPCI cases and treatment delays in STEMI patients, especially in the elderly. After adjusting the treatment strategy and widely applying the Xinnaolvsetongdao APP, the above indicators are significantly improved in 2021 as compared with 2020.


Assuntos
Infarto Miocárdico de Parede Anterior , COVID-19 , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Idoso , Masculino , Pessoa de Meia-Idade , Humanos , Pequim , Estudos Retrospectivos , Arritmias Cardíacas
4.
Phys Rev Lett ; 130(18): 185001, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37204906

RESUMO

Propagation of high-current relativistic electron beam (REB) in plasma is relevant to many high-energy astrophysical phenomena as well as applications based on high-intensity lasers and charged-particle beams. Here, we report a new regime of beam-plasma interaction arising from REB propagation in medium with fine structures. In this regime, the REB cascades into thin branches with local density a hundred times the initial value and deposits its energy 2 orders of magnitude more efficiently than that in homogeneous plasma, where REB branching does not occur, of similar average density. Such beam branching can be attributed to successive weak scatterings of the beam electrons by the unevenly distributed magnetic fields induced by the local return currents in the skeletons of the porous medium. Results from a model for the excitation conditions and location of the first branching point with respect to the medium and beam parameters agree well with that from pore-resolved particle-in-cell simulations.

5.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(6): 815-823, 2022 Jun 06.
Artigo em Chinês | MEDLINE | ID: mdl-35785864

RESUMO

Objective: To analyze the phenotypic and genomic characteristics of Salmonella isolates recovered from meat products in Beijing wholesale markets. Methods: A total of 336 Salmonella strains from meat products collected from wholesale markets in Beijing were tested for antimicrobial resistance to 25 antimicrobial compounds by micro-broth dilution method; whole genome data were sequenced, followed by the serotype and ST type prediction by Seqsero2 and SISTR software, and the drug resistance genes and virulence factors were also predicted with CARD and VFDB databases of Abricate software; Salmonella serotyping assay kit and serum agglutination method were used for serotype confirmation of some isolates with different genome prediction results. Results: The resistance rates to Nalidixic acid and Ampicillin were 62.5% (210/336) and 55.1% (185/336), respectively, and all isolates were susceptible to Tigecyclin, Cefoxitin and Carbapenem antimicrobial compounds; 207 isolates (61.6%, 207/336) were multi-drug resistant, some could even be resistant to ten categories of drugs at the same time, and the most common antimicrobial resistance spectrum was NAL-AMP-SAM. A total of 24 serotypes were detected with predominant serotypes of Enteritidis (34.5%, 116/336), Derby (17.3%, 58/336) and Indiana (10.4%, 35/336). A total of 27 ST types were detected, the dominant type was ST11; ST types were in good consistency with serotypes; The detection rates of resistant genes referred to aminoglycosides, fluoroquinolones, ß-lactams, sulfonamides and tetracyclines are more than 48%, and the first two reached 100%. The prediction of drug resistance genes was consistent with the results of antimicrobial resistance phenotype. A total of 122 virulence genes were predicted, 74 of which existing among all isolates. Conclusion: Salmonella in meat from the wholesale markets of Beijing has a high proportion of multiple drug resistance, a complex drug resistance spectrum, a variety of serotypes and ST types, and a high carrying rate of drug resistance gene and virulence gene; drug resistance phenotype and genotype are relatively consistent.


Assuntos
Anti-Infecciosos , Produtos da Carne , Antibacterianos/farmacologia , Pequim , Farmacorresistência Bacteriana/genética , Genômica , Testes de Sensibilidade Microbiana , Salmonella/genética , Sorogrupo
6.
Phys Rev Lett ; 127(24): 245002, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34951809

RESUMO

Transport of high-current relativistic electron beams in dense plasmas is of interest in many areas of research. However, so far the mechanism of such beam-plasma interaction is still not well understood due to the appearance of small time- and space-scale effects. Here we identify a new regime of electron beam transport in solid-density plasma, where kinetic effects that develop on small time and space scales play a dominant role. Our three-dimensional particle-in-cell simulations show that in this regime the electron beam can evolve into layered short microelectron bunches when collisions are relatively weak. The phenomenon is attributed to a secondary instability, on the space- and timescales of the electron skin depth (tens of nanometers) and few femtoseconds of strong electrostatic modulation of the microelectron current filaments formed by Weibel-like instability of the original electron beam. Analytical analysis on the amplitude, scale length, and excitation condition of the self-generated electrostatic fields is clearly validated by the simulations.

