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1.
Commun Biol ; 5(1): 1420, 2022 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-36577784

RESUMO

Cellular senescence caused by oncogenic stimuli is associated with the development of various age-related pathologies through the senescence-associated secretory phenotype (SASP). SASP is mediated by the activation of cytoplasmic nucleic acid sensors. However, the molecular mechanism underlying the accumulation of nucleotide ligands in senescent cells is unclear. In this study, we revealed that the expression of RNaseH2A, which removes ribonucleoside monophosphates (rNMPs) from the genome, is regulated by E2F transcription factors, and it decreases during cellular senescence. Residual rNMPs cause genomic DNA fragmentation and aberrant activation of cytoplasmic nucleic acid sensors, thereby provoking subsequent SASP factor gene expression in senescent cells. In addition, RNaseH2A expression was significantly decreased in aged mouse tissues and cells from individuals with Werner syndrome. Furthermore, RNaseH2A degradation using the auxin-inducible degron system induced the accumulation of nucleotide ligands and induction of certain tumourigenic SASP-like factors, promoting the metastatic properties of colorectal cancer cells. Our results indicate that RNaseH2A downregulation provokes SASP through nucleotide ligand accumulation, which likely contributes to the pathological features of senescent, progeroid, and cancer cells.


Assuntos
DNA , Neoplasias , Animais , Camundongos , Senescência Celular/genética , Fragmentação do DNA , Regulação para Baixo , Expressão Gênica , Genômica , Ligantes , Neoplasias/genética , Neoplasias/metabolismo , Nucleotídeos , Fenótipo , Humanos , Linhagem Celular
2.
Appl Opt ; 61(2): 352-361, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35200869

RESUMO

We have developed an active alignment of receiving beam (AARB) function for coaxial optics in wind sensing coherent Doppler lidar using feedback control based on the heterodyne-detected signal processing of backscattered light from the aerosols. The proposed method needs only the simple alignment components and contributes to the robustness for the coherent lidars with the high-power laser transmitter under the risky condition of misalignment, for example, in the airborne application. The concept, design, and evaluation results of the alignment precision are shown. The effect of the AARB is demonstrated for both cases of the hard target and soft target (i.e., wind sensing). To the best of our knowledge, this is the first demonstration of the AARB concept for the wind sensing coherent lidar.

3.
Opt Express ; 28(18): 27078-27096, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32906968

RESUMO

The 1.53-µm coherent differential absorption lidar (DIAL) is demonstrated for the simultaneous profiling of water vapor (H2O) density and wind speed. The optical setup is fiber-based. The wavelength locking circuit can achieve precise locking of 13.0 MHz by the combination of the line center locking to the hydrogen cyanide (HCN) absorption line and offset locking to the H2O absorption wavelength. The measurable range for the simultaneous profiling is up to 1.2 km. The DIAL-measured H2O density is compared with the one measured by an in-situ sensor. Qualitative good agreement is shown with the random error of 0.56 g/m3.

4.
Opt Express ; 27(17): 24175-24187, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31510311

RESUMO

We have developed a high-gain, high-peak-power laser amplifier at an eye-safe 1.55 µm wavelength using an Er,Yb:glass planar waveguide for wind sensing coherent Doppler lidars (CDLs). Our planar waveguide is free from stimulated Brillouin scattering and realizes high gain thanks to its multi-bounce optical-path configuration. A peak power of 5.5 kW with a pulse energy of 3.2 mJ is achieved at the repetition frequency of 4 kHz, which leads to an average power of 12.8 W. The gain is more than 23 dB. The wind sensing at more than 30 km is demonstrated with a CDL using the developed amplifier.

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