Prmt6 represses the pro-adipogenic Ppar-gamma-C/ebp-alpha transcription factor loop.

The feed-forward loop between the transcription factors Ppar-gamma and C/ebp-alpha is critical for lineage commitment during adipocytic differentiation. Ppar-gamma interacts with epigenetic cofactors to activate C/ebp-alpha and the downstream adipocytic gene expression program. Therefore, knowledge of the epigenetic cofactors associated with Ppar-gamma, is central to understanding adipocyte differentiation in normal differentiation and disease. We found that Prmt6 is present with Ppar-gamma on the Ppar-gamma and C/ebp-alpha promoter. It contributes to the repression of C/ebp-alpha expression, in part through its ability to induce H3R2me2a. During adipocyte differentiation, Prmt6 expression is reduced and the methyltransferase leaves the promoters. As a result, the expression of Ppar-gamma and C/ebp-alpha is upregulated and the adipocytic gene expression program is established. Inhibition of Prmt6 by a small molecule enhances adipogenesis, opening up the possibility of epigenetic manipulation of differentiation. Our data provide detailed information on the molecular mechanism controlling the Ppar-gamma-C/ebp-alpha feed-forward loop. Thus, they advance our understanding of adipogenesis in normal and aberrant adipogenesis.

High-efficiency non-ablative UV laser nano-scale processing of fused silica by stable filamentation.

Over the last decades, three-dimensional micro-manufacturing of fused silica via near-infrared ultrafast laser exposure combined with an etching step has become an established technique for producing complex three-dimensional components. Here, we explore the effect of ultraviolet exposure on process efficiency. Specifically, we demonstrate that shorter wavelengths not only enable enhanced resolution but also yield higher etching selectivity, with an order of magnitude lower pulse energy and significantly higher repetition rates than current practice. This result is obtained using an exposure regime where the laser beam alternates between regimes of self-focusing and defocusing in a stable manner, forming a localized filament. Using this principle, we demonstrate the fabrication of self-organized nano-channels with diameters as small as 120 nm after etching, reaching extreme aspect ratios, exceeding 1500.

Inverse-Designed Narrowband THz Radiator for Ultrarelativistic Electrons.

THz radiation finds various applications in science and technology. Pump-probe experiments at free-electron lasers typically rely on THz radiation generated by optical rectification of ultrafast laser pulses in electro-optic crystals. A compact and cost-efficient alternative is offered by the Smith-Purcell effect: a charged particle beam passes a periodic structure and generates synchronous radiation. Here, we employ the technique of photonic inverse design to optimize a structure for Smith-Purcell radiation at a single wavelength from ultrarelativistic electrons. The resulting design is highly resonant and emits narrowbandly. Experiments with a 3D-printed model for a wavelength of 900 µm show coherent enhancement. The versatility of inverse design offers a simple adaption of the structure to other electron energies or radiation wavelengths. This approach could advance beam-based THz generation for a wide range of applications.

Laser-Driven Modulation of Electron Beams in a Dielectric Micro-Structure for X-Ray Free-Electron Lasers.

We describe an application of laser-driven modulation in a dielectric micro-structure for the electron beam in a free-electron laser (FEL). The energy modulation is transferred into longitudinal bunching via compression in a magnetic chicane before entering the undulator section of the FEL. The bunched electron beam comprises a series of enhanced current spikes separated by the wavelength of the modulating laser. For beam parameters of SwissFEL at a total bunch charge of 30 pC, the individual spikes are expected to be as short as 140 as (FWHM) with peak currents exceeding 4 kA. The proposed modulation scheme requires the electron beam to be focused into the micrometer scale aperture of the dielectric structure, which imposes strict emittance and charge limitations, but, due to the small interaction region, the scheme is expected to require ten times less laser power as compared to laser modulation in a wiggler magnet, which is the conventional approach to create a pulse train in FELs.