7.
Zhonghua Xin Xue Guan Bing Za Zhi ; 49(2): 128-135, 2021 Feb 24.
Artigo em Chinês | MEDLINE | ID: mdl-33611898

RESUMO

Objective: To evaluate the 4-year clinical outcomes of patients following Firesorb bioresorbable scaffold (BRS) implantation. Methods: The study reported the 4-year follow-up results of the FUTURE I study. FUTURE I was a prospective, single-center, open-label, first-in-man study which evaluated the feasibility, preliminary safety, and efficacy of Firesorb stent in the treatment of coronary artery stenosis. A total of 45 patients with single de novo lesions in native coronary arteries ,who hospitalized in Fuwai Hospital from January to March 2016 were enrolled. After successfully stent implantation these patients were randomized in a 2∶1 ratio into cohort 1 (n=30) or cohort 2 (n=15). The patients in cohort 1 underwent angiographic, IVUS or OCT examination at 6 months and 2 years; and cohort 2 underwent angiographic, IVUS or OCT at 1 and 3 years. All patients underwent clinical follow-up at 1, 6 months and 1 year and annually thereafter up to 5 years. The primary endpoint was target lesion failure (TLF, including cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization). Secondary endpoints included patient-oriented composite endpoint (PoCE, defined as composite of all death, all miocardial infarction, or any revascularization). Results: A total of 45 patients were enrolled and implanted with Firesorb BRS, including 35 males (77.8%), and the age was (54.4±9.3) years. At 4 years, 10 patients in cohort 1 were reexamined by coronary angiography and OCT examination. Among them, 2 patients' stents were completely degraded and absorbed. Compared with the OCT images of the other 8 patients in cohort 2 at 3 years, the degree of stent degradation was increased, and no stent adherence was found. The 4-year clinical follow-up rate was 100%. In 4-year clinical following up, 2 patients suffered PoCE (4.4%): 1 patient underwent non-target vessel revascularization the day after index procedure and target vessel revascularization (Non-target lesion revascularization) at 2-year imaging follow-up; the other patient underwent target lesion revascularization during imaging follow-up at 4 years but not due to ischemic driven. There was no scaffold thrombosis or TLF events through 4 years. Conclusions: Four years after the implantation, complete degradation and absorption of the Firsorb stent are evidenced in some patients. Firesorb stent is feasible and effective in the treatment of patients with non-complex coronary lesions.


Assuntos
Fármacos Cardiovasculares , Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Implantes Absorvíveis , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sirolimo , Resultado do Tratamento
8.
Zhonghua Yan Ke Za Zhi ; 55(3): 228-233, 2019 Mar 11.
Artigo em Chinês | MEDLINE | ID: mdl-30841690

RESUMO

The idiopathic optic neuritis (ION) which is related to neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) is called optic neuritis related to neuromyelitis optica (NMO-ON). Because of the high rates of blindness, disability and fatality of NMO, the heterogeneous clinical presentation, severity of neurologic disability following relapses, and variability of therapeutic responses, reliable and sensitive biomarkers for onset, relapse, and progression in NMO are urgently needed. Currently, detecting aquaporin-4 (AQP4) antibodies (AQP4-IgG or NMO-IgG) in serum is employed as the major supporting approach for the diagnosis of seropositive NMO, however, AQP4-IgG seronegativity in 10% to 25% of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis. Collaborative international studies hold great promise for establishing and validating biomarkers of NMO. This article discusses known and potential biomarkers for NMO. The biomarkers of NMO maybe the potential biomarkers of NMO-ON, for ION is the initial presentation and the earliest stage. (Chin J Ophthalmol, 2019, 55:228-233).


