RESUMO
High-power femtosecond pulses delivered at a high-repetition rate will aid machining throughput and improve signal-to-noise ratios for sensitive measurements. Here we demonstrate a Kerr-lens mode-locked femtosecond Yb:YAG ring-cavity thin-disk oscillator with a multi-pass scheme for the laser beam. With four passes through the thin disk, 175-fs pulses were delivered from the oscillator at an average power of 71.5â W and a repetition rate of 65.3â MHz. The corresponding intra-cavity peak power of 110â MW is ample for intra-cavity nonlinear conversion into more exotic wavelength ranges. With six passes, the average output power reached 101.3â W. To the best of our knowledge, this is the highest average output power of any mode-locked ring laser. These results confirm the viability of using multi-pass configuration on a thin-disk ring oscillator for high-throughput femtosecond applications.
RESUMO
In this work, we propose an integrated terahertz mode adapter that couples broadband terahertz radiation from free-space to hollow-core fiber with a high mode conversion efficiency (Gaussian beam-to-T E 01) of up to 80%. The adapter consists of a pyramidal horn antenna, a broadband mode converter, and a conical horn. The simulation results indicate that the T E 01 mode in the hollow-core fiber can be efficiently excited by the terahertz mode adapter. The terahertz mode adapter successfully achieved a wide operating bandwidth of more than 15.7% ranging from 205 to 240 GHz in our simulation.
RESUMO
KAT8 is an evolutionarily conserved lysine acetyltransferase that catalyzes histone acetylation at H4K16 or H4K5 and H4K8 through distinct protein complexes. It plays a pivotal role in male X chromosome dosage compensation in Drosophila and is implicated in the regulation of diverse cellular processes in mammals. Mutations and dysregulation of KAT8 have been reported in human neurodevelopmental disorders and various cancers. However, the precise mechanisms by which these mutations disrupt KAT8's normal function, leading to disease pathogenesis, remain largely unknown. In this study, we focus on a hotspot missense cancer mutation, the R98W point mutation within the Tudor-knot domain. Our study reveals that the R98W mutation leads to a reduction in global H4K16ac levels in cells and downregulates the expression of target genes. Mechanistically, we demonstrate that R98 is essential for KAT8-mediated acetylation of nucleosomal histones by modulating substrate accessibility.
Assuntos
Histona Acetiltransferases , Histonas , Neoplasias , Nucleossomos , Domínio Tudor , Animais , Humanos , Masculino , Acetilação , Drosophila/metabolismo , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Histonas/genética , Histonas/metabolismo , Neoplasias/genética , Mutação de Sentido Incorreto , Nucleossomos/metabolismo , Domínio Tudor/genética , Linhagem Celular TumoralRESUMO
The lysine acetyltransferase KAT5 is a pivotal enzyme responsible for catalyzing histone H4 acetylation in cells. In addition to its indispensable HAT domain, KAT5 also encompasses a conserved Tudor-knot domain at its N-terminus. However, the function of this domain remains elusive, with conflicting findings regarding its role as a histone reader. In our study, we have employed a CRISPR tiling array approach and unveiled the Tudor-knot motif as an essential domain for cell survival. The Tudor-knot domain does not bind to histone tails and is not required for KAT5's chromatin occupancy. However, its absence leads to a global reduction in histone acetylation, accompanied with genome-wide alterations in gene expression that consequently result in diminished cell viability. Mechanistically, we find that the Tudor-knot domain regulates KAT5's HAT activity on nucleosomes by fine-tuning substrate accessibility. In summary, our study uncovers the Tudor-knot motif as an essential domain for cell survival and reveals its critical role in modulating KAT5's catalytic efficiency on nucleosome and KAT5-dependent transcriptional programs critical for cell viability.