Mutant dominant-negative rhodopsin∆I256 causes protein aggregates degraded via ERAD and prevents normal rhodopsin from proper membrane trafficking.

Dominant mutations in the rhodopsin gene (Rho) contribute to 25% of autosomal dominant retinitis pigmentosa (adRP), characterized by photoreceptor loss and progressive blindness. One such mutation, Rho ∆I256 , carries a 3-bp deletion, resulting in the loss of one of two isoleucines at codons 255 and 256. Our investigation, using recombinant expression in HEK293 and COS-7 cells, revealed that Rho ∆I256, akin to the known adRP mutation Rho P23H, induces the formation of rhodopsin protein (RHO) aggregates at the perinuclear region. Co-expression of Rho ∆I256 or Rho P23H with wild-type Rho WT, mimicking the heterozygous genotype of adRP patients, demonstrated the dominant-negative effect, as all isoforms were retained in perinuclear aggregates, impeding membrane trafficking. In retinal explants from WT mice, mislocalization of labeled adRP isoforms at the outer nuclear layer was observed. Further analysis revealed that RHO∆I256 aggregates are retained at the endoplasmic reticulum (ER), undergo ER-associated degradation (ERAD), and colocalize with the AAA-ATPase escort chaperone valosin-containing protein (VCP). These aggregates are polyubiquitinated and partially colocalized with the 20S proteasome subunit beta-5 (PSMB5). Pharmacological inhibition of proteasome- or VCP activity increased RHO∆I256 aggregate size. In summary, RHO∆I256 exhibits dominant pathogenicity by sequestering normal RHOWT in ER aggregates, preventing its membrane trafficking and following the ERAD degradation.

Ferroelectric Properties of Perovskite Thin Films and Their Implications for Solar Energy Conversion.

Whether or not methylammonium lead iodide (MAPbI3 ) is a ferroelectric semiconductor has caused controversy in the literature, fueled by many misunderstandings and imprecise definitions. Correlating recent literature reports and generic crystal properties with the authors' experimental evidence, the authors show that MAPbI3 thin-films are indeed semiconducting ferroelectrics and exhibit spontaneous polarization upon transition from the cubic high-temperature phase to the tetragonal phase at room temperature. The polarization is predominantly oriented in-plane and is organized in characteristic domains as probed with piezoresponse force microscopy. Drift-diffusion simulations based on experimental patterns of polarized domains indicate a reduction of the Shockley-Read-Hall recombination of charge carriers within the perovskite grains due to the ferroelectric built-in field and allow reproduction of the electrical solar cell properties.

3D whispering-gallery-mode microlasers by direct laser writing and subsequent soft nanoimprint lithography.

We demonstrate the realization of 3D whispering-gallery-mode (WGM) microlasers by direct laser writing (DLW) and their replication by nanoimprint lithography using a soft mold technique ("soft NIL"). The combination of DLW as a method for rapid prototyping and soft NIL offers a fast track towards large scale fabrication of 3D passive and active optical components applicable to a wide variety of materials. A performance analysis shows that surface-scattering-limited Q-factors of replicated resonators as high as 1×105 at 635 nm can be achieved with this process combination. Lasing in the replicated WGM resonators is demonstrated by the incorporation of laser dyes in the target material. Low lasing thresholds in the order of 15 kW/cm2 are obtained under ns-pulsed excitation.