Assuntos
Neuromielite Óptica , Neurite Óptica , Aquaporina 4 , Autoanticorpos , Biomarcadores , Humanos , Imunoglobulina G , Glicoproteína Mielina-Oligodendrócito
9.
Opt Express ; 26(13): 17132-17144, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-30119529

RESUMO

A quadrichromatic light-emitting diode (QLED) based visible light communication for mobile phone camera is proposed to improve data rate and enhance illumination effect at the same time. Different from color intensity modulation (CIM), we propose and use color ratio modulation (CRM) in CMOS image sensor based visible light communication to improve data rate. According to the spectral power distribution (SPD) of the QLED and the spectral response of the complementary-metal-oxide-semiconductor (CMOS) image sensor, color multiple-input multiple-output (CMIMO) channel model is set up first to obtain optimal 16-CRM constellation design. Taking full consideration of the high quality of color rendering index (CRI), tunable color temperature (CT), we design a specific data packet structure to realize illumination requirements. A decoding strategy is also addressed for demapping at the receiver. The experimental results demonstrate that the proposed scheme can realize a downlink data rate of 13.2kbit/s, meanwhile, the optical signal source is illumination compatible.

10.
Sci Rep ; 8(1): 10521, 2018 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-30002502

RESUMO

An effective resistivity relevant to collisionless magnetic reconnection (MR) in plasma is presented. It is based on the argument that pitch angle scattering of electrons in the small electron diffusion region around the X line can lead to an effective, resistivity in collisionless plasma. The effective resistivity so obtained is in the form of a power law of the local plasma and magnetic field parameters. Its validity is confirmed by direct collisionless particle-in-cell (PIC) simulation. The result agrees very well with the resistivity (obtained from available data) of a large number of environments susceptible to MR: from the intergalactic and interstellar to solar and terrestrial to laboratory fusion plasmas. The scaling law can readily be incorporated into existing collisional magnetohydrodynamic simulation codes to investigate collisionless MR, as well as serve as a guide to ab initio theoretical investigations of the collisionless MR process.

11.
Genet Mol Res ; 16(1)2017 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-28290617

RESUMO

The Rab protein family is the largest family of the small GTP-binding proteins. Among them, the RabG genes are known to be responsive to abiotic stresses, but the molecular mechanisms of the stress responses mediated by RabG genes in plants is poorly understood. To investigate the molecular mechanism of AhRabG gene in peanut, transgenic plants overexpressing the AhRabG gene (S6) with relatively higher salinity resistance than the non-transgenic plants (S7) were obtained. Digital gene expression (DGE) sequencing was performed with the leaves of S6 and S7 plants before and after salinity-stress treatment. The AhRabG gene in peanut was found to be involved in a few pathways such as "photosynthesis", "oxidative phosphorylation", "AMPK signaling pathway", "plant hormone signal transduction", etc. A total of 298 differentially expressed genes (DEGs) were found to be upregulated or downregulated at five sampling time points based on the comparison between S6 and S7 plants. Among them, 132 DEGs were responsive to salinity stress in S6 and/or S7 after salinity-stress treatment. These 132 DEGs included genes encoding various transcription factors and proteins involved in resistance to salinity stress such as MYB, AP2, RING-H2 zinc finger proteins, late embryogenesis abundant (LEA) proteins, dehydration-responsive protein RD22, peroxidases, CBL-interacting protein kinases, calcium-binding proteins, and others. The information from this study will be useful for further studies on elucidating the mechanism of salinity resistance conferred by RabG genein peanut.


Assuntos
Arachis/genética , Proteínas de Plantas/biossíntese , Plantas Tolerantes a Sal/genética , Proteínas rab de Ligação ao GTP/biossíntese , Adaptação Fisiológica/genética , Arachis/metabolismo , Proteínas de Ligação ao Cálcio/genética , Secas , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Salinidade , Plantas Tolerantes a Sal/metabolismo , Transdução de Sinais , Estresse Fisiológico/genética , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo
12.
Phys Rev E ; 95(1-1): 013201, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28208417

RESUMO

Generation of intense coherent THz radiation by obliquely incidenting an intense laser pulse on a wire target is studied using particle-in-cell simulation. The laser-accelerated fast electrons are confined and guided along the surface of the wire, which then acts like a current-carrying line antenna and under appropriate conditions can emit electromagnetic radiation in the THz regime. For a driving laser intensity ∼3×10^{18}W/cm^{2} and pulse duration ∼10 fs, a transient current above 10 KA is produced on the wire surface. The emission-cone angle of the resulting ∼0.15 mJ (∼58 GV/m peak electric field) THz radiation is ∼30^{∘}. The conversion efficiency of laser-to-THz energy is ∼0.75%. A simple analytical model that well reproduces the simulated result is presented.

13.
Phys Rev E ; 94(5-1): 053207, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27967162

RESUMO

A right-hand circularly polarized electromagnetic wave can propagate in a sufficiently magnetized plasma of any density without encountering cutoff in the whistler mode. With the recent realization of tens-kilotesla magnetic fields, laser propagation in highly magnetized high-density plasmas has become of practical interest, especially for heating plasmas to high energy density and igniting fusion targets. In this paper, the whistler regime of laser-plasma interaction is discussed. It is shown by one- and two-dimensional particle-in-cell simulations that moderately intense right-hand circularly polarized laser light can enter and propagate in high-density plasma and heat it efficiently because of the significantly reduced wave length and speed.

14.
Phys Rev E ; 94(3-1): 033206, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27739720

RESUMO

Radially polarized intense terahertz (THz) radiation behind a thin foil irradiated by ultrahigh-contrast ultrashort relativistic laser pulse is recorded by a single-shot THz time-domain spectroscopy system. As the thickness of the target is reduced from 30 to 2 µm, the duration of the THz emission increases from 5 to over 20 ps and the radiation energy increases dramatically, reaching ∼10.5mJ per pulse, corresponding to a laser-to-THz radiation energy conversion efficiency of 1.7%. The efficient THz emission can be attributed to reflection (deceleration and acceleration) of the laser-driven hot electrons by the target-rear sheath electric field. The experimental results are consistent with that of a simple model as well as particle-in-cell simulation.

15.
Phys Rev E ; 93(5): 053206, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27300994

RESUMO

Harmonic generation from linearly polarized high-intensity short-pulse laser normally impacting a solid plasma grating is investigated using analytical modeling and particle-in-cell simulation. It is found that when the radiation excited by the relativistic electron quiver motion in the laser fields suitably matches a harmonic of the grating periodicity, it will be significantly enhanced and peak with narrow angular spread in specific directions. The corresponding theory shows that the phenomenon can be attributed to an interference effect of the periodic grating on the excitation.

16.
Phys Rev E ; 93(5): 053209, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27300997

RESUMO

The effect of a transient magnetic field on right-hand circularly polarized (RHCP) laser light propagation in overcritical-density plasma is investigated. When the electron gyrofrequency is larger than the wave frequency, RHCP light can propagate along the external magnetic field in an overcritical density plasma without resonance or cutoff. However, when the magnetic field falls to below the cyclotron resonance point, the propagating laser pulse will be truncated and the local plasma electrons resonantly heated. Particle-in-cell simulation shows that when applied to a thin slab, the process can produce intense two-cycle light pulses as well as long-lasting self-magnetic fields.

17.
Opt Express ; 24(9): 10057-65, 2016 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-27137616

RESUMO

We have investigated the polarization of attosecond light pulses generated from relativistic few-cycle laser pulse interaction with the surface of overdense plasmas using particle-in-cell simulation. Under suitable conditions, a desired polarization state of the generated attosecond pulse can be achieved by controlling the polarization of the incident laser. In particular, an elliptically polarized laser pulse of suitable ellipticity can generate an almost circularly polarized attosecond pulse without compromising the harmonic generation efficiency. The process is thus applicable as a new tabletop circularly-polarized XUV radiation source for probing attosecond phenomena with high temporal resolution.

18.
Phys Rev E ; 94(6-2): 069903, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28085328

RESUMO

This corrects the article DOI: 10.1103/PhysRevE.94.053207.

19.
Genet Mol Res ; 14(4): 12710-22, 2015 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-26505422

RESUMO

Chitinase is an important pathogenesis-related protein in plants, and it can accumulate when induced by salicylic acid (SA) or other elicitors. Here, we found that chitinase mRNA levels were 4.5-times greater when peanut seedlings were sprayed with 1.5 mM SA, as compared to water. The upstream promoter sequence of the chitinase gene was cloned by TAIL-PCR and the potential cis-regulatory elements in this promoter were predicted by the cis-element databases PLACE and plantCARE. Elements in the promoter related to SA induction and disease resistance response included AS-1, GT1-motif, GRWAAW, TGTCA, W-box, and WB-box. The full-length promoter (P) and a series of 5'-deleted promoters (P1-P5) were cloned and then substituted for the 35S promoter of pCAMBIA1301-xylA, which carries the xylose isomerase gene as the selectable marker and GUS as the reporter gene. Six plant expression vectors (pCAMBIA1301-xylA-P-pCAMBIA1301-xylA-P5) were obtained. The six expression vectors were then transferred into onion epidermal cells and peanut plants by Agrobacterium-mediated transformation. Both the full-length and deleted promoters resulted in GUS staining of the onion epidermis cells when induced by SA. In onion epidermis cells, GUS enzyme activity was greater after SA induction. In transgenic peanut plants, GUS mRNA levels were greater after SA induction. Consideration of the cis-regulatory elements predicted by PLACE and plantCARE suggested that AS-1, GRWAAW, and W-box are positive regulatory elements in P2 and P3 and that GT1-motif and TGTCA are negative regulatory elements between P and P2.


Assuntos
Arachis/enzimologia , Arachis/genética , Quitinases/genética , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/enzimologia , Plantas Geneticamente Modificadas/genética
20.
Cell Death Dis ; 6: e1716, 2015 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-25855964

RESUMO

Methylated histone readers are critical for chromatin dynamics, transcription, and DNA repair. Human PHRF1 contains a plant homeodomain (PHD) that recognizes methylated histones and a RING domain, which ubiquitinates substrates. A recent study reveals that PHRF1 is a tumor suppressor that promotes TGF-ß cytostatic signaling through TGIF ubiquitination. Also, PHRF1 is a putative phosphorylation substrate of ataxia telangiectasia-mutated/ataxia telangiectasia and Rad3-related kinases; however, the role of PHRF1 in DNA damage response is unclear. Here we report a novel function of PHRF1 in modulating non-homologous end-joining (NHEJ). PHRF1 quickly localizes to DNA damage lesions upon genotoxic insults. Ablation of PHRF1 decreases the efficiency of plasmid-based end-joining, whereas PHRF1 overexpression leads to an elevated NHEJ in H1299 reporter cells. Immunoprecipitation and peptide pull-down assays verify that PHRF1 constitutively binds to di- and trimethylated histone H3 lysine 36 (H3K36) (H3K36me2 and H3K36me3) via its PHD domain. Substitution of S915DT917E to ADAE in PHRF1 decreases its affinity for NBS1. Both PHD domain and SDTE motif are required for its NHEJ-promoting activity. Furthermore, PHRF1 mediates PARP1 polyubiquitination for proteasomal degradation. These results suggest that PHRF1 may combine with H3K36 methylation and NBS1 to promote NHEJ and stabilize genomic integrity upon DNA damage insults.


Assuntos
Dano ao DNA , Reparo do DNA por Junção de Extremidades , Proteínas de Ligação a DNA/genética , Proteínas do Grupo Polycomb/genética , Sequência de Aminoácidos , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/metabolismo , Genoma Humano , Células HEK293 , Histonas/genética , Histonas/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Metilação , Dados de Sequência Molecular , Proteínas do Grupo Polycomb/metabolismo
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